Frequent sleep disturbances and desaturation during sleep are common at high altitude, but few data are available from the highest altitudes at which humans are known to sleep. Because sleep fragmentation at low altitude may impair mental function and oxygen deprivation produces lasting central nervous system abnormalities, a better understanding of the severity of sleep disturbances and oxygen desaturation at extreme altitudes is important. The purpose of this study was to determine the severity of sleep disturbance and the extent of arterial oxygen desaturation at extreme simulated altitude. Out of eight healthy male subject volunteers who started, five aged 27.2 +/- 1.5 yr completed the study during 6 weeks of progressive hypobaric hypoxia in a decompression chamber. The men were studied at barometric pressures of 760, 429, 347, 282 mm Hg and following return to 760 mm Hg. All demonstrated frequent nighttime awakenings (37.2 awakenings per subject per night at 282 mm Hg, decreasing significantly to 14.8 on return to sea level, p less than 0.05). Total sleep time decreased from 337 +/- 30 min at 760 mm Hg to 167 +/- 44 min at 282 mm Hg (p less than 0.01). Rapid eye movement (REM) sleep decreased from 17.9% +/- 6.0% of sleep time at sea level to 4.0% +/- 3.3% at 282 mm Hg (p less than 0.01). Sleep continuity as reflected by brief arousals increased from 22 +/- 6 arousals per hour of sleep at sea level to 161 +/- 66 arousals per hour at 282 mm Hg (p less than 0.01). All subjects showed arterial oxygen desaturation proportional to the altitude. The average oxygen saturation (SaO2) was 79% +/- 3% at 429 mm Hg, 66% +/- 6% at 347 mm Hg, and 52% +/- 2% at 282 mm Hg. Sleep stage had only a minimal effect on SaO2 at any altitude. SaO2 was negatively correlated with brief sleep arousals, r = -0.72, p less than 0.01. All subjects demonstrated periodic breathing with apneas throughout much of the night at 347 and 282 mm Hg. These data indicate that sleep quality progressively worsens as SaO2 decreases despite lack of progressive changes in sleep stages at altitude. This study extends previous information on the severity of desaturation during sleep, and suggests that improvements in oxygenation might prove beneficial in restoring consolidated sleep, possibly even improving daytime performance.

We aimed to determine the isolated and combined contribution of hypovolaemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxaemia at high altitude. In a double-blinded, randomised and placebo-controlled design, 12 healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5-10 days at 3800 m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of sildenafil (50 mg) to create four unique experimental conditions that were compared with SL values: high altitude (HA), Plasma Volume Expansion (HA-PVX), Sildenafil (HA-SIL) and Plasma Volume Expansion with Sildenafil (HA-PVX-SIL). High altitude exposure reduced plasma volume by 11% (P < 0.01) and increased pulmonary artery systolic pressure (19.6 ± 4.3 vs. 26.0 ± 5.4, P < 0.001); these differences were abolished by PVX and SIL respectively. LV end-diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA-PVX trial. LV EDV and SV were also elevated in the HA-SIL and HA-PVX-SIL trials compared to HA, but to a lesser extent. Neither PVX nor SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800 m both hypovolaemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, but restoring LV filling does not confer an improvement in maximal exercise performance.

Exposure to hypoxic environments is associated with decreased arterial oxygen saturation and increased pulmonary artery pressures. Ischemic preconditioning of an extremity (IPC) is a procedure that stimulates vasoactive and inflammatory pathways that protect remote organ systems from ongoing or future ischemic injury. To test the effects of IPC on oxygen saturation and pulmonary artery pressures at high altitude, 12 healthy adult volunteers were evaluated in a randomized cross-over trial. IPC was administered utilizing a standardized protocol. IPC or placebo was administered daily for 5 days prior to ascent to altitude. All participants were evaluated twice at 4342 m altitude (placebo and IPC conditions separated by 4 weeks, randomized). The pulmonary artery systolic pressure (PASP) at 4342 m was significantly lower in the IPC condition than the placebo condition (36 ± 6.0 mmHg vs. 38.1 ± 7.6 mmHg, respectively, p = 0.035). Oxygen saturation at 4342 m was significantly higher with IPC compared to placebo (80.3 ± 8.7% vs. 75.3 ± 9.6%, respectively, p = 0.003). Prophylactic IPC treatment is associated with improved oxygen saturation and attenuation of the normal hypoxic increase in pulmonary artery pressures following ascent to high altitude.

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Pulmonary function abnormalities after exercise are suggestive of pulmonary edema; however, radiographic evidence is lacking. Well-trained cyclists were studied to determine whether there is radiographic evidence of pulmonary edema after endurance exercise (cycling distance 5.3-131.5 km) at altitude. Chest radiographs obtained before exercise were coded for later interpretation. Films obtained after exercise were coded with a different number. A total of 74 sets of posteroanterior and lateral films were analyzed by three radiologists for signs of pulmonary edema. Radiographic changes were graded on a three-point scale. An edema score was calculated by summing the score for each individual radiographic finding for each radiologist and an overall edema score representing the mean scores from all three radiologists. The overall edema score increased from 0.8 +/- 1.2 before exercise to 1.8 +/- 1.6 after exercise (P < 0.01). These results suggest that, after prolonged high-intensity exercise at moderate altitude, there is radiographic evidence of early pulmonary edema in some cyclists.

Sleep at high altitude is characterized by poor subjective quality, increased awakenings, frequent brief arousals, marked nocturnal hypoxemia, and periodic breathing. A change in sleep architecture with an increase in light sleep and decreasing slow-wave and REM sleep have been demonstrated. Periodic breathing with central apnea is almost universally seen amongst sojourners to high altitude, although it is far less common in long-standing high altitude dwellers. Hypobaric hypoxia in concert with periodic breathing appears to be the principal cause of sleep disruption at altitude. Increased sleep fragmentation accounts for the poor sleep quality and may account for some of the worsened daytime performance at high altitude. Hypoxic sleep disruption contributes to the symptoms of acute mountain sickness. Hypoxemia at high altitude is most severe during sleep. Acetazolamide improves sleep, AMS symptoms, and hypoxemia at high altitude. Low doses of a short acting benzodiazepine (temazepam) may also be useful in improving sleep in high altitude.

Key Points Summary-Our objective was to quantify endothelial function (via brachial artery flow-mediated dilatation) at sea-level (344m) and high-altitude (3800m) at rest and following both maximal exercise and 30-minutes of moderate-intensity cycling exercise with and without administration of an 1-adrenergic blockade.-Brachial endothelial function did not differ between sea-level and high-altitude at rest, nor following maximal exercise.-At sea-level, endothelial function decreased following 30-minutes of moderate-intensity exercise, and this decrease was abolished with 1-adrenergic blockade. At high-altitude, endothelial function did not decrease immediately post 30-minutes of moderate-intensity exercise, and administration of 1-adrenergic blockade resulted in an increase in flow mediated dilatation.-Our data indicates that post-exercise endothelial function is modified at high-altitude (i.e. prolonged hypoxemia). The current study helps elucidate the physiological mechanisms associated with high-altitude acclimatization, and provides insight into the relationship between sympathetic nervous activity and vascular endothelial function. AbstractWe examined the hypotheses that 1) at rest, endothelial function would be impaired at high-altitude compared to sea-level, 2) endothelial function would be reduced to a greater extent at sea-level compared to high-altitude after maximal exercise, and 3) reductions in endothelial function following moderate-intensity exercise at both sea-level and high-altitude are mediated via an 1-adrenergic pathway. In a double-blinded, counter-balanced, randomized and placebo-controlled design, nine healthy participants performed a maximal-exercise test, and two 30-minute sessions of semi-recumbent cycling exercise at 50% peak Watt following either placebo or 1-adrenergic blockade (prazosin; 0.05mg/kg). These experiments were completed at both sea-level (344m) and high-altitude (3800m). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded prior to, during, and following exercise. Endothelial function assessed by brachial artery flow-mediated dilatation (FMD) was measured prior to, immediately following, and 60-minutes post-exercise. Our findings were: 1) at rest, FMD remained unchanged between sea-level and high-altitude (placebo P=0.287; prazosin: P=0.110); 2) FMD remained unchanged after maximal exercise at sea-level and high-altitude (P=0.244); 3) the 2.90.8% (P=0.043) reduction in FMD immediately after moderate-intensity exercise at sea-level was abolished via 1-adrenergic blockade. Conversely, at high-altitude, FMD was unaltered following moderate-intensity exercise, and administration of 1-adrenergic blockade elevated FMD (P=0.032). Our results suggest endothelial function is differentially affected by exercise when exposed to hypobaric hypoxia. These findings have implications for understanding the chronic impacts of hypoxemia on exercise...

A prospective randomized trial was conducted to evaluate the effects of exercise-based cardiac rehabilitation after myocardial revascularization surgery (MRS) on work capacity (measured in mets) and left ventricular function as determined from ejection fraction (LVEF). Twenty-eight patients undergoing MRS were randomly assigned to experimental (aerobic exercise, n = 19) or control (muscle relaxation and low-level exercise, n = 9) groups. Patients were studied before surgery (T1) and 2 (T2), 8 (T3), and 24 (T4) weeks after surgery with first-pass radionuclide angiography both while they were at rest and during maximal upright cycle ergometric exercise. Subsets of patients were also studied at T2, T3, and T4 at a standard workload of 75 W, and during maximal exercise 1 year after surgery (T5). Work capacity improved in both groups although significantly more so in the experimental group (3.9, 3.8, 6.0, and 7.3 mets and 3.7, 3.7, 4.9, and 5.7 mets at TI, T2, T3, and T4 in the experimental and control groups, respectively). The differences between groups were significant by T3. Peak exercise LVEF increased significantly in both groups from T1 to T2 then decreased at T3 and remained unchanged through T5. Peak exercise LVEF at T3 to T5 remained significantly above that observed at T 1. LVEF responses were not related to the exercise program. During a standard workload, heart rate decreased, blood pressure increased, and LVEF did not change in either group. After conclusion of the formal protocol (T4), work capacity and LVEF did not change for either group throughout an additional 6 months (T5). We conclude that exercise training significantly enhances both the magnitude and rate of the increase in work capacity after MRS, but that peak exercise LVEF is not influenced by the exercise program. Circulation 69, No. 4, 748-755, 1984. THE GROWTH of rehabilitation programs for patients with cardiovascular disease has been impressive during the 25 years since Hellerstein and Ford first presented "an orderly plan for the rehabilitation of the patient with heart disease. "' Exercise-based rehabilitation programs have a demonstrated beneficial effect on clinical status, as evidenced by improved work capacity,2' 3reduction in incidence of attacks of angina pectoris,4 and indications of a reduction in rates of morbidity/mortality.5 6 Their effect on left ventricular function, which is an important prognosticator of sur-