O2 extraction maintains O2 uptake during submaximal exercise with beta-adrenergic blockade at 4,300 m.

Whole body O2 uptake (VO2) during maximal and submaximal exercise has been shown to be preserved in the setting of beta-adrenergic blockade at high altitude, despite marked reductions in heart rate during exercise. An increase in stroke volume at high altitude has been suggested as the mechanism that preserves systemic O2 delivery (blood flow x arterial O2 content) and thereby maintains VO2 at sea-level values. To test this hypothesis, we studied the effects of nonselective beta-adrenergic blockade on submaximal exercise performance in 11 normal men (26 +/- 1 yr) at sea level and on arrival and after 21 days at 4,300 m. Six subjects received propranolol (240 mg/day), and five subjects received placebo. At sea level, during submaximal exercise, cardiac output and O2 delivery were significantly lower in propranolol- than in placebo-treated subjects. Increases in stroke volume and O2 extraction were responsible for the maintenance of VO2. At 4,300 m, beta-adrenergic blockade had no significant effect on VO2, ventilation, alveolar PO2, and arterial blood gases during submaximal exercise. Despite increases in stroke volume, cardiac output and thereby O2 delivery were still reduced in propranolol-treated subjects compared with subjects treated with placebo. Further reductions in already low levels of mixed venous O2 saturation were responsible for the maintenance of VO2 on arrival and after 21 days at 4,300 m in propranolol-treated subjects. Despite similar workloads and VO2, propranolol-treated subjects exercised at greater perceived intensity than subjects given placebo at 4,300 m. The values for mixed venous O2 saturation during submaximal exercise in propranolol-treated subjects at 4,300 m approached those reported at simulated altitudes >8,000 m. Thus beta-adrenergic blockade at 4,300 m results in significant reduction in O2 delivery during submaximal exercise due to incomplete compensation by stroke volume for the reduction in exercise heart rate. Total body VO2 is maintained at a constant level by an interaction between mixed venous O2 saturation, the arterial O2-carrying capacity, and hemodynamics during exercise with acute and chronic hypoxia.

Beta-adrenergic blockade does not prevent polycythemia or decrease in plasma volume in men at 4300 m altitude.

When humans ascend to high altitude (ALT) their plasma volume (PV) and total blood volume (BV) decrease during the first few days. With continued residence over several weeks, the hypoxia-induced stimulation of erythropoietin increases red cell production which tends to restore BV. Because hypoxia also activates the beta-adrenergic system, which stimulates red blood cell production, we investigated the effect of adrenergic beta-receptor inhibition with propranolol on fluid volumes and the polycythemic response in 11 healthy unacclimatized men (21-33 years old exposed to an ALT of 4300 m (barometric pressure 460 Torr) for 3 weeks on Pikes Peak, Colorado. PV was determined by the Evans blue dye method (PVEB), BV by the carbon monoxide method (BVCO), red cell volume (RCV) was calculated from hematocrit (Hct) and BVCO, and serum erythropoietin concentration ([EPO]) and reticulocyte count, were also determined. All determinations were made at sea level and after 9-11 (ALT-10) and 19-20 (ALT-20) days at ALT. At sea level and ALT, six men received propranolol (pro, 240 mg x day[-1]), and five received a placebo (pla). Effective beta-blockade did not modify the mean (SE) maximal values of [EPO] [pla: 24.9 (3.5) vs pro: 24.5 (1.5) mU x ml(-1)] or reticulocyte count [pla: 2.7 (0.7) vs pro: 2.2 (0.5)%]; nor changes in PVEB [pla: -15.8 (3.8) vs pro: -19.9 (2.8)%], RCVCO [pla: +7.0 (6.7) vs pro: + 10.1 (6.1)%], or BVCO [pla: -7.3 (2.3) vs pro: -7.1 (3.9)%]. In the absence of weight loss, a redistribution of body water with no net loss is implied. Hence, activation of the beta-adrenergic system did not appear to affect the hypovolemic or polycythemic responses that occurred during 3 weeks at 4300 m ALT in these subjects.

Systemic hypertension at 4,300 m is related to sympathoadrenal activity.

Residence at high altitude has been associated with elevation in systemic arterial blood pressure, but the time course has been little studied and the mechanism is unknown. Because plasma epinephrine (E) and norepinephrine (NE) also increase at altitude, we hypothesized that heightened sympathoadrenal activity may cause increased arterial pressure. We measured ambulatory blood pressure by cuff monitor in relation to 24-h urinary excretion of E and NE at sea level and during 3 wk of residence at 4,300 m (Pikes Peak, CO) in 11 healthy men. In five subjects taking placebo, arterial pressure progressively increased at 4,300 m from 82 +/- 1 (SE) mmHg at sea level to 88 +/- 3 on day 2, 91 +/- 3 on day 8, and 97 +/- 6 on day 17. In six subjects, propranolol (240 mg/day) decreased pressure from 85 +/- 4 to 77 +/- 1 mmHg at sea level but did not prevent sustained increase in pressure at 4,300 m (84 +/- 1, 81 +/- 1, and 85 +/- 3 mmHg on days 2, 8, and 17, respectively). Compared with the placebo group, blood pressure did not increase further over the initial elevation observed on day 2 in the propranolol group. There was interindividual variability in the blood pressure responses in both groups, with some subjects demonstrating a more marked increase in blood pressure. Urinary excretion of NE increased concomitantly with pressure at altitude in both groups, with a greater rise in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Body fluid alterations during head-down bed rest in men at moderate altitude.

To determine the effects of hypoxia on fluid balance responses to simulated zero-gravity, measurements were made in six subjects (acclimatized to 5,400 ft; 1,646 m) before and during -5 degrees continuous head-down bed rest (HDBR) over 8 d at 10,678 ft. The same subjects were studied again at this altitude without HDBR as a control (CON) using a cross-over design. During this time, they maintained normal upright day-time activities, sleeping in the horizontal position at night. Fluid balance changes during HDBR in hypoxia were more pronounced than similar measurements previously reported from HDBR studies at sea level. Plasma volume loss (-19% on day 6) was slightly greater and the diuresis and natriuresis were doubled in magnitude as compared to previous studies in normoxia and sustained for 4 d during hypoxia. These changes were associated with an immediate, but transient rise in plasma atrial natriuretic peptide (ANP) to day 4 of 140% in HDBR and 41% in CON (p < 0.005), followed by a decline towards baseline. Differences were less striking between HDBR and CON for plasma antidiuretic hormone and aldosterone, which were transiently reduced by HDBR. Plasma catecholamines showed a similar pattern to ANP (+122%) in both HDBR and CON, suggesting that elevated ANP and catecholamines together accounted for the enhanced fluid shifts with HDBR during hypoxia.

Effects of prolonged head-down bed rest on physiological responses to moderate hypoxia.

To determine the effects of hypoxia on physiological responses to simulated zero-gravity, cardiopulmonary and fluid balance measurements were made in 6 subjects (acclimatized to 5,400 ft) before and during 5 degrees head-down bed rest (HDBR) over 8 d at 10,678 ft and a second time at this altitude as controls (CON). The VO2max increased by 9% after CON, but fell 3% after HDBR (p < 0.05). This reduction in work capacity during HDBR could be accounted for by inactivity. The heart rate response to a head-up tilt was greatly enhanced following HDBR, while mean blood pressure was lower. No significant negative impact of HDBR was noted on the ability to acclimatize to hypoxia in terms of pulmonary mechanics, gas exchange, circulatory or mental function measurements. No evidence of pulmonary interstitial edema or congestion was noted during HDBR at the lower PIO2 and blood rheology properties were not negatively altered. Symptoms of altitude illness were more prevalent, but not marked, during HDBR and arterial blood gases and oxygenation were not seriously effected by simulated microgravity. Declines in base excess with altitude were similar in both conditions. The study demonstrated a minimal effect of HDBR on the ability to adjust to this level of hypoxia.

Pulmonary function and hypoxic ventilatory response in subjects susceptible to high-altitude pulmonary edema.

To determine if spirometric changes reflect early high-altitude pulmonary edema (HAPE) formation, we measured the FVC, FEV1, and FEF25-75 serially during the short-term period following simulated altitude exposure (4,400 m) in eight male subjects, four with a history of HAPE and four control subjects who had never experienced HAPE. Three of the four HAPE-susceptible subjects developed acute mountain sickness (AMS), based on their positive Environmental Symptom Questionnaire (AMS-C) scores. Clinical signs and symptoms of mild pulmonary edema developed in two of the three subjects with AMS after 4 h of exposure, which prompted their removal from the chamber. Their spirometry showed small decreases in FVC and greater decreases in FEV1 and FEF25-75 after arrival at high altitude in the presence of rales or wheezing on clinical examination and normal chest radiographs. One of the two subjects had desaturation (59 percent) and tachycardia during mild exercise, and excessive fatigue and inability to complete the exercise protocol developed in the other at 4 h. The six other subjects had minimal changes in spirometry and did not develop signs of lung edema. Further, we measured each subject's ventilatory response to hypoxia (HVR) prior to decompression to determine whether the HVR would predict the development of altitude illness in susceptible subjects. In contrast to anticipated results, high ventilatory responses to acute hypoxia, supported by increased ventilation during exposure to high altitude, occurred in the two subjects in whom symptoms of HAPE developed. The results confirm that HAPE can occur in susceptible individuals despite the presence of a normal or high ventilatory response to hypoxia.