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

Richard J. Gumina, Jo El Schultz, Zhenhai Yao, Dermot Kenny, David C. Warltier, Peter J. Newman, Garrett J. Gross

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Abstract

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 rate (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.

Original languageEnglish (US)
Pages (from-to)3327-3333
Number of pages7
JournalCirculation
Volume94
Issue number12
DOIs
Publication statusPublished - Jan 1 1996

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Keywords

  • endothelium
  • ischemia
  • leukocytes
  • myocardial infarction
  • reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Gumina, R. J., Schultz, J. E., Yao, Z., Kenny, D., Warltier, D. C., Newman, P. J., & Gross, G. J. (1996). Antibody to platelet/endothelial cell adhesion molecule-1 reduces myocardial infarct size in a rat model of ischemia-reperfusion injury. Circulation, 94(12), 3327-3333. https://doi.org/10.1161/01.CIR.94.12.3327