The Clinical Investigation Of Gradual Reperfusion Therapy Improving Myocardial Ischemia-reperfusion Injury

Background:Acute myocardial infarction is the major cause of death in the world.With the widespread application of thrombolytic therapy,percutaneous transluminal coronary angioplasty and coronary artery bypass graft in the clinic,coronary reperfusion therapy has become established for the management of acute myocardial infarction.Rapid reperfusion of the infarct-related coronary artery is essential in the treatment of acute ST-elevated myocardial infarction (STEMI). Paradoxically, restoration of the infarction-related artery blood flow to thrombolysis in Myocardial Infarction grade 3 can not attenuat furtherly the injury to the myocardium and improve its prognosis as ischemia myocardium has no effective reperfusion.This phenomenon is described as one of the all ischemia-reperfusion injury and the pathophysiological mechanisms are not fully elucidated.The different clinical manifestations of ischemia-reperfusion injury also include myocardial stunning,reperfusion arrhythmia,myocyte death and endothelial-and microvascular dysfunction.Consequently, ischemia-reperfusion injury has become a target for treatmentstrategies aimed at improving ischemia myocardial effective reperfusion and limiting damage secondary to ischemia.A cardioprotective effect of ischemic postconditioning(short repetitive cycles of reperfusion and re-occlusion) through ameliorating the ischemia myocardial effective reperfusion and attenuating myocardial ischemia-reperfusion injury has been demonstrated in all kinds of animal models and in pilot studies on patients with acute STEMI treated with primary percutaneous coronary intervention. However, there are some single-center clinical trial of small sample,so its safety and efficacy need to be further larg sample, multi-center, randomized, controlled clinical trials to be elucidated.For this, in our study, starting from the clinical practice, exprore a remodified postconditioning manner(gradually reperfusion therapy) whether to furtherly improve myocardial ischemia effective reperfusion and the short-term efficacy, thereby appraise it's myocardial protection and the potential clinical application.Objectives:1. Explore the effect of gradual reperfusion therapy on improving coronary flow and myocardial effective perfusion in patients with acute myocardial infarction treated by primary percutaneous coronary intervention by analyzing TIMI (Thrombolysis In Myocardial infarction) flow, TMPG ( TIMI myocardial perfusion grade), MBG(myocardial blush grade), STR(ST segment resolution), the peak value of CK-MB.2. To investigate the in-hospital clinical efficacy of gradual reperfusion therapy in patients with acute myocardial infarction undergoing primary PCI through observing LVEF (Left ventricular ejection fraction), the score index of regional wall motion, the incidence of in-hospital MACE and in-reperfusion MIRI. 3. To evaluate the myocardial protective effects and potential clinical application of gradual reperfusion therapy by analyzing the situation of its myocardial reperfusion and short-term efficacy.Methods:Characters of all subjects: 225 cases with acute myocardial infarction who were performed primary percutaneous coronary intervention between Fabruary, 2008 to March, 2011 and met inclusion criteria were selected, were randomized into two groups: the group of conventional reperfusion(n=117) and the group of gradual reperfusion(n=108).Drug therapy: All patients received aspirin 300mg before the procedure and continued 100mg/day, clopidogrel 600mg and 75mg/day afterwars. During PCI, all patients were gived intravenous unfractionated heparin, made ACT maintain between 200S and 300S. After PCI, lower molecular weight heparin was applied 5 day, Subcutaneous injection, once per 12 hour. All patients in two group conventionally took Satin, Betaloc, ACEI and Nitrate according to the patient's condition.PCI: All patients were undergone standard CAG with Judkins method to identify the IRA. Before stents were implanted to IRA, the conventional reperfusion group applied balloon by conventional method to pre-expand IRA, the gradual reperfusion group by controlling the degree of balloon dilation made IRA blood flow gradually recovery the normal level.Study end points: TIMI grade, TPMG, MBG, STR, LVEF, the score index of regional wall motion and the peak value of CK-MB were studied immediately after PCI. Baseline characteristics, TIMI grade, TPMG, MBG, STR, LVEF, the score index of regional wall motion and the peak value of CK-MB were compared. Incidence of in-hospital MACE and in-reperfusion MIRI were observed in both groups.Results:1. There was no significant difference between the two groups in baseline characteristics, including age, sex, IRA distribution, Drug therapy, the site of infarction, characteristics on admission (P>0.05).2. The rate of reperfusion of the two groups has no significant difference (100% vs 98.3%). The percentage of TIMI3 flow achieved has no significant difference in IRAs after PCI (92.6% vs 89.7%, P>0.05). However, higher percentage of TMPG3 (63.9% vs 39.3%, P<0.05)and MBG3 (66.7% vs 43.6%, P<0.05) of IARS were achieved. 2h After PCI, more patients in the GR group had complete ST-segment resolution (70.8% vs 57.5%, P<0.05). The peak of CK-MB in the CR group significantly increased (219.4±122 vs 360.5±158.9, P<0.05).3. There was no significant difference in the occurrence of in-hospital MACE and the reperfusion arrhythmia. The incidence of transient myocardial stunning (hypotension or slow heart rate) was lower in GR group (23.1% vs 35.7%, P<0.05). Five day to nine day after PCI, the left ventricle ejection fraction was better in the GR group (0.58±0.05 vs 0.45±0.1, P<0.05) and had a high regional wall motion score index (1.4±0.2 vs 1.2±0.1, P<0.05).Conclusion:1. As a modified postcondition, the gradual reperfusion can improve coronary flow and myocardial perfusion.2. Gradual reperfusion therapy in patients with acute myocardial infarction treated by primary percutaneous coronary intervention can make the incidence of MACE during in-hospital downtrend, the mechanism may influence occurrence of transient myocardial stunning , thereby improve cardiac function.3. Gradual reperfusion therapy can improve myocardial reperfusion and short-term efficacy, thereforce it have myocardial protective effect and clinical potential.