Expedition 5300: limits of human adaptations in the highest city in the world

Exposure to chronic hypobaric hypoxia imposes a significant physiological burden to more than 80 million humans living above 2500 m throughout the world. Among them, 50 000 live in the world's highest city, La Rinconada, located at 5000-5300 m in southern Peru. Expedition 5300 is the first scientific and medical programme led in La Rinconada to investigate the physiological adaptations and altitude-related health issues in this unique population. Dwellers from La Rinconada have very high haemoglobin concentration (20.3 +/- 2.4 g/dL; n = 57) and those with chronic mountain sickness (CMS) exhibit even higher concentrations (23.1 +/- 1.7 g/dL; n = 150). These values are associated with large total haemoglobin mass and blood volume, without an associated iron deficit. These changes in intravascular volumes lead to a substantial increase in blood viscosity, which is even larger in CMS patients. Despite these large haematological changes, 24 h blood pressure monitoring is essentially normal in La Rinconada, but some results suggest impaired vascular reactivity. Echocardiography revealed large right heart dilatation and high pulmonary arterial pressure as well as left ventricle concentric remodelling and grade I diastolic dysfunction. These changes in heart dimension and function tend to be more severe in highlanders with CMS. Polygraphy evaluations revealed a large reduction in nocturnal pulse oxygen saturation (median SpO2 = 79%), which is even more severe in CMS patients who also tended to show a higher oxygen desaturation index. The population of La Rinconada offers a unique opportunity to investigate the human responses to chronic severe hypoxia, at an altitude that is probably close to the maximum altitude human beings can permanently tolerate without presenting major health issues.image Abstract figure legend La Rinconada is the highest city in the world, spread over the mountain above the Peruvian Altiplano from 5000 to 5300 m. At this altitude, the inspiratory oxygen partial pressure is only 50% of the sea level value. The most striking physiological effect of chronic severe hypoxia in dwellers from La Rinconada is the large increase in haematocrit and red blood cell volume. This hypoxia response as well as other physiological mechanisms are important adaptive responses allowing these highlanders to cope with permanent severe hypoxia. Chronic severe hypoxia also induces in part of the population maladaptive mechanisms, including excessive erythrocytosis and symptoms of chronic mountain sickness. ABP, ambulatory blood pressure; CMS, chronic mountain sickness; PV, plasma volume; RBC, red blood cell; SpO2, arterial pulse oxygen saturation; PiO2${P_{{\mathrm{i}}{{\mathrm{O}}_2}}}$, inspiratory oxygen partial pressure; PaO2${P_{{\mathrm{a}}{{\mathrm{O}}_{\mathrm{2}}}}}$, arterial oxygen partial pressure.image