Structural basis of muscle O(2) diffusing capacity: evidence from muscle function in situ

Although evidence for muscle O(2) diffusion limitation of maximal O(2) uptake has been found in the intact organism and isolated muscle, its relationship to diffusion distance has not been examined. Thus we studied six sets of three purpose-bred littermate dogs (aged 10-12 mo), with 1 dog per litter allocated to each of three groups: control (C), exercise trained for 8 wk (T), or left leg immobilized for 3 wk (I). The left gastrocnemius muscle from each animal was surgically isolated, pump-perfused, and electrically stimulated to peak O(2) uptake at three randomly applied levels of arterial oxygenation [normoxia, arterial PO(2) (Pa(O(2))) 77 +/- 2 (SE) Torr; moderate hypoxia, Pa(O(2)): 33 +/- 1 Torr; and severe hypoxia, Pa(O(2)): 22 +/- 1 Torr]. O(2) delivery (ml. min(-1). 100 g(-1)) was kept constant among groups for each level of oxygenation, with O(2) delivery decreasing with decreasing Pa(O(2)). O(2) extraction (%) was lower in I than T or C for each condition, but calculated muscle O(2) diffusing capacity (Dmus(O(2))) per 100 grams of muscle was not different among groups. After the experiment, the muscle was perfusion fixed in situ, and a sample from the midbelly was processed for microscopy. Immobilized muscle showed a 45% reduction of muscle fiber cross-sectional area (P < 0.05), and a resulting 59% increase in capillary density (P < 0.05) but minimal reduction in capillary-to-fiber ratio (not significant). In contrast, capillarity was not significantly different in T vs. C muscle. The results show that a dramatically increased capillary density (and reduced diffusion distance) after short-term immobilization does not improve Dmus(O(2)) in heavily working skeletal muscle.