Cardioprotective actions of a monoclonal antibody against CD-18 in myocardial ischemia-reperfusion injury

Abstract

Background. Previous studies have demonstrated that polymorphonuclear leukocytes (PMNs) are locally activated in reperfused myocardium and contribute to the myocardial cell injury associated with reperfusion. It has been suggested that the adhesion of activated PMNs in reperfused myocardium is mediated by the PMN adhesion molecule CD-18. In the present study, we performed experiments to determine if the specific anti-CD-18 monoclonal antibody (MAb) R15.7 can prevent PMN adhesion and PMN-mediated reperfusion injury in the heart. Methods and Results. Studies were performed with isolated, Langendorff-perfused rat hearts (nine per group) in which the hearts were subjected to 20 minutes of global ischemia followed by 45 minutes of reperfusion. Human PMNs (50 million) and rat plasma (HNRP) were infused directly into the coronary circulation of nonischemic and postischemic hearts. When HNRP was administered to nonischemic hearts, no significant alterations in coronary flow, left ventricular developed pressure, or left ventricular end-diastolic pressure were observed. When hearts were reperfused in the presence of HNRP, however, marked impairment of contractile function was observed with more than 90% reduction in coronary flow throughout the reperfusion period (P