Effects of a monoclonal antibody directed against p-selectin following myocardial ischemia and reperfusion. Lefer, David J., David M. Flynn, 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.
APStracts 2:0293H, 1995.
Neutrophils (PMNs) play a role in tissue injury following ischemia and reperfusion. We investigated the effects of a monoclonal antibody (MAb), PB1.3, directed against P-selectin in an acute model of myocardial ischemia-reperfusion injury. Dogs were subjected to 120 minutes of coronary artery occlusion and 240 minutes of reperfusion. MAb PB1.3 (1 mg/kg), the non-blocking P-selectin antibody, MAb PNB1.6 (1 mg/kg), or saline was administered 5 minutes prior to reperfusion. Dogs treated with saline (n = 7), MAb PB1.3 (n = 7), and MAb PNB1.6 (n = 5) all experienced similar myocardial blood flows during ischemia and treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow. Measurement of myocardial contractility failed to demonstrate any beneficial effects of MAb PB1.3 on postischemic myocardial contractility. However, myocardial necrosis (% of the area-at-risk) was significantly reduced (p &LT 0.01) in dogs receiving MAb PB1.3 (20.8 +/- 4.8%) compared to dogs receiving either normal saline (41.7 +/- 4.5%) or MAb PNB1.6 (46.7 +/- 7.6%). Myocardial myeloperoxidase activity in the ischemic zone was 4.8 +/- 0.6 in the vehicle group and 3.7 +/- 0.5 in the MAb PNB1.6 group compared to 2.0 +/- 0.5 in MAb PB1.3 treated dogs (p &LT 0.01 vs. saline and p &LT 0.05 vs. PNB1.6). In summary, treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow or myocardial contractility. In contrast, P-selectin immunoneutralization reduced PMN accumulation and myocardial tissue injury in a canine model of coronary occlusion and reperfusion. 

Received 10 April 1995; accepted in final form 19 June 1995.
APS Manuscript Number H355-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.