Chronic Alcohol Intake Exacerbates Cardiac Dysfunction After Myocardial Infarction

Yu Liang; Xuewen Xu; Qin Li; Yan Deng; Maodi Xie; Yanyi Zheng; Wei Ou; Qinqin He; Xiaoyan Xu; WeiWu; Tao Li

Disclosures

Alcohol Alcohol. 2020;55(5):524-530. 

In This Article

Abstract and Introduction

Abstract

Aims: Alcohol intake is a risk factor for cardiovascular diseases. This study was designed to investigate whether chronic alcohol intake affects myocardial infarction (MI)-induced cardiac remodeling and heart failure.

Methods: Eight-week-old male C57BL/6 mice were randomly divided into four groups: Sham group (Sham), MI plus drinking water group (MI + Vehicle), and MI plus daily alcohol intake for 6 weeks with or without gavage of additional alcohol every 3 days (MI + Alcohol and MI + Alcohol + G). The MI were induced by permanent left anterior descending (LAD) coronary artery ligation surgery before vehicle or alcohol treatment. The blood alcohol concentration (BAC), cardiac function, release of cardiac enzymes, pathological changes and mitochondrial function were measured.

Results: As expected, supplementation of alcohol in drinking water significantly increased random BAC in mice. Long-term exposure to alcohol further reduced body weight, ejection fraction and fractional shortening in comparison with the MI + Vehicle group. Histopathological data showed that alcohol increased fibrosis in infarct zone, which was well correlated with the functional decline. Also, as compared to the MI + Vehicle group, the adenosine diphosphate-supported respiratory function of freshly isolated cardiac mitochondria was inhibited in the MI + Alcohol + G group. Besides, upon MI-induced cardiac damage, we did not observe further changes in heart weight, cardiomyocyte enlargement in remote zone, exercise capacity, lung edema and the release of cardiac enzyme after chronic alcohol intake.

Conclusions: Our study demonstrated that chronic daily alcohol exposure exacerbated MI-induced cardiac dysfunction, which is related to promoted myocardial fibrosis and inhibited mitochondrial function.

Introduction

Alcohol is the most consumed substance of abuse worldwide. The link between alcohol and heart disease is controversial. Although low to moderate alcohol consumption is reported to have beneficial effects on heart function (Stampfer et al., 2005), chronic heavy alcohol intake may cause cardiac systolic and diastolic dysfunction (Fernández-Solà, 2015; Wang and Ren, 2018). Moreover, alcohol is believed to be a risk factor for hemorrhagic stroke, atrial fibrillation, cardiac remodeling and heart failure (HF) (Rodrigues et al., 2018; Yang et al., 2019).

Myocardial infarction (MI) after acute ischemia is often associated with fibrosis and cardiac remodeling, which ultimately leads to HF (Chew et al., 2018; Swirski and Nahrendorf, 2013). Inhibition of the relaxation of myofilament after MI also causes contractile dysfunction (Hasenfuss and Pieske, 2002), thus the MI heart are unable to pump sufficient blood to meet the peripheral demand for oxygen, leading to a fatal outcome (Hoydal et al., 2018). Patients with MI are advised to limit alcohol consumption, but how alcohol affects this pathophysiologic process is still unclear (Millwood et al., 2019).

Mitochondrion is a double-membrane-bound organelle, providing most of the adenosine triphosphate (ATP) to support cell survival (He et al., 2018). It has been widely reported that mitochondrial dysfunction is involved in the development of HF, serving as a compelling target in HF therapy (Brown et al., 2017). However, the impacts of alcohol on mitochondrial function and the pathogenesis of HF are still poorly understood. In this study, we sought to elucidate the effects of chronic alcohol exposure on heart after MI. Our results demonstrated that alcohol aggravated systolic dysfunction, which is associated with increased fibrosis and inhibited mitochondrial respiratory function.

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