Impeding O2 unloading in muscle delays oxygen uptake response to exercise onset in humans.

We tested whether the leftward shift of the oxygen dissociation curve of hemoglobin with hyperpnea delays the oxygen uptake (V˙o 2) response to the onset of exercise. Six male subjects performed cycle ergometer exercise at a work rate corresponding to 80% of the ventilatory threshold (VT) V˙o 2 of each individual after 3 min of 20-W cycling under eupnea [control (Con) trial]. A hyperpnea procedure (minute ventilation = 60 l/min) was undertaken for 2 min before and during 80% VT exercise in hypocapnia (Hypo) and normocapnia (Normo) trials. In the Normo trial, the inspired CO2 fraction was 3% to prevent hypocapnia. The subjects completed two repetitions of each trial. To determine the kinetic variables ofV˙o 2 and heart rate (HR) at the onset of exercise, a nonlinear least-squares fitting was applied to the data averaged from two repetitions by a monoexponential model. The end-tidal CO2 partial pressure before the onset of exercise was significantly lower in the Hypo trial than in the Con and Normo trials (22 ± 1 vs. 38 ± 3 and 36 ± 1 mmHg, respectively, P < 0.05). The time constant ofV˙o 2 and HR was significantly longer in the Normo trial (28 ± 7 and 39 ± 18 s, respectively) than in the Con trial (21 ± 7, 34 ± 16 s, respectively, P < 0.05). TheV˙o 2 time constant of the Hypo trial (37 ± 12 s) was significantly longer than that of the Normo trial, although no significant difference in the HR time constant was seen (Hypo, 41 ± 28 s). These findings suggested that respiratory alkalosis delayed the kinetics of oxygen diffusion in active muscle as a result of the leftward shift of the oxygen dissociation curve of hemoglobin. This supports an important role for hemoglobin-O2 offloading in setting the V˙o 2 kinetics at exercise onset.