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Effect Of Aldehyde Dehydrogenase 2 Gene Polymorphism On Myocardial Ischemia/Reperfusion Injury In Patients Undergoing Cardiopulmonary Bypass Operation

Posted on:2022-12-12Degree:MasterType:Thesis
Country:ChinaCandidate:X D HuFull Text:PDF
GTID:2494306773954539Subject:Emergency Medicine
Abstract/Summary:PDF Full Text Request
Background Cardiac surgery under cardiopulmonary bypass(CPB)is the primary therapy for various cardiovascular diseases including valve diseases,congenital heart disease and ischemic cardiomyopathy etc.However,myocardium will inevitably suffer from ischemia/reperfusion injury(I/R)under CPB leading to serious perioperative complications and poor long-term survival for the patients with cardiac surgery.With the development of enhanced recovery after surgery and the innovation of cardioprotective strategies and surgical techniques,it have made great improvement in protecting heart against I/R injury after CPB.However,we are still unable to determine the specific mechanisms and factors of I/R injury until now.Acetaldehyde dehydrogenase-2(ALDH2)is not only a key enzyme catalyzing in alcohol metabolism,but also plays an important role in scavenging toxic aldehyde in the body.Reactive aldehyde,as the breakdown products from lipid peroxidation,are thought to be involved in the development of I/R injury,ischemic cardiomyopathy and chronic heart failure etc.Previous studies have showed that impaired ALDH2 enzyme activity resulting in aldehyde accumulation will aggravate the pathological process of I/R injury.One major reasons for the impairment of ALDH2 acticity is genetic deficiency which is found in more than 30% of the Asian population.At present,ALDH2 has been widely reported in basic research on myocardial I/R injury,but clinical studies are still scarce.Therefore,to investigate the effect of ALDH2 gene polymorphism on myocardial I/R Injury in patients undergoing CPB will contribute an important role in improving peiroperative outcomes and long-term survival after cardiac surgery.Methods Patients with scheduled cardiac surgery under CPB,as well as gender neutral and more than 18 years of age,were included in the study.Blood samples were harvested for detecting ALDH2 genotypes.Patients were divided into two groups:Wildtype(G/G)and Mutation(G/A and A/A)group according to the genotyping of ALDH2.Demograpgics and clinical characteristics,ecocardiographic parameters and serum biochemicals were collected in the preoperative.Hemodynamics parameters,inotropic score(IS),operation and anesthesia time,CPB time,aortic cross-clamp time,mechanical ventilation time,ICU time,hospitalization time and the levels of lactic acid(Lac)troponin I(c Tn I)and atrial urinary natriuretic peptide(BNP)were monitored in intro-and post-operation.Perioperative complications including stroke and acute myocardial infarction were recored in the study.Cardaic function and all-cause mortality rate had 30 days follow-up.Generalized linear model analysis was used to explore the c Tn I and BNP.Results Total of 91 patients were included in this study,with 47 in the wildtype group and 44 in the mutant group.No differences were observed from the baseline characteristics including age,BMI,echocardiography parametetrs and serum biochemicals between mutant and wildtype group(P > 0.05).However,there was a significant difference in gender distribution which 27 male patients with the percentage of 61.4% were confirmed in the mutant group,but only 18 male patients(38.3%)in the wildtype group(P<0.05).Operation related parameters,such as CPB time,ACC time,anesthesia time and operation time,were no different in the two groups(P >0.05).Patients with ALDH2 deficiency showed similar levels of c Tn I at 24 h of reperfusion compared with wildtype gourp(3.18[1.89-4.65] vs.3.62[2.11-6.66] ng/L,P=0.210).No differences were observed in Lac,IS,hemodynamic parameters and BNP in the two groups(P > 0.05).Compared with the wild group,There was no significantly changing in mechanical ventilation time(14.5[7.4-20.3] vs.16.5[6.0-23.0],P=0.642),ICU time(62.0[42.0-92.0] vs.67.0 [43.0-115.3],P=0.511)and hospitalization time(24.0[19.3-32.8] vs.25.0[18.0-35.0],P=0.905)between the two groups.Patients with ALDH2 deficiency showed much higher incidence of acute kidney injury at 43.18% compared with 27.66% in wildtype group,but there was no significant difference(P>0.05).Cardiovascular complications had no difference between the two groups.After 30 days follow-up,all patients are survival in wildtype group,but two patients(4.5%)died in the mutation group with no significant difference(P=0.231).Patients in the mutation group showed similar LVEF values compared with wildtype group(57.7±6.7% vs.56.2±9.7%,P=0.435).Conclusion Patients with ALDH2 deficiency didn’t show severe myocardial injury,and shared similar clinical performance and 30 days follow-up results with wildtype after CPB operation.
Keywords/Search Tags:Acetaldehyde dehydrogenase-2, Ischemia/Reperfusion injury, Cardiopulmonary bypass
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