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 adhes ion molecules decrease myocardial infarct size in vivo. Platelet/endot helial cell adhesion molecule-1 (PECAM-1) is an immunoglobulin gene su perfamily member expressed constitutively on neutrophils and endotheli um. F(ab')(2) fragments of antibody against PECAM-1 inhibit transendot helial migration of neutrophils in several in vivo models of acute inf lammation. Therefore, we examined the effect of F(ab')(2) fragments of anti-PECAM-1 antibody in a rat model of myocardial infarction. Method s and Results F(ab')(2) fragments of the anti-PECAM-1 antibody SEW16 a nd control normal rabbit Ige (NRIgG) were administered at 5 mg/kg to m ale Wistar rats, and the rats were subjected to a 30-minute coronary a rtery occlusion followed by 2 hours of reperfusion. At the completion of each experiment, the area at risk, infarct size (IS), and myelopero xidase (MPO) activity were determined. Compared with untreated (n=8; I S, 57+/-5%) or NRIgG-treated (n=10; IS, 62+/-3%) control rats, SEW16-t reated rats (n=15; IS, 28.5+/-4%) displayed a 54% decrease in myocardi al infarct size (P<.001). Hemodynamic parameters, leukocyte counts, to tal left ventricular weight, and area-at-risk weights did not differ s ignificantly 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 demo nstrate that blocking PECAM-1 exerts a significant protective effect i n a rat model of myocardial ischemia-reperfusion injury via blockade o f neutrophil accumulation in the myocardium.