Alcoholic Heart Muscle Disease Research Articles

Cardiac changes in patients with chronic liver disease: A prospective descriptive study

Background: The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed “cirrhotic cardiomyopathy”, which is an entity different from that seen in alcoholic heart muscle disease. Objective: To study cardiac changes in patients with chronic liver disease. Methodology: The present study was a prospective descriptive clinical study consisting of thirty five patients with cirrhosis who were inpatients in the department of Medicine, tertiary care Institute, from Oct 2011 to Oct 2013.The patients were evaluated for presence of cirrhotic cardiomyopathy. Results: In A group there is no patient, while in Child- Pugh Score- B group 14 subjects have cirrhotic cardiomyopathy out of 16 and in C group 18 have cirrhotic cardiomyopathy out of 19. We analyzed that there was no relation between severity of liver disease and cirrhotic cardiomyopathy (p value- 0.446). Conclusion: Indian patients with cirrhosis do have diastolic dysfunction. In the absence of other risk factors for cardiac disease, this dysfunction can be attributed only to cirrhotic cardiomyopathy.

Pattern of cardiovascular disease amongst medical admissions in a regional teaching hospital in Southeastern Nigeria

Background: Cardiovascular disease (CVD) is responsible for a large proportion of death and disability worldwide. However, a substantial portion of the increasing global impact of CVD is attributable to economic, social, and cultural changes that have led to increases in risk factors for CVD. These changes are most pronounced in the countries comprising the developing world. Because the majority of the world's population lives in the developing world, the increasing rate of CVD in these countries is the driving force behind the continuing dramatic worldwide increase in CVD. Objective: This study was aimed at determining the frequency and pattern of cardiovascular disorders in the medical wards as well as the emergency and intensive care units of the University of Nigeria Teaching Hospital (UNTH) Enugu, Southeast Nigeria. Methods: A retrospective study of consecutive adult patients with diagnosis of cardiovascular disorders admitted into the medical wards and/or the emergency/intensive care units of UNTH Enugu between January 2000 and January 2007 was carried out using the ward admission and discharge registers. Results: A total of 6,162 patients (males 3,385 (54.93%); female 2,777 (45.07%)) were admitted over the period covered by the study. Out of these; 1,261 (20.46%) patients were found to have cardiovascular disorder. Prevalence of cardiovascular disorders was found to be higher among the female patients than among the males: 693 (24.95%) and 568 (16.78%) years, respectively. The ages ranged between 18 and 92 years with a mean ± standard deviation (SD) of 55.13 ± 15.37. The pattern of CVD observed in this study were hypertension and its complications (86.36%), rheumatic heart disease (4.52%), dilated cardiomyopathy (3.09%), and alcoholic heart muscle disease (0.95%). Conclusion: CVDs were major causes of morbidity in the environment of study. Early detection, improved outpatient care, as well as inclusion of appropriate secondary prevention programs in patient's management especially at the community level is recommended in order to reduce complications and the need for hospital admissions.

Sex‐dependent molecular alterations during development of alcoholic cardiomyopathy in rat

Excessive, chronic alcohol consumption can result in alcoholic heart muscle disease (AHMD) and, ultimately, heart failure. Functional and structural damage to the myocardium is consistent with a shift in myocardial protein expression and activity that occurs as the disease progresses. The current study aims to link alcohol‐induced alterations in expression of specific proteins with the differences between male and female using a chronic rat model. This study uses isobaric tags for relative and absolute quantitation (iTRAQ) followed by mass spectrometry to delineate shifts in protein expression in rat myocardium as a consequence of chronic (18 week) alcohol intake. Echocardiography allowed the early detection of changes to the heart. Consuming alcohol for 16 weeks lowered stroke volume and left ventricular diastolic volume in both sexes. Males showed additional significant declines in left ventricular mass and end‐diastolic dimension. At the end of the alcohol‐feeding regimen, hearts were fractionated into myofibrillar, sarcoplasmic, mitochondrial, and nuclear fractions. Early interpretation of the proteomic data obtained from mitochondrial fractions identified variations in structural proteins as well as proteins involved in oxidative phosphorylation and electron transport.NIAAA R01 AA012814 (TCV) and PA Dept of Health Tobacco Settlement Award (RLF)

Cardiovascular complications of cirrhosis

Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and...

Proteomic analysis of rat myocardium in a model of chronic alcohol consumption

Heavy, chronic alcohol consumption is associated with a syndrome known as alcoholic heart muscle disease (AHMD), clinically characterized by ventricular dilation, thinning of the ventricular wall, and myocardial dysfunction. These changes occur as a result of a decreased rate of protein synthesis. The clinical manifestations of AHMD are consistent with alterations in structural and myofibrillar proteins. The current study used a proteomic approach with isotope coded affinity tag (ICAT) labeling and mass spectrometry to delineate changes in protein expression in a chronic (16 wk) alcohol rat model. Chronic alcohol ingestion was associated with falls in mitochondrial proteins associated with TCA cycle (citrate synthase, isocitrate dehydrogenase, succinyl‐CoA synthetase, malate dehydrogenase) as well as enzymes involved in electron transport (ubiquinone, adenine nucleotide translocator, F1‐ATPase, H+ transporting two‐sector ATPase) and energy transfer (nucleoside‐diphosphate kinase, creatine kinase). No changes were seen in pyruvate dehydrogenase complex, NADH coenzyme Q reductase, or ubiquinol cytochrome c reductase. The results indicate myocardial mitochondrial proteins are adversely affected in chronic alcoholism. (PHS; RO1 AA012814).

Ethanol and cardiac function

regular heavy ethanol consumption has been associated with a type of nonischemic dilated cardiomyopathy termed “alcoholic cardiomyopathy” (ACM), which is clinically expressed as an impairment of left ventricular function (nonsymptomatic stage) and occasionally as overt heart failure (symptomatic

354 Loss of actin and myosin proteins following chronic alcohol consumption: possible early indicator of alcoholic heart muscle disease

354 Loss of actin and myosin proteins following chronic alcohol consumption: possible early indicator of alcoholic heart muscle disease

Sex differences in L-type calcium current after chronic ethanol consumption in rats

Chronic ethanol consumption elicits a progressive cardiac contractile dysfunction, and studies in rats suggest that this alcoholic heart muscle disease is more pronounced in males than females. Cellular changes associated with the ethanol-induced cardiotoxicity remain largely undefined; however, it is possible that L-type Ca 2+ channel current ( I Ca,L) is affected. Using whole-cell patch-clamp techniques, this study examined I Ca,L in adult ventricular myocytes isolated from male and female P-rats that had consumed drinking water (controls) or a 25% ethanol/water mixture for 14 months. The peak amplitude and maximum conductance of I Ca,L were 32 and 26% greater, respectively, in cardiomyocytes isolated from ethanol-consuming compared to control male rats. In contrast, no differences in the amplitude or conductance of I Ca,L were observed when comparing myocytes isolated from control and ethanol-consuming females. Ethanol treatment had no significant effects on the kinetics I Ca,L inactivation or on steady-state activation and inactivation in either gender. In conclusion, male but not female cardiomyocytes respond to chronic ethanol consumption with an increased I Ca,L that may represent a compensatory response to the depressed contractility.

Testing Genetic Susceptibility Loci for Alcoholic Heart Muscle Disease

Background: Although many heavy alcohol users have subclinical alcoholic heart muscle disease, only a very few develop severe dilated cardiomyopathy. Therefore, and because cardiac abnormalities correlate only weakly with the duration or quantity of drinking, individual susceptibility differences may exist. In this work we examined whether common gene variants previously associated with cardiac hypertrophy or altered alcohol metabolism could modify the effects of alcohol on the heart.Methods: We studied 700 middle‐aged male victims of sudden death who underwent a medicolegal autopsy. In addition to routine postmortem examination, the weights and the cavity and wall dimensions of the left and right ventricle were measured. Coronary artery stenoses were determined from a silicone rubber cast of the arteries. Alcohol consumption and cardiovascular risk factors were assessed by a structured interview of the spouse. The following gene polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism and solid‐phase minisequencing techniques: angiotensin converting enzyme I/D, angiotensin II type 1 receptor 1166A/C, aldosterone synthase −344C/T, alcohol dehydrogenases 2 and 3, acetaldehyde dehydrogenase 2, and cytochrome P‐450 2E1 Dra I, Pst I, Rsa I, and Msp I.Results: The most consistent effects of alcohol (p < 0.05) were a higher total heart weight and a larger right ventricle size with increasing daily drinking. However, these and other effects of alcohol were statistically fully independent of the studied genotypes.Conclusions: The gene polymorphisms selected for and analyzed in our study are unlikely to modify the effects of alcohol on the heart. Other unknown factors determine the individual susceptibility to alcoholic heart muscle disease.

Testing genetic susceptibility loci for alcoholic heart muscle disease.

Although many heavy alcohol users have subclinical alcoholic heart muscle disease, only a very few develop severe dilated cardiomyopathy. Therefore, and because cardiac abnormalities correlate only weakly with the duration or quantity of drinking, individual susceptibility differences may exist. In this work we examined whether common gene variants previously associated with cardiac hypertrophy or altered alcohol metabolism could modify the effects of alcohol on the heart. We studied 700 middle-aged male victims of sudden death who underwent a medicolegal autopsy. In addition to routine postmortem examination, the weights and the cavity and wall dimensions of the left and right ventricle were measured. Coronary artery stenoses were determined from a silicone rubber cast of the arteries. Alcohol consumption and cardiovascular risk factors were assessed by a structured interview of the spouse. The following gene polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism and solid-phase minisequencing techniques: angiotensin converting enzyme I/D, angiotensin II type 1 receptor 1166A/C, aldosterone synthase -344C/T, alcohol dehydrogenases 2 and 3, acetaldehyde dehydrogenase 2, and cytochrome P-450 2E1 DraI, PstI, RsaI, and MspI. The most consistent effects of alcohol (p < 0.05) were a higher total heart weight and a larger right ventricle size with increasing daily drinking. However, these and other effects of alcohol were statistically fully independent of the studied genotypes. The gene polymorphisms selected for and analyzed in our study are unlikely to modify the effects of alcohol on the heart. Other unknown factors determine the individual susceptibility to alcoholic heart muscle disease.

A Rodent Model of Alcoholic Heart Muscle Disease and Its Evaluation by Echocardiography

Background: Transthoracic echocardiography was used in a rodent animal model to determine whether long-term alcohol consumption (8 and 12 months) was associated with the development of a dilated cardiomyopathy. We also investigated whether alcohol-induced changes in cardiac structure corresponded to activation of the renin-angiotensin system and the natriuretic peptide (NP) system. Methods: Male rats received either the Lieber-DeCarli liquid alcohol diet (EtOH) (9%v/v) (n= 8) or control diet (CON) (n= 8). Echocardiography (echo) was used to determine left-ventricular (LV) dimensions, and isolated heart studies (Langendorff and atrium) were used to assess ex vivo contractility. Plasma and tissue angiotensin-I converting enzyme (ACE) activity was measured. Gene expression, plasma, and tissue levels of the NPs were determined by northern blot analysis and radioimmunoassay, respectively. Results: After 8 months of alcohol consumption, there was a trend for the end diastolic dimension, end systolic dimension, and LV mass to be greater in the 8 month EtOH group compared with the CON group. However, after 12 months of alcohol consumption, significant increases were found between the groups in several echo parameters. Tissue ACE activity (nmoles/min/mg protein) was greater in the 12 month EtOH group compared with the 12 month CON and 8 month EtOH group (p < 0.05). We found no differences between groups in gene expression (messenger RNA), plasma, and tissue levels of the NPs. Conclusions: Echocardiography revealed that 8 to 12 months of alcohol consumption was associated with the development of a dilated cardiomyopathy. However, this was not preceded by an increase in tissue ACE activity, and these changes occurred in the absence of increased plasma and LV tissue levels of the NPs.

A Rodent Model of Alcoholic Heart Muscle Disease and Its Evaluation by Echocardiography

Transthoracic echocardiography was used in a rodent animal model to determine whether long-term alcohol consumption (8 and 12 months) was associated with the development of a dilated cardiomyopathy. We also investigated whether alcohol-induced changes in cardiac structure corresponded to activation of the renin-angiotensin system and the natriuretic peptide (NP) system. Male rats received either the Lieber-DeCarli liquid alcohol diet (EtOH) (9%v/v) (n = 8) or control diet (CON) (n = 8). Echocardiography (echo) was used to determine left-ventricular (LV) dimensions, and isolated heart studies (Langendorff and atrium) were used to assess ex vivo contractility. Plasma and tissue angiotensin-I converting enzyme (ACE) activity was measured. Gene expression, plasma, and tissue levels of the NPs were determined by northern blot analysis and radioimmunoassay, respectively. After 8 months of alcohol consumption, there was a trend for the end diastolic dimension, end systolic dimension, and LV mass to be greater in the 8 month EtOH group compared with the CON group. However, after 12 months of alcohol consumption, significant increases were found between the groups in several echo parameters. Tissue ACE activity (nmoles/min/mg protein) was greater in the 12 month EtOH group compared with the 12 month CON and 8 month EtOH group (p < 0.05). We found no differences between groups in gene expression (messenger RNA), plasma, and tissue levels of the NPs. Echocardiography revealed that 8 to 12 months of alcohol consumption was associated with the development of a dilated cardiomyopathy. However, this was not preceded by an increase in tissue ACE activity, and these changes occurred in the absence of increased plasma and LV tissue levels of the NPs.

Heavy long-term ethanol consumption induces an alpha- to beta-myosin heavy chain isoform transition in rat.

Alcoholic heart muscle disease is characterized by structural changes which include chamber dilation, ventricular hypertrophy, and myocyte damage. These effects often lead to contractile dysfunction and ultimately to heart failure if alcohol consumption is not terminated. In rat models for heart failure in which heart failure is induced by pressure or volume overload, there is a shift in the myosin heavy chain (MHC) isoforms, from alpha to beta. As a result of this MHC transition, there is typically a decrease in myosin ATPase activity. We utilized a rat model of chronic alcohol consumption in order to determine if alcohol causes a similar shift in MHC isoforms and changes in myosin ATPase activity. A liquid diet containing 9% ethanol (46% of daily calories; 11.8 g/kg/day) was administered to adult rats for a period of 60 or 90 days. This heavy consumption of ethanol resulted in an average blood ethanol content of 150 mg %. The relative abundance of beta-MHC isoform protein increased from a control level of 9.7% to 35.1% in hearts of ethanol-fed rats, following 90 days of ethanol consumption. In a separate set of experiments, the levels of alpha-MHC and beta-MHC mRNA were demonstrated to increase by 150% and 230%, respectively. Following a 60 day treatment, there was a significant reduction in the actomyosin Mg2+ -ATPase activity in the myofibrillar preparations from hearts of ethanol-fed rats compared to hearts from control-fed rats. In addition, the myosin Ca2+ -ATPase activity was decreased 17% and 30% after 60 and 90 days of ethanol consumption, respectively. The present study demonstrates that chronic ethanol consumption induces an increase in the proportion of the total MHC content composed of the beta-isoform. This isoform transition is accompanied by an accumulation of beta-MHC mRNA, suggesting that the switch is organized pretranslationally. A functional consequence of this transition in MHC phenotype is demonstrated by significant decreases in the myofibrillar and myosin ATPase activities.

Chronic alcoholism in a forensic material. 2. Causes and manners of death in alcoholics.

The causes and manners of death in medico-legal cases from a five-year period were examined. Alcoholics died more often of combined alcohol/drug intoxication and of carbon monoxide poisoning. They had a lower frequency of heart diseases, and there was no support for the existence of an alcoholic heart muscle disease. Lobar pneumonia was only found in alcoholics. There were, as expected, higher frequencies of the known alcohol-related diseases such as hepatic coma, bleeding oesophageal varices and alcohol intoxication. An observed higher frequency of death before the age of 35 could be attributed to alcohol-related diseases. The manners of death showed surprisingly small differences, as the main finding was a higher frequency of alcoholics with undeterminable manner of death.

Alcohol and the heart: biochemical alterations

A considerable amount of attention has focused on the cardiovascular events associated with ethanol consumption. The available evidence suggests that moderate ethanol consumption is associated with reduced risk of coronary heart disease, i.e., vessel events. In contrast, this review is primarily concerned with ethanol and heart muscle damage. Clinical features of the consequences of prolonged and excessive ethanol consumption encompass defects in myocardial contractility and derangement of cellular architecture, including disarray of the contractile elements. Although the incidence of heart muscle abnormalities in alcohol misusers is generally higher than previously considered, the mechanisms are only just being elucidated. This process has been facilitated by laboratory based studies in which animals receive either a single dose of ethanol (acute studies) or a continuous supply of ethanol in their daily diets (chronic studies). Results from these models show that acute ethanol dosage causes a marked decrease in the synthesis of contractile proteins. This occurs in the absence of overt mitochondrial abnormalities: ATP concentrations are generally unaffected. Paradoxically, the synthesis of mitochondrial proteins is reduced. Use of metabolic inhibitors suggests that the deleterious effects of acetaldehyde contribute to these reductions in protein synthesis. In chronic studies, ethanol causes a reduction in the amount of contractile proteins, and two dimensional protein profiling implicates selective loss of individual myocardial proteins. The differential activities of lysosomal proteases may contribute to this patterned response. However, in chronic ethanol feeding, adaptive mechanisms also become important, as the synthesis of the myofibrillary proteins increases. Overall, the mechanisms inherent in these biochemical responses may contribute to the genesis of a distinct disease entity, alcoholic heart muscle disease.

Protein synthesis in the heart in vivo, its measurement and patho-physiological alterations

Changes in cardiac protein composition occur in a variety of patho-physiological situations and are usually accompanied by modifications in protein synthesis. Although adjustments in protein synthesis during starvation may be adaptive, the alterations in protein synthesis seen in response to ethanol ingestion may be pathological and an important step in the genesis of alcoholic heart muscle disease. The alterations in heart muscle in hypertension are initially adaptive but in the long term they are deleterious, and involve both transcription and translation. While adequate methods exist for quantifying the amount of mRNA for contractile and non-contractile proteins, such studies of gene-expression provide no dynamic information on the rate at which tissue proteins are lost or accrued. This can only be determined by measuring the rate of protein turnover, i.e. either protein synthesis or protein breakdown. Techniques for directly determining the rates of protein breakdown are limited or involve surgical procedures. Methods for measuring the rate of protein synthesis are described, and are illustrated by their application to the investigation of starvation and ethanol toxicity. In particular, attention is focused on the fact that reliable rates of protein synthesis are obtained only if the specific radioactivity of the precursor at the site of protein synthesis (aminoacyl-tRNA) is assessed.

799-5 Point Mutations of Mitochondrial DNA in Alcoholic Heart Muscle Disease

Point mutations of mitochondrial DNA (mtDNA) were reported in various diseases. We studied them in patients with alcoholic heart muscle disease (AHMD). In habitual heavy drinkers with heart failure (ten men, mean age 53.1 ± 8.2 years, mean daily ethanol intake 119.5 ± 40.0 ml, mean drinking duration 30.3 ± 7.9 years), right ventricular endomyocardial biopsies were performed. MtDNA was extracted from the specimens and amplified using PCR. Then the total base-sequence was analysed and compared with the wild type. Eight point mutations which cause amino acid substitution were detected among five patients. These point mutations were the same as previously reported in mitochondrial diseases or cardiomyopathies. Thus, Point mutations of mtDNA may be related to the pathogenesis of AHMD.

THE DELETERIOUS EFFECTS OF ALCOHOL ON THE HEART: INVOLVEMENT OF PROTEIN TURNOVER

Ethanol ingestion can induce a variety of metabolic changes in the heart, and recent studies have even suggested that moderate ethanol intake confers cardio-protective effects in reducing mortality due to coronary artery disease. However, in this review we explore the consequences of excessive ethanol intake or alcohol misuse. We investigate the epidemiology of alcohol misuse, and thereafter present evidence supporting the existence of a specific alcoholic heart muscle disease (AHMD). The prevalence of AHMD is described and the contributing mechanisms are discussed. These include the involvement of free radicals, defects in intermediary metabolism and the formation of acetaldehyde adducts. Special attention has been paid to ethanol-induced changes in protein turnover. Our studies show that ethanol impairs the protein synthetic pathways, affecting the contractile proteins per se, as well as the subcellular organelles as exemplified by the mitochondria. Acetaldehyde appears to be a particularly potent toxin. The experiments described in this review emphasize the need for investigative studies in intact models. The mechanisms inherent in the pathogenesis of AHMD may be applicable to other heart muscle disorders.

Ethanol induced cardiovascular disease.

Although the beneficial effects of mild or moderate ethanol consumption have been implied with respect to coronary artery disease, excessive ethanol consumption can result in alcoholic heart muscle disease (AHMD). The latter is characterized by features consistent with dilated cardiomyopathy with concomitant ventricular dysfunction and histopathological abnormalities. By definition, no other cause for the abnormalities in AHMD is demonstrated, other than excessive alcohol consumption. The metabolic basis of AHMD is probably multi-factorial, and the alterations of myocardial biochemistry are contributing factors for the precipitation and progression of the disease. The latter may reverse with abstention. Evidence is provided to support the contention that the abnormalities include central defects in protein metabolism, which perhaps are engendered by free radicals and/or the formation of acetaldehyde adducts. The latter may initiate the formation of auto-antibodies, therefore providing an auto-immune basis for AHMD in chronic alcohol misuse. Evidence is also provided to show that acetaldehyde is a potent perturbant of protein synthesis, and reduces the formation of new contractile proteins.

Antibodies to Acetaldehyde Adducts of Human Heart in Patients with Alcoholic Heart Muscle Disease

Antibodies to Acetaldehyde Adducts of Human Heart in Patients with Alcoholic Heart Muscle Disease