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

Gumina RJ, el Schultz J, Yao Z, Kenny D, Warltier DC, Newman PJ, Gross GJ
Circulation. 1996 94 (12): 3327-33

PMID: 8989147 · DOI:10.1161/01.cir.94.12.3327

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.

MeSH Terms (15)

Analysis of Variance Animals Hemodynamics Humans Immunoglobulin Fab Fragments Immunoglobulin G Leukocytes Male Myocardial Infarction Myocardial Reperfusion Injury Peroxidase Platelet Endothelial Cell Adhesion Molecule-1 Rabbits Rats Rats, Wistar

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