The Effects Of Two Different Anesthesia Methods On Myocardial Ischmia Reperfusion Injury In Pigs

Background:Myocardial ischemia-reperfusion injury?MIRI?is a series of complex pathophysiological processes defined as the myocardial dysfunction and myocardial cell injury,which is caused by coronary repatency and myocardial reperfusion.It brings damages to myocardial infarction patients again.Thus,reducing intraoperative reperfusion injury has become a hot research topic.In recent years,studies have shown that some conventional anesthetics used in surgery can alleviate reperfusion injury,but the mechanisms remain unknown.Therefore,there is an urgent requirement for seeking an ideal anesthetic scheme and exploring its potential mechanisms.Objective:The paper aims to study the effect oftotal intravenous anesthesia?IV?and combined intravenous inhalational anesthesia?IA?on the hemodynamics,blood gas analysis,biochemical parameters,myocardial infarction markers,echocardiogram and myocardial infarct area of Bama miniature pigs with myocardial ischemia reperfusion and to make a prelimanary discussion on the mechanisms of the two different anesthetic methods on MIRI.Methods:Thoracotomy-left anterior descending coronary artery ligation at the third of cardiac apex was used to establish a Bama miniature pig model of myocardial ischemia-reperfusion.Thirty Bama miniature pigs were at random allocated into 2 groups,namely the IV group and the IA group with 15 pigs in each group.The IV group was induced with propofol,sufentanil and vecuronium,followed by endotracheal intubation and maintained anesthesia with remifentanil and dexmedetomidine.The IA group was anesthetized with sevoflurane inhalational anesthesia based on IV group.The vital signs of these pigs were monitored in the whole process of experiment.The determination of hemodynamics,blood gas analysis,biochemical parameters,myocardial infarction markers,SOD,MDA and ROS of myocardial tissue,echocardiography and myocardial infarct size in each group were carried out to compare the effects of IV and IA on myocardial injury.Based on the ROS theory,calcium overload theory,inflammatory mediator theory and cell apoptosis,the mechanisms of MIRI and the relations between anesthesia methods and MIRI injury were preliminarily discussed,the content of NO,the catalase in myocardial tissues,intracytoplasmic Ca²⁺in myocardial cells,inflammatory factors at the different stages,and the protein expression of Caspase-3,Bax and Bcl-2 of pigs in the two groups were determined during the establishing of the myocardial ischemia reperfusion model.Results:The results of two different anesthesia methods indicated that the 30 pigs models of myocardial ischemia reperfusion were made successfully regardless of using IV or IA methods without ventricular fibrillation or death happened in surgery.After 6 hours,the myocardial infarct area of these experimental pigs was calculated and analyzed,which showed that the myocardial infarct area existed and was up to 25%to 38%after modeling.2.The hemodynamic changes of IVgroup were greater than those of IA group,and the value of HR,MAP and CVP were obviously abnormal compared with those of the IA group after ischemia for 1 h and reperfusion for 60 min and 120 min.3.The results of blood gas monitoring test showed that the PaO2 and PaCO2 values in IA group changed slowly before and after ischemia,which is in a stable state.While,the PaO₂ and PaCO₂ values of IV group after ischemia for 1 h and reperfusion for 30 min,60 min and 120 min had a statistically significant difference?P<0.05?compared with the normal values before surgery.4.The biochemical markers of CK-MB,LDH,ALT/GPT,AST/GOT in IV group were more abnormal.5.cTnI in IA group had a statistical difference?P<0.05?compared with that in IV group after ischemia for 1 h and reperfusion for3 h?I1hR3h?and after ischemia for 1 h and reperfusion for 6 h?I1hR6h?.6.The oxidation index of myocardial tissue showed that the SOD and ROS values of IV group decreased significantly compared with the normal level with statistical difference?P<0.05?,while the MDA value increased significantly with statistical difference?P<0.05?.Although the values of SOD,MDA and ROS all changed in the IA group,there was no significant difference compared with the normal level?P>0.05?.7.Echocardiogram indicated that after ischemia-reperfusion for 2 weeks,the myocardial activity,its motion amplitude,left ventricular ejection fraction?EF?and fractional shortening?FS?in IV group obviously decreased compared with those in IA group with statistical significant difference?P<0.05?.8.The infarct area measured by TTC staining showed that the area of myocardial infarction in IA group was obviously less than that in IV group and had a statistical significance?P<0.05?.The results of MIRI mechanisms showed that after 6 h-reperfusion,the NO content in myocardial tissue of pigs in IV group had a statistical significance?P<0.05?compared with its normal value.The NO content in myocardial tissue of IA group after 6-h reperfusion had a statistical significance?P<0.05?compared with its normal value.There was a statistical significance?P<0.05?between NO content in myocardial tissue of pigs of IV after 6-h reperfusion and that of IA group.2.The catalase content in pigs of both IV and IA groups had significantly decreased after 6-h reperfusion with a statistical significance?P<0.05?compared with its normal value.There was a statistical significance?P<0.05?between the catalase content in myocardial tissue of pigs of TIVA group and that of IA group.3.The contents of intracytoplasmic Ca²⁺in cardiocytes of the two group pigs were increased constantly after ligation and after reperfusion.The contents of intracytoplasmic Ca²⁺in TIVA group and IA group had a statistical significance?P<0.05?compared with the normal values after 6-h reperfusion.While the contents of intracytoplasmic Ca²⁺in cardiocytes had no statistical significance?P>0.05?both in IV group and IA group after 1-h ischemia and reperfusion for 6h.4.The levels of IL-6,IL-1?,TNF-?and the inflammatory factors in IV group had a statistical significance?P<0.05?after ischemia for 1h-reperfusion for 1h,3h and6h compared with their normal values.The levels of IL-6,IL-1?,TNF-?and the inflammatory factors both in IV and IA groups had a statistical significance?P<0.05?after ischemia for 1h-reperfusion for 3h and 6h.The levels of IL-6,IL-1?,TNF-?and the inflammatory factors in IA group had a statistical significance?P<0.01?after ischemia for 1h-reperfusion for 3h and6hcompared with their normal values.5.The protein expression of Caspase-3,Bax,Bcl-2 in IV group after ischemia for 1h-reperfusion for 1h,3h and 6hhad a statistical significance?P<0.05?compared with the normal values.the protein expression of Caspase-3,Bax,Bcl-2after ischemia for 1 h-reperfusion for 1h,3h and 6h between IV and IA groups had a statistical significance?P<0.05?.And the protein expression of Caspase-3,Bax,Bcl-2 in IA group after ischemia for 1 h-reperfusion for 1h,3h and 6hhada statistical significance?P<0.05?compared with the normal values.Conclusions:1.The Bama miniature pig myocardial ischemia-reperfusion model can be established successfully by IV or IA in thoracotomy-left anterior descending coronary artery ligation.The MIRI model has the characteristics of stability,operability and replicability,etc.2.The IA method can effectively reduce the degree of MIRI.3.Compared with IV,IV can effectively reduce the release of free radicals,Ca²⁺fluxes,the release of serum inflammatory mediators and the cardiomyocyte apoptosis.