Determinants of maximal oxygen uptake in severe acute hypoxia

Abstract

To unravel the mechanisms by which maximal oxygen uptake (V˙o 2 max) is reduced with severe acute hypoxia in humans, nine Danish lowlanders performed incremental cycle ergometer exercise to exhaustion, while breathing room air (normoxia) or 10.5% O 2 in N 2(hypoxia, ∼5,300 m above sea level). With hypoxia, exercise Pa O 2 dropped to 31–34 mmHg and arterial O 2 content (Ca O 2 ) was reduced by 35% ( P < 0.001). Forty-one percent of the reduction in Ca O 2 was explained by the lower inspired O 2 pressure (Pi O 2 ) in hypoxia, whereas the rest was due to the impairment of the pulmonary gas exchange, as reflected by the higher alveolar-arterial O 2 difference in hypoxia ( P < 0.05). Hypoxia caused a 47% decrease inV˙o 2 max (a greater fall than accountable by reduced Ca O 2 ). Peak cardiac output decreased by 17% ( P < 0.01), due to equal reductions in both peak heart rate and stroke volume ( P < 0.05). Peak leg blood flow was also lower (by 22%, P < 0.01). Consequently, systemic and leg O 2 delivery were reduced by 43 and 47%, respectively, with hypoxia ( P < 0.001) correlating closely with V˙o 2 max( r = 0.98, P < 0.001). Therefore, three main mechanisms account for the reduction ofV˙o 2 max in severe acute hypoxia: 1) reduction of Pi O 2 , 2) impairment of pulmonary gas exchange, and 3) reduction of maximal cardiac output and peak leg blood flow, each explaining about one-third of the loss inV˙o 2 max.