Effects Of Tirofiban On The Reperfusion-related No-reflow In Rats With Acute Myocardial Infarction

ObjectiveTo investigate the effects of tirofiban on the no-reflow phenomenon of acutemyocardial infarction (AMI) rats received reperfusion, as well as the underlyingmechanisms.MethodsFifty-six male Sprague-Dawley rats were randomly divided into fourgroups: Sham operation group (Sham), AMI/reperfusion group (AMI/R),Tirofiban group (Tiro) and Tiro+N-nitro-L-arginine group (L-NNA; an endothelialnitric oxide synthase inhibitor). To generate the animal model mimicking theno-reflow phenomenon, the rats first received occlusion of the left anteriordescending coronary artery for60min and then followed by reperfusion for120min. Area of no-reflow, area at risk and area of necrosis were measured bythioflavine S, Evans blue and triphenyl tetrazolium chloride staining,respectively. Haemodynamic function was measured at the end. In themeantime, nitric oxide synthase (NOS) activity was determined by a NOS assaykit. The expression of myocardial endothelial nitric oxide synthase (eNOS),phosphorylated eNOS at ser1177(p-eNOS ser1177) and vascularendothelial–cadherin (VE-cadherin) were determined by western blot. Thedegree of microvascular endothelial injury was observed by electronmicroscopy.ResultsCompared with AMI/R group, tirofiban significantly reduced the no-reflow area and infarct size (all P <0.01). Tirofiban elevated eNOS activity, lesseninducible nitric oxide synthase (iNOS) activity and increased the expression ofSer1177phosphorylated eNOS and VE-cadherin in the ischemic myocardium (allP <0.01). No statistical differences were found in the expression of eNOSamong the four groups. Also, tirofiban improved cardiac function withsignificantly higher levels of left ventricular end systolic pressure, maximumchange rate of left ventricular pressure rise and fall, lower HR and lower level ofleft ventricular end diastolic pressure than those of the AMI/R group (all P <0.05).Whereas, these effects of tirofiban were partially abolished by L-NNA.Conclusions①Tirofiban treatment significantly reduced myocardial no-reflow and infarctarea, improved heart function, by alleviating myocardial microvascular structuraland endothelial dysfunction in the ischemic area.②Tirofiban could induce thephosphorylation of eNOS, increase the activity of eNOS enzyme and enhancesthe production of endothelium-derived NO, leading to the protection of themicrovascular endothelial function. Tirofiban could also increase the content ofVE-cadherin, decrease the structural damage to vascular endothelium, thusreduce no-reflow and finfarct size, suggesting tirofiban-mediated reduction ofmyocardial no-reflow might be related with the protection of microvascularendothelial structure and function.③NOS inhibitor L-NNA can partially eliminatethe effects of tirofiban, suggesting the maintenance of structural and functionalintegrity of microvascular endothelial may related to the increased eNOSactivity.