A 45-year-old healthy man wishes to climb Mount Kilimanjaro (5895 m) in a 5-day period, starting at 1800 m. The results of a recent exercise stress test were normal; he runs 10 km 4 or 5 times per week and finished a marathon in less than 4 hours last year. He wants to know how he can prevent becoming ill at high altitude and whether training or sleeping under normobaric hypoxic conditions in the weeks before the ascent would be helpful. What would you advise?

T his review focuses on the effects of altitude exposure from 1 to several days or weeks as occurs in tourists, trekkers, and mountaineers who visit high altitude and normally reside near sea level. We briefly review the acute physiological adjustments and early acclimatization that occur in the cardiovascular system and the lungs of healthy individuals. These ensure life-sustaining oxygen delivery to the tissues despite a reduction in the partial pressure of inspired oxygen between 20% and 60% at 2500 and 8000 m, respectively. One of the acute adjustments, hypoxic pulmonary vasoconstriction (HPV), may be disadvantageous in those with a vigorous response and lead to 2 potentially lethal illnesses, high-altitude pulmonary edema (HAPE) and subacute mountain sickness (SAMS), which we present in more detail. Finally, on the basis of knowledge about the acute physiological adjustments and acclimatization and, when available, a review of the literature, we discuss the highaltitude tolerance of patients with coronary artery disease, congestive heart failure, arrhythmias, systemic hypertension, and pulmonary hypertension. Effects of Exposure to High Altitude on the Normal Cardiovascular System CirculationThe major effects of acute hypoxia on the heart and lung are shown in Figure 1. Hypoxia directly affects the vascular tone of the pulmonary and systemic resistance vessels and increases ventilation and sympathetic activity via stimulation of the peripheral chemoreceptors. 1 Interactions occur between the direct effects of hypoxia on blood vessels and the chemoreceptor-mediated responses in the systemic and pulmonary circulation. Unraveling the underlying mechanisms of the hypoxic vasodilatation of systemic arterioles is an active area of research. Several mechanisms appear to regulate local oxygen delivery according to the needs of the tissues 2,3 ; for instance, the release of ATP from red blood cells and the generation of NO by various ways appear to regulate local oxygen delivery according to the needs of the tissue. These mechanisms may decrease with prolonged stay at high altitude when oxygen content of the blood increases because of ventilatory acclimatization, an increase in hematocrit associated with plasma volume reduction, and an increase in red blood cell mass due to erythropoiesis.Peripheral chemoreceptor afferent activity rises hyperbolically as hypoxia increases. 4 Ventilation and sympathetic activity are augmented, as demonstrated by increased urinary and plasma concentration of catecholamines 5 and skeletal muscle sympathetic activity. 6 With exposure over days to weeks, the sensitivity of the peripheral chemoreceptors to hypoxia increases, leading to further enhancement of ventilation (ventilatory acclimatization). This presumably also accounts for the further increase of sympathetic activity documented by microneurography after 3 weeks at 5200 m 6 and elevated catecholamines in urine and plasma. 5 As shown in Figure 1, there is antagonism between the direct effects of hypoxia on the resistance vessels ...

At any point 1-5 days following ascent to altitudes ⩾2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases.