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 relationshi p 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 a llocated 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 stimu lated to peak O-2 uptake at three randomly applied levels of arterial oxyge nation [normoxia, arterial PO2 (PaO2)77 +/- 2 (SE) Torr; moderate hypoxia, PaO2: 33 +/- 1 Torr; and severe hypoxia, PaO2: 22 +/- 1 Torr]. O-2 delivery (ml.min(-1).100g(-1)) was kept constant among groups for each level of oxy genation, with O-2 delivery decreasing with decreasing PaO2. O-2 extraction (%) was lower in I than T or C for each condition, but calculated muscle O -2 diffusing capacity (DmusO(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 m uscle 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, capi llarity was not significantly different in T vs. C muscle. The results show that a dramatically increased capillary density (and reduced diffusion dis tance) after short-term immobilization does not improve Dmus(O2) in heavily working skeletal muscle.