Cardiac ischemia and endothelial function in the isolated rabbit heart

Abstract Truly effective prevention of reperfusion myocardial damage is precluded in part by a lack of understanding of the earliest events which accompany ischemia. The purpose of this study was to assess the coronary endothelial response to two forms of ischemic injury in an isolated crystalloid perfused rabbit heart. Global cardiac ischemia, confirmed by NADH fluorescence photography, was induced either by mechanically reducing coronary flow by 90% (MRCF, N = 11) or by an infusion of N -formyl-methionyl-leucyl-phenylalanine (fMLP, N = 11), a known stimulus for leukotriene synthesis and coronary vasospasm. Compared with control, MRCF resulted in an increase in effluent concentrations of both prostacyclin (152 ± 22 pg/ml vs 951 ± 214 pg/ml, P P 2 or leukotriene C 4 concentrations. fMLP infusion resulted in an immediate reduction in coronary flow coincident with diffuse myocardial ischemia. In contrast to MRCF, however, fMLP-induced ischemia resulted in a significant but smaller increase in effluent prostacyclin concentration (210 ± 47 pg/ml vs 606 ± .55 pg/ml, P = 0.05) and a marked increase in both thromboxane B 2 (⩽33 ± 4 pg/ml vs 1141 ± 375 pg/ml, P 4 ( P N = 4). We conclude that endothelial response to ischemia varies not only with the magnitude of but also the nature of the initiating stimulus. Thus a truly specific intervention to prevent postischemic reperfusion injury is likely to require therapy tailored to the initiating ischemic stimulus.