The aim of this study was to determine whether the formation of
edema that occurs secondary to the neutrophil-dependent increase in microvascular permeability contributes to the genesis of no-reflow in postischemic skeletal muscle. To address this issue, four experimental approaches were used. In the first group, capillary perfusion was assessed in nonischemic canine gracilis muscles in which interstitial fluid volume was increased to a level similar to that in postischemic muscle. In the second and third groups,
edema formation was prevented in postischemic skeletal muscles by administration of
phalloidin or a hypertonic hyperosmotic saline-
dextran solution (HSD; 7.5% saline-6%
Dextran 70), and the extent of capillary no-reflow was assessed. In the final group of experiments, a
monoclonal antibody (MAb) that binds to the common beta-subunit of the leukocyte
integrin CD11/CD18 (MAb IB4) was administered after the development of postischemic
edema, and capillary perfusion was determined. Formation of
edema in nonischemic preparations and
ischemia-reperfusion (I-R) were associated with marked reduction in the number of patent capillaries per fiber (1.2 +/- 0.1 and 0.4 +/- 0.1, respectively) compared with nonedematous nonischemic controls (2.5 +/- 0.3). Treatment with
phalloidin or HSD prevented
edema formation and attenuated the reduction in the number of patent capillaries per fiber (1.62 +/- 0.2 and 1.71 +/- 0.2, respectively) induced by I-R, whereas administration of MAb IB4 after the formation of
edema in reperfused muscles failed to limit capillary no-reflow (0.5 +/- 0.1 patent capillaries/fiber).(ABSTRACT TRUNCATED AT 250 WORDS)