Central regulation of skeletal muscle recruitment explains the reduced maximal cardiac output during exercise in hypoxia

To unravel the mechanisms by which maximal oxygen uptake (V ˙O2 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 N2 (hypoxia, ϳ5,300 m above sea level).With hypoxia, exercise PaO 2 dropped to 31-34 mmHg and arterial O2 content (CaO 2 ) was reduced by 35% (P Ͻ 0.001).Forty-one percent of the reduction in CaO 2 was explained by the lower inspired O2 pressure (PIO 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 Ͻ 0.05).Hypoxia caused a 47% decrease in V ˙O2 max (a greater fall than accountable by reduced CaO 2 ).Peak cardiac output decreased by 17% (P Ͻ 0.01), due to equal reductions in both peak heart rate and stroke volume (P Ͻ 0.05).Peak leg blood flow was also lower (by 22%, P Ͻ 0.01).Consequently, systemic and leg O 2 delivery were reduced by 43 and 47%, respectively, with hypoxia (P Ͻ 0.001) correlating closely with V ˙O2 max (r ϭ 0.98, P Ͻ 0.001).Therefore, three main mechanisms account for the reduction of V ˙O2 max in severe acute hypoxia: 1) reduction of PIO 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 in V ˙O2 max.