Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following ischemia and reperfusion

• Published in: The American journal of physiology Vol. 271; no. 6 Pt 2; p. H2421
• Main Authors: Lefer, D J, Flynn, D M, Anderson, D C, Buda, A J
• Format: Journal Article
• Language: English
• Published: United States 01.12.1996
• Subjects: Animals; Antibodies, Monoclonal - immunology; Arteries - physiopathology; Blood Cell Count; Coronary Circulation; Coronary Vessels - physiopathology; Dogs; Female; Hemodynamics; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - metabolism; Leukocyte Count; Male; Myocardial Ischemia - blood; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Myocardial Reperfusion Injury - pathology; Myocardium - pathology; Necrosis; Neutrophils - pathology; Neutrophils - physiology; P-Selectin - immunology; P-Selectin - metabolism
• ISSN: 0002-9513
• DOI: 10.1152/ajpheart.1996.271.6.H2421

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.