Establishment Of VA-ECMO In Acute Myocardial Infarction Rats And Preliminary Explore The Protective Mechanism

Acute myocardial infarction（AMI）induced cardiogenic shock（CS）remains a leading cause of death in AMI patients.Venoarterial extracorporeal membrane oxygenation（VA-ECMO）as one of the most important mechanical circulatory support（MCS）device which could maintain hemodynamic stability and reduce preload for further percutaneous coronary intervention（PCI）.However,the underlying mechanisms and long-term effects on cardiac functions remain unclear,a small animal model is of great importance for further studies.In this study,AMI was established by left anterior descending（LAD）ligation,and VA-ECMO was established through the right jugular vein for venous drainage and right femoral artery for arterial infusion.Mean arterial pressure（MAP）,arterial blood gas analysis,serum myocardial enzyme level,myocardial infarction area and myocardial histological staining were examined to evaluate the model.To further explore the underlying mechanism,the invasion of inflammatory cells was observed by immunohistochemical staining,the levels of inflammatory factors were detected by ELISA Kit,and the expression of apoptosisrelated proteins were determined by Western Blot.Finally,the effects of VA-ECMO on myocardial fibrosis and cardiac function of AMI rats were evaluated by Masson staining,fibrosis related protein quantification and echocardiography.The main experimental results are as follows: 1.The MAP significantly decreased after 30 minutes of LAD ligation（P<0.01）,but was stabilized by VA-ECMO,with the MAP of the VA-ECMO group between 75-90 mm Hg which is much higher than the AMI group（P<0.01）.In addition,the MAP returned to baseline levels after weaning from VAECMO;2.Serum myocardial enzymes increased significantly after AMI modeling（P<0.001）,but decreased significantly after ECMO support（P<0.01）,ECMO could reduce myocardial injury.TTC staining showed that the infarct size in the ECMO group was also significantly reduced（P<0.05）,and HE staining showed that the pathological injury was alliviated;3.To preliminarily explore its potential mechanism,immunohistochemical staining with MPO and CD68 antibody showed that the invasion of neutrophils（P<0.001）and macrophages（P<0.01）was significantly reduced in the ECMO group,serum levels of inflammatory factors including IL-6（P<0.05）,IL-1β（P<0.01）,and TNFα（P<0.05）were significantly decreased which were detected by ELISA Kit.WB showed that the expression of apoptosis-related proteins including Casepase3,Cle-Casepase3 and Bax was significantly decreased in ECMO group（P<0.05）while anti-apoptotic protein Bcl-2 was significantly increased（P<0.01）;4.Finally,to explore the effects on myocardial fibrosis and cardiac function,after 28 days of survival,Masson staining of myocardial tissue showed decreased myocardial fibrosis size in ECMO group（P<0.001）and expression of fibrosis-related proteins including α-SMA and Collagen-I were significantly increased（P<0.05）.Echocardiography found that ECMO could slow deteriorated cardiac function,significantly increased EF and FS（P<0.001,P<0.05）but significantly decreased EDV and ESV（P<0.05,P<0.01）.Moreover,serum NT-pro BNP was significantly decreased（P<0.001）.In this study,we established VA-ECMO in AMI rats,and found that ECMO could reduce myocardial injury and infarct size.Further exploration of the potential mechanism found that ECMO may reduce myocardial injury by alleviating myocardial inflammation and reducing cardiomyocyte apoptosis.In addition,ECMO could slow the deterioration of cardiac function and reduce the degree of myocardial fibrosis in the long-term survival.