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ABSTRACT: BACKGROUND: -Left ventricular assist devices (LVADs) are now widely accepted as an option for patients with advanced heart failure. First generation devices were pulsatile, but they had poor longevity and durability. Newer generation devices are non-pulsatile and more durable, but remain associated with an increased risk of stroke and hypertension. Moreover, little is understood about the physiological effects of the chronic absence of pulsatile flow in humans. METHODS AND RESULTS: -We evaluated patients with pulsatile (n=6) and non-pulsatile (n=11) LVADs and healthy controls (n=9) during head-up tilt (HUT) while measuring hemodynamics and muscle sympathetic nerve activity (MSNA). Patients with non-pulsatile devices had markedly elevated supine and upright MSNA (mean±SD: 43±15 supine and 60±21 bursts/min at 60° HUT) compared to patients with pulsatile devices (24±7 and 35±8 bursts/min; P<0.01) and controls (11±6 and 31±6 bursts/min; P<0.01); however, MSNA was not different between patients with pulsatile flow and controls (P=0.34). Heart rate, mean arterial pressure, and total peripheral resistance were greater, while cardiac output was smaller, in LVAD patients compared to controls in both supine and upright postures. However, these hemodynamic variables were not significantly different between patients with pulsatile and non-pulsatile flow. CONCLUSIONS: -Heart failure patients with continuous, non-pulsatile LVADs have marked sympathetic activation, which is likely due, at least in part, to baroreceptor unloading. We speculate that such chronic sympathetic activation may contribute to, or worsen end-organ diseases, and reduce the possibility of ventricular recovery. Strategies to provide some degree of arterial pulsatility, even in continuous flow LVADs may be necessary to achieve optimal outcomes in these patients.
Circulation Heart Failure 12/2012; · 6.29 Impact Factor
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ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) is a disease of the elderly with cardiovascular stiffening and reduced exercise capacity. Exercise training appears to improve exercise capacity and cardiovascular function in heart failure with reduced ejection fraction. However, it is unclear whether exercise training could improve cardiovascular stiffness, exercise capacity, and ventricular-arterial coupling in HFpEF.
Eleven HFpEF patients and 13 healthy controls underwent invasive measurements with right heart catheterization to define Starling and left ventricular (LV) pressure-volume curves; secondary functional outcomes included Doppler echocardiography, arterial stiffness, cardiopulmonary exercise testing with cardiac output measurement, and ventricular-arterial coupling assessed by the dynamic Starling mechanism. Seven of 11 HFpEF patients (74.9 ± 6 years; 3 men/4 women) completed 1 year of endurance training followed by repeat measurements. Pulmonary capillary wedge pressures and LV end-diastolic volumes were measured at baseline during decreased and increased cardiac filling. LV compliance was assessed by the slope of the pressure-volume curve. Beat-to-beat LV end-diastolic pressure (estimated from pulmonary arterial diastolic pressure) and stroke volume index were obtained, and spectral transfer function analysis was used to assess the dynamic Starling mechanism.
Before training, HFpEF patients had reduced exercise capacity, distensibility and dynamic Starling mechanism but similar LV compliance and end-diastolic volumes compared to controls albeit with elevated filling pressure and increased wall stress. One year of training had little effect on LV compliance and volumes, arterial stiffness, exercise capacity or ventricular-arterial coupling.
Contrary to our hypothesis, 1 year of endurance training failed to impart favorable effects on cardiovascular stiffness or function in HFpEF.
American heart journal 12/2012; 164(6):869-77. · 4.65 Impact Factor
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ABSTRACT: BACKGROUND: A reduction in maximal stroke volume (SV(max)) and total blood volume (TBV) has been hypothesized to contribute to the decline in maximal oxygen uptake (VO(2)max) with healthy aging. However, these variables have rarely been collected simultaneously in a board age range to support or refute this hypothesis. It is also unclear to what extent scaling size-related cardiovascular determinants of VO(2)max affects the interpretation of age-related differences. METHODS: A retrospective analysis of VO(2)max, maximal cardiac output (Q(C)max), TBV, and body composition including fat-free mass (FFM) in 95 (51% M) healthy adults ranging from 19-86 years. RESULTS: Absolute and indexed VO(2)max, Q(C)max, and maximal heart rate decreased in both sexes with age (p ≤ .031). SV(max) declined with age when scaled to total body mass or body surface area (p ≤ .047) but not when expressed in absolute levels (p = .120) or relative to FFM (p = .464). Absolute and indexed TBVs (mL/kg; mL/m(2)) were not significantly affected by age but increased with age in both sexes when scaled to FFM (p ≤ .013). A lower arteriovenous oxygen difference (a-vO(2)diff) contributed to the reduction in VO(2)max with age in treadmill exercisers (p = .004) but not in the entire cohort (p = .128). CONCLUSION: These results suggest (a) a reduction in absolute SV(max), and TBV do not contribute substantially to the age-related reduction in VO(2)max, which instead results from a smaller Q(C)max due to a lower maximal heart rate, and (b) body composition scaling methods should be used to accurately describe the effect of aging on physical function and cardiovascular variables.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2012; · 4.60 Impact Factor
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ABSTRACT: Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min(-1), 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min(-1); main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm(-5); P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.(-1) min(-1); P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml(-1), P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml(-1), P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications.
The Journal of Physiology 06/2012; 590(Pt 15):3535-43. · 4.72 Impact Factor
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ABSTRACT: Doppler ultrasound measures of left ventricular (LV) active relaxation and diastolic suction are slowed with healthy aging. It is unclear to what extent these changes are related to alterations in intrinsic LV properties and/or cardiovascular loading conditions. Seventy carefully screened individuals (38 female, 32 male) aged 21-77 were recruited into four age groups (young: <35; early middle age: 35-49; late middle age: 50-64 and seniors: ≥65 yr). Pulmonary capillary wedge pressure (PCWP), stroke volume, LV end-diastolic volume, and Doppler measures of LV diastolic filling were collected at multiple loading conditions, including supine baseline, lower body negative pressure to reduce LV filling, and saline infusion to increase LV filling. LV mass, supine PCWP, and heart rate were not affected significantly by aging. Measures of LV relaxation, including isovolumic relaxation time and the time constant of isovolumic pressure decay increased progressively, whereas peak early mitral annular longitudinal velocity decreased with advancing age (P < 0.001). The propagation velocity of early mitral inflow, a noninvasive measure of LV suction, decreased with aging with the greatest reduction in seniors (P < 0.001). Age-related differences in LV relaxation and diastolic suction were not attenuated significantly when PCWP was increased in older subjects or reduced in the younger subjects. There is an early slowing of LV relaxation and diastolic suction beginning in early middle age, with the greatest reduction observed in seniors. Because age-related differences in LV dynamic diastolic filling parameters were not diminished significantly with significant changes in LV loading conditions, a decline in ventricular relaxation is likely responsible for the alterations in LV diastolic filling with senescence.
AJP Heart and Circulatory Physiology 06/2012; 303(3):H315-22. · 3.71 Impact Factor
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ABSTRACT: Recent studies have suggested the presence of cardiac atrophy as a key component of the pathogenesis of the postural orthostatic tachycardia syndrome (POTS), similar to physical deconditioning. It has also been shown that exercise intolerance is associated with a reduced stroke volume (SV) in POTS, and that the high heart rate (HR) observed at rest and during exercise in these patients is due to this low SV. We tested the hypotheses that (a) circulatory control during exercise is normal in POTS; and (b) that physical ‘reconditioning' with exercise training improves exercise performance in patients with POTS. Nineteen (18 women) POTS patients completed a 3 month training programme. Cardiovascular responses during maximal exercise testing were assessed in the upright position before and after training. Resting left ventricular diastolic function was evaluated by Doppler echocardiography. Results were compared with those of 10 well-matched healthy sedentary controls. A lower SV resulted in a higher HR in POTS at any given oxygen uptake (V(O(2))) during exercise while the cardiac output (Q(c))-V(O(2)) relationship was normal. V(O(2peak)) was lower in POTS than controls (26.1 ± 1.0 (SEM) vs. 36.3 ± 0.9 ml kg-1 min-1; P < 0.001) due to a lower peak SV (65 ± 3 vs. 80 ± 5 ml; P = 0.009). After training in POTS, HR became lower at any given due to increased SV without changes in the – relationship. V(O(2peak)) increased by 11% (P < 0.001) due to increased peak SV (P = 0.021) and was proportional to total blood volume. Peak HR was similar, but HR recovery from exercise was faster after training than before training (P = 0.036 for training and 0.009 for interaction). Resting diastolic function was mostly normal in POTS before training, though diastolic suction was impaired (P = 0.023). There were no changes in any Doppler index after training. These results suggest that short-term exercise training improves physical fitness and cardiovascular responses during exercise in patients with POTS.
The Journal of Physiology 05/2012; 590(Pt 15):3495-505. · 4.72 Impact Factor
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ABSTRACT: This study examined the effectiveness of a short-duration but high-intensity exercise countermeasure in combination with a novel oral volume load in preventing bed rest deconditioning and orthostatic intolerance. Bed rest reduces work capacity and orthostatic tolerance due in part to cardiac atrophy and decreased stroke volume. Twenty seven healthy subjects completed 5 wk of -6 degree head down bed rest. Eighteen were randomized to daily rowing ergometry and biweekly strength training while nine remained sedentary. Measurements included cardiac mass, invasive pressure-volume relations, maximal upright exercise capacity, and orthostatic tolerance. Before post-bed rest orthostatic tolerance and exercise testing, nine exercise subjects were given 2 days of fludrocortisone and increased salt. Sedentary bed rest led to cardiac atrophy (125 ± 23 vs. 115 ± 20 g; P < 0.001); however, exercise preserved cardiac mass (128 ± 38 vs. 137 ± 34 g; P = 0.002). Exercise training preserved left ventricular chamber compliance, whereas sedentary bed rest increased stiffness (180 ± 170%, P = 0.032). Orthostatic tolerance was preserved only when exercise was combined with volume loading (-10 ± 22%, P = 0.169) but not with exercise (-14 ± 43%, P = 0.047) or sedentary bed rest (-24 ± 26%, P = 0.035) alone. Rowing and supplemental strength training prevent cardiovascular deconditioning during prolonged bed rest. When combined with an oral volume load, orthostatic tolerance is also preserved. This combined countermeasure may be an ideal strategy for prolonged spaceflight, or patients with orthostatic intolerance.
Journal of Applied Physiology 02/2012; 112(10):1735-43. · 3.75 Impact Factor
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ABSTRACT: Healthy, but sedentary ageing leads to marked atrophy and stiffening of the heart, with substantially reduced cardiac compliance; but the time course of when this process occurs during normal ageing is unknown. Seventy healthy sedentary subjects (39 female; 21–77 years) were recruited from the Dallas Heart Study, a population-based, random community sample and enriched by a second random sample from employees of Texas Health Resources. Subjects were highly screened for co-morbidities and stratified into four groups according to age: G(21−34): 21–34 years, G(35−49): 35–49 years, G5(0−64): 50–64 years, G(≥65): ≥65 years. All subjects underwent invasive haemodynamic measurements with right heart catheterization to define Starling and left ventricular (LV) pressure–volume curves. LV end-diastolic volumes (EDV) were measured by echocardiography at baseline, −15 and −30 mmHg lower-body negative pressure, and 15 and 30 ml kg(−1) saline infusion with simultaneous measurements of pulmonary capillary wedge pressure. There were no differences in heart rate or blood pressures among the four groups at baseline. Baseline EDV index was smaller in G(≥65) than other groups. LV diastolic pressure–volume curves confirmed a substantially greater LV compliance in G(21−34) compared with G(50−64) and G(≥65), resulting in greater LV volume changes with preload manipulations. Although LV chamber compliance in G(50−64) and G(≥65) appeared identical, pressure–volume curves were shifted leftward, toward a decreased distensibility, with increasing age. These results suggest that LV stiffening in healthy ageing occurs during the transition between youth and middle-age and becomes manifest between the ages of 50 to 64. Thereafter, this LV stiffening is followed by LV volume contraction and remodelling after the age of 65.
The Journal of Physiology 02/2012; 590(Pt 8):1871-80. · 4.72 Impact Factor
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ABSTRACT: Arteriosclerosis with aging leads to central arterial stiffening in humans, which could be a prime cause for increased cardiac afterload in the elderly. The purpose of the present study was to assess the effects of 1 yr of progressive exercise training on central aortic compliance and left ventricular afterload in sedentary healthy elderly volunteers. Ten healthy sedentary seniors and 11 Masters athletes (>65 yr) were recruited. The sedentary seniors underwent 1 yr of progressive exercise training so that at the end of the year, they were exercising ∼200 min/wk. Central aortic compliance was assessed by the Modelflow aortic age, which reflects the intrinsic structural components of aortic compliance. Cardiac afterload was assessed by effective arterial elastance (Ea) with its contributors of peripheral vascular resistance (PVR) and systemic arterial compliance (SAC). After exercise training, Ea, PVR, and SAC were improved in sedentary seniors and became comparable with those of Masters athletes although the Modelflow aortic age was not changed. Moreover, after exercise training, when stroke volume was restored with lower body negative pressure back to pretraining levels, the exercise training-induced improvements in Ea, PVR, and SAC were eliminated. Aortic stiffening with aging was not improved even after 1 yr of progressive endurance exercise training in the previously sedentary elderly, while left ventricular afterload was reduced. This reduced afterload after exercise training appeared to be attributable to cardiovascular functional modulation to an increase in stroke volume rather than to intrinsic structural changes in the arterial wall.
AJP Heart and Circulatory Physiology 01/2012; 302(6):H1340-6. · 3.71 Impact Factor
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Paul S Bhella,
Anand Prasad,
Katja Heinicke,
Jeff L Hastings,
Armin Arbab-Zadeh,
Beverley Adams-Huet,
Eric L Pacini, Shigeki Shibata,
M Dean Palmer,
Bradley R Newcomer,
Benjamin D Levine
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ABSTRACT: Peak oxygen uptake (VO(2)) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients.
Eleven HFpEF patients (73 ± 7 years, 7 females/4 males) and 13 healthy controls (70 ± 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Q(c), acetylene rebreathing) response to exercise was determined from linear regression of Q(c) and VO(2) (Douglas bags) at rest, ∼30% and ∼60% of peak VO(2), and maximal exercise. Peak VO(2) was lower in HFpEF patients than in controls (13.7 ± 3.4 vs. 21.6 ± 3.6 mL/kg/min; P < 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output [CPO = Q(c) × mean arterial pressure (MAP); HFpEF 1790 ± 509 vs. controls 2119 ± 581 L/mmHg/min; P = 0.20]; peak stroke work [SW = stroke volume (SV) × MAP; HFpEF 13 429 ± 2269 vs. controls 13 200 ± 3610 mL/mmHg; P = 0.80]. The ΔQ(c)/ΔVO(2) slope was abnormally elevated in HFpEF patients vs. controls (11.2 ±3.6 vs. 8.3 ± 1.5; P = 0.015).
Contrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO(2), increased ΔQ(c)/ΔVO(2) slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.
European Journal of Heart Failure 12/2011; 13(12):1296-304. · 4.90 Impact Factor
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ABSTRACT: Previous human studies have shown that large-artery stiffness contributes to an age-related decrease in cardiovagal baroreflex sensitivity. Whether this is also true with sympathetic baroreflex sensitivity is unknown. We tested the hypothesis that sympathetic baroreflex sensitivity is associated with the stiffness of baroreceptor segments (the carotid artery and the aorta) in elderly individuals and that sex affects this relationship. Sympathetic baroreflex sensitivity was assessed from the spontaneous changes in beat-by-beat diastolic pressure and corresponding muscle sympathetic nerve activity (microneurography) during supine rest in 30 men (mean±SEM: 69±1 years) and 31 women (68±1 years). Carotid artery stiffness (B-mode ultrasonography) and aortic stiffness (MRI) were also determined. We found that elderly women had lower sympathetic baroreflex sensitivity than elderly men (-2.33±0.25 versus -3.32±0.25 bursts · 100 beats(-1) · mm Hg(-1); P=0.007). β-Stiffness indices of the carotid artery and the aorta were greater in elderly women than in men (6.68±0.48 versus 5.10±0.50 and 4.03±0.47 versus 2.68±0.42; both P<0.050). Sympathetic baroreflex sensitivity was inversely correlated with carotid artery stiffness in both men and women (r=0.49 and 0.50; both P<0.05), whereas this relation was shifted in parallel upward (toward a reduced sensitivity) in women with no changes in the slope (0.26 versus 0.24 arbitrary units). Sympathetic baroreflex sensitivity and aortic stiffness showed similar trends. Thus, barosensory artery stiffness seems to be one independent determinant of sympathetic baroreflex sensitivity in elderly men and women. The lower sympathetic baroreflex sensitivity in elderly women may predispose them to an increased prevalence of hypertension.
Hypertension 11/2011; 59(1):98-104. · 6.21 Impact Factor
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ABSTRACT: This study tested the hypothesis that reduction in cerebral blood flow (CBF) during orthostatic stress after bed rest can be ameliorated with volume loading, exercise, or both. Transcranial Doppler was used to measure changes in CBF velocity during lower body negative pressure (LBNP) before and after an 18-day bed rest in 33 healthy subjects. Subjects were assigned into four groups with similar age and sex: 1) supine cycling during bed rest (Exercise group; n = 7), 2) volume loading with Dextran infusion after bed rest to restore reduced left ventricular filling pressure (Dextran group; n = 7), 3) exercise combined with volume loading to prevent orthostatic intolerance (Ex-Dex group; n = 7), and 4) a control group (n = 12). LBNP tolerance was measured using a cumulative stress index (CSI). After bed rest, CBF velocity was reduced at a lower level of LBNP in the Control group, and the magnitude of reduction was greater in the Ex-Dex group. However, reduction in orthostatic tolerance was prevented in the Ex-Dex group. Notably, volume loading alone prevented greater reductions in CBF velocity after bed rest, but CSI was reduced still by 25%. Finally, decreases in CBF velocity during LBNP were correlated with reduction in cardiac output under all conditions (r(2) = 0.86; P = < 0.001). Taken together, these findings demonstrate that volume loading alone can ameliorate reductions in CBF during LBNP. However, the lack of associations between changes in CBF velocity and orthostatic tolerance suggests that reductions in CBF during LBNP under steady-state conditions by itself are unlikely to be a primary factor leading to orthostatic intolerance.
AJP Heart and Circulatory Physiology 11/2011; 302(2):H489-97. · 3.71 Impact Factor
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ABSTRACT: We have found recently that exercise training is effective in the treatment of the postural orthostatic tachycardia syndrome (POTS). Whether this nondrug treatment is superior to "standard" drug therapies, such as β-blockade, is unknown. We tested the hypothesis that exercise training but not β-blockade treatment improves symptoms, hemodynamics, and renal-adrenal responses in POTS patients. Nineteen patients (18 women and 1 man) completed a double-blind drug trial (propranolol or placebo) for 4 weeks, followed by 3 months of exercise training. Fifteen age-matched healthy individuals (14 women and 1 man) served as controls. A 2-hour standing test was performed before and after drug treatment and training. Hemodynamics, catecholamines, plasma renin activity, and aldosterone were measured supine and during 2-hour standing. We found that both propranolol and training significantly lowered standing heart rate. Standing cardiac output was lowered after propranolol treatment (P=0.01) but was minimally changed after training. The aldosterone:renin ratio during 2-hour standing remained unchanged after propranolol treatment (4.1±1.7 [SD] before versus 3.9±2.0 after; P=0.46) but modestly increased after training (5.2±2.9 versus 6.5±3.0; P=0.05). Plasma catecholamines were not affected by propranolol or training. Patient quality of life, assessed using the 36-item Short-Form Health Survey, was improved after training (physical functioning score 33±10 before versus 50±9 after; social functioning score 37±9 versus 48±6; both P<0.01) but not after propranolol treatment (34±10 versus 36±11, P=0.63; 39±7 versus 39±5, P=0.73). These results suggest that, for patients with POTS, exercise training is superior to propranolol at restoring upright hemodynamics, normalizing renal-adrenal responsiveness, and improving quality of life.
Hypertension 06/2011; 58(2):167-75. · 6.21 Impact Factor
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ABSTRACT: Arterial compliance, the inverse of arterial stiffness, is a prognostic indicator of arterial health. Central and peripheral arterial compliance decrease with acute cold stress and may increase postexercise when exercise-induced elevations in core temperature are likely still to be present. Increased blood flow through the conduit arteries associated with elevated core temperature increases shear stress, which in turn releases nitric oxide and other endothelium-derived factors. These changes, in conjunction with supportive in vitro data, suggest that elevated core temperature may indirectly increase central and peripheral arterial compliance (i.e. decrease arterial stiffness). The purpose of this study was to test the hypothesis that increased core temperature decreases central and peripheral arterial stiffness, as measured with pulse wave velocity (PWV). Using Doppler ultrasound, carotid-femoral (central) and carotid-radial (peripheral) arterial PWVs were measured from eight subjects (age 37 ± 11 years; mass 68.8 ± 11.1 kg; height 171 ± 3 cm) before and during passive heat-stress-induced increases in core temperature of 0.47 ± 0.05, 1.03 ± 0.12 and 1.52 ± 0.07°C (i.e. baseline, 0.5, 1.0 and 1.5°C, respectively). Changes in PWV were evaluated with one-way repeated-measures ANOVA. When analysed as group means, neither central (677 ± 161, 617 ± 72, 659 ± 74 and 766 ± 207 cm s(-1); P = 0.12) nor peripheral PWV (855 ± 192, 772 ± 95, 759 ± 49 and 858 ± 247 cm s(-1); P = 0.56) changed as core temperature increased from baseline to 0.5, 1.0 and 1.5°C, respectively. However, individual changes in central (average r = -0.89, P < 0.05) and peripheral PWV (average r = -0.93, P < 0.05) with heat stress were significantly correlated with normothermic baseline PWV. In conclusion, these data suggest that the magnitude by which heat stress reduced PWV was predicated upon normothermic PWV, with the individuals having the highest normothermic PWV being most responsive to the heat-stress-induced reductions in PWV.
Experimental physiology 06/2011; 96(9):919-26. · 3.17 Impact Factor
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ABSTRACT: This study explored a novel method for measuring cerebrovascular impedance to quantify the relationship between pulsatile changes in cerebral blood flow (CBF) and arterial pressure. Arterial pressure in the internal or common carotid artery (applanation tonometry), CBF velocity in the middle cerebral artery (transcranial Doppler), and end-tidal CO(2) (capnography) were measured in six young (28 ± 4 yr) and nine elderly subjects (70 ± 6 yr). Transfer function method was used to estimate cerebrovascular impedance. Under supine resting conditions, CBF velocity was reduced in the elderly despite the fact that they had higher arterial pressure than young subjects. As expected, cerebrovascular resistance index was increased in the elderly. In both young and elderly subjects, impedance modulus was reduced gradually in the frequency range of 0.78-8 Hz. Phase was negative in the range of 0.78-4.3 Hz and fluctuated at high frequencies. Compared with the young, impedance modulus increased by 38% in the elderly in the range of 0.78-2 Hz and by 39% in the range of 2-4 Hz (P < 0.05). Moreover, increases in impedance were correlated with reductions in CBF velocity. Collectively, these findings demonstrate the feasibility of assessing cerebrovascular impedance using the noninvasive method developed in this study. The estimated impedance modulus and phase are similar to those observed in the systemic circulation and other vascular beds. Moreover, increases in impedance in the elderly suggest that arterial stiffening, besides changes in cerebrovascular resistance, contributes to reduction in CBF with age.
Journal of Applied Physiology 05/2011; 111(2):376-81. · 3.75 Impact Factor
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ABSTRACT: Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents.
AJP Regulatory Integrative and Comparative Physiology 04/2011; 301(1):R193-200. · 3.34 Impact Factor
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ABSTRACT: Pericardial constraint and ventricular interaction influence left ventricular (LV) performance when preload is high. However, it is unclear if these constraining forces modulate LV filling when the heart is unloaded, such as during upright posture, in humans. Fifty healthy individuals underwent right heart catheterization to measure pulmonary capillary wedge (PCWP) and right atrial pressure (RAP). To evaluate the effects of pericardial constraint on hemodynamics, transmural filling pressure (LVTMP) was defined as PCWP-RAP. Beat-to-beat blood pressure (BP) waveforms were recorded, and stroke volume (SV) was derived from the Modelflow method. After measurements at -30 mmHg lower body negative pressure (LBNP), which approximates the upright position, LBNP was released, and beat-to-beat measurements were performed for 15 heartbeats. At -30 mmHg LBNP, RAP and PCWP were significantly decreased. During the first six beats of LBNP release, heart rate (HR) was unchanged, while BP increased from the fourth beat. RAP increased faster than PCWP resulting in an acute decrease in LVTMP from the fourth beat. A corresponding drop in SV by 3% was observed with no change in pulse pressure. From the 7th to 15th beats, LVTMP and SV increased steadily, followed by a decreased HR due to the baroreflex. A decreased TMP, but not PCWP, caused a transient drop in SV with no changes in HR or pulse pressure during LBNP release. These results suggest that the pericardium constrains LV filling during LBNP release, enough to cause a small but significant drop of SV, even at low cardiac filling pressure in healthy humans.
AJP Heart and Circulatory Physiology 03/2011; 300(5):H1688-95. · 3.71 Impact Factor
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ABSTRACT: Indexes for arterial stiffness are, by their nature, influenced by the ambient blood pressure due to the curvilinear nature of arterial compliance. We developed a new concept of the "Modelflow aortic age," which is, theoretically, not influenced by the ambient blood pressure and provides an easily understood context (biological vs. chronological age) for measures of arterial stiffness. The purpose of the present study was to validate this pressure-independent index for aortic stiffness in humans. Twelve sedentary elderly (65-77 yr), 11 Masters athletes (65-73 yr), and 12 sedentary young individuals (20-42 yr) were studied. Modelflow aortic ages were comparable with chronological ages in both sedentary groups, indicating that healthy sedentary individuals have age-appropriate aortas. In contrast, Masters athletes showed younger Modelflow aortic ages than their chronological ages. The coefficient of variation of sedentary subjects was three times smaller with the Modelflow aortic age (21%) than with other indexes, such as static systemic arterial stiffness (61%), central pulse wave velocity (61%), or carotid β-stiffness index (58%). The typical error was very small and two times smaller in the Modelflow aortic age (<7%) than in static systemic arterial stiffness (>13%) during cardiac unloading by lower body negative pressure. The Modelflow aortic age can more precisely and reliably estimate aortic stiffening with aging and modifiers, such as life-long exercise training compared with the pressure-dependent index of static systemic arterial stiffness, and provides a physiologically relevant and clinically compelling context for such measurements.
Journal of Applied Physiology 02/2011; 110(4):981-7. · 3.75 Impact Factor
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ABSTRACT: Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ~40~50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients (n = 10) compared with healthy age-matched controls (n = 12) (HFpEF: 0.23 ± 0.10 ml·m⁻²·mmHg⁻¹ and control: 0.37 ± 0.11 ml·m⁻²·mmHg⁻¹, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg² and control: 3.8 ± 2.9 mmHg², P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward output and pulmonary congestion.
Journal of Applied Physiology 02/2011; 110(4):964-71. · 3.75 Impact Factor
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ABSTRACT: Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia in the upright position. To test the hypothesis that patients with POTS have impaired arterial-cardiac baroreflex function, while exercise training normalizes the baroreflex function in these patients.
Seventeen POTS patients aged 27 ± 9 (mean ± SD) years underwent an exercise training program for 3 months. Arterial-cardiac baroreflex function was assessed by spectral and transfer function analysis of beat-to-beat R-R interval (RRI) and systolic blood pressure (SBP) variability in the supine position and at 60° upright tilt during spontaneous breathing before and after training. Data were compared with 17 healthy sedentary controls.
Even though upright heart rate (HR) was greater in patients than controls, indexes of RRI variability did not differ between groups. Transfer function gain (SBP to RRI), used as an index of arterial-cardiac baroreflex sensitivity was similar between patients and controls in both low- (LF, P = 0.470) and high-frequency (HF, P = 0.663) ranges. Short-term exercise training decreased upright HR and increased RRI variability in POTS patients. LF baroreflex gain increased significantly in the supine position and during upright tilt [analysis of variance (ANOVA), P = 0.04 for training], while HF gain increased modestly after training (ANOVA, P = 0.105 for training) in these patients; however, the baroreflex gains remained within the normal ranges when compared with healthy controls.
These data suggest that patients with POTS have normal arterial-cardiac baroreflex function in both supine and upright postures. Short-term exercise training increases the baroreflex sensitivity in these patients, associated with a decrease in upright heart rate.
Clinical Autonomic Research 11/2010; 21(2):73-80. · 1.30 Impact Factor
