Components of alveolar-arterial O₂ gradient during rest and exercise at sea level and high altitude

To determine the effects of exercise and high altitude on the contributions of shunt, ventilation-perfusion (V/Q) nonhomogeneity, and diffusion limitation to the alveolar-arterial O₂ gradient (AaDO₂), we measured pulmonary exchange of O₂, CO₂, and six inert gases (SF₆, ethane, cyclopropane, halothane, diethyl ether, and acetone) during rest and exercise in unanesthetized dogs at sea level and after acute exposure to an altitude of 6,096 m in a hypobaric chamber. Shunt and dead-space fractions, calculated from inert gas measurements, did not change. High altitude decreased the inert gas partial pressure gradients between mixed alveolar gas and mixed end-capillary blood, indicating that V/Q relationships became more homogeneous. Exercise had no effect on these gradients. At sea level, AaDO₂ was mainly due to V/Q nonhomogeneity, with a small portion due to shunt. At high altitude, the contribution of shunt became negligible and that of V/Q nonhomogeneity diminished. These improvements were partially offset, however, by a gradient due to diffusion limitation. Exercise had no effect on AaDO₂ or any of its components. At high altitude, estimated pulmonary O₂ diffusing capacity averaged 20.8 ml.min^-1.Torr^-1 during exercise.