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Abstract
Reflex inputs to the circulatory and ventilatory centers from dynamically contracting muscles and their interaction with extramuscular inputs were studied in anesthetized dogs. Dynamic work of hindlimb muscles was evoked by electrical stimulation of sciatic nerve branches (40 tetani/min with square wave pulses: 0.2-1.0 V, 0.3-0.7 msec, 30-100 Hz). These pulses activated group I and II nerve fibers and they affected heart rate (HR), minute ventilation (VE), and mean arterial pressure (MAP) only to a small degree when neuromuscular transmission was blocked by cooling distally from the electrodes. Comparable small changes were obtained if these fibers were excited by their natural stimuli when moving and stretching the legs and muscles, respectively. But these responses disappeared when the legs were moved and the muscles stretched after the dogs had been immobilized with drugs, indicating that they were caused by increased muscle tension and not movement per se. If neuromuscular transmission was restored, muscular contractions were induced which caused great reflexogenic increases of HR, VE, and MAP. Muscular reflex drives to the center were then eliminated by cold blockade of nervous transmission in both sciatic nerves proximally from the stimulating electrodes while contractions were not interrupted. Blood metabolically enriched in this way entered the systemic circulation, thereby creating humoral extramuscular drives. Muscular reflex inputs accounted for the major and humoral drives for the minor portion of the total cardiovascular and respiratory responses during onset as well as during steady state of dynamic work, although humoral drives increased with time. The time courses of the reflexly induced changes tallied with those of muscular blood flow, indicating a relation with similar metabolic processes. The reflex drives were abolished if a blocking temperature typical for nonmyelinated or small myelinated group IV or III nerve fibers was reached. Similarly, the main responses were only obtained if electrical stimuli were raised to levels where they activated group III or IV afferents.
... Also, e has been reported to increase when muscle contractions (static or dynamic) are induced in anesthetized animals by stimulation of the appropriate ventral spinal roots, motor nerves or the muscles themselves; the hyperpnea being abolished by interruption of the reflex arc (e.g., by afferent nerve cold block, section of the dorsal spinal roots or spinal-cord transection) (e.g., [184,187,188]). Furthermore, selective electrical stimulation of Groups III and IV afferents (but not of the larger Groups I and II afferents) leads to an increase in e which can be abolished by differential blockade of these small-diameter fibers (e.g., [187,188]). Also, exercise induced by electrical stimulation of the mesencephalic locomotor region in decerebrate cats has been shown to increase the discharge of Groups III and IV afferents from locomotor muscles (reviewed in [102,175]). ...
... Also, e has been reported to increase when muscle contractions (static or dynamic) are induced in anesthetized animals by stimulation of the appropriate ventral spinal roots, motor nerves or the muscles themselves; the hyperpnea being abolished by interruption of the reflex arc (e.g., by afferent nerve cold block, section of the dorsal spinal roots or spinal-cord transection) (e.g., [184,187,188]). Furthermore, selective electrical stimulation of Groups III and IV afferents (but not of the larger Groups I and II afferents) leads to an increase in e which can be abolished by differential blockade of these small-diameter fibers (e.g., [187,188]). Also, exercise induced by electrical stimulation of the mesencephalic locomotor region in decerebrate cats has been shown to increase the discharge of Groups III and IV afferents from locomotor muscles (reviewed in [102,175]). ...
... These observations were reinforced by the demonstration that conditions in which the phase 1 cardiac output response was likely to be smaller and more sluggish than normal, the corresponding e response showed an essentially similar profile-with P ET co 2 , P ET o 2 and R still being relatively stable across this period. As discussed earlier (see 4. [175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193]1982. Figure 1. the experiment; e.g., light exercise [45,47,139,140] or posture [141,142], but nonetheless with relative stability of P ET co 2 , P ET o 2 and R. That cardiac output adopts a similar profile is evident from direct measurements (e.g., [46,215,216]) and also from the smaller and more sluggish phase 1 O 2 and co 2 responses [47,142] (see 3.1.1. ...
History of Exercise Physiology brings together leading authorities in the profession to present this unique resource that is certain to become an essential reference for exercise physiology researchers and practitioners. The contributing authors have all made significant contributions to the field, including many examples in which they were part of seminal research. The result of this vast undertaking is the most comprehensive resource on exercise physiology research ever compiled. Exercise physiology research is ongoing and its knowledge base is stronger than ever, but today’s scholars owe much of their success to their predecessors. The contributors to this book believe it is essential for exercise physiologists to understand the past when approaching the future and they have compiled this reference to aid in that process. From studying great thinkers of antiquity and work done by pioneers at research institutions, to exploring the inner workings of all the body’s systems, researchers will gain a precise understanding of what happens when human bodies move and who influenced and furthered that understanding.
... During experimental stimulations of limb muscle afferents, two major effects on respiration can be observed: entrainment of breathing and hyperpnoea. During entrained breathing the respiratory rhythm resets and follows the frequency of stimulus applied to muscle afferents (Iscoe and Polosa, 1976;Iscoe, 1981;Morin and Viala, 2002;Potts et al., 2005), whereas hyperpnoea is characterized by increased frequency of breathing and tidal volume (Koizumi et al., 1961;Tibes, 1977;Persegol et al., 1993). Entrainment of breathing is more related to locomotorrespiratory coupling, while hyperpnoea to exercise in general. ...
... In contrast, however, most investigators believe that exercise hyperpnoea is triggered exclusively by stimulation of type III/IV fibers (Mateika and Duffin, 1995;Amann et al., 2010;Kaufman, 2010;Amann, 2012). Experiments with selective blocking and deactivating of the different afferent types have shown that activation of type III/IV non-nociceptive fibers significantly contribute to changes in ventilation during limb muscle activity (McCloskey and Mitchell, 1972b;Tibes, 1977;Amann et al., 2010). ...
... Worth noting, however, is that in most animals used in electrophysiological experiments (mice, rats, cats, rabbits, dogs), the hindlimb muscles have larger muscle mass than forelimbs. This fact makes hindlimb muscles more popular for experimental and clinical research (Koizumi et al., 1961;Iscoe and Polosa, 1976;Tibes, 1977;Viala, 1986;Viala et al., 1987;Palisses et al., 1988;Persegol et al., 1993). However, some investigations have used forelimb muscle stimulation as well (Potts et al., 2005). ...
Breathing constantly adapts to environmental, metabolic or behavioral changes by responding to different sensory information, including afferent feedback from muscles. Importantly, not just respiratory muscle feedback influences respiratory activity. Afferent sensory information from rhythmically moving limbs has also been shown to play an essential role in the breathing. The present review will discuss the neuronal mechanisms of respiratory modulation by activation of peripheral muscles that usually occurs during locomotion or exercise. An understanding of these mechanisms and finding the most effective approaches to regulate respiratory motor output by stimulation of limb muscles could be extremely beneficial for people with respiratory dysfunctions. Specific attention in the present review is given to the muscle stimulation to treat respiratory deficits following cervical spinal cord injury.
... locomotor pathways) provides an anatomical and functional substrate that can be harnessed to modulate respiratory function post-injury (Isaev et al., 2004;Morin and Viala, 2002;Palisses et al., 1988;Persegol et al., 1993;Viala et al., 1987). Experimental studies have shown that stimulation of peripheral nerves innervating either the upper or lower limbs, as well limb muscles themselves, can rapidly induce changes in respiration (D'Orangeville et al., 2013;McCloskey and Mitchell, 1972;Persegol et al., 1993;Potts et al., 2005;Tibes, 1977;Waldrop et al., 1986b). The two main effects that have been observed during peripheral nerve stimulation are respiratory rhythm entrainment Morin and Viala, 2002;Potts et al., 2005) and increased phrenic output (Persegol et al., 1993;Tibes, 1977;Waldrop et al., 1986b). ...
... Experimental studies have shown that stimulation of peripheral nerves innervating either the upper or lower limbs, as well limb muscles themselves, can rapidly induce changes in respiration (D'Orangeville et al., 2013;McCloskey and Mitchell, 1972;Persegol et al., 1993;Potts et al., 2005;Tibes, 1977;Waldrop et al., 1986b). The two main effects that have been observed during peripheral nerve stimulation are respiratory rhythm entrainment Morin and Viala, 2002;Potts et al., 2005) and increased phrenic output (Persegol et al., 1993;Tibes, 1977;Waldrop et al., 1986b). More specifically, a number of studies have demonstrated that activation of group III and IV muscle afferents may be primarily responsible for the effects seen in the respiratory output (Hill et al., 1996;Mateika and Duffin, 1995;Tibes, 1977). ...
... The two main effects that have been observed during peripheral nerve stimulation are respiratory rhythm entrainment Morin and Viala, 2002;Potts et al., 2005) and increased phrenic output (Persegol et al., 1993;Tibes, 1977;Waldrop et al., 1986b). More specifically, a number of studies have demonstrated that activation of group III and IV muscle afferents may be primarily responsible for the effects seen in the respiratory output (Hill et al., 1996;Mateika and Duffin, 1995;Tibes, 1977). In addition, coupling between respiratory and locomotor systems at the spinal and supraspinal levels may contribute to observed changes in respiration. ...
Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals. One strategy with demonstrated therapeutic potential is the use of treatments that increase neural and muscular activity (e.g. locomotor training, neural and muscular stimulation) and promote plasticity. With a focus on respiratory function post-SCI, this review will discuss advances in the use of neural interfacing strategies and activity-based treatments, and highlights some recent results from our own research.
... Also, e has been reported to increase when muscle contractions (static or dynamic) are induced in anesthetized animals by stimulation of the appropriate ventral spinal roots, motor nerves or the muscles themselves; the hyperpnea being abolished by interruption of the reflex arc (e.g., by afferent nerve cold block, section of the dorsal spinal roots or spinal-cord transection) (e.g., [184,187,188]). Furthermore, selective electrical stimulation of Groups III and IV afferents (but not of the larger Groups I and II afferents) leads to an increase in e which can be abolished by differential blockade of these small-diameter fibers (e.g., [187,188]). Also, exercise induced by electrical stimulation of the mesencephalic locomotor region in decerebrate cats has been shown to increase the discharge of Groups III and IV afferents from locomotor muscles (reviewed in [102,175]). ...
... Also, e has been reported to increase when muscle contractions (static or dynamic) are induced in anesthetized animals by stimulation of the appropriate ventral spinal roots, motor nerves or the muscles themselves; the hyperpnea being abolished by interruption of the reflex arc (e.g., by afferent nerve cold block, section of the dorsal spinal roots or spinal-cord transection) (e.g., [184,187,188]). Furthermore, selective electrical stimulation of Groups III and IV afferents (but not of the larger Groups I and II afferents) leads to an increase in e which can be abolished by differential blockade of these small-diameter fibers (e.g., [187,188]). Also, exercise induced by electrical stimulation of the mesencephalic locomotor region in decerebrate cats has been shown to increase the discharge of Groups III and IV afferents from locomotor muscles (reviewed in [102,175]). ...
... These observations were reinforced by the demonstration that conditions in which the phase 1 cardiac output response was likely to be smaller and more sluggish than normal, the corresponding e response showed an essentially similar profile-with P ET co 2 , P ET o 2 and R still being relatively stable across this period. As discussed earlier (see 4. [175][176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193]1982. Figure 1. the experiment; e.g., light exercise [45,47,139,140] or posture [141,142], but nonetheless with relative stability of P ET co 2 , P ET o 2 and R. That cardiac output adopts a similar profile is evident from direct measurements (e.g., [46,215,216]) and also from the smaller and more sluggish phase 1 O 2 and co 2 responses [47,142] (see 3.1.1. ...
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The control of breathing during exercise remains the source of considerable debate. Classical schemes of the exercise hyperpnea have incorporated elements of proportional feed-back from chemoreceptor sites (carotid body and brainstem) and feed-forward neurogenic (central command and muscle reflex) control. However, the precise details of the control process are still not fully resolved, reflecting in part technical and interpretational limitations inherent in isolating putative control mechanisms in the intact exercising human and also the challenges presented by the ventilatory and gas-exchange complexities encountered at work rates which engender a metabolic (lactic) acidosis. Although some combination of neurogenic, chemoreflex, and circulatory-coupled processes are likely to contribute to the control, intriguingly, the overall system appears to evidence considerable redundancy. This, coupled with the lack of appreciable steady-state error signals in the mean levels of arterial PCO2, PO2, and pH over a wide range of work rates, has motivated the formulation of innovative control models that reflect not only spatial interactions but also temporal interactions (i.e., short-term and longer-term ‘memory’). The challenge remains to discriminate between robust control schemes that (a) integrate such processes within plausible physiological equivalents, and (b) account for both the dynamic and steady-state system response over the entire range of exercise intensities.
Table of Contents: Introduction / Ventilatory Requirements / Ventilatory Responses / Ventilatory Control / Conclusions / References
... 3. Moderate Exercise 863 +The anaerobic threshold represents the highest 02 uptake (CO2), which may be attained (on a given task), without sustained elevation of blood lactate concentration (91,97). Phase 1. Neurogenic mechanisms originating in the exercising limbs (8,18,45,60,64,69,79,81,87) and/or the cerebral cortex (28,50,65,72,88) are traditionally acknowledged to initiate and maintain 1 of the exercise hyperpnea. This contention derives support from several sources. ...
... Thus, electrical stimulation of the somatic afferent projections from a variety of muscle and joint receptors, including proprioceptors, can elicit reflex hyperpnea in the cat *The aortie bodies have been demonstrated not to subserve significant ventilatory chemoreception in man (56,67,85,89). and the dog (8,18,45,64,69,79,81,87). Of these, however, it appears that the receptors or nerve endings that project to small diameter myelinated group III and nonmyelinated group IV somatic afferent fibers are most likely to be involved in controlling the hyperpnea of exercise. ...
... Of these, however, it appears that the receptors or nerve endings that project to small diameter myelinated group III and nonmyelinated group IV somatic afferent fibers are most likely to be involved in controlling the hyperpnea of exercise. For the magnitude of the ventilatory response to electrically induced hindlimb exercise in the cat and the dog can be significantly diminished or even abolished when these particular afferent projections are inactivated, either by graded cooling of muscle nerves (87), by anesthetizing the dorsal spinal roots (69), or by lesioning the lateral spinothalamic tracts (60). In contrast, interference with the transmission of proprioceptive traffic in larger diameter myelinated group I and II afferent fibers is without effect (60,69,87). ...
... A number of investigators have previously attempted to block/inhibit afferent neurological feedback from skeletal muscle in both animal and human models (Tibes, 1977;Fernandes et al. 1990;Friedman et al. 1993;Amann et al. 2008). However, it is apparent that the method used to modulate afferent feedback in these studies may have influenced efferent neuromuscular control and resulted in altered central command. ...
... Animal models provide insight on the impact of blocking afferent activity from working muscle (Kao, 1963;Coote et al. 1971;McCloskey & Mitchell, 1972;Tibes, 1977). ...
New Findings
What is the central question of this study?
Patients with heart failure often develop ventilatory abnormalities at rest and during exercise, but the mechanisms underlying these abnormalities remain unclear. This study investigated the influence of inhibiting afferent neural feedback from locomotor muscles on the ventilatory response during exercise in heart failure patients.
What is the main finding and its importance?
Our results suggest that inhibiting afferent feedback from locomotor muscle via intrathecal opioid administration significantly reduces the ventilatory response to exercise in heart failure patients.
Patients with heart failure (HF) develop ventilatory abnormalities at rest and during exercise, but the mechanism(s) underlying these abnormalities remain unclear. We examined whether the inhibition of afferent neural feedback from locomotor muscles during exercise reduces exercise ventilation in HF patients. In a randomized, placebo‐controlled design, nine HF patients (age, 60 ± 2 years; ejection fraction, 27 ± 2%; New York Heart Association class 2 ± 1) and nine control subjects (age, 63 ± 2 years) underwent constant‐work submaximal cycling (65% peak power) with intrathecal fentanyl (impairing the cephalad projection of opioid receptor‐sensitive afferents) or sham injection. The hypercapnic ventilatory response was measured to determine whether cephalad migration of fentanyl occurred. There were no differences in hypercapnic ventilatory response within or between groups in either condition. Despite a lack of change in ventilation, tidal volume or respiratory rate, HF patients had a mild increase in arterial carbon dioxide ( ) and a decrease in oxygen ( ; P < 0.05 for both) at rest. The control subjects demonstrated no change in , , ventilation, tidal volume or respiratory rate at rest. In response to fentanyl during exercise, HF patients had a reduction in ventilation (63 ± 6 versus 44 ± 3 l min ⁻¹ , P < 0.05) due to a lower respiratory rate (30 ± 1 versus 26 ± 2 breaths min ⁻¹ , P < 0.05). The reduced ventilation resulted in lower (97.6 ± 2.5 versus 79.5 ± 3.0 mmHg, P < 0.05) and increased (37.3 ± 0.9 versus 43.5 ± 1.1 mmHg, P < 0.05), with significant improvement in ventilatory efficiency (reduction in the ventilatory equivalent for carbon dioxide; P < 0.05 for all). The control subjects had no change in ventilation or measures of arterial blood gases. These data suggest that inhibition of afferent feedback from locomotor muscle significantly reduces the ventilatory response to exercise in HF patients.
... These metabolic changes in contracting skeletal muscle have spillover effects into the interstitium where the free nerve endings of the metaboreceptors (CIII/IV afferents) reside. There are pronounced increases in interstitial fluid [K + ], [H + ], and osmolality (146,195,305) that increase afferent firing rate and hence are implicated in the control of ventilation (126)(127)(128)305). It is postulated that the central control of breathing is strongly modified by inputs from CIII/IV afferents during the onset of skeletal muscle activity (23,280). ...
... These metabolic changes in contracting skeletal muscle have spillover effects into the interstitium where the free nerve endings of the metaboreceptors (CIII/IV afferents) reside. There are pronounced increases in interstitial fluid [K + ], [H + ], and osmolality (146,195,305) that increase afferent firing rate and hence are implicated in the control of ventilation (126)(127)(128)305). It is postulated that the central control of breathing is strongly modified by inputs from CIII/IV afferents during the onset of skeletal muscle activity (23,280). ...
This paper describes the interactions between ventilation and acid-base balance under a variety of conditions including rest, exercise, altitude, pregnancy, and various muscle, respiratory, cardiac, and renal pathologies. We introduce the physicochemical approach to assessing acid-base status and demonstrate how this approach can be used to quantify the origins of acid-base disorders using examples from the literature. The relationships between chemoreceptor and metaboreceptor control of ventilation and acid-base balance summarized here for adults, youth, and in various pathological conditions. There is a dynamic interplay between disturbances in acid-base balance, that is, exercise, that affect ventilation as well as imposed or pathological disturbances of ventilation that affect acid-base balance. Interactions between ventilation and acid-base balance are highlighted for moderate- to high-intensity exercise, altitude, induced acidosis and alkalosis, pregnancy, obesity, and some pathological conditions. In many situations, complete acid-base data are lacking, indicating a need for further research aimed at elucidating mechanistic bases for relationships between alterations in acid-base state and the ventilatory responses. © 2012 American Physiological Society. Compr Physiol 2:2203-2254, 2012.
... 4, 8) e deglienzimi urinari sia lisosomiali (NAG 0 N-acetil glucosaminidasi) che del brushborder tubulare (alfa-glucosidasi e AAP o Alanino-aminopeptidasi) (Figg. [5][6][7][9][10][11]. I risultati ottenuti dal nostro studio si accordano bene con i meccanismi di adattamento dell'organismo allo sforzo. ...
... The most commonly used painful stimulus is the cold pressor test (49), which evokes remarkable increase in MSNA and a consequent marked increase in ABP (50). A previous study also noted that the pain pathway may interact with group III and IV afference feedback and potentially augment the pressor response to mechanoreflex (51). Thus, the pain pathway and mechanical skeletal muscle afferents summate the pressor response in PPS. ...
Introduction The muscle mechanoreflex has been considered to make a small contribution to the cardiovascular response to exercise in healthy humans because no pressor response has been observed during stimulation of mechanosensitive receptors, such as static passive stretching, during many human studies. There is room for rethinking this consideration since the pressor response to upper limb exercise is greater than that to lower limb exercise. We examined whether static passive stretching of the forearm muscles causes a muscle mechanoreflex-induced pressor response in humans. Methods Eighteen healthy men were recruited for this study. After a 15-min rest period in the supine position with a neutral (0°) wrist joint angle, all participants completed static passive stretching of the forearm for 60s at four different intensities: minimal painful passive stretching (PPS); moderate-intensity passive stretching (MPS); low-intensity passive stretching (LPS); and no load (NL). During the procedure, beat-to-beat arterial blood pressure was measured using finger photoplethysmography. The force generated between the passively stretched hand and the experimenter's hands was recorded using a force transducer. Results Mean arterial pressure (MAP) during PPS and MPS significantly increased from baseline during the last 40s (P < 0.05). MAP was significantly greater at 50s and 60s, depending on the intensity. MPS induced a greater peak response in MAP than lower intensities (P < 0.05). None of the subjects reported pain during the MPS and LPS trials. Conclusion Static passive stimulation of the forearm is an effective method of isolating the muscle mechanoareflex-induced pressor response in humans.
... The muscle reflex is triggered by the excitation of mechanoand metabosensitive group III and IV muscle afferents during exercise (16,34,42,45,57). Both animal (6,30,52) and human (1,27) studies have demonstrated a crucial role of the neural feedback from these muscle afferents in determining adequate ventilatory responses to exercise. ...
We examined the interactive influence of the muscle reflex (MR) and the chemoreflex (CR) on the ventilatory response to exercise. Eleven healthy subjects (5 women/6 men) completed 3 bouts of constant-load single-leg knee-extension exercise in a control trial and an identical trial conducted with lumbar intrathecal fentanyl to attenuate neural feedback from lower limb group III/IV muscle afferents. The exercise during the two trials was performed while breathing ambient air (S a O 2 ~97%, P a O 2 ~84 mmHg, P a CO 2 ~32 mmHg, pH ~7.39), or under normocapnic hypoxia (S a O 2 ~79%, P a O 2 ~43 mmHg, P a CO 2 ~33 mmHg, pH ~7.39) or normoxic hypercapnia (S a O 2 ~98%, P a O 2 ~105 mmHg, P a CO 2 ~50 mmHg, pH ~7.26). During co-activation of the MR and the hypoxia-induced CR (O 2 -CR), minute ventilation (V̇ E ) and tidal volume (V T ) were significantly greater when compared with the sum of the responses to the activation of each reflex alone; there was no difference between the observed and summated responses in terms of breathing frequency (f B ; p = 0.4). During co-activation of the MR and the hypercapnia-induced CR (CO 2 -CR), the observed ventilatory responses were similar to the summated responses of the reflexes (p ≥ 0.1). Therefore, the interaction between the MR and the O 2 -CR exerts a hyper-additive effect on V̇ E and V T , and an additive effect on f B , whereas the interaction between the MR and the CO 2 -CR is simply additive for all ventilatory parameters. These findings reveal that the MR:CR interaction further augments the ventilatory response to exercise in hypoxia.
... McCloskey and Mitchell (1972) demonstrated that when the group HI and group IV muscle afferent activity was abolished the exercise hyperpnoea was largely attenuated, as were the associated cardiovascular responses. Tibes et al. (1977) demonstrated that the non steady-state changes in Ve during Phase 2 hyperpnoea correlated most closely with the changes in concentration in the venous effluent, which they postulated was stimulating the small diameter group m and group IV fibres. ...
The ventilatory response to exercise is well described in the literature, starting with an abrupt increase in ventilation coincident with the start of exercise. This is superseded some 20-40 seconds later by a more gradual rise, reaching steady-state some 3 to 5 min after the start of exercise. Despite considerable research throughout the last century, the mechanisms responsible for the control of breathing during exercise remain controversial. In 1963 Dejours published his neurohumoral hypothesis, whereby the initial increase is a response to neural stimuli and later increase is a response to humorally mediated stimuli. In this thesis I have addressed the following questions: 1. Highly trained athletes are reported to exhibit a large initial ventilatory response to the onset of exercise. Does the ventilatory response to exercise of highly trained sportsmen follow a similar profile to those reported in the literature for normal individuals? 2. Is exercise hyperpnoea a response to a neural and a humoral stimulus? 3. Is it possible to separate the ventilatory responses to the two stimuli by changing arterial Pco2? In addition I have addressed the following questions: Does pedal frequency affect a subject's exercise responses? Does the act of prior hyperventilation directly affect a subject's initial ventilatory response to the onset of exercise? Does lowering arterial Pco2 affect postural sway - a control mechanism with a subcortical CNS component? The results reported in this thesis support the view that CO2 plays a major part in the control of the ventilatory response to moderate intensity exercise. They raise questions concerning the origin of the stimulus responsible for the initial increase in ventilation seen on commencing exercise or following a step-increase in workload, and they highlight the effect of forewarning on the initial ventilatory and pulmonary gas exchange response to an increase in exercise intensity.
... The seminal work that defined the exercise pressor reflex and its afferent, efferent and central components was performed primarily in the cat and dog (Coote et al. 1971;McCloskey & Mitchell, 1972;Mizumura & Kumazawa, 1976;Tibes, 1977;Victor et al. 1989b;Matsukawa et al. 1990;Hill et al. 1992;Matsukawa et al. 1994;Hayes & Kaufman, 2001;Chatterjee et al. 2011). Numerous studies, however, demonstrated variable results, ultimately due to the use of anaesthetic agents, in several large animal species (Mitchell et al. 1968;Clement et al. 1973;Clement, 1976;Tallarida et al. 1985). ...
Key points
The decerebrate mouse provides a novel working model of the exercise pressor reflex (EPR).
The decerebrate mouse model of the EPR is similar to the previously described decerebrate rat model.
Studying the EPR in transgenic mouse models can define exact mechanisms of the EPR in health and disease.
Abstract
The exercise pressor reflex (EPR) is defined by a rise in mean arterial pressure (MAP) and heart rate (HR) in response to exercise and is necessary to match metabolic demand and prevent premature fatigue. While this reflex is readily tested in humans, mechanistic studies are largely infeasible. Here, we have developed a novel murine model of the EPR to allow for mechanistic studies in various mouse models. We observed that ventral root stimulation (VRS) in an anaesthetized mouse causes a depressor response and a reduction in HR. In contrast, the same stimulation in a decerebrate mouse causes a rise in MAP and HR which is abolished by dorsal rhizotomy or by neuromuscular blockade. Moreover, we demonstrate a reduced MAP response to VRS using TRPV1 antagonism or in Trpv1 null mice while the response to passive stretch remains intact. Additionally, we demonstrate that intra‐arterial infusion of capsaicin results in a dose‐related rise in MAP and HR that is significantly reduced by a selective and potent TRPV1 antagonist or is completely abolished in Trpv1 null mice. These data serve to validate the development of a decerebrate mouse model for the study of cardiovascular responses to exercise and further define the role of the TRPV1 receptor in mediating the EPR. This novel model will allow for extensive study of the EPR in unlimited transgenic and mutant mouse lines, and for an unprecedented exploration of the molecular mechanisms that control cardiovascular responses to exercise in health and disease.
... Indeed, it has been suggested that group III-IV muscle afferents are sensitive to changes in muscle acidosis and extracellular potassium concentration [38,39]. The chemo-sensitive activation of these afferents could elicit a marked stimulation of the respiratory neurones [40,41], thus leading to an abrupt increase in minute ventilation. Based on this sensorimotor reflex loop, it might be hypothesized that ventilation exhibits a first breakpoint (VT 1 ) when an abrupt increase in the number of active motor units (EMG T1 ) occurs, and a second breakpoint (VT 2 ), coinciding with the change in motor unit recruitment from predominantly slow twitch motor units to fast twitch motor units (EMG T2 ). ...
(1) Background: The aim of this study was to investigate the validity and reliability of surface electromyography (EMG) for automatic detection of the aerobic and anaerobic thresholds during an incremental continuous cycling test using 1 min exercise periods in elite cyclists. (2) Methods: Sixteen well-trained cyclists completed an incremental exercise test (25 W/1 min) to exhaustion. Surface bipolar EMG signals were recorded from the vastus lateralis, vastus medialis, biceps femoris, and gluteus maximus, and the root mean square (RMS) were assessed. The multi-segment linear regression method was used to calculate the first and second EMG thresholds (EMGT1 and EMGT2). During the test, gas exchange data were collected to determine the first and second ventilatory thresholds (VT1 and VT2). (3) Results: Two breakpoints (thresholds) were identified in the RMS EMG vs. time curve for all muscles in 75% of participants. The two breakpoints, EMGT1 and EMGT2, were detected at around 70%–80% and 90%–95% of VO2MAX, respectively. No significant differences were found between the means of VT1 and EMGT1 for the vastii and biceps femoris muscles (p > 0.05). There were no significant differences between means of EMGT2 and VT2 (p > 0.05). (4) Conclusions: It is concluded that the multi-segment linear regression algorithm is a valid non-invasive method for analyzing the aerobic-anaerobic transition during incremental tests with 1 min stage durations.
... The mechanoreflex may be studied in humans and animals by investigating the autonomic and/or cardiovascular responses to passive movement or stretch of limb skeletal muscles (e.g., Tibes 1977;Stebbins et al. 1988;Smith et al. 2001;Fisher et al. 2005;Cui et al. 2006;Ives et al. 2016;Drew et al. 2017). In decerebrate, unanesthetized rats, Copp et al. (2016a) recently investigated the effect of GsMTx4, a tarantula peptide that inhibits mechanically activated channels (Bae et al. 2011), on the mechanoreflex evoked by static hindlimb muscle stretch and the exercise pressor reflex evoked by dynamic hindlimb muscle contraction. ...
Mechanical signals within contracting skeletal muscles contribute to the generation of the exercise pressor reflex; an important autonomic and cardiovascular control mechanism. In decerebrate rats, the mechanically activated channel inhibitor GsMTx4 was found to reduce the pressor response during static hindlimb muscle stretch; a maneuver used to investigate specifically the mechanical component of the exercise pressor reflex (i.e., the mechanoreflex). However, the effect was found only during the initial phase of the stretch when muscle length was changing and not during the later phase of stretch when muscle length was relatively constant. We tested the hypothesis that in decerebrate, unanesthetized rats, GsMTx4 would reduce the pressor response throughout the duration of a 30 sec, 1 Hz dynamic hindlimb muscle stretch protocol that produced repetitive changes in muscle length. We found that the injection of 10 μg of GsMTx4 into the arterial supply of a hindlimb reduced the peak pressor response (control: 15 ± 4, GsMTx4: 5 ± 2 mmHg, P < 0.05, n = 8) and the pressor response at multiple time points throughout the duration of the stretch. GsMTx4 had no effect on the pressor response to the hindlimb arterial injection of lactic acid which indicates the lack of local off‐target effects. Combined with the recent finding that GsMTx4 reduced the pressor response only initially during static stretch in decerebrate rats, the present findings suggest that GsMTx4‐sensitive channels respond primarily to mechanical signals associated with changes in muscle length. The findings add to our currently limited understanding of the channels that contribute to the activation of the mechanoreflex.
... Stimulation of the hind leg musclestretch afferents in cat increases respiratory rate and rhythm, blood pressure, and heart rate (18,23). In the dog, stimulation of the proximal cut end had similar effects proportional to the frequency of stimulation (17,23,29). A neuronal tract tracer (biocytin) injected into the iliac segment of the sciatic nerve suggests the central circuit for these brainstem effects might involve the retrotrapezoid nucleus and dorsal lateral medulla (1,14). ...
Obstructive sleep apnea (OSA) is a disorder characterized by collapse of the velopharynx and/or oropharynx during sleep when drive to the upper airway is reduced. Here, we explore an indirect approach for activation of upper airway muscles that might affect airway dynamics, namely, unilateral electrical stimulation of the afferent fibers of the sciatic nerve, in an anesthetized rabbit model. A nerve cuff electrode was placed around the sciatic and hypoglossal nerves to deliver stimulus while airflow, air pressure, and alae nasi electromyogram (EMG) were monitored both before and after sciatic transection. Sciatic nerve stimulation increased respiratory effort, rate, and alae nasi EMG, which persisted for seconds after stimulation; however, upper airway resistance was unchanged. Hypoglossal stimulation reduced resistance without altering drive. Although sciatic nerve stimulation is not ideal for treating OSA, it remains a target for altering respiratory drive.
NEW & NOTEWORTHY Previously, sciatic nerve stimulation has been shown to activate upper airway and chest wall muscles. The supposition that resistance through the upper airway would be reduced with this afferent reflex was disproven. Findings were in contrast with the effect of hypoglossal nerve stimulation, which was shown to decrease resistance without changing muscle activation or ventilatory drive.
... 4, 8) e deglienzimi urinari sia lisosomiali (NAG 0 N-acetil glucosaminidasi) che del brushborder tubulare (alfa-glucosidasi e AAP o Alanino-aminopeptidasi) (Figg. [5][6][7][9][10][11]. I risultati ottenuti dal nostro studio si accordano bene con i meccanismi di adattamento dell'organismo allo sforzo. ...
... First, group IV (i.e., primarily metabolically sensitive) muscle afferents have been found to increase their responsiveness during even very lowintensity dynamic exercise (1). Second, although static hindlimb muscle stretch in the cat was found to have no impact on muscle effluent venous blood pH, lactate, or K ϩ (39), we cannot rule out the possibility that dynamic muscle stretch produced some chemical substance that contributed to the evoked pressor response to a small degree (20,43). Third, muscle mechanoreceptors were stimulated differently during dynamic stretch and contraction in our experiments. ...
Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease (PAD) in which a femoral artery is chronically (~72 hours) ligated, the mechanically-sensitive component of the exercise pressor reflex during 1 Hz dynamic contraction is exaggerated compared to that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats we tested the hypothesis that the increases in mean arterial blood pressure (MAP) and renal sympathetic nerve activity (RSNA) during 1 Hz dynamic stretch are larger when evoked from a previously "ligated" hindlimb compared to those evoked from the contralateral "freely perfused" hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that replicated closely the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in MAP (freely perfused: 14±1, ligated: 23±3 mmHg, p=0.02) and RSNA were significantly greater during dynamic stretch of the ligated hindlimb compared to the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically-sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated PAD involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization.
... Isometric exercise provides a convenient and easy way to activate the cardiovascular system and define the role of the sympathetic nervous system in the exercise response. Isometric muscle contraction evokes large increase in mean arterial pressure, heart rate and muscle sympathetic nerve activity(MSNA) with a minor rise in central hemodynamics [15][16][17] .The increases in MSNA are thought to result, primarily from activation of the muscle metaboreflex or exercise pressor reflex in the exercising muscle [18][19][20] .This reflex originates in sensory receptors which appear to be sensitive to ischemic metabolites generated during muscular contraction, via small myelinated or unmyelinated (group III or IV) afferent fibers, and elicits cardiovascular and vasomotor reflexes [21][22][23][24] . ...
Cigarette smoking is a worldwide major risk factor for the development of atherosclerosis, coronary heart disease acute myocardial infarction and sudden cardiac death in the younger age in south Asia. Smoking affects the cardiovascular system by several mechanisms. The present study was planned to study the effect of smoking on sympathetic nerve activity by isometric handgrip test in normal healthy young adults. Hundred male subjects in the age group of 18 to 25 years were involved. It included 50 smokers and 50 non - smokers (control group).Sympathetic nerve activity was assessed by isometric hand grip test. BMI, hand grip strength, endurance time, blood pressure before and after hand grip, and diastolic difference were assessed and compared between both the groups. Statistical analysis was done using SPSS 21. Student t test was performed to compare the variables between two groups.There was statistically significant increase in resting systolic pressure (p<0.01), diastolic Pressure (p<0.01), resting Heart Rate (p<0.01), resting mean arterial pressure (p<0.006), and significant diastolic pressure difference (p<0.001) in smokers when compared to nonsmokers. This reflects defect in sympathetic vasomotor tone. Thus the study concludes that smoking possibly has an effect on baroreflex suppression of sympathetic activation in habitual young smokers. Cessation of smoking is associated with reduced cardiovascular mortality and morbidity. © 2016, Oriental Scientific Publishing Company. All rights reserved.
... Previous magnetic resonance spectroscopy studies suggest that the rate of substrate depletion and metabolite accumulation at a given workload is highly sensitive to arterial oxygenation and therefore exacerbated by compromised muscle O 2 delivery (Hogan et al. 1999;Vanhatalo et al. 2010). It is in this context important to recognize that group III/IV afferent blockade during exercise removes a potent stimulator of the respiratory and the cardiovascular control system during exercise (Kao, 1963;McCloskey & Mitchell, 1972;Tibes, 1977;. This resulted in hypoventilation (as evidenced by the 7% decrease inVE/V CO 2 in the present study) and probably attenuated limb blood flow (Amann et al. 2011b) which, in combination, compromised muscle O 2 delivery. ...
... Previous magnetic resonance spectroscopy studies suggest that the rate of substrate depletion and metabolite accumulation at a given workload is highly sensitive to arterial oxygenation and, therefore, exacerbated by compromised muscle O 2 delivery (Hogan et al., 1999;Vanhatalo et al., 2010). It is in this context important to recognize that group III/IV afferent blockade during exercise removes a potent stimulator of the respiratory and the cardiovascular control system during exercise (Kao, 1963;McCloskey & Mitchell, 1972;Tibes, 1977;. This resulted in hypoventilation (as evidenced by the 7% decrease in ̇E / ̇C O 2 in the present study) and likely attenuated limb blood flow (Amann et al., 2011b) which, in combination, compromised muscle O 2 delivery. ...
Key points:
The purpose of this study was to determine the role of group III/IV muscle afferents in limiting the endurance exercise-induced metabolic perturbation assayed in muscle biopsy samples taken from locomotor muscle. Lumbar intrathecal fentanyl was used to attenuate the central projection of μ-opioid receptor-sensitive locomotor muscle afferents during a 5 km cycling time trial. The findings suggest that the central projection of group III/IV muscle afferent feedback constrains voluntary neural 'drive' to working locomotor muscle and limits the exercise-induced intramuscular metabolic perturbation. Therefore, the CNS might regulate the degree of metabolic perturbation within locomotor muscle and thereby limit peripheral fatigue. It appears that the group III/IV muscle afferents are an important neural link in this regulatory mechanism, which probably serves to protect locomotor muscle from the potentially severe functional impairment as a consequence of severe intramuscular metabolic disturbance.
Abstract:
To investigate the role of metabo- and mechanosensitive group III/IV muscle afferents in limiting the intramuscular metabolic perturbation during whole body endurance exercise, eight subjects performed 5 km cycling time trials under control conditions (CTRL) and with lumbar intrathecal fentanyl impairing lower limb muscle afferent feedback (FENT). Vastus lateralis muscle biopsies were obtained before and immediately after exercise. Motoneuronal output was estimated through vastus lateralis surface electromyography (EMG). Exercise-induced changes in intramuscular metabolites were determined using liquid and gas chromatography-mass spectrometry. Quadriceps fatigue was quantified by pre- to post-exercise changes in potentiated quadriceps twitch torque (ΔQTsingle ) evoked by electrical femoral nerve stimulation. Although motoneuronal output was 21 ± 12% higher during FENT compared to CTRL (P < 0.05), time to complete the time trial was similar (∼8.8 min). Compared to CTRL, power output during FENT was 10 ± 4% higher in the first half of the time trial, but 11 ± 5% lower in the second half (both P < 0.01). The exercise-induced increase in intramuscular inorganic phosphate, H(+) , adenosine diphosphate, lactate and phosphocreatine depletion was 55 ± 30, 62 ± 18, 129 ± 63, 47 ± 14 (P < 0.001) and 27 ± 14% (P < 0.01) greater in FENT than CTRL. ΔQTsingle was greater following FENT than CTRL (-52 ± 2 vs -31 ± 1%, P < 0.001) and this difference was positively correlated with the difference in inorganic phosphate (r(2) = 0.79; P < 0.01) and H(+) (r(2) = 0.92; P < 0.01). In conclusion, during whole body exercise, group III/IV muscle afferents provide feedback to the CNS which, in turn, constrains motoneuronal output to the active skeletal muscle. This regulatory mechanism limits the exercise-induced intramuscular metabolic perturbation, preventing an abnormal homeostatic challenge and excessive peripheral fatigue.
... An input via muscular group IV fibers proved to be particularly effective in evoking excitatory CV reflexes (Laporte et al. 1960, Johansson 1962, Sato et al. 1981; whereas, stimulation of presumably all group I fibers in a dorsal root was ineffective (Laporte et al. 1962). Additional evidence for an involvement of small-diameter afferents in the reflexes was obtained in experiments employing cold blockage of the large-diameter fibers (Tibes 1977). The effects of group III fiber activation on blood pressure were found to be dependent on the frequency of stimulation, a low frequency leading to a fall and a high frequency to a rise in blood pressure (Fernandez et al. 1953, Laporte et al. 1960). ...
Subjective sensations from deep tissues, which are probably mediated by slowly conducting afferent fibers, play an important role in everyday life. Thus, deep pain is a much commoner reason for consulting a physician than is cutaneous pain. Similarly, reflexes elicited by these fibers (e.g., cardiopulmonary (CP) adjustments during exercise) are essential for the normal functioning of a living organism. Yet most studies dealing with the function of afferent fiber systems have concentrated either on cutaneous fibers or on deep receptors with rapidly conducting afferent fibers. For example, in two of the most elaborate reviews on muscle receptors published to date (Matthews 1972, Barker 1974), only a few pages are devoted to receptive endings with fibers of small diameter. The present report gives an overview of the current knowledge of the physiology and morphology of these afferent units.
... Mechanism fw isoaretric excmise-induced isckmia. Experimental studies (20)(21)(22)(23)(24)(25) have demonstrated a sympathetic nerve reflex during handgrip exercise with the tierent limb in skeletal muscle stretch receptors and the efferent limb mediated by sympathetic nerve fibers impinging directly on coronary arteries and by increased circulating epinephrine and norepinephrine levels. An Inappropriate alpha-adrenergic coronary constriction has b:en hypothesized in humans as the dominant mechanism for handgripinduced myocardial ischemia, minimizing the importance CT the slight in-lACC Vol. ...
The effects of isometric exercise on regional left ventricular mechanical function and regional coronary blood flow were evaluated in 17 patients with significant proximal stenosis of the left anterior descending coronary artery and 10 patients with normal coronary arteriograms. All patients had normal myocardial contractility in the basal condition. All performed isometric handgrip exercise at 50% of the maximal voluntary contraction for 3 min during two-dimensional echocardiographic monitoring and hemodynamic evaluation of great cardiac vein flow by thermodilution technique.During isometric exercise, 7 of the 17 patients with left anterior descending coronary stenosis developed asynergy in the anterior territory (anterior or septal segment, or both) (group I); the remaining 10 showed normal myocardial contraction during the test (group II). The 10 normal subjects manifested no regional asynergy during the test (control group). The increase in great cardiac vein flow at peak isometric exercise was significantly smaller (p < 0.01) in group I (+15 ± 8%) than that in group II (+98 ± 48%) and the control group (+64 ± 22%). Anterior coronaryvascular resistance decreased in group II (−32 ± 13%) and in the control group (−25 ± 8%) bus increased in group I (+6 ± 8%, p < 0.01 versus group II and control group).These data demonstrate that handgrip-induced myocardial asynergy is associated, in our study patients, with an abnormal response of the regional coronary circulation. The increase in coronary vascular resistance in group I patients with asynergy demonstrates that functional mechanisms play a dominant role in left ventricular mechanical dysfunction induced by isometric exercise.
... Metaborezeptoren sind Muskelafferenzen der Gruppe III und IV, welche durch chemische Mediatoren stimuliert werden, die während Muskelarbeit freigesetzt werden. Die Aktivierung dieser Afferenzen wirkt sich auf die Herzfrequenz, den Blutdruck, das Herzzeitvolumen , das Schlagvolumen, die Ventilation und die sympathische Nervenaktivität aus (McCloskey und Mitchell, 1972; Mark et al., 1985; Tibes, 1977; Sterns et al., 1991; Piepoli et al., 1995; Negrao et al., 2001 ...
... The role of group III/IV muscle afferents on the development of peripheral fatigue is manifested through their contribution to the cardiovascular, hemodynamic, and ventilatory adjustments occurring during exercise. Increases in these parameters arising with the onset of exercise are, next to central command (Waldrop et al., 1996), largely determined by neural feedback from the working muscle and assure augmented blood flow and O 2 delivery to the working muscle (Asmussen et al., 1943;Coote et al., 1971;Hollander and Bouman, 1975;Kao, 1963;McCloskey and Mitchell, 1972;Tibes, 1977). Both of these variables depict key components in the rate of development of peripheral fatigue during exercise (Barclay, 1986;Fulco et al., 1996;Katayama et al., 2007). ...
Group III and IV muscle afferents originating in exercising limb muscle play a significant role in the development of fatigue during exercise in humans. Feedback from these sensory neurons to the central nervous system (CNS) reflexively increases ventilation and central (cardiac output) and peripheral (limb blood flow) hemodynamic responses during exercise and thereby assures adequate muscle blood flow and O2 delivery. This response depicts a key factor in minimizing the rate of development of peripheral fatigue and in optimizing aerobic exercise capacity. On the other hand, the central projection of group III/IV muscle afferents impairs performance and limits the exercising human via its diminishing effect on the output from spinal motoneurons which decreases voluntary muscle activation (i.e. facilitates central fatigue). Accumulating evidence from recent animal studies suggests the existence of two subtypes of group III/IV muscle afferents. While one subtype only responds to physiological and innocuous levels of endogenous intramuscular metabolites (lactate, ATP, protons) associated with ?normal?, predominantly aerobic exercise, the other subtype only responds to higher and concurrently noxious levels of metabolites present in muscle during ischaemic contractions or following, for example, hypertonic saline infusions. This review discusses the mechanisms through which group III/IV muscle afferent feedback mediates both central and peripheral fatigue in exercising humans. We also briefly summarize accumulating evidence from recent animal and human studies documenting the existence of two subtypes of group III/IV muscle afferents and the relevance of this discovery for the interpretation of previous work and the design of future studies.
... Studies that have used electrically induced contractions of the hind limbs of dogs (264,265) and cats (296) have shown that a peripheral neurogenic drive contributes, at least in part, to the exercise hyperpnea. However, other studies have shown that spinal cord trans-section does not abolish the hyperpnea of electrically induced muscle contraction in anesthetized animals (112,524,566). These experimental findings in animals are consistent with data on electrically induced contractions in humans with spinal cord injury (77,79) or in spinal cord-intact humans with epidural anesthesia to block peripheral afferents (160). ...
During dynamic exercise, the healthy pulmonary system faces several major challenges, including decreases in mixed venous oxygen content and increases in mixed venous carbon dioxide. As such, the ventilatory demand is increased, while the rising cardiac output means that blood will have considerably less time in the pulmonary capillaries to accomplish gas exchange. Blood gas homeostasis must be accomplished by precise regulation of alveolar ventilation via medullary neural networks and sensory reflex mechanisms. It is equally important that cardiovascular and pulmonary system responses to exercise be precisely matched to the increase in metabolic requirements, and that the substantial gas transport needs of both respiratory and locomotor muscles be considered. Our article addresses each of these topics with emphasis on the healthy, young adult exercising in normoxia. We review recent evidence concerning how exercise hyperpnea influences sympathetic vasoconstrictor outflow and the effect this might have on the ability to perform muscular work. We also review sex-based differences in lung mechanics. © 2012 American Physiological Society. Compr Physiol 2:1093-1142, 2012.
... In experiments using graded electrical stimulation of the muscle nerve and measuring the concomitant changes in circulatory or respiratory variables, it became clear that receptors with thin afferent fibres formed the afferent branch of the reflex arc (Colle & Gybels, 1957;Laporte, Bessou & Bouisset, 1960;Coote et al. 1971;Sato, Sato & Schmidt, 1981). Some authors employed chemical stimulation of muscle receptors (Mizumura & Kumazawa, 1976) or differential nerve blocking techniques (McCloskey & Mitchell, 1972), partly in combination with mechanical stimulation (Kalia, Senapati, Parida & Panda, 1972) or evoked muscular activity (Tibes, 1977;Kalia, Mei & Kao, 1981) in order to establish that the thick muscle afferents (group I and II) were not of importance for the induction of the reflexes. There is some evidence, though, that respiration can be influenced by activity in these afferents (Bessou, Dejours & Laporte, 1959;Koizumi, Ushiyama & Brooks, 1961). ...
The aim of the study was to find out to what extent muscle receptors with slowly conducting afferent fibres (group III and IV) are activated by muscular contractions of moderate force, and what kind of muscle afferents could mediate the pain of ischaemic exercise. In chloralose-anaesthetized cats, the impulse activity of single afferent units from the triceps surae muscle was recorded from dorsal root filaments during muscular contractions with intact blood supply and after occlusion of the muscle artery. Two types of responses were observed to contractions without muscular ischaemia. One was characterized by sudden onset and a graded response amplitude to contractions of increasing force. In most cases stretching the muscle was also an effective stimulus. Units showing this response behaviour were labelled c.s.m (contraction-sensitive with mechanical mechanism of activation). The other response type had a more delayed onset and often outlasted the exercise period; because of the unknown mechanism of activation, units of this kind were labelled c.s.x. The proportion of c.s.m receptors was significantly higher amongst group III than amongst group IV units. During ischaemic contractions of comparable force the c.s.m and c.s.x receptors exhibited an unchanged or a decreased response amplitude. Under these conditions another receptor type (N, for nociceptive) was activated which did not respond to contractions with intact blood supply. Vigorous activations during ischaemic work were only observed in group IV receptors. The majority of the 131 group III and IV units tested did not respond to contractions at all. These contraction-insensitive (c.i.) endings probably comprised different receptor populations (nociceptors, thermoreceptors, low-threshold mechanoreceptors). It is concluded that the various central nervous effects of muscular exercise without ischaemia which are known to be due to raised activity in thin muscle afferents (e.g. cardiopulmonary adjustments, spinal locomotor reflexes) are probably produced by the c.s.m and c.s.x types. The pain of ischaemic contractions is most likely mediated by the N receptors most of which possess non-myelinated afferent fibres.
Substantial advances have been made recently into the discovery of fundamental mechanisms underlying the neural control of breathing and even some inroads into translating these findings to treating breathing disorders. Here, we review several of these advances, starting with an appreciation of the importance of V̇A:V̇CO2:PaCO2 relationships, then summarizing our current understanding of the mechanisms and neural pathways for central rhythm generation, chemoreception, exercise hyperpnea, plasticity, and sleep-state effects on ventilatory control. We apply these fundamental principles to consider the pathophysiology of ventilatory control attending hypersensitized chemoreception in select cardiorespiratory diseases, the pathogenesis of sleep-disordered breathing, and the exertional hyperventilation and dyspnea associated with aging and chronic diseases. These examples underscore the critical importance that many ventilatory control issues play in disease pathogenesis, diagnosis, and treatment.
In health, the near-eucapnic, highly efficient hyperpnea during mild-to-moderate intensity exercise is driven by three obligatory contributions, namely, feedforward central command from supra-medullary locomotor centers, feedback from limb muscle afferents, and respiratory CO2 exchange (V̇CO2). Inhibiting each of these stimuli during exercise elicits a reduction in hyperpnea even in the continuing presence of the other major stimuli. However, the relative contribution of each stimulus to the hyperpnea remains unknown as does the means by which V̇CO2 is sensed. Mediation of the hyperventilatory response to exercise in health is attributed to the multiple feedback and feedforward stimuli resulting from muscle fatigue. In patients with COPD, diaphragm EMG amplitude and its relation to ventilatory output are used to decipher mechanisms underlying the patients’ abnormal ventilatory responses, dynamic lung hyperinflation and dyspnea during exercise. Key contributions to these exercise-limiting responses across the spectrum of COPD severity include high dead space ventilation, an excessive neural drive to breathe and highly fatigable limb muscles, together with mechanical constraints on ventilation. Major controversies concerning control of exercise hyperpnea are discussed along with the need for innovative research to uncover the link of metabolism to breathing in health and disease.
Blood pressure is one of the vital signs and its regulation is crucial for survival. Several mechanisms contribute to maintain it in a physiological range: renin-angiotensin-aldosterone system, the autonomous nervous system and specialized baroreceptors neurons. In this study, we demonstrate the existence of a new population of sensory neurons marked by TrkC and TH that innervate blood vessels and are important in the control of blood pressure, blood flow and heart rate. Using an inducible Cre line driven from the TrkC locus, we show that TrkC is expressed in 30% of DRG neurons and that a fourth of these neurons are TH+ and project to blood vessels. Activation of TrkC+ TH+ neurons leads to high blood pressure, decreased blood flow and increased heart rate variability. Loss of function experiments revealed that TrkC+ TH+ sensory neurons are crucial for life. Ablation of TrkC+ neurons results in low blood pressure, alteration of blood flow and increased heart rate variability. All these cardiovascular alterations lead ablate mice to death within 48 hours. We also demonstrate that TrkC+ neurons do not act directly on blood vessels, but they exert their functions through a circuit with the sympathetic nervous system. We thus identified a new population of sensory neurons involved in the regulation of blood pressure, blood flow and heart rate and we hope that this can lead to the development of new therapeutic strategies in the near future.
Maintenance of adequate perfusion to the tissues is achieved by circulation of limited volume blood driven by the intermittently contracting heart through different components of the vasculature. Each component of vasculature has unique properties suited to its function. A clear understanding of the haemodynamic principles that govern the blood flow is critical for appreciating the physiological mechanism that operates to maintain cardiac output during changing metabolic demands. A large number of reflexes modulate the properties of heart and vasculature for homeostatic maintenance of the haemodynamics and its modulation during emotions and motivated behaviours such as exercise.
The control of rate, rhythm and depth of different phases of respiration is required not only for exchange of gases but also during non-respiratory motor behaviours and emotional states. A network of rhythm-generating and pattern-generating neural groups in the ponto-medullary region of brain controls the activity of inspiratory, expiratory and accessory muscles of respiration. This network is intricately connected to the higher subcortical and cortical regions of the brain for state and behaviour-specific modulation respiration. The network also receives afferent information from periphery to modulate the ongoing respiratory activity to match the respiration with the metabolic needs. This chapter details the most recent information regarding neural substrate and models that underlie the control of respiration.
The partial pressures of carbon dioxide and oxygen in the blood are the dominant homeostatic controller of respiration. Over the course of evolution, in addition to its primary purpose of exchange of gases, the control of ventilatory apparatus has become a part of a large number of non-respiratory motor behaviours such as swallowing, vocalization and abdominal straining during parturition. The emotional states and sleep–wakefulness states are associated with altered respiratory pattern. A number of reflexes protect the respiratory tract from environmental irritants, from aspiration of mucous and from food during ingestion. The thorough information regarding the patterns of respiratory modulation during a wide variety of the physiological activities shall be presented this chapter along with the most recent information on the neural basis for such modulations.
New findings:
What is the topic of this review? This review examines the evidence for control mechanisms underlying the exercise hyperpnoea, with particular attention placed on the feedback from thin fibre skeletal muscle afferents, and highlights the often conflicting findings and difficulties encountered by researchers using a variety of experimental models. What advances does it highlight? There has been a recent resurgence of interest in the role of skeletal muscle afferent involvement, not only as a mechanism of the healthy exercise hyperpnoea but also for its involvement in the manifestation of breathlessness and exercise intolerance in chronic disease.
Abstract:
The ventilatory response to dynamic submaximal exercise is immediate and proportional to metabolic rate, which maintains isocapnia. How these respiratory responses are controlled remains poorly understood given that the most tightly controlled variable (PaCO2 /H+ ) provides no error signal for arterial chemoreceptors to trigger reflex increases in ventilation. This review discusses evidence for different postulated control mechanisms with a focus on the feedback from group III/IV skeletal muscle mechanosensitive and metabosensitive afferents. This concept is attractive as the stimulation of muscle mechanoreceptors may account for the immediate increase in ventilation exercise onset, and signals from metaboreceptors may be proportional to metabolic rate. A variety of experimental models have been used to establish the contribution of thin fibre muscle afferents in exercise ventilatory control with equivocal results. Inhibiting afferent feedback via the application of lumbar intrathecal fentanyl during exercise supresses ventilation, which provides the most compelling supportive evidence to date. However, stimulating afferent feedback at rest has no consistent effect on respiratory output. However, evidence is emerging for synergistic interactions between muscle afferent feedback and other stimulatory inputs to the central respiratory neuronal pool. These seemingly hyperadditive effects might explain the conflicting findings encountered when using different experimental models. The review also discusses the increasing evidence that patients with certain chronic diseases exhibit exaggerated muscle afferent activation during exercise resulting in enhanced cardiorespiratory responses. This may provide a neural link between the well-established limb muscle dysfunction and associated exercise intolerance and exertional dyspnoea, and hence offer therapeutic targets for these patients. This article is protected by copyright. All rights reserved.
When exercise starts, various cardiorespiratory adjustments take place for accommodating the greatly increased metabolic requirements. It is well known that the transition from rest to light or moderate intensity exercise is typically accompanied by an abrupt step-1ike increment in ventilation at the first exercise breath. This rapid increment of ventilation at the onset of exercise (phase I) is observed during not only voluntary and passive exercise, but also during electrically induced muscle contraction. A rapid response in ventilation (phase I) may be at least useful for preventing oxygen deficiency and for increasing alveolar ventilation, oxygen tension, and oxygen uptake even if it is a small quantity. Although mechanisms of phase I have extensively been explored by many investigators, they have still remained obscure until now. At present, the causal factors of phase I are classified as central (descending) and peripheral (ascending) neurogenic stimulus, or as both. In the awake condition, abrupt ventilatory increment immediately after voluntary and passive exercise in man could be attributed to the drives from the central command including cortical and hypothalamic activities as well as some peripheral afferent information mainly through group III and IV fibers. However, further investigation to clarify many unsolved problems regarding neurogenic mechanisms of phase I should be advanced in future.
During incremental work-rate exercise there is a work-rate termed the anaerobic threshold (AT) above which lactic acid accumulates in the blood (Tlact) and minute ventilation (V) increases non-linearly with respect to work-rate (Tvent) resulting in hyperventilation and consequently arterial hypocapnia.1 The mechanisms of ventilatory control during exercise below the AT (mild-moderate exercise) remain unknown with evidence being presented for all of the control being of either neural origin2,3 or humoral origin4 as well as for combinations of these mechanisms.5,6 Above the AT (heavy exercise), it has generally been believed that the lactic acidosis, acting exclusively via the carotid bodies, stimulates virtually all of the hyperventilatory response,7,8 The usual coincidence of Tlact and Tvent,1 the lack of respiratory compensation to metabolic acidosis of heavy exercise in carotid body-resected bronchial asthmatics,7 and a substantial and persistent ventilatory depression with hyperoxic suppression of the carotid body during heavy exercise7,8 have been the usual reasons cited for this position. This position has been challenged by many recent studies.
Muscular work can only be sustained if two transport chains function effectively: the electron transport chain and the oxygen transport chain. These may be considered to be “linked” at cytochrome oxidase. This chapter focuses on the effective functioning of the primary systems that comprise the oxygen transport chain in humans; the effective function of the electron transport chain is considered elsewhere (Chap. 71).
Muscular exercise can only be performed at the expense of energy stores which are readily accessible to the contractile mechanisms of skeletal muscle; specifically, through the utilization of the free energy of hydrolysis of ATP. Intramuscular ATP concentrations are themselves maintained at the expense of creatine phosphate breakdown and through increased rates of ATP production resulting from aerobic or anaerobic metabolism.
Unsere Untersuchungen haben zum Ziel, die Beteiligung chemosensitiver Rezeptoren in der Skelettmuskulatur (metabolische Muskelrezeptoren) an Kreislaufantrieben während körperlicher Arbeit zu klären [4]. Kniffki et al. [2] neigten aufgrund ihrer Untersuchungen zu der Hypothese, daß kontraktionssensitive Afferenzen als Ergorezeptoren der Muskelarbeit dienen. Die chemosensitiven Gruppe-III- und IV-Einheiten wurden von diesen Autoren eher der Nozizeption zugerechnet. Andererseits ist gezeigt worden, daß Substanzen, deren Konzentrationen sich bei Muskelarbeit erhöhen (Kalium, Milchsäure, Phosphat), über Gruppe-HI- und/oder Gruppe-IV-Äfferenzen Kreislaufreaktionen auslösen [5, 8; vgl. auch 6, 7]. Es ist daher zu fragen, in welcher Weise sich metabolische Muskelrezeptoren und Nozizeptoren voneinander unterscheiden lassen. In diesem Zusammenhang konzipierten wir drei Versuchsserien:
1)
Lokale Applikation verschiedener Substanzen, deren Konzentrationen sich bei Muskelarbeit erhöhen, bei gleichzeitiger Registrierung der Herzfrequenz [6].
2)
Erzeugung von ischämie-ähnlichen Zuständen in kreislaufisolierten Hinterbeinmuskeln, bei gleichzeitiger Registrierung der Herzfrequenz [7].
3)
Elektrophysiologische Ableitungen von Nervenfasern von langsam leitenden und mittelschnell leitenden Nervenfasern (Gruppe III und IV) des N. personaeus bei Applikation verschiedener Substanzen, deren Konzentrationen sich bei Muskelarbeit erhöhen, in die kreislaufisolierte Hinterbeinmuskulatur [5].
In 1972, Clark and von Euler1 proposed the inspiratory off-switch theory to explain the relationship between inspiratory activity and duration. It was proposed that the inspiratory activity is terminated, and inspiratory duration (TI) is determined when the tidal inspiratory activity reaches a certain off-switch level. One major difference between the study of inspiratory and expiratory activities is that the volume curve does not give as much information on expiratory activity as it does on inspiratory activity. Thus, direct measurements from the expiratory neuromuscular units are necessary to study the relationship between expiratory activity and duration. This is possible in brachial plexus injury (root avulsion type) patients who have undergone the intercostal transfer operation.2 From the studies of the expiratory activity in both humans and lab animals, an “expiratory off-switch mechanism” has been proposed. This mechanism is considered to be an independent system from the inspiratory off-switch system.2,3,4 Another substage within the second stage of expiration (E2 stage)5 has been defined from the onset of the tidal expiratory activity to the suppression of the expiratory activity by the off-switch mechanism. Masato Sibuya would like to dedicate this paper to his grandmother, Raku Sibuya, who passed away during the time of the Oxford Meeting. This was designated the stage of active expiration (Ea stage).2
In psychophysiological research concerning the mechanisms underlying behavioral reactions to stimuli of widely different origins, it is not uncommon to use heart rate (HR) or its inverse, cardiac cycle length, as a measure of the mental events involved in the processing of those stimuli. On the other hand, it has been recognized that the rhythm of our heart beat is continuously controlled by neural, humoral and mechanical factors in order to adjust its function to the variable needs of the organism’s tissues. Among these, one of the most variable types of demand arises from skeletal muscles. It is our daily experience that our heart beats the more frequently, the more intense the physical exertion. This phenomenon is only the most conspicious of a series of events that occur in order to adapt the circulation to the muscles’ need of blood. The physiology of the control mechanism underlying this adaptation will be the subject of the present paper.
Bei den meßtechnischen Limitationen von Herzschrittmachern können aus der Gruppe der respiratorischen Parameter derzeit nur die Atemfrequenz und das Atemzugvolumen erfaßt werden.
Although the response kinetics of ventilatory and gas exchange variables to incremental ramp exercise have been studied intensively in connection with the development of noninvasive techniques for detecting the AT,1, 3 analysis of responses to decrementai ramp forcings is scarce except for the early work of Karlsson and Wigertz.4 They found that with decreasing ramp slope, in both the incremental and decrementai phases of the ramp exercise, the lag of the ventilation and heart rate responses behind the input stimulus became increasingly prolonged.
Until recently, the quantitative analysis of the cardiovascular system was focused primarily on the mechanical properties of the heart and the cardiovascular tree, as well as on the physicochemical properties of the blood. A variety of models were developed dealing either with overall input-output relationships (mostly lumped parameter models) or with the pulsatile nature of blood flow and pressure (mostly distributed parameter models). The investigation of cardiovascular control systems by means of such models was limited largely to isolated control functions such as cardiac and blood volume control, chemo- and baroreceptor reflex loops, and autoregulation [4, 10, 14, 16, 18].
Die Breite des Themas erlaubt es, hier einen Aspekt aus dem Themenkomplex „Herz und Kreislauf beim Sport“ herauszusuchen, der dem Titel dieses Buches „Kardiales Risiko im Sport“ angemessen scheint: die Steuerung des vegetativen Systems bei Leistung. Schließlich bestimmt der vegetative Tonus die Höhe der Frequenz des Herzens und die Kraft seiner Kontraktion (5), während das Herzzeitvolumen im wesentlichen vom venösen Rückfluß abhängt (9). Es ist hinreichend bekannt, daß der Sauerstoffverbrauch des Herzens für eine gegebene Leistung — also der Wirkungsgrad — mit der Kraft-Geschwindigkeits-Relation der Myokardkontraktion variiert. Diese wird über das vegetative System geregelt.
At the onset of exercise abrupt hyperpnea is elicited before metabolites formed in exercising limbs can reach the known sites of ventilatory chemoreception. Therefore, concerning this rapid hyperpnea, defined as Phase 1 of exercise hyperpnea by Wasserman et al.1, it has long been considered that neurogenic stimuli for ventilation may be involved. The neurogenic stimuli include two entities, a reflex activity from the exercising limbs2–9 and supraspinal control.10–12 Despite the intensive investigations hitherto conducted, the understanding of mechanisms of hyperpnea at the onset of muscular exercise is still incomplete. One major difficulty is to distinguish between the neural drives emanating from the exercising muscles and from the higher centers. The first purpose of the present study was to evaluate the quantitative role of both drives by comparing the ventilatory and circulatory responses to voluntary, electrically induced and passive exercise in healthy males and spinal cord transected patients with an equivalent work load.
One hypothesis to explain the rapid neural component of exercise hyperpnea contends that afferent stimuli originating in the ventricles of the heart act reflexly on the respiratory center at the onset of exercise, ie, "cardiodynamic hyperpnea." Orthotopic cardiac transplantation (Tx) results in the loss of afferent information from the ventricles. Thus, Tx possibly results in transient hypercapnia and hypoxemia in deafferented heart transplant recipients (HTR) at the onset of exercise due to hypoventilation. To examine the cardiodynamic hypothesis, we collected serial arterial blood gas (ABG) samples during both the transient and the steady-state responses to moderate cycle exercise in 5 HTRs (55 +/- 7 years) 14 +/- 7 months post-Tx and 5 control subjects matched with respect to gender, age, and body composition. Forced vital capacity, forced expiratory volume in 1 s, total lung capacity, and diffusion capacity did not differ (p > or = 0.05) between groups. Resting arterial PO2, PCO2, and pH did not differ between groups (p > or = 0.05). The ABGs were drawn every 30 s during the first 5 min and at 6, 8, and 10 min of constant load square wave cycle exercise at 40 percent of the peak power output (watts). Absolute and relative changes in arterial PO2, PCO2, and pH were similar (p > or = 0.05) between HTR and the control group at all measurement periods during exercise. Heart rate (%HRmax reserve), rating of perceived exertion, and reductions in plasma volume (% delta from baseline) did not differ between HTR and control during exercise at 40 percent of peak power output (p > or = 0.05). Our results demonstrate that there is no discernible abnormality in ABG dynamics during the transient response to exercise at 40 percent of peak power output in patients with known cardiac denervation. These data do not support the cardiodynamic hyperpnea hypothesis of ventilatory control in humans. The absence of hypercapnia in HTRs is further evidence for the existence of redundant mechanisms capable of stimulating exercise hyperpnea.
The purpose of this study was to investigate the effect of electroacupuncture stimulation (EA) of different frequency on pulse rate and skin temperature. Sixteen healthy male medical student volunteers received EA of 2 Hz, and 100 Hz, respectively on the both Zusanli acupoints (St-36) while resting. Their pulse rates were measured on the middle finger, and skin temperature was taken between the thumb and index finger before, during, and after EA stimulation. Each test took 35 minutes. The initial 10 min were defined as baseline period (no EA), the following 15 min as the EA period and the last 10 min as the post-EA period. Three assessments were performed on each subject as follows: A) control assessment: no EA was done throughout the test; B) 2 Hz EA assessment: 2 Hz EA was applied to both Zusanli acupoints during the EA period; and C) 100 Hz EA assessment: 100 Hz EA was applied to both Zusanli acupoints during the EA period. Our results indicate that both 2 Hz EA and 100 Hz EA decreased pulse rates during the EA period, and these changes remained throughout the post-EA period in 2 Hz EA assessment, but not in 100 Hz EA assessment. Both 2 Hz and 100 Hz EA resulted in decreases of skin temperature during the EA period. Our conclusions are that 2 Hz EA and 100 Hz EA applied to both Zusanli acupoints resulted in the decrease of pulse rate, which possibly evoked greater parasympathetic nerve activity on heart beats. 2 Hz EA had a more sustained effect on heart beats than 100 Hz EA. Decreased skin temperatures in the EA period may have resulted from cutaneous vasoconstriction caused by EA induced sympathetic stress response, suggesting EA at least remains for 15 min in clinical application.
L'objet de cette étude est d'examiner l'effet d'une exposition au froid sur le seuil ventilatoire. Dans ce but, 8 sujets accomplissent sur ergocycle 2 exercices musculaires d'intensité croissante dans une chambre thermostatée, soit à 24°C soit à −2°C. Le protocole consiste à accroître l'intensité de l'exercice de 30 W toutes les 2 min jusqu'à épuisement du sujet. Le débit ventilatoire et la consommation d'oxygène sont mesurés au repos et dans la dernière minute de chaque palier. Des échantillons sanguins destinés à la mesure de la lactatémie sont recueillis à la fin de chaque palier. A 24°C, le seuil ventilatoire (SV) suit le seuil anaérobie lactique (SL). Il existe une corrélation positive entre ces 2 seuils. A −2°C, on observe un frisson intense au niveau du tronc et des membres supérieurs de tous les sujets. La et le obtenus au repos et à chaque puissance d'exercice sont plus élevés que ceux obtenus à 24°C. Le seuil ventilatoire déterminé à −2°C (SVF) survient pour une supérieure de 0,5l·min−1 à celle déterminée au SV. Toutefois, ces 2 seuils se situent à la même puissance d'exercice. La différence de obtenue entre les 2 seuils peut être attribuée au coût de la thermogenèse. Le SVF tend à précéder le seuil anaérobie lactique déterminé à −2°C (SLF). Il n'existe aucune corrélation entre le SVF et le SLF. On peut conclure que le coût de la thermogenèse n'altère pas la relation généralement établie entre et . Le SV dépend de la puissance mécanique fournie par les membres inférieurs plutôt que du niveau atteint par le et le métabolisme aérobie. Dès que l'on s'écarte des températures de confort thermique, le SV semble être un meilleur indicateur de fatigue des membres inférieurs que le SL.
The respiratory behaviour of Locusta migratoria is altered at the onset of flight. The neuronal processes and some of the mechanisms underlying these alterations were studied by using intracellular recording and staining techniques.
It has previously been reported that abdominal pumping ceases for the first seconds of flight. Our data indicate that this phenomenon is not due to inhibition of the respiratory system, since most interneurones and some motoneurones maintain a respiratory rhythm during the onset of flight activity. Likely explanations for the cessation of the abdominal pumping are: (1) increased stiffness of the abdomen due to maintained activation of abdominal muscles and (2) decreased rhythmic modulation in abdominal motor units due to tonic excitatory input.
Two major changes occur in the respiratory system at the onset of flight: (1) the rhythm is reset by an activation of inspiratory and inactivation of expiratory neurones, and (2) the respiratory rate is increased. The increase in the respiratory rate at the onset of flight is in part due to an activation of inspiratory interneurones which are capable of accelerating the respiratory rhythm.
The changes in the respiratory system coinciding with the initiation of flight suggest a feedforward mechanism linking both behaviours. Tonic interneurones, involved in the initiation of flight and influencing respiration, might be involved in linking respiration and flight. At flight onset, one group of these simultaneously disinhibited respiration and flight and thus contributed both to an increase in the respiratory rate and to an activation of the flight system. Another group evoked flight and had variable effects on respiration. One tonic interneurone had a depressing effect on the respiratory rate.
We conclude that respiration is centrally linked to flight in part by the same interneurones controlling the initiation of flight. The existence of such a feedforward mechanism in the locust resembles the situation found in vertebrates, where locomotory and respiratory behaviour can be driven from the same brainstem region.
The reflex increase in ventilation (Ve) produced by natural stimulation of certain sensory receptors in gastrocnemius muscle was studied in dogs anesthetized with Na pentobarbital. Reflex increase in Ve occurred when the endings of group III fibers and nonmedullated fibers were stimulated (by stretching, pressing, or squeezing the muscle locally), whereas the endings of group I and group II fibers were blocked by repetitive antidromic stimulation. Stimulation of endings of nonmedullated fibers alone also increased Ve after all the medullated fibers were blocked either by cooling the medial gastrocnemius nerve to 5 C or by stimulating lateral gastrocnemius nerve repetitively. It was concluded that there were sensory endings of nonmedullated fibers in muscles which are stimulated by stretching, pressing, or squeezing the muscle locally; these endings produce reflex hyperventilation.
antidromic stimulation; gastrocnemius muscle
Experiments were performed to find the adequate stimulus for peripheral muscle chemoreceptors which are assumed to control respiration and circulation during exercise. It could be shown that occlusion of blood flow in the hind limbs of dogs by inflating a small rubber balloon in the abdominal aorta caused similar respiratory and circulatory responses as described in previous papers when the blood flow in the legs of humans was occluded by inflating cuffs. Furthermore, equal volumes of gaseous CO2 were bubbled alternately into the inferior vena cava and the abdominal aorta. When CO2 was bubbled into the inferior vena cava, heart rate and blood pressure remained constant, the respiration and the end tidal CO2-pressure (paCO2) were slightly increased. Insufflation of CO2 into the abdominal aorta, however, caused a marked increase in heart rate, blood pressure and total ventilation (
) while end tidal pCO2 was considerably decreased. When CO2 was replaced by nitrogen no effects could be observed. It is therefore concluded that the effects are specific for CO2.
The adjustments of the cardiovascular system to muscular exercise were studied in dogs running on a treadmill at different speeds and at the incline of +10%. The cardiac output, measured by the thermodilution method, increased with increasing O 2 consumption, reaching 520 ml/kg min at an O 2 consumption of 70 ml/kg min. At still higher metabolic levels the cardiac output remained constant and the O 2 consumption increased by an increase of the arteriovenous O 2 difference only, which was calculated to attain 17 vol % at the highest O 2 consumption value reached in this study, 90 ml/kg min. The increase of the cardiac output was mainly due to increase of the heart rate, whereas the average maximum increment of the stroke volume was about 30% only. The mean arterial and the central venous blood pressures increased with exercise. The time course of the adjustment of the cardiac output was measured after the exercise of varied intensity had been abruptly begun or stopped. Both for start and recovery the “half reaction time” was about 20 sec; after 1 min no further measurable change of the cardiac output was detectable.
cardiac output and O 2 consumption at increasing metabolic levels; heart rate and stroke volume in running dogs recovery following exercise
Submitted on July 15, 1963
In a series of experiments the cardiac output, the blood pressure and the pulse rate have been determined during electrically induced—and normal voluntary Work. The results showed that the circulation was increased corresponding to the oxygen consumption independently of the kind of work performed. From these results it is concluded, that the cortical impulses play no part-in the regulation of the circulation in the steady state of muscular work. This together with other evidence discussed in this paper makes it probable, that the regulation of the circulation during muscular work is governed by reflex impulses from the working muscles.
In experiments with voluntary and electrically induced work on a normal subject and on a patient (tabes dorsalis) in whom all the ordinary kinesthetic sensations were completely extinguished, the pulmonary ventilation increased during both kinds of work in the normal way i.e. corresponding to the oxygen consumption, in spite of the fact, that the cortical innervation during the electrically induced work was substituted by the apparatus for electrical stimulation.
Prom these experiments it is concluded, that the nervous impulses which increase the excitability of the respiratory centre, thus causing the rise in the ventilation during work, are not of cortical origin, but most probably must be brought about reflexly from the working muscles.
The experiments with the patient suffering from tabes dorsalis show further, that the reflex impulses must be carried to the centre through nerve paths outside the posterior fascicles, which are known to be destroyed in this disease.
Rabbits were anaesthetized with urethane and pentobarbitone sodium. The K+ and Na+ activity in the blood of the femoral vein or in the interstitial space of a skeletal muscle (vastus medialis of M. quadriceps femoris) were measured continuously by means of glass microelectrodes during stimulation of the muscles of the hindlimb. The blood flow in the femoral artery was recorded simultaneously by means of a Statham flowmeter. The K+ activity (at rest about 4 mmole/l) rose during the stimulation of the musculature. The course of the K+ increase was similar to that of the functional hyperemia. Maximum values obtained by frequent supramaximal stimulation (40 cps) were 6–6.5 mmole/l in the venous blood and 8–8.5 mmole/l in the interstitial space. The Na+ activity also rose from about 135 mmole/l to 136–140 mmole/l. The findings support the assumption that potassium shifts play a role in the regulation of functional hyperemia.
The relationship of femoral venous [K+], [H+], osmolality (OSM), PO2, and [inorganic phosphate] ([Pi]) with heart rate (HR), ventilation (VE), and calculated leg blood flow (Q) were investigated during bicycle exercise in endurance trained (TR) and untrained (UT) test subjects. At a given VO2 the increases of [K+], OSM, [Pi] and the decrease of PO2 were significantly lower in TR than in UT. In the same proportion the increases of HR, VE, and Q were diminished. Thus in TR and UT identical and highly significantly correlated regression lines of [K+], [H+], OSM, [Pi] and PO2 with HR, VE, and Q were obtained. These constituents changed in the same proportion as the relative VO2 in TR and UT. No relationships with [Na+], [Ca++], and [ Mg++] were found. By means of a multiple regression analysis the partial influence of K+, H+, OSM, PO2, and Pi upon the total change of HR, VE and Q was estimated to compare with data from infusion experiments. The findings were discussed in view of the hypothesis that these candidates may provide linkage between metabolic events, circulatory, and ventilatory adjustments during work.
To evaluate to what metabolic event in contracting muscles heart rate (HR) and \(\dot V\)
E are related, time courses of femoral and cubital venous [K+], osmolality (OSM), pH, PCO2, PO2, [lactate], and [orthophosphate] ([Pi]) at onset of exercise were studied in athletes (TR) and non-athletes (UT) and compared to time courses of HR and \(\dot V\)
E. During ischaemic work with the calf muscles it could be shown that most of these blood constituents were only released from contracting muscles. Thus their time courses reflected the metabolic events in working muscles being not essentially disturbed by non-working parts of the body. Ischaemic work induced, however, substantial increases of HR and \(\dot V\)
E. In the course of non-ischaemic bicycle work HR and \(\dot V\)
E rose more rapidly in TR than in UT but were lower in TR during the steady state. During non-ischaemic work only the increases of femoral venous [K+] closely mimicked the cardiorespiratory transients in TR as well as in UT. None of the other femoral venous substances showed such a rapid change or such typical variations between TR and UT. Cubital venous [K+] and [Pi] approached femoral venous concentrations only in the second minute after start whereas pH, PCO2, and OSM increased mainly in venous outflow from contracting muscles. PO2 decreased in femoral venous blood of TR and UT, but in cubital venous blood it remained depressed only in UT. It was discussed that the cardiorespiratory adjustment during the initial stages of work was related to K+ release in working muscles and not to O2 consuming or H+ producing processes, nor to release of Pi or increase of OSM.
The cerebral ventricular system of anesthetized dogs was perfused with synthetic isotonic CSF and, for 80 s intervals, with hypertonic CSF of various compositions. Hypertonic perfusion evoked centrally mediated marked increases in arterial blood pressure, heart rate, respiratory rate, and ventilation and, after some delay, an excitatory reaction resembling arousal. The responses were coordinated in time with the induced CSF hypertonicity, graded in relation to its magnitude, and reversible on return to isotonicity. The effects, which seemed to be elicited from periventricular structures in the brain stem, were more pronounced and consistent when CSF hypertonicity was produced by adding NaCl or Na-lactate than monosacharides to the isotonic CSF solution. Analysis of the cardiobascular responses indicated that they were caused by increased sympathetic vasoconstrictor and cardiac accelerance fibre activity and by inhibition of vagal discharge to the heart. The described pattern of response much resembles that evoked by physical exercise, a state which might lead to osmolar changes in the brain and CSF of a similar kind to that in the present study as a consequence of the pronounced work-induced arterial hyperosmolality. It is suggested that such an osmotic mechanism might constitute a "metabolic link" in the centrally mediated circulatory and respiratory adjustments in exercise.
The excitation of muscular group IV afferent units by the pain-producing substances 5-hydroxytryptamine (5-HT), histamine, and potassium ions was studied in cats and compared with the bradykinin effects of an earlier investigation. The substances were injected into the sural artery and the action potentials of single group IV afferent fibres from the gastrocnemius-soleus muscle were recorded extracellularly. About half of the 180 units tested with chemical stimulation could be excited by amounts of the above agents which are likely to be present in pathologically altered tissues. Of the tested substances, 5-HT was the most and potassium the least effective stimulant; in comparison with bradykinin, 5-HT was by far less potent, though. The molar ratios of approximately equivalent doses of bradykinin, 5-HT, histamine, and potassium were found to be about 1:30:66:4000. The threshold injection doses of KC1 for activation of muscular group IV units were such that an unspecific depolarizaing mode of action seems probable. Differences in the chemosensitivity of individual group IV units might be indicative of the existence of different receptor sites at the nerve endings. The sensitivity of muscle receptors with group IV afferent fibres to pain-producing substances--especially to bradykinin and 5-HT--supports the view that these units might participate in the mediation of muscle pain.
1. Small‐amplitude high‐frequency longitudinal vibration (for example, 100 μ peak to peak amplitude at 250 c/s) was applied to the triceps surae muscle of the decerebrate cat without producing any appreciable change in its respiration.
2. Manual squeezing of the same muscle produced a large increase in ventilation.
3. As vibration is known to be a powerful stimulus for the primary endings of the muscle spindle it is concluded that these receptors are unlikely to have any significant role to play in the reflex regulation of breathing.
The ventilatory response to exercise was studied on awake dogs trained to run on a treadmill. The exercise were performed at a grade and speed inducing an increase in the energy metabolic level up to 7 times the resting value. The roles of nervous and humoral stimuli in ventilatory control were analyzed by measuring ventilatory flow rate, tidal volume and respiratory frequency during exercise in three gaseous environments (air, hypoxia and hypercapnia) before and after carotid chemodenervation.At the start of exercise, the marked early rapid change of ventilation was unaffected by the gaseous environment. The terminal fall of ventilation was smaller than the early increase and its magnitude was decreased by hypoxia and hypercapnia. The 02 stimulus was lessened by exercise. For given levels of energy metabolism and of rectal temperature, hypoxia and hypercapnia altered the ventilatory pattern: the ventilatory frequency was decreased while the ventilatory flow rate and tidal volume were increased, inducing then an increase in alveolar ventilation. Hyperpnea related to hyperthermia was unaffected by the gaseous environment.Sinocarotid chemodenervation altered the exercise ventilatory pattern: for a given energy metabolism level, tidal volume was decreased and respiratory frequency increased. The transient rapid changes of ventilation of both the beginning and the end of exercise were altered.
1. In anaesthetized and decerebrate cats isometric exercise of the hind limb muscles was elicited by stimulating the spinal ventral roots L7‐S1. This caused a rise in arterial blood pressure, with small increases in heart rate and pulmonary ventilation. These changes were abolished by cutting the dorsal roots receiving afferents from the exercising muscle.
2. When the triceps surae muscle was made to exercise by ventral root stimulation, occlusion of the femoral artery and vein through and beyond the period of exercise caused the blood pressure to remain raised until the occlusion was removed. The ventilatory and heart rate responses were not markedly altered or prolonged by such circulatory occlusion.
3. Injection of small volumes of 5% NaCl or isotonic KCl into the arterial blood supplying hind limb muscles gave cardiovascular and respiratory responses similar to those evoked by exercise. Like the responses to exercise, these responses were abolished by dorsal root section.
4. Direct current anodal block of the dorsal roots receiving afferents from the exercising muscle was used to block preferentially large myelinated fibres: this form of block did not abolish the evoked cardiovascular and respiratory responses. Local anaesthetic block of the dorsal roots was used to block preferentially unmyelinated and small myelinated fibres: this form of block abolished the cardiovascular and respiratory responses. It is concluded that the reflex responses are mediated by fibres within groups III and IV (small myelinated fibres and unmyelinated fibres).
1. The effects of low temperature on conduction in single myelinated and non‐myelinated axons of the feline saphenous nerve were examined and compared. Nerves were cooled by a conventional thermode, but thermal gradients were minimized by an insulating layer of agar‐saline gel over the nerve and the face of the thermode.
2. The mean blocking temperature of thirty‐one non‐myelinated axons, 2·7° C, was significantly lower than that of 111 myelinated axons, 7·2° C. No evidence for a differential block of myelinated axons according to their normal conduction velocity could be demonstrated.
3. Reductions in the proportional conduction velocities of both myelinated and non‐myelinated axons were nearly identical between 17 and 37° C. However, below 17° C the rate at which the proportional conduction velocity of the non‐myelinated axons fell during cooling was significantly less than for the myelinated axons and was sufficient to account for their lower blocking temperatures. As a result, critical minimum conduction velocities were reached at higher temperatures in myelinated axons than in non‐myelinated axons.
4. The conduction velocity of successive impulses in a train slowed progressively to a constant value which depended on the frequency of stimulation. Consequently, the early impulses were separated by intervals that exceeded those between stimuli and were not affected by temperatures that blocked later impulses. The pattern of block was consistent with an increasing refractoriness of the axons as the temperature fell.
5. The maximal frequency of discharge that myelinated axons could carry at temperatures between normal and 12° C was related directly to fibre size. Non‐myelinated axons could conduct low frequency trains of impulses at temperatures that blocked such activity in myelinated axons. In all axons, high frequency trains of impulses could be completely blocked at temperatures which permitted lower frequency trains to pass uninterrupted.
6. Hysteresis in the blocking temperatures of axons was related to the hysteresis in their conduction velocities.
Pulmonary ventilation and oxygen consumption of three groups of cats, anesthetized, decerebrated and anesthetized decerebrate, were measured before and after metabolic stimulation by 2:4-dinitrophenol. It was found that anesthesia does not alter quantitatively the respiratory response to an increase in metabolism. Comparison with earlier data shows that a unit increase in oxygen consumption produces a similar response in ventilation in man, dogs and cats, anesthetized or normal. This finding supports the theory that the muscles embody ‘metaboreceptors’ sensitive to metabolic activity which stimulate respiration in exercise. It is postulated that the classical ‘blood-gas’ control of breathing is of minor importance under normal conditions and that the variations in ventilation required during light and moderate exercise are brought about by neural mechanism only.
Submitted on June 30, 1958
The capacity for exercise was studied in dogs before and after cardiac denervation by the technic of regional neural ablation. Measurements were made of cardiac output (indicator-dilution technic and electromagnetic flowmeter), heart rate, oxygen consumption, oxygen saturation of mixed venous blood and aortic blood pressure before and during work of graded severity. Each animal was studied on several occasions over a period of several months. No deterioration in the capacity for exercise was noted after cardiac denervation; as in the control period, at maximal levels of work there was a three- to fourfold increase in cardiac output and an eight- to tenfold increase in oxygen consumption. In contrast to the normal dog in which increase in cardiac output was achieved by an increase in heart rate, in the dog with cardiac denervation increase in cardiac output was effected principally by an increase in stroke volume.
The relation between stimulus interval and performance of skeletal muscle was investigated under conditions of controlled and spontaneous blood flow. Vascular resistance, arteriovenous oxygen saturation difference, oxygen consumption, and peak isometric tension and blood flow were used as indices of muscle performance. In all cases vascular resistance decreased while oxygen consumption increased as the stimulus interval was shortened. The relative contributions of alteration flow (where permitted) and alteration of arteriovenous oxygen difference to changes in oxygen consumption were assessed. The latter proved to be the more important contributor. The apparent oxygen cost per unit of tension change rate decreased to a nearly steady level as the stimulus interval shortened. Changes in these variables brought about by intra-arterial infusion of acetylcholine or d-tubocurarine were shown. The results illustrate some features of the myovascular interaction which occurs during muscular activity. A model of the blood flow-oxygen consumption relation, based on considerations of oxygen extraction, is presented.
Peripheral drive on circulatory and ventilatory centers from muscular metabolic receptors (abstr)
- B Tibes U Hemmer
Tibes U, Hemmer B: Peripheral drive on circulatory and ventilatory centers from muscular metabolic receptors (abstr). Pfluegers Arch 347 (suppl R 47), 1974
Aktivitat mit Mikro-Glaselek-troden im Extrazellularraum des Kaninchenskeletmuskels bei Muske-larbeit
- G Gebert
- K Messung
Gebert G: Messung der K + -und Na + -Aktivitat mit Mikro-Glaselek-troden im Extrazellularraum des Kaninchenskeletmuskels bei Muske-larbeit. Pfluegers Arch 331: 204-214, 1972
Activation of muscle affer-ents by nonproprioceptive stimuli Oxygen debt and high-energy phosphates in gastrocnemius muscle of the dog
- P Hnik
- O Hudlicka
- J Kucera
- Payne
- J Piiper
- Diprampero Pe
- Cerretelli
Hnik P, Hudlicka O, Kucera J, Payne R: Activation of muscle affer-ents by nonproprioceptive stimuli. Am J Physiol 217: 1451-1458, 33. Piiper J, DiPrampero PE, Cerretelli P: Oxygen debt and high-energy phosphates in gastrocnemius muscle of the dog. Am J Physiol 215: 523-531, 1968
Allgemeine Elektrophysiologie der erregbaren Struk-turen
- H-D Henatsch
Henatsch H-D: Allgemeine Elektrophysiologie der erregbaren Struk-turen. In Lehrbuch der Physiologie des Menschen, ed 28, vol II, edited by Landois-Rosemann, Miinchen, Berlin, Von Urban and Schwarzenberg, 1962, pp 547-613
Heart rate and ventilation in relation to venous
- U Tibes
- B Hemmer
- D Boning
Tibes U, Hemmer B, Boning D: Heart rate and ventilation in relation
to venous [K + ], osmolality, pH, PcOi, POj, [orthophosphate], and
[lactate] at transition from rest to exercise in athletes and non-athletes.
Control of respiration in muscular exercise
- P Dejours
Dejours P: Control of respiration in muscular exercise. In Handbook
of Physiology, section 3, Respiration, vol. 1, edited by WO Fenn, A
Rahn. Washington, D.C., American Physiological Society, 1964, pp
631-648
Ventilation and cardiac output in exercise; interaction of chemical and work stimuli
- Ff Kao
- S Lahiri
- C Wang
- Mei
Kao FF, Lahiri S, Wang C, Mei SS: Ventilation and cardiac output in exercise; interaction of chemical and work stimuli. Circ Res 20/21 (suppl I): 179-191, 1967
Allgemeine Elektrophysiologie der erregbaren Strukturen. In Lehrbuch der Physiologie des Menschen, ed 28, vol II, edited by Landois-Rosemann, Miinchen, Berlin
- Henatsch H-D
Control of respiration in muscular exercise. In Handbook of Physiology, section 3, Respiration, vol. 1, edited by WO Fenn, A Rahn. Washington, D.C
- P Dejours
- Wo Fenn
- Rahn
- Dejours P