Effect of ischemic preconditioning on endothelial dysfunction and granulocyte adhesion in isolated guinea-pig hearts...

It has been demonstrated that ischemic preconditioning (IPC) affords protection against the post-ischemic endothelial dysfunction. Here, a hypothesis was tested that IPC, by protecting the endothelium, prevents also the adherence of granulocytes (PMNs) in the post-ischemic heart. Langendorff-perfused guinea-pig hearts were subjected to 30 min ischemia/30 min reperfusion (IR) and peritoneal PMNs were infused between 15 and 25 min of the reperfusion. Acetylcholine (ACh)-induced coronary vasodilatation and nitrite outflow were used to measure endothelial function and coronary flow response to sodium nitroprusside (SNP) served as a measure of endothelium-independent vascular function. The endothelial adherence of PMNs to the coronary microvessels was assessed in histological preparation of the myocardium. In the hearts subjected to IR, ACh-induced vasodilatation and nitrite outflow were reduced by 55% and 69%, respectively, SNP response remained unaltered, and 22% of microvessels were occupied by PMNs, as compared to 2% in the sheam perfused 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 leads to the endothelial dysfunction and to the selectin-mediated PMNs adhesion in the isolated guinea-pig and that IPC attenuates both alterations. We speculate 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.