Bright light affects alertness and performance rhythms during a 24-h constant routine.

The aim of the present study was to assess the stimulating effects of bright light (BL) on subjective and objective alertness. Eight subjects were exposed to either bright light or dim light (DL) during a 24-h constant routine (0900-0900). Bright light failed to modify either the 24-h course or the level of body temperature. Compared to DL, BL delayed the circadian trough of motor activity by 2 h. During the night, relative to the dim-light condition, BL significantly increased subjective and objective (EEG test) alertness and improved performances. Thus, BL exposure partly counteracted the effects of sleep deprivation and/or the circadian trough on alertness and performances. During the day, BL only improved the mood and motivation levels. However, the time course of mood and motivation was not affected by the BL exposure, a nocturnal circadian trough occurring at 0630 in both light conditions.

MIBG scintigraphic assessment of cardiac adrenergic activity in response to altitude hypoxia.

High altitude hypoxia induces a decrease in the cardiac chronotropic function at maximal exercise or in response to isoproterenol infusion, suggesting an alteration in the cardiac sympathetic activation. Iodine-123 metaiodobenzylguanidine [( 123I]MIBG) was used to map scintigraphically the cardiac sympathetic neuronal function in six male subjects (aged 32 +/- 7 yr) after an exposure to high altitude that created hypoxic conditions. Results obtained just after return to sea level (RSL) were compared with the normal values obtained after 2 or 3 mo of normoxia (N). A static image was created as the sum of the 16-EKG gated images recorded for 10 min in the anterior view of the chest at 20, 60, 120, and 240 min after injection. Regions of interest were located over the heart (H), lungs (L), and mediastinum (M) regions. There was a significant decrease in the H/M and the L/M ratios in RSL compared to N condition. Plasma norepinephrine concentration was elevated during the stay at altitude but not significantly different in RSL compared to N. In conclusion, cardiac [123I]MIBG uptake is reduced after an exposure to altitude hypoxia, supporting the hypothesis of an hypoxia-induced reduction of adrenergic neurotransmitter reserve in the myocardium. Furthermore, the observed significant decrease in pulmonary MIBG uptake suggests an alteration of endothelial cell function after exposure to chronic hypoxia.

[Cardiac response to hypoxia and susceptibility to mountain sickness]. / Réponse cardiaque á l'hypoxie et susceptibilité au mal des montagne

Exercising in high altitude is impeded during the first days of exposure to altitude hypoxia by the symptoms of Acute Mountain Sickness (AMS). Susceptibility to AMS is independent of endurance training and determined by the sensitivity of carotid chemoreceptors to hypoxemia and induced hyperventilation and tachycardia. Cardiac response to hypoxia is not as well known as ventilatory response, especially at exercise. A group of 138 male alpinists has been explored before their departure to a high altitude expedition using an hypoxic gas mixture (equivalent altitude = 4.800 m), at rest and at exercise (5 minutes at 50 p. 100 maximal O2 consumption). Cardiac response to hypoxia was assessed by the ratio DFc/DSaO2: variation in heart rate (hypoxia - normoxia)/variation in arterial O2 saturation, at rest (r) and during exercise (e). After the expedition, subjects were classified in AMS+ or AMS- group if they suffered or not from severe AMS, and also following their climbing skill. Cardiac response to hypoxia at rest is lower in AMS+ subjects (DFc/DSaO2 = - 0.86 +/- 0.40 nn - 1.% - 1) than in AMS- subjects (-1.12 +/- 0.69, p less than 0.05), but is not linked to the climbing skill. Similar differences were observed at exercise: DFc/DSaO2e = - 0.88 +/- 0.32 (AMS+) and - 1.05 +/- 0.50 (AMS-) (p less than 0.05). Associated with the respiratory response to hypoxia, the cardiac response allows the detection of AMS high-risk subjects and may be used in an much less than aptitude to altitude much greater than test.

Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion.

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.

Effect of beta-adrenoceptor blockade on renin-aldosterone and alpha-ANF during exercise at altitude.

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.

Diurnal variations of acute mountain sickness, colour vision, and plasma cortisol and ACTH at high altitude.

Time dependence of colour vision in the green/red axis, signs of acute mountain sickness (AMS), and plasma cortisol and ACTH concentrations were studied in eight sea-level male natives exposed 79 h to altitude hypoxia at 4,350 m. Colour vision (CV) was explored every 2 h from 08:00 to 20:00 hours by means of two portable anomaloscopes, one derived from Essilor CHROMOTEST and the other from the OSCAR. Significant diurnal variations in CV were found using both anomaloscopes, major alterations in green relative to red sensitivity being seen in the early morning. AMS scores also showed remarkable diurnal variations, parallel to those of plasma cortisol and CV, with maximum values observed at 08:00 hours. Cortisol diurnal rhythm was maintained in hypoxia, with mean concentrations higher than in normoxia. ACTH followed the same trend, but variations were not significant. Significant correlations were found between instant values of CV, cortisol, and AMS score, but no causal relationship between these variables can be ascertained.

Decreased cardiac response to isoproterenol infusion in acute and chronic hypoxia.

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)

Modification of colour vision in the green/red axis in acute and chronic hypoxia explored with a portable anomaloscope.

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.

[Photoplethysmography and laser Doppler velocimetry in the study of cutaneous vasomotility at high altitudes]. / Utilisation de la photopléthysmographie et de la vélocimétrie laser Doppler dans l'exploration de la vasomotricité cutanée en haute altitude.

During the second French scientific medical expedition to the Himalaya (ARPE, Annapurna IV, 1985), modifications of cutaneous circulation in hypoxia were studied. Two techniques were used for the first time to evaluate cutaneous vasoactivity under such conditions: laser Doppler velocimetry and photoplethysmography. Measurements were performed on the pulp of the third and fourth fingers of the right hand in 6 subjects native of sea-level countries: first at sea level, then in hypoxia after 15 days at 4,800 m before and after ingestion of a vasodilator drug (nicardipine 20 mg). Cutaneous circulation was explored under three thermal conditions: baseline (ambient temperature); after vasodilation obtained by immersion of the hand in hot water (40 degrees C), and after immersion of the hand in cold water (12 degrees C). In prolonged hypoxia a reduction in vasoconstriction at 12 degrees C was observed with both techniques. No significant change was observed at 40 degrees C. After dosing with nicardipine, the results differed according to the exploratory technique: a slight increase of the laser Doppler signal (NS) and a decrease of the photoplethysmographic signal were recorded. Acclimatization to cold and to hypoxia may concur to determine this response of cutaneous circulation. The action of vasodilating agents on cutaneous microcirculation in prolonged hypoxia is not clear and deserves further investigation. These drugs must be used with caution in the prevention and treatment of frostbite.

Acute hypoxia decreases cardiac response to catecholamines in exercising humans.

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.

[Periodic respiration during sleep at high altitude. Effects of a hypnotic benzodiazepine, loprazolam]. / Respiration périodique pendant le sommeil en altitude. Effets d'une benzodiazépine hypnotique, le loprazolam.

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.

[Characteristics of the partial derivative of hemoglobin saturation with respect ot oxygen pressure : delta S 02/delta P 02]. / Caractéristiques de la dérivée partielle de la saturation de l'hémoglobine par rapport à la pression d'oxygène : delta S02/delta P02.

The first (delta S/delta P) and second (delta 2S/delta [H+] delta P) partial derivatives of hemoglobin saturation with respect to oxygen pressure and [H+] were numerically calculated for the blood of non-smoking young adult at different pH, PCO2 and [2.3-DPG]. Their functional value in respiratory physiology was stressed.