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 c ell 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. Monoc lonal antibodies PB1.3 (anti-P-selectin) and CL 18/6 (anti-ICAM-1) wer e administered to dogs subjected to coronary artery occlusion and repe rfusion. After reperfusion, untreated dogs experienced a 61% decline ( P < 0.01 vs. baseline) in myocardial blood flow and a ninefold increas e in ischemic zone neutrophil accumulation (4.7 +/- 0.9 U/100 mg tissu e myeloperoxidase activity). In contrast, PB1.3 and CL 18/6 administer ed individually preserved myocardial blood flow (11 and 24% decrease f rom baseline, respectively, both P < 0.01 vs. saline), and significant ly 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 myoc ardial protection that was not superior to treatment with either antib ody alone. Thus the coadministration of anti-P-selectin and anti-ICAM- 1 monoclonal antibodies does not enhance the degree of myocardial prot ection in this model of reperfusion injury.