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.


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.
Gumina
R J
RJ
Medical College of Wisconsin, Department of Cellular Biology and Anatomy, Milwaukee 53226, USA.
el Schultz
J
J
Yao
Z
Z
Kenny
D
D
Warltier
D C
DC
Newman
P J
PJ
Gross
G J
GJ
D000704:Analysis of Variance; D000818:Animals; D006439:Hemodynamics; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology; D009195:Peroxidase / Q000032:analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D009195:Peroxidase