Cardiovascular response to acute hypovolemia in relation to age. Implications for orthostasis and hemorrhage

Venous compliance in the legs of aging man has been found to be reduced with decreased blood pooling (capacitance response) in dependent regions, and this might lead to misinterpretations of age-related changes in baroreceptor function during orthostasis. The hemodynamic response to hypovolemic circulatory stress was studied with the aid of lower-body negative pressure (LBNP) of 60 cmH(2)O in 33 healthy men [18 young (mean age 22 yr) and 15 old (mean age 65 yr)]. Volumetric technique was used in the study of capacitance responses in the calf and arm as well as transcapillary fluid absorption in the arm. LBNP led to smaller increase in heart rate (P < 0.001) and peripheral resistance (P < 0.01) and reduced transcapillary fluid absorption in the arm (P < 0.05) in old subjects. However, blood pooling in the calf was reduced in old subjects (1.66 +/- 0.10 vs. 2.17 +/- 0.13 ml/100 ml tissue; P < 0. 01). Accordingly, during similar blood pooling in the calf (LBNP 80 cmH(2)O in old subjects), no changes in cardiovascular reflex responses with age were found. The capacitance response in the arm (mobilization of peripheral blood to the central circulation) was still reduced, however (0.67 +/- 0.10 vs. 1.37 +/- 0.11 ml/100 ml tissue; P < 0.01). Thus the reduced cardiovascular reflex response found in the elderly during orthostatic stress seems to be caused by a reduced capacitance response in the legs with age and a concomitant smaller central hypovolemic stimulus rather than a reduced efficiency of the reflex response. With similar hypovolemic circulatory stress, no changes in cardiovascular reflex responses are seen with age. The capacitance response in the arm (mobilization of peripheral blood toward the central circulation) is reduced, however, by approximately 50% in the elderly. This might seriously impede the possibility of survival of an acute blood loss.     

Effect of hypovolemia on forearm vascular resistance control during exercise in the heat.

To determine the influence of hypovolemia on the control of forearm vascular resistance (FVR) during dynamic exercise, we studied five physically active men during 60 min of supine cycle ergometer exercise bouts at 35 degrees C in control (normovolemic) and hypovolemic conditions. Hypovolemia was achieved by 3 days of diuretic administration and resulted in an average decrease in plasma volume of 15.9%. Relative to normovolemia, hypovolemia caused an attenuation of the progressive rise in forearm blood flow (P less than 0.05) and an increase in heart rate (P less than 0.05) during exercise. Because mean arterial blood pressure during hypovolemic exercise was well maintained, the attenuation of forearm blood flow was due entirely to a relative increase in FVR. At the onset of dynamic exercise, FVR was increased significantly in control and hypovolemic conditions by 13.2 and 27.1 units, respectively. The increase in FVR was significantly different between control and hypovolemic conditions as well. We attributed the increased vasoconstrictor bias during hypovolemia to cardiopulmonary baroreceptor unloading and/or an increased sensitivity to cardiopulmonary baroreceptor unloading. We concluded that reduced blood flow to the periphery during exercise in the hypovolemic condition was caused entirely by an increase in vascular resistance, thereby preserving arterial blood pressure and adequate perfusion to the organs requiring increased flow.     

Role of cardiopulmonary baroreflexes during dynamic exercise

To examine the role of cardiopulmonary (CP) mechanoreceptors in the regulation of arterial blood pressure during dynamic exercise in humans, we measured mean arterial pressure (MAP), cardiac output (Q), and forearm blood flow (FBF) during mild cycle ergometer exercise (77 W) in 14 volunteers in the supine position with and without lower-body negative pressure (LBNP). During exercise, MAP averaged 103 +/- 2 mmHg and was not altered by LBNP (-10, -20, or -40 mmHg). Steady-state Q during exercise was reduced from 10.2 +/- 0.5 to 9.2 +/- 0.5 l/min (P less than 0.05) by application of -10 mmHg LBNP, whereas heart rate (97 +/- 3 beats/min) was unchanged. MAP was maintained during -10 mmHg LBNP by an increase in total systemic vascular resistance (TSVR) from 10.3 +/- 0.5 to 11.4 +/- 0.6 U and forearm vascular resistance (FVR) from 17.5 +/- 1.9 to 23.3 +/- 2.6 U. The absence of a reflex tachycardia or reduction in arterial pulse pressure during -10 mmHg LBNP supports the hypothesis that the increase in TSVR and FVR results primarily from the unloading of CP mechanoreceptors. Because CP mechanoreceptor unloading during exercise stimulates reflex circulatory adjustments that act to defend the elevated MAP, we conclude that the elevation in MAP during exercise is regulated and not merely the consequence of differential changes in Q and TSVR. In addition, a major portion of the reduction in FBF in our experimental conditions occurs in the cutaneous circulation. As such, these data support the hypothesis that CP baroreflex control of cutaneous vasomotor tone is preserved during mild dynamic exercise.     

Sex-related effects on venous compliance and capillary filtration in the lower limb

Recent studies in humans have suggested sex differences in venous compliance of the lower limb, with lower compliance in women. Capillary fluid filtration could, however, be a confounder in the evaluation of venous compliance. The venous capacitance and capillary filtration response in the calves of 12 women (23.2 +/- 0.5 years) and 16 men (22.9 +/- 0.5 years) were studied during 8 min lower body negative pressure (LBNP) of 11, 22, and 44 mmHg. Calf venous compliance is dependent on pressure and was determined using the first derivative of a quadratic regression equation that described the capacitance-pressure relationship [compliance = beta1 + (2 x beta2 x transmural pressure)]. We found a lower venous compliance in women at low transmural pressures, and the venous capacitance in men was increased (P < 0.05). However, the difference in compliance between sexes was reduced and not seen at higher transmural pressures. Net capillary fluid filtration and capillary filtration coefficient (CFC) were greater in women than in men during LBNP (P < 0.05). Furthermore, calf volume increase (capacitance response + total capillary filtration) during LBNP was equivalent in both sexes. When total capillary filtration was not subtracted from the calf capacitance response in the calculation of venous compliance, the sex differences disappeared, emphasizing that venous compliance measurement should be corrected for the contribution of CFC.     

Effects of gender and hypovolemia on sympathetic neural responses to orthostatic stress

We tested the hypothesis that women have blunted sympathetic neural responses to orthostatic stress compared with men, which may be elicited under hypovolemic conditions. Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in eight healthy young women and seven men in supine position and during 6 min of 60 degrees head-up tilt (HUT) under normovolemic and hypovolemic conditions (randomly), with approximately 4-wk interval. Acute hypovolemia was produced by diuretic (furosemide) administration approximately 2 h before testing. Orthostatic tolerance was determined by progressive lower body negative pressure to presyncope. We found that furosemide produced an approximately 13% reduction in plasma volume, causing a similar increase in supine MSNA in men and women (mean +/- SD of 5 +/- 7 vs. 6 +/- 5 bursts/min; P = 0.895). MSNA increased during HUT and was greater in the hypovolemic than in the normovolemic condition (32 +/- 6 bursts/min in normovolemia vs. 44 +/- 15 bursts/min in hypovolemia in men, P = 0.055; 35 +/- 9 vs. 45 +/- 8 bursts/min in women, P < 0.001); these responses were not different between the genders (gender effect: P = 0.832 and 0.814 in normovolemia and hypovolemia, respectively). Total peripheral resistance increased proportionately with increases in MSNA during HUT; these responses were similar between the genders. However, systolic blood pressure was lower, whereas diastolic blood pressure was similar in women compared with men during HUT, which was associated with a smaller stroke volume or stroke index. Orthostatic tolerance was lower in women, especially under hypovolemic conditions. These results indicate that men and women have comparable sympathetic neural responses during orthostatic stress under normovolemic and hypovolemic conditions. The lower orthostatic tolerance in women is predominantly because of a smaller stroke volume, presumably due to less cardiac filling during orthostasis, especially under hypovolemic conditions, which may overwhelm the vasomotor reserve available for vasoconstriction or precipitate neurally mediated sympathetic withdrawal and syncope.     

Sympathetic vascular transduction is augmented in young normotensive blacks.

The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.     

Human cardiovascular reactions to simulated hypovolaemia, modified by the opiate antagonist naloxone

Six healthy males were exposed to 20 mm Hg lower body negative pressure (LBNP) for 8 min followed by 40 mm Hg LBNP for 8 min. Naloxone (0.1 mg.kg-1) was injected intravenously during a 1 h resting period after which the LBNP protocol was repeated. Systolic, mean, and diastolic arterial blood pressures (SAP, MAP, DAP), and central venous pressure (CVP) were obtained using indwelling catheters. Cardiac output (CO), forearm blood flow (FBF), heart rate (HR), left ventricular ejection time (LVET), and electromechanical systole (EMS) were measured non-invasively. Pulse pressure (PP), stroke volume (SV), total peripheral resistance (TPR), forearm vascular resistance (FVR), systolic ejection rate (SER), pre-ejection period (PEP), PEP/LVET and indices for the systolic time intervals (LVETI, EMSI, PEPI) were calculated. During the second LBNP exposure, only two parameters differed from the pre-injection values: DAP at LBNP = 40 mm Hg increased from 60.0 +/- 4.8 mm Hg to 64.8 +/- 4.1 mm Hg (N = 4, p less than 0.02) and LVETI at LBNP = 20 mm Hg increased from 384.4 +/- 5.2 ms to 396.8 +/- 6.2 ms (N = 6, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Aging and the skin blood flow response to the unloading of baroreceptors during heat and cold stress.

Control of skin blood flow (SkBF) is on the efferent arm of both thermoregulatory and nonthermoregulatory reflexes. To what extent aging may affect the SkBF response when these two reflex systems interact is unknown. To determine the response of aged skin to the unloading of baroreceptors in thermoneutral, cold stress, and heat stress conditions, sequential bouts of nonhypotensive lower body negative pressure (LBNP) were applied at -10, -20, and -30 mmHg in 14 young (18-25 yr) and 14 older (63-78 yr) men. SkBF was measured by laser-Doppler velocimetry (averaged over 2 forearm sites), and data are expressed as percentage of maximal cutaneous vascular conductance (%CVC(max)). Total forearm blood flow was measured by venous occlusion plethysmography, and forearm vascular conductance (FVC) was calculated as the ratio of forearm blood flow to mean arterial pressure. In young men, all three intensities of LBNP in thermoneutrality decreased FVC significantly (P < 0.05), but FVC at -10 mmHg did not change in the older men. There were no significant LBNP effects on %CVC(max). Application of LBNP during cold stress did not significantly change %CVC(max) or FVC in either age group. During heat stress, -10 to -30 mmHg of LBNP decreased FVC significantly (P < 0.05) in both age groups, but these decreases were attenuated in the older men (P < 0.05). %CVC(max) decreased at -30 mmHg in the younger men only. These results suggest that older men have an attenuated skin vasoconstrictor response to the unloading of baroreceptors in heat stress conditions. Furthermore, the forearm vasoconstriction elicited by LBNP in older men reflects that of underlying tissue (i.e., muscle) rather than that of skin, whereas -30 mmHg LBNP also decreases SkBF in young hyperthermic men.     

Decreased capillary filtration but maintained venous compliance in the lower limb of aging women

There are sex-related differences in venous compliance and capillary filtration in the lower limbs, which to some extent can explain the susceptibility to orthostatic intolerance in young women. With age, venous compliance and capacitance are reduced in men. This study was designed to evaluate age-related changes in venous compliance and capillary filtration in the lower limbs of healthy women. Included in this study were 22 young and 12 elderly women (23.1 +/- 0.4 and 66.4 +/- 1.4 yr). Lower body negative pressure (LBNP) of 11, 22, and 44 mmHg created defined transmural pressure gradients in the lower limbs. A plethysmographic technique was used on the calf to assess venous capacitance and net capillary filtration. Venous compliance was calculated with the aid of a quadratic regression equation. No age-related differences in venous compliance and capacitance were found. Net capillary filtration and capillary filtration coefficient (CFC) were lower in elderly women at a LBNP of 11 and 22 mmHg (0.0032 vs. 0.0044 and 0.0030 vs. 0.0041 ml.100 ml(-1).min(-1).mmHg(-1), P < 0.001). At higher transmural pressure (LBNP, 44 mmHg), CFC increased by approximately 1/3 (0.010 ml.100 ml(-1).min(-1).mmHg(-1)) in the elderly (P < 0.001) but remained unchanged in the young women. In conclusion, no age-related decrease in venous compliance and capacitance was seen in women. However, a decreased CFC was found with age, implying reduced capillary function. Increasing transmural pressure increased CFC in the elderly women, indicating an increased capillary susceptibility to transmural pressure load in dependent regions. These findings differ from earlier studies on age-related effects in men, indicating sex-specific vascular aging both in the venous section and microcirculation.     

Plasma hyperosmolality augments peripheral vascular response to baroreceptor unloading during heat stress

The aim of this study was to elucidate the interactive effect of central hypovolemia and plasma hyperosmolality on regulation of peripheral vascular response and AVP secretion during heat stress. Seven male subjects were infused with either isotonic (0.9%; NOSM) or hypertonic (3.0%; HOSM) NaCl solution and then heated by perfusing 42 degrees C (heat stress; HT) or 34.5 degrees C water (normothermia; NT) through water perfusion suits. Sixty minutes later, subjects were exposed to progressive lower body negative pressure (LBNP) to -40 mmHg. Plasma osmolality (P(osmol)) increased by approximately 11 mosmol/kgH(2)O in HOSM conditions. The increase in esophageal temperature before LBNP was much larger in HT-HOSM (0.90 +/- 0.09 degrees C) than in HT-NOSM (0.30 +/- 0.07 degrees C) (P < 0.01) because of osmotic inhibition of thermoregulation. During LBNP, mean arterial pressure was well maintained, and changes in thoracic impedance and stroke volume were similar in all conditions. Forearm vascular conductance (FVC) before application of LBNP was higher in HT than in NT conditions (P < 0.001) and was not influenced by P(osmol) within the thermal conditions. The reduction in FVC at -40 mmHg in HT-HOSM (-9.99 +/- 0.96 units; 58.8 +/- 4.1%) was significantly larger than in HT-NOSM (-6.02 +/- 1.23 units; 44.7 +/- 8.1%) (P < 0.05), whereas the FVC response was not different between NT-NOSM and NT-HOSM. Plasma AVP response to LBNP did not interact with P(osmol) in either NT or HT conditions. These data indicate that there apparently exists an interactive effect of P(osmol) and central hypovolemia on the peripheral vascular response during heat stress, or peripheral vasodilated conditions, but not in normothermia.     

Reflex control of the cutaneous circulation during passive body core heating in humans.

The impact of body core heating on the interaction between the cutaneous and central circulation during blood pressure challenges was examined in eight adults. Subjects were exposed to -10 to -90 mmHg lower body negative pressure (LBNP) in thermoneutral conditions and -10 to -60 mmHg LBNP during heat stress. We measured forearm vascular conductance (FVC; ml. min(-1). 100 ml(-1). mmHg(-1)) by plethysmography; cutaneous vascular conductance (CVC) by laser-Doppler techniques; and central venous pressure, arterial blood pressure, and cardiac output by impedance cardiography. Heat stress increased FVC from 5.7 +/- 0.9 to 18.8 +/- 1.3 conductance units (CU) and CVC from 0.21 +/- 0.07 to 1.02 +/- 0.20 CU. The FVC-CVP relationship was linear over the entire range of LBNP and was shifted upward during heat stress with a slope increase from 0. 46 +/- 0.10 to 1.57 +/- 0.3 CU/mmHg CVP (P < 0.05). Resting CVP was lower during heat stress (6.3 +/- 0.6 vs. 7.7 +/- 0.6 mmHg; P < 0. 05) but fell to similar levels during LBNP as in normothermic conditions. Data analysis indicates an increased capacity, but not sensitivity, of peripheral baroreflex responses during heat stress. Laser-Doppler techniques detected thermoregulatory responses in the skin, but no significant change in CVC occurred during mild-to-moderate LBNP. Interestingly, very high levels of LBNP produced cutaneous vasodilation in some subjects.     

Splanchnic and peripheral vascular resistance during lower body negative pressure (LBNP) and tilt

We tested the hypothesis that vasoconstriction in response to LBNP or head up tilt would be reflected in a reduction in splanchnic (portal vein) blood flow (PVF) and increases in forearm and total peripheral vascular resistance (TPR). Changes in vascular resistance indicators were obtained from measurement of PVF from portal vein cross-sectional area and blood velocity by Doppler ultrasound, from forearm vascular resistance (FVR, by Doppler) and total peripheral resistance (TPR, by impedance cardiography). 21 subjects were tested during LBNP (0, -10, -20 and -30 mmHg) and 9 subjects during tilt (0, 45 and 70 degrees). During progressive LBNP, PVF decreased approximately linearly with LBNP (-30, -48 and -64% at -10, -20 and -30 mmHg) and with tilt angle (-39 and -58% at 45 and 70 degrees). The increase in FVR approximately mirrored these changes during LBNP (20.1, 44.7 and 55.3%) and tilt (45.6 and 63.6%). However, the changes in TPR during LBNP (12.0, 16.9 and 26.4%) and tilt (25.2 and 29.2%) were markedly less. This observation of different percent changes in forearm versus total peripheral resistance might reflect true physiological differences in the forearm (and splanchnic) circulations compared with the whole body, or the data might suggest that impedance cardiography did not provide a reliable indicator of cardiac output and therefore TPR under these conditions. The primary observation in this study was that Doppler ultrasound measurement of portal vein blood flow provided a non-invasive estimate of splanchnic vascular resistance during postural or LBNP challenge and that using the reduction in portal vein flow as an index of increased vasoconstriction paralleled the change in forearm vascular resistance.     

Association of sex and age with responses to lower-body negative pressure

Responses of 21 women and 29 men (29-56 yr of age) to -50 Torr lower body negative pressure (LBNP) were examined for differences due to sex or age. Responses to LBNP were normal, including fluid shift from thorax to lower body, increased heart rate and peripheral resistance, and decreased stroke volume, cardiac output, and Heather index of ventricular function. Mean arterial blood pressure did not change. Comparison of responses of the women to responses of an age-matched subset of the men (n = 26) indicated the men had larger relative increases in calf circumference and greater increases in peripheral resistance during LBNP than the women, whereas the women experienced greater increases in thoracic impedance and heart rate. Analyses of responses of the 29 men for age-related differences indicated older subjects had greater increases in peripheral resistance and less heart rate elevation in response to LBNP (P less than 0.05 for all differences, except sex-related heart rate difference, where P less than 0.10). Based on these data and the data of other investigators, we hypothesize the age-related circulatory differences in response to LBNP are due to a reduction in vagal response and a switch to predominant sympathetic nervous system influence in older men. We cannot exclude the possibility that diminished responsiveness in the afferent arm of the baroreceptor reflex also plays a role in the attenuated heart rate response of older men to LBNP.     

Haemodynamic responses to nonhypotensive central hypovolaemia induced by lower body negative pressure in men and women.

Haemodynamic responses to low levels of lower body negative pressure (LBNP) were investigated in two groups of healthy, normotensive volunteers (8 men and 8 women) during two repeated experimental runs on two occasions, the latter determined by the different phases of the menstrual cycle in the women. The data consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP), pulse rate (fc), forearm blood flow (FBF) and forearm vascular conductance (FC). The resting cardiovascular status was similar in men and women, except that women had a significantly higher fc than men. LBNP (1.3, 2.7 and 4 kPa) had no significant effect on any BP variable or on fc. However, FBF and FC were reduced at all levels of LBNP. Significant overshoots in FBF and FC were seen in all subjects following the release of LBNP of 2.7 and 4 kPa and, in most cases, after release of LBNP of 1.3 kPa. There were no significant gender differences in any of the responses to LBNP. Furthermore, none of the cardiovascular variables measured showed significant differences between the follicular and luteal phases of the menstrual cycle in women, either at rest or during exposure to LBNP, and the responses in the men on the two occasions were not different. These findings indicate that gender differences in responses to LBNP hypothesized previously are not apparent during and after exposure to low levels of LBNP.     

Hemodynamics of orthostatic intolerance: implications for gender differences

Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 +/- 55.0 vs. 927.7 +/- 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 +/- 2.0 vs. 7.1 +/- 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 +/- 0.8 vs. 4.29 +/- 0.6 ml.m-2.mmHg-1, P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance.     

Forebrain neural patterns associated with sex differences in autonomic and cardiovascular function during baroreceptor unloading

Generally, women demonstrate smaller autonomic and cardiovascular reactions to stress, compared with men. The mechanism of this sex-dependent difference is unknown, although reduced baroreflex sensitivity may be involved. Recently, we identified a cortical network associated with autonomic cardiovascular responses to baroreceptor unloading in men. The current investigation examined whether differences in the neural activity patterns within this network were related to sex-related physiological responses to lower body negative pressure (LBNP, 5, 15, and 35 mmHg). Forebrain activity in healthy men and women (n = 8 each) was measured using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast. Stroke volume (SV), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were collected on a separate day. Men had larger decreases in SV than women (P < 0.01) during 35 mmHg LBNP only. At 35 mmHg LBNP, HR increased more in males then females (9 +/- 1 beats/min vs. 4 +/- 1 beats/min, P < 0.05). Compared with women, increases in total MSNA were similar at 15 mmHg LBNP but greater during 35 mmHg LBNP in men [1,067 +/- 123 vs. 658 +/- 103 arbitrary units (au), P < 0.05]. BOLD signal changes (P < 0.005, uncorrected) were identified within discrete forebrain regions associated with these sex-specific HR and MSNA responses. Men had larger increases in BOLD signal within the right insula and dorsal anterior cingulate cortex than women. Furthermore, men demonstrated greater BOLD signal reductions in the right amygdala, left insula, ventral anterior cingulate, and ventral medial prefrontal cortex vs. women. The greater changes in forebrain activity in men vs. women may have contributed to the elevated HR and sympathetic responses observed in men during 35 mmHg LBNP.     

Cardiopulmonary baroreflex is reset during dynamic exercise.

The purpose of this study was to examine the hypothesis that the operating point of the cardiopulmonary baroreflex resets to the higher cardiac filling pressure of exercise associated with the increased cardiac filling volumes. Eight men (age 26 +/- 1 yr; height 180 +/- 3 cm; weight 86 +/- 6 kg; means +/- SE) participated in the present study. Lower body negative pressure (LBNP) was applied at 8 and 16 Torr to decrease central venous pressure (CVP) at rest and during steady-state leg cycling at 50% peak oxygen uptake (104 +/- 20 W). Subsequently, two discrete infusions of 25% human serum albumin solution were administered until CVP was increased by 1.8 +/- 0.6 and 2.4 +/- 0.4 mmHg at rest and 2.9 +/- 0.9 and 4.6 +/- 0.9 mmHg during exercise. During all protocols, heart rate, arterial blood pressure, and CVP were recorded continuously. At each stage of LBNP or albumin infusion, forearm blood flow and cardiac output were measured. During exercise, forearm vascular conductance increased from 7.5 +/- 0.5 to 8.7 +/- 0.6 U (P = 0.024) and total systemic vascular conductance from 7.2 +/- 0.2 to 13.5 +/- 0.9 l.min(-1).mmHg(-1) (P < 0.001). However, there was no significant difference in the responses of both forearm vascular conductance and total systemic vascular conductance to LBNP and the infusion of albumin between rest and exercise. These data indicate that the cardiopulmonary baroreflex had been reset during exercise to the new operating point associated with the exercise-induced change in cardiac filling volume.     

The cardiovascular response to lower body negative pressure in humans depends on seal location

We tested whether seal location at iliac crest (IC) or upper abdomen (UA), before and during lower body negative pressure (LBNP), would affect thoracic electrical impedance, hepatic blood flow, and central cardiovascular responses to LBNP. After 30 min of supine rest, LBNP at -40 mm Hg was applied for 15 min, either at IC or UA, in 14 healthy males. Plasma density and indocyanine green concentrations assessed plasma volume changes and hepatic perfusion. With both sealing types, LBNP-induced effects remained unchanged for mean arterial pressure (-3.0+/-1.1 mm Hg), cardiac output (-1.0 l min(-1)), and plasma volume (-11 %). Heart rate was greater during UA (80.6+/-3.3 bpm) than IC (76.0+/-2.5 bpm) (p<0.01) and thoracic impedance increased more using UA (3.2+/-0.2 Omega) than IC (1.8+/-0.2 Omega) (p<0.0001). Furthermore, during supine rest, UA was accompanied by lower thoracic impedance (26.9+/-1.1 vs 29.0+/-0.8 Omega, p<0.001) and hepatic perfusion (1.6 vs 1.8 l.min(-1), p<0.05) compared to IC. The data suggest that the reduction in central blood volume in response to LBNP depends on location of the applied seal. The sealing in itself altered blood volume distribution and hepatic perfusion in supine resting humans. Finally, application of LBNP with the seal at the upper abdomen induced a markedly larger reduction in central blood volume and greater increases in heart rate than when the seal was located at the iliac crest.     

Altered baroreflex control of forearm vascular resistance during simulated microgravity

Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.