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...
Saved in:
Published in | The American journal of physiology Vol. 271; no. 6 Pt 2; p. H2421 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.12.1996
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Summary: | 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. |
---|---|
ISSN: | 0002-9513 |
DOI: | 10.1152/ajpheart.1996.271.6.H2421 |