The Effect Mechanism Of Chronic Ethanol Intake On Heart Failure In Mice

Objective:To investigate the functional effects of chronic ethanol(EtOH)intake on ischemic heart failure(HF)caused by myocardial infarction(MI)and pressure overload HF caused by transverse aortic constriction(TAC).Materials and Methods:(1)The effect of chronic EtOH intake on cardiac function of mice after MI.Eight-week old male C57BL/6 mice were randomly divided into 4 groups: Sham group,MI group,MI plus daily ethanol intake for 6 weeks with or without gavage of additional ethanol every 3 days,the cardiac function and exercise tolerance were evaluated,pathological changes and mitochondrial function were also quantified.(2)The effect of chronic EtOH intake on cardiac function of mice after TAC.Eight-week old male C57 BL / 6 mice were randomly divided into 4 groups: sham group,TAC group,TAC plus daily EtOH intake for 8 weeks with or without gavage of additional EtOH every 3 days,the cardiac function and exercise tolerance of the mice under the above treatment were evaluated,and the histologic changes of cardiomyocytes were also detected;(3)The effect of EtOH on mitochondrial oxidative stress of cardiomyocytes under hypertrophy.The cell model of hypertrophy was replicated and the H9C2 cells were divided into 4 groups: control group,isoproterenol group,50 mM EtOH group,200 mM EtOH group.The levels of total oxidative stress and mitochondrial oxidative stress in cardiomyocytes were evaluated.Results:(1)Part 1: Compared to the Vehicle group,daily EtOH intake significantly decreased the in vivo cardiac function of mice subjected to MI,as evidenced by a remarkable reduction of ejection fraction(EF)(Vehicle vs EtOH,P < 0.01).Histological results showed that EtOH intake prompted fibrosis and hypertrophy in mice subject to MI(Vehicle vs EtOH,P < 0.001).We also found that EtOH significantly inhibitedmitochondrial complex II-dependent mitochondrial respiration(Vehicle vs EtOH + G,P< 0.05).(2)Part 2: EtOH did not aggravate the in vivo cardiac function in mice after TAC(Vehicle vs EtOH,P > 0.05,Vehicle vs EtOH+G,P > 0.05),and the postoperative exercise tolerance of mice was not changed by EtOH(Vehicle vs EtOH,P > 0.05,Vehicle vs EtOH+G,P > 0.05).(3)Part 3: EtOH up-regulated the total oxidative stress level and mitochondrial oxidative stress level of H9C2 cells under hypertrophy(Vehicle vs EtOH,P < 0.05).Conclusion:This study confirmed that daily EtOH intake aggravates cardiac dysfunction of mice with hypoxic heart failure by increasing mitochondrial oxidative stress,inhibiting mitochondrial complex II-dependent mitochondrial respiration,and promoting cardiomyocyte fibrosis and hypertrophy,while there is no significant effect of EtOH on cardiac function in mice with pressure overload heart failure.