Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration

Adaptation to spaceflight or head-down-tilt bed rest leads to hypovolemia and an apparent abnormality of baroreflex regulation of cardiac period. In a previous study, we demonstrated that both chronic (2 wk) head-down-tilt bed rest and acute induced hypovolemia led to similar impairments in spontaneous baroreflex control of cardiac period, suggesting that a reduction in plasma volume may be responsible for this abnormality after bed rest. Therefore we hypothesized that this reduced "baroreflex function" could be restored by intravenous volume infusion equivalent to the reduction in plasma volume after bed rest. Six healthy subjects underwent 2 wk of -6 degrees head-down bed rest. Beat-by-beat arterial blood pressure and ECG were recorded during 6 min of spontaneous respiration and fixed-rate breathing (0.2 Hz), and transfer function analysis between systolic blood pressure and R-R interval was performed. Plasma volume was measured with Evans blue dye, and cardiac filling pressures were directly measured (Swan-Ganz catheter). After bed rest, studies were repeated before and after plasma volume restoration, with which both plasma volume and left ventricular end-diastolic pressure were restored to pre-bed rest levels by intravenous dextran40 infusion (288 +/- 31 ml). Transfer function gain in the high-frequency range, used as an index of vagally mediated arterial-cardiac baroreflex function, decreased significantly (13.4 +/- 3.1 to 8.1 +/- 2.9 ms/mmHg, P < 0.05) after bed rest. However, reduced transfer function gain was normalized to the pre-bed rest level (12.2 +/- 3.6 ms/mmHg) after precise plasma volume restoration. This result confirms that reductions in plasma volume, rather than a unique autonomic nervous system adaptation to bed rest, are largely responsible for the observed changes in spontaneous arterial-cardiac baroreflex function after bed rest.     

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.     

Short-term variability of blood pressure: effects of lower-body negative pressure and long-duration bed rest

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Women's International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (-10 mmHg, -20 mmHg, -30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ~0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% (P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to -20 and -30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.     

Baroreflex control of muscle sympathetic nerve activity after 120 days of 6 degrees head-down bed rest

To examine how long-lasting microgravity simulated by 6 degrees head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60 degrees HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60 degrees HUT was not different between before and after HDBR, but mean blood pressure decreased in 60 degrees HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.     

Short-duration spaceflight impairs human carotid baroreceptor-cardiac reflex responses.

Orthostatic intolerance is a predictable but poorly understood consequence of space travel. Because arterial baroreceptors modulate abrupt pressure transients, we tested the hypothesis that spaceflight impairs baroreflex mechanisms. We studied vagally mediated carotid baroreceptor-cardiac reflex responses (provoked by neck pressure changes) in the supine position and heart rate and blood pressure in the supine and standing positions in 16 astronauts before and after 4- to 5-day Space Shuttle missions. On landing day, resting R-R intervals and standard deviations, and the slope, range, and position of operational points on the carotid transmural pressure-sinus node response relation were all reduced relative to preflight. Stand tests on landing day revealed two separate groups (one maintained standing arterial pressure better) that were separated by preflight slopes, operational points, and supine and standing R-R intervals and by preflight-to-postflight changes in standing pressures, body weights, and operational points. Our results suggest that short-duration spaceflight leads to significant reductions in vagal control of the sinus node that may contribute to, but do not account completely for, orthostatic intolerance.     

Influence of physical training on heart rate variability and baroreflex circulatory control

Nineteen males (aged 45-68 yr) were studied before and after either a period of regular endurance exercise [walk/jog 3-4 days/wk for 30 +/- 1 (SE) wk, n = 11] or unchanged physical activity (38 +/- 2 wk, n = 8) (controls) to determine the influence of physical training on cardiac parasympathetic (vagal) tone and baroreflex control of heart rate (HR) and limb vascular resistance (VR) at rest in middle-aged and older men. Training resulted in a marked increase in maximal O2 uptake (31.6 +/- 1.2 vs. 41.0 +/- 1.8 ml.kg-1.min-1, 2.56 +/- 0.16 vs. 3.20 +/- 0.18 l/min, P less than 0.05) and small (P less than 0.05) reductions in body weight (81.2 +/- 3.5 vs. 78.7 +/- 4.0 kg) and body fat (23.8 +/- 1.3 vs. 20.9 +/- 1.3%). HR at rest was slightly, but consistently, lower after training (63 +/- 2 vs. 58 +/- 1 beats/min, P less than 0.05). In general, HR variability (index of cardiac vagal tone) was greater after training. Chronotropic responsiveness to either brief carotid baroreflex stimulation (neck suction) or inhibition (neck pressure), or to non-specific arterial baroreflex inhibition induced by a hypotensive level of lower body suction, was unchanged after training. In contrast, the magnitude of the reflex increase in forearm VR in response to three levels of lower body suction was markedly attenuated after training (38-59%; P less than 0.05 at -10 and -30 mmHg; P = 0.07 at -20 mmHg). None of these variables or responses was altered over time in the controls. These findings indicate that in healthy, previously sedentary, middle-aged and older men, strenuous and prolonged endurance training 1) elicits large increases in maximal exercise capacity and small reductions in HR at rest, 2) may increase cardiac vagal tone at rest, 3) does not alter arterial baroreflex control of HR, and 4) results in a diminished forearm vasoconstrictor response to reductions in baroreflex sympathoinhibition.     

Vagal cardiac function and arterial blood pressure stability

This study was designed to investigate the importance of vagal cardiac modulation in arterial blood pressure (ABP) stability before and after glycopyrrolate or atropine treatment. Changes in R-R interval (RRI) and ABP were assessed in 10 healthy young (age, 22 +/- 1.8 yr) volunteers during graded lower body negative pressure (LBNP) before and after muscarinic cholinergic (MC) blockade. Transient hypertension was induced by phenylephrine (1 microg/kg body wt), whereas systemic hypotension was induced by bilateral thigh cuff deflation after a 3-min suprasystolic occlusion. Power spectral densities of systolic [systolic blood pressure (SBP)] and diastolic ABP variability were examined. Both antimuscarinic agents elicited tachycardia similarly without significantly affecting baseline ABP. The increase in SBP after phenylephrine injection (+14 +/- 2 mmHg) was significantly augmented with atropine (+26 +/- 2 mmHg) or glycopyrrolate (+27 +/- 3 mmHg) and associated with a diminished reflex bradycardia. The decrease in SBP after cuff deflation (-9.2 +/- 1.2 mmHg) was significantly greater after atropine (-15 +/- 1 mmHg) or glycopyrrolate (-14 +/- 1 mmHg), with abolished reflex tachycardia. LBNP significantly decreased both SBP and RRI. However, after antimuscarinic agents, the reduction in SBP was greater (P < 0.05) and was associated with less tachycardia. Antimuscarinic agents reduced (P < 0.05) the low-frequency (LF; 0.04-0.12 Hz) power of ABP variability at rest. The LF SBP oscillation was significantly augmented during LBNP, which was accentuated (P < 0.05) after antimuscarinic agents and was correlated (r = -0.79) with the decrease in SBP. We conclude that antimuscarinic agents compromised ABP stability by diminishing baroreflex sensitivity, reflecting the importance of vagal cardiac function in hemodynamic homeostasis. The difference between atropine and glycopyrrolate was not significant.     

Comparison of phenylephrine bolus and infusion methods in baroreflex measurements

Phenylephrine (PE) bolus and infusion methods have both been used to measure baroreflex sensitivity in humans. To determine whether the two methods produce the same values of baroreceptor sensitivity, we administered intravenous PE by both bolus injection and graded infusion methods to 17 normal subjects. Baroreflex sensitivity was determined from the slope of the linear relationship between the cardiac cycle length (R-R interval) and systolic arterial pressure. Both methods produced similar peak increases in arterial pressure and reproducible results of baroreflex sensitivity in the same subjects, but baroreflex slopes measured by the infusion method (9.9 +/- 0.7 ms/mmHg) were significantly lower than those measured by the bolus method (22.5 +/- 1.8 ms/mmHg, P less than 0.0001). Pretreatment with atropine abolished the heart rate response to PE given by both methods, whereas plasma catecholamines were affected by neither method of PE administration. Naloxone pretreatment exaggerated the pressor response to PE and increased plasma beta-endorphin response to PE infusion but had no effect on baroreflex sensitivity. Thus our results indicate that 1) activation of the baroreflex by the PE bolus and infusion methods, although reproducible, is not equivalent, 2) baroreflex-induced heart rate response to a gradual increase in pressure is less than that seen with a rapid rise, 3) in both methods, heart rate response is mediated by the vagus nerves, and 4) neither the sympathetic nervous system nor the endogenous opiate system has a significant role in mediating the baroreflex control of heart rate to a hypertensive stimulus in normal subjects.     

Baroreflex during exercise in different postures before and after 20-days bed rest

Vagal-cardiac baroreflex functions in young healthy humans (n=6) were investigated in four different conditions; supine rest, seated rest, supine and seated exercise (50 watts) before and after 20-day horizontal bed rest. By selectively stimulating carotid baroreceptors using a neck pressure and suction technique, the primary finding was that the baroreflex sensitivity tuation at which we observed a tendency for an attenuation (0.05相似文献   

Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans

Volume expansion often ameliorates symptoms of orthostatic intolerance; however, the influence of this increased volume on integrated baroreflex control of vascular sympathetic activity is unknown. We tested whether acute increases in central venous pressure (CVP) diminished subsequent responsiveness of muscle sympathetic nerve activity (MSNA) to rapid changes in arterial pressure. We studied healthy humans under three separate conditions: control, acute 10 degrees head-down tilt (HDT), and saline infusion (SAL). In each condition, heart rate, arterial pressure, CVP, and peroneal MSNA were measured during 5 min of rest and then during rapid changes in arterial pressure induced by sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). Sensitivities of integrated baroreflex control of MSNA and heart rate were assessed as the slopes of the linear portions of the MSNA-diastolic blood pressure and R-R interval-systolic pressure relations, respectively. CVP increased approximately 2 mmHg in both SAL and HDT conditions. Resting heart rate and mean arterial pressure were not different among trials. Sensitivity of baroreflex control of MSNA was decreased in both SAL and HDT condition, respectively: -3.1 +/- 0.6 and -3.3 +/- 1.0 versus -5.0 +/- 0.6 units.beat(-1).mmHg(-1) (P < 0.05 for SAL and HDT vs. control). Sensitivity of baroreflex control of the heart was not different among conditions. Our results indicate that small increases in CVP decrease the sensitivity of integrated baroreflex control of sympathetic nerve activity in healthy humans.     

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.     

Effects of lower-leg rhythmic cuff inflation on cardiovascular autonomic responses during quiet standing in healthy subjects

To determine the effects of muscle pump function on cardiac autonomic activity in response to quiet standing, we simulated the muscle pump effect by rhythmic lower-leg cuff inflation (RCI) with four cuff pressures of 0 (sham), 40, 80, and 120 mmHg at 5 cycles/min. The R-R interval (RRI) and beat-to-beat blood pressure (BP) were acquired in healthy subjects (6 males and 5 females, aged 21-24 yr). From the continuous BP measurement, stroke volume (SV) was calculated by a pulse-contour method. Using spectral and cross-spectral analysis, RRI and systolic BP variability as well as the gain of spontaneous cardiac baroreflex sensitivity (sBRS) were estimated for the low- and high-frequency (HF) bands. Compared with the sham condition, RCI with cuff pressures of 80 and 120 mmHg led to increases in the mean RRI (P < 0.01) and HF power of RRI fluctuation (P < 0.05 for 80 mmHg and P < 0.01 for 120 mmHg) during quiet standing. Reduction in SV during standing was suppressed, and the sBRS of the HF band for standing were increased by RCI for either cuff pressure (P < 0.05 for 80 mmHg and P < 0.01 for 120 mmHg). However, at 40 mmHg RCI, these remained unchanged. These results suggest that, during standing, RCI of the lower leg increases cardiac vagal outflow when the cuff pressure is raised enough to oppose the hydrostatic-induced venous pressure in the calf.     

Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.     

Arterial baroreflex control of heart rate during exercise in postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) have excessive tachycardia without hypotension during orthostasis as well as exercise. We tested the hypothesis that excessive tachycardia during exercise in POTS is not related to abnormal baroreflex control of heart rate (HR). Patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter) and HR (ECG) were measured. Baroreflex sensitivity of HR was assessed by bolus intravenous infusion of phenylephrine at each workload. In both positions, HR was higher in the patients than the controls during exercise. Supine baroreflex sensitivity (HR/systolic pressure) in POTS patients was -1.3 +/- 0.1 beats.min(-1).mmHg(-1) at rest and decreased to -0.6 +/- 0.1 beats.min(-1).mmHg(-1) during 75-W exercise, neither significantly different from the controls (P > 0.6). In the upright position, baroreflex sensitivity in POTS patients at rest (-1.4 +/- 0.1 beats.min(-1).mmHg(-1)) was higher than the controls (-1.0 +/- 0.1 beats.min(-1).mmHg(-1)) (P < 0.05), and it decreased to -0.1 +/- 0.04 beats.min(-1).mmHg(-1) during 75-W exercise, lower than the controls (-0.3 +/- 0.09 beats.min(-1).mmHg(-1)) (P < 0.05). The reduced arterial baroreflex sensitivity of HR during upright exercise was accompanied by greater fluctuations in systolic and pulse pressure in the patients than in the controls with 56 and 90% higher coefficient of variations, respectively (P < 0.01). However, when baroreflex control of HR was corrected for differences in HR, it was similar between the patients and controls during upright exercise. These results suggest that the tachycardia during exercise in POTS was not due to abnormal baroreflex control of HR.     

Carotid baroreflex responsiveness in high-fit and sedentary young men

The influence of fitness on cardiac vagal activity and baroreflex-mediated control of heart rate has not been clearly established in humans. Therefore, we studied resting cardiac vagal activity by evaluating respiratory sinus arrhythmia (RSA) and examined carotid-cardiac baroreflex responsiveness with a neck collar in 11 high-fit and 9 sedentary [based on maximal O2 consumption (VO2max) and history of physical activity] healthy young men (19-31 yr of age). Resting cardiac vagal activity was determined from the standard deviation of 100 consecutive resting R-R intervals. Baroreflex responsiveness was determined from the R-R interval responses to neck suction and pressure (repeated trials of 5-s stimuli of -20, -40, and 35 mmHg). Both RSA and the bradycardic (R-R interval) responses to neck suction of -40 mmHg were significantly greater (P less than 0.05) in the high-fit individuals (RSA, 116.5 +/- 11.5 ms; neck-suction response, 145.3 +/- 17.0 ms; mean +/- SE) compared with sedentary subjects (RSA, 65.2 +/- 6.6 ms; neck-suction response, 86.9 +/- 12.5 ms). Responses of the high-fit volunteers to the other intensities of neck stimuli (-20 and 35 mmHg) showed a similar trend but were not significantly different from those of the sedentary volunteers. The baroreflex slope derived from these data was significantly greater in the high-fit subjects (4.00 +/- 0.39 ms/mmHg) compared with the sedentary controls (2.53 +/- 0.28 ms/mmHg). These data suggest that resting cardiac vagal activity is greater, carotid-to-cardiac activity is well maintained, and baroreflex sensitivity, i.e., slope, is augmented in high-fit subjects.     

Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men

Cardiovagal baroreflex sensitivity (BRS) declines with advancing age in healthy men. We tested the hypothesis that oxidative stress contributes mechanistically to this age-associated reduction. Eight young (23 +/- 1 yrs, means +/- SE) and seven older (63 +/- 3) healthy men were studied. Cardiovagal BRS was assessed using the modified Oxford technique (bolus infusion of 50-100 microg sodium nitroprusside, followed 60 s later by a 100- to 150-microg bolus of phenylephrine hydrochloride) in triplicate at baseline and during acute intravenous ascorbic acid infusion. At baseline, cardiovagal BRS (slope of the linear portion of the R-R interval-systolic blood pressure relation during pharmacological changes in arterial blood pressure) was 56% lower (P < 0.01) in older (8.3 +/- 1.6 ms/mmHg) compared with young (19.0 +/- 3.1 ms/mmHg) men. Ascorbic acid infusion increased plasma concentrations similarly in young (62 +/- 9 vs. 1,249 +/- 72 micromol/l for baseline and during ascorbic acid; P < 0.05) and older men (62 +/- 4 vs. 1,022 +/- 55 micromol/l; P < 0.05) without affecting baseline blood pressure, heart rate, carotid artery compliance, or the magnitude of change in systolic blood pressure in response to bolus sodium nitroprusside and phenylephrine hydrochloride infusion. Ascorbic acid (vitamin C) infusion increased cardiovagal BRS in older (Delta58 +/- 16%; P < 0.01), but not younger (Delta - 4 +/- 4%) men. These data provide experimental support for the concept that oxidative stress contributes mechanistically to age-associated reductions in cardiovagal BRS in healthy men.     

Effect of muscle metaboreflex activation on carotid-cardiac baroreflex function in humans

Whether the activation of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) influences cardiac baroreflex responsiveness remains incompletely understood. A potential explanation for contrasting findings of previous reports may be related to differences in the magnitude of muscle metaboreflex activation utilized. Therefore, the present study was designed to investigate the influence of graded intensities of muscle metaboreflex activation on cardiac baroreflex function. In eight healthy subjects (24 +/- 1 yr), the graded isolation of the muscle metaboreflex was achieved by post-exercise ischemia (PEI) following moderate- (PEI-M) and high- (PEI-H) intensity isometric handgrip performed at 35% and 45% maximum voluntary contraction, respectively. Beat-to-beat heart rate (HR) and blood pressure were measured continuously. Rapid pulse trains of neck pressure and neck suction (+40 to -80 Torr) were applied to derive carotid baroreflex stimulus-response curves. Mean blood pressure increased significantly from rest during PEI-M (+13 +/- 3 mmHg) and was further augmented during PEI-H (+26 +/- 4 mmHg), indicating graded metaboreflex activation. However, the operating point gain and maximal gain (-0.51 +/- 0.09, -0.48 +/- 0.13, and -0.49 +/- 0.12 beats.min(-1).mmHg(-1) for rest; PEI-M and PEI-H) of the carotid-cardiac baroreflex function curve were unchanged from rest during PEI-M and PEI-H (P > 0.05 vs. rest). Furthermore, the carotid-cardiac baroreflex function curve was progressively reset rightward from rest to PEI-M to PEI-H, with no upward resetting. These findings suggest that the muscle metaboreflex contributes to the resetting of the carotid baroreflex control of HR; however, it would appear not to influence carotid-cardiac baroreflex responsiveness in humans, even with high-intensity activation during PEI.     

Assessment of cardiovascular reflexes: influence of posture and period of preceding rest

The aim of the present study was to investigate the effects of a pretest redistribution of blood volume and of a change in the neurohumoral condition on the blood pressure (BP) and heart rate (HR) responses to three commonly used cardiovascular reflex tests: standing up, forced breathing, and the Valsalva maneuver in 10 healthy male subjects. Base-line conditions were altered by changing posture and the duration of rest preceding the test stimulus. A continuous recording of finger BP was obtained noninvasively by a Finapres. The main observations from this study are with respect to standing up: lengthening the period of preceding rest from 1 to 20 min enlarges the initial BP (systolic/diastolic) decrease (from 8 +/- 10/9 +/- 4 to 27 +/- 8/19 +/- 4 mmHg, P less than 0.01) and the subsequent BP overshoot (from 17 +/- 10/12 +/- 7 to 31 +/- 10/18 +/- 7 mmHg, P less than 0.05); to forced breathing: inspiratory-expiratory changes in BP but not in HR are larger in the upright posture (P less than 0.05); and to the Valsalva maneuver: change in posture from supine to standing increases the phase II BP decrease (from 18 +/- 12/8 +/- 6 to 45 +/- 16/21 +/- 9 mmHg), phase IV systolic BP overshoot (from 26 +/- 16 to 71 +/- 17 mmHg), delta HRmax (from 30 +/- 10 to 47 +/- 12 beats/min), and the Valsalva ratio (HRmax/HRmin), from 2.0 +/- 0.3 to 2.6 +/- 0.7, all significant at P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of autonomic blockade on cardiac function at rest and during upright exercise in humans

The cardiac function was studied by radionuclide cardiography in eight healthy subjects at rest and during submaximal upright exercise before and after autonomic blockade with metoprolol and atropine. At rest the median stroke volume was reduced by 21% during autonomic blockade (P less than 0.01), but cardiac output was maintained by a concomitant increase in heart rate. The systolic blood pressure was reduced from 120 to 105 mmHg (P less than 0.01), and left ventricular ejection fraction was reduced from 61 to 56% (P less than 0.05). After autonomic blockade the heart rate reached during exercise was the same. Stroke volume and cardiac output were maintained through cardiac dilation. The increase in left ventricular end-diastolic volume was 31 vs. 10% during control conditions (P less than 0.01). The systolic blood pressure was reduced from 174 to 135 mmHg (P less than 0.01). Left ventricular ejection fraction was reduced from 75 to 67% (P less than 0.05), but the increase from rest to exercise was preserved. Total peripheral resistance was reduced by 17% (P less than 0.05). These findings suggest that the heart possesses intrinsic mechanisms to maintain cardiac output during submaximal upright exercise. End-diastolic dilation results in a preserved stroke volume despite a reduced contractility.     

Alterations in autonomic function and cerebral hemodynamics to orthostatic challenge following a mountain marathon.

We examined potential mechanisms (autonomic function, hypotension, and cerebral hypoperfusion) responsible for orthostatic intolerance following prolonged exercise. Autonomic function and cerebral hemodynamics were monitored in seven athletes pre-, post- (<4 h), and 48 h following a mountain marathon [42.2 km; cumulative gain approximately 1,000 m; approximately 15 degrees C; completion time, 261 +/- 27 (SD) min]. In each condition, middle cerebral artery blood velocity (MCAv), blood pressure (BP), heart rate (HR), and cardiac output (Modelflow) were measured continuously before and during a 6-min stand. Measurements of HR and BP variability and time-domain analysis were used as an index of sympathovagal balance and baroreflex sensitivity (BRS). Cerebral autoregulation was assessed using transfer-function gain and phase shift in BP and MCAv. Hypotension was evident following the marathon during supine rest and on standing despite increased sympathetic and reduced parasympathetic control, and elevations in HR and cardiac output. On standing, following the marathon, there was less elevation in normalized low-frequency HR variability (P < 0.05), indicating attenuated sympathetic activation. MCAv was maintained while supine but reduced during orthostasis postmarathon [-10.4 +/- 9.8% pre- vs. -15.4 +/- 9.9% postmarathon (%change from supine); P < 0.05]; such reductions were related to an attenuation in BRS (r = 0.81; P < 0.05). Cerebral autoregulation was unchanged following the marathon. These findings indicate that following prolonged exercise, hypotension and postural reductions in autonomic function or baroreflex control, or both, rather than a compromise in cerebral autoregulation, may place the brain at risk of hypoperfusion. Such changes may be critical factors in collapse following prolonged exercise.