CD18-dependent adherence reactions play an important role in the development of the no-reflow phenomenon

The aim of this study was to determine whether immunoneutralization of the common beta-subunit of the neutrophil CD11/CD18 glycoprotein adherence complex with monoclonal antibody IB4 (mAb IB4) or neutrophil depletion with a specific canine polyclonal antineutrophil serum (ANS) would reduce the extent of no-reflow in postischemic skeletal muscle. Microvascular patency was assessed by infusion of india ink contrast media and quantified by counting ink-containing microvessels < 15 microns diameter in histological sections obtained from isolated canine gracilis muscles subjected to 4.5 h of continuous perfusion (nonischemic control), 4 h of ischemia and 30 min of reperfusion [ischemia/reperfusion (I/R)] alone, I/R plus ANS, and I/R plus mAb IB4. I/R was associated with a marked reduction in microvascular patency compared with nonischemic controls (0.9 +/- 0.1 vs. 2.3 +/- 0.1 ink-containing microvessels per muscle fiber, respectively). Neutrophil depletion or prevention of neutrophil adherence attenuated the I/R-induced reduction in the number of ink-containing capillaries (1.6 +/- 0.1 and 2.2 +/- 0.2 ink-containing microvessels per muscle fiber, respectively). These data indicate that neutrophils play an important role in the genesis of no-reflow in postischemic skeletal muscle by a mechanism that appears to involve CD18-dependent neutrophil adhesion to the endothelium.