Polycythemia is one of the key factors involved in chronic mountain sickness syndrome (CMS), a condition frequent in Andean natives but whose causes still remain unclear. Polycythemia may be secondary to abnormalities in ventilation, which in turn stimulate excessive erythropoietin (Epo) production, or may occur in specific circumstances, for example during sleep, through sleep disturbances. Alternatively, polycythemia and excessive Epo secretion may result from autogenous production or be dependent on sustained stimulation by co-factors which can induce erythropoiesis independently of ventilatory abnormalities.Several studies have addressed subjects with and without CMS and with/without elevated hematocrit levels.Compared with healthy controls, individuals with polycythemia tend to have higher Epo levels, which is related to lower oxygen saturation and slightly reduced hypoxic ventilatory responses. Higher levels of carbon dioxide have also been reported. The latter finding might per se indicate either relative hypoventilation and/or pulmonary dysfunction. However, in many subjects elevated carbon dioxide levels coexist with normal pulmonary function, thus excluding the causal role of pulmonary dysfunction as a necessary condition. Increased serum levels of stimulating co-factors (cobalt) have been documented, but this finding has not been confirmed by subsequent tests, again indicating that this is not a general condition. Finally, preliminary experiments by our group with subjects with or without polycythemia have shown that Epo levels reverse with improved oxygenation.Current information indicates that increased Epo production is mainly related to greater ventilatory inefficiency; pulmonary dysfunction, sleep disorders, and in certain cases, toxic factors may lead to the disease, but do not appear to be the main cause. Therefore improved oxygenation may potentially reverse the chain of events that produces polycythemia and CMS.
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