Effect of ischemic preconditioning on endothelial dysfunction and granulocyte adhesion in isolated guinea-pig hearts subjected to ischemia/reperfusion

It has been demonstrated that ischemic preconditioning (IPC) affords protec tion against the post-ischemic endothelial dysfunction. Here, a hypothesis was tested that IPC, by protecting the endothelium, prevents also the adher ence of granulocytes (PMNs) in the post-ischemic heart. Langendorff-perfuse d guinea-pig hearts were subjected to 30 min ischemia/30 min reperfusion (I R) and peritoneal PMNs were infused between 15 and 25 min of the reperfusio n. Acetylcholine (ACh)-induced coronary vasodilatation and nitrite outflow were used to measure endothelial function and coronary flow response to sod ium nitroprusside (SNP) served as a measure of endothelium-independent vasc ular function. The endothelial adherence of PMNs to the coronary microvesse ls was assessed in histological preparation of the myocardium. In the heart s subjected to IR, ACh-induced vasodilatation and nitrite outflow were redu ced by 55% and 69%, respectively, SNP response remained unaltered, and 22% of microvessels were occupied by PMNs, as compared to 2% in the sheam perfu sed hearts. These alterations were attenuated by IPC (3 x 5 min ischemia). A selectin blocker, sulfatide, prevented IR-induced PMNs adherence and did not affect the responses to ACh and SNP. These data demonstrate that IR lea ds to the endothelial dysfunction and to the selectin-mediated PMNs adhesio n in the isolated guinea-pig and that IPC attenuates both alterations. We s peculate that the pro-adhesive effect of IR is secondary to the endothelial injury and that the anti-PMNs action represents a novel cardioprotective, mechanism of IPC.