Another genetic factor which may contribute to high-altitude performance is a polymorphism in the angiotensin-converting enzyme gene that appears to be more prevalent in elite mountaineers and in endurance athletes than in the general population.49 Saracatinib research buy Individuals differ widely in their susceptibility to high-altitude disorders; some suffer the life-threatening complications of high-altitude cerebral or pulmonary edema at altitudes Inhibitors,research,lifescience,medical as low as 3,000 m, whereas others can climb to 8,000 m without supplemental oxygen. Genetic influences remain an active area of investigation.50

PRE-EXISTING DISEASES Recreational travelers, hikers, and skiers with Inhibitors,research,lifescience,medical underlying cardiac or pulmonary diseases often seek advice regarding high-altitude travel. Asymptomatic patients with coronary disease generally do well, although it is probably prudent to avoid highly strenuous exercise; patients with heart failure should avoid the hypoxia of high altitude.51 Severe anemia and sickle cell disease Inhibitors,research,lifescience,medical are also contra-indications to high-altitude travel.51 The advice for patients with lung disease depends on the underlying disease, its severity, and the anticipated altitude and activity

level; specific recommendations are contained in an extensive review of the subject.52 HIGH-ALTITUDE CEREBRAL Inhibitors,research,lifescience,medical EDEMA High-altitude cerebral edema (HACE) is likely a continuum of AMS. AMS is generally self-limiting, whereas HACE can be fatal. Individuals with high Lake Louise scores should be carefully

monitored for the signs of ataxia, confusion, and hallucinations which may mark the onset of HACE. HACE is a clinical diagnosis and consists of ataxia and altered consciousness in someone with AMS or high-altitude pulmonary edema. Individuals with AMS should not ascend until symptoms have resolved; if symptoms fail to resolve, they should descend. Individuals with HACE should descend immediately if at all Inhibitors,research,lifescience,medical possible and should never descend unaccompanied. The exact processes leading to high-altitude cerebral edema are MTMR9 unknown although the edema is probably extracellular, due to blood–brain barrier leakage (vasogenic edema), rather than intracellular, due to cellular swelling (cytotoxic edema).53 Vasogenic edema preferentially spreads along white matter tracts, whereas cytotoxic edema affects both gray and white matter. MRI studies of patients with HACE showed that the majority had intense T2 signal in white matter areas, particularly the splenium of the corpus callosum, but no gray matter abnormalities.53 The predilection for the splenium and corpus callosum is puzzling. Possibly the splenium has more easily perturbed cellular fluid mechanics than surrounding tissues.