| Myocardial ischemia-reperfusion injury is common in clinic and its pathogenesis that is mainly related to inflammation, intracellular Ca2+-overload and energy metabolism is complicated. Recently neutrophil infiltration has been implicated as a key mediator in the pathogenesis of myocardial ischemia-reperfusion injury. Inhibition of neutrophil infiltration has significantly alleviated myocardial ischemia-reperfusion injury, which shows anti-neutrophil therapy will be an effective method in prevention and treatment of myocardial ischemia-reperfusion injury. Producing a rabbit myocardial ischemia-reperfusion model in this study, we observed changes of the myocardial infarct size, myocardial enzymes and neutrophil infiltration in the myocardium, in order to investigate the cardioprotection of recombinant hirudin (r-hirudin) and its protective mechanism against myocardial ischemia-reperfusion injury and to provide a new way in treatmentof ischemic heart disease and some directions in the administration of r-hirudin in clinic.Objective:1. To produce the myocardial ischemia-reperfusion model by reversibly ligating and releasing the coronary artery in rabbits after thoracotomy.2. To compare changes in the cardiac function, levels of myocardial enzymes, infarct size, area at risk, and neutrophil infiltration in ischemic cardiac tissues in r-hirudin group with those in control group.3. To investigate the cardioprotection of r-hirudin and its protective mechanism against myocardial ischemia-reperfusion injury in rabbits.Methods:A total of 28 rabbits were randomly divided into r- hirudin group (n=14) and control group (w=14). (I) In r-hirudin group the left anterior descending coronary artery was occluded for 45 min followed by 120 min reperfusion. And r-hirudin treatment began with the intravenous administration of lmg/kg bolus 15 min before reperfusion and continued with an intravenous infusion of 1mg/kg/h for 120 min following reperfusion. (II) In control group, the operation on rabbits was the same as r-hirudin group and equal saline was infused 15 min before reperfusion and during reperfusion. The following indexes were measured:(l) Measurement of left ventricular end dilated pressure (LVEDP) and left ventricular peak systolic pressure (LVPSP) 15 min beforeischemia, 45 min after ischemia and 120 min after reperfusion. (2) Measurement of plasma levels of creatine kinase (CK) and lacate dehydrogenase (LDH) 15 min before ischemia, 45 min after ischemia and 120 min after reperfusion. (3) Determination of infarct size and area at risk at the completion of the 120-minute reperfusion period. (4) Count of the number of neutrophils in ischemic myocardial tissues under light microscope.Results:1.The animal model of myocardial ischemia-reperfusion was successfully produced by reversibly ligating and releasing the coronary artery in rabbits. At the completion of the 120-minute reperfusion period, we dyed the myocardium with evans blue dye and observed the normal ventricular myocardium was blue and the myocardium of the ventricle at risk for injury was non-blue. Then we dyed the area at risk with triphenyltetrazolium chloride (TTC). TTC stained the viable tissue into brick red, leaving the necrotic area pale white. The levels of plasma CK and LDH in control group significantly increased during myocardial ischemia-reperfusion, and moreover, levels of CK and LDH at 120 min after reperfusion further increased in comparison with those at 45 min after ischemia (P <0.05).2.Compared with control group, the infiltration of neutrophils in ischemic cardiac tissues, the infarct size, and the levels of plasma CK and LDH in r-hirudin group decreased significantly, alleviating the myocardial reperfusion injury and improving the cardiac function (P <0.05). But there was no significantdifference in the area at risk between r-hirudin group and control group (P >0.05).Conclusion:1.The animal model of myocardial ischemia-reperfusion is successfully produced, which provides the pract...
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