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.

Mechanisms for decreased exercise capacity after bed rest in normal middle-aged men.

The mechanisms responsible for the decrease in exercise capacity after bed rest were assessed in 12 apparently healthy men aged 50 +/- 4 years who underwent equilibrium gated blood pool scintigraphy during supine and upright multistage bicycle ergometry before and after 10 days of bed rest. After bed rest, echocardiographically measured supine resting left ventricular end-diastolic volume decreased by 16% (p less than 0.05). Peak oxygen uptake during supine effort after bed rest was diminished by 6% (p = not significant [NS]), whereas peak oxygen uptake during upright effort declined by 15% (p less than 0.05). After bed rest, increases in heart rate were also greater during exercise in the upright than in the supine position (p less than 0.05). Values of left ventricular ejection fraction increased normally during both supine and upright effort after bed rest and were higher than corresponding values before bed rest (p less than 0.05). After bed rest, increased left ventricular ejection fraction and heart rate largely compensated for the reduced cardiac volume during supine effort, but these mechanisms were insufficient to maintain oxygen transport capacity at levels during upright effort before bed rest. These results indicate that orthostatically induced cardiac underfilling, not physical deconditioning or left ventricular dysfunction, is the major cause of reduced effort tolerance after 10 days of bed rest in normal middle-aged men.

Fluid homeostasis after heart transplantation: the role of cardiac denervation.

BACKGROUND: Orthotopic heart transplantation may interrupt key neural and humoral homeostatic mechanisms that normally adjust Na+ and fluid excretion to changes in intake. Such an interruption could lead to plasma volume expansion. METHODS: We measured plasma volume and fluid regulatory hormones under standardized conditions in 11 heart transplant recipients (58 +/- 7 years old; mean +/- standard deviation) 21 +/- 4 months after transplantation, in 6 liver transplant recipients (51 +/- 6 years old) 13 +/- 8 months after transplantation (cyclosporine control group), and in 7 normal healthy control subjects (61 +/- 9 years old). Administration of all diuretics and antihypertensive drugs was discontinued before the study. After 3 days during which subjects ate a constant diet containing 87 mEq of Na+ per 24 hours, plasma volume was measured by a modified Evans blue dye (T-1824) dilution technique. Renal creatinine clearance was measured and blood samples were drawn for determination of plasma levels of vasopressin, angiotensin II, aldosterone, atrial natriuretic peptide, and plasma renin activity. RESULTS: Supine resting plasma renin activity, angiotensin II, and aldosterone (renin-angiotensin-aldosterone axis) and vasopressin levels were not different among the control, heart transplant, and liver transplant groups. However, there was a trend toward elevated angiotensin II (p < or = 0.08) and aldosterone (p < or = 0.08) levels in the heart transplant recipients. Atrial natriuretic peptide levels were significantly elevated two to threefold in the heart transplant recipients when compared with those in the two control groups. Blood volume, normalized for body weight (milliliters per kilogram), was significantly greater (14%) in the heart transplant recipients when compared with that in liver transplant recipients and normal healthy control subjects. Blood volume values did not differ (p > or = 0.05) between the two control groups. CONCLUSIONS: Extracellular fluid volume expansion (+14%) occurs in clinically stable heart transplant recipients who become hypertensive. Although hyperactivity of the renin-angiotensin-aldosterone axis is not apparent during supine resting conditions, our data suggest that the renin-angiotensin-aldosterone system is not responsive to a hypervolemic stimulus and this is likely a consequence of chronic cardiac deafferentation. Thus, poor adaptation of the renin-angiotensin-aldosterone system to fluid retention may be partly responsible for the incidence and severity of posttransplantation hypertension in some heart transplant recipients.

Hormonal responses in elders experiencing pre-syncopal symptoms during head-up tilt before and after exercise training.

BACKGROUND: Hormonal responses of elderly individuals experiencing pre-syncopal symptoms during head-up tilt testing (HUT) were compared with responses of nonsymptomatic subjects both before (T1) and after (T2) 6 months of endurance training. METHODS: Based on responses to HUT at T1, 35 men and women (ages 61-79 years) were placed into symptomatic and nonsymptomatic groups for analysis. Symptomatic subjects (n = 5) experienced lightheadedness, nausea, sweating, or syncope during T1 HUT but completed 15 minutes of HUT at T2. Training consisted of treadmill walking or stairclimbing 3 x/wk, 30-45 min/day, at 75-85% of maximal heart rate reserve. Adrenocorticotropic hormone (ACTH), vasopressin, aldosterone, norepinephrine, epinephrine, hemoglobin, and hematocrit were measured during supine rest prior to HUT, and either at the end of the 15-minute HUT or at symptom onset. Plasma volume (PV) was measured at supine rest; tilt-induced changes in PV were calculated from changes in hemoglobin and hematocrit. RESULTS: During T1 HUT, symptomatic subjects had greater increases in vasopressin and a greater rate of PV loss (p < .05). Increases in ACTH and aldosterone were greater in symptomatic subjects at T1 and T2, while increases in norepinephrine were greater at T2 (p < .05). Reductions in tilt-induced vasopressin concentration and a decreased rate of PV loss were seen at T2 in symptomatic subjects. CONCLUSIONS: T1 results from symptomatic subjects are consistent with greater stimulation of volume-sensitive receptors induced by a greater rate of fall in PV. Exercise training resulted in increased tilt tolerance for symptomatic subjects associated with reductions in vasopressin concentration and rate of PV loss during tilt.

Plasma aldosterone and sweat sodium concentrations after exercise and heat acclimation.

This investigation was designed to determine the relationship between the levels of plasma aldosterone and eccrine sweat gland sodium excretion following exercise and heat acclimation. Ten subjects exercised at 45% of their maximal O2 uptake in a hot (40 degrees C), moderately humid (45% relative humidity) environment for 2 h/day on ten consecutive days. Acclimation was verified by significant reductions in exercise heart rate, rectal temperature, and heat storage, as well as significant elevation of resting plasma volume (12%, P less than 0.05) and exercise sweat rate on day 10 compared with day 1 of acclimation. During exercise, the concentration and total content of sodium in sweat as well as plasma aldosterone were significantly decreased from day 1 to day 10. The ratio of sweat sodium reabsorbed to plasma aldosterone concentration was significantly increased from day 1 to day 10 after both 1 and 2 h of exercise. These data indicate that plasma aldosterone concentrations decrease following heat acclimation; and eccrine gland responsiveness to aldosterone, as represented by sweat sodium reabsorption, may be augumented through exercise and heat acclimation.

Catecholaminergic effects of prolonged head-down bed rest.

Prolonged head-down bed rest (HDBR) provides a model for examining responses to chronic weightlessness in humans. Eight healthy volunteers underwent HDBR for 2 wk. Antecubital venous blood was sampled for plasma levels of catechols [norepinephrine (NE), epinephrine, dopamine, dihydroxyphenylalanine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid] after supine rest on a control (C) day and after 4 h and 7 and 14 days of HDBR. Urine was collected after 2 h of supine rest during day C, 2 h before HDBR, and during the intervals 1-4, 4-24, 144-168 (day 7), and 312-336 h (day 14) of HDBR. All subjects had decreased plasma and blood volumes (mean 16%), atriopeptin levels (31%), and peripheral venous pressure (26%) after HDBR. NE excretion on day 14 of HDBR was decreased by 35% from that on day C, without further trends as HDBR continued, whereas plasma levels were only variably and nonsignificantly decreased. Excretion rates of dihydroxyphenylglycol and dihydroxyphenylalanine decreased slightly during HDBR; excretion rates of epinephrine, dopamine, and dihydroxyphenylacetic acid and plasma levels of catechols were unchanged. The results suggest that HDBR produces sustained inhibition of sympathoneural release, turnover, and synthesis of NE without affecting adrenomedullary secretion or renal dopamine production. Concurrent hypovolemia probably interferes with detection of sympathoinhibition by plasma levels of NE and other catechols in this setting. Sympathoinhibition, despite decreased blood volume, may help to explain orthostatic intolerance in astronauts returning from spaceflights.

Changes in size and compliance of the calf after 30 days of simulated microgravity.

Increased leg venous compliance may contribute to postflight orthostatic intolerance in astronauts. We reported that leg compliance was inversely related to the size of the muscle compartment. The purpose of this study was to test the hypothesis that reduced muscle compartment after long-duration exposure to microgravity would cause increased leg compliance. Eight men, 31-45 yr old, were measured for vascular compliance of the calf and serial circumferences of the calf before and after 30 days of continuous 6 degrees head-down bed rest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the calf were determined before and after bed rest by computed tomography. From before to after bed rest, calculated calf volume (cm3) decreased (P less than 0.05) from 1,682 +/- 83 to 1,516 +/- 76. Calf muscle compartment CSA (cm2) also decreased (P less than 0.05) from 74.2 +/- 3.6 to 70.6 +/- 3.4; calf compliance (ml.100 ml-1.mmHg-1.100) increased (P less than 0.05) from 3.9 +/- .7 to 4.9 +/- .5. The percent change in calf compliance after bed rest was significantly correlated with changes in calf muscle compartment CSA (r = 0.72, P less than 0.05). The increased leg compliance observed after exposure to simulated microgravity can be partially explained by reduced muscle compartment. Countermeasures designed to minimize muscle atrophy in the lower extremities may be effective in ameliorating increased venous compliance and orthostatic intolerance after spaceflight.

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.

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.

Altered thermoregulatory responses after 15 days of head-down tilt.

To determine whether extended exposure to a simulation of microgravity alters thermoregulatory reflex control of skin blood flow, six adult males (mean age 40 +/- 2 yr) were exposed to 15 days of 6 degrees head-down tilt (HDT). On an ambulatory control day before HDT exposure and on HDT day 15, the core temperature of each subject was increased by 0.5-1.0 degree C by whole body heating with a water-perfused suit. Mean skin temperature, oral temperature (Tor), mean arterial pressure, and forearm blood flow were measured throughout the protocol. Forearm vascular conductance (FVC) was calculated from the ratio of forearm blood flow to mean arterial pressure. After HDT exposure, the Tor threshold at which reflex thermally induced increases in FVC began was elevated (36.87 +/- 0.06 to 37.00 +/- 0.09 degrees C; P = 0.043), whereas the slope of the Tor-FVC relationship after this threshold was reduced (13.7 +/- 2.3 to 9.5 +/- 1.1 FVC units/degrees C; P = 0.038). Moreover, normothermic FVC and FVC at the highest common Tor between pre- and post-HDT trials were reduced after HDT (normothermic: 4.2 +/- 0.5 to 3.0 +/- 0.4 ml.100 ml-1.min-1.100 mmHg-1, P = 0.04; hyperthermic: 12.4 +/- 1.0 to 7.8 +/- 0.7 ml.100 ml-1.min-1.100 mmHg-1, P < 0.001). These data suggest that HDT exposure reduces thermoregulatory responses to heat stress. The mechanisms resulting in such an impaired thermoregulatory response are unknown but are likely related to the relative dehydration that accompanies this exposure.

Leg size and muscle functions associated with leg compliance.

Leg compliance is "causally related with greater susceptibility" to orthostatic stress. Since peak O2 uptake (peak VO2) and muscle strength may be related to leg compliance, we examined the relationships between leg compliance and factors related to muscle size and physical fitness. Ten healthy men, 25-52 yr, underwent tests for determination of vascular compliance of the calf (Whitney mercury strain gauge), peak VO2 (Bruce treadmill), calf muscle strength (Cybex isokinetic dynamometer), body composition (densitometry), and anthropometric measurements of the calf. Cross-sectional areas (CSA) of muscle, fat, and bone in the calf were determined by computed tomography scans. Leg compliance was not significantly correlated with any variables associated with physical fitness per se (peak VO2, calf strength, age, body weight, or composition). Leg compliance correlated with calf CSA (r = -0.72, P less than 0.02) and calculated calf volume (r = -0.67, P less than 0.03). The most dominant contributing factor to the determination of leg compliance was CSA of calf muscle (r = -0.60, P less than 0.06), whereas fat and bone were poor predictors (r = -0.11 and 0.07, respectively). We suggest that leg compliance is less when there is a large muscle mass providing structural support to limit expansion of the veins. This relationship is independent of aerobic and/or strength fitness level of the individual.

Aortic baroreflex control of heart rate after 15 days of simulated microgravity exposure.

To determine the effects of simulated microgravity on aortic baroreflex control of heart rate, we exposed seven male subjects (mean age 38 +/- 3 yr) to 15 days of bed rest in the 6 degrees head-down position. The sensitivity of the aortic-cardiac baroreflex was determined during a steady-state phenylephrine-induced increase in mean arterial pressure combined with lower body negative pressure to counteract central venous pressure increases and neck pressure to offset the increased carotid sinus transmural pressure. The aortic-cardiac baroreflex gain was assessed by determining the ratio of the change in heart rate to the change in mean arterial pressure between baseline conditions and aortic baroreceptor-isolated conditions (i.e., phenylephrine + lower body negative pressure + neck pressure stage). Fifteen days of head-down tilt increased the gain of the aortic-cardiac baroreflex (from 0.45 +/- 0.07 to 0.84 +/- 0.18 beats.min-1.mmHg-1; P = 0.03). Reductions in blood volume and/or maximal aerobic capacity may represent the underlying mechanism(s) responsible for increased aortic baroreflex responsiveness after exposure to a ground-based analogue of microgravity.

Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension.

We studied vagally mediated carotid baroreceptor-cardiac reflexes in 11 healthy men before, during, and after 30 days of 6 degrees head-down bed rest to test the hypothesis that baroreflex malfunction contributes to orthostatic hypotension in this model of simulated microgravity. Sigmoidal baroreflex response relationships were provoked with ramped neck pressure-suction sequences comprising pressure elevations to 40 mmHg followed by serial R-wave-triggered 15-mmHg reductions to -65 mmHg. Each R-R interval was plotted as a function of systolic pressure minus the neck chamber pressure applied during the interval. Compared with control measurements, base-line R-R intervals and the minimum, maximum, range, and maximum slope of the R-R interval-carotid pressure relationships were reduced (P less than 0.05) from bed rest day 12 through recovery day 5. Baroreflex slopes were reduced more in four subjects who fainted during standing after bed rest than in six subjects who did not faint (-1.8 +/- 0.7 vs. -0.3 +/- 0.3 ms/mmHg, P less than 0.05). There was a significant linear correlation (r = 0.70, P less than 0.05) between changes of baroreflex slopes from before bed rest to bed rest day 25 and changes of systolic blood pressure during standing after bed rest. Although plasma volume declined by approximately 15% (P less than 0.05), there was no significant correlation between reductions of plasma volume and changes of baroreflex responses. There were no significant changes of before and after plasma norepinephrine or epinephrine levels before and after bed rest during supine rest or sitting.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood volume: its adaptation to endurance training.

Expansion of blood volume (hypervolemia) has been well documented in both cross-sectional and longitudinal studies as a consequence of endurance exercise training. Plasma volume expansion can account for nearly all of the exercise-induced hypervolemia up to 2-4 wk; after this time expansion may be distributed equally between plasma and red cell volumes. The exercise stimulus for hypervolemia has both thermal and nonthermal components that increase total circulating plasma levels of electrolytes and proteins. Although protein and fluid shifts from the extravascular to intravascular space may provide a mechanism for rapid hypervolemia immediately after exercise, evidence supports the notion that chronic hypervolemia associated with exercise training represents a net expansion of total body water and solutes. This net increase of body fluids with exercise training is associated with increased water intake and decreased urine volume output. The mechanism of reduced urine output appears to be increased renal tubular reabsorption of sodium through a more sensitive aldosterone action in man. Exercise training-induced hypervolemia appears to be universal among most animal species, although the mechanisms may be quite different. The hypervolemia may provide advantages of greater body fluid for heat dissipation and thermoregulatory stability as well as larger vascular volume and filling pressure for greater cardiac stroke volume and lower heart rates during exercise.

Endurance exercise training: conditions of enhanced hemodynamic responses and tolerance to LBNP.

In cross-sectional comparisons, several investigators have reported highly trained endurance athletes to have a prevalence toward orthostatic hypotension and intolerance compared with average fit individuals. These observations have raised concern that regular exercise designed to increase aerobic capacity may impair regulatory mechanisms of blood pressure control and that perhaps certain populations of individuals with a predisposition for fainting exhibit an inability to elevate heart rate, vasoactive hormones, and peripheral resistance during an orthostatic challenge. In longitudinal experiments, when exercise training was performed by subjects who increased their aerobic capacity by 20% but maintained VO2max below 50 ml.kg-1.min-1, tolerance to lower body negative pressure (LBNP) was increased by 28%. Exercise training did not compromise baroreflex functions despite evidence of increased resting vagal cardiac tone and reduced sympathetic tone. In contrast to fainters, increased orthostatic tolerance in the exercised-trained subjects was associated with no alteration in their ability to elevate heart rate, vasoactive hormones, and peripheral resistance at peak LBNP. However, cardiac output and mean arterial blood pressure were maintained during higher submaximal LBNP levels by a 20% increase in stroke volume. The elevation in stroke volume during LBNP after training was associated with blood volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular consequences of bed rest: effect on maximal oxygen uptake.

Maximal oxygen uptake (VO2max) is reduced in healthy individuals confined to bed rest, suggesting it is independent of any disease state. The magnitude of reduction in VO2max is dependent on duration of bed rest and the initial level of aerobic fitness (VO2max), but it appears to be independent of age or gender. Bed rest induces an elevated maximal heart rate which, in turn, is associated with decreased cardiac vagal tone, increased sympathetic catecholamine secretion, and greater cardiac beta-receptor sensitivity. Despite the elevation in heart rate, VO2max is reduced primarily from decreased maximal stroke volume and cardiac output. An elevated ejection fraction during exercise following bed rest suggests that the lower stroke volume is not caused by ventricular dysfunction but is primarily the result of decreased venous return associated with lower circulating blood volume, reduced central venous pressure, and higher venous compliance in the lower extremities. VO2max, stroke volume, and cardiac output are further compromised by exercise in the upright posture. The contribution of hypovolemia to reduced cardiac output during exercise following bed rest is supported by the close relationship between the relative magnitude (% delta) and time course of change in blood volume and VO2max during bed rest, and also by the fact that retention of plasma volume is associated with maintenance of VO2max after bed rest. Arteriovenous oxygen difference during maximal exercise is not altered by bed rest, suggesting that peripheral mechanisms may not contribute significantly to the decreased VO2max. However reduction in baseline and maximal muscle blood flow, red blood cell volume, and capillarization in working muscles represent peripheral mechanisms that may contribute to limited oxygen delivery and, subsequently, lowered VO2max. Thus, alterations in cardiac and vascular functions induced by prolonged confinement to bed rest contribute to diminution of maximal oxygen uptake and reserve capacity to perform physical work.

Exercise as a countermeasure for physiological adaptation to prolonged spaceflight.

Exercise represents the primary countermeasure used during spaceflight to maintain or restore maximal aerobic capacity (VO2max), musculoskeletal structure, and orthostatic function. However, no single exercise or combination of prescriptions has proven entirely effective in restoring cardiovascular and musculoskeletal functions to preflight levels following prolonged spaceflight. As human spaceflight exposures increase in duration, assessment and development of various effective exercise-based protective procedures become paramount. This must involve improvement in specific countermeasure prescription as well as development of additional approaches that will allow space travelers greater flexibility and medical safety during long flights. Effective exercise prescription will be based on identification of basic physiological stimuli that maintain normal function in terrestrial gravity and understanding of how specific combinations of exercise characteristics e.g., duration, frequency, intensity, mode) can mimic these stimuli and affect the overall process of adaptation to microgravity. This can be accomplished only with greater emphasis of research on ground-based experiments. Future attention must be directed to improving exercise compliance while minimizing both crew time and the impact of the exercise on life-support resources.

Clinical aspects of the control of plasma volume at microgravity and during return to one gravity.

Plasma volume is reduced by 10-20% within 24-48 h of exposure to simulated or actual microgravity. The clinical importance of microgravity induced hypovolemia is manifested by its relationship with orthostatic intolerance and reduced maximal oxygen uptake (VO2max) after return to one gravity (1G). Since there is no evidence to suggest that plasma volume reduction during microgravity is associated with thirst or renal dysfunctions, a diuresis induced by an immediate blood volume shift to the central circulation appears responsible for microgravity-induced hypovolemia. Since most astronauts choose to restrict their fluid intake before a space mission, absence of increased urine output during actual space flight may be explained by low central venous pressure (CVP) which accompanies dehydration. Compelling evidence suggests that prolonged reduction in CVP during exposure to microgravity reflects a "resetting" to a lower operating point, which acts to limit plasma volume expansion during attempts to increase fluid intake. In ground based and space flight experiments, successful restoration and maintenance of plasma volume prior to returning to an upright posture may depend upon development of treatments that can return CVP to its baseline IG operating point. Fluid-loading and lower body negative pressure (LBNP) have not proved completely effective in restoring plasma volume, suggesting that they may not provide the stimulus to elevate the CVP operating point. On the other hand, exercise, which can chronically increase CVP, has been effective in expanding plasma volume when combined with adequate dietary intake of fluid and electrolytes. The success of designing experiments to understand the physiological mechanisms of and development of effective counter measures for the control of plasma volume in microgravity and during return to IG will depend upon testing that can be conducted under standardized controlled baseline conditions during both ground-based and space flight investigations.

Heart rate and sweat rate responses associated with exercise-induced hypervolemia.

The purpose of this study was to determine the relationships between the plasma volume (PV) expansion accompanying exercise training and the associated changes in heart rate (HR) and sweat rate (SR) during sub-maximal and maximal exercise. Eight male subjects (21 +/- 1 yr) rode a cycle ergometer 2 h/d for 8 consecutive days at 65% maximal oxygen uptake (VO2max). Average HR and SR were measured each day during exercise, and PV (T-1824) was measured prior to, on day 4, and the day following exercise training. The VO2max and maximal HR (HRmax) were measured before and after the 8-d exercise period. Following exercise training, VO2max increased by 8.3% (P less than 0.05), HRmax decreased by 4.1% (P less than 0.05), and PV increased by 430 ml (+ 12.2%, P less than 0.05). During the 2-h ergometer exercise, mean SR increased from 0.83 1 . h-1 on day 1 to 0.97 1 . h-1 on day 8 (P less than 0.05) while mean HR decreased from 169 beats per min (bpm) on day 1 to 148 bpm on day 8 (P less than 0.05). The percent change (% delta) in PV was correlated with % delta SR (r = 0.93, P less than 0.05), % delta HR at 65% VO2max (r = -0.89, P less than 0.05), and % delta HRmax (r = -0.82, P less than 0.05). The data indicated that plasma volume expansion may be necessary for the cardiovascular and thermoregulatory adaptations accompanying chronic exercise.