Pathophysiology and treatment of high-altitude pulmonary vascular disease.

Abstract

It is estimated that >140 million people live above 2500 m in various regions of the world.1 There are many challenges to living at high altitude, but chronic exposure to alveolar hypoxia is prominent among them. Inspired Po2 falls from ≈150 mm Hg at sea level to ≈100 mm Hg at 3000 m and 43 mm Hg on the summit of Everest (8400 m).2,3 The body responds by hyperventilating, increasing resting heart rate, and stimulating red cell production in an attempt to maintain the oxygen content of arterial blood at or above sea level values.2 However, hypoxic pulmonary vasoconstriction (HPV) and vascular remodeling, together with increased erythropoiesis, place an increased pressure load on the right ventricle (RV). How well healthy humans adapt to hypoxia depends on their rate of ascent to altitude, the severity and duration of their exposure, and their genetic background. ### Pulmonary Vascular Response to Hypoxia For most mammals, including humans, a rise in pulmonary artery pressure (PAP) is an early and inevitable consequence of ascent to high altitude. Resting mean PAP increases along a parabolic curve from 15 mm Hg at 2000 m to ≈30 mm Hg at 4500 m.4 The exceptions and interindividual variation in the magnitude of response offer a natural experiment that might provide insight into fundamental underlying mechanisms ( vide infra ). The initial rise in PAP on exposure to hypoxia is attributed to HPV. With chronic hypoxia, other mechanisms that likely drive vascular remodeling soon contribute to the elevated pressure (Figure 1A). After 2 or 3 weeks of hypoxia, there is little response to rebreathing 100% oxygen, indicating a structural resistance to pulmonary blood flow rather than one based solely on increased vasomotor tone.6 A fall in PAP on re-exposure to a normal oxygen environment is evident in rats monitored by telemetry over days …