Alcohol-induced Cardiomyopathy Research Articles

Dilated Cardiomyopathy: A Genetic Journey from Past to Future.

Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field.

Possible involvement of Protein Tyrosine Phosphatase in Alcoholic Cardiomyopathy

Protein tyrosine phosphatases (PTPase’s) are the enzymes that dephosphorylate survival kinase PI3K/Akt pathway this may be a key mechanism in alcohol-induced cardiomyopathy. Therefore, the present study was designed to investigate the role of PTPase in alcohol-induced cardiomyopathy. Ethanol (20%) at the dose of 7.9 g/kg P.o was given regularly for 60 days that produced Alcohol-induced Cardiomyopathy (ACM). CM (cardiomyopathy) was assessed in terms of decrease in LVDP, dp/dtmax, dp/dtmin, LV protein content, CFR and increase in LVEDP, LVW/BW, MABP, LV collagen, LV cholesterol content, TNF-α, nitrite levels and iNOS expression in alcoholic cardiomyopathic rats. Sodium Orthovanadate (SOV) (PTPase inhibitor) at the dose of 2.5, 5 and 10mg/kg significantly increased LVDP, dp/dtmax, dp/dtmin, CFR, LV protein content. Moreover, significant decrease in the elevated MABP, LVEDP, LVW/BW, LV collagen, LV cholesterol content, nitrite, TNF-α and iNOS level was observed. Furthermore, administration of SMT (S-methylisothiourea), an iNOS inhibitor (5mg/kg., i.p) with SOV (10mg/kg., p.o) significantly increased the ameliorative effect of SOV (10mg/kg., p.o). The findings suggested that PTPases may have a function in regulating alcohol-induced cardiomyopathy by interfering with Akt/Pi3k and its downstream pathways, which include TNF-alpha and iNOS.

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.

Socio-economic association of alcohol use disorder and cardiovascular and alcohol-associated liver disease from 2010to 2019.

Alcohol use leads to disabilities and deaths worldwide. It not only harms the liver but also causes alcohol use disorder (AUD) and heart disease. Additionally, alcohol consumption contributes to health disparities among different socio-economic groups. We estimated global and regional trends in the burden of AUD, liver disease, and cardiovascular disease from alcohol using the methodology of the Global Burden of Disease study. In 2019, the highest disability-adjusted life years rate per 100,000 population was due to AUD (207.31 [95% Uncertainty interval (UI) 163.71-261.66]), followed by alcohol-associated liver disease (ALD) (133.31 [95% UI 112.68-156.17]). The prevalence rate decreased for AUD (APC [annual percentage change] -0.38%) and alcohol-induced cardiomyopathy (APC -1.85%) but increased for ALD (APC 0.44%) and liver cancer (APC 0.53%). Although the mortality rate for liver cancer from alcohol increased (APC 0.30%), mortality rates from other diseases decreased. Between 2010 and 2019, the burden of alcohol-associated complications increased in countries with low and low-middle sociodemographic index (SDI), contributing more significantly to the global burden. The global burden of AUD, liver, and cardiovascular disease has been high and increasing over the past decade, particularly for liver complications. Lower SDI countries are contributing more to this global burden. There is a pressing need for effective strategies to address this escalating burden.

Mitochonic Acid 5 Improves Mitochondrial Respiration Following Alcohol-Induced Mitochondrial Dysfunction

Chronic alcohol exposure can lead to the development of Alcohol Induced Cardiomyopathy (ACM). The pathological changes in ACM have been suggested to be largely caused by mitochondrial damage, reduction of ATP, oxidative stress, and apoptosis of the cardiomyocytes. Cardiomyocytes, as cells with high energy demand, rely greatly on mitochondrial homeostasis and ATP production. Thus, therapeutic intervention to specifically target the mitochondria and ATP production can potentially alleviate ACM. Mitochonic acid 5 (MA-5) has been recently identified as a potential therapeutic compound that increases cellular ATP and improves mitochondrial function in several cardiac disorders. Given the potential role of MA-5 in improving mitochondrial function, I speculate that MA-5 could be an effective treatment for alcohol-induced cardiotoxicity. In the present study, I test the hypothesis that MA-5 can mitigate mitochondrial energetics in cultured cardiomyocytes exposed to alcohol. To investigate this, neonatal mouse cardiomyocytes (NMCMs) were isolated from mice at day 1-2 of age and cultured for 6 days with alcohol (50mM). The cells were treated with MA-5 (1μM, 5μM, or 10μM) for 4 hours with serum starvation and then cellular energetic changes were measured using the Mito Stress assay with the Seahorse Bioanalyzer (XF96pro, Agilent). To investigate the impacts of chronic alcohol exposure, rat embryonic myoblasts, H9C2 cells, were treated with 50mM alcohol for 3 weeks. Subsequently, cells were treated with MA-5 (1μM, 5μM, or 10μM) for 24 hours and then attached to the Resipher system (Lucid Lab) for continuous oxygen consumption monitoring and recording. NMCMs treated with 50mM alcohol showed a substantial reduction in basal respiration, maximal respiration, and spare respiratory capacity compared to controls. NMCMs treated with 10μM MA-5 showed a significant improvement in these parameters. Chronically exposed H9C2 cells showed a prolonged decline in OCR. MA-5 treatment improved and maintained oxygen consumption in these cells. In summary, these results demonstrated that alcohol exposed cardiomyocytes experience a decline in cellular energetics that could be corrected by MA-5 treatment. Future in vivo studies on preclinical ACM animal models are warranted to yield further insights into a potential novel therapy for ACM in patients. This research was supported by grant #T32AA007577 from the NIAAA at the National Institutes of Health. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Restoring Cardiac Health: Abstinence Leads to Recovery from Alcohol-Induced Cardiomyopathy

Chronic drinking can lead to alcohol-induced cardiomyopathy (ACM), a disease currently without a cure. Using a mouse model of ACM, we observed significant cardiac dysfunction after 30 days. Our study’s goal was to investigate the potential restoration of cardiac function following a period of abstinence. Our hypothesis is that abstinence can lead to an observable recovery in overall cardiac function. C57BL/6J mice were given the Lieber-DeCarli liquid diet with 5% ethanol for 30 days, with two ethanol binges on days 10 and 30 (5 g/kg). After the 30-day ethanol exposure, the mice were transitioned to an ethanol-free diet for an additional 30 days. Left ventricular catheterization and echocardiography were conducted at the 30- and 60-day timepoints. 30 days of ethanol consumption led to significant decreases in both systolic and diastolic function. However, following a period of alcohol abstinence, there was a marked improvement. Specifically, the 30-day ethanol mice exhibited increases in stroke work and dP/dt max after 30 days of abstinence; stroke work increased from 1119 ± 89 mmHg*μL to 2032 ± 139 mmHg*μL (p < 0.0001), and dP/dt max increased from 8054 ± 664 mmHg/s to 11967 ± 449 mmHg/s (p < 0.001). Diastolic function also improved; dP/dt min from -7711 ± 561 mmHg/s to -10202 ± 594 (p < 0.01). We also found a significant increase in load-independent cardiac contractility, i.e. the slope of end systolic pressure volume relation: 6.89 ± 0.6 mmHg/μL to 10.59 ± 1.57 mmHg/μL (p < 0.05). In conclusion, abstinence after chronic ethanol exposure can lead to a restoration of cardiac function in C57BL/6J mice. This model parallels limited clinical data on abstinence and will allow us to study the underlying mechanisms responsible for the restoration of function. R21AA029747 (JG, CB), F30AA030472 (JE). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstinence Restores Cardiac Function in Mice with Established Alcohol-Induced Cardiomyopathy.

Alcohol-induced cardiomyopathy (ACM) has a poor prognosis with up to a 50% chance of death within four years of diagnosis. There are limited studies investigating the potential of abstinence for promoting repair after alcohol-induced cardiac damage, particularly in a controlled preclinical study design. Here, we developed an exposure protocol that led to significant decreases in cardiac function in C57BL6/J mice within 30 days; dP/dt max decreased in the mice fed alcohol for 30 days (8054 ± 664.5 mmHg/s compared to control mice: 11,188 ± 724.2 mmHg/s, p < 0.01), and the dP/dt min decreased, as well (-7711 ± 561 mmHg/s compared to control mice: -10,147 ± 448.2 mmHg/s, p < 0.01). Quantitative PCR was used to investigate inflammatory and fibrotic biomarkers, while histology was used to depict overt changes in cardiac fibrosis. We observed a complete recovery of function after abstinence (dP/dt max increased from 8054 ± 664 mmHg/s at 30 days to 11,967 ± 449 mmHg/s after abstinence, p < 0.01); further, both inflammatory and fibrotic biomarkers decreased after abstinence. These results lay the groundwork for future investigation of the molecular mechanisms underlying recovery from alcohol-induced damage in the heart.

Abstract 14097: State-Wise Burden of Alcohol-Induced Cardiomyopathy in the United States From 1990-2019: Results From the Global Burden of Disease Study 2019

Introduction: Alcoholic cardiomyopathy (ACM) causes 140,000+ alcohol-related deaths yearly. Alcohol consumption and the burden of ACM vary significantly across states within the US. Methods: To assess the burden of ACM in the USA, we used the Global Health Data Exchange. Adult alcohol per capita consumption was obtained from the National Institute on Alcohol Abuse and Alcoholism. Results: Over 30 years, ACM prevalence increased by around 53.15%, reaching 198000(k). Only three US states experienced a decline in the Age-Standardized Prevalence (ASP): the District of Columbia (DC), Maryland, and Virginia. New Hampshire and Utah had the highest and lowest ASP rates, correlating with per capita alcohol consumption. Notably, total US deaths decreased by 9.7%. This decrease is primarily due to a significant reduction in female mortality by about 70%, while mortality in men continues to increase steadily. In DC, Maryland, and Hawaii, females showed the most significant improvement, with DC having the highest reduction in Age-Standardized Death Rates (ASDR) by 83%. South Dakota had the lowest ASDR for both sexes, with 25.6% and 71.88% reductions in males and females, respectively. The Age-Standardized rate of Disability-Adjusted Life Years (ASDALYs) in the US has shown a slight downward trend and has decreased to 174k. However, ASDALYs for males increased by 8.5%. DC continues to have the highest ASDALYs, but with a significant reduction (64%), while South Dakota remained the state with the lowest ASDALYs per 100k, dropping from 35.3 to 22.84. Conclusions: Significant disparities were observed among states, with a higher burden in males. However, these trends were not as pronounced among females, except for increased prevalence. Notably, states with higher per capita alcohol consumption showed a more significant burden of ACM. Targeted interventions aimed at high-risk populations can play a crucial role in reducing the morbidity and mortality associated with this disease.

Cholecystalgia: An Atypical Presentation of Congestive Heart Failure in a New Diagnosis of Alcohol-Induced Cardiomyopathy

Right upper quadrant (RUQ) pain is a frequent presenting symptom in the emergency department, and gallstone-induced acute cholecystitis is one of the main causes; in addition, RUQ pain can be a consequence of several other conditions. Although rare, it may also indicate cholecystalgia from gallbladder edema, which is usually related to other conditions, such as congestive heart failure (CHF), alcoholic and nonalcoholic liver cirrhosis, acute viral or drug-induced hepatitis, renal failure, and hypoproteinemia. We present a case of cholecystalgia resulting from gallbladder edema in a patient with a newly diagnosed alcohol-induced cardiomyopathy without the common CHF signs and symptoms.

Abstract 14745: Recurrent Cardiogenic Shock Secondary to Shoshin Beriberi in s Patient With Heavy Alcohol Use

Introduction: Thiamine is an essential enzyme cofactor in cellular metabolism. Its deficiency can manifest as wet beriberi with high-output heart failure. Its more severe and fulminant form is known as shoshin beriberi, characterized by cardiogenic shock, hemodynamic collapse, and multiorgan failure. Case Description: A 67-year-old male presented with dyspnea on exertion and orthopnea. On exam, he was tachycardic and cold to the touch. Initial workup showed metabolic acidosis, elevated lactate, acute kidney and liver injury, and elevated NT proBNP. ECG showed atrial fibrillation with RVR. His past medical history included heavy alcohol use and a similar presentation two years prior with new-onset heart failure complicated by shock and acute kidney injury, requiring CRRT. At that time, he improved with high-dose thiamine and decompensation was attributed to shoshin beriberi. Shortly after admission, the patient developed worsening shock, with liver failure, renal failure, and DIC. He was started on pressors, broad-spectrum antibiotics, high-dose thiamine and CRRT. TTE showed biventricular dysfunction and global hypokinesis with LVEF of 20%. Hemodynamic monitoring was consistent with cardiogenic shock. Infectious workup was negative. Within 96h of the initiation of thiamine, the patient’s mental status and hemodynamics significantly improved, with resolution of cardiogenic shock. He remained hemodynamically stable, his laboratory abnormalities improved, and he was started on GDMT. He required intermittent HD for several months, after which it was discontinued. He later underwent LHC that showed nonobstructive CAD. Discussion: The diagnosis of shoshin beriberi is challenging and requires a high index of suspicion for presumed thiamine deficiency, particularly in critically ill patients with many comorbidities. An empiric therapeutic trial of thiamine supplementation in this group of patients can lead to improvement of hemodynamics within hours to days, as in this case. Even though his LVEF has not yet fully recovered, we suspect that his presentation was due to an acute-on-chronic insult, in the setting of alcohol-induced cardiomyopathy. To the best of our knowledge, this is the first report of recurrent shoshin beriberi in the literature.

Alcohol-Induced Cardiomyopathy Presenting with Left Ventricular Apical Thrombus

Alcohol-Induced Cardiomyopathy Presenting with Left Ventricular Apical Thrombus

The alcohol-induced cardiomyopathy: A cardiovascular magnetic resonance characterization

BackgroundAlcoholic cardiomyopathy(ACM) is part of the non-ischaemic dilated cardiomyopathy(NI-DCM) spectrum. Little is known about cardiovascular magnetic resonance(CMR) features in ACM patients. The aim of this study is to describe CMR findings and their prognostic impact in ACM patients. MethodsConsecutive ACM patients evaluated in five referral CMR centres from January 2005 to December 2018 were enrolled. CMR findings and their prognostic value were compared to idiopathic NI-DCM(iNI-DCM) patients. The main outcome was a composite of death/heart transplantation/life-threatening arrhythmias. ResultsOverall 114 patients (52 with ACM and 62 with iNI-DCM) were included. ACM patients were more often males compared to iNI-DCM (90% vs 64%, respectively, p ≤ 0.001) and were characterized by a more pronounced biventricular adverse remodelling than iNI-DCM, i.e. lower LVEF (31 ± 12% vs 38 ± 11% respectively, p = 0.001) and larger left ventricular end-diastolic volume (116 ± 40 ml/m2 vs 67 ± 20 ml/m2 respectively, p < 0.001). Similarly to iNI-DCM, late gadolinium enhancement (LGE), mainly midwall, was present in more than 40% of ACM patients but, conversely, it was not associated with adverse outcome(p = 0.15). LGE localization was prevalently septal (87%) in ACM vs lateral in iNI-DCM(p < 0.05). Over a median follow-up of 42 months [Interquartile Range 24–68], adverse outcomes were similar in both groups(p = 0.67). ConclusionsACM represents a specific phenotype of NI-DCM, with severe morpho-functional features at the onset, but similar long-term outcomes compared to iNI-DCM. Despite the presence and pattern of distribution of LGE was comparable, ACM and iNI-DCM showed a different LGE localization, mostly septal in ACM and lateral in iNI-DCM, with different prognostic impact.

The protective effect of fibroblast growth factor‐21 in alcoholic cardiomyopathy: a role in protecting cardiac mitochondrial function

Alcoholic cardiomyopathy (ACM) resulting from chronic alcohol misuse is one of the main contributors leading to heart failure and cardiovascular mortality. Fibroblast growth factor 21 (FGF21) is a well-established cardioprotective factor. We aimed to study the role of FGF21 in experimentally induced models and clinical affected patients with cardiac damage due to chronic alcohol consumption. We found that circulating FGF21 levels and cardiac FGF21 and β-klotho protein levels were increased in subjects with chronic alcohol consumption. As an experimental model of ACM, we fed wild-type and Fgf21 knockout (Fgf21-/- ) mice with a 4% alcohol liquid diet for 4 and 12 weeks. FGF21 circulating levels and FGF21 expression in the myocardium were also increased in wild-type mice after chronic alcohol intake. Fgf21-/- mice develop a higher degree of cardiac hypertrophy, fibrosis, and cardiac dysfunction after chronic alcohol consumption than wild-type mice. Moreover, the myocardium of Fgf21-/- mice showed signs of metabolic deregulation, oxidative stress, and mitochondrial dysfunction after alcohol intake. Finally, human cardiac biopsies from patients with chronic alcohol consumption developing ACM presented a higher degree of oxidative stress which positively correlated with the FGF21 protein levels in the myocardium. We conclude that plasma levels and cardiac myocyte FGF21 expression were induced in response to chronic alcohol consumption. The lack of FGF21 aggravated cardiac damage produced by ACM, in association with enhanced mitochondrial and oxidative stress, thus pointing to FGF21 as a protective agent against development of alcohol-induced cardiomyopathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

MiR-155-5p alleviates ethanol-induced myocardial insulin resistance in H9C2 cells via regulating the mTOR signalling pathway.

Alcohol exposure impairs myocardium insulin sensitivity, which links to heart dysfunction. miR-155 regulates mTOR signaling pathway and is involved in multiple functions. However, the underlying mechanism of miR-155 in ethanol-induced myocardial insulin resistance remains unclear. Here, in this study we aimed to identify the role of miR-155 in myocardial insulin sensitivity and the involvement of mTOR pathway. H9C2 cells were cultured with or without 100mM ethanol for 24h. miR-155-5p inhibitor, miR-155-5p mimics or their respective negative control (inhibitor NC and mimic NC) were transfected to regulate miR-155-5p expression. mTOR signaling, including Ras homolog enriched in brain (Rheb), rapamycin insensitive companion of mTOR (Rictor) and ribosomal protein S6 kinase B2 (S6K2), was investigated by western blotting and qPCR, and insulin responsiveness was evaluated by glucose uptake and phosphorylation of insulin receptor substrate-1 (p-IRS1). The miR-155-5p level increased under ethanol exposure, accompanied by a decrease in glucose uptake, an increase in p-IRS1(ser 307) and activation of the mTOR signaling pathway in H9C2 cells. In addition, miR-155-5p downregulation decreased the glucose uptake, increased the p-IRS1(ser 307) level and activated the mTOR signaling pathway. miR-155-5p upregulation increased the glucose uptake, decreased the p-IRS1(ser 307) level and suppressed the mTOR signaling pathway. Collectively, these findings suggest miR-155-5p upregulation ameliorates myocardial insulin resistance via mTOR signaling in vitro, and miR-155-5p downregulation attenuates myocardial insulin resistance, which might become a potential therapeutic target for alcohol-induced cardiomyopathy.

A Rare Twist of the Forgotten Disease: A Case of Fusobacterium necrophorum Sepsis with Porto-mesenteric Thrombosis

Fusobacterium Necrophorum, an anaerobic organism, is the primary causative agent of Lemierre's syndrome, which primarily manifests as internal jugular thrombophlebitis. Only a handful of cases involving portal or mesenteric veins thromboses have been documented in the literature. A 57-year old female with a history of alcohol-induced cardiomyopathy was admitted to the hospital with pyrexia and myalgias for three days. A comprehensive review of systems was negative. On physical examination, she appeared ill, was febrile to 39.1°C and was tachycardiac to 113 bpm. Her initial labs were unremarkable, except for a sodium level of 129 mEq/L and a platelet count of 91x109/L. A nasal swab for influenza virus was negative. A urinalysis was unremarkable. A chest X-ray showed no abnormalities. The patient deteriorated and developed shock in a few hours. She was fluid resuscitated and blood cultures were obtained. Broad-spectrum antibiotic coverage with Vancomycin and Meropenem was initiated. On day two, the patient complained of profuse watery diarrhea. C. Difficile testing and stool cultures were negative. An abdominal CT-scan showed colonic diverticulosis with sigmoid thickening but no evidence of diverticulitis along with a non-occlusive thrombus involving the mesenteric vein and portal vein. Intravenous heparin was initiated. On day four of the admission, blood cultures returned positive for Fusobacterium Necrophorum. The patient's septic shock resolved and she was discharged to complete a 14-day course of Ertapenem. She was also switched to Apixaban for anticoagulation for 3 months. Often referred to as ‘the forgotten disease,' Lemierre's syndrome is the most frequent life-threatening manifestation of Fusobacterium Necrophorum bacteremia. The disease course is typically pharyngitis that is complicated with septic internal jugular vein thrombosis. Abdominal variants, manifesting with pylephlebitis and mesenteric veins thromboses, are exceedingly rare, yet extremely important to recognize due to the high mortality rate when left untreated. In the reported case, the identified bacterium is part of the gastrointestinal microflora. We believe that gastrointestinal translocation due to subclinical colonic inflammation was what introduced the bacteremia. This case aims to underscore the importance of widening the differential diagnosis of nonspecific symptoms to include this potentially lethal yet treatable condition.

Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis.

Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative/nitrative stress, impaired mitochondrial function and biogenesis, and enhanced cardiac steatosis.

Effects of Alcohol Consumption on Hypertension

Prevention of hypertension and lowering blood pressure with non-pharmacological treatment and lifestyle changes may reduce cardiovascular morbidity and mortality associated with alcohol while they also play an important role in reducing the cost of medical treatment. Reduction of alcohol consumption is one of the recommended lifestyle changes in the JNC VII report. Excessive amounts of alcohol consumption leads to an increase in blood pressure in both normotensive and hypertensive individuals. At the same time, alcohol can lead to resistance to antihypertensive drug treatment. Effects of alcohol on blood pressure is depent on the amount of alcohol rather than the type of alcohol. As far as heart diseases are concerned, mild-to-moderate alcohol consumption, despite its tendency to increase blood pressure, is associated with decreased risk of coronary artery diseases and ischemic stroke by way of elevating high-density lipoprotein cholesterol levels, reducing fibrinogen and platelet aggregation, and producing positive effects on antioxidants systems. However, increased alcohol consumption is accompanied by increased blood pressure, hemorrhagic and ischemic strokes, alcohol-induced cardiomyopathy, arrhythmia, and sudden cardiac death. Therefore, people with hypertension should avoid or reduce alcohol consumption in addition to drug treatment. A positive relationship has been detected between decreasing alcohol consumption and systolic and diastolic blood pressures. Reducing alcohol consumption provides a 2-4 mmHg reduction in systolic blood pressure levels. For this reason, 1-2 drinks per day for men and up to one drink for women and people with poor health seem to be optimal amounts. People who use alcohol should keep in mind that moderation and unexcessive consumption are the key words in avoiding alcohol related medical conditions. Key Words: Alcohol; Hypertension; Cardiovascular Disease.

Decreased Cardiac Allograft Survival in Patients Transplanted for Alcohol-Induced Cardiomyopathy: Data from the United Network for Organ Sharing (UNOS) Registry

The outcomes of heart transplantation in patients with alcohol-induced cardiomyopathy (ACM) are unknown. The objective of this analysis is to investigate the outcomes of patients with end-stage ACM treated with heart transplantation.

Akt/PI3K signaling sustains the chronic alcoholic effects on the heart (862.6)

Cardiovascular diseases are the leading causes of increased mortality and morbidity rates. Specifically, alcohol induced cardiomyopathy is a preventable dysfunction that is associated with premature deaths. High alcohol (HA) intake has been shown to negatively impact the heart function into having reduced contractility with dilated cardiomyopathy. However, low alcohol (LA) intake has been clinically shown to be beneficial. Prior studies in our lab have linked the Akt/PI3K pathway to cardiac dysfunction. In this study, we investigate the role of Akt activity (western blot) that contributes to changes in cardiac contraction and calcium mobilization (Ionoptix), cell survival (Cell Viability Assay), caspase activity (caspase 3/7 assay) and oxidative stress associated with chronic LA (0.02%) and HA (0.45%) consumption using Lieber‐DeCarli alcohol diet (4 months). Our results demonstrate that rats on a LA liquid diet experienced decreased caspase activity and increased calcium mobilization and cellular/sarcomere contraction. However, the above Akt‐mediated effects are diminished with rats on a HA diet. Our results also show that the inhibition of NFkB causes further aggravation of alcohol‐induced cardiomyopathy. Our data suggests that Akt signaling plays an important role in supporting the beneficial effects of LA which is diminished with HA exposure having detrimental effects on cardiac function.Grant Funding Source: This work was supported in part by grants NIH/NIAAA/1R15AAA019816‐01A1, and 2G12 RR003048 RCMI/NCRR/

Alcohol‐Induced Electrical Remodeling: Effects of Sustained Short‐Term Ethanol Infusion on Ion Currents in Rabbit Atrium

In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. Ethanol infusion did not alter current densities of I(to) [58.7 +/- 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 +/- 5.0 pA/pF (EG, n = 24)], I(sus) [11.3 +/- 1.4 pA/pF (PG, n = 20) vs. 10.2 +/- 1.0 pA/pF (EG, n = 24)], and I(K1) [-1.6 +/- 0.3 pA/pF (PG, n = 17) vs. -2.0 +/- 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of I(Ca,L) current densities [-28.4 +/- 1.8 pA/pF (PG, n = 20) vs. -15.2 +/- 1.4 pA/pF (EG, n = 22)] and I(Na) [-75.4 +/- 3.6 pA/pF (PG, n = 17) vs. -35.4 +/- 4.4 pA/pF (EG, n = 21)], respectively. Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.