Oxidative capacity interacts with oxygen delivery to determine maximal O2 uptake in rat skeletal muscles in situ

Based on proportional changes in (V)over dot(O2,max) with alterations in O-2 delivery, it is widely held that O-2 availability limits (V)over dot(O2,max). In contrast, reductions in (V)over dot(O2,max) are also seen when mitochondrial oxidative capacity is reduced. Taken collectively, these prior results are consistent with the notion that there is not a single-step limitation to We used a pump-perfused rat hindlimb model to test the hypothesis that combining moderate reductions in O-2 delivery and mitochondrial oxidative capacity would yield a greater reduction in (V)over dot(O2,max) than seen when performing each intervention independently, demonstrating an interaction between O-2 supply and mitochondrial oxidative capacity in determining (V)over dot(O2,max). Four groups of animals were studied: two in high 0, delivery conditions (hindlimb O-2 delivery: 88 I mumol O-2 min(-1); mean S.E.M.) and two in moderately reduced 0, delivery conditions (66 +/- 2 mumol O-2 min(-1)). One group at each level of O-2 delivery was treated with 0.1 muM myxothiazol to reduce mitochondrial oxidative capacity via competitive inhibition of NADH cytochrome c reductase (V)over dot(O2,max) in control animals (no myxothiazol) was 29 % lower in the moderately reduced O-2 delivery group (592 +/- 24 mmol O-2 min(-1) (100 g)(-1)); P < 0.05) than in the high O-2 delivery group (833 +/- 63 mumol O-2 min(-1) (100 g) (-1)). Similarly, (V)over dot(O2,max) was reduced by 29 % (594 +/- 22 mumol O-2 min(-1) (100 g)(-1)); P < 0.05) in myxothiazol-treated animals in high O-2 delivery conditions compared to control animals in high O-2 delivery conditions. When myxothiazol treatment was combined with moderately reduced O-2 delivery, (V)over dot(O2,max) was reduced by an additional 18 % (484 +/- 21 mumol O-2 min(-1) (100 g)(-1)); P < 0.05) compared to either intervention performed independently. These results show that O-2 supply and mitochondrial oxidative capacity interact to determine (V)over dot(O2,max).