EFFECTS OF A MONOCLONAL-ANTIBODY DIRECTED AGAINST P-SELECTIN AFTER MYOCARDIAL-ISCHEMIA AND REPERFUSION

Neutrophils (polymorphonuclear leukocytes, PMNs) play a role in tissue injury after 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 subj ected to 120 min of coronary arterial occlusion and 240 min of reperfu sion. MAb PB1.3 (1 mg/kg), the nonblocking P-selectin antibody, MAb PN B1.6 (1 mg/kg), or saline was administered 5 min before reperfusion. D ogs treated with saline (n = 7), MAb PB1.3 (n = 7), and MAb PNB1.6 (n = 5) all experienced similar myocardial blood flows during ischemia, a nd treatment with MAb PB1.3 failed to preserve postischemic myocardial blood flow. Measurement of myocardial contractility failed to demonst rate any beneficial effects of MAb PB1.3 on postischemic myocardial co ntractility. However, myocardial necrosis (% of area at risk) was sign ificantly reduced (P < 0.01) in dogs receiving MAb PB1.3 (20.8 +/- 4.8 %) compared with dogs receiving either normal saline 141.7 +/- 4.5%) o r MAb PNB1.G (46.7 +/- 7.6%). Myocardial myeloperoxidase activity in t he ischemic zone was 4.8 +/- 0.6 in the vehicle group and 3.7 +/- 0.5 in the MAb PNB1.G group compared with 2.0 +/- 0.5 in MAb PB1.3-treated dogs (P < 0.01 vs. saline; P < 0.05 vs. PNB1.6). In summary, treatmen t with MAb PB1.3 failed to preserve postischemic myocardial blood flow or myocardial contractility. In contrast, P-selectin immunoneutraliza tion reduced PMN accumulation and myocardial tissue injury in a canine model of coronary occlusion and reperfusion.