Influence of simulated microgravity on the sympathetic response to exercise.

Rats exposed to simulated conditions of microgravity exhibit reductions in aerobic exercise capacity that may be due to an impaired ability of the sympathetic nervous system (SNS) to mediate an increase in cardiac output and to redistribute blood flow. The purpose of this study was to quantify the sympathetic response to exercise in rats after exposure to 14 days of simulated microgravity or control conditions. To achieve this aim, rats were exposed to 14 days of head-down suspension (HDS) or cage control (CC) conditions. On day 14, norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the rate of NE depletion after synthesis blockade was used to estimate SNS activity in the left ventricle, spleen, and soleus muscle during treadmill exercise at 75% of maximal oxygen uptake. When compared with CC rats, the sympathetic response to exercise in HDS rats was characterized by a lower rate of NE depletion in the left ventricle (-82%) and spleen (-42%). The rate of NE depletion in the soleus muscle was 47% higher. These differences could contribute to the decrement in aerobic capacity of HDS rats by impairing their ability to augment cardiac output and to redirect blood flow to actively contracting skeletal muscle during exercise.

Postural tachycardia syndrome: time frequency mapping.

Orthostatic tachycardia is common but its specificity remains uncertain. Our preliminary work suggested that using autonomic function testing in conjunction with time-frequency mapping (TFM), it might be possible to characterize a subset of the postural tachycardia syndrome (POTS), that is due to a restricted autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43 years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years). Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and sudomotor) and severity, a symptom profile was generated, and spectral indices, based on modified Wigner distribution during rest and head-up tilt (80 degrees) were evaluated. During tilt-up POTS patients differed from controls by an excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P < 0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF]) and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal postganglionic sudomotor failure was observed, and impairment of the BP responses to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction. Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and palpitations were common in POTS patients. It is possible to identify a subset of POTS patients who have a length-dependent autonomic neuropathy, affecting the peripheral adrenergic and cardiovagal fibers, with relative preservation of cardiac adrenergic fibers.

Evaluation of transit-time and electromagnetic flow measurement in a chronically instrumented nonhuman primate model.

The Physiology Research Branch at Brooks AFB conducts both human and nonhuman primate experiments to determine the effects of microgravity and hypergravity on the cardiovascular system and to identify the particular mechanisms that invoke these responses. Primary investigative efforts in our nonhuman primate model require the determination of total peripheral resistance, systemic arterial compliance, and pressure-volume loop characteristics. These calculations require beat-to-beat measurement of aortic flow. This study evaluated accuracy, linearity, biocompatability, and anatomical features of commercially available electromagnetic (EMF) and transit-time flow measurement techniques. Five rhesus monkeys were instrumented with either EMF (3 subjects) or transit-time (2 subjects) flow sensors encircling the proximal ascending aorta. Cardiac outputs computed from these transducers taken over ranges of 0.5 to 2.0 L/min were compared to values obtained using thermodilution. In vivo experiments demonstrated that the EMF probe produced an average error of 15% (r = .896) and 8.6% average linearity per reading, and the transit-time flow probe produced an average error of 6% (r = .955) and 5.3% average linearity per reading. Postoperative performance and biocompatability of the probes were maintained throughout the study. The transit-time sensors provided the advantages of greater accuracy, smaller size, and lighter weight than the EMF probes. In conclusion, the characteristic features and performance of the transit-time sensors were superior to those of the EMF sensors in this study.

Subnormal norepinephrine release relates to presyncope in astronauts after spaceflight.

Postflight orthostatic intolerance is experienced by virtually all astronauts but differs greatly in degree of severity. We studied cardiovascular responses to upright posture in 40 astronauts before and after spaceflights lasting up to 16 days. We separated individuals according to their ability to remain standing without assistance for 10 min on landing day. Astronauts who could not remain standing on landing day had significantly smaller increases in plasma norepinephrine levels with standing than did those who could remain standing (105 +/- 41 vs. 340 +/- 62 pg/ml; P = 0.05). In addition, they had significantly lower standing peripheral vascular resistance (23 +/- 3 vs. 34 +/- 3 mmHg.1l-1).min; P = 0.02) and greater decreases in systolic (-28 +/- 4 vs. -11 +/- 3 mmHg; P = 0.002) and diastolic (-14 +/- 7 vs. 3 +/- 2 mmHg; P = 0.0003) pressures. The presyncopal group also had significantly lower supine (16 +/- 1 vs. 21 +/- 2 mmHg.1l-1).min; P = 0.04) and standing (23 +/- 2 vs. 32 +/- 2 mmHg.1l-1).min; P = 0.038) vascular resistance, supine (66 +/- 2 vs. 73 +/- 2 mmHg; P = 0.008) and standing (69 +/- 4 vs. 77 +/- 2 mmHg; P = 0.007) diastolic pressure, and supine (109 +/- 3 vs. 114 +/- 2 mmHg; P = 0.05) and standing (99 +/- 4 vs. 108 +/- 3 mmHg; P = 0.006) systolic pressures before flight. This is the first study to clearly document these differences among presyncopal and nonpresyncopal astronauts after spaceflight and also offer the possibility of preflight prediction of postflight susceptibility. These results clearly point to hypoadrenergic responsiveness, possibly centrally mediated, as a contributing factor in postflight orthostatic intolerance. They may provide insights into autonomic dysfunction in Earthbound patients.

Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight.

BACKGROUND/HYPOTHESIS: To simulate exposure to microgravity and to determine the effectiveness of intermittent exposure to passive and active +1 Gz force (head-to-foot) in preventing head-down bed rest (HDBR) deconditioning, 4 d of 6 degrees HDBR were used. METHODS: Volunteers were 9 males, 30-50 yr, who performed periodic standing or controlled walking for 2 or 4 h.d-1 in 15-min bouts, one bout per hour, or remained in a continuous HDBR control condition (0 Gz). RESULTS: Standing 4 h (S4) completely prevented, and standing 2 h (S2) partially prevented, decreases in post-HDBR orthostatic tolerance (survival rates with 30 min of upright tilt at 60 degrees). Walking, both 2 h (W2) and 4 h (W4), and S4 attenuated decreases in peak oxygen uptake compared to 0 Gz. Compared to 0 Gz, both S4 and W4 attenuated plasma volume loss during HDBR. Urinary Ca2+ excretion increased over time with HDBR; the quadratic trend for urinary Ca2+, however, was attenuated with W2 and W4. CONCLUSIONS: We concluded that various physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz and, in addition to the duration of the stimulus, the number of exposures to postural stimuli may be an important moderating factor.

Lessons from operational cardiovascular studies in space.

The Space Shuttle program has produced a database of information on the cardiovascular responses to spaceflight, based on in-flight as well as pre- and post-flight assessments undertaken as part of the assessment of the health, safety, and efficiency of Shuttle crews. The methods used in routine cardiovascular assessments of Space Shuttle astronauts are reviewed, and the major findings of these investigations are presented.

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.

Animal models and their importance to human physiological responses in microgravity.

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

Role of physical countermaneuvers in the management of orthostatic hypotension: efficacy and biofeedback augmentation.

OBJECTIVE: To evaluate the efficacy of various physical countermaneuvers in reducing orthostatic hypotension and its associated symptoms and to assess the efficacy of biofeedback training in enhancing the effectiveness of physical countermaneuvers. MATERIAL AND METHODS: In nine study subjects with neurogenic orthostatic hypotension, four training sessions on physical countermaneuvers were performed after tilt-up, three with visual feedback on the effect of physical countermaneuvers on blood pressure and other cardiovascular variables. Blood pressure change and orthostatic symptoms during tilt-up were determined, as were the changes in total peripheral resistance, stroke index, and heart rate. RESULTS: The five female and four male patients had a mean age of 53 years and a mean duration of symptoms of 4.2 years. On an orthostatic symptom scale of 0 to 10, these patients had a mean symptom score of 7.3. The increment in systolic blood pressure was better for some maneuvers (such as leg crossing and a combination) than others (such as neck flexion and abdominal contraction). Three patterns of responses to biofeedback were found. Simple maneuvers such as squatting did not improve with training; visual feedback was needed for maneuvers such as thigh contraction, and performance declined without biofeedback; the third pattern, seen in maneuvers such as leg crossing, showed continued improvement with training, even without biofeedback. A survey at 3 to 4 months after training revealed continued use of physical maneuvers (3.8 +/- 3.1 per day), increased standing time with each episode of presyncopal symptoms (8.3 +/- 5.8 minutes), and continued global symptomatic improvement. Total peripheral resistance, but not heart rate or stroke index, showed significant regression with blood pressure improvement. CONCLUSION: Physical countermaneuvers are efficacious in reducing orthostatic hypotension, can be augmented by use of biofeedback, and may significantly improve the functional outcome. The major mechanism of improvement is an increase in total peripheral resistance, presumably by reducing the vascular capacitance.

Certain cardiovascular indices predict syncope in the postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) represent a patient population with orthostatic intolerance; some are prone to syncope, others are not. The underlying neurocardiovascular mechanisms are not completely understood. The current study was undertaken to assess if certain cardiovascular indices are predictive of syncope in POTS. We compared the response to tilt-up and the Valsalva maneuver in four groups: POTS patients who fainted (POTS-f; n = 11;31 +/- 11 years): POTS patients who did not faint (POTS-nf; n = 9; 29 +/- 9 years); normal controls (NLS; n = 13; 39 +/- 11 years); patients with generalized autonomic failure with orthostatic hypotension and syncope (n = 10; 59 +/- 14 years). Beat-to-beat heart rate (HR), systolic arterial pressure, diastolic arterial pressure (DAP) and pulse pressure (PP) were monitored using Finapres. Cardiac output, stroke volume (SV) and end-diastolic volume (EDV), and calculated total peripheral resistance (TPR) were recorded using thoracic electrical bioimpedance. An autonomic reflex screen which quantitates the distribution and severity of autonomic failure was also done. With the patient supine, all POTS patients (POTS-nf; POTS-f) had increased HR (p < 0.001) and reduced SV/EDV (p < 0.001) when compared with NLS. On tilt-up, POTS-f patients were significantly different from both NLS and POTS-nf patients; the most consistent alteration was a fall instead of an increase in TPR; other changes were a greater reduction in PP, a reduction (instead of an increment) in DAP, and a different pattern of changes during the Valsalva maneuver (excessive early phase II, attenuated or absent late phase II). Our results suggest alpha-adrenergic impairment with increased pooling or hypovolemia in POTS-f patients. We conclude that it is possible to identify the mechanism of syncope in POTS patients, and perhaps other patients with orthostatic intolerance and an excessive liability to syncope.

Central venous pressure in space.

Gravity affects cardiac filling pressure and intravascular fluid distribution significantly. A major central fluid shift occurs when all hydrostatic gradients are abolished on entry into microgravity (microG). Understanding the dynamics of this shift requires continuous monitoring of cardiac filling pressure; central venous pressure (CVP) measurement is the only feasible means of accomplishing this. We directly measured CVP in three subjects: one aboard the Spacelab Life Sciences-1 space shuttle flight and two aboard the Spacelab Life Sciences-2 space shuttle flight. Continuous CVP measurements, with a 4-Fr catheter, began 4 h before launch and continued into microG. Mean CVP was 8.4 cmH2O seated before flight, 15.0 cmH2O in the supine legs-elevated posture in the shuttle, and 2.5 cmH2O after 10 min in microG. Although CVP decreased, the left ventricular end-diastolic dimension measured by echocardiography increased from a mean of 4.60 cm supine preflight to 4.97 cm within 48 h in microG. These data are consistent with increased cardiac filling early in microG despite a fall in CVP, suggesting that the relationship between CVP and actual transmural left ventricular filling pressure is altered in microG.

Orthostatic intolerance after spaceflight.

Orthostatic intolerance occurs commonly after spaceflight, and important aspects of the underlying mechanisms remain unclear. We studied 14 individuals supine and standing before and after three space shuttle missions of 9-14 days. After spaceflight, 9 of the 14 (64%) crew members could not complete a 10-min stand test that all completed preflight. Pre- and postflight supine hemodynamics were similar in both groups except for slightly higher systolic and mean arterial pressures preflight in the finishers [15 +/- 3.7 and 8 +/- 1.2 (SE) mmHg, respectively; P < 0.05]. Postflight, finishers and nonfinishers had equally large postural reductions in stroke volume (-47 +/- 3.7 and -48 +/- 3.3 ml, respectively) and increases in heart rate (35 +/- 6.6 and 51 +/- 5.2 beats/min, respectively). Cardiac output during standing was also similar (3.6 +/- 0.4 and 4.1 +/- 0.3 l/min, respectively). However, the finishers had a greater postflight vasoconstrictor response with higher total peripheral resistance during standing (22.3 +/- 1.2 units preflight and 29.4 +/- 2.3 units postflight) than did the nonfinishers (20.1 +/- 1.1 units preflight and 19.9 +/- 1.4 units postflight). We conclude that 1) the primary systemic hemodynamic event, i.e., the postural decrease in stroke volume, was similar in finishers and nonfinishers and 2) the heart rate response and cardiac output during standing were not significantly different, but 3) the postural vasoconstrictor response was significantly greater among the finishers (P < 0.01).

Forced expirations and maximum expiratory flow-volume curves during sustained microgravity on SLS-1.

Gravity is known to influence the mechanical behavior of the lung and chest wall. However, the effect of sustained microgravity (microG) on forced expirations has not previously been reported. Tests were carried out by four subjects in both the standing and supine postures during each of seven preflight and four postflight data-collection sessions and four times during the 9 days of microG exposure on Spacelab Life Sciences-1. Compared with preflight standing values, peak expiratory flow rate (PEFR) was significantly reduced by 12.5% on flight day 2 (FD2), 11.6% on FD4, and 5.0% on FD5 but returned to standing values by FD9. The supine posture caused a 9% reduction in PEFR. Forced vital capacity and forced expired volume in 1 s were slightly reduced (approximately 3-4%) on FD2 but returned to preflight standing values on FD4 and FD5, and by FD9 both values were slightly but significantly greater than standing values. Forced vital capacity and forced expiratory volume in 1 s were both reduced in the supine posture (approximately 8-10%). Forced expiratory flows at 50% and between 25 and 75% of vital capacity did not change during microG but were reduced in the supine posture. Analysis of the maximum expiratory flow-volume curve showed that microG caused no consistent change in the curve configuration when individual in-flight days were compared with preflight standing curves, although two subjects did show a slight reduction in flows at low lung volumes from FD2 to FD9. The interpretation of the lack of change in curve configuration must be made cautiously because the lung volumes varied from day to day in flight. Therefore, the flows at absolute lung volumes in microG and preflight standing are not being compared. The supine curves showed a subtle but consistent reduction in flows at low lung volumes. The mechanism responsible for the reduction in PEFR is not clear. It could be due to a lack of physical stabilization when performing the maneuver in the absence of gravity or a transient reduction in respiratory muscle strength.

Control of red blood cell mass in spaceflight.

The effect of spaceflight on red blood cell mass (RBCM), plasma volume (PV), erythron iron turnover, serum erythropoietin, and red blood cell (RBC) production and survival and indexes were determined for six astronauts on two shuttle missions, 9 and 14 days in duration, respectively. PV decreased within the first day. RBCM decreased because of destruction of RBCs either newly released or scheduled to be released from the bone marrow. Older RBCs survived normally. On return to Earth, plasma volume increased, hemoglobin concentration and RBC count declined, and serum erythropoietin increased. We propose that entry into microgravity results in acute plethora as a result of a decrease in vascular space. PV decreases, causing an increase in hemoglobin concentration that effects a decrease in erythropoietin or other growth factors or cytokines. The RBCM decreases by destruction of recently formed RBCs to a level appropriate for the microgravity environment. Return to Earth results sequentially in acute hypovolemia as vascular space dependent on gravity is refilled, an increase in plasma volume, a decrease in hemoglobin concentration (anemia), and an increase in serum erythropoietin.

An optimized index of human cardiovascular adaptation to simulated weightlessness.

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

Fundamental relations between short-term RR interval and arterial pressure oscillations in humans.

BACKGROUND: One of the principal explanations for respiratory sinus arrhythmia is that it reflects arterial baroreflex buffering of respiration-induced arterial pressure fluctuations. If this explanation is correct, then elimination of RR interval fluctuations should increase respiratory arterial pressure fluctuations. METHODS AND RESULTS: We measured RR interval and arterial pressure fluctuations during normal sinus rhythm and fixed-rate atrial pacing at 17.2+/-1.8 (SEM) beats per minute greater than the sinus rate in 16 healthy men and 4 healthy women, 20 to 34 years of age. Measurements were made during controlled-frequency breathing (15 breaths per minute or 0.25 Hz) with subjects in the supine and 40 degree head-up tilt positions. We characterized RR interval and arterial pressure variabilities in low-frequency (0.05 to 0.15 Hz) and respiratory-frequency (0.20 to 0.30 Hz) ranges with fast Fourier transform power spectra and used cross-spectral analysis to determine the phase relation between the two signals. As expected, cardiac pacing eliminated beat-to-beat RR interval variability. Against expectations, however, cardiac pacing in the supine position significantly reduced arterial pressure oscillations in the respiratory frequency (systolic, 6.8+/-1.8 to 2.9 +/-0.6 mm Hg2/Hz, P=.017). In contrast, cardiac pacing in the 40 degree tilt position increased arterial pressure variability (systolic, 8.0+/-1.8 to 10.8 +/-2.6, P=.027). Cross-spectral analysis showed that 40 degree tilt shifted the phase relation between systolic pressure and RR interval at the respiratory frequency from positive to negative (9 +/-7 degrees versus -17+/-11 degrees, P=.04); that is, in the supine position, RR interval changes appeared to lead arterial pressure changes, and in the upright position, RR interval changes appeared to follow arterial pressure changes. CONCLUSIONS: These results demonstrate that respiratory sinus arrhythmia can actually contribute to respiratory arterial pressure fluctuations. Therefore, respiratory sinus arrhythmia does not represent simple baroreflex buffering of arterial pressure.

Blood vessel adaptation to gravity in a semi-arboreal snake.

The effects of vasoactive agonists on systemic blood vessels were examined with respect to anatomical location and gravity acclimation in the semi-arboreal snake, Elaphe Obsoleta. Major blood vessels were reactive to putative neurotransmitters, hormones or local factors in vessel specific patterns. Catecholamines, adenosine triphosphate, histamine and high potassium (80 mM) stimulated significantly greater tension per unit vessel mass in posterior than anterior arteries. Anterior vessels were significantly more sensitive to catecholamines than midbody and posterior vessels. Angiotensin II stimulated significantly greater tension in carotid artery than in midbody and posterior dorsal aorta. Arginine vasotocin strongly contracted the left and right aortic arches and anterior dorsal aorta. Veins were strongly contracted by catecholamines, high potassium and angiotensin II, but less so by adenosine triphosphate, arginine vasotocin and histamine. Precontracted vessel were relaxed by acetylcholine and sodium nitroprusside, but not by atrial natriuretic peptide or bradykinin. Chronic exposure of snakes to intermittent hypergravity stress ( + 1.5 Gz at tail) did not affect the majority of vessel responses. These data demonstrate that in vitro tension correlates with that catecholamines, as well as other agonists, are important in mediating vascular responses to gravitational stresses in snakes.

Influence of simulated microgravity on cardiac output and blood flow distribution during exercise.

Rats exposed to simulated conditions of microgravity by head-down suspension (HDS) exhibit reductions in aerobic capacity. This may be due to an impaired ability to augment cardiac output and to redistribute blood flow during exercise. The purpose of this investigation was to measure cardiac output and blood flow distribution in rats that were exposed to 14 days of HDS or cage control conditions. Measurements were obtained at rest and during light-intensity (15 m/min) and heavy-intensity (25 m/min; 10% grade) treadmill exercise. Cardiac output was similar in HDS and cage control rats at rest and light exercise but was significantly lower in HDS rats (-33%) during heavy exercise. Soleus muscle blood flow (ml/min) was lower at rest and during exercise in HDS rats; however, when expressed relative to muscle mass (ml.min-1.100 g-1), soleus blood flow was lower only during light exercise. Plantaris muscle blood flow was lower in HDS rats during heavy exercise. Blood flow to the ankle flexor, knee extensor, and knee flexor muscles was not altered by HDS. Blood flow to the spleen and kidney was significantly higher in HDS rats. It was concluded that the reduction in aerobic capacity associated with HDS is due in part to an impaired ability to augment cardiac output during exercise.