Cardiac Output Is Decreased and Hypoxic Vasoconstriction Is Intact in Chronically Hypoxic Sheep 1

Abstract

Previous studies have shown that although sheep have a pulmonary pressor response to acute hypoxia, they fail to develop pulmonary hypertension during chronic exposure to high altitude. We wondered if this failure was due to decreased cardiac output or to blunted hypoxic pulmonary vasoconstriction. After 12 days at a simulated altitude of 4573 m, six sheep developed mild pulmonary hypertension with increased pulmonary arterial pressure (17 ± 1 before to 25 ± 2 mm Hg after), decreased cardiac output (6.0 ± 0.4 before to 5.1 ± 0.6 liter/min after), and increased pulmonary vascular resistance (1.6 ± 0.2 before to 3.4 ± 0.5 mm Hg/liter/min after). The pulmonary vasoconstrictor response to acute hypoxia was studied before and after 12 days of exposure to 4573 m by exposing the sheep to increasing altitudes in a dose-response manner. During acute hypoxia, pulmonary arterial pressures were the same before and after chronic hypoxia, but cardiac outputs were decreased after chronic high altitude exposure. Thus, after 12 days at 4573 m, pulmonary vascular resistances were higher at each of four levels of acute hypoxia, although the magnitude of the resistance increase in going from 1524 to 4573 m was not changed (Δ = 1.0 ± 0.3 before and 1.2 ± 0.3 mm Hg/liter/min after). We conclude that pulmonary vasoconstrictor responses to acute hypoxia were not blunted after 12 days of exposure to high altitude. Decreased cardiac output may be an important factor in the adaptation of the pulmonary circulation of sheep to chronic hypoxia.