Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following ischemia and reperfusion.
Neutrophil-endothelial cell interactions are mediated by a number of cell adhesion proteins. We investigated the effects of inhibition of P-selectin and intercellular adhesion molecule-1 (ICAM-1), individually or in combination, in the ischemic-reperfused canine myocardium. Monoclonal antibodies PB1.3 (anti-P-selectin) and CL 18/6 (anti-ICAM-1) were administered to dogs subjected to coronary artery occlusion and reperfusion. After reperfusion, untreated dogs experienced a 61% decline (P < 0.01 vs. baseline) in myocardial blood flow and a ninefold increase in ischemic zone neutrophil accumulation (4.7 +/- 0.9 U/100 mg tissue myeloperoxidase activity). In contrast, PB1.3 and CL 18/6 administered individually preserved myocardial blood flow (11 and 24% decrease from baseline, respectively, both P < 0.01 vs. saline), and significantly attenuated myeloperoxidase activity (1.4 +/- 0.3 and 1.5 +/- 0.26 U/100 mg tissue, respectively, both P < 0.01 vs. saline). PB1.3 and CL 18/6 in combination resulted in significant coronary vascular and myocardial protection that was not superior to treatment with either antibody alone. Thus the coadministration of anti-P-selectin and anti-ICAM-1 monoclonal antibodies does not enhance the degree of myocardial protection in this model of reperfusion injury.
Lefer
D J
DJ
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Flynn
D M
DM
Anderson
D C
DC
Buda
A J
AJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001158:Arteries / Q000503:physiopathology; D001772:Blood Cell Count; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1