Effects of muscle contraction on cytochrome a,a3 redox state

The relationships among mitochondrial O2 availability, O2 delivery, and lactate formation in exercising skeletal muscle remain unclear. Some data suggest that muscle O2 provision is sufficient at maximal O2 consumption (VO2max) to challenge the concept of a mitochondrial O2 limitation at VO2max. The relationships among VO2, mitochondrial O2 availability, and net lactate production were studied over a wide range of exercise intensities. Using near-infrared spectroscopy, the oxidation-reduction state of cytochrome a,a3 was monitored in the canine gracilis in vivo. Twenty adult dogs were anesthetized with alpha-chloralose, intubated, and mechanically ventilated on room air. Five-minute stimulation periods at rates of 2, 3, 4, 5, 7, 8, 10, or 12 stimuli/s were performed. VO2max generally was achieved at a stimulation rate of 8 stimuli/s; mean VO2max was 0.12 +/- 0.09 (SE) ml.min-1 x g-1. The concentration of oxidized mitochondrial cytochrome a,a3 decreased at all work loads relative to resting state and demonstrated a near-linear relationship with muscle VO2 (r2 = 0.99). Muscle lactate efflux and the lactate-pyruvate ratio also were correlated positively with cytochrome a,a3 reduction, suggesting a common regulatory mechanism coupling the processes of aerobic glycolysis and oxidative phosphorylation. At VO2max, the corresponding cytochrome oxidation was not significantly different from that observed at death. Thus, in the gracilis maximal exercise leads to near-complete reduction of cytochrome a,a3 secondary to deficient O2 provision. We conclude that VO2max is limited primarily by O2 delivery to this muscle and not by other factors limiting mitochondrial ATP production or substrate oxidation.