MICROVASCULAR RESPONSE TO ISCHEMIA, AND TISSUE STRUCTURE, IN NORMAL AND ATROPHIED SKELETAL-MUSCLE

The objective of this study was to explain why the normally observed reactive hyperemia in frog sartorius muscle following ischemia is absent when this muscle atrophies. Two possibilities were addressed: (1) absence is due to lowered O2 consumption, making the muscle more tolerant to ischemia, and (2) absence is linked to impaired vascular function in atrophy. We used 10 frogs after 2-3 months and 8 frogs after 7-14 months of laboratory captivity. Animals in the latter group had a significantly lower sartorius muscle weight, i.e., 85 ± 33 vs 24 ± 11 SD mg. Using intravital video microscopy, we measured red cell velocity in capillaries at the muscle surface, and densities of capillaries with moving (NCPER) and stationary red cells (NCSTAT) before and after 30 min ischemia. Ischemia induced a significant temporary increase in overall velocity (from 0.10 to 0.27 mm/sec) in normal muscles, but no increase in atrophied muscles. It resulted in no difference in NCPER between the two groups (preischemic levels in both groups: 15.0 cap/mm of test line), but in a significant difference in NCSTAT (3.8 vs 11.5 cap/mm in atrophy). Using light and electron microscopy, we also measured structural and ultrastructural parameters in both groups. In atrophied muscles the mean fiber cross-sectional area was lower (568 vs 1935 μm2) and anatomical capillary density higher (892 vs 282 cap/mm2) than in normal muscles. Mitochondrial volume density was not statistically different from the 1.5% level in the normal muscle, while the lipid droplet volume density was larger (2.33 vs 0.58%). The percentage of capillaries with damaged endothelium was larger (33.5 vs 12.6%). Using histology, the white cell volume density per capillary volume was also found to be larger in atrophy (1.96 vs 0.83%). From the discrepancy between the lack of intergroup difference in preischemic NCPER and the 3.2-fold difference in anatomical capillary density we estimate that about 60% of capillaries were perfused with red cells in atrophied muscles. Although the preischemic rate of perfusion in these capillaries was comparable between the two groups, the postischemic response was not: reactive hyperemia was absent in atrophy. Our mitochondrial and lipid volume density data do not support the possibility that this absence was due to lowered O2 consumption, as these densities did not decrease with atrophy. Recent literature reports show a close relationship between (i) impaired vascular smooth muscle function and loss of endothelial integrity, and (ii) white cell trapping in capillaries and poor postischemic flow. On the basis of these reports and on our own observation that endothelial damage, incidence of white cells in capillaries and postischemic NCSTAT increased in atrophy, we propose that the lack of response could reflect an impaired vascular function (both at the arteriolar and at the capillary level) due to deterioration of endothelium during atrophy. © 1990.