Neutrophil Accumulation and Infarct Size After Ischemia and Reperfusion in Dogs

Background. Polymorphonuclear neutrophils (PMNs) accumulate in postischemic myocardium and may cause injury to myocardium or to vessels by production of oxygen free radicals or by release of proteases and lipases. PMN accumulation is dependent on adherence to endothelium, which is mediated by a family of glycoproteins on the PMN surface, each of which has a common f-subunit (CD18). The purpose of this study was to determine whether an antibody (IB4) against the CD18 protein could attenuate PMN accumulation and limit myocardial infarct size. Methods and Results. F(ab')2 fragments of a mouse monoclonal antibody to human adherence-promoting leukocyte glycoprotein (CD18) were used. Infarct size after 90 minutes of ischemia and 3 hours of reperfusion was compared in dogs with (n=8) and without (n=8) the anti-CD18 treatment. Myocardial PMN accumulation was assessed with '`1In-labeled autologous PMNs. Anti-CD18 treatment significantly reduced the number of PMNs in the ischemic region (19,123±5,352/mg versus 5,204±927/mg in the control and treated groups, respectively; p<O.OS). In addition, the ratio of myocardial blood flow (ischemic/nonischemic wall) at 45 minutes into reperfusion was higher in the treated than in the control