Effects of tirofiban on the reperfusion-related no-reflow in rats with acute myocardial infarction

Objective To investigate the effects of tirofiban on the no-reflow phenomenon of acute myocardial infarction (AMI) rats received reperfusion, as well as the underlying mechanisms. Methods Fifty-six male Sprague-Dawley rats were randomly divided into four groups: Sham operation group (Sham), AMI/reperfusion group (AMI/R), Tirofiban group (Tiro) and Tiro+N-nitro-L-arginine group (L-NNA; an endothelial nitric oxide synthase inhibitor). To generate the animal model mimicking the no-reflow phenomenon, the rats first received occlusion of the left anterior descending coronary artery for 60 min and then followed by reperfusion for 120 min. Area of no-reflow, area at risk and area of necrosis were measured by thioflavine S, Evans blue and triphenyl tetrazolium chloride staining, respectively. Haemodynamic function was measured at the end. In the meantime, nitric oxide synthase (NOS) activity was determined by a NOS assay kit. The expression of myocardial endothelial nitric oxide synthase (eNOS) was determined by an enzyme-linked immunosorbent assay (ELISA). The expression of phosphorylated eNOS at ser sup>1177 (p-eNOS ser1177) and vascular endothelial-cadherin (VE-cadherin) were determined by western blot. Results Compared with AMI/R group, tirofiban significantly reduced the no-reflow area and infarct size (all P 1177 phosphorylated eNOS and VE-cadherin in the ischemic myocardium (all P P Conclusions Tirofiban could reduce the size of no-reflow and infarct. A possible mechanism underlying this effect is that tirofiban could protect the structural and functional integrity of microvascular endothelium which is partially regulated by eNOS activity.