With the rapid development of the social economy in China, the incidence of diseases caused by excessive drinking is gradually increasing as well. Alcoholic cardiomyopathy refers to long-term high intake of ethanol, and has typical dilated cardiomyopathy characteristics, such as, hemodynamic changes, symptoms, signs, and morphological features. It is a kind of cardiomyopathy that excludes other causes of dilated cardiomyopathy. Due to the lack of specific pathological changes, the forensic pathological identification of alcoholic cardiomyopathy can only be based on the patient's medical history and by ruling out other causes of cardiomyopathy. This paper reviews the pathogenesis and forensic identification of alcoholic cardiomyopathy in order to provide reference for forensic pathologists and clinicians.
Cardiomyopathy, Alcoholic/pathology* ; China ; Ethanol ; Forensic Pathology/trends* ; Humans

BACKGROUND: The hepatic and neuropsychiatric disorders caused by long term excessive alcohol abuse have been well documented. However the pathogenesis and clinical characteristics of cardiovascular disorder caused by excessive alcohol abuse has not been documented. Many patients diagnosed as idiopathic dilated cardiomyopathy(IDCM) are apt to have a history of heavy alcohol consumption and are categorized as having alcoholic ardiomyopathy(ACM). METHODS: Twenty men(agedd 32 to 63 yrs, mean age 48.6 yrs) with dilated dcardiomyopathy, with the history of excessive alcohol abuse, were analyzed with fifteen patients with IDCM as control. RESULTS: The most common alcoholic beverage consumed in ACM is Diluted soju(85.0%) followed by Takju(10.0%), beer(5.0%). Average daily alcohol consumption is 134.5+/-40.3 g, frequency of alcohol intake in a week 5.4+/-1.4 times, total life time dose of ethanol 20.0+/-7.8kg/kg of body weight and duration of alcohol intake 26.9+/-8.4 years. There were no significant differences in symptoms between the two groups. In electrocardiography, atrial fibrillation is more frequent in ACM group(40%) than IDCM group(20%). In ACM group, serum concentrations of triglyceride and total cholesterol are higher than IDCM group, but no differences in serum HDL-cholesterol, SGOT, SGPT concentrations. In echocardiography, left ventricular systolic internal dimension and right ventricular internal dimension is smaller and ejection fraction is larger in ACM group than IDCM group. CONCLUSION: We studied the clinical, laboratory, electrocardiographic and echocardiographic characteristics of alcoholic cardiomyopathy comparing with idiopathic dilated cardiomyopathy.
Alanine Transaminase ; Alcohol Drinking ; Alcoholic Beverages ; Alcoholics* ; Alcoholism ; Aspartate Aminotransferases ; Atrial Fibrillation ; Body Weight ; Cardiomyopathy, Alcoholic* ; Cardiomyopathy, Dilated ; Cholesterol ; Echocardiography* ; Electrocardiography ; Ethanol ; Humans ; Triglycerides

OBJECTIVETo study a simple and reliable method to produce the rat model of alcoholic cardiomyopathy, evaluating the model with isoprenaline provocation test (IPT) and morphological indicators.

METHODSAdult male rats were intragastrically infused of wine (52% v/v) at 20 g/(kg x d) for 15 days with the general condition, the change of eating amount and weight being observed. The levels of mean left ventricle systolic pressure (mLVSP), mean left ventricle diastolic pressure (mLVDP), mean left ventricle pressure (mLVP), heart ratio (HR), maximal rise velocity of left ventricular pressure (+ dp/dtmax), maximal fall velocity of left ventricular pressure (- dp/dtmax) and the reaction of isoprenaline were examined by left ventricular cannulation, and the morphological change was observed with optical microscope and transmission electron microscopy.

RESULTSBoth diastolic and systolic function of the model rats was lower than that of the control group as well as the cardiac energy reserve induced by IPT. Pathological observation demonstrated myocardial hypertrophy, myocardiocyte necrosis and infiltration of inflammatory cells. The transmission electron microscopy showed that mitochondria became enlarged or crimpled with fused or disappeared cristae and myofibrils dissolved and fractured.

CONCLUSIONThe adult male SD model rats exhibit diabetic cardiomyopathy by intragastric infusion of wine (52% v/v) at 20 g/(kg x d) for 15 days. IPT can induce the cardiac energy reserve and evaluate that accurately, displaying the hidden heart dysfunction.

Animals ; Cardiomyopathy, Alcoholic ; physiopathology ; Disease Models, Animal ; Isoproterenol ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVES: To establish an electrophysiological model of alcoholic cardiomyopathy by inducing pluripotent stem cells (iPSCs) to differentiate into cardiomyocytes (iPSC-CM) in vitro. METHODS: The human iPSC were expanded in vitro and differentiated into iPSC-CM. The iPSC-CM were divided into a blank control group, an alcoholic experiment group (according to the concentration of alcoholic, the alcoholic experiment was also divided into many subgroups), and a KN93 treatment group. Then the efficiency of iPSC differentiated to iPSC-CM was detected by immunofluorescence, the function of iPSC-CM was detected by cell counting kit-8 (CCK8) assay and lactate dehydrogenase (LDH) activity assay kit. The electrophysiological activity of iPSC-CM was monitored by real time cellular analysis (RTCA), the injury of iPSC-CM caused by alcohol was further verified by the mitochondrial membrane potential fluorescence probe JC-1 staining combined with RTCA analysis. RESULTS: Compared with the blank control group, the different doses (25, 50, 100, 150, 200, 250, 300 mmol/L) of alcohol could significantly inhibit the proliferation of iPSC-CM in a dose-dependent manner (all <0.05). Compared with the blank control group, the activity of iPSC-CM was significantly reduced by 100 mmol/L alcohol, resulting in the increase of LDH release, the decrease of mitochondrial membrane potential, the amplitude and beating rate (all <0.05). Compared with the 100 mg/mL alcoholic experiment group, the KN93 treatment group significantly alleviated the damage of alcohol to iPSC-CM by blocking the necrotic apoptotic pathway, resulting in the decrease of LDH release, the increase of mitochondrial membrane potential, the amplitude and beating rate (all <0.05). CONCLUSIONS The electrophysiological model of alcoholic cardiomyopathy based on the differentiation of cardiomyocytes are successfully established, which can be used to study the electrophysiological activity and the molecular mechanism for relevant diseases, and it may provide a more reasonable and effective research tool for drug screening and clinical study.
Cardiomyopathy, Alcoholic ; Cell Differentiation ; Electrophysiological Phenomena ; Humans ; Induced Pluripotent Stem Cells ; Myocytes, Cardiac

BACKGROUND AND PURPOSE OF THE RESEARCH: It is believed that a long-term drinking will be one of the causes of congestive cardiomyopathy (CM). It is also possible for diagnosis of alcoholic cardiomyopathy in the majority of the patients diagnosed as idiopathic dilated cardiomyopathy if the history of mass alcoholic drinking is taken into consideration or proper blood test is conducted. This study is to confirm whether there is an improvement in the clinical result and cardiac function as has so far been known the case in the patients suspected of alcoholic. METHODS: Among 39 patients with dilated CM who were diagnosed by echocardiographic criteria and clinical evaluation, 11 patients who drank more than 77 g of alcoholic everyday for more than 10 years were defined as alcoholic CM. The changes of their clinical manifestations and m-mode echocardiographic findings in the patients with alcoholic CM were compared before and after treatment. RESULTS: All studied patients were male with the mean age of 52.6+8.0 and the mean follow up period was 38.6 months. Of the 11 patients, 3 patients could not completely free themselves from drinking. Their symptoms on first visit ranged in such order as dyspnea (63.6%), tachycardia (54.5%), and generalized edema (27.3%). Following the treatment, dyspnea and tachycardia showed a statistically significant improvement. Echocardio-graphic parameters, ie, LV diastolic dimension (6.7+/-0.6 cm before treatment and 6.3+/-1.2 cm after treatment), LV systolic dimension (5.6+/-0.7 cm before treatment and 5.2+/-1.4 cm after treatment) and E point septal separation (13.6+/-9.6 mm before treatment and 10.9+/-6.6 mm after treatment) decreased after treatment without a significant meanings in a statistical view point. Their ejection fraction (29.6+/-6% before treatment and 34.5+/-11.1% after treatment) increased after treatment. CONCLUSION: Cardiac symptoms of congestive heart failure and echo-cardiographic parameters in patients with alcoholic CM were improved after abstinence from alcoholic ingestion and medical treatment.
Alcoholics* ; Cardiomyopathy, Alcoholic* ; Cardiomyopathy, Dilated ; Diagnosis ; Drinking ; Dyspnea ; Eating ; Echocardiography* ; Edema ; Follow-Up Studies ; Heart Failure ; Hematologic Tests ; Humans ; Male ; Tachycardia

BACKGROUND AND OBJECTIVES: About 25% of the patients with non-ischemic left ventricular (LV) systolic dysfunction will improve spontaneously. However, little has been known about the fate of the patients stricken with heart failure after recovery from LV dysfunction. We hypothesized that the patients who recovered from non-ischemic LV dysfunction have a substantial risk for recurrent heart failure. SUBJECTS AND METHODS: Fifty patients (32 males, mean age: 54.9+/-12.4 years) who recovered from systolic heart failure (LV ejection fraction; an EF of 28.8+/-7.2% at the initial presentation) to near-normal (LVEF > 40% and a 10% or more increase in the absolute value) were monitored for the recurrence of heart failure. Patients with significant coronary artery disease were excluded. The etiologies of heart failure were idiopathic dilated cardiomyopathy (n=39), alcoholic cardiomyopathy (n=7), adriamycin-induced cardiomyopathy (n=2), and tachycardia-induced cardiomyopathy (n=2). After recovery of LV dysfunction, the patients were followed up for a mean of 41.0+/-26.3 months. RESULTS: In 9 patients (18%), the LV systolic dysfunction recurred during follow-up (LVEF 32.6+/-7.3%). There was no significant difference in the baseline clinical and echocardiographic variables between the patients with and without recurrent heart failure. However, cessation of anti-heart failure medication was more frequently observed in the patients with recurrent LV systolic dysfunction (55.6% vs 4.9%, respectively, p<0.05). CONCLUSION: Recurrent heart failure may ensue in the patients with reversible non-ischemic LV systolic dysfunction. The maintenance of anti-heart failure medication in these patients may be a significant influencing factor for their clinical prognosis.
Cardiomyopathies ; Cardiomyopathy, Alcoholic ; Cardiomyopathy, Dilated ; Coronary Artery Disease ; Echocardiography ; Follow-Up Studies ; Heart Failure ; Heart Failure, Systolic ; Humans ; Male ; Prognosis ; Recurrence

OBJECTIVETo explore the time course of renin-angiotensin system (RAS), peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma change in an animal model of alcoholic cardiomyopathy (ACM).

METHODSAdult rats were divided into three groups: ACM group (A, 10% alcohol as drinking water plus 5 ml 60% alcohol.kg(-1).d(-1) per gavage in the 1st week; 10% alcohol as drinking water plus 10 ml 60% alcohol/kg bid per gavage in the 2nd week, 20% alcohol as drinking water plus 15 ml 60% alcohol/kg bid per gavage during week 3 to week 16), ACM/ARB group(B, A + Irbesartan 5 mg.kg(-1).d(-1) per gavage) and control group (C). mRNA expressions and activities of renin, angiotensin, ACE and AT1 were detected with RT-PCR and radioimmunoassay methods. Protein expressions of PPARalpha and PPARgamma were determined with Western blot. Echocardiogram, optic (HE) and electron microscope examinations were also performed. Parameters were obtained at 2 or 6 months (n = 7 - 10 each).

RESULTSCompared with group C, LV/BW ratio was significantly increased and LVEF significantly decreased, activities and expressions of Ang I, Ang II and renin were gradually increased, protein expressions of PPARalpha were gradually decreased at 2 and 6 months in group A (all P < 0.05). These changes could be partly attenuated by Irbesartan.

CONCLUSIONActivated RAS and decreased protein expressions of PPARalpha and PPARgamma contributed to the development of ACM.

Animals ; Cardiomyopathy, Alcoholic ; metabolism ; Disease Models, Animal ; Male ; PPAR alpha ; metabolism ; PPAR gamma ; metabolism ; Rats ; Rats, Wistar ; Renin-Angiotensin System

OBJECTIVES: It is well known that many chronic alcoholics manifest diastolic dysfunction of left ven tricle in its early stage. But the effects of chronic alcohol drinking on right ventricular function are not well understood. Thus left ventricular filling impair ment and its effects to right ventricular diastolic function were evaluated in young chronic alcoholics. METHODS: For the evaluation of left and right ventricular diastolic function in chronic alcoholics, 30 young chronic alcoholics and 28 control subjects were studied by pulsed Doppler echocardiography at the left and right ventricular inflow. Peak E velocity, peak A velocity, E/A velocity ratio, acceleration time and deceleration time were measured as diastolic filling parameters. RESULTS: 1) In the chronic alcoholics, the interventricular septum and posterior wall were thicker and left ventricular muscle mass was significantly increased than that in controls. 2) Among 30 cases of chronic alcoholics, 8 cases(26.7%) showed that the E/A ratio of the left ventricle was less than 1.0 and the deceleration time of the left ventricle was more than 240msec, where as 12 cases(40.0%) showed that the E/A ratio of the left ventricle was less than 1.0. 3) Among 30 cases of chronic alcoholics, 8 cases (26.7%) showed that the E/A ratio of the right ventri cle was less than 1.0 and the deceleration time of the right ventricle was more than 232msec, whereas 14 cases(46.7%) showed that the E/A ratio of the right ventricle was less than 1.0. 4) The RV E/A ratio was significantly correlated with the LV E/A ratio(r=0.697, p<0.001). 5) Blood pressure, ejection fraction, left ventricular mass, E/A ratio and deceleration time of both ventricles were not significantly different in comparison with the daily average amount, duration of ingestion, and total lifetime dose of alcohol. CONCLUSION: In all chronic alcoholics less than 50 years of age, the left ventricular systolic function was normal. But Doppler echocardiography showed that diastolic dysfunction of the left and right ventricles was present in 8 cases of 30 chronic alcoholics. Right ventricular diastolic dysfunction was closely related with left ventricular diastolic dysfunction. In conclu sion, diastolic dysfunction of both ventricle in chronic alcoholics may be the earliest functional sign of preclinical alcoholic cardiomyopathy.
Acceleration ; Alcohol Drinking ; Alcoholics* ; Blood Pressure ; Cardiomyopathy, Alcoholic ; Deceleration ; Eating ; Echocardiography* ; Echocardiography, Doppler ; Echocardiography, Doppler, Pulsed ; Heart Ventricles ; Humans ; Ventricular Function, Right

OBJECTIVETo investigate the protective effect of puerarin on the myocardium of rats with acute and chronic alcoholism.

METHODSIn acute alcoholism experiment, normal male SD rats were randomly divided into the control group, alcoholism group and puerarin group (n=8), and high- and low-dose puerarin was administered. In chronic alcoholism experiment, increasing puerarin doses were given. Serum and myocardial levels of spartate aminotransferase (AST) and creatine phosphokinase (CPK) were determined using enzymatic methed, and superoxide dismutase (SOD), malondialdehyde (MDA), Ca(2+)-Mg(2+)-ATPase, and Na(+)-K(+)-ATPase in the myocardium were assayed with colorimetric method. HE staining was used to observe the microscopic changes of the myocardium.

RESULTSCompared with alcoholism group, puerarin-treated groups showed significantly lowered myocardial contents of MDA, CPK and AST and serum levels of AST and CPK (P<0.05, P<0.01) and increased myocardial SOD (P<0.05, P<0.01), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity (P<0.05, P<0.01), but Na(+)-K(+)-ATPase was similar between the two groups (P>0.05). HE staining of the myocardium showed cell swelling and obscure cell boundaries in alcoholism group, especially in chronic alcoholism group. The myocardial structure in puerarin group remained clear and regular.

CONCLUSIONPuerarin can protect from myocardial injuries induced by acute and chronic alcoholism in rats.

Alcoholism ; drug therapy ; Animals ; Cardiomyopathy, Alcoholic ; metabolism ; pathology ; prevention & control ; Ethanol ; toxicity ; Isoflavones ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of carnitine on cardiac function, collagen contents, peroxisome proliferator-activated receptor alpha (PPARalpha) and retinoid X receptor alpha (RXRct) expressions in a rat alcoholic cardiomyopathy modeL.

METHODSAdult male Wistar rats were randomly divided into alcohol group (A) , alcohol/carnitine group (B) and control group. Six months later, protein expressions of collagen I, collagen III, matrix metalloproteinase-9 (MMP-9) and Smad-3 were determined by immunohistochemical staining. Protein expressions of PPARalpha and RXRalpha were detected by Western blot.

RESULTSExpressions of collagen I, collagen III, MMP-9 and Smad-3 were significantly increased in groups A and B compared to group C (P < 0.01 or P < 0.05). Expressions of PPARalpha and RXRalpha (0.156 and 0.192, respectively, in group A; 0.248 and 0.385, respectively, in group B) were decreased compared to group C (P < 0.01 or P < 0.05). These changes were significantly attenuated by carnitine (all P < 0.05, group B vs. group A). Moreover, PPARalpha and RXRalpha positively correlated with EF and FS, and negatively correlated LVEDd, collagen I , collagen III, MMP-9 and Smad-3 (all P < 0.01).

CONCLUSIONPPARalpha and RXRalpha downregulation is significantly correlated with cardiac dysfunction in this alcoholic cardiomyopathy model, carnitine ameliorated the cardiac fibrosis and remodeling possibly through upregulating the metabolic pathways of PPARalpha and RXRalpha.

Animals ; Cardiomyopathy, Alcoholic ; metabolism ; pathology ; prevention & control ; Carnitine ; therapeutic use ; Male ; Myocardium ; metabolism ; pathology ; PPAR alpha ; metabolism ; Rats ; Rats, Wistar ; Retinoid X Receptor alpha ; metabolism