Hypoxemia and acute mountain sickness: which comes first?

Hypoxemia is usually associated with acute mountain sickness (AMS), but most studies have varied in time and magnitude of altitude exposure, exercise, diet, environmental conditions, and severity of pulmonary edema. We wished to determine whether hypoxemia occurred early in subjects who developed subsequent AMS while resting at a simulated altitude of 426 mmHg (approximately 16,000 ft or 4880 m). Exposures of 51 men and women were carried out for 8 to 12 h. AMS was determined by Lake Louise (LL) and AMS-C scores near the end of exposure, with spirometry and gas exchange measured the day before (C) and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude and arterial blood at C, A1, and A12. Responses of 16 subjects having the lowest AMS scores (nonAMS: mean LL=1.0, range=0-2.5) were compared with the 16 having the highest scores (+AMS: mean LL=7.4, range=5-11). Total and alveolar ventilation responses to altitude were not different between groups. +AMS had significantly lower PaO2 (4.6 mmHg) and SaO2 (4.8%) at A1 and 3.3 mmHg and 3.1% at A12. Spirometry changes were similar at A1, but at A6 and A12 reduced vital capacity (VC) and increased breathing frequency suggested interstitial pulmonary edema in +AMS. The early hypoxemia in +AMS appears to be the result of diffusion impairment or venous admixture, perhaps due to a unique autonomic response affecting pulmonary perfusion. Early hypoxemia may be useful to predict AMS susceptibility.

Role of hypobaria in fluid balance response to hypoxia.

To estimate the separate and combined effects of reduced P(B) and O2 levels on body fluid balance and regulating hormones, measurements were made during reduced PB (altitude, ALT; P(B) = 432 mm Hg, F(I(O2)) = 0.207), reduced inspired O2 concentration (normobaric hypoxia, HYX; P(B) = 614 mm Hg, F(I(O2)) = 0.142), and lowered ambient pressure without hypoxia (normoxic hypobaria HYB; P(B) = 434 mm Hg, F(I(O2)) = 0.296). Nine fit and healthy young men were exposed to these conditions for 10 h in a decompression chamber. Lake Louise AMS scores, urine collections, and blood samples were obtained every 3 h, with recovery measurements 2 h after exposure. AMS was significantly greater during ALT than HYX, as previously reported (J. Appl. Physiol. 81:1908-1910. 1996), because the combination of reduced P(B) and P(O2) over the 10 h favored fluid retention by reducing urine volume, while plasma volume (PV) remained higher than during HYX. At ALT the plasma Na+ fell significantly at 6 h, probably from dilution of extracellular fluid, and antidiuretic hormone (ADH) was highest (p = 0.006 versus HYB). The PV, urine flow, free water clearance, and plasma renin activity (PRA) rose significantly during recovery from ALT as AMS symptoms subsided, suggesting increased intravascular fluid and reduced adrenergic tone. During HYB, the plasma aldosterone (ALDO) and K+ levels were significantly elevated, and PRA was highest and ADH lowest, without fluid retention. During HYX, fluid balance was similar to HYB, but PV and ALDO were significantly lower, and ALDO increased significantly in recovery from HYX. The fluid retention at ALT in AMS-susceptible subjects appears related to a synergistic interaction involving reduced P(B) and ADH and ALDO.