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The hypothesis of a blunted chronotropic response of cardiac beta-adrenergic receptors in altitude hypoxia was tested in nine subjects at sea level (SL) by infusion of isoproterenol. Observations were made at SL, in acute hypoxia (2 days at 4,350 m, condition H1), in more prolonged hypoxia [13 days between 850 and 4,800 m, condition H2] and in chronic hypoxia [21 days at 4,800 m, condition H3]. Resting heart rate was higher in all hypoxic conditions. Resting norepinephrine concentrations were found to be significantly higher in conditions H2 (1.64 +/- 0.59) and H3 (1.74 +/- 0.76) than at SL (0.77 +/- 0.18 ng/ml). Isoproterenol, diluted in saline, was infused at increasing doses of 0.0, 0.02, 0.04, and 0.06 micrograms.kg-1.min-1. For the highest dose, there was a significantly smaller increase in heart rate in conditions H1 (35 +/- 9), H2 (33 +/- 11), and H3 (31 +/- 11) than at SL (45 +/- 8 min-1). The increase in pulse (systolic/diastolic) pressure, considered as the vascular response to isoproterenol infusion, was smaller in condition H3 (29 +/- 16) than at SL (51 +/- 24 mmHg). There was a significant increase in the dose of isoproterenol required to increase heart rate by 25 min-1 and decrease in slope of heart rate increase vs. log(dose) relationship in conditions H2 and H3. Thus an hypoxia-related attenuated response of beta-adrenergic receptors to exogenous stimulation was found in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep and respiration studies were carried out in 12 subjects (9 males, 3 females) at an altitude of 4,800 metres, during effect of a French expedition in the Himalayas. The effect of loprazolam, a hypnotic benzodiazepine, was investigated in a double-blind, 2 parallel group, 1 mg loprazolam versus placebo trial. Sleep was evaluated by means of electroencephalographic recordings and questionnaires. The effects of altitude in each subject were intercurrent wakefulness increase, slow wave sleep and paradoxical sleep decrease and nocturnal periodic breathing. The mean duration of sleep apnea episodes was 12 seconds with a maximum of 24 seconds. These episodes occurred during stages 1 or 2 of sleep and during paradoxical sleep. Female subjects exhibited less periodic breathing than males. Acclimatization to high altitude increased total sleep time, stage 3 duration and percentage of paradoxical sleep. Loprazolam tended to decrease stage 2 latency and did not worsen slow wave sleep depression or episodes of apnea. Normal amounts of slow wave sleep and intrasleep wakefulness appeared in the loprazolam group after acclimatization.

The renin-aldosterone system may be depressed in subjects exercising at high altitude, thereby preventing excessive angiotensin I (ANG I) and aldosterone levels, which could favor the onset of acute mountain sickness. The role of beta-adrenoceptors in hormonal responses to hypoxia was investigated in 12 subjects treated with a nonselective beta-blocker, pindolol. The subjects performed a standardized maximal bicycle ergometer exercise with (P) and without (C) acute pindolol treatment (15 mg/day) at sea level, as well as during a 5-day period at high altitude (4,350 m, barometric pressure 450 mmHg). During sea-level exercise, pindolol caused a reduction in plasma renin activity (PRA, 2.83 +/- 0.35 vs. 5.13 +/- 0.7 ng ANG I.ml-1.h-1, P less than 0.01), an increase in plasma alpha-atrial natriuretic factor (alpha-ANF) level (23.1 +/- 2.9 (P) vs. 10.4 +/- 1.5 (C) pmol/1, P less than 0.01), and no change in plasma aldosterone concentration [0.50 +/- 0.04 (P) vs. 0.53 +/- 0.03 (C) nmol/1]. Compared with sea-level values, PRA (3.45 +/- 0.7 ng ANG I.ml-1.h-1) and PA (0.39 +/- 0.03 nmol/1) were significantly lower (P less than 0.05) during exercise at high altitude. alpha-ANF was not affected by hypoxia. When beta-blockade was achieved at high altitude, exercise-induced elevation in PRA was completely abolished, but no additional decline in PA occurred. Plasma norepinephrine and epinephrine concentrations tended to be lower during maximal exercise at altitude; however, these differences were not statistically significant. Our results provide further evidence that hypoxia has a suppressive effect on the renin-aldosterone system. However, beta-adrenergic mechanisms do not appear to be responsible for inhibition of renin secretion at high altitude.

The effects of acute (4350 m), subacute (4800 m) and chronic (4800 m) altitude hypoxia on colour vision in the green/red axis were explored in eight sea-level natives by means of a simple portable anomaloscope. Subjects were required to create a yellow colour from a mixture of red (635 nm) and green (565 nm) obtained from two electroluminescent diodes. A relative decrease in green, compared to red, sensitivity was observed in each hypoxic condition (p less than 0.001). Acclimatization to altitude, evidenced by the improvement of arterial O2 saturation (earoximeter) was accompanied by a slight but not significant return to normal colour sensitivities. The influence of factors such as fatigue, season, and age is discussed and does not seem likely to account for the observed variations.

A decrease in heart rate response to isoproterenol (IP) infusion has been previously described in humans exposed to acute (2–3 days) or chronic (21 days) exposure to altitude hypoxia (J. Appl. Physiol. 65: 1957–1961, 1988). To evaluate this cardiac response in subacute (8 days) hypoxia and to explore its reversal with restoration of normoxia, six subjects received an IP infusion under normoxia (condition N), after 8 days in altitude (4,350 m, condition H8), on the same day in altitude after inhalation of O2 restoring normoxic arterial O2 saturation (SaO2, condition HO), and 6–11 h (condition RN) and 4–5 mo (condition ND) after the return to sea level. Cardiac chronotropic response to IP, evaluated by the mean increase in heart rate from base value (delta HR, min-1), was lower in condition H8 [mean 30 +/- 13 (SD)] than in condition N (50 +/- 14, P less than 0.03); it was slightly higher in condition HO (38 +/- 14) or condition RN (42 +/- 15) than condition H8 but still significantly different from condition N (P less than 0.03), despite normal values of SaO2. delta HR in condition ND (55 +/- 10) returned to base N value. These findings confirm the hypothesis of a hypoxia-induced decrease in cardiac chronotropic function. Two possible mechanisms are suggested: an O2-dependent one, rapidly reversible with recent restoration of normoxia, and a more slowly reversible mechanism, probably a downregulation of the cardiac beta-receptors.

Cardiac chronotropic response to adrenergic activity at rest and exercise has been studied in 8 sea-level natives on the first two days of exposure to high altitude hypoxia (3823 m, 473 mmHg). Maximal O2 uptake (VO2max) was determined at low altitude (day 0:D0) and high altitude (day 2:D2). Submaximal exercise tests were performed at low altitude (day 1:D1) and high altitude (days 3 and 4: D3, D4). Plasma venous norepinephrine (NE) and epinephrine (E) concentrations were determined at rest and at the end of submaximal exercise. From D0 to D2, maximal heart rate decreased by 7% (p less than 0.01), and VO2max decreased by 17% (p less than 0.01). During submaximal exercise, plasma NE did not vary significantly (D1: 1.36 +/- 0.57, D3: 1.48 +/- 0.51, D4: 1.31 +/- 0.54 ng.ml-1). In contrast, relative work load decreased at high altitude (% VO2max at D1, D3 and D4 were respectively: 90.2 +/- 6.1, 83.3 +/- 9.8, 76.9 +/- 8.2). Linear relationships were found, both at low and high altitudes, between NE and VO2, NE and % VO2max, and between the increases in NE and heart rate during exercise. Covariance analysis indicates that these relations shifted to the left at high altitude:for the same NE or increase in NE, VO2 or increase in heart rate was lower at high altitude. Variations in E were similar but not significant. We conclude that hypoxia induced a decrease in cardiac chronotropic response to adrenergic activation during submaximal exercise.