Quantitative analysis of microcirculatory disorders after prolonged ischemia in skeletal muscle

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Abstract
Reperfusion injury following prolonged ischemia is thought to be caused primarily by microvascular failure. The aim of the present study was to investigate whether prophylactic isovolemic hemodilution with Dextran 60 (hct 30%) could improve microvascular perfusion after 4h of pressure-induced ischemia in skeletal muscle. In 28 Syrian golden hamsters (6–8 weeks/60–80 g b. wt.) a dorsal skinfold chamber and permanent arterial and venous catheters were implanted under Nembutal anesthesia (50 mg/kg b. wt.). Following a recovery period of 48 h pressure-induced ischemia was applied to the skeletal muscle within the skinfold chamber by means of a transparent stamp. Quantitative analyses of microhemodynamics were performed in the awake animal prior to and 15 min, 1, 2, 4 and 24 h after ischemia using vital fluorescence microscopy. In non-treated animals, functional capillary density decreased after 4 h of ischemia to 30% of the initial values (P < 0.001); after 24-h reperfusion only 50% of the initially perfused capillaries were reperfused (P < 0.001). The heterogeneity of functional capillary density increased after ischemia to a maximum of 2.19 ± 0.94 as compared to 0.48 ± 0.11 prior to ischemia. Capillary RBC-velocity suffered a marked reduction in the early reperfusion phase and did not recover up to the 24-h observation time. In contrast, prophylactic isovolemic hemodilution was associated with only a small and reversible reduction of functional capillary density after 4-h ischemia. At 24-h reperfusion 90% of the initially perfused capillaries were reperfused. Capillary RBC-velocity was reduced in the early reperfusion phase, but returned to normal values within 24h. Thus, prophylactic isovolemic hemodilution resulted in a marked reduction of microvascular reperfusion failure in skeletal muscle. A hematocrit lower than normal prior to ischemia provides better conditions for capillary reperfusion after prolonged ischemia.