Alcoholic cardiomyopathy: an update.

Alcohol-induced cardiomyopathy (AC) is an acquired form of dilated cardiomyopathy (DCM) caused by prolonged and heavy alcohol intake in the absence of other causes. The amount of alcohol required to produce AC is generally considered as >80 g/day over 5 years, but there is still some controversy regarding this definition. This review on AC focuses on pathogenesis, which involves different mechanisms. Firstly, the direct toxic effect of ethanol promotes oxidative stress in the myocardium and activation of the renin-angiotensin system. Moreover, acetaldehyde, the best-studied metabolite of alcohol, can contribute to myocardial damage impairing actin-myosin interaction and producing mitochondrial dysfunction. Genetic factors are also involved in the pathogenesis of AC, with DCM-causing genetic variants in patients with AC, especially titin-truncating variants. These findings support a double-hit hypothesis in AC, combining genetics and environmental factors. The synergistic effect of alcohol with concomitant conditions such as hypertension or liver cirrhosis can be another contributing factor leading to AC. There are no specific cardiac signs and symptoms in AC as compared with other forms of DCM. However, natural history of AC differs from DCM and relies directly on alcohol withdrawal, as left ventricular ejection fraction recovery in abstainers is associated with an excellent prognosis. Thus, abstinence from alcohol is the most crucial step in treating AC, and specific therapies are available for this purpose. Otherwise, AC should be treated according to current guidelines of heart failure with reduced ejection fraction. Targeted therapies based on AC pathogenesis are currently being developed and could potentially improve AC treatment in the future.

Astaxanthin attenuates alcoholic cardiomyopathy via inhibition of endoplasmic reticulum stress-mediated cardiac apoptosis.

Chronic excessive ethanol consumption is associated with a high incidence of mortality due to ethanol-induced dilated cardiomyopathy, known as alcoholic cardiomyopathy (ACM). Mechanistic studies have demonstrated that apoptosis is key to the pathogenesis of ACM, and endoplasmic reticulum (ER) stress-associated apoptosis contributes to various ethanol-related diseases. Astaxanthin (AST) is a natural carotenoid that exerts an anti-ER stress effect. Importantly, strong evidence has shown that AST induces beneficial effects in various cardiovascular diseases. The present study aimed to investigate whether AST induces beneficial effects on ACM by suppressing cardiac apoptosis mediated by ER stress. We showed that after 2 months of chronic excessive ethanol consumption, mice displayed obvious cardiac dysfunction and morphological changes associated with increased fibrosis, oxidative stress, ER stress and apoptosis. However, cardiac damage above was attenuated in response to AST treatment. The cardioprotective effect of AST against ethanol toxicity was also confirmed in both H9c2 cells and primary cardiomyocytes, indicating that AST-induced protection directly targets cardiomyocytes. Both in vivo and in vitro studies showed that AST inhibited all three ER stress signaling pathways activated by ethanol. Furthermore, administration of the ER stress inhibitor sodium 4-phenylbutyrate (4-PBA) strongly suppressed ethanol-induced cardiomyocyte damage. Interestingly, AST induced further anti-apoptotic effects once co-treated with 4-PBA, indicating that AST protects the heart from ACM partially by attenuating ER stress, but other mechanisms still exist. This study highlights that administration of AST ablated chronic excessive ethanol consumption-induced cardiomyopathy by suppressing cardiac ER stress and subsequent apoptosis.

Nebivolol Prevents Up-Regulation of Nox2/NADPH Oxidase and Lipoperoxidation in the Early Stages of Ethanol-Induced Cardiac Toxicity.

Changes in redox state are described in the early stages of ethanol-induced cardiac toxicity. Here, we evaluated whether nebivolol would abrogate ethanol-induced redox imbalance in the heart. Male Wistar rats were treated with a solution of ethanol (20% v/v) for 3 weeks. Treatment with nebivolol (10 mg/kg/day; p.o. gavage) prevented the increase of both superoxide (O2•-) and thiobarbituric acid reactive substances (TBARS) in the left ventricle of rats chronically treated with ethanol. Neither ethanol nor nebivolol affected the expression of Nox4, p47phox, or Rac-1. Nebivolol prevented ethanol-induced increase of Nox2 expression in the left ventricle. Superoxide dismutase (SOD) activity as well as the concentration of reduced glutathione (GSH) was not altered by ethanol or nebivolol. Augmented catalase activity was detected in the left ventricle of both ethanol- and nebivolol-treated rats. Treatment with nebivolol, but not ethanol increased eNOS expression in the left ventricle. No changes in the activity of matrix metalloproteinase (MMP)2 or in the expressions of MMP2, MMP9, and tissue inhibitor metalloproteinase (TIMP)1 were detected after treatment with ethanol or nebivolol. However, ethanol increased the expression of TIMP2, and this response was prevented by nebivolol. Our results provided novel insights into the mechanisms underlying the early stages of the cardiac injury induced by ethanol consumption. We demonstrated that Nox2/NADPH oxidase-derived ROS play a role in ethanol-induced lipoperoxidation and that this response was prevented by nebivolol. In addition, we provided evidence that MMPs are not activated in the early stages of ethanol-induced cardiac toxicity.

Cirrhotic cardiomyopathy.

The presence of cardiocirculatory dysfunction in liver cirrhosis has been described since 1960 and it was exclusively attributed to alcoholic cardiomyopathie. Only in the last two decades, the term of cirrhotic cardiomyopathy (CCM) was introduced to describe cardiac dysfunction in patients with cirrhosis. This entity is currently underdiagnosed because the disease is usually latent and manifests when the patient is under stress. However, overt cardiac failure has been described after transjugular intrahepatic portosystemic shun and liver transplantation. The diagnosis of CCM is still difficult to determine because of the lack of specific diagnosis tools. CCM is characterized by systolic dysfunction, diastolic dysfunction and electrophysiological abnormalities. At present, there is no specific treatment outside liver transplantation in the light of increased mortality and postoperative complications.Our review provides an overview of CCM, its definition, prevalence, pathogenic mechanisms, clinical presentation, various explorations and management in light of the most recent published literature.

The Effects of Ethanol on the Heart: Alcoholic Cardiomyopathy.

Alcoholic-dilated Cardiomyopathy (ACM) is the most prevalent form of ethanol-induced heart damage. Ethanol induces ACM in a dose-dependent manner, independently of nutrition, vitamin, or electrolyte disturbances. It has synergistic effects with other heart risk factors. ACM produces a progressive reduction in myocardial contractility and heart chamber dilatation, leading to heart failure episodes and arrhythmias. Pathologically, ethanol induces myocytolysis, apoptosis, and necrosis of myocytes, with repair mechanisms causing hypertrophy and interstitial fibrosis. Myocyte ethanol targets include changes in membrane composition, receptors, ion channels, intracellular [Ca2+] transients, and structural proteins, and disrupt sarcomere contractility. Cardiac remodeling tries to compensate for this damage, establishing a balance between aggression and defense mechanisms. The final process of ACM is the result of dosage and individual predisposition. The ACM prognosis depends on the degree of persistent ethanol intake. Abstinence is the preferred goal, although controlled drinking may still improve cardiac function. New strategies are addressed to decrease myocyte hypertrophy and interstitial fibrosis and try to improve myocyte regeneration, minimizing ethanol-related cardiac damage. Growth factors and cardiomyokines are relevant molecules that may modify this process. Cardiac transplantation is the final measure in end-stage ACM but is limited to those subjects able to achieve abstinence.

AIN-93 Diet as an Alternative Model to Lieber-DeCarli Diet for Alcoholic Cardiomyopathy.

BACKGROUND: The Lieber-DeCarli alcoholic liquid diet is a classical method for establishing animal models of alcoholic cardiomyopathy (ACM). No study has reported whether the AIN-93 diet, which is widely used as a standard diet for both long-term and short-term studies with laboratory animals, could be used to construct the ACM animal model. The present study intended to investigate whether the AIN-93 diet could be used to establish a mouse ACM model. METHODS: Twenty-four C57BL/6 male mice were randomly divided into 4 equally sized groups. In ethanol (EtOH)-fed groups, mice were fed a 4%-EtOH (w/v, 28% of total calories) alcoholic liquid diet of Lieber-DeCarli or the AIN-93 diet for chronic alcohol exposure for 180 days. In control-fed groups, mice were fed with non-EtOH liquid diets with the same calories as EtOH-fed groups. Morphological observations of the hearts and molecular investigation of the brain natriuretic peptide (BNP) were carried out by echocardiography, hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining, real-time quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay. RESULTS: Echocardiography showed that mice fed with either the 4%-EtOH Lieber-DeCarli diet or the 4%-EtOH AIN-93 diet had dilated ventricles and poor cardiac function. IHC staining of BNP, qPCR of BNP mRNA, and plasma concentration of BNP showed an up-regulated expression in mice fed with both the 4%-EtOH Lieber-DeCarli and 4%-EtOH AIN-93 diets. Less fatty liver was also observed in mice fed the AIN-93 alcoholic diet than those fed the Lieber-DeCarli alcoholic diet. CONCLUSIONS: The AIN-93 alcoholic liquid diet can be used to establish ACM animal models, as with the conventional Lieber-DeCarli alcoholic liquid diet.

Genetic Etiology for Alcohol-Induced Cardiac Toxicity.

BACKGROUND: Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol. OBJECTIVES: This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity. METHODS: The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM. RESULTS: Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10-5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: -2.3% to -15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients. CONCLUSIONS: TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.

Etiology of alcoholic cardiomyopathy: Mitochondria, oxidative stress and apoptosis.

Putative mechanisms leading to the development of alcoholic cardiomyopathy (ACM) include the interrelated cellular processes of mitochondria metabolism, oxidative stress and apoptosis. As mitochondria fuel the constant energy demands of this continually contracting tissue, it is not surprising that alcohol-induced molecular changes in this organelle contribute to cardiac dysfunction and ACM. As the causal relationship of these processes with ACM has already been established, the primary objective of this review is to provide an update of the experimental findings to more completely understand the aforementioned mechanisms. Accordingly, recent data indicate that alcohol impairs mitochondria function assessed by membrane potential and respiratory chain activity. Indictors of oxidative stress including superoxide dismutase, glutathione metabolites and malondialdehyde are also adversely affected by alcohol oftentimes in a sex-dependent manner. Additionally, myocardial apoptosis is increased based on assessment of TUNEL staining and caspase activity. Recent work has also emerged linking alcohol-induced oxidative stress with apoptosis providing new insight on the codependence of these interrelated mechanisms in ACM. Attention is also given to methodological differences including the dose of alcohol, experimental model system and the use of males versus females to highlight inconsistencies and areas that would benefit from establishment of a consistent model.

[Thiamine (vitamin B1) treatment in patients with alcohol dependence]. / Le traitement par thiamine (vitamine B1) dans l'alcoolodépendance.

Thiamine deficiency (vitamin B1) is common in patients with alcohol dependence. Cognitive impairments may be an early consequence of thiamine deficiency. Wernicke's encephalopathy is underdiagnosed and undertreated. In patients with established Wernicke's encephalopathy, parenteral thiamine 200-500mg three times a day should be given for 3-5 days, followed by oral thiamine 250-1000mg/day. In patients with suspected Wernicke's encephalopathy, parenteral thiamine 250-300mg should be given two times a day for 3-5 days, followed by oral thiamine 250-300mg/day. In patients at high risk of thiamine deficiency, parenteral thiamine 250-500mg/day should be given for 3-5 days, followed by oral thiamine 250-300mg/day. In patients at low risk (with uncomplicated alcohol dependence), oral thiamine 250-500mg/day should be given for 3-5 days, followed by oral thiamine 100-250mg/day.

Alcoholic cardiomyopathy : The result of dosage and individual predisposition.

The individual amount of alcohol consumed acutely or chronically decides on harm or benefit to a person's health. Available data suggest that one to two drinks in men and one drink in women will benefit the cardiovascular system over time, one drink being 17.6 ml 100 % alcohol. Moderate drinking can reduce the incidence and mortality of coronary artery disease, heart failure, diabetes, ischemic and hemorrhagic stroke. More than this amount can lead to alcoholic cardiomyopathy, which is defined as alcohol toxicity to the heart muscle itself by ethanol and its metabolites. Historical examples of interest are the Munich beer heart and the Tübingen wine heart. Associated with chronic alcohol abuse but having different etiologies are beriberi heart disease (vitamin B1 deficiency) and cardiac cirrhosis as hyperdynamic cardiomyopathies, arsenic poising in the Manchester beer epidemic, and cobalt intoxication in Quebec beer drinker's disease. Chronic heavy alcohol abuse will also increase blood pressure and cause a downregulation of the immune system that could lead to increased susceptibility to infections, which in turn could add to the development of heart failure. Myocardial tissue analysis resembles idiopathic cardiomyopathy or chronic myocarditis. In the diagnostic work-up of alcoholic cardiomyopathy, the confirmation of alcohol abuse by carbohydrate deficient transferrin (CDT) and increased liver enzymes, and the involvement of the heart by markers of heart failure (e.g., NT-proBNP) and of necrosis (e.g., troponins or CKMb) is mandatory. Treatment of alcoholic cardiomyopathy consists of alcohol abstinence and heart failure medication.

Enzymes and signal pathways in the pathogenesis of alcoholic cardiomyopathy.

Owing to its acute psychotropic effects, ethanol is the most frequently consumed toxic agent worldwide. However, excessive alcohol intake results in an array of health, social, and economic consequences, which are related to its property as an addictive substance. It has been well established that exposure to high levels of alcohol for a long period leads to the onset and progression of nonischemic cardiomyopathy through direct toxic mechanisms of ethanol and its metabolite, acetaldehyde. Excessive alcohol ingestion causes myocardial damage including disruptions of the myofibrillar architecture and is associated with reduced myocardial contractility and decreased ejection volumes. Key features of alcoholic cardiomyopathy are cardiac hypertrophy and ventricular dilatation, and the disease is manifested mainly as cardiomegaly, congestive heart failure, and even cardiac death. Mechanisms that have been postulated to underlie the pathogenesis of alcoholic cardiomyopathy include apoptosis, mitochondrial alterations, acetaldehyde protein adduct formation, oxidative stress, and imbalances in fatty acid metabolism. In the following, we give a brief overview of the molecular effects of ethanol-metabolizing enzymes and their impact on myocardial signal transduction pathways.

Cardiac manifestations in alcoholic liver disease.

Alcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%-20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction.

Disfunción cardiocirculatoria en pacientes con cirrosis hepática / Cardiocirculatory dysfunction in patients with liver cirrhosis

Introducción: la existencia de alteraciones cardíacas en los pacientes cirróticos ha merecido especial atención en estos últimos años.Objetivo: determinar las alteraciones eléctricas y ecocardiográficas en los pacientes con cirrosis hepática atendidos en la Consulta de Hepatología del Hospital Universitario Dr. Antonio Luaces Iraola de Ciego de Ávila y su asociación con la etiología y la escala pronóstica de Child-Pugh.Método: se realizó un estudio observacional analítico de corte transversal, en el período de mayo de 2012 hasta mayo de 2014.Resultados: se encontró que el mayor número de pacientes pertenecían al sexo masculino y estaban comprendidos en el estadio A de Child-Pugh; la causa más frecuente de la cirrosis hepática fue el alcoholismo. La disfunción diastólica estuvo presente en la mayoría de los pacientes pero no hubo relación estadísticamente significativa entre su severidad, el estadio de Child-Pugh y la etiología.Conclusiones: el diámetro diastólico del ventrículo izquierdo mostró relación estadísticamente significativa con la etiología de la cirrosis hepática; el diámetro de la aurícula izquierda, la presión sistólica y media de la arteria pulmonar estuvieron estadísticamente relacionadas con el estadio de Child-Pugh. El crecimiento de la aurícula izquierda y la hipertrofia del ventrículo izquierdo fueron los hallazgos electrocardiográficos más frecuentes, aunque no guardaron relación estadística ni con la etiología ni con el estadio de Child-Pugh(AU)

Introduction: the presence of cardiac disturbances in cirrhotic patients has received special attention in these last years.Objective: to determine the electrocardiographic and echocardiographic disturbances in patients with cirrhosis of the liver attending the Hepatology Doctor´s Office in the University Hospital “Dr. Antonio Luaces Iraola”, as well as its association with the etiology and the prognosis Child-Pugh scoring system.Method: a cross-sectional observational analytic study was conducted, from May 2012 to May 2014. The universe included 31 patients. All the patients fulfilled the inclusion criteria.Results: most of the patients were male and were in the “A” stage of the Child-Pugh score. Alcoholism was the most frequent cause of liver cirrhosis. Most of the patients had diastolic dysfunction, but there was not statistically significant relationship among its severity, the Child-Pugh stage and the etiology.Conclusions: the diastolic diameter of the left ventricle showed statistically significant relationship with the etiology of liver cirrhosis; the diameter of the left atrium, systolic and mean pulmonary artery were statistically related to the Child-Pugh stage. Left atrium enlargement and left ventricle hypertrophy were the most frequent electrocardiographic findings, although no statistical association was observed between them and the etiology of the Child-Pugh stage(AU)

[The myocardial histo-hematic barrier as a morphological criterion to be used for forensic medical diagnostics of alcoholic cardiomyopathy].

The author estimates the effectiveness of morphological diagnostics of alcoholic cardiomyopathy taking into consideration the general patterns of the structural and functional organization of the heart with special reference to myocardial histo-hematic barrier (HHB) the components of which are characterized by specific structural and functional properties and close relationships between them. It was shown that the morphological changes in the histo-hematic barrier reflect the range of variability of its morphological components and may be used as the indicators of its integrity and stability in the case of disorder. The study has demonstrated that the structural and functional degradation as well as decay of myocardial components may occur under the influence of both an ultrastrong acute impact and latent chronic intoxication or the diseases accompanied by rapid or slow persisting disintegration of the structural organization of the organ. The author maintains that the maximally high informative value of the assessment of the morphological criteria for alcoholic cardiomyopathy can be achieved with the use of special immunohistochemical methods allowing the concrete components of the biological structures to be identified and giving the exact location of the cellular and tissue components in the affected regions. Such an approach permits to detect the developing pathological changes at the molecular level with a high degree of accuracy and visualize the structural reorganization, if any, of each component of the myocardial histo-hematic barrier responsible for the lesions associated with alcoholic cardiomyopathy.

Peculiar characteristics of portal-hepatic hemodynamics of alcoholic cirrhosis.

Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes that occur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis.

Disfunción cardiaca en la cirrosis hepática / Cardiac dysfunction in liver cirrhosis

Objetivo: determinar las alteraciones de la función cardiaca en las personas que padecen cirrosis hepática. Métodos: se desarrolló un estudio descriptivo transversal en el Instituto de Gastroenterología durante el período 2011-2012, en 33 cirróticos de causa viral y alcohólica, 57,6 por ciento del sexo masculino, con una edad promedio de 50 años, la mayoría (84,8 por ciento) tenía la enfermedad compensada. Resultados: la disfunción diastólica fue la alteración cardiaca más frecuente (39,3 por ciento) seguida de la prolongación del intervalo QT (12,1 por ciento), disfunción sistólica (6,1 por ciento) y miocardiopatía cirrótica (3 por ciento). No se identificaron rasgos distintivos epidemiológicos y/o clínicos que caracterizara a estos pacientes. La circulación hiperdinámica fue más evidente en los que presentaron disfunción diastólica y en la cirrosis de origen alcohólico; las dimensiones cardiacas fueron normales en todos los casos. Conclusiones: las personas que padecen cirrosis son susceptibles de presentar alteraciones de la función cardiaca, incluso, desde la etapa compensada de la enfermedad, lo que debe considerarse por las implicaciones terapéuticas que demanda este tipo de paciente...

Objective: to determine abnormalities of cardiac function in subjects with liver cirrhosis. Methods: a descriptive cross-sectional study was conducted at the Institute of Gastroenterology from 2011 to 2012, in 33 cirrhotic patients due to alcoholic and viral causes, 57.6 percent male, with an average age of 50 years, most (84,8 percent) had compensated disease. Results: diastolic dysfunction was the most common cardiac disorders (39.3 percent) followed by QT prolongation (12.1 percent), systolic dysfunction (6.1 percent) and cirrhotic (3 percent) cardiomyopathy interval. No distinctive epidemiological and/or clinical studies were identified to characterize these patients. The hyperdynamic circulation was more evident in those presenting diastolic dysfunction and alcohol-related cirrhosis. Cardiac dimensions were normal in all cases. Conclusions: people with cirrhosis are susceptible to alterations in cardiac function, even from the compensated stage of the disease, which should be considered by the therapeutic implications of this type of patient demand...

Alcoholic cardiomyopathy: pathophysiologic insights.

Alcoholic cardiomyopathy (ACM) is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. ACM is associated with a number of adverse histological, cellular, and structural changes within the myocardium. Several mechanisms are implicated in mediating the adverse effects of ethanol, including the generation of oxidative stress, apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements in fatty acid metabolism and transport, and accelerated protein catabolism. In this review, we discuss the evidence for such mechanisms and present the potential importance of drinking patterns, genetic susceptibility, nutritional factors, race, and sex. The purpose of this review is to provide a mechanistic paradigm for future research in the area of ACM.

Binge drinking-induced subtle myocardial injury.

BACKGROUND: Most of the clinical, histopathological, and biochemical studies consider the effect of chronic alcohol intoxication on myocardial injury. Much less attention has been paid to acute alcohol (binge drinking)-induced cardiotoxicity, even though alcohol binging is much more common than alcohol dependence. METHODS: We briefly present some of the binge drinking-induced "holiday heart" effects. The literature was searched to find effects of alcohol on heart. RESULTS: In binge drinking, the literature has demonstrated transient myocardial subtle changes in cardiac magnetic resonance, increased serological markers of myocardial injury and inflammation, abnormal cardiac rhythm, changes in other biochemical and ultrastructural indices of myocardial dysfunction, as well as changes in metabolism, blood pressure, heart rate, thrombosis/fibrinolysis processes, and coronary vasoconstriction. CONCLUSIONS: Although acute low alcohol exposure has widely proven positive effect on myocardial function, heavy acute drinking frequent events are related to adverse cardiovascular effects.