[Improving vital organs perfusion by the respiratory pump: physiology and clinical use]. / Amélioration de la perfusion des organes vitaux par la valve d'impédance inspiratoire et le concept de pompe respiratoire : rationnel physiologique et application clinique.

OBJECTIVE: In this article, we review the effects of the respiratory pump to improve vital organ perfusion by the use of an inspiratory threshold device. DATA SOURCES: Medline and MeSH database. STUDY SELECTION: All papers with a level of proof of I to III have been used. DATA EXTRACTION: The analysis of the papers has focused on the physiological modifications induced by intrathoracic pressure regulation. DATA SYNTHESIS: Primary function of breathing is to provide gas exchange. Studies of the mechanisms involved in animals and humans provide the physiological underpinnings for "the other side of breathing": to increase circulation to the heart and brain. We describe studies that focus on the fundamental relationship between the generation of negative intrathoracic pressure during inspiration through a low-level of resistance created by an impedance threshold device and the physiologic effects of a respiratory pump. A decrease in intrathoracic pressure during inspiration through a fixed resistance resulting in an intrathoracic pressure of -7 cmH2O has multiple physiological benefits including: enhanced venous return, cardiac stroke volume and aortic blood pressure; lower intracranial pressure; resetting of the cardiac baroreflex; elevated cerebral blood flow oscillations and increased tissue blood flow/pressure gradient. CONCLUSION: The clinical and animal studies support the use of the intrathoracic pump to treat different clinical conditions: hemorrhagic shock, orthostatic hypotension, septic shock, and cardiac arrest.

Monitoring non-invasive cardiac output and stroke volume during experimental human hypovolaemia and resuscitation.

BACKGROUND: Multiple methods for non-invasive measurement of cardiac output (CO) and stroke volume (SV) exist. Their comparative capabilities are not clearly established. METHODS: Healthy human subjects (n=21) underwent central hypovolaemia through progressive lower body negative pressure (LBNP) until the onset of presyncope, followed by termination of LBNP, to simulate complete resuscitation. Measurement methods were electrical bioimpedance (EBI) of the thorax and three measurements of CO and SV derived from the arterial blood pressure (ABP) waveform: the Modelflow (MF) method, the long-time interval (LTI) method, and pulse pressure (PP). We computed areas under receiver-operating characteristic curves (ROC AUCs) for the investigational metrics, to determine how well they discriminated between every combination of LBNP levels. RESULTS: LTI and EBI yielded similar reductions in SV during progressive hypovolaemia and resuscitation (correlation coefficient 0.83) with ROC AUCs for distinguishing major LBNP (-60 mm Hg) vs resuscitation (0 mm Hg) of 0.98 and 0.99, respectively. MF yielded very similar reductions and ROC AUCs during progressive hypovolaemia, but after resuscitation, MF-CO did not return to baseline, yielding lower ROC AUCs (ΔROC AUC range, -0.18 to -0.26, P < 0.01). PP declined during hypovolaemia but tended to be an inferior indicator of specific LBNP levels, and PP did not recover during resuscitation, yielding lower ROC curves (P < 0.01). CONCLUSIONS: LTI, EBI, and MF were able to track progressive hypovolaemia. PP decreased during hypovolaemia but its magnitude of reduction underestimated reductions in SV. PP and MF were inferior for the identification of resuscitation.

Combat casualty care research at the U.S. Army Institute of Surgical Research.

The Institute of Surgical Research is the U.S. Army's lead research laboratory for improving the care of combat casualties. The Institute follows a rigorous process for analyzing patterns of injury and the burden of disease to determine where research can be conducted in order to positively impact care. These analyses led the ISR to focus research on: preventing death from bleeding; developing improved pain control techniques; developing improved vital signs analysis techniques; improving the treatment of extremity injuries; preventing burn injuries on the battlefield; and improving critical care for combat casualties. This process has resulted in numerous improvements in care on the battlefield. Highlights include development, fielding, and efficiency testing of tourniquets and improved dressings for bleeding control. Significant progress has also been made in the resuscitation of combat casualties using blood products instead of crystalloid or colloid solutions. Improvements in pain control include assessments of the effect of perioperative anaesthetics on the development of post-traumatic stress disorder [PTSD]. Novelvital signs analyses have been successful in identifying promising techniques which may improve the medic's ability to accurately triage patients. Current research in extremity injuries has focused on optimizing the use of negative pressure wound therapy for contaminated wounds. Burn research has focused on improving personnel protective equipment and implementing continuous renal replacement therapy. This research program is soldier focused and addresses care from self aid and buddy aid through all echelons of care. Many of these advances have been adopted in civilian medical centres as well, benefiting not only the military trauma patient, but also the civilian trauma patient.

Comparison of cardiac output monitoring methods for detecting central hypovolemia due to lower body negative pressure.

Reduction in mean arterial pressure (MAP) is a late indictor of progressive circulatory pathology. Non-invasive monitoring methods that are superior indicators of circulatory compromise would be clinically valuable. With IRB approval, 21 healthy volunteers were subjected to progressive lower body negative pressure (LBNP) until the onset of presyncopal symptoms. We evaluated the usefulness of four investigational methods of arterial blood pressure waveform analysis during progressive hypovolemia: mean arterial pressure (MAP); the ModelFlow cardiac output algorithm (MF); the long time interval method (LTI); and the product of pulse pressure and heart rate (PP*HR). Electrical bioimpedance measurement of cardiac output (EBI) provided a reference. When results were analyzed, we found significant differences between the methods. MF, LTI, and EBI all corresponded with LBNP severity, while MAP and PP*HR did not. In terms of discriminating between (a) decompression to -45 mmHg; versus (b) recovery five minutes after LBNP cessation, there was a significant difference between MF and LTI: the receiver operating characteristic area-under-the-curve (ROC AUC) for MF was 0.57 and for LTI was 0.76. In terms of discriminating between (a) the 11 subjects who tolerated the protocol (i.e., tolerated higher levels of LBNP); versus (b) the 10 non-tolerant subjects, there was also a significant difference between MF and LTI: the ROC AUC for MF was 0.40 and for LTI was 0.66. There were no significant differences between MF nor EBI, however. In conclusion, LTI is notable as the only method which (a) correlated with decompression: (b) distinguished between decompression to -45 mmHg versus recovery; and (c) distinguished between those subjects who adequately compensated for central hypovolemia (tolerant) and those who did not have such robust physiologic compensation (non-tolerant).

Evidence for central venous pressure resetting during initial exposure to microgravity.

We measured central venous pressure (CVP); plasma volume (PV); urine volume rate (UVR); renal excretion of sodium (UNa); and renal clearances of creatinine, sodium, and osmolality before and after acute volume infusion to test the hypothesis that exposure to microgravity causes resetting of the CVP operating point. Six rhesus monkeys underwent two experimental conditions in a crossover counterbalance design: 1) continuous exposure to 10 degrees head-down tilt (HDT) and 2) a control, defined as 16 h/day of 80 degrees head-up tilt and 8 h prone. After 48 h of exposure to either test condition, a 120-min course of continuous infusion of isotonic saline (0.4 ml. kg(-1). min(-1) iv) was administered. Baseline CVP was lower (P = 0.011) in HDT (2.3 +/- 0.3 mmHg) compared with the control (4.5 +/- 1.4 mmHg) condition. After 2 h of saline infusion, CVP was elevated (P = 0.002) to a similar magnitude (P = 0.485) in HDT (DeltaCVP = 2.7 +/- 0.8 mmHg) and control (DeltaCVP = 2.3 +/- 0.8 mmHg) conditions and returned to preinfusion levels 18 h postinfusion in both treatments. PV followed the same pattern as CVP. The response relationships between CVP and UVR and between CVP and UNa shifted to the left with HDT. The restoration of CVP and PV to lower preinfusion levels after volume loading in HDT compared with control supports the notion that lower CVP during HDT may reflect a new operating point about which vascular volume is regulated. These results may explain the ineffective fluid intake procedures currently employed to treat patients and astronauts.

Blood pressure changes during orthostatic stress: evidence of gender differences in neuroeffector distribution.

BACKGROUND: Research has demonstrated that exogenous adrenergic agonists produce dose-related vasoconstriction in men but not women. This suggests that the distribution of adrenergic receptor sites differ with gender. Women may have a higher density of receptor sites in the arterioles (fast acting with low gain) while men may have higher density in the larger vessels (slow acting with high gain). METHODS: To partially test this hypothesis, the time course in beat-to-beat responses in systolic and diastolic BP, and heart rate was compared between six men and six women during the transition from a supine to an upright posture and during prolonged standing. RESULTS: The transient change in systolic and diastolic BP was very rapid in women, but completed within 15 to 30 s after assuming an upright position. Men increased BP at a much slower rate, but continued to produce higher BPs over the complete testing session (up to 15 min). The rate of change for men (15 mm Hg systolic and 10 mm Hg diastolic) was approximately half that for women (30 mm Hg systolic and 15 mm Hg diastolic) during the first 30 s of upright posture. However, after 60 s of standing, absolute change in systolic BP for the men exceeded that of the women by approximately 5 mm Hg for both systolic and diastolic BP. While men's heart rate remained relatively constant during standing, women compensated for the lower change in BP by a continual increase in heart rate throughout the duration of the test. Although both men and women demonstrated increases in norepinephrine at 5 and 15 min during standing, no difference between genders was observed. Similarly, there were no differences in dominant periodicity of heart rate during standing, although women demonstrated slightly higher beat-to-beat variation (RMS) than men. CONCLUSION: The results support the hypothesis of distributional differences in neuroeffector responses between men and women and have implications for how men and women respond to orthostatic stress across a variety of environmental conditions.

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration.

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

Left ventricular, systemic arterial, and baroreflex responses to ketamine and TEE in chronically instrumented monkeys.

Effects of prescribed doses of ketamine five minutes after application and influences of transesophageal echocardiography (TEE) on left ventricular, systemic arterial, and baroreflex responses were investigated to test the hypothesis that ketamine and/or TEE probe insertion alter cardiovascular function. Seven rhesus monkeys were tested under each of four randomly selected experimental conditions: (1) intravenous bolus dose of ketamine (0.5 ml), (2) continuous infusion of ketamine (500 mg/kg/min), (3) continuous infusion of ketamine (500 mg/kg/min) with TEE, and (4) control (no ketamine or TEE). Monkeys were chronically instrumented with a high fidelity, dual-sensor micromanometer to measure left ventricular and aortic pressure and a transit-time ultrasound probe to measure aortic flow. These measures were used to calculate left ventricular function. A 4-element Windkessel lumped-parameter model was used to estimate total peripheral resistance and systemic arterial compliance. Baroreflex response was calculated as the change in R-R interval divided by the change in mean aortic pressure measured during administration of graded concentrations of nitroprusside. The results indicated that five minutes after ketamine application heart rate and left ventricular diastolic compliance decreased while TEE increased aortic systolic and diastolic pressure. We conclude that ketamine may be administered as either a bolus or continuous infusion without affecting cardiovascular function 5 minutes after application while the insertion of a TEE probe will increase aortic pressure. The results for both ketamine and TEE illustrate the classic "Hawthorne Effect," where the observed values are partly a function of the measurement process. Measures of aortic pressure, heart rate, and left ventricular diastolic pressure should be viewed as relative, as opposed to absolute, when organisms are sedated with ketamine or instrumented with a TEE probe.

Lower body negative pressure as a tool for research in aerospace physiology and military medicine.

Lower body negative pressure (LBNP) has been extensively used for decades in aerospace physiological research as a tool to investigate cardiovascular mechanisms that are associated with or underlie performance in aerospace and military environments. In comparison with clinical stand and tilt tests, LBNP represents a relatively safe methodology for inducing highly reproducible hemodynamic responses during exposure to footward fluid shifts similar to those experienced under orthostatic challenge. By maintaining an orthostatic challenge in a supine posture, removal of leg support (muscle pump) and head motion (vestibular stimuli) during LBNP provides the capability to isolate cardiovascular mechanisms that regulate blood pressure. LBNP can be used for physiological measurements, clinical diagnoses and investigational research comparisons of subject populations and alterations in physiological status. The applications of LBNP to the study of blood pressure regulation in spaceflight, groundbased simulations of low gravity, and hemorrhage have provided unique insights and understanding for development of countermeasures based on physiological mechanisms underlying the operational problems.

Is there resetting of central venous pressure in microgravity?

In the early phase of the Space Shuttle program, NASA flight surgeons implemented a fluid-loading countermeasure in which astronauts were instructed to ingest eight 1-g salt tablets with 960 ml of water approximately 2 hours prior to reentry from space. This fluid loading regimen was intended to enhance orthostatic tolerance by replacing circulating plasma volume reduced during the space mission. Unfortunately, fluid loading failed to replace plasma volume in groundbased experiments and has proven minimally effective as a countermeasure against post-spaceflight orthostatic intolerance. In addition to the reduction of plasma volume, central venous pressure (CVP) is reduced during exposure to actual and groundbased analogs of microgravity. In the present study, we hypothesized that the reduction in CVP due to exposure to microgravity represents a resetting of the CVP operating point to a lower threshold. A lower CVP 'setpoint' might explain the failure of fluid loading to restore plasma volume. In order to test this hypothesis, we conducted an investigation in which we administered an acute volume load (stimulus) and measured responses in CVP, plasma volume and renal functions. If our hypothesis is true, we would expect the elevation in CVP induced by saline infusion to return to its pre-infusion levels in both HDT and upright control conditions despite lower vascular volume during HDT. In contrast to previous experiments, our approach is novel in that it provides information on alterations in CVP and vascular volume during HDT that are necessary for interpretation of the proposed CVP operating point resetting hypothesis.

Renal responsiveness to aldosterone during exposure to simulated microgravity.

We measured renal functions and hormones associated with fluid regulation after a bolus injection of aldosterone (Ald) during head-down tilt (HDT) bed rest to test the hypothesis that exposure to simulated microgravity altered renal responsiveness to Ald. Six male rhesus monkeys underwent two experimental conditions (HDT and control, 72 h each) with each condition separated by 9 days of ambulatory activities to produce a crossover counterbalance design. One test condition was continuous exposure to 10 degrees HDT; the second was a control, defined as 16 h per day of 80 degrees head-up tilt and 8 h prone. After 72 h of exposure to either test condition, monkeys were moved to the prone position, and we measured the following parameters for 4 h after injection of 1-mg dose of Ald: urine volume rate (UVR); renal Na(+)/K(+) excretion ratio; renal clearances of creatinine, Na(+), osmolality, and free water; and circulating hormones [Ald, renin activity (PRA), vasopressin (AVP), and atrial natriuretic peptide (ANP)]. HDT increased Na(+) clearance, total renal Na(+) excretion, urine Na(+) concentration, and fractional Na(+) excretion, compared with the control condition, but did not alter plasma concentrations of Ald, PRA, and AVP. Administration of Ald did not alter UVR, creatinine clearance, Ald, PRA, AVP, or ANP but reduced Na(+) clearance, total renal Na(+) excretion, urinary Na(+)/K(+) ratio, and osmotic clearance. Although reductions in Na(+) clearance and excretion due to Ald were greater during HDT than during control, the differential (i.e., interaction) effect was minimal between experimental conditions. Our data suggest that exposure to microgravity increases renal excretion of Na(+) by a natriuretic mechanism other than a change in renal responsiveness to Ald.

Validity of VO(2 max) in predicting blood volume: implications for the effect of fitness on aging.

A multiple regression model was constructed to investigate the premise that blood volume (BV) could be predicted using several anthropometric variables, age, and maximal oxygen uptake (VO(2 max)). To test this hypothesis, age, calculated body surface area (height/weight composite), percent body fat (hydrostatic weight), and VO(2 max) were regressed on to BV using data obtained from 66 normal healthy men. Results from the evaluation of the full model indicated that the most parsimonious result was obtained when age and VO(2 max) were regressed on BV expressed per kilogram body weight. The full model accounted for 52% of the total variance in BV per kilogram body weight. Both age and VO(2 max) were related to BV in the positive direction. Percent body fat contributed <1% to the explained variance in BV when expressed in absolute BV (ml) or as BV per kilogram body weight. When the model was cross validated on 41 new subjects and BV per kilogram body weight was reexpressed as raw BV, the results indicated that the statistical model would be stable under cross validation (e.g., predictive applications) with an accuracy of +/- 1,200 ml at 95% confidence. Our results support the hypothesis that BV is an increasing function of aerobic fitness and to a lesser extent the age of the subject. The results may have implication as to a mechanism by which aerobic fitness and activity may be protective against reduced BV associated with aging.

Vasoactive neuroendocrine responses associated with tolerance to lower body negative pressure in humans.

The purpose of this investigation was to test the hypothesis that peripheral vasoconstriction and orthostatic tolerance are associated with increased circulating plasma concentrations of noradrenaline, vasopressin and renin-angiotensin. Sixteen men were categorized as having high (HT, n=9) or low (LT, n=7) tolerance to lower body negative pressure (LBNP) based on whether the endpoint of their pre-syncopal-limited LBNP (peak LBNP) exposure exceeded -60 mmHg. The two groups were matched for age, height, weight, leg volume, blood volume and maximal oxygen uptake, as well as baseline blood volume and plasma concentrations of vasoactive hormones. Peak LBNP induced similar reductions in mean arterial pressure in both groups. The reduction in leg arterial pulse volume (measured by impedance rheography), an index of peripheral vascular constriction, from baseline to peak LBNP was greater (P<0.05) in the HT group (-0.041 +/- 0.005 ml 100 ml-1) compared to the reduction in the LT group (-0. 025 +/- 0.003 ml 100 ml-1). Greater peak LBNP in the HT group was associated with higher (P<0.05) average elevations in plasma concentrations of vasopressin (pVP, Delta=+7.2 +/- 2.0 pg ml-1) and plasma renin-angiotensin (PRA, Delta=+2.9 +/- 1.3 ng Ang II ml-1 h-1) compared to average elevations of pVP (+2.2 +/- 1.0 pg ml-1) and PRA (+0.1 +/- 0.1 ng Ang II ml-1 h-1) in the LT group. Plasma noradrenaline concentrations were increased (P<0.05) from baseline to peak LBNP in both HT and LT groups, with no statistically distinguishable difference between groups. These data suggest that the renin-angiotensin and vasopressin systems may contribute to sustaining arterial pressure and orthostatic tolerance by their vasoconstrictive actions.

Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness.

This paper reviews the influence of several perturbations (physical exercise, heat stress, terrestrial altitude, microgravity, and trauma/sickness) on adaptations of blood volume (BV), erythrocyte volume (EV), and plasma volume (PV). Exercise training can induce BV expansion: PV expansion usually occurs immediately, but EV expansion takes weeks. EV and PV expansion contribute to aerobic power improvements associated with exercise training. Repeated heat exposure induces PV expansion but does not alter EV. PV expansion does not improve thermoregulation, but EV expansion improves thermoregulation during exercise in the heat. Dehydration decreases PV (and increases plasma tonicity) which elevates heat strain and reduces exercise performance. High altitude exposure causes rapid (hours) plasma loss. During initial weeks at altitude, EV is unaffected, but a gradual expansion occurs with extended acclimatization. BV adjustments contribute, but are not key, to altitude acclimatization. Microgravity decreases PV and EV which contribute to orthostatic intolerance and decreased exercise capacity in astronauts. PV decreases may result from lower set points for total body water and central venous pressure, while EV decreases may result from increased erythrocyte destruction. Trauma, renal disease, and chronic diseases cause anemia from hemorrhage and immune activation which suppresses erythropoiesis. The re-establishment of EV is associated with healing, improved life quality, and exercise capabilities for these injured/sick persons.

Effect of G-suit protection on carotid-cardiac baroreflex function.

INTRODUCTION: To test the hypothesis that G-suit inflation could increase cardiac chronotropic responses to baroreceptor stimulation and enhance baroreflex buffering of BP, the carotid-cardiac baroreflex response of 12 subjects was measured across two levels of lower body negative pressure (LBNP = 0 and 50 mm Hg) and two levels of G-suit inflation (0 and 50 mm Hg) in random order. METHODS: Carotid-cardiac baroreflex stimulation was delivered via a silastic neck pressure cuff and responsiveness quantified by determination of the maximum slope of the stimulus-response function between R-R intervals (ms) and their respective carotid distending pressures (mmHg). RESULTS: Mean +/- SE baseline control baroreflex responsiveness was 3.8+/-0.4 ms x mm Hg(-1). LBNP reduced the baroreflex response to 2.7+/-0.4 ms x mm Hg(-1), but G-suit inflation with LBNP restored the baroreflex response to 4.3+/-0.6 ms x mm Hg(-1). CONCLUSIONS: These results suggest that, in addition to increased venous return and elevated peripheral resistance, G-suit inflation may provide protection against the debilitating effects of blood distribution to the lower extremities during orthostatic challenges such as standing or high +Gz acceleration by increasing cardiovascular responsiveness to carotid baroreceptor stimulation.

Renal responsiveness to aldosterone during exposure to head-down tilt bedrest.

The kidneys represent a fundamental organ system responsible in part for the control of vascular volume. A 10% to 20% reduction in plasma volume is one of the fundamental adaptations during exposure to low gravity environments such as bedrest and space flight. Bedrest-induced hypovolemia has been associated with acute diuresis and natriuresis. Elevated baseline plasma renin activity and aldosterone levels have been observed in human subjects following exposure to head-down tilt and spaceflight without alterations in renal sodium excretion. Further, attempts to restore plasma volume with isotonic fluid drinking or infusion in human subjects exposed to head-down bedrest have failed. One explanation for these observations is that renal distal tubular cells may become less sensitive to aldosterone following exposure to head-down tilt, with a subsequent reduction in renal capacity for sodium retention. We hypothesized that elevated sodium and water excretion observed during prolonged exposure to bedrest and the subsequent inability to restore body fluids by drinking might be reflected, at least in part, by reduced renal tubular responsiveness to aldosterone. If renal tubular responsiveness to aldosterone were reduced with confinement to bedrest, then we would expect measures of renal sodium retention to be reduced when a bolus of aldosterone was administered in head-down tilt (HDT) bedrest compared to a control experimental condition. In order to test this hypothesis, we conducted an investigation in which we administered an acute bolus of aldosterone (stimulus) and measured responses in renal functions that included renal clearances of sodium and free water, sodium/potassium ratio in urine, urine sodium concentration, and total and fractional renal sodium excretion.

Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects.

Cardiovascular responses during a graded lower body negative pressure (LBNP) protocol were compared before and after atropine and propranolol administration to test the hypothesis that both sympathetic and parasympathetic control of cardio-acceleration are associated with syncopal predisposition to orthostatic stress in healthy subjects. Eleven men were categorized into two groups having high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before the onset of presyncopal symptoms. HT and LT groups were similar in physical characteristics, fitness, and baseline cardiovascular measurements. Atropine treatment had no effect on LBNP tolerance or mean arterial pressure at presyncope, despite an atropine-induced increase in heart rate. Propranolol treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP tolerance after propranolol administration was associated with reductions in cardiac output, whereas increase in systemic peripheral resistance from baseline to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP tolerance after beta blockade reflected a chronotropic effect because lower LBNP tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without significant effects on stroke volume at presyncope. Absence of an atropine-induced difference in cardiac output and systemic peripheral resistance between HT and LT groups failed to support the notion that cardiac vagal withdrawal represents a predominant mechanism that could account for differences in orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT groups after propranolol treatment was most closely associated with reduced tachycardia, the data suggest that a primary autonomically mediated mechanism for maintenance of mean arterial pressure and orthostatic tolerance in healthy subjects is beta adrenergic-induced tachycardia.

Exercise training and intensity does not alter vascular volume responses in women.

PURPOSE: The effect of endurance training on vascular volumes in females has received little research attention. Further, the effect of exercise training intensity on vascular volumes is unknown. Therefore, we investigated the hypothesis that greater hematologic changes would be induced in women by higher exercise intensity during endurance training. METHODS: There were 26 healthy, sedentary adult females with the following characteristics (mean +/- SD): maximal oxygen consumption (VO2max) = 30.0+/-6.6 ml x kg(-1) x min(-1); age = 32+/-5 yr; body mass index (BMI) = 23.7+/-3.6 kg x m(-2)) who were randomly assigned to control (CON, n = 8); high intensity (HI, 80% of VO2max, n = 10), or low intensity (LO, 40% of VO2max, n = 8) cycle ergometer training groups. Training, conducted 3-5 (3.37+/-0.05) d x wk(-1) for 12 wk, was supervised. Estimated exercise energy expenditure was equated across training groups, progressing from 150-375 kcal per session (mean +/- SE across training weeks = 298+/-0.34 and 297+/-0.37 kcal per session for HI and LO, respectively). Plasma volume (PV, T-1824 dilution); calculated total blood (TBV) and red cell volumes (RCV); calculated total hemoglobin (THb); erythropoietin concentration ([Epo]) and selected hematologic variables were measured at baseline and weeks 2, 4, 8 and 12 of training. RESULTS: The observed relative (percent) changes in PV, TBV, RCV and THb from pre-training baseline values were not statistically significant. Decreases (p < 0.05) in hematocrit (Hct), hemoglobin ([Hb]) and RBC count were observed in both training groups. Mean corpuscular Hb (MCH) and Hb concentration (MCHC) increased (p < 0.05) during training. [Epo] was decreased at week 2 compared with baseline (p < 0.03), but was similar to baseline at weeks 4, 8 and 12. CONCLUSIONS: Within the limits of this study, endurance training did not increase PV, TBV, RCV and THb in previously sedentary females regardless of the intensity of training.

Acute manipulations of plasma volume alter arterial pressure responses during Valsalva maneuvers.

The effects of changes in blood volume on arterial pressure patterns during the Valsalva maneuver are incompletely understood. In the present study we measured beat-to-beat arterial pressure and heart rate responses to supine Valsalva maneuvers during normovolemia, hypovolemia induced with intravenous furosemide, and hypervolemia induced with ingestion of isotonic saline. Valsalva responses were analyzed according to the four phases as previously described (W. F. Hamilton, R. A. Woodbury, and H. T. Harper, Jr. JAMA 107: 853-856, 1936; W. F. Hamilton, R. A. Woodbury, and H. T. Harper, Jr. Am. J. Physiol. 141: 42-50, 1944). Phase I is the initial onset of straining, which elicits a rise in arterial pressure; phase II is the period of straining, during which venous return is impeded and pressure falls (early) and then partially recovers (late); phase III is the initial release of straining; and phase IV consists of a rapid "overshoot" of arterial pressure after the release. During hypervolemia, early phase II arterial pressure decreases were significantly less than those during hypovolemia, thus making the response more "square." Systolic pressure hypervolemic vs. hypovolemic falls were -7.4 +/- 2.1 vs. -30.7 +/- 7 mmHg (P = 0.005). Diastolic pressure hypervolemic vs. hypovolemic falls were -2.4 +/- 1.6 vs. -15.2 +/- 2.6 mmHg (P = 0.05). A significant direct correlation was found between plasma volume and phase II systolic pressure falls, and a significant inverse correlation was found between plasma volume and phase III-IV systolic pressure overshoots. Heart rate responses to systolic pressure falls during phase II were significantly less during hypovolemia than during hypervolemia (0.7 +/- 0.2 vs. 2.82 +/- 0.2 beats. min-1. mmHg-1; P = 0.05) but were not different during phase III-IV overshoots. We conclude that acute changes in intravascular volume from hypovolemia to hypervolemia affect cardiovascular responses, particularly arterial pressure changes, to the Valsalva maneuver and should be considered in both clinical and research applications of this maneuver.

G-factor as a tool in basic research: mechanisms of orthostatic tolerance.

The inability to tolerate upright standing posture due to development of orthostatic hypotension is a clinical problem experienced by more than 500,000 people in the United States. In addition, orthostatic intolerance is an operational problem since as many as 25 to 64 percent of the crew members from U.S. space shuttle flights have been reported to experience presyncopal incidents during postflight stand tests. Last year alone, more than 10,000 cases of unexplained syncope were reported in active duty personnel in all U.S. military services. Many clinical investigations have focused on measurements of physiological functions in patients with orthostatic instability in an effort to identify possible mechanisms that underlie the problem. Although this approach has provided important insight into mechanisms associated with syncope, identification of causal relationships are limited by pre-existing pathologic conditions. Causal relationships can be better defined when physiological mechanisms that underlie blood pressure regulation are altered in healthy subjects by increasing or decreasing their gravity environment (so-called "G-factor" approach) and subsequent changes in orthostatic tolerance are induced. The purpose of this paper is to review data on physiological functions measured from healthy human subjects who have undergone exposure to various levels of low or high gravity in an effort to assess our understanding about mechanisms of orthostatic tolerance. Specifically, results from human subjects exposed to bedrest, spaceflight, and high sustained acceleration will be used to provide insight into the plasticity of mechanisms underlying adaptations of blood pressure regulation orthostatic performance.