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.
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