907-106 A Specific Anti-ICAM Antibody Prevents Neutrophil Mediated Injury in the Postischemic Heart

It has been hypothesized that PMN-mediated reperfusion (R) injury is triggered by increased expression of intracellular adhesion molecule 1, (ICAM1), on the surface of the coronary endothelium follOWing ischemia and reperfusion which in turn triggers CD18-mediated adhesion of circulating neutrophils (PMN) and subsequent postischemic inflammation. In order to evaluate the role of ICAM in the pathogensis of postischemic injury, experiments were performed in an isolated rat heart model perfused with isolated PMNs and plasma. The efficacy of a specific monoclonal antibody (MAb) against ICAM, IA-29 (Upjohn), was studied in hearts subjected to 20min of global ischemia and 45min of R. 3 × 107PMNs and plasma were infused during the first 5 min of R, with or without IA-29 (20mg/ml); N=10/group. Contractile function and PMN retention were measured. This specific anti ICAM-l antibody markedly increased the recovery of contractile function and decreased PMN retention. These experiments demonstrate that a blocking antibody to ICAM-l can be effective in reducing PMN accumulation and subsequent PMN-mediated reperfusion injury. Thus, the use of a MAb against ICAM-l could be an effective therapeutic approach to prevent myocardial reperfusion injury.Summary data of (%) recovery at 45min are shown belowGroupCFLVDPRPPPMNRetentioncontrol13±335±533±559±4%IA-2975±2*76±5*80±6*4±3%*CF=coronary flow, LVDP=left ventricular developed pressure, RPP=rate-pressure product.*p<0.05 vs contro