Heavy Ethanol Consumption Research Articles

Diabetes in First-Degree Family Members: A Predictor of Type 2 Diabetes in 159 Nonscreening Alabama Hemochromatosis Probands With HFE C282Y Homozygosity

OBJECTIVE We sought to identify predictors of diabetes diagnosed before hemochromatosis. RESEARCH DESIGN AND METHODS We studied these 16 variables in 159 nonscreening hemochromatosis probands with HFE C282Y homozygosity: age; sex; BMI; diabetes reports in first-degree family members (dichotomous); heavy ethanol consumption; cigarette smoking; elevated serum alanine aminotransferase/aspartate aminotransferase levels; nonalcoholic fatty liver; chronic viral hepatitis; cirrhosis; hand arthropathy; iron removed by phlebotomy; and positivity for HLA-A*01, B*08; A*03, B*07; and A*03, B*14 haplotypes. We performed univariable and multivariable analyses. RESULTS Twenty-three probands (14.5%) had diabetes; 19 were men. Each of the 23 probands had type 2 diabetes. Mean BMI was greater in probands with diabetes (31.7 ± 8.5 [SD] kg/m(2) vs. 27.6 ± 5.1 kg/m(2); P = 0.032). Reports of any first-degree family member with diabetes were more prevalent in probands with than in probands without diabetes (69.6 vs. 17.6%; P < 0.0001). In probands with diabetes, the odds ratio (OR) of maternal diabetes was 6.7 (95% CI 2.3-19.7; P = 0.0005) and of sibling diabetes was 11.7 (3.0-45.5; P = 0.0004). In a logistic regression model, predictors of diabetes at hemochromatosis diagnosis in 159 probands were diabetes reports in family members (OR 8.5 [95% CI 2.9-24.8]; P < 0.0001) and BMI (1.1 [1.0-1.2]; P = 0.049). This model explained 26.0% of total deviance contributing to diabetes. CONCLUSIONS In nonscreening hemochromatosis probands with HFE C282Y homozygosity, a heritable factor(s) increases the risk of diabetes diagnosed before hemochromatosis.

Ethanol Consumption Increases Endothelin-1 Expression and Reactivity in the Rat Cavernosal Smooth Muscle

We investigated the effects of chronic ethanol consumption on the cavernosal smooth muscle (CSM) reactivity to endothelin-1 (ET-1) and the expression of ET system components in this tissue. Male Wistar rats were treated with heavy dose of ethanol (20% v/v) for 6 weeks. Reactivity experiments were performed in the isolated rat CSM. Plasma and CSM nitrate generation and also superoxide anion generation in rat CSM were measured by chemiluminescence. Protein and mRNA levels of pre-pro-ET-1, endothelin-converting enzyme-1 (ECE-1), ETA and ETB receptors, eNOS, nNOS and iNOS were assessed by western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Chronic ethanol consumption increased plasma ET-1 levels and the contractile response induced by this peptide in the isolated CSM. The relaxation induced by acetylcholine, but not IRL1620, a selective ETB receptor agonist, was reduced in CSM from ethanol-treated rats. BQ123, a selective ETA receptor antagonist, produced a rightward displacement of the ET-1 concentration-response curves in CSM from control, but not ethanol-treated rats. Reduced levels of nitrate were found in the plasma and CSM from ethanol-treated rats. Ethanol consumption increased superoxide anion generation in the rat CSM. The mRNA levels of pre-pro-ET-1, ECE-1, ETA and ETB receptors, eNOS, nNOS and iNOS were not altered by ethanol consumption. Protein levels of ET-1, ETA receptor and iNOS were higher in the CSM from rats chronically treated with ethanol. The major findings of the present study are that heavy ethanol consumption increases plasma ET-1 levels and the contraction induced by the peptide in the CSM. Increased CSM reactivity to ET-1 and altered protein levels of ET-1 and ETA receptors could play a role in the pathogenesis of erectile dysfunction associated with chronic ethanol consumption.

Vasoprotective effect of vitamin E: Rescue of ethanol-induced atherosclerosis and inflammatory stress in rat vascular wall

Chronic ethanol consumption increases the incidence of cardiovascular disease. The mechanisms underlying ethanol-induced susceptibility to cardiovascular disease continue to be defined. This study examines the hypothesis that chronic ethanol consumption plausibly induces vascular wall abnormalities via inflammatory reactions. In addition, it intends to find out whether vitamin E inhibits the abnormalities induced by ethanol in rats' vascular wall. Twenty four male Wistar rats were divided into three groups (n=8): Control ©, ethanol (E), and vitamin E treated ethanol (VETE) group. After 6weeks, the aortic and coronary wall changes, vascular endothelial growth factor (VEGF), alpha-1 glycoprotein and haptoglobin amounts in plasma, C-reactive protein levels(CRP), as well as the amount of aortic IL-6 were evaluated. The results revealed the elevation of polymorphonuclear (PMN) leukocyte in the vascular wall, disorganization of endothelium with ballooning of cells, proliferation of vasa-vasorum with an increase in the IL-6, CRP, as well as a decrease in VEGF and an increase in alpha-1 glycoprotein and haptoglobin in the ethanol group compared to the control group. Significant amelioration of aortic and coronary wall changes, along with the restoration of elevated level of IL6, CRP, and the decreased level of VEGF compared to that of the controls were found in vitamin E-treated animals. These findings strongly support the idea that heavy and chronic ethanol consumption initiates atherosclerosis by inflammatory stress, and that these effects can be alleviated by vitamin E as an anti-inflammatory agent.

A retrospective analysis of glycol and toxic alcohol ingestion: utility of anion and osmolal gaps

BackgroundPatients ingesting ethylene glycol, isopropanol, methanol, and propylene glycol ('toxic alcohols') often present with non-specific signs and symptoms. Definitive diagnosis of toxic alcohols has traditionally been by gas chromatography (GC), a technique not commonly performed on-site in hospital clinical laboratories. The objectives of this retrospective study were: 1) to assess the diagnostic accuracy of the osmolal gap in screening for toxic alcohol ingestion and 2) to determine the common reasons other than toxic alcohol ingestion for elevated osmolal gaps.MethodsElectronic medical records from an academic tertiary care medical center were searched to identify all patients in the time period from January 1, 1996 to September 1, 2010 who had serum/plasma ethanol, glucose, sodium, blood urea nitrogen, and osmolality measured simultaneously, and also all patients who had GC analysis for toxic alcohols. Detailed chart review was performed on all patients with osmolal gap of 9 or greater.ResultsIn the study period, 20,669 patients had determination of serum/plasma ethanol and osmolal gap upon presentation to the hospitals. There were 341 patients with an osmolal gap greater than 14 (including correction for estimated contribution of ethanol) on initial presentation to the medical center. Seventy-seven patients tested positive by GC for one or more toxic alcohols; all had elevated anion gap or osmolal gap or both. Other than toxic alcohols, the most common causes for an elevated osmolal gap were recent heavy ethanol consumption with suspected alcoholic ketoacidosis, renal failure, shock, and recent administration of mannitol. Only 9 patients with osmolal gap greater than 50 and no patients with osmolal gap greater than 100 were found to be negative for toxic alcohols.ConclusionsOur study concurs with other investigations that show that osmolal gap can be a useful diagnostic test in conjunction with clinical history and physical examination.

Dupuytren's Contracture in AlabamaHFEHemochromatosis Probands

BackgroundDupuytren’s contracture (DC) and HFE hemochromatosis occur in some of the same at-risk populations and present with similar comorbid conditions.MethodsWe estimated DC prevalence in two cohorts of white Alabama hemochromatosis probands (294 C282Y homozygotes, 67 C282Y/H63D compound heterozygotes) in a retrospective study. We performed logistic regressions on DC using the following independent variables: age, body mass index, heavy ethanol consumption, serum ferritin, elevated serum AST/ALT, non-alcoholic fatty liver disease, viral hepatitis, cirrhosis, and diabetes.ResultsOne man and two women with C282Y homozygosity had DC (prevalence 1.02%; 95% CI 0.35%–2.96%). A man with C282Y/H63D had DC (prevalence 1.49%; 95% CI 0.26%–7.98%). DC occurred as an autosomal dominant trait in his kinship. In regression analyses, no single variable predicted DC. We observed no new DC cases after the diagnosis of hemochromatosis (mean follow-up 12.9 ± 7.5 years (1 SD), and 9.0 ± 5.1 years, respectively).ConclusionsOur prevalence estimates of DC in white Alabama hemochromatosis probands are similar to those found in the white US population cohorts. DC risk was unrelated to the variables we studied.

Holiday Heart Syndrome

Holiday heart syndrome is an acute cardiac rhythm or conduction disturbance associated with heavy ethanol consumption in a person without other clinical evidence of heart disease. Typically, this resolves rapidly with spontaneous recovery during subsequent abstinence from alcohol use. Two adolescents were presented with different degrees of heart block following acute alcohol ingestion. The electrocardiograph abnormalities resolved within 12 hours. Further investigations, including echocardiography and 24-hour electrocardiograph, were normal. Emergency Department physicians should be aware of the possibility of acute alcohol ingestion causing changes in cardiac conduction which has a potential to develop into life-threatening arrhythmias, thus, can occur in children and young adolescents.

Holiday Heart Syndrome

Holiday heart syndrome is an acute cardiac rhythm or conduction disturbance associated with heavy ethanol consumption in a person without other clinical evidence of heart disease. Typically, this resolves rapidly with spontaneous recovery during subsequent abstinence from alcohol use. Two adolescents were presented with different degrees of heart block following acute alcohol ingestion. The electrocardiograph abnormalities resolved within 12 hours. Further investigations, including echocardiography and 24-hour electrocardiograph, were normal. Emergency Department physicians should be aware of the possibility of acute alcohol ingestion causing changes in cardiac conduction which has a potential to develop into life-threatening arrhythmias, thus, can occur in children and young adolescents.

Alcoholic Optic Neuropathy: Another Complication of Alcohol Abuse

Back to table of contents Previous article Next article LETTERFull AccessAlcoholic Optic Neuropathy: Another Complication of Alcohol AbuseThomas Paparrigopoulos M.D.Elias Tzavellas M.D.Dimitris Karaiskos M.D.Ioannis Liappas M.D.,Thomas Paparrigopoulos M.D.Search for more papers by this authorElias Tzavellas M.D.Search for more papers by this authorDimitris Karaiskos M.D.Search for more papers by this authorIoannis Liappas M.D.Search for more papers by this author,Published Online:1 Jul 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Alcohol affects both the central and the peripheral nervous system; hence, cognitive dysfunction as well as sensory and motor peripheral neuropathy are frequent complications of chronic abuse. 1 However, symptoms of cranial nerve neuropathy are not routinely examined in alcohol abusing patients. To emphasize the necessity of such an assessment, we report on a man who abused alcohol and presented with progressive visual loss attributed to optic nerve neuropathy. Case Report A 55-year-old man was admitted to the clinic for alcohol detoxification. He smoked one pack of cigarettes per day for many years and heavily abused alcohol for 15 years, which he had reduced over the last 2 years. Clinical examination revealed numbness and weakness, particularly of the lower limbs, diminished tendon reflexes, and progressive painless blurring of central vision bilaterally; these symptoms, developed over the last 2 years and had seriously compromised his daily functioning. A motor and sensory nerve conduction study showed slowed motor conduction and low-amplitude response to sensory stimuli, mostly on the right. Visual fields testing revealed an infero-temporal and central defect in the right eye and a superonasal, inferior, and central defect in the left. Humphrey 10–2 static perimetry showed bilateral caecocentral scotomas. Visual acuity was 8/10 in the right and 5/10 in the left eye. Color vision was normal. Intraocular pressure was 15 mmHg in both eyes and anterior segments were normal. Funduscopy findings were unremarkable. Blood count, serum vitamin B 12 and folate levels were normal, but macrocytosis was present (MCV: 104fl.); also, transaminases were elevated. Following alcohol withdrawal and a 6-month vitamin supplementation (vitamins C, E, B complex, folate, taken both orally and intramuscularly), peripheral neuropathy considerably improved but optic neuropathy remained refractory to treatment. Discussion Tobacco-alcohol amblyopia was often described prior to World War II in patients with heavy tobacco and ethanol consumption. At the present time, tobacco-alcohol amblyopia is either far less common or is seldom checked for and reported. 2 – 3 It is characterized by subacute or gradual loss of central vision, decreased visual acuity, and dyschromatopsia. Fundi may appear normal, with few abnormalities on detailed examination; temporal atrophy of the optic disk may become evident at later stages. Metabolic optic neuropathies are characterized by specific loss of the nerve fiber layer in the papillomacular bundle. 2 – 4 They are etiologically distinguished from hereditary-degenerative neuropathies, neuropathies due to nutritional deficiencies (e.g., thiamine, vitamin B 12 and folic acid deficiency), and neuropathies caused by various toxic agents (e.g., ethambutol and cyanide). Impairment of mitochondrial oxidative phosphorylation has been proposed as the common underlying pathophysiological mechanism. 5 In tobacco-alcohol amblyopia, gradual accumulation of formic acid, malnutrition, thiamine depletion, poor B 12 absorption in the presence of ethanol, and a number of toxic tobacco ingredients, particularly cyanide, act synergistically to the development of neuropathy. Vitamin and nutritional deficiencies are considered especially important factors for its development and recovery is purportedly complete with abstinence from alcohol and smoking and vitamin supplementation. 3 – 5The present case, the first reported in the literature, does not fulfill the characteristic tobacco-alcohol amblyopia criteria, in that dyschromatopsia, an essential component of tobacco-alcohol amblyopia, is absent and no recovery of vision loss was recorded following sobriety from alcohol and tobacco and protracted vitamin treatment. These findings point to the possibility of a nonreversible atypical form of optic nerve neuropathy due to alcohol abuse.Athens University Medical School, Department of Psychiatry, Drug and Alcohol Addiction Clinic, Eginition Hospital, Athens, GreeceReferences1 . McIntosh C, Chick J: Alcohol and the nervous system. J Neurol Neurosurg Psychiatry 2004; 75:iii16–21Google Scholar2 . Behbehani R, Sergott RC, Savino PJ: Tobacco-alcohol amblyopia: a maculopathy? Br J Ophthalmol 2005; 89:1543–1544Google Scholar3 . Kesler A, Pianka P: Toxic optic neuropathy. Curr Neurol Neurosci Rep 2003; 3:410–414Google Scholar4 . Sadun AA: Metabolic optic neuropathies. Semin Ophthalmol 2002; 17:29–32Google Scholar5 . Carelli V, Ross-Cisneros FN, Sadun AA: Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int 2002; 40:573–584Google Scholar FiguresReferencesCited byDetailsCited ByAcute Motor Axonal Neuropathy: A Severe Complication of Alcohol AbuseSevki Sahin, M.D.Nilgun CinarM.D.,Gulbuz SezginM.D.,Sunay Ayalp, M.D.Sibel KarsidagM.D.,1 October 2010 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 22, No. 4Current World LiteratureCurrent Opinion in Neurology, Vol. 23, No. 1 Volume 20Issue 3 Summer, 2008Pages 368-369 Metrics PDF download History Published online 1 July 2008 Published in print 1 July 2008

NF-κB Gene Signatures and p53 Mutations in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) has traditionally been attributed to carcinogen exposure, through heavy tobacco and ethanol consumption. Disruption of tumor suppressor pathways, notably regulated through p53 and Rb, has served as a paradigm for studying HNSCC carcinogenesis and the

Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma

To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specific antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitative score based on their intensity, and the percentage of immunostained cells was measured. A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.

Ethanol Self‐Administration and Alterations in the Livers of the Cynomolgus Monkey, Macaca fascicularis

Most of the studies of alcoholic liver disease use models in which animals undergo involuntary administration of high amounts of ethanol and consume diets that are often high in polyunsaturated fatty acids. The objectives of this study were (1) to evaluate whether cynomolgus monkeys (Macaca fascicularis) drinking ethanol voluntarily and consuming a diet with moderate amounts of lipid would demonstrate any indices of alcoholic liver disease past the fatty liver stage and (2) to determine whether these alterations were accompanied by oxidative stress. Six adult male and 6 adult female cynomolgus monkeys were allowed to consume ethanol voluntarily for 18 to 19 months. Additional monkeys were maintained on the same consumption protocol, but were not provided with ethanol. During the course of the study, liver biopsy samples were monitored for lipid deposition and inflammation, serum for levels of liver enzymes, and urine for concentrations of the isoprostane (IsoP) metabolite, 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP, a biomarker for oxidative stress. Liver mitochondria were monitored for respiratory control and liver for concentrations of neutral lipids, adenine nucleotides, esterified F(2) isoprostanes, oxidized proteins, 4-hydroxynonenal (HNE)-protein adducts, and protein levels of cytochrome P-450 2E1 and 3A4. Ethanol consumption ranged from 0.9 to 4.05 g/kg/d over the period of the study. Serum levels of aspartate amino transferase were elevated in heavy-consuming animals compared with those in ethanol-naïve or moderate drinkers. Many of the ethanol consumers developed fatty liver and most showed loci of inflammation. Both hepatic energy charge and phosphorylation potential were decreased and NADH-linked respiration was slightly, but significantly depressed in coupled mitochondria as a result of heavy ethanol consumption. The urinary concentrations of 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP increased as high as 33-fold over that observed in ethanol-abstinent animals. Liver cytochrome P-450 2E1 concentrations increased in ethanol consumers, but there were no ethanol-elicited increases in hepatic concentrations of the esterified F(2) isoprostanes, oxidized proteins, or HNE-protein adducts. Our studies show that cynomolgus monkeys undergoing voluntary ethanol consumption for 1.5 years exhibit many of the features observed in the early stages of human alcoholic liver disease. Ethanol-elicited fatty liver, inflammation, and elevated serum aspartate amino transferase were evident with a diet that contained modest amounts of polyunsaturated lipids. The dramatic increases in urinary IsoP demonstrated that the animals were being subjected to significant oxidative stress that correlated with their level of ethanol consumption.

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

Chronic Heavy Ethanol Consumption Is Associated with Decreased Platelet Aggregation in Rats

Although moderate alcohol consumption seems to be protective against atherosclerosis, coronary artery disease rate increases with its higher doses. Platelet aggregation is an important process which contributes to the atherosclerosis. The aim of this study was to determine whether heavy ethanol consumption stimulates or inhibits platelet aggregation. Fourteen adult male Wistar rats were used. Ethanol (7.2%, v/v) in a modified liquid diet was given to eight rats for 21 days, which mimicked characteristics similar to human chronic alcoholism. Six rats constituted the control group. Adenosine diphophate (ADP) and collagen-induced platelet aggregation was measured in whole blood. We found reduced ADP-induced mean maximal aggregation in the alcoholic rat group compared to the control group at dose of 5 microM (p < 0.005). We also found decreased platelet aggregation responses to collagen in the alcoholic group (p < 0.006 for 2 microg/ml collagen, and p < 0.05 for 5 microg/ml collagen). In conclusion, chronic heavy ethanol consumption results in the decreased platelet aggregation in a rat model of alcoholism. Therefore, increased mortality from coronary artery disease in chronic alcoholism may be explained by other factors such as dietary imbalances and coexisting conditions, which include hypertension and depression.

Alcohol and hepatocellular carcinoma

More than 18 million adults in the United States abuse alcohol, a prevalence 5 times higher than that of hepatitis C. Chronic alcohol use of greater than 80 g/day for more than 10 years increases the risk for hepatocellular carcinoma (HCC) approximately 5-fold; alcohol use of less than 80 g/day is associated with a nonsignificant increased risk for HCC. The risk for HCC in decompensated alcohol induced cirrhosis approaches 1% per year. The risk does not decrease with abstinence, and HCC can occur in a noncirrhotic liver. Alcohol use in chronic hepatitis C doubles the risk for HCC as compared with the risk in hepatitis C alone. Furthermore, there may be synergism between alcohol and hepatitis C in the development of HCC, and in these patients HCC may occur at an earlier age and the HCC may be histologically more advanced. Studies in the United States and Italy suggest that alcohol is the most common cause of HCC (accounting for 32%-45% of HCC). The mechanisms by which alcohol causes HCC are incompletely understood, but may include chromosomal loss, oxidative stress, a decreased retinoic acid level in the liver, altered DNA methylation, and genetic susceptibility. Alcohol use is increasing in many countries, suggesting that alcohol will continue to be a common cause of HCC throughout the world.

The High-Ethanol Preferring rat as a model to study the shift between alcohol abuse and dependence

The High-Ethanol Preferring line of rats (HEP), recently selected by R.D. Myers, is characterised by a high voluntary consumption of alcohol (3–4 g/kg/day for males and 6–8 g/kg/day for females, when a 10% ethanol solution is available as a choice vs. water) and a high sensitivity to taste reinforcement (saccharin, quinine). Our previous data obtained with HEP rats showed no evidence of development of dependence after long-term sustained alcohol intake. In this study, we subjected these rats to several long-term administration protocols suggested to favour the development of alcohol dependence, including multiple alcohol concentrations or sweetened alcohol solutions (ethanol 10% or 20%+saccharin), and deprivation periods. The results showed no increase in alcohol consumption, no shift of preference for alcohol solutions when offered as a free choice vs. a preferred saccharin solution, and a very limited alcohol-deprivation effect when alcohol is made available after a period of deprivation, the three criteria used to demonstrate the development of dependence. Regardless of the method used, HEP rats failed to show dependence after long-term, heavy ethanol consumption. Resistance to ethanol dependence may in fact be genetically influenced and the HEP rat appears as a valuable model to search for factors involved in the transition from alcohol abuse to dependence.

Effects of alcohol on the heart.

Some evidence suggests that light to moderate alcohol consumption protects against cardiovascular diseases. However, this cardioprotective effect of alcohol consumption in adults is absent at the population level. Approximately 20 to 30% of patients admitted to a hospital are alcohol abusers. In medical practice, it is essential that patients' levels of consumption are known because of the many adverse effects that might result in the course of routine care. Ethanol damage to the heart is evident if alcohol consumption exceeds 90 to 100 g/d. Heavy ethanol consumption leads to increased risk for sudden cardiac death and cardiac arrhythmias. In patients with coronary heart disease, alcohol use was associated with increased mortality. An early response to drinking was an increased ventricular wall thickness to diameter ratio, possibly proceeding with continuous drinking to alcoholic cardiomyopathy, which had a worse outcome compared with idiopathic dilative cardiomyopathy if drinking was not stopped or at least reduced (< 60 g/d). In the ICU, patients with chronic alcoholism have more cardiac complications postoperatively. These complications probably are caused by biventricular dysfunction, particularly with the occurrence of severe infections or septic shock, events that are three to four times more frequent among chronic alcoholics than occasional drinkers or nondrinkers. To prevent further complications from drinking and for long-term management of drinking, patients with alcohol abuse and heart failure should be treated in brief intervention and follow-up programs. Prognosis is good even in patients with New York Heart Association class IV heart failure caused by cardiomyopathy if complete abstinence is accomplished. Noncompliance to smoking and alcohol restrictions, which are amenable to change, dramatically increases the risk for hospital readmissions among patients with heart failure.

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.

Induction of Transient Proteinuria, Hematuria, and Glucosuria by Ethanol Consumption in Japanese Alcoholics

Urinalysis was carried out in 231 inpatients with alcohol dependence syndrome (215 males and 16 females). Fifty-nine patients (25.5%) showed proteinuria, 97 (42.0%) showed glucosuria, and 62 patients (26.8%) showed hematuria on admission. A total of 135 out of 231 patients (58.4%) showed abnormal urinalysis. Proteinuria was related to high blood pressure, high serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, uric acid, and triglyceride levels, and high urinary amylase concentration. Glucosuria was related to high serum glutamic-oxaloacetic transaminase concentration and a history of gastrectomy. Hematuria was related to high age and high urinary amylase levels. By chi-square test, there was a significant correlation between proteinuria and hematuria (p < 0.001) and between hematuria and glucosuria (p < 0.001), but no correlation was found between proteinuria and glucosuria. The incidence of diabetes mellitus was 10.8% (25 out of 231 patients), but transient hyperglycemia was observed in some patients without diabetes mellitus on admission. Elevated hemoglobin A1, hemoglobin A1c, and fructosamine concentrations were observed in patients with either impaired glucose tolerance or transient hyperglycemia, which suggested the presence of persistent hyperglycemia before admission. On discharge, only 12 out of 198 patients (6.1%) showed abnormal urinalysis. We report that heavy ethanol consumption induces transient abnormal urinalysis results in Japanese alcoholics.

Effects of Chronic Moderate and Heavy Ethanol Consumption on Myocardial Recovery from Ischemia

The purpose of this study was to determine the effects of chronic moderate and heavy ethanol consumption on myocardial ischemia/reperfusion injury. Three groups (n = 18) of 6-month-old female Sprague-Dawley rats were fed a nutritionally balanced liquid diet. Control, moderate alcohol, and heavy alcohol groups consumed 0%, 20%, and 35% of their calories from ethanol, respectively. After 10 weeks of feeding, hearts were isolated and subjected to 21.5 min of ischemia alone, or 21.5 min of ischemia followed by 30 min reperfusion. Hearts were evaluated for hemodynamic characteristics and high-energy phosphate content. Hearts from animals exposed to moderate and heavy amounts of ethanol recovered significantly less (30.61% and 29.45%, respectively) of their preischemic cardiac external work than control hearts (65.52%). Postischemic diastolic stiffness was increased ˜7-fold, and high-energy phosphate content, both creatine phosphate and adenosine triphosphate, decreased >25% by both chronic moderate and heavy ethanol consumption. In conclusion, both chronic moderate and heavy ethanol consumption exacerbate myocardial ischemia/reperfusion injury. The ethanol-induced reduction in postischemic energy status may be the mechanism of increased diastolic stiffness and subsequent reduced cardiac external work.

Effects of Chronic Moderate and Heavy Ethanol Consumption on Myocardial Recovery from Ischemia

The purpose of this study was to determine the effects of chronic moderate and heavy ethanol consumption on myocardial ischemia/ reperfusion injury. Three groups (n = 18) of 6-month-old female Sprague-Dawley rats were fed a nutritionally balanced liquid diet. Control, moderate alcohol, and heavy alcohol groups consumed 0%, 20%, and 35% of their calories from ethanol, respectively. After 10 weeks of feeding, hearts were isolated and subjected to 21.5 min of ischemia alone, or 21.5 min of ischemia followed by 30 min reperfusion. Hearts were evaluated for hemodynamic characteristics and high-energy phosphate content. Hearts from animals exposed to moderate and heavy amounts of ethanol recovered significantly less (30.61% and 29.45%, respectively) of their preischemic cardiac external work than control hearts (65.52%). Postischemic diastolic stiffness was increased approximately 7-fold, and high-energy phosphate content, both creatine phosphate and adenosine triphosphate, decreased >25% by both chronic moderate and heavy ethanol consumption. In conclusion, both chronic moderate and heavy ethanol consumption exacerbate myocardial ischemia/reperfusion injury. The ethanol-induced reduction in postischemic energy status may be the mechanism of increased diastolic stiffness and subsequent reduced cardiac external work.