Antibody to platelet endothelial cell adhesion molecule-1 reduces myocardial infarct size in a rat model of ischemia-reperfusion injury

Background Antibodies to selected neutrophil or endothelial cell adhesion molecules decrease myocardial infarct size in vivo. Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is an immunoglobulin gene superfamily member expressed constitutively on neutrophils and endothelium. F(ab')(2) fragments of antibody against PECAM-1 inhibit transendothelial migration of neutrophils in several in vivo models of acute inflammation. Therefore, we examined the effect of F(ab')(2) fragments of anti-PECAM-1 antibody in a rat model of myocardial infarction. Methods and Results F(ab')(2) fragments of the anti-PECAM-1 antibody SEW16 and control normal rabbit Ige (NRIgG) were administered at 5 mg/kg to male Wistar rats, and the rats were subjected to a 30-minute coronary artery occlusion followed by 2 hours of reperfusion. At the completion of each experiment, the area at risk, infarct size (IS), and myeloperoxidase (MPO) activity were determined. Compared with untreated (n=8; IS, 57+/-5%) or NRIgG-treated (n=10; IS, 62+/-3%) control rats, SEW16-treated rats (n=15; IS, 28.5+/-4%) displayed a 54% decrease in myocardial infarct size (P<.001). Hemodynamic parameters, leukocyte counts, total left ventricular weight, and area-at-risk weights did not differ significantly between the treatment groups. However, measurement of MPO activity revealed that neutrophil accumulation was reduced 83% (NRIgG, 975+/-55 mU/g; SEW16, 167+/-62 mU/g). Conclusions These results demonstrate that blocking PECAM-1 exerts a significant protective effect in a rat model of myocardial ischemia-reperfusion injury via blockade of neutrophil accumulation in the myocardium.