Oxidative capacity interacts with oxygen delivery to determine maximal O(2) uptake in rat skeletal muscles in situ

Based on proportional changes in V(O(2))(,max) with alterations in O(2) delivery, it is widely held that O(2) availability limits V(O(2))(,max). In contrast, reductions in V(O(2))(,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 V(O(2))(,max). 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(O(2))(,max) than seen when performing each intervention independently, demonstrating an interaction between O(2) supply and mitochondrial oxidative capacity in determining V(O(2))(,max). Four groups of animals were studied: two in high O(2) delivery conditions (hindlimb O(2) delivery: 88 +/- 1 micromol O(2) min(-1); mean +/- S.E.M.) and two in moderately reduced O(2) delivery conditions (66 +/- 2 micromol O(2) min(-1)). One group at each level of O(2) delivery was treated with 0.1 microM myxothiazol to reduce mitochondrial oxidative capacity via competitive inhibition of NADH cytochrome c reductase. V(O(2))(,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 micromol O(2) min(-1) (100 g)(-1)). Similarly, V(O(2))(,max) was reduced by 29 % (594 +/- 22 micromol 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(O(2))(,max) was reduced by an additional 18 % (484 +/- 21 micromol 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(O(2))(,max).