Determinants of maximal oxygen uptake in severe acute hypoxia

To unravel the mechanisms by which maximal oxygen uptake ((V) over dotO(2max)) 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, similar to5,300 m above sea level). With hypoxia, exercise Pa-O2 dropped to 31-34 mmHg and arterial O-2 content (Ca-O2) was reduced by 35% (P < 0.001). Forty-one percent of the reduction in Ca-O2 was explained by the lower inspired O-2 pressure (PIO2) 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 in (V) over dot O-2max (a greater fall than accountable by reduced Ca-O2). 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) over dotO(2max) (r = 0.98, P < 0.001). Therefore, three main mechanisms account for the reduction of (V) over dotO(2max) in severe acute hypoxia: 1) reduction of PIO2, 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 in (V) over dot O-2max.