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(Circulation. 1996;94:3327-3333.)
© 1996 American Heart Association, Inc.
Articles |
Antibody to Platelet/Endothelial Cell Adhesion Molecule-1 Reduces Myocardial Infarct Size in a Rat Model of Ischemia-Reperfusion Injury
the Medical College of Wisconsin, Departments of Cellular Biology and Anatomy (R.J.G., P.J.N.), Pharmacology (J.E.S., Z.Y., D.C.W., G.J.G, P.J.N.), Anesthesiology (D.C.W.), and Medicine, Division of Cardiology (D.K., D.C.W.), and the Blood Research Institute, the Blood Center of Southeastern Wisconsin (R.J.G., D.K., P.J.N.).
Correspondence to Garrett J. Gross, PhD, Department of Pharmacology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail gjgross@post.its.mcw.edu.
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 IgG (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.
Key Words: endothelium • ischemia • leukocytes • reperfusion • myocardial infarction
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