Combined inhibition of p-selectin and icam-1 reduces myocardial
injury following ischemia and reperfusion.
Lefer, David J., David M. Flynn, Donald C. Anderson, and Andrew J.
Buda.
Department of Medicine, Cardiology Section, Tulane University
School of Medicine, 1430 Tulane Avenue, SL48, New Orleans, Louisiana
70112, U.S.A. and Discovery Research, The Upjohn Company, 301
Henrietta Street, Kalamazoo, Michigan 49001
APStracts 3:0333H, 1996.
Neutrophil-endothelial cell interactions are mediated by a number of
cell adhesion proteins. We investigated the effects of inhibition of
P-selectin and 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. Following
reperfusion, untreated dogs experienced a 61% decline (p < 0.01
vs. baseline) in myocardial blood flow and a nine-fold 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
signficant coronary vascular and myocardial protection which was not
superior to treatment with the either antibody alone. Thus, the co
-administration of anti-P-selectin and anti-ICAM-1 monoclonal
antibodies does enhance the degree of myocardial protection in this
model of reperfusion injury.
Received 20 April 1995; accepted in final form 28 May 1996.
APS Manuscript Number H377-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996