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Aim: It is an ongoing discussion the extent to which oxygen delivery and oxygen extraction contribute to an increased muscle oxygen uptake during dynamic exercise. It has been proposed that local muscle factors including the capillary bed and mitochondrial oxidative capacity play a large role in prolonged low-intensity training of a small muscle group when the cardiac output capacity is not directly limiting. The purpose of this study was to investigate the relative roles of circulatory and muscle metabolic mechanisms by which prolonged low-intensity exercise training alters regional muscle VO2 . Methods: In nine healthy volunteers (seven males, two females), haemodynamic and metabolic responses to incremental arm cycling were measured by the Fick method and biopsy of the deltoid and triceps muscles before and after 42 days of skiing for 6 h day(-1) at 60% max heart rate. Results: Peak pulmonary VO2 during arm crank was unchanged after training (2.38 ± 0.19 vs. 2.18 ± 0.2 L min(-1) pre-training) yet arm VO2 (1.04 ± 0.08 vs. 0.83 ± 0.1 L min(1) , P < 0.05) and power output (137 ± 9 vs. 114 ± 10 Watts) were increased along with a higher arm blood flow (7.9 ± 0.5 vs. 6.8 ± 0.6 L min(-1) , P < 0.05) and expanded muscle capillary volume (76 ± 7 vs. 62 ± 4 mL, P < 0.05). Muscle O2 diffusion capacity (16.2 ± 1 vs. 12.5 ± 0.9 mL min(-1) mHg(-1) , P < 0.05) and O2 extraction (68 ± 1 vs. 62 ± 1%, P < 0.05) were enhanced at a similar mean capillary transit time (569 ± 43 vs. 564 ± 31 ms) and P50 (35.8 ± 0.7 vs. 35 ± 0.8), whereas mitochondrial O2 flux capacity was unchanged (147 ± 6 mL kg min(-1) vs. 146 ± 8 mL kg min(-1) ). Conclusion: The mechanisms underlying the increase in peak arm VO2 with prolonged low-intensity training in previously untrained subjects are an increased convective O2 delivery specifically to the muscles of the arm combined with a larger capillary-muscle surface area that enhance diffusional O2 conductance, with no apparent role of mitochondrial respiratory capacity.

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... Nevertheless, when the VO 2 by the muscles of the trunk, which represents 1/3 of the pulmonary VO 2 , is discounted (i.e., by determining O 2 delivery and extraction using a-v differences in combination with blood flow assessment by thermodilution), the peak VO 2 values per kg of arm or leg muscle are similar (Calbet et al., 2015a). This is in contrast to the fact that in vitro assessment of maximal mitochondrial respiration in permeabilized muscle fibers reveals higher values for the legs (Boushel et al., 2011(Boushel et al., , 2014a(Boushel et al., , 2015, indicating a greater functional reserve in mitochondrial VO 2 in the leg than arm muscles. Although the arms contain a higher proportion of type II fibers, this does not appear to impede or limit their capacity to increase their VO 2 peak in response to sprint-training. ...
... Indicative of central cardiovascular adaptations, the submaximal (80 W) heart rate after training was 10% lower during arm-cranking, but not during leg-pedaling. This difference could reflect a greater improvement in peripheral O 2 extraction during submaximal arm exercise, facilitated by the increased number of capillaries per fiber (Boushel et al., 2014a), which reduces the hyperemia required after SIT (Hellsten and Nyberg, 2015). Increasing the capillary density is not only advantageous for submaximal exercise, it also provides a functional reserve to increase peak blood flow without shortening mean transit time, that could otherwise occur when the peak blood flow increases without a concomitant enhancement of capillary density (Boushel et al., 2014a). ...
... This difference could reflect a greater improvement in peripheral O 2 extraction during submaximal arm exercise, facilitated by the increased number of capillaries per fiber (Boushel et al., 2014a), which reduces the hyperemia required after SIT (Hellsten and Nyberg, 2015). Increasing the capillary density is not only advantageous for submaximal exercise, it also provides a functional reserve to increase peak blood flow without shortening mean transit time, that could otherwise occur when the peak blood flow increases without a concomitant enhancement of capillary density (Boushel et al., 2014a). ...
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To elucidate the mechanisms underlying the differences in adaptation of arm and leg muscles to sprint training, over a period of 11 days 16 untrained men performed six sessions of 4–6 × 30-s all-out sprints (SIT) with the legs and arms, separately, with a 1-h interval of recovery. Limb-specific VO 2 peak, sprint performance (two 30-s Wingate tests with 4-min recovery), muscle efficiency and time-trial performance (TT, 5-min all-out) were assessed and biopsies from the m. vastus lateralis and m. triceps brachii taken before and after training. VO 2 peak and Wmax increased 3–11% after training, with a more pronounced change in the arms (P < 0.05). Gross efficiency improved for the arms (+8.8%, P < 0.05), but not the legs (−0.6%). Wingate peak and mean power outputs improved similarly for the arms and legs, as did TT performance. After training, VO 2 during the two Wingate tests was increased by 52 and 6% for the arms and legs, respectively (P < 0.001). In the case of the arms, VO 2 was higher during the first than second Wingate test (64 vs. 44%, P < 0.05). During the TT, relative exercise intensity, HR, VO 2 , VCO 2 , V E , and V t were all lower during arm-cranking than leg-pedaling, and oxidation of fat was minimal, remaining so after training. Despite the higher relative intensity, fat oxidation was 70% greater during leg-pedaling (P = 0.017). The aerobic energy contribution in the legs was larger than for the arms during the Wingate tests, although VO 2 for the arms was enhanced more by training, reducing the O 2 deficit after SIT. The levels of muscle glycogen, as well as the myosin heavy chain composition were unchanged in both cases, while the activities of 3-hydroxyacyl-CoA-dehydrogenase and citrate synthase were elevated only in the legs and capillarization enhanced in both limbs.
... 13 Furthermore, during arm cycling, engaging a small muscle mass (~6 kg) characterized by a substantially lower maximal mitochondrial respiratory capacity (OXPHOS; measured in permeabilized muscle fibers ex vivo) than its maximal O 2 delivery, 14 endurance training has proven to enhance O 2 extraction. 15 Although there is some controversy whether O 2 extraction improves after endurance training during exercise with a large muscle mass, [16][17][18][19] these data, in conjunction with animal data, 20 suggest that the potential for improvement is greater during exercise with a small muscle mass. ...
... 39 The latter concurs with the study by Boushel and coworkers in which maximal exercise arm O 2 extraction was raised from 62% to 68% after low-intensity training. 15 During arm cycling, the active muscle mass is small (~6 kg) and the mass-specific blood flow is large. 40 Thus, our results combined with previous studies strongly suggest that O 2 extraction during small muscle mass exercise is improved after endurance training, particularly when the exercise intensity is close to maximal. ...
... 27,42 Thus, even though conflicting evidence exists on whether systemic a-vO 2 diff increases after short-term endurance training during large muscle mass exercise, compelling evidence suggests that the O 2 extraction increases when measured directly with arterial and venous blood sampling in the exercising limbs. 15,17,18,21,39,43 ...
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When exercising with a small muscle mass, the mass-specific O2 delivery exceeds the muscle oxidative capacity resulting in a lower O2 extraction compared to whole-body exercise. We elevated the muscle oxidative capacity and tested its impact on O2 extraction during small muscle mass exercise. Nine individuals conducted six weeks of one-legged knee extension (1L-KE) endurance training. After training, the trained leg (TL) displayed 45% higher citrate synthase and COX-IV protein content in vastus lateralis and 15-22% higher pulmonary oxygen uptake (VO2peak ) and peak power output (Wpeak ) during 1L-KE than the control leg (CON; all P<0.05). Leg O2 extraction (catheters) and blood flow (ultrasound Doppler) were measured while both legs exercised simultaneously during 2L-KE at the same submaximal power outputs (real-time feedback-controlled). TL displayed higher O2 extraction than CON (main effect: 1.7±1.6%-points; P=0.010; 40-83% of Wpeak ) with the largest between-leg difference at 83% of Wpeak (O2 extraction: 3.2±2.2%-points; arteriovenous O2 difference: 7.1±4.8 mL·L-1 ; P<0.001). At 83% of Wpeak , muscle O2 conductance (DMO2 ; Fick law of diffusion) and the equilibration index Y were higher in TL (P<0.01), indicating reduced diffusion limitations. The between-leg difference in O2 extraction correlated with the between-leg ratio of citrate synthase and COX-IV (r=0.72-0.73; P=0.03), but not with the difference in the capillary-to-fibre ratio (P=0.965). In conclusion, endurance training improves O2 extraction during small muscle mass exercise by elevating the muscle oxidative capacity and the recruitment of DMO2 ; especially evident during high-intensity exercise exploiting a larger fraction of the muscle oxidative capacity.
... D uring exercise, blood flow regulation to the working muscles is tightly coupled and results in adequate oxygen delivery and utilization to meet the metabolic demands of the muscle (1)(2)(3). The upper limbs, when compared with lower limbs, exhibit lower vascular conductance and oxygen extraction values that have been speculated to result from poor blood flow distribution, large oxygen diffusion distances, and reduced capillary mean transit time (4). ...
... In healthy individuals, this exercise is not limited by maximal cardiac output or ventilatory demand, and therefore exercise-induced blood flow responses can be examined at or near maximal levels (17,18). Indeed, progressive, rhythmic handgrip exercise is one such modality that results in stepwise increases in brachial artery (BA) dilation and blood flow mediated, in part, by the vasoactive component nitric oxide (NO) (14) and is highly related to absolute workload (2) and, thus, metabolic cost (3,19). This modality is often used to provide enhanced insight into vascular function and blood flow alterations resulting from augmented vascular conductance (20) and/or work efficiency (6). ...
... Alternatively, the arms display much lower oxygen extraction during submaximal exercise that can be explained by poor capillary diffusion, reduced perfusion pressure, and/or the high percentage of glycolytic fibers in the arm (4). Training-induced plasticity in oxygen extraction is evident during maximal exercise with higher oxygen extraction values observed in trained individuals driving subsequent increases in blood flow and oxygen utilization (3,4,32). By contrast, during submaximal exercise, oxygen extraction appears to be similar between trained (3,4,32) and untrained (18) individuals resulting in a similar blood flow response independent of training status (3,4,32). ...
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Vascular function and blood flow responses to upper limb exercise are differentially altered in response to different exercise training modalities. Rowing is a unique exercise modality that incorporates the upper limbs and can significantly augment upper limb endurance, strength, and power capacity. Purpose: This study sought to determine whether vascular function and blood flow regulation during handgrip exercise are altered in row-trained males. Methods: Nine young row-trained males (ROW, 20 ± 1 yr; V˙O2peak = 51 ± 2 mL·kg·min) and 14 recreationally active male controls (C: 22 ± 1 yr; V˙O2peak = 37 ± 2 mL·kg·min) were recruited for this study. Subjects performed multiple bouts of progressive rhythmic handgrip exercise. Brachial artery (BA) diameter, blood flow, shear rate, and mean arterial pressure were measured at rest and during the last minute of each exercise workload. Results: Resting values for BA diameter, blood flow, shear rate, and mean arterial pressure were not different between groups. During handgrip exercise, the ROW group reported significantly lower BA blood flow (ROW vs C: 4 kg [146 ± 21 vs 243 ± 13 mL·min], 8 kg [248 ± 29 vs 375 ± 17 mL·min], 12 kg [352 ± 43 vs 490 ± 22 mL·min]) across all workloads when compared with controls. The examination of BA dilation, when controlled for the shear rate stimulus and evaluated across all workloads, was revealed to be significantly greater in ROW group versus controls. Conclusion: This study revealed that vascular function and blood flow regulation were significantly different in row-trained males when compared with untrained controls evidenced by greater shear-induced BA dilation and lower arm blood flow during progressive handgrip exercise.
... We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO 2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. ...
... In healthy adults, mitochondrial oxidative capacity is in excess of O 2 delivery at maximal exercise (Boushel et al., 2011; Boushel & Saltin, 2013), and while high-intensity training induces signals for both a higher O 2 delivery and mitochondrial biogenesis (Gollnick et al., 1973; Saltin et al., 1976; Gibala et al., 2012; Esposito et al., 2011), there is no firm evidence for an obligatory upregulation of mitochondrial capacity for increasing VO 2max . Accordingly, muscle VO 2 increases primarily through a higher O 2 delivery directed to contracting muscle along with elevated O 2 diffusion capacity and O 2 supply to mitochondria (Saltin, 1985; Richardson et al., 1993; Calbet et al., 2009; Wagner, 2011; Boushel et al., 2014a,b). For a given O 2 supply, muscle mitochondrial VO 2 during exercise is defined by its activation state, e.g., by ADP, corresponding p50 and the provision of reducing equivalents to the electron transfer system (Gnaiger et al., 1998; Gnaiger, 2003). ...
... A lower mitochondrial p50 and thus higher O 2 affinity may increase mitochondrial VO 2 at a given O 2 supply and ADP activation state which is measureable by a change in mitochondrial p50 and a parallel change in muscle O 2 diffusion capacity. Low-intensity training has been shown to upregulate metabolic pathways involved in fat oxidation, and to increase regional muscle VO 2 without changes in muscle mitochondrial V max or peak whole body aerobic power (Daussin et al., 2008; Boushel et al., 2014a,b). This indicates that relative activation of mitochondria (by exercise intensity and therefore ADP concentration) varies substantially for a given level of mitochondrial V max and peak muscle VO 2 . ...
Article
We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. Peak pulmonary VO2 (3.52 ± 0.18 L.min−1 pre vs 3.52 ± 0.19 post) and VO2 across the leg (2.8 ± 0.4L.min−1 pre vs 3.0 ± 0.2 post) were unchanged after the ski journey. Peak leg O2 delivery (3.6 ± 0.2 L.min−1 pre vs 3.8 ± 0.4 post), O2 extraction (82 ± 1% pre vs 83 ± 1 post), and muscle capillaries per mm2 (576 ± 17 pre vs 612 ± 28 post) were also unchanged; however, leg muscle mitochondrial OXPHOS capacity was reduced (90 ± 3 pmol.sec−1.mg−1 pre vs 70 ± 2 post, P < 0.05) as was citrate synthase activity (40 ± 3 μmol.min−1.g−1 pre vs 34 ± 3 vs P < 0.05). These findings indicate that peak muscle VO2 can be sustained with a substantial reduction in mitochondrial OXPHOS capacity. This is achieved at a similar O2 delivery and a higher relative ADP-stimulated mitochondrial respiration at a higher mitochondrial p50. These findings support the concept that muscle mitochondrial respiration is submaximal at VO2max, and that mitochondrial volume can be downregulated by chronic energy demand.
... Nielsen and colleagues build their hypothesis on three previously published studies (Pesta et al. 2011;Jacobs & Lundby, 2013;Boushel et al. 2014) supposedly showing that endurance training results in higher respiration rate per mitochondrion. Unfortunately, none of these are suitable in this respect. ...
... However, mitochondrial content was evaluated by mtDNA (Pesta et al. 2011), which some of the authors in Nielsen et al. (2017) themselves have shown to be a very poor marker for mitochondrial content (Larsen et al. 2012). Thirdly, the paper by Boushel et al. (2014) is referenced to support the concept, and in this study arm muscles are used. However, Boushel and colleagues actually report no differences in the mitochondrial respiratory rates in the deltoid muscle after the training intervention, and data on mitochondrial content are not reported. ...
... It is allowing abdomen lifts slowly and chest fully expands, increase maximal alveolar inflation, increase muscle relaxation, improve effective coughing mechanisms, prevent atelectasis, increase the strength of respiratory muscles, mobility of the chest and thoracic vertebr, also correct abnormal breathing patterns. 3,9,10 Deep breathing exercise will improve compliance of the lung parenchyma and respiratory muscles so that it will increase oxygen intake into the body. ...
... the three-step rotational method has been shown to be statistically not significantly different from walking straight. [9][10][11] This test measures the distance that patient can travel by walking on a flat track and hard surface within 6 minutes. This test as a whole evaluates the response of all organ systems involved during exercise including the pulmonary, cardiac and circulatory systems, blood, neuromuscular and muscle metabolism. ...
Article
Introduction: Restrictive pulmonary disorder is reducing VO2 max values. It can be caused by lung can’t take oxygen from outside air freely. Pulmonary rehabilitation is known to increase the VO2 max. One of the pulmonary rehabilitation is deep breathing exercise. In this study aimed to know the improvement VO2 max after deep breathing exercise. Methods: This was an experimental without control pre and post-experimental study. The Six Minutes Walking Test (6MWT) was measured in patients with restrictive pulmonary disorder, after deep breathing exercise two times a day, for four weeks in May 2018. Results: Fifteen subjects were recruited, with the mean age was 70,76 ± 5,33 years old, 6MWT was 375,13 ± 44,19 m and VO2 Max 31,61±0,86 ml/kg/minute. After four weeks intervention, 6MWT value was 401±44,57 m (p=0.000) and VO2 Max score was 32,11±0,87 ml/kg/minute (p=0.000). Conclusion: Four weeks of deep breathing exercise can improve the VO2 max in restrictive lung disorder. Keywords: Deep breathing exercise, Restrictive pulmonary disorder, VO2 max.
... For example, chronic stimulation of cat muscles for 28 days did not alter the cristae density (Schwerzmann et al. 1989), nor did 10 weeks of endurance training change the biochemical composition of mitochondria in rats (Davies et al. 1981). By contrast, recent studies show that endurance-trained athletes have a higher respiration rate per mitochondria (Jacobs & Lundby, 2013) and that endurance training results in higher respiration rates without changes in mitochondrial content (Pesta et al. 2011;Boushel et al. 2014b). However, an understanding of the mechanism responsible for this is lacking. ...
... Our data unequivocally demonstrate that human skeletal muscle mitochondria cristae density varies between populations with different physical activity levels. This is in agreement with endurance-trained athletes having a higher respiration rate per mitochondria (Pesta et al. 2011;Jacobs and Lundby, 2013;Boushel et al. 2014b) and the fact that aerobic training is known to increase mitochondrial fusion (Iqbal et al. 2013), which increases mitochondrial intrinsic ATP production (Mitra et al. 2009). Elevated cristae density could provide the mechanism for enhancing skeletal muscle endurance via a more optimal selection of fuel stores, delaying exhaustion of endogenous glycogen reserves and, in turn, fatigue during prolonged physical activity (Allen et al. 2008),as well as confer an evolutionary advantage in energy savings during prolonged fasting by some animals (Monternier et al. 2014). ...
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Key points: In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand. Abstract: Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.
... When arm blood flow during maximal exercise is related to the active muscle mass, evaluated by dual X-ray absorptiometry (DXA), a perfusion of ϳ140 ml·min Ϫ1 ·100 g Ϫ1 in nonarm trained subjects and ϳ185 ml·min Ϫ1 ·100 g Ϫ1 in rowers is revealed (Fig. 2; Ref. 218). The effect of endurance training on increasing peak arm blood flow has been confirmed, albeit to a lesser extent due to the low intensity and relatively short training period in a longitudinal study (19). Even though computerized tomography and magnetic resonance imaging are standards for measuring skeletal muscle mass, the availability and the minimal exposure to radiation makes DXA an attractive alternative (222). ...
... DO2 is defined as the slope of the regression lines extended to the origin (220). Each data point is the calculated mean DO2 from knee extension (9,118,20,157,168,157), skiing (23), cycling (22,25,93,160), arm cranking (19,77,207,218), and arm skiing (22). The data confirm across exercise modalities a twofold higher muscle DO2 in the legs compared with the arms. ...
Article
It has been considered whether during whole body exercise the increase in cardiac output is large enough to support skeletal muscle blood flow. This review addresses four lines of evidence for a flow limitation to skeletal muscles during whole body exercise. First, even though during exercise the blood flow achieved by the arms is lower than that achieved by the legs (~160 vs. ~385 ml/min/100 g) the muscle mass that can be perfused with such flow is limited by the capacity to increase cardiac output (42 l/min, highest recorded value). Secondly, activation of the exercise pressor reflex during fatiguing work with one muscle group limits flow to other muscle groups. Another line of evidence comes from evaluation of regional blood flow during exercise where there is a discrepancy between flow to a muscle group when it is working exclusively and when it works together with other muscles. Finally, regulation of peripheral resistance by sympathetic vasoconstriction in active muscles by the arterial baroreflex is critical for blood pressure regulation during exercise. Together, these findings indicate that during whole body exercise muscle blood flow is subordinate to the control of blood pressure.
... The diffusion of O 2 from the muscle capillaries to the mitochondria is driven by the O 2 pressure gradient between the capillaries and the mitochondria, where the latter is close to 0 mmHg (ß1.5-3 mmHg), particularly at near maximal exercise intensities (Severinghaus, 1994). In the case of O 2 diffusion limitation due to structural constraints (Richardson et al. 1995), as for example reduced capillary density (Hepple et al. 2000) or number of capillary-to-sarcolemmal contacts (Krogh, 1919a, b;Boushel et al. 2014a), a reduction of the pressure gradient driving O 2 diffusion should cause a reduction ofV O 2 . However, our experimental data demonstrate that musclė V O 2 was insensitive to severe hypoxia during the first 15 s of the sprints despite a reduction of the mean P O 2 gradient from 52 to 18 mmHg. ...
... It has been suggested that the sarcolemma and other structural elements interposed between the erythrocytes and the mitochondria pose a resistance to O 2 diffusion during exercise (Krogh, 1919a, b;Wagner, 2000;Boushel et al. 2014a) and that this resistance plays a greater limiting role onV O 2 peak in hypoxia than in normoxia, due to the lower P O 2 gradient driving diffusion in hypoxia (Wagner, 1993). During the first 10 s of the normoxic sprint exercise, O 2 delivery was so high that O 2 fractional J Physiol 00.0 extraction was even reduced, compared to that observed just before the start of the sprint. ...
Article
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To determine the contribution of convective and diffusive limitations to (V) over dot(O2 peak) during exercise in humans, oxygen transport and haemodynamics were measured in 11 men (22 +/- 2years) during incremental (IE) and 30s all-out cycling sprints (Wingate test, WgT), in normoxia (Nx, P-IO2: 143mmHg) and hypoxia (Hyp, P-IO2: 73mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg (V) over dot(O2 peak) was measured by the Fick method and leg blood flow (BF) with thermodilution, and muscle O-2 diffusing capacity (D-MO2) was calculated. In the WgT mean power output, leg BF, leg O-2 delivery and leg O2 were 7, 5, 28 and 23% lower in Hyp than Nx (P<0.05); however, peak WgT D-MO2 was higher in Hyp (51.5 +/- 9.7) than Nx (20.5 +/- 3.0mlmin(-1)mmHg(-1), P<0.05). Despite a similar P-aO2 (33.3 +/- 2.4 and 34.1 +/- 3.3mmHg), mean capillary P-O2 (16.7 +/- 1.2 and 17.1 +/- 1.6mmHg), and peak perfusion during IE and WgT in Hyp, D-MO2 and leg (V) over dot(O2) were 12 and 14% higher, respectively, during WgT than IE in Hyp (both P<0.05). D-MO2 was insensitive to COHb (COHb: 0.7 vs. 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O-2 transfer in both Nx and Hyp. In conclusion, muscle (V) over dot(O2) during sprint exercise is not limited by O-2 delivery, O-2 offloading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O-2 diffusing capacity.
... It is allowing abdomen lifts slowly and chest fully expands, increase maximal alveolar inflation, increase muscle relaxation, improve effective coughing mechanisms, prevent atelectasis, increase the strength of respiratory muscles, mobility of the chest and thoracic vertebr, also correct abnormal breathing patterns. 3,9,10 Deep breathing exercise will improve compliance of the lung parenchyma and respiratory muscles so that it will increase oxygen intake into the body. ...
... the three-step rotational method has been shown to be statistically not significantly different from walking straight. [9][10][11] This test measures the distance that patient can travel by walking on a flat track and hard surface within 6 minutes. This test as a whole evaluates the response of all organ systems involved during exercise including the pulmonary, cardiac and circulatory systems, blood, neuromuscular and muscle metabolism. ...
Article
Full-text available
Introduction: Restrictive pulmonary disorder is reducing VO2 max values. It can be caused by lung can’t take oxygen from outside air freely. Pulmonary rehabilitation is known to increase the VO2 max. One of the pulmonary rehabilitation is deep breathing exercise. In this study aimed to know the improvementVO2 max after deep breathing exercise.Methods: This was an experimental without control pre and post-experimental study. The Six Minutes Walking Test (6MWT) was measured in patients with restrictive pulmonary disorder, after deep breathing exercise two times a day, for four weeks in May 2018.Results: Fifteen subjects were recruited, with the mean age was 70,76 ± 5,33 years old, 6MWT was 375,13 ± 44,19 m and VO2 Max 31,61±0,86 ml/kg/minute. After four weeks intervention, 6MWT value was 401±44,57 m (p=0.000) and VO2 Max score was 32,11±0,87 ml/kg/minute (p=0.000).Conclusion: Four weeks of deep breathing exercise can improve the VO2 max in restrictive lung disorder.Keywords: Deep breathing exercise, Restrictive pulmonary disorder, VO2 max.
... STUDY LIMITATIONS. We used an isometric exercise protocol consisting of forearm handgrip exercise, as opposed to dynamic exercise such as arm cranking.This may have led to differences in the peak forearm VO 2 measurements achieved in our study compared with other studies(48) and may also have affected our DmO 2 estimations(48). However, handgrip exercise more likely reflects the type of forearm exercise encountered by patients with HFpEF during routine activities of daily living, as opposed to arm cranking.We recognize, though, that the type of exercise and its characteristics (e.g., duty cycle) could affect fore-arm DmO 2 estimations (49). ...
... STUDY LIMITATIONS. We used an isometric exercise protocol consisting of forearm handgrip exercise, as opposed to dynamic exercise such as arm cranking.This may have led to differences in the peak forearm VO 2 measurements achieved in our study compared with other studies(48) and may also have affected our DmO 2 estimations(48). However, handgrip exercise more likely reflects the type of forearm exercise encountered by patients with HFpEF during routine activities of daily living, as opposed to arm cranking.We recognize, though, that the type of exercise and its characteristics (e.g., duty cycle) could affect fore-arm DmO 2 estimations (49). ...
Article
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The aim of this study was to determine the arteriovenous oxygen content difference (ΔAVo2) in adult subjects with and without heart failure with preserved ejection fraction (HFpEF) during systemic and forearm exercise. Subjects with HFpEF had reduced ΔAVo2. Forearm diffusional conductance for oxygen, a lumped conductance parameter that incorporates all impediments to the movement of oxygen from red blood cells in skeletal muscle capillaries into the mitochondria within myocytes, was estimated. Forearm diffusional conductance for oxygen was not different among adults with HFpEF, those with hypertension, and healthy control subjects; therefore, diffusional conductance cannot explain the reduced forearm ΔAVo2. Instead, adiposity was strongly associated with ΔAVo2, suggesting an active role for adipose tissue in reducing exercise capacity in patients with HFpEF.
... Data are mean values (±95% confidence limits, where available) from studies reported in Table 2 0.6 0.9 1. SKATTEBO ET Al was measured directly during maximal exercise (arterial and venous catheters), the vast majority found an increased O 2 extraction fraction after training. 12,30,[45][46][47] A particular case, concerning the relationship between one-leg V O 2max and O 2 extraction fraction ( Figure 4C) and between pulmonary V O 2max and two-LBF ( Figure 4D) deserves some attention (the white squares). These data were collected during combined upper-and lower-body exercise (cross-country skiing using the diagonal technique) and 6.6 L·min −1 of Q max was distributed to the two arms. ...
... In support, similar improvements in arm blood flow and capillary density have been observed after a period of arm training, causing no change in the calculated MTT. 47 The arm O 2 extraction fraction was increased in the same study, suggesting that elevated MTT is not the primary mechanism by which O 2 extraction is improved after training. However, this may differ between arms and legs (ie, small vs large muscle mass exercise). ...
Article
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We analysed the importance of systemic and peripheral arteriovenous O2 difference (a‐vO2 and a‐vfO2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake (VO2max). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion vs perfusion limitations vary with VO2max. Articles (n=17) publishing individual data (n=154) on VO2max, maximal cardiac output (Qmax; indicator‐dilution or Fick method), a‐vO2 difference (catheters or Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group‐mean data (articles: n=27; subjects: n=234) on leg blood flow (LBF; thermodilution), a‐vfO2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. Qmax and two‐LBF increased linearly by 4.9‐6.0 L·min‐1 per 1 L·min‐1 increase in VO2max (R²=0.73 and R²=0.67, respectively; both P<0.001). The a‐vO2 difference increased from 118‐168 mL·L‐1 from a VO2max of 2‐4.5 L·min‐1 followed by a reduction (second‐order polynomial: R²=0.27). After accounting for a hypoxemia‐induced decrease in arterial O2 content with increasing VO2max (R²=0.17; P<0.001), systemic O2 extraction fraction increased up to ~90% (VO2max: 4.5 L·min‐1) with no further change (exponential decay model: R²=0.42). Likewise, leg O2 extraction fraction increased with VO2max to approach a maximal value of ~90‐95% (R²=0.83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with VO2max (R²=0.77 and R²=0.31, respectively; both P<0.01), reflecting decreasing O2 diffusional limitations and accentuating O2 delivery limitations. In conclusion, although O2 delivery is the main limiting factor to VO2max, enhanced O2 extraction fraction (≥90%) contributes to the remarkably high VO2max in endurance‐trained individuals.
... Muscle fibers can be identified as pure (i.e., type I, IIa, and IIx) or hybrid fibers that coexpress two or more myosin heavy-chain isoforms (i.e., I/IIa, I/IIa/IIx, IIa/IIx, and I/IIx) (16). Although type IIa fibers can possess equally high or even higher mitochondrial volume than type I fibers in endurance-trained athletes (19,57), the cross-bridges (74) and sarcoplasmic reticulum Ca 2ϩ pumps (58) of these fibers consume more ATP than type I fibers. This would result in a mismatch between the rate of energy supply and the rate of energy use, likely resulting in more pronounced impairments in sarcoplasmic reticulum Ca 2ϩ release and greater fatigability. ...
... These findings suggest that runners with an estimated higher proportion of type I fibers are able to better cope with increases in training volume and achieve superior performance adaptations. Although type II fibers can possess equally high or even higher mitochondrial volume as type I fibers in endurancetrained athletes (19,57), differences in cross-bridge (74) and sarcoplasmic reticulum Ca 2ϩ pump ATP consumption (58) may result in greater fatigability (48,49,67) and delayed recovery (27,49) in type II fibers. Conversely, type I fibers are fatigue-resistant (35) but may adapt optimally to low-frequency, higher-volume contractions (60). ...
Article
The aim of this study was to identify markers of training stress and characteristics of middle-distance runners related to the incidence of overreaching following overload training. Twenty-four highly-trained runners (n=16 male; VO 2peak =73.3(4.3) mL·kg·min ⁻¹ ; n=8 female, VO 2peak =63.2(3.4) mL·kg·min ⁻¹ ) completed 3 weeks of normal training (NormTr), 3 weeks of high-volume training (HVTr; a 10, 20 and 30% increase in training volume each successive week from NormTr), and a 1-week taper (TapTr; 55% exponential reduction in training volume from HVTr week 3). Before, and immediately after each training period, an incremental treadmill-running test was performed, while resting metabolic rate (RMR), subjective fatigue responses and various resting blood biomarkers were assessed. Muscle fiber typology of the gastrocnemius was estimated by quantification of muscle carnosine using proton magnetic resonance spectroscopy and expressed as a z-score relative to a non-athlete control group. Twelve runners were classified as functionally overreached (FOR) following HVTr (decreased running TTE), whereas the other twelve were classified as acutely fatigued (AF; no decrease in running TTE). The FOR group did not demonstrate systematic alterations in RMR, resting blood biomarkers or submaximal exercise responses compared to the AF group. Gastrocnemius carnosine z-score was significantly higher in FOR (-0.44 ± 0.57) compared to AF (-1.25 ± 0.49, p = 0.004, d = 1.53) and was also associated with changes in running TTE from pre- to post-HVTr (r=-0.55, p=0.005) and pre-HVTr to post-TapTr (r=-0.64, p=0.008). Muscle fiber typology is related to the incidence of overreaching and performance super-compensation following increased training volume and a taper.
... In the present study, V˙O 2 peak in the able-bodied group was 8% higher than reported in previous studies of recreationally active ablebodied individuals performing arm-ergometry (Tiller et al., 2019) and was 109% higher than the highly-trained C-SCI group. Peak V˙E and VT in the able-bodied group were higher than previously reported during arm-ergometry, whereas Ti/Ttot, f b , and HRpeak were similar (Boushel et al., 2014;Tiller et al., 2019). In the C-SCI group, peak f b was similar and peak VT higher than that previously reported in athletes with C-SCI (West et al., 2014). ...
... Previous research has shown that injury to these pathways leads to a neurologically limited HR, impaired LVSV response, an impaired thermoregulatory capacity, and exercise induced hypotension, that culminate in reduced exercise performance compared to athletes with C-SCI in which these pathways are intact (i.e., individuals with an autonomically incomplete C-SCI) (Claydon et al., 2006;Gee et al., 2020;Griggs et al., 2015;West et al., 2015). Although local muscle factors rather than cardiac output likely limit aerobic capacity in able-bodied arm-ergometry (Boushel et al., 2014), we believe that cardiac factors are the primary limitation to .V . O 2 peak in highly trained individuals with C-SCI who have smaller left ventricular volumes and an impaired volumetric response to exercise (Hopman et al., 1996). ...
Article
We compared cardiopulmonary responses to arm-ergometry, in individuals with cervical spinal cord injury (C-SCI) and able-bodied controls. We hypothesized that individuals with C-SCI would have higher respiratory frequency (fb) but lower tidal volume (VT) at a given work rate and dynamically hyperinflate during exercise, whereas able-bodied individuals would not. Participants completed pulmonary function testing, an arm-ergometry test to exhaustion, and a sub-maximal exercise test consisting of four-minute stages at 20, 40, 60, and 80% peak work rate. Able-bodied individuals completed a further sub-maximal test with absolute work rate matched to C-SCI. During work rate matched sub-maximal exercise, C-SCI had smaller VT (main effect p < 0.001) compensated by an increased fb (main effect p = 0.009). C-SCI had increased end-expiratory lung volume at 80% peak work rate vs. rest (p < 0.003), whereas able-bodied did not. In conclusion, during arm-ergometry, individuals with C-SCI exhibit altered ventilatory patterns characterized by reduced VT, higher fb, and dynamic hyperinflation that may contribute to the observed reduced aerobic exercise capacity.
... Thus, the results from Pesta et al. (2011) cannot stand alone, but should be placed in a context with other observations as well. In this context, the respiration rate of fatty acids has been reported to be elevated following low-intensity training, without changes in maximal respiration, indicating no change in mitochondrial content but improved ability to oxidise fatty acids (Boushel et al. 2014). This has recently been confirmed (Boushel et al. 2015). ...
... One function of this overcapacity could be to constitute a necessary buffer to avoid energy limitations caused by oxidative inactivation by aconitase and thereby mitochondrial respiration. The improvements in VO 2peak could be attributable to structural and functional components unrelated to intrinsic mitochondrial capacity (28). ...
Article
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Intense exercise training is a powerful stimulus that activates mitochondrial biogenesis pathways and thus increases mitochondrial density and oxidative capacity. Moderate levels of reactive oxygen species (ROS) during exercise are considered vital in the adaptive response, but high ROS production is a serious threat to cellular homeostasis. Although biochemical markers of the transition from adaptive to maladaptive ROS stress are lacking, it is likely mediated by redox sensitive enzymes involved in oxidative metabolism. One potential enzyme mediating such redox sensitivity is the citric acid cycle enzyme aconitase. In this study, we examined biopsy specimens of vastus lateralis and triceps brachii in healthy volunteers, together with primary human myotubes. An intense exercise regimen inactivated aconitase by 55–72%, resulting in inhibition of mitochondrial respiration by 50–65%. In the vastus, the mitochondrial dysfunction was compensated for by a 15–72% increase in mitochondrial proteins, whereas H2O2 emission was unchanged. In parallel with the inactivation of aconitase, the intermediary metabolite citrate accumulated and played an integral part in cellular protection against oxidative stress. In contrast, the triceps failed to increase mitochondrial density, and citrate did not accumulate. Instead, mitochondrial H2O2 emission was decreased to 40% of the pretraining levels, together with a 6-fold increase in protein abundance of catalase. In this study, a novel mitochondrial stress response was highlighted where accumulation of citrate acted to preserve the redox status of the cell during periods of intense exercise.—Larsen, F. J., Schiffer, T. A., Ørtenblad, N., Zinner, C., Morales-Alamo, D., Willis, S. J., Calbet, J. A., Holmberg, H. C., Boushel R. High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation.
... The incremental tests were counterbalanced across the participants and were undertaken in a ß22°C environment with fan cooling. Details of the experimental protocols used in study 1 have been reported (Calbet et al. 2007;Boushel et al. 2011;Helge et al. 2011;Boushel et al. 2014). ...
Article
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Temperature-sensitive mechanisms may contribute to blood flow regulation, but the influence of temperature on perfusion to exercising and non-exercising human limbs is not established. Blood temperature (TB ), blood flow and oxygen uptake (VO2 ) in the legs and arms were measured in 16 healthy humans during 90 min of leg and arm exercise and during exhaustive incremental leg or arm exercise. During prolonged exercise, leg blood flow (LBF) was 4-fold higher than arm blood flow (ABF) in association with higher TB and limb VO2 . Leg and arm vascular conductance during exercise compared to rest was related closely to TB (R(2) = 0.91; P < 0.05), plasma adenosine triphosphate (ATP) (R(2) = 0.94; P < 0.05) and limb VO2 (R(2) = 0.99; P < 0.05). During incremental leg exercise, LBF increased in association with elevations in TB and limb VO2 whereas ABF, arm TB and VO2 remained largely unchanged. During incremental arm exercise, both ABF and LBF increased in relation to similar increases in VO2 . In 12 trained males, increases in femoral TB and LBF during incremental leg exercise were mirrored by similar pulmonary artery TB and cardiac output dynamics, suggesting that processes in active limbs dominate central temperature and perfusion responses. The present data reveal a close coupling among perfusion, TB and aerobic metabolism in exercising and non-exercising extremities and a tight association between limb vasodilatation and increases in plasma ATP. These findings suggest that temperature and VO2 contribute to the regulation of limb perfusion through control of intravascular ATP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
... A total of 35 studies for which the full text was reviewed were excluded from qualitative synthesis, as follows: previously sedentary nature of the participants (n = 5) [54][55][56][57][58], not using endurance-trained athletes (n = 2) [59,60], inducing a decline in performance that was not due to an overreaching intervention (i.e., athletes were allowed to detrain) (n = 1) [61], not including/reporting a valid measure of exercise performance (n = 7) [12,[62][63][64][65][66][67], not assessing an autonomic HR parameter of interest (n = 11) [68][69][70][71][72][73][74][75][76][77][78], not assessing a vagal-related index of HRV (n = 2) [79,80], not identifying what HRV index was assessed (n = 1) [81], being a case study of an individual (n = 1) [82], being a secondary analysis of study data for which the original publication [31,37,41,44] had already been included for analysis (n = 4 [83][84][85][86], and not inducing a decline in performance during a deliberate overreaching intervention (and thus any associated change in autonomic HR regulation was not due to a change in training status) (n = 1) [87]. ...
Article
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Background Autonomic regulation of heart rate (HR) as an indicator of the body’s ability to adapt to an exercise stimulus has been evaluated in many studies through HR variability (HRV) and post-exercise HR recovery (HRR). Recently, HR acceleration has also been investigated. Objective The aim of this systematic literature review and meta-analysis was to evaluate the effect of negative adaptations to endurance training (i.e., a period of overreaching leading to attenuated performance) and positive adaptations (i.e., training leading to improved performance) on autonomic HR regulation in endurance-trained athletes. Methods We searched Ovid MEDLINE, Embase, CINAHL, SPORTDiscus, PubMed, and Academic Search Premier databases from inception until April 2015. Included articles examined the effects of endurance training leading to increased or decreased exercise performance on four measures of autonomic HR regulation: resting and post-exercise HRV [vagal-related indices of the root-mean-square difference of successive normal R–R intervals (RMSSD), high frequency power (HFP) and the standard deviation of instantaneous beat-to-beat R–R interval variability (SD1) only], and post-exercise HRR and HR acceleration. Results Of the 5377 records retrieved, 27 studies were included in the systematic review and 24 studies were included in the meta-analysis. Studies inducing increases in performance showed small increases in resting RMSSD [standardised mean difference (SMD) = 0.58; P < 0.001], HFP (SMD = 0.55; P < 0.001) and SD1 (SMD = 0.23; P = 0.16), and moderate increases in post-exercise RMSSD (SMD = 0.60; P < 0.001), HFP (SMD = 0.90; P < 0.04), SD1 (SMD = 1.20; P = 0.04), and post-exercise HRR (SMD = 0.63; P = 0.002). A large increase in HR acceleration (SMD = 1.34) was found in the single study assessing this parameter. Studies inducing decreases in performance showed a small increase in resting RMSSD (SMD = 0.26; P = 0.01), but trivial changes in resting HFP (SMD = 0.04; P = 0.77) and SD1 (SMD = 0.04; P = 0.82). Post-exercise RMSSD (SMD = 0.64; P = 0.04) and HFP (SMD = 0.49; P = 0.18) were increased, as was HRR (SMD = 0.46; P < 0.001), while HR acceleration was decreased (SMD = −0.48; P < 0.001). Conclusions Increases in vagal-related indices of resting and post-exercise HRV, post-exercise HRR, and HR acceleration are evident when positive adaptation to training has occurred, allowing for increases in performance. However, increases in post-exercise HRV and HRR also occur in response to overreaching, demonstrating that additional measures of training tolerance may be required to determine whether training-induced changes in these parameters are related to positive or negative adaptations. Resting HRV is largely unaffected by overreaching, although this may be the result of methodological issues that warrant further investigation. HR acceleration appears to decrease in response to overreaching training, and thus may be a potential indicator of training-induced fatigue.
... Yet, applying Piiper and Scheid's diffusion model (Piiper & Scheid 1999) to Anderson and Saltin's one-leg knee extension data yields D O2 values per kilogram muscle that are close to double that found during two-leg cycling, and demonstrate the profound influence of flow onV O2 . With training, elevated blood flow and expanded capillary volume increase the number of red blood cells adjacent to contracting muscle fibres, and D O2 is increased in proportion to blood flow when transit time is maintained (Boushel et al. 2014). We suggest that a diffusion limitation atV O2max exists but is small, and when assessing the inter-relationships between flow, O 2 carriage by the blood and O 2 diffusion to tissue mitochondria, interpretations are context dependent as illustrated by the seminal findings of Saltin and Wagner. ...
Article
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Dr Wagner defends that increasing cardiac output will shorten red cell transit time reducing the time for O2 unloading and consequently limiting O2 diffusion (Wagner, 2015). This can only be true if O2 unloading is already diffusion-limited at V˙ O2max in normoxia. Moreover, these calculations neglect the possibility of changes in the regulation of mitochondrial p50 (Gnaiger, 2001) and changes in O2 diffusivity inside the muscle fibres (Honig & Gayeski, 1993). Moreover, we have recently shown that there is a remarkable functional reserve in muscle diffusing capacity (DMO2 ) at V˙ O2max. In healthy young men, DMO2 was 25.2 ± 5.2 and 46.0 ± 7.3 ml min−1 mmHg−1 in normoxia and acute hypoxia, respectively (Calbet et al. 2015). In the same experiment DMO2 was even higher (51.5 ± 9.7) during sprint exercise in hypoxia despite the fact that carboxyhaemoglobin (COHb) was increased to 7.3%. COHb left-shifted the oxygen dissociation curve, resulting in higher SaO2 during the sprint in hypoxia. The latter combined with an almost similar leg blood flow permitted a greater maximal leg O2 delivery during sprint than incremental exercise to exhaustion in hypoxia and, hence, a greater leg V˙ O2 , despite a similarly low PaO2 (33.3 vs. 34.1 mmHg). Thus, like at the lung, the skeletal muscle has a remarkable functional reserve in DMO2 at V˙ O2max in normoxia, which can be recruited during exercise in hypoxia (like at the lung). Thus, recent experimental evidence (Calbet et al. 2015; Morales-Alamo et al. 2015) indicates that DMO2 does not limit V˙ O2max (Lundby & Montero, 2015)
... It has been shown that arm muscle extracts less oxygen than leg muscle during exercise (Calbet et al. 2005), and this has been attributed among other factors to reduced mitochondrial oxidative capacity and muscle capillarization in the deltoid compared to the vastus lateralis (Calbet et al. 2005). Conversely, increasing triceps muscle capillarization with prolonged low-intensity exercise has been associated with increased arm oxygen extraction ( Boushel et al. 2014). Since PGC-1α stimulates angiogenesis ( Chinsomboon et al. 2009), the trend toward greater capillarization of the leg compared to the arm muscle described in a prior paper ( Ara et al. 2011) may well be linked to the observed higher PGC-1α expression in the leg than in the arm muscle. ...
Article
The aim of this study was to determine if the expression of the mitochondrial biogenesis-regulating proteins SIRT1, SIRT3 and PGC-1alpha in human skeletal muscle is influenced by adiposity. Twenty-nine male subjects were recruited into three groups: control (n = 10), obese (n = 10) and post-obese (n = 9). Intentionally, groups were matched by age, aerobic capacity and in addition the control and post-obese groups also by BMI. Muscle biopsies were obtained from the m. deltoid and vastus lateralis. PGC-1alpha, SIRT1 and SIRT3 protein expression was analyzed by Western blot. PGC-1alpha, SIRT1 and SIRT3 protein expression was similar regardless of the level of adiposity. Only a main effect of group on SIRT1 protein showed a trend toward higher expression in post-obese than control and obese (P = 0.09). Despite similar muscle fiber-type composition (previously reported), PGC-1alpha, SIRT1 and SIRT3 protein expression was higher in leg compared to arm muscle in all groups (P < 0.05). This study shows that PGC-1alpha, SIRT1 and SIRT3 protein expression in basal conditions was not altered in humans with different levels of adiposity but similar aerobic capacity. The expression of PGC-1alpha, SIRT1 and SIRT3 was higher in vastus lateralis than in deltoid muscle, indicating that local rather than systemic factors prevail in regulating the level of expression of these proteins.
... Swimming mainly involves upper limbs, which have different metabolic responses to exercise than lower limbs. Indeed, mitochondrial responses to training differ between arms and legs (Boushel et al., 2014). Moreover, Larsen et al. (2015) showed that in response to high-intensity training, the triceps brachii shows a greater oxidative stress than the quadriceps, leading to a robust expression of mitochondrial antioxidant enzymes. ...
Article
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Casuso, Rafael A., Jerónimo Aragón-Vela, Gracia López-Contreras, Silvana N. Gomes, Cristina Casals, Yaira Barranco-Ruiz, Jordi J. Mercadé, and Jesus R. Huertas. Does swimming at a moderate altitude favor a lower oxidative stress in an intensity-dependent manner? Role of nonenzymatic antioxidants. High-Alt Med Biol. 00:000-000, 2016-we aimed to describe oxidative damage and enzymatic and nonenzymatic antioxidant responses to swimming at different intensities in hypoxia. We recruited 12 highly experienced swimmers who have been involved in competitive swimming for at least 9 years. They performed a total of six swimming sessions carried out at low (LOW), moderate (MOD), or high (HIGH) intensity at low altitude (630 m) and at 2320 m above sea level. Blood samples were collected before the session (Pre), after the cool down (Post), and after 15 minutes of recovery (Rec). Blood lactate (BL) and heart rate were recorded throughout the main part of the session. Average velocities did not change between hypoxia and normoxia. We found a higher BL in response to MOD intensity in hypoxia. Plasmatic hydroperoxide level decreased at all intensities when swimming in hypoxia. This effect coincided with a lower glutation peroxidase activity and a marked mobilization of the circulating levels of α-tocopherol and coenzyme Q10 in an intensity-dependent manner. Our results suggest that, regardless of the intensity, no oxidative damage is found in response to hypoxic swimming in well-trained swimmers. Indeed, swimmers show a highly efficient antioxidant system by stimulating the mobilization of nonenzymatic antioxidants.
... The reduction in O 2 utilization in the face of a decline in O 2 delivery in the arms during combined exercise agrees with the previously discussed observations from studies utilizing handgrip exercise in which O 2 supply appears to be limiting oxidative metabolism both at the onset of exercise as well as during intense sustained contractions. Furthermore, a training-induced increase in peak arm muscle O 2 uptake during arm-cranking was also demonstrated to be an effect of increases in convective and diffuse O 2 transport (Boushel et al., 2014). It should be noted that during maximal exercise in untrained individuals, O 2 saturation in the venous drainage of the legs (femoral vein) reaches levels of~15% (Mortensen et al., 2005;Mortensen et al., 2008), whereas venous blood returning from the arms (subclavian vein) remains 40% saturated (Volianitis et al., 2004). ...
Article
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Skeletal muscle is one of the most dynamic metabolic organs as evidenced by increases in metabolic rate of >150-fold from rest to maximal contractile activity. Because of limited intracellular stores of ATP, activation of metabolic pathways is required to maintain the necessary rates of ATP re-synthesis during sustained contractions. During the very early phase, phosphocreatine hydrolysis and anaerobic glycolysis prevails but as activity extends beyond ∼1 min, oxidative phosphorylation becomes the major ATP-generating pathway. Oxidative metabolism of macronutrients is highly dependent on the cardiovascular system to deliver O2 to the contracting muscle fibres, which is ensured through a tight coupling between skeletal muscle O2 utilization and O2 delivery. However, to what extent O2 delivery is ideal in terms of enabling optimal metabolic and contractile function is context-dependent and determined by a complex interaction of several regulatory systems. The first part of the review focuses on local and systemic mechanisms involved in the regulation of O2 delivery and how integration of these influences the matching of skeletal muscle O2 demand and O2 delivery. In the second part, alterations in cardiovascular function and structure associated with aging and heart failure, and how these impact metabolic and contractile function, will be addressed. Where applicable, the potential of exercise training to offset/reverse age- and disease-related cardiovascular declines will be highlighted in the context of skeletal muscle metabolic function. The review focuses on human data but also covers animal observations.
... How this is obtained remains unclear (Holmberg, 2015). VSC skiers report high volumes of upper body training (see Table 1), and an earlier investigation reported that high-volume, low-intensity training improved arm crank VO 2peak (Boushel et al., 2014). ...
Article
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Longer distance cross-country ski (14-220 km) races such as the Visma Ski Classics (VSC) has recently gained attention in addition to the traditional Olympic distances (5-50 km) associated with cross-country (XC) skiing. These long-distance races are characterized by extensive use of the upper body while double poling (DP). While there is a substantial amount of research on Olympic distance XC skiing, the physiological capacities of VSC skiers has not yet been explored. We recruited seven elite male VSC skiers and seven well-trained national level male XC skiers to undergo three tests in the laboratory: (1) a one repetition maximum (1RM) strength test in a cable pulldown; (2) roller skiing tests on a treadmill (10.5% inclination) for determination of gross efficiency (GE) at submaximal speeds (8 and 10 km·h-1) in DP and diagonal stride (DS); (3) two ramp protocols to exhaustion (15% inclination, starting speed 7 km·h-1) in DP and DS for the assessment of peak and maximal oxygen uptake ( V . O2peak and V . O2max), respectively. Compared with the national level XC skiers, the VSC skiers performed similar in the 1RM cable pulldown, displayed 12.2% higher GE in DP at 8 km·h-1 but did not display any difference at 10 km·h-1, and had lower blood lactate concentration and heart rate at both submaximal speeds. The VSC skiers had longer time to exhaustion compared with the national level XC skiers during the two ramp protocols in DS (18%) and in DP (29%). The V . O2max was 10% higher in DS compared with DP, with no differences between the groups. The V . O2peak/ V . O2max-ratio of 90% did not differ between the two groups. In conclusion, the main differences were lower cardiorespiratory and metabolic responses at submaximal speeds as well as longer time to exhaustion in VSC skiers compared with national level XC skiers. This suggest efficiency to be the main difference between VSC and national level XC skiers.
... It has earlier been speculated by Nielsen and coworkers (2017) that mitochondrial cristae density is plastic to endurance training based on previous findings showing an increase in intrinsic respiration following endurance training (Boushel et al., 2014;Pesta et al., 2011). Unfortunately, the findings in the referenced studies are based upon problematic evidence highlighted in a letter from Larsen and colleagues (2017). ...
Article
Introduction: High intensity interval training (HIIT) has shown to be as effective as moderate intensity endurance training to improve metabolic health. However, the current knowledge on the effect of HIIT in older individuals is limited and it is uncertain whether the adaptations are sex specific. The aim was to investigate effects of HIIT on mitochondrial respiratory capacity and mitochondrial content in older females and males. Methods: Twenty-two older sedentary males (n = 11) and females (n = 11) completed 6 weeks of supervised HIIT 3 days per week. The training consisted of 5 × 1 min cycling (124 ± 3% of max power output at session 2–6 and 135 ± 3% of max power output at session 7–20) interspersed by 1½ min recovery. Before the intervention and 72 h after last training session a muscle biopsy was obtained and mitochondrial respiratory capacity, citrate synthase activity and proteins involved in mitochondria metabolism were assessed. Furthermore, body composition and ⩒O2max were measured. Results: ⩒O2max increased and body fat percentage decreased after HIIT in both sexes (p < 0.05). In addition, CS activity and protein content of MnSOD and complex I-V increased in both sexes. Coupled and uncoupled mitochondrial respiratory capacity increased only in males. Mitochondrial respiratory capacity normalised to CS activity (intrinsic mitochondrial respiratory capacity) did not change following HIIT. Conclusion: HIIT induces favourable adaptions in skeletal muscle in older subjects by increasing mitochondrial content, which may help to maintain muscle oxidative capacity and slow down the process of sarcopenia associated with ageing.
... In the present study, muscle fibre hypertrophy was accompanied by only a minor increase in the capillary-to-fibre ratio, causing no change in capillary density. If we calculate the capillary volume within the leg muscle mass engaged during cycling 1 3 (Boushel et al. 2014) and subtract a non-leg blood flow of 6.5 l min −1 from the total Q peak (Calbet et al. ,2006Lundby et al. 1985;Mortensen et al. 2005), there would be a trend towards shorter erythrocyte MTT after ET during upright peak exercise (508 ± 138 vs 452 ± 132 ms before and after ET, respectively). Therefore, due to reduced time for O 2 unloading, peripheral adaptations such as increased muscle oxidative capacity (CS and COX-IV) may have been crucial in maintaining the pre-ET level of a-vO 2 diff. ...
Article
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Purpose: The endurance training (ET)-induced increases in peak oxygen uptake (VO2peak) and cardiac output (Qpeak) during upright cycling are reversed to pre-ET levels after removing the training-induced increase in blood volume (BV). We hypothesised that ET-induced improvements in VO2peak and Qpeak are preserved following phlebotomy of the BV gained with ET during supine but not during upright cycling. Arteriovenous O2 difference (a-vO2diff; VO2/Q), cardiac dimensions and muscle morphology were studied to assess their role for the VO2peak improvement. Methods: Twelve untrained subjects (VO2peak: 44 ± 6 ml kg-1 min-1) completed 10 weeks of supervised ET (3 sessions/week). Echocardiography, muscle biopsies, haemoglobin mass (Hbmass) and BV were assessed pre- and post-ET. VO2peak and Qpeak during upright and supine cycling were measured pre-ET, post-ET and immediately after Hbmass was reversed to the individual pre-ET level by phlebotomy. Results: ET increased the Hbmass (3.3 ± 2.9%; P = 0.005), BV (3.7 ± 5.6%; P = 0.044) and VO2peak during upright and supine cycling (11 ± 6% and 10 ± 8%, respectively; P ≤ 0.003). After phlebotomy, improvements in VO2peak compared with pre-ET were preserved in both postures (11 ± 4% and 11 ± 9%; P ≤ 0.005), as was Qpeak (9 ± 14% and 9 ± 10%; P ≤ 0.081). The increased Qpeak and a-vO2diff accounted for 70% and 30% of the VO2peak improvements, respectively. Markers of mitochondrial density (CS and COX-IV; P ≤ 0.007) and left ventricular mass (P = 0.027) increased. Conclusion: The ET-induced increase in VO2peak was preserved despite removing the increases in Hbmass and BV by phlebotomy, independent of posture. VO2peak increased primarily through elevated Qpeak but also through a widened a-vO2diff, potentially mediated by cardiac remodelling and mitochondrial biogenesis.
... Leg VO 2 was calculated as the product of LBF and the a-vO 2 diff. Muscle O 2 diffusion capacity (MDO 2 ) was calculated by an integration procedure incorporating the measured LBF, arterial and venous O 2 pressures, extraction and VO 2 at peak exercise across the leg to determine mean capillary PO 2. 43,44 Additionally, the following assumptions were made (i) MDO 2 is constant along the capillary, (ii) perfusion and/or VO 2 heterogeneity and perfusional/diffusional shunt are considered negligible. 43 ...
Article
Aim We examined the Fick components together with mitochondrial O2 affinity (p50mito) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER). Methods Seven individuals performed two incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and two on a one‐legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP‐stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibers and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery. Results The ex vivo p50mito increased from 0.06±0.02 to 0.17±0.04 kPa with varying substrate supply and O2 flux rates from 9.84±2.91 to 16.34±4.07 pmol O2·s⁻¹·μg⁻¹ respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery, and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time. Conclusion O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise. This article is protected by copyright. All rights reserved.
... There are several lines of evidence in support of significant sympathetic vasoconstrictor influences over local vasodilation in muscle during exercise in healthy humans, including the following examples: 1) increases in locomotor muscle vascular conductance and blood flow that occur via ␣-adrenergic blockade in rhythmically exercising humans and dogs (16,44,75); 2) the compromised leg vascular conductance and blood flow observed at near maximal and maximal exercise during twolegged cycling but not during one-legged knee extension exercise (55); 3) the reduced vascular conductance and flow in the vasculature of the arms and trunk relative to the legs during two-legged cycling at-and near-maximal work rates (17,38); and 4) the specific preferential effects of training of the arms, which increased peak exercise work rate with the arms and increased the share of cardiac output to the arms, while maintaining the share of total flow to the trunk and reducing it to the legs: the latter achieved presumably via an enhanced sympathetic vasoconstriction (15). ...
Article
Sympathetically-induced vasoconstrictor modulation of local vasodilation occurs in contracting skeletal muscle during exercise to ensure appropriate perfusion of a large active muscle mass and to also maintain arterial blood pressure. In this synthesis, we discuss the contribution of group III-IV muscle afferents to the sympathetic modulation of blood flow distribution to locomotor and respiratory muscles during exercise. This is followed by an examination of the conditions under which diaphragm and locomotor muscle fatigue occur. Emphasis is given to those studies in humans and animal models that experimentally changed respiratory muscle work to evaluate blood flow redistribution and its effects on locomotor muscle fatigue; and conversely, those that evaluated the influence of coincident limb muscle contraction on respiratory muscle blood flow and fatigue. We propose the concept of a "two-way street of sympathetic vasoconstrictor activity" emanating from both limb and respiratory muscle metaboreceptors during exercise, which constrains blood flow and O2 transport thereby promoting fatigue of both sets of muscles. We end with considerations of a hierarchy of blood flow distribution during exercise between respiratory vs. locomotor musculatures and the clinical implications of muscle afferent feedback influences on muscle perfusion, fatigue and exercise tolerance.
... These changes in fiber metabolic characteristics are clearly not fiber-type-dependent, and a considerable variation exists within each fiber type with a clear overlay between fiber types. In line with this, a recent study indicated that type 2a fibers can possess equally high or even higher mitochondrial respiration as type 1 fibers (Boushel et al., 2014). The equal volume density of mitochondria and CS activity in different types of fibers suggest that the intrinsic characteristics of mitochondria are variable and not determined solely by fiber type. ...
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As one of the most physically demanding sports in the Olympic Games, cross-country skiing poses considerable challenges with respect to both force generation and endurance during the combined upper- and lower-body effort of varying intensity and duration. The isoforms of myosin in skeletal muscle have long been considered not only to define the contractile properties, but also to determine metabolic capacities. The current investigation was designed to explore the relationship between these isoforms and metabolic profiles in the arms (triceps brachii) and legs (vastus lateralis) as well as the range of training responses in the muscle fibers of elite cross-country skiers with equally and exceptionally well-trained upper and lower bodies. The proportion of myosin heavy chain (MHC)-1 was higher in the leg (58 ± 2% [34–69%]) than arm (40 ± 3% [24–57%]), although the mitochondrial volume percentages [8.6 ± 1.6 (leg) and 9.0 ± 2.0 (arm)], and average number of capillaries per fiber [5.8 ± 0.8 (leg) and 6.3 ± 0.3 (arm)] were the same. In these comparable highly trained leg and arm muscles, the maximal citrate synthase (CS) activity was the same. Still, 3-hydroxy-acyl-CoA-dehydrogenase (HAD) capacity was 52% higher (P < 0.05) in the leg compared to arm muscles, suggesting a relatively higher capacity for lipid oxidation in leg muscle, which cannot be explained by the different fiber type distributions. For both limbs combined, HAD activity was correlated with the content of MHC-1 (r2 = 0.32, P = 0.011), whereas CS activity was not. Thus, in these highly trained cross-country skiers capillarization of and mitochondrial volume in type 2 fiber can be at least as high as in type 1 fibers, indicating a divergence between fiber type pattern and aerobic metabolic capacity. The considerable variability in oxidative metabolism with similar MHC profiles provides a new perspective on exercise training. Furthermore, the clear differences between equally well-trained arm and leg muscles regarding HAD activity cannot be explained by training status or MHC distribution, thereby indicating an intrinsic metabolic difference between the upper and lower body. Moreover, trained type 1 and type 2A muscle fibers exhibited similar aerobic capacity regardless of whether they were located in an arm or leg muscle.
... The reason for this difference is probably related to the amount of muscle tissue, such that when considering total tissue volume, the arms have a smaller fraction of oxygen extraction when compared with the legs (Clausen et al. 1973). The arms have demonstrated a great capacity to improve in peak oxygen consumption with training [~ 10% increase (Clausen et al. 1973); 11.4% increase in arms compared with 7.9% in legs during a 5-min time-trial, and 52% increase in arms and only 6% in legs with Wingate (Zinner et al. 2016); and muscle oxygen consumption (Boushel et al. 2014)] in comparison with the legs. However, it remains practically uncertain how to improve oxygen extraction with training, particularly in the arms (Holmberg 2015). ...
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Purpose The aim was to compare changes in peripheral and cerebral oxygenation, as well as metabolic and performance responses during conditions of blood flow restriction (BFR, bilateral vascular occlusion at 0% vs. 45% of resting pulse elimination pressure) and systemic hypoxia (~ 400 m, FIO2 20.9% vs. ~ 3800 m normobaric hypoxia, FIO2 13.1 ± 0.1%) during repeated sprint tests to exhaustion (RST) between leg- and arm-cycling exercises. Methods Seven participants (26.6 ± 2.9 years old; 74.0 ± 13.1 kg; 1.76 ± 0.09 m) performed four sessions of RST (10-s maximal sprints with 20-s recovery until exhaustion) during both leg and arm cycling to measure power output and metabolic equivalents as well as oxygenation (near-infrared spectroscopy) of the muscle tissue and prefrontal cortex. Results Mean power output was lower in arms than legs (316 ± 118 vs. 543 ± 127 W; p < 0.001) and there were no differences between conditions for a given limb. Arms demonstrated greater changes in concentration of deoxyhemoglobin (∆[HHb], − 9.1 ± 6.1 vs. − 6.5 ± 5.6 μm) and total hemoglobin concentration (∆[tHb], 15.0 ± 10.8 vs. 11.9 ± 7.9 μm), as well as the absolute maximum tissue saturation index (TSI, 62.0 ± 8.3 vs. 59.3 ± 8.1%) than legs, respectively (p < 0.001), demonstrating a greater capacity for oxygen extraction. Further, there were greater changes in tissue blood volume [tHb] during BFR only compared to all other conditions (p < 0.01 for all). Conclusions The combination of BFR and/or hypoxia led to increased changes in [HHb] and [tHb] likely due to greater vascular resistance, to which arms were more responsive than legs.
... Also the accompanying improvements in global and physical aspects of Quality of Life (four included studies assessing Quality of Life found clinical relevant changes) indicated the improvement in VO 2 peak being of clinical relevance [21,[25][26][27]. Aerobic training has been shown to effect several central and peripheral CV adap- tations such as improved cardiac output, decreased peripheral vascular resistance, higher blood volume, expanded capillary volume and increased peripheral O 2 -extraction, improving maximal oxygen uptake [36], with shear stress as key factor in vascular adaptations [37]. It is well documented that plasma volume expands up to 25% after 10-14 exercise sessions through increased plasma albumin levels and sodium retention in sedentary healthy subjects. ...
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Background CKD is associated with several comorbidities, cardiovascular disease being the most significant. Aerobic training has a beneficial effect on cardiovascular health in healthy and some well-defined non-healthy populations. However, the effect of aerobic training on glomerular filtration rate in patients with CKD stages 3–4 is unclear. Objective To review the effects of aerobic exercise training on kidney and cardiovascular function in patients with chronic kidney disease (CKD) stages 3–4. Methods A random-effects meta-analysis was performed to analyse published randomized controlled trials through February 2018 on the effect of aerobic training on estimated glomerular filtration rate, blood pressure and exercise tolerance in patients with CKD stages 3–4. Web of Science, PubMed and Embase databases were searched for eligible studies. Results 11 randomized controlled trials were selected including 362 participants in total. Favourable effects were observed on estimated glomerular filtration rate (+2.16 ml/min per 1.73m²; [0.18; 4.13]) and exercise tolerance (+2.39 ml/kg/min; [0.99; 3.79]) following an on average 35-week aerobic training program when compared to standard care. No difference in change in blood pressure was found. Conclusions There is a small beneficial effect of aerobic training on estimated glomerular filtration rate and exercise tolerance, but not on blood pressure, in patients with CKD stages 3–4. However, data are limited and pooled findings were rated as of low to moderate quality.
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To determine the accuracy and precision of constant infusion transpulmonary thermodilution cardiac output (CITT-Q) assessment during exercise in humans, using indocyanine green (ICG) dilution and bolus transpulmonary thermodilution (BTD) as reference methods, cardiac output (Q) was determined at rest and during incremental one- and two-legged pedaling on a cycle ergometer, and combined arm cranking with leg pedaling to exhaustion in 15 healthy men. Continuous infusions of iced saline in the femoral vein (n = 41) or simultaneously in the femoral and axillary (n = 66) veins with determination of temperature in the femoral artery were used for CITT-Q assessment. CITT-Q was linearly related to ICG-Q (r = 0.82, CITT-Q = 0.876 × ICG-Q + 3.638, P < 0.001; limits of agreement ranging from -1.43 to 3.07 L/min) and BTD-Q (r = 0.91, CITT-Q = 0.822 × BTD + 4.481 L/min, P < 0.001; limits of agreement ranging from -1.01 to 2.63 L/min). Compared with ICG-Q and BTD-Q, CITT-Q overestimated cardiac output by 1.6 L/min (≈ 10% of the mean ICG and BTD-Q values, P < 0.05). For Q between 20 and 28 L/min, we estimated an overestimation < 5%. The coefficient of variation of 23 repeated CITT-Q measurements was 6.0% (CI: 6.1-11.1%). In conclusion, cardiac output can be precisely and accurately determined with constant infusion transpulmonary thermodilution in exercising humans. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Thesis
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This thesis includes four research papers, based on four separate studies aiming to elucidate the importance of O2 extraction and blood volume (BV) for maximal O2 uptake (VO2max). In study I, twelve untrained subjects (VO2max: 44 ml · kg-1 · min-1) completed ten weeks of supervised endurance training (three sessions per week). VO2max and maximal cardiac output (Qmax) were measured during upright and supine cycling before and after training, as well as immediately after the training-induced gain in BV was reversed by blood withdrawal. The supine position increases venous return to the heart and may thus counteract potential adverse effects of blood withdrawal. The BV increased by 4% (~2 dl) with training. After reversing BV to the pre-training level, VO2max and Qmax remained 11% and 9% higher than before training, respectively, regardless of exercise position. By using the Fick principle (VO2 = Q × a-v ̅O2diff), it was calculated that 30% and 70% of the increase in VO2max was attributed to increased O2 content difference between arterial and mixed venous blood (a-v ̅O2diff) and increased Qmax, respectively. These improvements coincided with increased protein content of mitochondrial enzymes, a small increase in the capillary-to-fibre ratio (m. vastus lateralis) and an increased left ventricular mass (echocardiography). Thus, VO2max may increase with endurance training independent of BV expansion, caused by combined central and peripheral adaptations. In study II, thirteen subjects (VO2max: 63 ml · kg-1 · min-1) performed maximal exercise on a cycle ergometer in three experimental conditions: with normal BV and immediately after acute BV reductions of 150 ml and 450 ml, representing 2.5% and 7.6% of the total BV (6.0 l), respectively. After the 150 ml reduction, VO2max was preserved compared with the control test (non-significant reduction of 1%), likely caused by a rapid plasma volume (PV) restoration (calculated from changes in haematocrit and haemoglobin concentration). After the 450 ml BV reduction, VO2max was reduced by 7% despite partial PV restoration, increased maximal heart rate and increased leg O2 extraction as indicated by near-infrared spectroscopy. The reduction in VO2max was 2.5-fold larger after withdrawing 450 compared with 150 ml blood after normalising to the BV removed. Therefore, the body may cope with small but not moderate blood loss to preserve VO2max. These data may enhance our understanding regarding the impact of, e.g., acute BV manipulations, PV reduction following dehydration induced by prolonged exercise or hyperthermia, or daily oscillations of PV. In study III, the muscle oxidative capacity in one leg was increased by six weeks of one-legged endurance training (3-4 sessions per week) in nine subjects (VO2max: 56 ml · kg-1 · min-1). The impact on leg O2 extraction fraction (arterial and femoral venous catheters) vs the untrained control leg was investigated during dynamic two-legged knee extension exercise with both legs performing the same power output. This exercise model involves a small muscle mass, does not tax Qmax and is thus not perfusion limited. Therefore, the muscle oxidative capacity may potentially be the principal limiting factor for O2 extraction and VO2 before training. At low to moderate exercise intensities, O2 extraction fraction was similar in both legs. At higher exercise intensities, which are associated with greater mitochondrial activation and lower time for haemoglobin-O2 off-loading, the O2 extraction fraction was increased in the trained leg. The between-leg difference in O2 extraction correlated with the between-leg difference in mitochondrial protein content (m. vastus lateralis). Therefore, our data suggest that endurance training improves O2 extraction in exercise models where the mitochondria do not possess an apparent excess oxidative capacity over O2 delivery, particularly when the exercise intensity is close to maximal. In study IV, the relationships between pulmonary VO2max and systemic and leg O2 extraction fractions were investigated by statistically analysing data from 43 previously published catheterisation studies, comprising 377 subjects. It was observed that a-v ̅O2diff (mostly calculated by the Fick principle, and Qmax measured by the indicator-dilution method) increased curvilinearly and reached its maximum at ~4.5 l · min-1 in VO2max (moderately trained subjects), and was, if anything, slightly lower in those subjects with the highest VO2max (> 5 l · min-1). However, after accounting for the hypoxemia-induced lowering of arterial O2 content (CaO2) with increasing VO2max, the calculated systemic O2 extraction fraction (a-v ̅O2diff / CaO2) increased with VO2max up to ~4.5-5.0 l · min-1 and approached a plateau at ~90%. This pattern was strengthened by the direct measurements using arterial and femoral venous catheters, with leg O2 extraction fraction increasing progressively with VO2max until reaching ~90-95%. These analyses emphasise that a-v ̅O2diff and systemic O2 extraction fraction cannot be used interchangeably, and that the systemic and peripheral O2 extraction fractions improves with increasing VO2max and training status. By using the theoretical model of Piiper and Scheid, it appeared that the limiting factors to VO2max change with increasing VO2max: untrained, but healthy individuals display mixed perfusion-diffusion limitations, and this diffusion limitation reduces as VO2max increase.
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Chronic heart failure (CHF) impairs critical structural and functional components of the O2 transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing skeletal muscle O2 delivery-utilization matching (QmO2 and VmO2, respectively). The QmO2/VmO2 ratio determines the microvascular O2 partial pressure (PmvO2) which represents the ultimate force driving blood-myocyte O2 flux (Figure 1). Improvements in perfusive and diffusive O2 conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster VmO2 kinetics during metabolic transitions) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2 deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations and improved physical capacity (i.e., elevated critical power and maximal VmO2). This brief review focuses on the mechanistic bases for improved QmO2/VmO2 matching (and enhanced PmvO2) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O2 convection within the muscle microcirculation, O2 diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs are also presented in light of their therapeutic potential. Adaptations within the skeletal muscle O2 transport and utilization system underlie improvements in physical capacity and quality of life in CHF and thus take center stage in the therapeutic management of these patients. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
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Background: Children with repaired congenital heart disease (CHD) have impaired maximal aerobic capacity (VO2max). Determining the causes of their VO2max alteration remains challenging. Cardiac output measure using thoracic impedancemetry during cardiopulmonary exercise tests (CPET) can help to understand the determinants of VO2max in children with open-heart repaired CHD. Method: We analyzed CPET in 77 children with repaired CHD. Among them, 55 patients had residual lesions. Patients with repaired CHD were compared with 44 age-matched healthy individuals. Maximal oxygen content brought to capillaries (QO2max) and oxygen muscle diffusion capacity (DO2) were assessed using cardiac output measure, Fick principle and simplified Fick law. Results: In the 55 patients with residual lesion, VO2max, QO2max and DO2 were lower than those of controls (76.1 vs 86% of theoretical value, p < 0.01; 2.15 vs 2.81 L/mn, p < 0.001; 24.7 vs 28.8 ml/min/mmHg, p < 0.05). Decrease in QO2max was due to both impaired stroke volume and chronotropic insufficiency (48 vs 53 ml/m2 and p < 0.05; 171 vs 185/min p < 0.001). Patients without residual lesion (22/77) had normal VO2max with lower maximal heart rate compensated by higher SV (p < 0.05). Conclusion: Aerobic capacity was normal in children without residual lesions after CHD repair. Patients with residual lesion have impaired VO2max due to both lower central and peripheral determinants. Measuring cardiac performance during CPET allowed a better selection of patients with altered cardiac reserve that can benefit from residual lesion treatment and find the good timing for intervention. Detection of peripheral deconditioning can lead to a rehabilitation program.
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In humans, arm exercise is known to elicit larger increases in arterial blood pressure (BP) than leg exercise. However, the precise regulation of regional vascular conductances (VC) for the distribution of cardiac output with exercise intensity remains unknown. Hemodynamic responses were assessed during incremental upright arm cranking (AC) and leg pedalling (LP) to exhaustion (Wmax) in nine males. Systemic VC, peak cardiac output (Qpeak) (indocyanine green) and stroke volume (SV) were 18%, 23%, and 20% lower during AC than LP. The mean BP, the rate-pressure product and the associated myocardial oxygen demand were 22%, 12%, and 14% higher, respectively, during maximal AC than LP. Trunk VC was reduced to similar values at Wmax. At Wmax, muscle mass-normalized VC and fractional O2 extraction were lower in the arm than the leg muscles. However, this was compensated for during AC by raising perfusion pressure to increase O2 delivery, allowing a similar peak VO2 per kg of muscle mass in both extremities. In summary, despite a lower Qpeak during arm cranking the cardiovascular strain is much higher than during leg pedalling. The adjustments of regional conductances during incremental exercise to exhaustion depend mostly on the relative intensity of exercise and are limb-specific.
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Successful cross-country skiing, one of the most demanding of endurance sports, involves considerable physiological challenges posed by the combined upper- and lower-body effort of varying intensity and duration, on hilly terrain, often at moderate altitude and in a cold environment. Over the years, this unique sport has helped physiologists gain novel insights into the limits of human performance and regulatory capacity. There is a long-standing tradition of researchers in this field working together with coaches and athletes to improve training routines, monitor progress, and refine skiing techniques. This review summarizes research on elite cross-country skiers, with special emphasis on the studies initiated by Professor Bengt Saltin. He often employed exercise as a means to learn more about the human body, successfully engaging elite endurance athletes to improve our understanding of the demands, characteristics, and specific effects associated with different types of exercise.
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During evolution, mitochondrial DNA haplogroups of arctic populations may have been selected for lower coupling of mitochondrial respiration to ATP production in favor of higher heat production. We show that mitochondrial coupling in skeletal muscle of traditional and westernized Inuit habituating northern Greenland is identical to Danes of western Europe haplogroups. Biochemical coupling efficiency was preserved across variations in diet, muscle fiber type, and uncoupling protein-3 content. Mitochondrial phenotype displayed plasticity in relation to lifestyle and environment. Untrained Inuit and Danes had identical capacities to oxidize fat substrate in arm muscle, which increased in Danes during the 42 days of acclimation to exercise, approaching the higher level of the Inuit hunters. A common pattern emerges of mitochondrial acclimatization and evolutionary adaptation in humans at high latitude and high altitude where economy of locomotion may be optimized by preservation of biochemical coupling efficiency at modest mitochondrial density, when submaximum performance is uncoupled from VO2max and maximum capacities of oxidative phosphorylation.
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Background: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with a pressing shortage of therapies. Exercise intolerance is a cardinal symptom of HFpEF, yet its pathophysiology remains uncertain. Methods: We investigated the mechanism of exercise intolerance in 134 patients referred for cardiopulmonary exercise testing: 79 with HFpEF and 55 controls. We performed cardiopulmonary exercise testing with invasive monitoring to measure hemodynamics, blood gases, and gas exchange during exercise. We used these measurements to quantify 6 steps of oxygen transport and utilization (the O2 pathway) in each patient with HFpEF, identifying the defective steps that impair each one's exercise capacity (peak Vo2). We then quantified the functional significance of each O2 pathway defect by calculating the improvement in exercise capacity a patient could expect from correcting the defect. Results: Peak Vo2 was reduced by 34±2% (mean±SEM, P<0.001) in HFpEF compared with controls of similar age, sex, and body mass index. The vast majority (97%) of patients with HFpEF harbored defects at multiple steps of the O2 pathway, the identity and magnitude of which varied widely. Two of these steps, cardiac output and skeletal muscle O2 diffusion, were impaired relative to controls by an average of 27±3% and 36±2%, respectively (P<0.001 for both). Due to interactions between a given patient's defects, the predicted benefit of correcting any single one was often minor; on average, correcting a patient's cardiac output led to a 7±0.5% predicted improvement in exercise intolerance, whereas correcting a patient's muscle diffusion capacity led to a 27±1% improvement. At the individual level, the impact of any given O2 pathway defect on a patient's exercise capacity was strongly influenced by comorbid defects. Conclusions: Systematic analysis of the O2 pathway in HFpEF showed that exercise capacity was undermined by multiple defects, including reductions in cardiac output and skeletal muscle diffusion capacity. An important source of disease heterogeneity stemmed from variation in each patient's personal profile of defects. Personalized O2 pathway analysis could identify patients most likely to benefit from treating a specific defect; however, the system properties of O2 transport favor treating multiple defects at once, as with exercise training.
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Is this true? As an editor, you actually have a chance to get to the bottom of this question by taking a measure for quality (downloads or citations) and correlating that with the referees' scoring. The results are indeed surprising, as demonstrated by our five most-cited original articles in 2014 (Wall et al., 2014, Pruis et al., 2014, Boushel et al., 2014, Yu et al., 2014, Dirks et al., 2014) and 2015(Dahl et al., 2015, Heimlich et al., 2015, Uchida et al., 2015, Tam et al., 2015, Chen et al., 2015). This article is protected by copyright. All rights reserved.
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Cardiac function, skeletal (soleus) muscle oxidative metabolism and the effects of exercise training were evaluated in a transgenic murine model (Tgαq*44) of chronic heart failure (CHF) during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e. from 10 to 12 months of age). Forty-eight Tgαq*44 mice and 43 wild-type (WT) FVB controls were randomly assigned to control groups and to groups undergoing 2 months of intense exercise training (spontaneous running on a instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype (myosin heavy chain [MHC] isoforms content; citrate synthase [CS] activity) and variables related to the energy status of muscle fibers (p-AMPK/AMPK) and mitochondrial biogenesis and function (PGC-1α). In the untrained Tgαq*44 mice functional impairments of exercise performance, cardiac function and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased % of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance.
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With considerable interest, we are following developments concerning the increasingly popular practice of breathing oxygen (O2)-enriched air (normobaric hyperoxia) in an attempt to improve both athletic performance and recovery, especially by elite endurance athletes. Administration of supplemental O2 is not prohibited by the World Anti-Doping Agency, and indeed, there is striking evidence that when administered at sea-level, hyperoxia (i.e., an inspired fraction of O2 (FiO2) greater than normoxic FiO2 >0.2095) improves power output by 2.4–16.5% during both maximal and submaximal cycling. Hyperoxia increases the arterial O2 pressure (PaO2), the saturation of hemoglobin (Hb) with O2 (SaO2), and the amount of oxygen dissolved in the plasma. Consequently, the arterial oxygen content (CaO2) is greater during hyperoxic breathing, implying that for a given cardiac output systemic O2 delivery, which has been shown to be a major determinant of VO2max and endurance, is enhanced . From a practical point of view, an athlete could benefit from hyperoxia in three different ways: 1. Improvement of performance when hyperoxia is administered during exercise (as illustrated in Fig. 1) 2. Faster recovery between bouts of exercise 3. Enhancement of the effects of training through concomitant use of hyperoxia
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Over the last 50 years, Bengt Saltin's contributions to our understanding of physiology of the circulation, the matching of the circulation to muscle metabolism, and the underlying mechanisms that set the limits for exercise performance were enormous. His research addressed the key questions in the field using sophisticated experimental methods including field expeditions. From the Dallas Bedrest Study to the 1-leg knee model to the physiology of lifelong training, his prodigious body of work was foundational in the field of exercise physiology and his leadership propelled integrative human physiology into the mainstream of biological sciences.
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[Purpose] This study aims to investigate the effects of upper-limb exercises on the respiratory functions of stroke patients. [Subjects and Methods] This study was performed with 25 stroke patients. The subjects were divided into the control group (n=12) which did not perform upper arm training and the experimental group (n=13) which conducted upper arm training. Forced vital capacity and forced expiratory volume in the first second, both of which are used in this study, are well-known indicators of respiratory capabilities. Peak cough flow is used to indicate cough capability. [Results] Concerning changes in forced vital capacity, forced expiratory volume in the first second and the peak cough flow of each group after the exercise, while the control group did not show significant differences, the experimental group showed statistically significant increases. [Conclusion] The results of the study indicate that exercise programs that increase the mobility of upper limbs and increase muscular strength have the effect of normalizing vertebral alignment for stroke patients, and thus can provide effective interventions for improving respiratory function.
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The vascular strain is very high during heavy handgrip exercise, but the intensity and kinetics to reach peak blood flow, and peak oxygen uptake, are uncertain. We included 9 young (25±2yr) healthy males to evaluate blood flow and oxygen uptake responses during continuous dynamic handgrip exercise with increasing intensity. Blood flow was measured using Doppler-ultrasound and venous blood was drawn from a deep forearm vein to determine arteriovenous oxygen difference (a-vO2diff) during 6-minutes bouts of 60, 80 and 100% of maximal work rate (WRmax), respectively. Blood flow and oxygen uptake increased (p<0.05) from 60%WRmax (557±177(SD) mL∙min(-1); 56.0±21.6 mL∙min(-1)) to 80%WRmax (679±190 mL∙min(-1); 70.6±24.8 mL∙min(-1)), but no change was seen from 80%WRmax to 100%WRmax Blood velocity (49.5±11.5 cm∙sec(-1) to 58.1±11.6 cm∙sec(-1)) and brachial diameter (0.49±0.05cm to 0.50±0.06 cm) showed concomitant increases (p<0.05) with blood flow from 60% to 80%WRmax, while no differences were observed in a-vO2diff Shear rate also increased (p<0.05) from 60% (822±196 s(-1)) to 80% (951±234 s(-1)) of WRmax The mean response time (MRT) was slower (p<0.05) for blood flow (60%WRmax:50±22s; 80%WRmax:51±20s; 100%WRmax:51±23s) than a-vO2diff (60%WRmax:29±9s; 80%WRmax:29±5s; 100%WRmax:20±5s), but not different from oxygen uptake (60%WRmax:44±25s; 80%WRmax:43±14s; 100%WRmax:41±32s). No differences were observed in MRT for blood flow or oxygen uptake with increased exercise intensity. In conclusion, when approaching maximal intensity, oxygen uptake appeared to reach a critical level at ~80% of WRmax and be regulated by blood flow. This implies that high, but not maximal, exercise intensity may be an optimal stimulus for shear stress-induced small muscle mass training adaptations.
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One in five adults following physical activity guidelines are reported to not demonstrate any improvement in cardiorespiratory fitness (CRF). Herein, we sought to establish whether CRF non-response to exercise training is dose-dependent, using a between- and within-subject study design. Seventy-eight healthy adults were divided into five groups (1–5) respectively comprising one, two, three, four and five 60 min exercise sessions per week but otherwise following an identical 6-week endurance training (ET) programme. Non-response was defined as any change in CRF, determined by maximal incremental exercise power output (Wmax), within the typical error of measurement (±3.96%). Participants classified as non-responders after the ET intervention completed a successive 6-week ET period including two additional exercise sessions per week. Maximal oxygen consumption (V̇O2 max ), haematology and muscle biopsies were assessed prior to and after each ET period. After the first ET period, Wmax increased (P < 0.05) in groups 2, 3, 4 and 5, but not 1. In groups 1, 2, 3, 4 and 5, 69%, 40%, 29%, 0% and 0% of individuals, respectively, were non-responders. After the second ET period, non-response was eliminated in all individuals. The change in V̇O2 max with exercise training independently determined Wmax response (partial correlation coefficient, rpartial ≥ 0.74, P < 0.001). In turn, total haemoglobin mass was the strongest independent determinant of V̇O2 max (rpartial = 0.49, P < 0.001). In conclusion, individual CRF non-response to exercise training is abolished by increasing the dose of exercise and primarily a function of haematological adaptations in oxygen-carrying capacity.
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We have previously predicted that the decrease in maximal oxygen uptake (VO2max) that accompanies time in microgravity reflects decrements in both convective and diffusive O2 transport to the mitochondria of the contracting myocytes. The aim of this investigation was therefore to quantify the relative changes in convective O2 transport (QO2) and O2 diffusing capacity (DO2) following long duration spaceflight. In 9 astronauts, resting hemoglobin concentration ([Hb]), VO2max, maximal cardiac output (QTmax), and differences in arterial and venous O2 contents (CaO2-CvO2) were obtained retrospectively for International Space Station Increments 19 through 33 (April 2009-November 2012). QO2 and DO2 were calculated from these variables via integration of Fick's Principle of Mass Conservation and Fick's Law of Diffusion. VO2max significantly decreased from pre- to post-flight (-53.9 ± 45.5%, P =0.008). The significant decrease in Q ̇_Tmax (-7.8±9.1%, P =0.05), despite an unchanged [Hb] resulted in a significantly decreased QO2 (-11.4±10.5%, P = 0.02). DO2 significantly decreased from pre- to post-flight by -27.5±24.5% (P =0.04), as did the peak CaO2-CvO2 (-9.2±7.5%, P =0.007). Using linear regression analysis, changes in VO2max were significantly correlated with changes in DO2 (R2=0.47; P = 0.04). These data suggest that space flight decreases both convective and diffusive O2 transport. These results have practical implications for future long-duration space missions and highlight the need to resolve the specific mechanisms underlying these spaceflight-induced changes along the O2 transport pathway.
Article
Maximal strength training (MST) improves work efficiency. However, since blood flow is greatly dictated by muscle contractions in arms during exercise, and vascular conductance is lower, it has been indicated that arms rely more upon adapting oxygen extraction than legs in response to the enhanced work efficiency. Thus, to investigate if metabolic and vascular responses are arm-specific, we utilized Doppler-ultrasound and a catheter placed in the subclavian vein to measure blood flow and a-vO2diff during steady state work in seven young males (24{plus minus}3(SD) years) following six-weeks of handgrip MST. As expected, MST improved maximal strength (49{plus minus}9 to 62{plus minus}10kg) and rate of force development (923{plus minus}224 to 1086{plus minus}238N·s-1), resulting in a reduced submaximal V̇O2 (30{plus minus}9 to 24{plus minus}10ml·min-1) and concomitantly increased work efficiency (9.3{plus minus}2.5 to 12.4{plus minus}3.9%) (all p<0.05). In turn, the work efficiency improvement was associated with a reduced blood flow (486{plus minus}102 to 395{plus minus}114ml·min-1), mediated by a lower blood velocity (43{plus minus}8 to 32{plus minus}6cm·s-1) (all p<0.05). Conduit artery diameter and a-vO2diff remained unaltered. The maximal work test revealed increased time to exhaustion (949{plus minus}239 to 1102{plus minus}292seconds) and maximal work rate (both p<0.05), but no change in peak oxygen uptake. In conclusion, despite prior indications of metabolic and vascular limb-specific differences, these results reveal that improved work efficiency following small muscle mass strength training in the upper extremities is accompanied by a blood flow reduction, and coheres with what has been documented for lower extremities.
Article
Exposure to a microgravity environment decreases the maximal rate of O2 uptake (V˙O2max) in healthy individuals returning to a gravitational environment. The magnitude of this decrease in V˙O2max is, in part, dependent on the duration of microgravity exposure, such that long-duration exposure may result in up to a 38% decrease in V˙O2max. This review identifies the components within the O2 transport pathway that determine the decrease in post-microgravity V˙O2max and highlights the potential contributing physiological mechanisms. A retrospective analysis revealed that the decline in V˙O2max is initially mediated by a decrease in convective and diffusive O2 transport that occurs as the duration of microgravity exposure is extended. Mechanistically, the attenuation of O2 transport is the combined result of a deconditioning across multiple organ systems including decreases in total blood volume, red blood cell mass, cardiac function and mass, vascular function, skeletal muscle mass, and potentially capillary hemodynamics which become evident during exercise upon re-exposure to the head-to-foot gravitational forces of upright posture on Earth. In summary, V˙O2max is determined by the integration of central and peripheral O2 transport mechanisms, which if not maintained during microgravity, will have a substantial long-term detrimental impact on space mission performance and astronaut health.
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The present study investigated metabolic rate (MR) and gross efficiency (GE) at moderate and high work rates, and the relationships to gross kinematics and physical characteristics in elite cross-country skiers. Eight world class (WC) and eight national level (NL) male sprint cross-country skiers performed three 5-min stages using the skating G3 technique, whilst roller skiing on a treadmill. GE was calculated by dividing work rate by MR. Work rate was calculated as the sum of power against gravity and frictional rolling forces. MR was calculated using gas exchange and blood lactate values. Gross kinematics, i.e. cycle length (CL) and cycle rate (CR) were measured by video analysis. Furthermore, the skiers were tested for time to exhaustion (TTE), peak oxygen uptake (VO2peak), and maximal speed (V max) on the treadmill, and maximal strength in the laboratory. Individual performance level in sprint skating was determined by FIS points. WC skiers did not differ in aerobic MR, but showed lower anaerobic MR and higher GE than NL skiers at a given speed (all P < 0.05). Moreover, WC skiers skated with longer CL and had higher V max and TTE (all P < 0.05). In conclusion, the present study shows that WC skiers are more efficient than NL skiers, and it is proposed that this might be due to a better technique and to technique-specific power.
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Performance tests and measurements of maximal aerobic capacity were performed during the competition period in elite cross-country skiers. Muscle biopsies were taken in the middle of January. Histochemical fibre typing, determination of fibre areas and number of capillaries as well as assays for citrate synthetase (CS), 3-hydroxyacyl coenzyme A dehydrogenase (HAD), lactate dehydrogenase (LDHtot and LDH1-2) were performed on biopsies from the triceps brachii (TRI) and vastus lateralis muscles (VAS). The relative percentage of slow-twitch fibres was 51.3 and 68.6 in TRI and VAS, respectively. The FTa fibre area in TRI was significantly larger than in VAS. No differences were found in the number of capillaries per fibre in TRI (2.7) and VAS (2.5). The number of capillaries per area was significantly lower in TRI (373) as compared to VAS (422). The LDHtot enzyme level was significantly higher in TRI than VAS, while the oxidative enzyme activities (CS and HAD) were significantly lower in TRI as compared with VAS. From all independent variables, only the maximal aerobic power was related significantly to performance time. The difference in maximal aerobic power between the skiers could explain 45% of the total variance in performance.
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The mean minimal transit time for blood in muscle capillaries (tc) was estimated in six species, spanning two orders of magnitude in body mass and aerobic capacity: horse, steer, dog, goat, fox and agouti. Arterial (CaO2) and mixed venous (CvO2) blood O2 concentrations, blood hemoglobin concentrations ([Hb]) and oxygen uptake rates were measured while the animals ran on a treadmill at a speed that elicited the maximal oxygen consumption rate (VO2max) from each animal. Blood flow to the muscles (Qm) was assumed to be 85% of cardiac output, which was calculated using the Fick relationship. Total muscle capillary blood volume (Vc) and total muscle mitochondrial volume were estimated by morphometry, using a whole-body muscle sampling scheme. The tc was computed as Vc/Qm. The tc was 0.3-0.5 s in the 4 kg foxes and agoutis, 0.7-0.8 s in the 25 kg dogs and goats, and 0.8-1.0 s in the 400 kg horses and steers. The tc was positively correlated with body mass and negatively correlated with transcapillary O2 release rate per unit capillary length. Mitochondrial content was positively correlated with VO2max and with the product of Qm and [Hb]. These data suggested that Qm, Vc, maximal hemoglobin flux, and consequently tc, are co-adjusted to result in muscle O2 supply conditions that are matched to the O2 demands of the muscles at VO2max.
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Although evidence for muscle O(2) diffusion limitation of maximal O(2) uptake has been found in the intact organism and isolated muscle, its relationship to diffusion distance has not been examined. Thus we studied six sets of three purpose-bred littermate dogs (aged 10-12 mo), with 1 dog per litter allocated to each of three groups: control (C), exercise trained for 8 wk (T), or left leg immobilized for 3 wk (I). The left gastrocnemius muscle from each animal was surgically isolated, pump-perfused, and electrically stimulated to peak O(2) uptake at three randomly applied levels of arterial oxygenation [normoxia, arterial PO(2) (Pa(O(2))) 77 +/- 2 (SE) Torr; moderate hypoxia, Pa(O(2)): 33 +/- 1 Torr; and severe hypoxia, Pa(O(2)): 22 +/- 1 Torr]. O(2) delivery (ml. min(-1). 100 g(-1)) was kept constant among groups for each level of oxygenation, with O(2) delivery decreasing with decreasing Pa(O(2)). O(2) extraction (%) was lower in I than T or C for each condition, but calculated muscle O(2) diffusing capacity (Dmus(O(2))) per 100 grams of muscle was not different among groups. After the experiment, the muscle was perfusion fixed in situ, and a sample from the midbelly was processed for microscopy. Immobilized muscle showed a 45% reduction of muscle fiber cross-sectional area (P < 0.05), and a resulting 59% increase in capillary density (P < 0.05) but minimal reduction in capillary-to-fiber ratio (not significant). In contrast, capillarity was not significantly different in T vs. C muscle. The results show that a dramatically increased capillary density (and reduced diffusion distance) after short-term immobilization does not improve Dmus(O(2)) in heavily working skeletal muscle.
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That muscular blood flow may reach 2.5 l kg(-1) min(-1) in the quadriceps muscle has led to the suggestion that muscular vascular conductance must be restrained during whole body exercise to avoid hypotension. The main aim of this study was to determine the maximal arm and leg muscle vascular conductances (VC) during leg and arm exercise, to find out if the maximal muscular vasodilatory response is restrained during maximal combined arm and leg exercise. Six Swedish elite cross-country skiers, age (mean +/-s.e.m.) 24 +/- 2 years, height 180 +/- 2 cm, weight 74 +/- 2 kg, and maximal oxygen uptake (VO(2,max)) 5.1 +/- 0.1 l min(-1) participated in the study. Femoral and subclavian vein blood flows, intra-arterial blood pressure, cardiac output, as well as blood gases in the femoral and subclavian vein, right atrium and femoral artery were determined during skiing (roller skis) at approximately 76% of VO(2,max) and at VO(2,max) with different techniques: diagonal stride (combined arm and leg exercise), double poling (predominantly arm exercise) and leg skiing (predominantly leg exercise). During submaximal exercise cardiac output (26-27 l min(-1)), mean blood pressure (MAP) (approximately 87 mmHg), systemic VC, systemic oxygen delivery and pulmonary VO2(approximately 4 l min(-1)) attained similar values regardless of exercise mode. The distribution of cardiac output was modified depending on the musculature engaged in the exercise. There was a close relationship between VC and VO2 in arms (r= 0.99, P < 0.001) and legs (r= 0.98, P < 0.05). Peak arm VC (63.7 +/- 5.6 ml min(-1) mmHg(-1)) was attained during double poling, while peak leg VC was reached at maximal exercise with the diagonal technique (109.8 +/- 11.5 ml min(-1) mmHg(-1)) when arm VC was 38.8 +/- 5.7 ml min(-1) mmHg(-1). If during maximal exercise arms and legs had been vasodilated to the observed maximal levels then mean arterial pressure would have dropped at least to 75-77 mmHg in our experimental conditions. It is concluded that skeletal muscle vascular conductance is restrained during whole body exercise in the upright position to avoid hypotension.
Article
Muscle mitochondrial respiratory capacity measured ex vivo provides a physiological reference to assess cellular oxidative capacity as a component in the oxygen cascade in vivo. In this article, the magnitude of muscle blood flow and oxygen uptake during exercise involving a small-to-large fraction of the body mass will be discussed in relation to mitochondrial capacity measured ex vivo. These analyses reveal that as the mass of muscle engaged in exercise increases from one-leg knee extension, to 2-arm cranking, to 2-leg cycling and x-country skiing, the magnitude of blood flow and oxygen delivery decrease. Accordingly, a 2-fold higher oxygen delivery and oxygen uptake per unit muscle mass are seen in vivo during 1-leg exercise compared to 2-leg cycling indicating a significant limitation of the circulation during exercise with a large muscle mass. This analysis also reveals that mitochondrial capacity measured ex vivo underestimates the maximal in vivo oxygen uptake of muscle by up to ∼2-fold. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.
Article
• The effects of bed rest on the cardiovascular and muscular parameters which affect maximal O2 consumption (VO2,max) were studied. The fractional limitation of VO2,max imposed by these parameters after bed rest was analysed. • The VO2,max, by standard procedure, and the maximal cardiac output (Q˙max), by the pulse contour method, were measured during graded cyclo-ergometric exercise on seven subjects before and after a 42-day head-down tilt bed rest. Blood haemoglobin concentration ([Hb]) and arterialized blood gas analysis were determined at the highest work load. • Muscle fibre types, oxidative enzyme activities, and capillary and mitochondrial densities were measured on biopsy samples from the vastus lateralis muscle before and at the end of bed rest. The measure of muscle cross-sectional area (CSA) by NMR imaging at the level of biopsy site allowed computation of muscle oxidative capacity and capillary length. • The VO2max was reduced after bed rest (−16.6%). The concomitant decreases in Q˙max (−30.8%), essentially due to a change in stroke volume, and in [Hb] led to a huge decrease in O2 delivery (−39.7%). • Fibre type distribution was unaffected by bed rest. The decrease in fibre area corresponded to the significant reduction in muscle CSA (−17%). The volume density of mitochondria was reduced after bed rest (−16.6%), as were the oxidative enzyme activities (−11%). The total mitochondrial volume was reduced by 28.5%. Capillary density was unchanged. Total capillary length was 22.2% lower after bed rest, due to muscle atrophy. • The interaction between these muscular and cardiovascular changes led to a smaller reduction in VO2max than in cardiovascular O2 transport. Yet the latter appears to play the greatest role in limiting VO2max after bed rest (>70% of overall limitation), the remaining fraction being shared between peripheral O2 diffusion and utilization.
Article
7 young, healthy, male subjects performed exercise on bicycle ergometers in two 20 min periods with an interval of 1 h. The first 10 min of each 20 min period consisted of arm exercise (38–62% of Vdot;o2 max for arm exercise) or leg exercise (58–78% of Vdot;o2 max for leg exercise). During the last 10 min the subjects performed combined arm and leg exercise (71–83% of Vdot;o2 max for this type of exercise). The following variables were measured during each type of exercise: oxygen uptake, heart rate, mean arterial blood pressure, cardiac output, leg blood flow (only during leg exercise and combined exercise), arterio-venous concentration differences for O2 and lactate at the levels of the axillary and the external iliac vessels.Superimposing a sufficiently strenuous arm exercise (oxygen uptake for arm exercise 40% of oxygen uptake for combined exercise) on leg exercise caused a reduction in blood flow and oxygen uptake in the exercising legs with unchanged mean arterial blood pressure. Superimposing leg exercise on arm exercise caused a decrease in mean arterial blood pressure and an increased axillary arterio-venous oxygen difference. These findings indicate that the oxygen supply to one large group of exercising muscles may be limited by vasoconstriction or by a fall in arterial pressure, when another large group of muscles is exercising simultaneously.
Article
We analyzed the capillarity of the heart, diaphragm, M. vastus medialis and M. semitendinosus of dogs, goats, ponies and calves (n = 3 each). Blocks of tissue were preserved, processed and photographed bye electron microscopy. Using morphometric techniques we estimated capillary density, capillary lenght density and total capillary length in these muscles. The highly aerobic dogs and ponies had greater total capillary lenghts and larger muscles than the less aerobic goats and calves. A significant correlation was found between capillary length density (JV(c,f)) and mitochondrial volume density (VV(mt,f)) which was: JV(c,f) = 258 + 1.25·104 VV(mt,f). From this correlation we calculated an average of 14 km or 0.22 ml of capillaries per milliliter of mitochondria. With these values and data from blood gas analysis (Karas et al., 1987), we calculated a mean minimum transit time for blood in capillaries of approximately 0.5 sec for all four species. At the tissue level, the greater aerobic metabolic capacity of dogs and ponies was supported in equal parts by the larger capillary supply of the muscle tissue and by the higher oxygen carrying capacity of the blood.
Article
This study sought to elucidate the mechanisms responsible for the benefits of small muscle mass exercise training in patients with chronic heart failure (CHF). How central cardiorespiratory and/or peripheral skeletal muscle factors are altered with small muscle mass training in CHF is unknown. We studied muscle structure, and oxygen (O(2)) transport and metabolism at maximal cycle (whole-body) and knee-extensor exercise (KE) (small muscle mass) in 6 healthy controls and 6 patients with CHF who then performed 8 weeks of KE training (both legs, separately) and repeated these assessments. Pre-training cycling and KE peak leg O(2) uptake (Vo(2peak)) were ~17% and ~15% lower, respectively, in the patients compared with controls. Structurally, KE training increased quadriceps muscle capillarity and mitochondrial density by ~21% and ~25%, respectively. Functionally, despite not altering maximal cardiac output, KE training increased maximal O(2) delivery (~54%), arterial-venous O(2) difference (~10%), and muscle O(2) diffusive conductance (D(M)O(2)) (~39%) (assessed during KE), thereby increasing single-leg Vo(2peak) by ~53%, to a level exceeding that of the untrained controls. Post-training, during maximal cycling, O(2) delivery (~40%), arterial-venous O(2) difference (~15%), and D(M)O(2) (~52%) all increased, yielding an increase in Vo(2peak) of ~40%, matching the controls. In the face of continued central limitations, clear improvements in muscle structure, peripheral convective and diffusive O(2) transport, and subsequently, O(2) utilization support the efficacy of local skeletal muscle training as a powerful approach to combat exercise intolerance in CHF.
Article
Across a wide range of species and body mass a close matching exists between maximal conductive oxygen delivery and mitochondrial respiratory rate. In this study we investigated in humans how closely in-vivo maximal oxygen consumption (VO(2) max) is matched to state 3 muscle mitochondrial respiration. High resolution respirometry was used to quantify mitochondrial respiration from the biopsies of arm and leg muscles while in-vivo arm and leg VO(2) were determined by the Fick method during leg cycling and arm cranking. We hypothesized that muscle mitochondrial respiratory rate exceeds that of systemic oxygen delivery. The state 3 mitochondrial respiration of the deltoid muscle (4.3±0.4 mmol o(2)kg(-1) min(-1)) was similar to the in-vivo VO(2) during maximal arm cranking (4.7±0.5 mmol O(2) kg(-1) min(-1)) with 6 kg muscle. In contrast, the mitochondrial state 3 of the quadriceps was 6.9±0.5 mmol O(2) kg(-1) min(-1), exceeding the in-vivo leg VO(2) max (5.0±0.2 mmol O(2) kg(-1) min(-1)) during leg cycling with 20 kg muscle (P<0.05). Thus, when half or more of the body muscle mass is engaged during exercise, muscle mitochondrial respiratory capacity surpasses in-vivo VO(2) max. The findings reveal an excess capacity of muscle mitochondrial respiratory rate over O(2) delivery by the circulation in the cascade defining maximal oxidative rate in humans.
Article
Maximal endurance exercise capacity is determined by a variety of factors, including maximal ability to transport O₂ to the muscle mitochondria and to use this O₂ for ATP generation ((.)V(O₂MAX)). This analysis combines the individually well-known O₂ mass conservation equations for the four critical steps in the O₂ transport pathway (ventilation, alveolar/capillary diffusion, circulation and muscle diffusion) into an analytical, closed form, model showing how (.)V(O₂MAX) depends on all four steps. It further shows how changes in any one step affect the function of the others. This analytical approach however requires approximating the O₂Hb dissociation curve as linear. Removing this condition to allow for the real O₂Hb curve requires numerical analysis best explained graphically. Incorporating maximal mitochondrial metabolic capacity to use O₂ allows prediction of when (.)V(O₂MAX) is limited by transport or by metabolic capacity. This simple approach recapitulates in vivo behavior and clarifies the determinants of maximal exercise.
Article
In this review we integrate ideas about regional and systemic circulatory capacities and the balance between skeletal muscle blood flow and cardiac output during heavy exercise in humans. In the first part of the review we discuss issues related to the pumping capacity of the heart and the vasodilator capacity of skeletal muscle. The issue is that skeletal muscle has a vast capacity to vasodilate during exercise [approximately 300 mL (100 g)(-1) min(-1)], but the pumping capacity of the human heart is limited to 20-25 L min(-1) in untrained subjects and approximately 35 L min(-1) in elite endurance athletes. This means that when more than 7-10 kg of muscle is active during heavy exercise, perfusion of the contracting muscles must be limited or mean arterial pressure will fall. In the second part of the review we emphasize that there is an interplay between sympathetic vasoconstriction and metabolic vasodilation that limits blood flow to contracting muscles to maintain mean arterial pressure. Vasoconstriction in larger vessels continues while constriction in smaller vessels is blunted permitting total muscle blood flow to be limited but distributed more optimally. This interplay between sympathetic constriction and metabolic dilation during heavy whole-body exercise is likely responsible for the very high levels of oxygen extraction seen in contracting skeletal muscle. It also explains why infusing vasodilators in the contracting muscles does not increase oxygen uptake in the muscle. Finally, when approximately 80% of cardiac output is directed towards contracting skeletal muscle modest vasoconstriction in the active muscles can evoke marked changes in arterial pressure.
Article
Hill's equation can be slightly modified to fit the standard human blood O2 dissociation curve to within plus or minus 0.0055 fractional saturation (S) from O less than S less than 1. Other modifications of Hill's equation may be used to compute Po2 (Torr) from S (Eq. 2), and the temperature coefficient of Po2 (Eq. 3). Variations of the Bohr coefficient with Po2 are given by Eq. 4. S = (((Po2(3) + 150 Po2)(-1) x 23,400) + 1)(-1) (1) In Po2 = 0.385 In (S-1 - 1)(-1) + 3.32 - (72 S)(-1) - 0.17(S6) (2) DELTA In Po2/delta T = 0.058 ((0.243 X Po2/100)(3.88) + 1)(-1) + 0.013 (3) delta In Po2/delta pH = (Po2/26.6)(0.184) - 2.2 (4) Procedures are described to determine Po2 and S of blood iteratively after extraction or addition of a defined amount of O2 and to compute P50 of blood from a single sample after measuring Po2, pH, and S.
Article
13 male subjects were studied and placed in 3 groups. Each group exercised one leg with sprint (S), or endurance (E) training and the other leg oppositely or not at all (NT). Oxygen uptake (Vo2), heart rate and blood lactate were measured for each leg separately and for both legs together during submaximal and maximal bicycle work before and after 4 weeks of training with 4-5 sessions per week. Muscle samples were obtained from the quadriceps muscle and assayed for succinate dehydrogenase (SDH) activity, and stained for myofibrillar ATPase. In addition, eight of the subjects performed after the training two-legged exercise at 70% Vo2 max for one hour. The measurements included muscle glycogen and lactate concentrations of the two legs as well as the blood flow and the a-v difference for O2, glucose and lactate.
Article
Succinate dehydrogenase (SDH) and cytochrome oxidase activities in the lateral vastus of the human quadriceps femoris muscle together with total body VO2 max were followed during an 8-10 week period of endurance training (n = 13) and a successive 6 week period without training (n = 8). During the training period there was a gradual increase in both VO2 max and muscle oxidative enzyme activities, all being significantly different from the pre-training levels after 3 weeks of training. After 8 weeks of training VO2 max was 19%, vastus lateralis SDH 32%, and cytochrome oxidase activity 35% above the pre-training levels respectively. 6 weeks post training VO2 max was still 16% above the pre-training level, and not significantly different from the level at the end of training (p greater than 0.2). In contrast vastus lateralis SDH activity had returned to the pre-training level. Cytochrome oxidase activity had returned to the pre-training level within two weeks post-training. The significantly faster post-training decline in skeletal muscle oxidative enzyme activities in contrast to that of the VO2 max indicates that an enhancement of the oxidative potential in skeletal muscle is not a necessity for a high VO2 max. Moreover, the fast return to the pre-training level of both SDH and cytochrome oxidase activities indicate a high turnover rate of enzymes in the TCA cycle as well as the respiratory chain.
Article
1. Five subjects trained for 8 weeks on a bicycle ergometer for an average of 40 min/day, four times a week at a work load requiring 80% of the maximal oxygen uptake (V(O2 max.)). V(O2 max.) determinations were performed, and muscle biopsies from the quadriceps femoris muscle (vastus lateralis) were taken before, as well as repeatedly during, the training period. The muscle biopsies were histochemically stained for fibre-types (myofibrillar ATPase) and capillaries (amylase-PAS method), and analysed biochemically for succinate dehydrogenase and cytochrome oxidase activities.2. The training programme resulted in a 16% increase in V(O2 max.), a 20% increase in capillary density, a 20% increase in mean fibre area, and an approximately 40% increase in the activities of succinate dehydrogenase and cytochrome oxidase.3. The capillary supply to type I, IIA and IIB fibres, expressed as the mean number of capillaries in contact with each fibre-type, relative to fibre-type area, increased equally.4. The present study shows that endurance training constitutes a powerful stimulus for capillary proliferation in human skeletal muscle.
Article
Distribution of O2 within and among arterioles and venules was determined in dog and rat gracilis muscles with a cryospectrophotometric method. Saturation in 40-microns arterioles was not demonstrably different from saturation in the aorta even when flow was abnormally low. Arterioles greater than 40 microns ran parallel to venules. Measurements and a mathematical model indicate that diffusive shunting is negligible for typical separation distances between arterioles and venules. Most separation distances were greater than 30 microns. In some venule segments less than 15 microns from an arteriole, saturation within 10 microns of the wall facing the arteriole was higher than at other locations within the venule. However, saturation in the population of venules did not increase with venule diameter, and mean venular saturation was not different from saturation in effluent blood. We make the following conclusions: 1) a small arteriovenous diffusive O2 flux exists in postural muscles; 2) contribution of this flux to O2 mass balance is negligible; 3) O2 diffusivity of the arteriolar wall and surrounding tissue in vivo cannot be much higher than O2 diffusivity determined in vitro; and 4) effluent PO2 closely approximates mean end-capillary PO2.
Article
Capillary orientation (anisotropy) was compared in hindlimb muscles of mammals of different size and/or different aerobic capacity (dog, goat, pony, and calf). All muscles were fixed by vascular perfusion at sarcomere lengths ranging from 1.5 to 2.7 micron. The ratios of capillary counts per fiber cross-sectional area on two sets of sections (0 and 90 degrees) to the muscle fiber axis were used to estimate capillary anisotropy and the coefficient c(K,0) relating 1) capillary counts on transverse sections (a commonly used parameter to assess muscle capillarity) and 2) capillary length per volume of fiber (i.e., capillary length density). Capillary orientation parallel to the muscle fiber axis decreased substantially with muscle fiber shortening. In muscles fixed at sarcomere lengths of 2.69 microns (dog vastus intermedius) and 1.52 microns (dog gastrocnemius), capillary tortuosity and branching added 7 and 64%, respectively, to capillary length density. The data obtained in this study are highly consistent with the previously demonstrated relationship between capillary anisotropy and sarcomere length in extended vs. contracted rat muscles, by use of the same method. Capillary anisotropy in mammalian locomotory muscles is curvilinearly related to sarcomere length. No systematic difference was found in capillary tortuosity with either body size, athletic ability, or aerobic capacity. Capillary tortuosity is a consequence of fiber shortening rather than an indicator of the O2 requirements of the tissue.
Article
The intracellular distribution of O2 in cross sections of dog gracilis muscles was determined by myoglobin (Mb) cryospectrophotometry. The volume sampled by the photometer was approximately 30 micron3 and contained 1-2 mitochondria. Measurements could be made to within 3 micron of capillaries without interference from hemoglobin. Mb saturation was uniform at all loci examined when respiration was blocked with cyanide. During twitch contraction at maximum O2 consumption, saturations within a cell cross section varied by up to 20%. The corresponding difference in partial pressure of O2 (PO2) was 1.5 Torr. Circumferential O2 gradients parallel to and 5 micron from the sarcolemma were greatest near capillaries. They did not exceed 0.1 Torr/micron and were dissipated within 25 micron of the sarcolemma. Gradients perpendicular to the sarcolemma were less than 0.02 Torr/micron. Saturation was not significantly correlated with cell diameter. Minimum PO2 was seldom located at the center of the cell cross section. Differences in saturation between contiguous cells often exceeded 10%. The distribution of O2 within cells appeared to reflect both an intercellular O2 flux and and an O2 flux from adjacent capillaries. Data agree qualitatively and quantitatively with mathematical models that take account of the particulate nature of blood and facilitated diffusion by Mb.
Article
It is not currently known whether central hemodynamic or peripheral (vascular or metabolic) factors limit maximal oxygen uptake. By measuring the blood flow and oxygen uptake of exercising muscles when only a small fraction of the total muscle mass is engaged in exercise, it has been demonstrated that the skeletal muscle of man could accommodate a blood flow of at least 200 ml/100 g min, and consume 300 ml O2/100 g min at exhaustive exercise. Thus, in whole body exercise the limiting factor is the capacity of the heart to deliver oxygen, not the muscle. It has also been observed that at high perfusion of the muscle the arteriovenous O2 difference is small (14 to 15 vol %), and that the low extraction of oxygen is related to the mean transit time (MTT) of red blood cells passing through the capillaries. It has been concluded that the primary importance of enlargement of the capillary bed with endurance training is not to accommodate flow but to maintain or elongate MTT. It has also been concluded that, in whole body exercise, the capacity of the muscles to receive a flow exceeds by a factor of 2 to 3 the capacity of the heart to supply the flow. Thus, vasoconstrictor tone must also be present in the arteries that "feed" exercising muscles.
Article
Five subjects exercised with the knee extensor of one limb at work loads ranging from 10 to 60 W. Measurements of pulmonary oxygen uptake, heart rate, leg blood flow, blood pressure and femoral arterial-venous differences for oxygen and lactate were made between 5 and 10 min of the exercise. Flow in the femoral vein was measured using constant infusion of saline near 0 degrees C. Since a cuff was inflated just below the knee during the measurements and because the hamstrings were inactive, the measured flow represented primarily the perfusion of the knee extensors. Blood flow increased linearly with work load right up to an average value of 5.7 l min-1. Mean arterial pressure was unchanged up to a work load of 30 W, but increased thereafter from 100 to 130 mmHg. The femoral arterial-venous oxygen difference at maximum work averaged 14.6% (v/v), resulting in an oxygen uptake of 0.80 l min-1. With a mean estimated weight of the knee extensors of 2.30 kg the perfusion of maximally exercising skeletal muscle of man is thus in the order of 2.5 l kg-1 min-1, and the oxygen uptake 0.35 l kg-1 min-1. Limitations in the methods used previously to determine flow and/or the characteristics of the exercise model used may explain why earlier studies in man have failed to demonstrate the high perfusion of muscle reported here. It is concluded that muscle blood flow is closely related to the oxygen demand of the exercising muscles. The hyperaemia at low work intensities is due to vasodilatation, and an elevated mean arterial blood pressure only contributes to the linear increase in flow at high work rates. The magnitude of perfusion observed during intense exercise indicates that the vascular bed of skeletal muscle is not a limiting factor for oxygen transport.
Article
STUDIES on normal and pathological striated muscle are increasingly clouded by inconsistencies in the definition of fiber types and lack of correlation between different systems of nomenclature. The purpose of the present communication is to point out some of the problems involved in the classification of fibers and to add new information of value in the analysis of human biopsy material. The histochemical reaction for myosin adenosine triphosphatase (ATPase) and the pH lability of this reaction is used to characterize the various types of fibers. Material and Methods Muscle was obtained by biopsy in man, rat, and rabbit. Gastrocnemius and soleus were investigated in the animals. The human biopsies were taken from the biceps. The methods used for histochemical analysis have been given elsewhere.1 In summary, unfixed frozen material was sectioned at 10μ thickness in the cryostat and the following histochemical reactions were carried out: (1) reduced diphosphopyridine
Article
In 2 groups of young healthy subjects who performed arm training (n = 5) and leg training (n = 8), respectively, the circulatory response to exercise done with trained and nontrained muscle groups was compared by measurement of heart rate (HR), cardiac output (Q), regional arteriovenous oxygen differences, (axillary and femoral (a v)O2 diff), hepatic clearance of indocyanine green (ICG clearance), and aortic blood pressure during moderate and heavy submaximal exercise. Arm training caused a pronounced reduction in HR during arm exercise, whereas only a small reduction was seen during exercise performed with nontrained leg muscles. Leg training, however, reduced HR almost equally during leg exercise and arm exercise. After both types of training during exercise with trained muscles, ICG clearance and (a v)02 diff suggested less pronounced sympathetic vasoconstriction in nonexercising tissues and increased oxygen extracting from exercising muscles. Q and aortic blood pressures were unchanged except during heavy arm exercise after leg training, in which a 10-12% increase in Q and aortic blood pressures occurred. From these findings, it is concluded that alterations in the trained muscles and central circulatory changes both contribute to the effects of physical training on circulation.