At sea-level, this exercise-induced pressure differential is accompanied by a ventilatory response that rises out of proportion to increasing oxygen demands; this heightened ventilatory response is usually

sufficient to maintain the arterial PO2 and prevent the development of hypoxemia.32 Under the hypoxic conditions of high altitude, however, the ventilatory response is no longer sufficient to prevent arterial oxygen desaturation with exercise; and even mild arterial desaturation (< 94% SaO2) is associated with a significant reduction in Caspase inhibitor maximum oxygen consumption Inhibitors,research,lifescience,medical and endurance performance.33 Maximum oxygen consumption is reduced to about 85% of its value at sea-level at 3,000 m, and it falls to 60% at 5,000 m.14 When combined with rapid ascent, strenuous exercise and over-exertion Inhibitors,research,lifescience,medical are risk factors for AMS. In a controlled study of subjects experiencing a simulated altitude gain of 3,000 m in a decompression chamber, exercise significantly reduced arterial saturation (SaO2) and increased the AMS symptom scores.34 The effect of physical conditioning in preventing AMS is more difficult to evaluate since those in good physical Inhibitors,research,lifescience,medical condition are apt to engage in more strenuous exercise and undertake more rapid ascent, both risk factors for AMS. Data suggest, however, that subjects in excellent physical condition probably have a risk of AMS similar to

that in less highly trained individuals.3,35,36 AMS: RISK FACTORS AMS is associated with a Inhibitors,research,lifescience,medical number of potential risk factors including home elevation, maximum sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, hemoglobin saturation, pre-acclimatization, prior experience at altitude, genetic make-up, and pre-existing diseases. HOME ELEVATION AND MAXIMUM SLEEPING ALTITUDE Travelers ascending from sea-level are at higher risk for AMS than those living at higher elevations. This difference Inhibitors,research,lifescience,medical is illustrated by a study at a Colorado ski resort showing that

the risk of developing AMS was 27% for residents arriving from sea-level compared to 8.4% for those residing above 1,000 m.3 The risk of AMS increases with sleeping altitude; among mountaineers staying at huts in the Swiss Thymidine kinase Alps, the prevalence of AMS ranged from 9% at 2,850 m to 53% at 4,559 m (Table 2).5 These results are comparable to the prevalence of AMS among trekkers staying at tea houses in Nepal which ranged from 10% at 3,000–4,000 m to 51% at 4,500–5,000 m (Table 2).4 Interestingly, in this study, the prevalence of AMS decreased from 51% at 4,500–5,000 m to 34% above 5,000 m (Table 2) and was likely due to self-selection or prior experience at altitude among those ascending above 5,000 m. RATE OF ASCENT AND KILIMANJARO A rapid rate of ascent is an important contributor to the development of AMS.