| Abstrakt: |
Previous studies have demonstrated that monoclonal antibodies (MAbs) that neutralize ICAM-l reduce myocardial necrosis following ischemia and reperfusion, We investigated the effects of a MAb directed against rat ICAM-l (1A29) in a rat model of myocardial reperfusion injury, Isolated, Krebs buffer perfused rat hearts (n=7/group) were subjected to 20min of global ischemia followed by 45min of reperfusion, Forty million human neutrophils (PMNs) and 5 cc of rat plasma were infused into each heart during the first 5min of reperfusion, Immunohistochemical staining of ischemic-reperfused myocardium revealed prominent endothelial ICAM-1 expression and PMN accumulation in coronary arterioles and venules in untreated hearts, In addition, left ventricular developed pressure (LVDP), pressure-rate product (PRP). and coronary flow (CF) were measured at baseline and at 5minute intervals throughout the 45min reperfusion period, When compared to control hearts receiving human PMNs and rat plasma alone, treatment with lA29 1300μg/heart) significantly (p<0.01) enhanced recovery of LVDP after 45min of reperfusion (90.8±12.7% vs. 42.8±5.5%), The recovery of PRP at 45min of reperfusion was 89.7±15.6% in lA29 treated hearts compared to 42.2±5.3% in the control hearts (p<0.02), Furthermore, treatment with 1A29 significantly preserved CF at 45min of reperfusion (73.9±5.3% vs, 48.9±6.9%, P<0.05). Histological analysis of hearts receiving lA29 demonstrated a significant reduction in PMN accumulation, We conclude that inhibition of ICAM-l mediated PMN adhesion in the initial phase of reperfusion significantly attenuates neutrophil induced postischemic myocardial contractile dysfunction. |
