CD18 ANTIBODY TREATMENT LIMITS EARLY MYOCARDIAL REPERFUSION INJURY AFTER INITIAL LEUKOCYTE DEPOSITION

Following myocardial ischemia, initial reperfusion with whole blood im pairs the recovery of ventricular function, The exact mechanisms under lying early myocardial reperfusion injury are not clear, but leukocyte s play an important role. In this study, we tested if treating the ini tial blood reperfusate with a monoclonal antibody (CL26) against the l eukocyte adhesion protein CD18 would reduce the leukocyte contribution to early reperfusion injury. We reasoned that blocking CD18 would red uce the initial retention of leukocytes in the heart and thereby limit the inflammatory response. Rat hearts were isolated and perfused at c onstant flow with a red cell-rich solution (K2RBC), The perfusate was not recirculated. Baseline measures were made of coronary flow, perfus ion pressure, and ventricular pump function, No-how, normothermic isch emia was induced for 30 min, followed immediately by reperfusion, at t he preischemic flowrate, with diluted whole blood (DWB, treated with e ither vehicle or CL26), Reperfusion was continued with K2RBC for 40 mi n more, during which postischemic measures were made. We found that th e cardiac retention of leukocytes was not significantly different for the two groups, nor were the recoveries of ventricular function, Later in reperfusion (R35), the coronary blood flowrate and the coronary va scular resistances were not different; however, the recoveries of vent ricular pump function were significantly different (+dP/dt @ R35 (%Pre -I): Vehicle: 27 +/- 9% (n = 8); CL26: 51 +/- 6% (n = 7); P < 0.05). A lso, at R35, the voltage required to capture and pace the vehicle-trea ted hearts was significantly greater than the voltage required to pace the CL26 hearts (P < 0.05). Because the coronary flowrate and leukocy te retention were similar for both groups, the improved recovery obser ved in the CL26-treated group was not due to either improved flow or t o reduced leukocyte retention. Rather, the findings suggest that the b eneficial effect of antibody treatment was to attenuate step(s) in the acute inflammatory response that occurred after the initial depositio n of leukocytes in the heart. (C) 1996 Academic Press, Inc.