Russell T Hepple — Page 2

PubMed2002

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).

Animals↗

PubMed2002

Muscle structural capacity for oxygen flux from capillary to fiber mitochondria.

The concept of major functional resistance to O2 flux at the capillary-fiber interface implies that muscle structural capacity for O2 flux from capillary to fiber mitochondria needs to be assessed in terms of capillary surface per fiber surface. Morphological data support this notion and show the importance of assessing the size of the capillary-fiber interface relative to muscle fiber O2 demand.

Animals↗

PubMed2002

The role of O2 supply in muscle fatigue.

It is well established that altering O2 delivery to contracting skeletal muscle affects human performance. In this respect, a reduced O2 supply (e.g., hypoxia) increases the rate of muscle fatigue, whereas increasing O2 supply (e.g., hyperoxia) reduces the rate of fatigue. Interestingly, the faster onset of fatigue in moderate hypoxia does not appear to be a consequence of mitochondrial O2 limitation because these effects occur at submaximal rates of O2 consumption for these conditions and at O2 tensions well above that which impairs mitochondrial O2 uptake in vitro. Alterations in O2 supply modulate the regulation of cellular respiration and may affect the onset of impaired Ca2+ handling with fatigue. Specifically, changes in O2 supply alter the coupling between phosphocreatine hydrolysis and O2 uptake in contracting muscles, which by determining the rate of inorganic phosphate (Pi) accumulation may affect Ca2+ release. Partial ischemia differs somewhat in that the reduction in force could be due to reduced O2 supply and/or impaired removal of metabolic by-products secondary to insufficient blood flow. Nonetheless, recent evidence shows a parallel decline and restoration of force with alterations in O2 supply but not blood flow alone during submaximal contractions. Furthermore, the causes of fatigue are similar when O2 is plentiful and when it is reduced.

Humans↗