Ethanol acutely and reversibly suppresses excitation-contraction coupling in cardiac myocytes.

Danziger, Robert S.; Sakai, Makoto; Capogrossi, M. C.; Spurgeon, Harold A.; Hansford, Richard G.; Lakatta, Edward G.

doi:10.1161/01.res.68.6.1660

Cited by 93 publications

(72 citation statements)

References 32 publications

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“…The hallmarks of alcoholic cardiomyopathy are altered cardiac contractile function and impaired intracellular Ca 2ϩ mobilization such as decreased SR Ca 2ϩ function, which may underlie the altered cardiac mechanics (2,3,8,24,29,30). It is postulated that inhibition by ethanol of Ca 2ϩ regulatory proteins such as Ca 2ϩ pumps and channels may play a role in the decreased cytosolic Ca 2ϩ concentration.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes

Duan¹,

McFadden²,

Borgerding

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes. Am J Physiol Heart Circ Physiol 282: H1216-H1222, 2002. First published December 13, 2001; 10.1152/ajpheart.00780.2001.-Alcoholic cardiomyopathy is characterized by impaired ventricular function although its toxic mechanism is unclear. This study examined the impact of cardiac overexpression of alcohol dehydrogenase (ADH), which oxidizes ethanol into acetaldehyde (ACA), on ethanol-induced cardiac contractile defect. Mechanical and intracellular Ca 2ϩ properties were evaluated in ventricular myocytes from ADH transgenic and wild-type (FVB) mice. ACA production was assessed by gas chromatography. ADH myocytes exhibited similar mechanical properties but a higher efficiency to convert ACA compared with FVB myocytes. Acute exposure to ethanol depressed cell shortening and intracellular Ca 2ϩ in the FVB group with maximal inhibitions of 23.3% and 23.4%, respectively. Strikingly, the ethanol-induced depression on cell shortening and intracellular Ca 2ϩ was significantly augmented in the ADH group, with maximal inhibitions of 43.7% and 40.6%, respectively. Pretreatment with the ADH inhibitor 4-methylpyrazole (4-MP) or the aldehyde dehydrogenase inhibitor cyanamide prevented or augmented the ethanol-induced inhibition, respectively, in the ADH but not the FVB group. The ADH transgene also substantiated the ethanol-induced inhibition of maximal velocity of shortening/relengthening and unmasked an ethanol-induced prolongation of the duration of shortening/relengthening, which was abolished by 4-MP. These data suggest that elevated cardiac ACA exposure due to enhanced ADH expression may play an important role in the development of alcoholic cardiomyopathy. transgene; acetaldehyde; shortening; intracellular calcium ion transient CHRONIC ALCOHOLISM causes heart muscle damage leading to the onset of alcoholic cardiomyopathy, which accounts for ϳ33% of dilated cardiomyopathy (6). The incidence of cardiomyopathy is increased up to 50% in patients with chronic alcoholism, and a high proportion of these patients die from cardiac disease. Alcoholic cardiomyopathy is manifested by cardiomegaly, disruptions of the myofibrillary architecture, reduced myocardial contractility, decreased ejection volumes, and enhanced risk of stroke and hypertension (21,27). Clinical studies indicate that alcoholic cardiomyopathy can be reversed by abstinence from alcohol before its progression beyond a certain, as yet poorly defined, point of severity. Diagnosis of alcoholic cardiomyopathy is often made on the basis of deteriorating cardiac function, increased heart size, and a history of alcohol abuse (31). Although several hypotheses have been postulated for the development of alcoholic cardiomyopathy, including direct and indirect cardiotoxicity of alcohol (22) and accumulation of fatty acid ethyl esters (13), no hypothesis has received convincing and consistent clinical and experimental support to be fully validated.Acetaldehyde (ACA), the...

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Section: Discussionmentioning

confidence: 99%

Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes

Duan¹,

McFadden²,

Borgerding

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Rat cardiomyocytes exposed to alcohol have a dose dependant depression in contractility due, at least in part, to a depletion of sarcoplasmic calcium (59). Studies in mice and human tissue have shown that alcohol causes direct myocardial ultrastructural damage, including edema of sarcoplasmic reticulum, fragmentation of contractile elements, expansion of intercalated disc, and fatty deposits (60,61).…”

Section: Animal Models Relating To Alcohol Induced Arrhythmiasmentioning

confidence: 99%

Alcohol and arrhythmias: a comprehensive review

George

Figueredo

2010

Journal of Cardiovascular Medicine

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“…In addition, heavy drinking may cause myocyte dysfunction (through abnormalities in calcium homeostasis) and elevated levels of norepinephrine [10,11]. Increasing doses of ethanol have been associated with a negative inotropic effect on myocytes in animal experiments [12]. In humans, acute ethanol ingestion may also lead to depressed myocardial contractility [13].…”

Section: Heavy Alcohol Consumption and Risk Of Hfmentioning

confidence: 99%

Alcohol consumption and heart failure: A systematic review

Djoussé

Gaziano²

2008

Curr Atheroscler Rep

115

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Heart failure (HF) remains a major public health issue. It is estimated that about 500,000 Americans per year are diagnosed with HF. Despite advanced medical and surgical treatments for HF, mortality after the onset of HF is still high, thereby underscoring the importance of primary prevention. Among modifiable lifestyle factors, alcohol consumption appears to play a role in the development of HF. Although excessive drinking has been known to lead to alcoholic cardiomyopathy and light-tomoderate drinking may confer some cardiovascular benefits, recent studies suggest it is not only the quantity, but also drinking patterns and genetic factors, that may influence the relation between alcohol consumption and cardiovascular disease. This article reviews current evidence on the association between alcohol consumption and HF.

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Ethanol acutely and reversibly suppresses excitation-contraction coupling in cardiac myocytes.

Abstract: We used adult rat cardiac myocytes to examine the acute effects of 0.1-5.0% (vol/vol)

Cited by 93 publications

References 32 publications

Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes

Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes

Alcohol and arrhythmias: a comprehensive review

Alcohol consumption and heart failure: A systematic review

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