Carotid distensibility, baroreflex sensitivity, and orthostatic stress.

In this study, we tested the hypothesis that carotid arteries undergo rapid changes in distensibility on moving from the supine to head-up tilt (HUT) postures and, subsequently, that this change in carotid distensibility (cDa) might be associated with concurrent reductions in cardiovagal baroreflex sensitivity (BRS). Thus the effect of posture on carotid vascular mechanics and cardiovagal BRS with consideration for altered central hemodynamics (i.e., stroke volume; Doppler ultrasound) was examined. Carotid pulse pressure (cPP; Millar transducer) and contralateral B-mode ultrasound images were assessed at the carotid artery during supine and 60 degrees HUT postures. From these measures, cDa was calculated at 5-mmHg pressure increments experienced during the cardiac cycle (n = 6). cPP (n = 9) was not different in the two postures. A smaller stroke volume being ejected into a smaller carotid artery in HUT explained the maintenance of cPP in HUT. Also, compared with supine, cDa was reset to a lower level in HUT (main effect of posture; P < 0.05). Cardiovagal BRS (sequence method) was diminished in HUT vs. supine (P < 0.05). A positive correlation was observed between the tilt-induced changes in maximal cDa (in early systole) and cardiovagal BRS (r2 = 0.75; P < 0.05), but there was little predictive relationship between changes in cPP, systolic vessel dimensions, or average cDa and the corresponding change in BRS. The present results indicate that HUT elicits rapid changes in carotid artery mechanics and further suggest that reductions in the maximal cDa measured in early systole contribute to reduced cardiovagal BRS with HUT.     

Modeling baroreflex regulation of heart rate during orthostatic stress

During orthostatic stress, arterial and cardiopulmonary baroreflexes play a key role in maintaining arterial pressure by regulating heart rate. This study presents a mathematical model that can predict the dynamics of heart rate regulation in response to postural change from sitting to standing. The model uses blood pressure measured in the finger as an input to model heart rate dynamics in response to changes in baroreceptor nerve firing rate, sympathetic and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations of norepinephrine and acetylcholine. We formulate an inverse least squares problem for parameter estimation and successfully demonstrate that our mathematical model can accurately predict heart rate dynamics observed in data obtained from healthy young, healthy elderly, and hypertensive elderly subjects. One of our key findings indicates that, to successfully validate our model against clinical data, it is necessary to include the vestibulo-sympathetic reflex. Furthermore, our model reveals that the transfer between the nerve firing and blood pressure is nonlinear and follows a hysteresis curve. In healthy young people, the hysteresis loop is wide, whereas, in healthy and hypertensive elderly people, the hysteresis loop shifts to higher blood pressure values, and its area is diminished. Finally, for hypertensive elderly people, the hysteresis loop is generally not closed, indicating that, during postural change from sitting to standing, baroreflex modulation does not return to steady state during the first minute of standing.     

Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans

Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (> 0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope = -1.95 ± 0.18 bursts·(100 beats)?1)·mmHg?1; r = -0.86 ± 0.03] or total MSNA [slope = -438 ± 91 units·(beat)?1 mmHg?1; r = -0.76 ± 0.06]. During mental stress, the slope between burst incidence and DAP was significantly reduced [slope = -1.14 ± 0.12 bursts·(100 beats)?1·mmHg?1; r = -0.72 ± 0.03; P < 0.01], indicating attenuation of sympathetic BRS. A more detailed analysis revealed an attenuation of sympathetic BRS during the first 2 min of mental stress (P < 0.01) but no change during the final 3 min of mental stress (P = 0.25). The present study demonstrates that acute mental stress attenuates sympathetic BRS, which may partially contribute to sympathoexcitation during the mental stress-pressor response. However, this attenuation appears to be isolated to the onset of mental stress. Moreover, variable MSNA responses to mental stress do not appear to be directly related to sympathetic BRS.     

Heat acclimation increases skin vasodilation and sweating but not cardiac baroreflex responses in heat-stressed humans.

In the present study, to test the hypothesis that exercise-heat acclimation increases orthostatic tolerance via the improvement of cardiac baroreflex control in heated humans, we examined cardiac baroreflex and thermoregulatory responses, including cutaneous vasomotor and sudomotor responses, during whole body heating before and after a 6-day exercise-heat acclimation program [4 bouts of 20-min exercise at 50% peak rate of oxygen uptake separated by 10-min rest in the heat (36 degrees C; 50% relative humidity)]. Ten healthy young volunteers participated in the study. On the test days before and after the heat acclimation program, subjects underwent whole body heat stress produced by a hot water-perfused suit during supine rest for 45 min and 75 degrees head-up tilt (HUT) for 6 min. The sensitivity of the arterial baroreflex control of heart rate (HR) was calculated from the spontaneous changes in beat-to-beat arterial pressure and HR. The HUT induced a presyncopal sign in seven subjects in the preacclimation test and in six subjects in the postacclimation test, and the tilting time did not differ significantly between the pre- (241 +/- 33 s) and postacclimation (283 +/- 24 s) tests. Heat acclimation did not change the slope in the HR-esophageal temperature (Tes) relation and the cardiac baroreflex sensitivity during heating. Heat acclimation decreased (P < 0.05) the Tes thresholds for cutaneous vasodilation in the forearm and dorsal hand and for sweating in the forearm and chest. These findings suggest that short-term heat acclimation does not alter the spontaneous baroreflex control of HR during heat stress, although it induces adaptive change of the heat dissipation response in nonglabrous skin.     

Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation

Increasing arterial blood pressure (AP) decreases ventilation, whereas decreasing AP increases ventilation in experimental animals. To determine whether a "ventilatory baroreflex" exists in humans, we studied 12 healthy subjects aged 18-26 yr. Subjects underwent baroreflex unloading and reloading using intravenous bolus sodium nitroprusside (SNP) followed by phenylephrine ("Oxford maneuver") during the following "gas conditions:" room air, hypoxia (10% oxygen)-eucapnia, and 30% oxygen-hypercapnia to 55-60 Torr. Mean AP (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), expiratory minute ventilation (V(E)), respiratory rate (RR), and tidal volume were measured. After achieving a stable baseline for gas conditions, we performed the Oxford maneuver. V(E) increased from 8.8 ± 1.3 l/min in room air to 14.6 ± 0.8 l/min during hypoxia and to 20.1 ± 2.4 l/min during hypercapnia, primarily by increasing tidal volume. V(E) doubled during SNP. CO increased from 4.9 ± .3 l/min in room air to 6.1 ± .6 l/min during hypoxia and 6.4 ± .4 l/min during hypercapnia with decreased TPR. HR increased for hypoxia and hypercapnia. Sigmoidal ventilatory baroreflex curves of V(E) versus MAP were prepared for each subject and each gas condition. Averaged curves for a given gas condition were obtained by averaging fits over all subjects. There were no significant differences in the average fitted slopes for different gas conditions, although the operating point varied with gas conditions. We conclude that rapid baroreflex unloading during the Oxford maneuver is a potent ventilatory stimulus in healthy volunteers. Tidal volume is primarily increased. Ventilatory baroreflex sensitivity is unaffected by chemoreflex activation, although the operating point is shifted with hypoxia and hypercapnia.     

Cyclooxygenase inhibition and baroreflex sensitivity in humans

Animal studies suggest that prostanoids (i.e., such as prostacyclin) may sensitize or impair baroreceptor and/or baroreflex responsiveness depending on the site of administration and/or inhibition. We tested the hypothesis that acute inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and muscle sympathetic nerve activity (MSNA) in humans and augments pressor reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion) and 60 min after (postinfusion) intravenous infusion of a COX antagonist (ketorolac; 45 mg) (24 +/- 1 yr; n = 12) or saline (25 +/- 1 yr; n = 12). BRS was assessed by using the modified Oxford technique (bolus intravenous infusion of nitroprusside followed by phenylephrine). BRS was quantified as the slope of the linear portion of the 1) R-R interval-systolic blood pressure relation (cardiovagal BRS) and 2) MSNA-diastolic blood pressure relation (sympathetic BRS) during pharmacological changes in arterial blood pressure. Ketorolac did not alter cardiovagal (19.4 +/- 2.1 vs. 18.4 +/- 2.4 ms/mmHg preinfusion and postinfusion, respectively) or sympathetic BRS (-2.9 +/- 0.7 vs. -2.6 +/- 0.4 arbitrary units.beat(-1).mmHg(-1)) but significantly decreased a plasma biomarker of prostanoid generation (plasma thromboxane B2) by 53 +/- 11%. Cardiovagal BRS (21.3 +/- 3.8 vs. 21.2 +/- 3.0 ms/mmHg), sympathetic BRS (-3.4 +/- 0.3 vs. -3.2 +/- 0.2 arbitrary units.beat(-1).mmHg(-1)), and thromboxane B2 (change in -1 +/- 12%) were unchanged in the control (saline infusion) group. Pressor responses to steady-state incremental (0.5, 1.0, and 1.5 microg.kg(-1).min(-1)) infusion (5 min/dose) of phenylephrine were not altered by ketorolac (n = 8). Collectively, these data indicate that acute pharmacological antagonism of the COX enzyme does not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in healthy young adults.     

Time course analysis of baroreflex sensitivity during postural stress

Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (tau) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (alpha). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in tau toward higher values. In 10 healthy young volunteers, alpha included 20 degrees head-down tilt (-20 degrees), supine (0 degree), 30 and 70 degrees head-up tilt (30 degrees, 70 degrees), and free standing (90 degrees). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in alpha. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (-20 degrees) to 45 (90 degrees) xBRS estimates per minute became available. Following a change in alpha, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing alpha, BRS decreased: BRS = -10.1.sin(alpha) + 18.7 (r(2) = 0.99) with tight correlation between xBRS and cross-spectral gain (r(2) approximately 0.97). Delay tau shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(alpha), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short tau may be the result of reduced vagal activity with increasing alpha.     

Influence of age on cardiac baroreflex function during dynamic exercise in humans

We investigated the influence of aging on cardiac baroreflex function during dynamic exercise in seven young (22 +/- 1 yr) and eight older middle-aged (59 +/- 2 yr) healthy subjects. Carotid-cardiac baroreflex function was assessed at rest and during moderate-intensity steady-state cycling performed at 50% heart rate reserve (HRR). Five-second pulses of neck pressure and neck suction from +40 to -80 Torr were applied to determine the operating point gain (G(OP)) and maximal gain (G(MAX)) of the full carotid-cardiac baroreflex function curve and examine baroreflex resetting during exercise. At rest, mean arterial pressure (MAP) and heart rate were similar between the younger and older subjects. In contrast, the resting G(OP) and G(MAX) were significantly lower in the older subjects. The increase in MAP from rest to exercise was greater in the older subjects (Delta +20 +/- 2 older vs. Delta +6 +/- 3 younger mmHg; P < 0.001). However, the G(OP) was similar in both groups during exercise because of a reduction in the younger subjects. In contrast, G(MAX) was unchanged from rest and therefore remained lower in older subjects (-0.19 +/- 0.05 older vs. -0.42 +/- 0.05 younger beats.min(-1).mmHg(-1); 50% HRR; P < 0.001). Furthermore, exercise resulted in an upward and rightward resetting of the cardiac baroreflex function curve in both groups. Collectively, these findings suggest that the cardiac baroreflex function curve appropriately resets during exercise in older subjects but operates at a reduced G(MAX) primarily because of age-related reductions in carotid-cardiac control manifest at rest.     

Enhanced baroreflex sensitivity in free-moving calponin knockout mice

Calponin is an actin binding protein in vascular smooth muscle that modifies contractile responses. However, its role in mean arterial pressure (MAP) regulation has not been clarified. To assess this, MAP and heart rate (HR) were measured in calponin knockout (KO) mice, and the results were compared with those in wild-type (WT) mice. The measurements were performed every 100 ms during a 60-min free-moving state each day for 3 days. Mice in both groups rested during approximately 70% of the total measuring period. The mean HR during rest was significantly lower in KO mice than in WT mice but with no significant difference in MAP between the groups. The change in HR response (deltaHR) to spontaneous change in MAP (deltaMAP) varied in a wider range in KO mice with an 80% increase in the coefficient of variation for HR (P < 0.05), whereas MAP in KO mice was controlled in a narrow range similar to that in WT mice. The baroreflex sensitivity (deltaHR/deltaMAP), determined from the change in HR to the spontaneous change in MAP, was twofold higher in KO mice than that in WT mice (P < 0.01), whereas there were no significant differences in the baroreflex sensitivity determined by intravascular administration of phenylephrine and sodium nitroprusside between the two groups (P > 0.1). The MAP response to the administrated doses of phenylephrine in KO mice was reduced to one-half of that in WT mice (P < 0.01) but with no significant difference in the response to sodium nitroprusside between the groups. The differences in HR variability and the spontaneous baroreflex sensitivity between the two groups completely disappeared after carotid sinus denervation. These results suggest that the higher variability in HR for KO mice was caused by the increased spontaneous arterial baroreflex sensitivity, though not detected by the intra-arterial administration of the drug, and that the higher variability of HR may be a compensatory adaptation to the blunted alpha-adrenergic response of peripheral vessels to sympathetic nervous activity.     

Modulation of control of muscle sympathetic nerve activity during orthostatic stress in humans

We tested the hypothesis that orthostatic stress would modulate the arterial baroreflex (ABR)-mediated beat-by-beat control of muscle sympathetic nerve activity (MSNA) in humans. In 12 healthy subjects, ABR control of MSNA (burst incidence, burst strength, and total activity) was evaluated by analysis of the relation between beat-by-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (CON) and at two levels of lower body negative pressure (LBNP: -15 and -35 mmHg). At -15 mmHg LBNP, the relation between burst incidence (bursts per 100 heartbeats) and DAP showed an upward shift from that observed during CON, but the further shift seen at -35 mmHg LBNP was only marginal. The relation between burst strength and DAP was shifted upward at -15 mmHg LBNP (vs. CON) and further shifted upward at -35 mmHg LBNP. At -15 mmHg LBNP, the relation between total activity and DAP was shifted upward from that obtained during CON and further shifted upward at -35 mmHg LBNP. These results suggest that ABR control of MSNA is modulated during orthostatic stress and that the modulation is different between a mild (nonhypotensive) and a moderate (hypotensive) level of orthostatic stress.     

Change in spontaneous baroreflex control of pulse interval during heat stress in humans.

Spontaneous baroreflex control of pulse interval (PI) was assessed in healthy volunteers under thermoneutral and heat stress conditions. Subjects rested in the supine position with their lower legs in a water bath at 34 degrees C. Heat stress was imposed by increasing the bath temperature to 44 degrees C. Arterial blood pressure (Finapres), PI (ECG), esophageal and skin temperature, and stroke volume were continuously collected during each 5-min experimental stage. Spontaneous baroreflex function was evaluated by multiple techniques, including 1) the mean slope of the linear relationship between PI and systolic blood pressure (SBP) with three or more simultaneous increasing or decreasing sequences, 2) the linear relationship between changes in PI and SBP (deltaPI/DeltaSBP) derived by using the first differential equation, 3) the linear relationship between changes in PI and SBP with simultaneously increasing or decreasing sequences (+deltaPI/+deltaSBP or -deltaPI/-deltaSBP), and 4) transfer function analysis. Heat stress increased esophageal temperature by 0.6 +/- 0.1 degrees C, decreased PI from 1,007 +/- 43 to 776 +/- 37 ms and stroke volume by 16 +/- 5 ml/beat. Heat stress reduced baroreflex sensitivity but increased the incidence of baroreflex slopes from 5.2 +/- 0.8 to 8.6 +/- 0.9 sequences per 100 heartbeats. Baroreflex sensitivity was significantly correlated with PI or vagal power (r2 = 0.45, r2 = 0.71, respectively; P < 0.05). However, the attenuation in baroreflex sensitivity during heat stress appeared related to a shift in autonomic balance (shift in resting PI) rather than heat stress per se.     

Vestibulosympathetic reflex during orthostatic challenge in aging humans

Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.     

Effect of clonidine on cardiac baroreflex delay in humans and rats

The delay τ between rising systolic blood pressure (SBP) and baroreflex bradycardia has been found to increase when vagal tone is low. The α(2)-agonist clonidine increases cardiac vagal tone, and this study tested how it affects τ. In eight conscious supine human volunteers clonidine (6 μg/kg po) reduced τ, assessed both by cross correlation baroreflex sensitivity and sequence methods (both P < 0.05). Experiments on urethane-anaesthetized rats reproduced the phenomenon and investigated the underlying mechanism. Heart rate (HR) responses to increasing SBP produced with an arterial balloon catheter showed reduced τ (P < 0.05) after clonidine (100 μg/kg iv). The central latency of the reflex was unaltered, however, as shown by the unchanged timing with which antidromically identified cardiac vagal motoneurons (CVM) responded to the arterial pulse. Testing the latency of the HR response to brief electrical stimuli to the right vagus showed that this was also unchanged by clonidine. Nevertheless, vagal stimuli delivered at a fixed time in the cardiac cycle (triggered from the ECG R-wave) slowed HR with a 1-beat delay in the baseline state but a 0-beat delay after clonidine (n = 5, P < 0.05). This was because clonidine lengthened the diastolic period, allowing the vagal volleys to arrive at the heart just in time to postpone the next beat. Calculations indicate that naturally generated CVM volleys in both humans and rats arrive around this critical time. Clonidine thus reduces τ not by changing central or efferent latencies but simply by slowing the heart.     

Controlled 5-mo aerobic training improves heart rate but not heart rate variability or baroreflex sensitivity.

Endurance-trained athletes have increased heart rate variability (HRV), but it is not known whether exercise training improves the HRV and baroreflex sensitivity (BRS) in sedentary persons. We compared the effects of low- and high-intensity endurance training on resting heart rate, HRV, and BRS. The maximal oxygen uptake and endurance time increased significantly in the high-intensity group compared with the control group. Heart rate did not change significantly in the low-intensity group but decreased significantly in the high-intensity group (-6 beats/min, 95% confidence interval; -10 to -1 beats/min, exercise vs. control). No significant changes occurred in either the time or frequency domain measures of HRV or BRS in either of the exercise groups. Exercise training was not able to modify the cardiac vagal outflow in sedentary, middle-aged persons.     

Carotid baroreflex sensitivity at rest and during exercise is not influenced by opioid receptor antagonism

Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound cardiovascular adaptations. The aim of the present study was to investigate with the use of the variable neck chamber technique, the influence of the endogenous opioids on the carotid baroreflex control of blood pressure and heart rate at rest as well as during exercise. Ten normal volunteers exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg.h-1). During exercise a progressive attenuation of the carotid baroreceptor reflex control of blood pressure and heart rate was noted. However, neither at rest nor during exercise, did opioid antagonism influence the carotid baroreceptor control of blood pressure and heart rate. Intra-arterial pressure and heart rate also remained unaffected. In contrast, both at rest and during exercise, naloxone administration produced a significant increase in the plasma concentration of cortisol. The latter suggests that in vivo the opioid receptors were effectively antagonized. In conclusion the present study confirms that opioids play only a minor role in cardiovascular homeostasis at rest. In addition, this study demonstrates that they are not involved in the cardiovascular adaptation to exercise, nor in the exercise-related attenuation of the carotid baroreceptor control of pressure and heart rate.     

Carotid baroreflex function during and following voluntary apnea in humans

Muscle sympathetic nerve activity (MSNA) and arterial pressure increase concomitantly during apnea, suggesting a possible overriding of arterial baroreflex inhibitory input to sympathoregulatory centers by apnea-induced excitatory mechanisms. Apnea termination is accompanied by strong sympathoinhibition while arterial pressure remains elevated. Therefore, we hypothesized that the sensitivity of carotid baroreflex control of MSNA would decrease during apnea and return upon apnea termination. MSNA and heart rate responses to -60-Torr neck suction (NS) were evaluated during baseline and throughout apnea. Responses to +30-Torr neck pressure (NP) were evaluated during baseline and throughout 1 min postapnea. Apnea did not affect the sympathoinhibitory or bradycardic response to NS (P > 0.05); however, whereas the cardiac response to NP was maintained postapnea, the sympathoexcitatory response was reduced for 50 s (P < 0.05). These data demonstrate that the sensitivity of carotid baroreflex control of MSNA is not attenuated during apnea. We propose a transient rightward and upward resetting of the carotid baroreflex-MSNA function curve during apnea and that return of the function curve to, or more likely beyond, baseline (i.e., a downward and leftward shift) upon apnea termination may importantly contribute to the reduced sympathoexcitatory response to NP.     

Error and individual difference in cardiovascular responses to orthostatic stress in humans

Variations in cardiovascular responses to orthostatic stress were investigated in terms of physiological polymorphism. Variations of physiological measurements are subdivided into individual differences and measurement errors. However, individual differences are often considered to be an error in statistical analysis due to its limitations in experimental design. In order to discuss about the relative contribution of individual difference in cardiovascular responses to postural changes, percent contribution (PC) was estimated using the Taguchi method. Six healthy male adults (age range: 21-27) were subjected to orthostatic stress by inducing a postural inclination of 60 degrees head-up-tilting to the horizontal, and the responses were measured thrice in each subject on different days. The respective changes of heart rate (HR) and stroke volume (SV) in the period from the resting supine to the head-up-tilt position were significantly increased (p < 0.01) and decreased (p < 0.01) without affecting the mean blood pressure (MBP). The PC of individual difference in HR showed a significantly higher ratio of individual difference during the head-up-tilt (71.4-76.2%) compared with supine rest (0.0-50.4%). While the main variations of HR during supine rest were not the individual differences between the subjects, the day-to-day differences within the subject were significant. The PC of individual differences in MBP and SV constantly displayed a significant difference between the subjects. These results suggest that the strategy for maintaining stable cardiovascular regulation may be different even in normal subjects. In the perspective of physiological parameters, PC monitoring may serve as an empirical approach to evaluate physiological polymorphism.     

Protein kinase A changes calcium sensitivity but not crossbridge kinetics in human cardiac myofibrils

We investigated the effect of PKA treatment (1 U/ml) on the mechanical properties of isolated human cardiac myofibrils. PKA treatment was associated with significant incorporation of radiolabeled phosphate into several sarcomeric proteins including troponin I and myosin binding protein C and was also associated with a right shift in the tension-pCa relation (ΔpCa(50) = 0.2 ± 0.1). PKA treatment also caused right shifts in the pCa dependence of the rate of tension development, tension redevelopment, and the linear and exponential phases of myofibril relaxation. However, there was no change in the same measures of crossbridge turnover when expressed as a function of tension. We conclude that the changes in crossbridge kinetics as a function of calcium concentration reflect a reduced tension due to a lower calcium sensitivity and that the relationship between crossbridge kinetics and tension was unchanged, indicating no direct effect of PKA treatment on crossbridge cycling.     

Heat-stress-induced changes in central venous pressure do not explain interindividual differences in orthostatic tolerance during heat stress

The extent to which heat stress compromises blood pressure control is variable among individuals, with some individuals becoming very intolerant to a hypotensive challenge, such as lower body negative pressure (LBNP) while heat stressed, while others are relatively tolerant. Heat stress itself reduces indexes of ventricular filling pressure, including central venous pressure, which may be reflective of reductions in tolerance in this thermal condition. This study tested the hypothesis that the magnitude of the reduction in central venous pressure in response to heat stress alone is related to the subsequent decrement in LBNP tolerance. In 19 subjects, central hypovolemia was imposed via LBNP to presyncope in both normothermic and heat-stress conditions. Tolerance to LBNP was quantified using a cumulative stress index (CSI), and the difference between normothermic CSI and heat-stress CSI was calculated for each individual. The eight individuals with the greatest CSI difference between normothermic and heat-stress tolerances (LargeDif), and the eight individuals with the smallest CSI difference (SmallDif), were grouped together. By design, the difference in CSI between thermal conditions was greater in the LargeDif group (969 vs. 382 mmHg × min; P < 0.001). Despite this profound difference in the effect of heat stress in decreasing LBNP tolerance between groups, coupled with no difference in the rise in core body temperatures to the heat stress (LargeDif, 1.4 ± 0.1°C vs. SmallDif, 1.4 ± 0.1°C; interaction P = 0.89), the reduction in central venous pressure during heat stress alone was similar between groups (LargeDif: 5.7 ± 1.9 mmHg vs. SmallDif: 5.2 ± 2.0 mmHg; interaction P = 0.85). Contrary to the proposed hypothesis, differences in blood pressure control during LBNP are not related to differences in the magnitude of the heat-stress-induced reductions in central venous pressure.     

Diastolic ventricular interactions in endurance-trained athletes during orthostatic stress

Enhanced left-ventricular (LV) compliance is a common adaptation to endurance training. This adaptation may have differential effects under conditions of altered venous return. The purpose of this investigation was to assess the effect of cardiac (un)loading on right ventricular (RV) cavity dimensions and LV volumes in endurance-trained athletes and normally active males. Eight endurance-trained (Vo(2max), 65.4 +/- 5.7 ml.kg(-1).min(-1)) and eight normally active (Vo(2max), 45.1 +/- 6.0 ml.kg(-1).min(-1)) males underwent assessments of the following: 1) Vo(2max), 2) orthostatic tolerance, and 3) cardiac responses to lower-body positive (0-60 mmHg) and negative (0 to -80 mmHg) pressures with echocardiography. In response to negative pressures, echocardiographic analysis revealed a similar decrease in RV end-diastolic cavity area in both groups (e.g., at -80 mmHg: normals, 21.4%; athletes, 20.8%) but a greater decrease in LV end-diastolic volume in endurance-trained athletes (e.g., at -80 mmHg: normals, 32.3%; athletes, 44.4%; P < 0.05). Endurance-trained athletes also had significantly greater decreases in LV stroke volume during lower-body negative pressure. During positive pressures, endurance-trained athletes showed larger increases in LV end-diastolic volume (e.g., at +60 mmHg; normals, 14.1%; athletes, 26.8%) and LV stroke volume, despite similar responses in RV end-diastolic cavity area (e.g., at +60 mmHg: normals, 18.2%; athletes, 24.2%; P < 0.05). This investigation revealed that in response to cardiac (un)loading similar changes in RV cavity area occur in endurance-trained and normally active individuals despite a differential response in the left ventricle. These differences may be the result of alterations in RV influence on the left ventricle and/or intrinsic ventricular compliance.