CD18 antibody treatment limits early myocardial reperfusion injury after initial leukocyte deposition

被引:15
作者
McDonagh, PF [1 ]
Wilson, DS [1 ]
Iwamura, H [1 ]
Smith, CW [1 ]
Williams, SK [1 ]
Copeland, JG [1 ]
机构
[1] BAYLOR COLL MED, DEPT MED, LEUKOCYTE BIOL LAB, HOUSTON, TX 77030 USA
关键词
D O I
10.1006/jsre.1996.0320
中图分类号
R61 [外科手术学];
学科分类号
摘要
Following myocardial ischemia, initial reperfusion with whole blood impairs the recovery of ventricular function, The exact mechanisms underlying early myocardial reperfusion injury are not clear, but leukocytes play an important role. In this study, we tested if treating the initial blood reperfusate with a monoclonal antibody (CL26) against the leukocyte adhesion protein CD18 would reduce the leukocyte contribution to early reperfusion injury. We reasoned that blocking CD18 would reduce the initial retention of leukocytes in the heart and thereby limit the inflammatory response. Rat hearts were isolated and perfused at constant flow with a red cell-rich solution (K2RBC), The perfusate was not recirculated. Baseline measures were made of coronary flow, perfusion pressure, and ventricular pump function, No-how, normothermic ischemia was induced for 30 min, followed immediately by reperfusion, at the preischemic flowrate, with diluted whole blood (DWB, treated with either vehicle or CL26), Reperfusion was continued with K2RBC for 40 min more, during which postischemic measures were made. We found that the 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 vascular resistances were not different; however, the recoveries of ventricular pump function were significantly different (+dP/dt @ R35 (%Pre-I): Vehicle: 27 +/- 9% (n = 8); CL26: 51 +/- 6% (n = 7); P < 0.05). Also, at R35, the voltage required to capture and pace the vehicle-treated hearts was significantly greater than the voltage required to pace the CL26 hearts (P < 0.05). Because the coronary flowrate and leukocyte retention were similar for both groups, the improved recovery observed in the CL26-treated group was not due to either improved flow or to reduced leukocyte retention. Rather, the findings suggest that the beneficial effect of antibody treatment was to attenuate step(s) in the acute inflammatory response that occurred after the initial deposition of leukocytes in the heart. (C) 1996 Academic Press, Inc.
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收藏
页码:139 / 149
页数:11
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