Both the absence of a direct correlation and the theory of the existence of a threshold dose (above which some alcoholics develop ACM) require the presence of individual susceptibility to alcohol induced cardiac damage63. It is unknown whether individual susceptibility would be related to increased vulnerability at the myocardial level and/or to impaired alcohol metabolism. Myocardial impairment following chronic excessive alcohol intake has been evaluated using echocardiographic and haemodynamic measurements in a significant number of reports. In these studies, haemodynamic and echocardiographic parameters were measured in individuals starting an alcohol withdrawal program. The findings were analysed taking into account the amount and chronicity of intake and they were compared with the same parameters measured in a control group of non-drinkers. Apoptosis may be induced by ethanol through mitochondrial membrane permeabilization and the release of pro-apoptotic factors (cytochrome c) from the mitochondrial inter-membrane space to the cytosol.
2. Ethanol-induced Myocyte Apoptosis and Autophagy
Although no significant changes were found using conventional microscopy, when electron microscopy was employed he discovered intracellular swelling, glycogen and lipid accumulation, and alterations in the structure of the sarcoplasmic reticulum and of the mitochondria (Figure 2). These changes, though subtle, were similar to those found by Ferrans and Hibbs in eight deceased individuals diagnosed with ACM42,43. On histological examination, various degrees of fibrosis, patchy areas of endocardial fibroelastosis, intramural blood clots and focal collections of swollen cells in both the epicardium and endocardium were found. Also, there were significant size variations in the myofibrils and they showed a relative decrease in the number of striations, in addition to swelling, vacuolisation and hyalinisation. Cell nuclei were larger than normal, morphologically difficult to define and they occasionally showed hyperpigmentation. The authors highlighted alcoholic cardiomyopathy the presence of an extensive intracellular accumulation of neutral lipids, principally in the form of small cytoplasmic droplets.
- Heberden 89 described angina so elegantly in 1786 and also added that ”considerable relief“ through ”wine and spirituous liquors“ could be expected.
- More studies today report alcohol consumption in terms of either “drinks” or grams/units of ethanol per day or week, and alcohol consumption is measured by self-report.
- Recent data favored a role for micro RNA, such as the involvement of miR-378a-5p in cardiomyocyte apoptosis and ACM development through ALDH2 gene suppression 120.
- These authors found a relationship between the reduction or cessation of alcohol consumption and higher survival rates without a heart transplant.
- Commonly seen cellular structural alterations include changes in the mitochondrial reticulum, cluster formation of mitochondria and disappearance of inter-mitochondrial junctions.
Heart Health
These genotypes have been shown to have a significant effect on the incidence of alcohol-induced cardiomyopathy and may explain the variable effects of long-term alcohol consumption amongst patients 108,109. Ang II is the bioactive molecule produced by the angiotensin converting enzyme (ACE) and linked to cardiac hypertrophy and other vascular disorders. Ang II activates a myriad of intracellular pathways among them cytochrome P450, calmodulin-dependent protein kinase II, NAD(P)H oxidase and inducible nitric oxide synthase (iNOS) 110,111. Thus in addition to raising intracellular calcium, AT1 receptor activation stimulates the production of the free radical species superoxide anion and nitric oxide 111,112. Ricci et al. observed two distinct phases of robust oxidant generation in cardiomyocytes exposed to Ang II 111. One of the relevant facts in ACM is the existence of a clear gender difference, women being more susceptible to the toxic effects of alcohol than men at the same level of lifetime ethanol consumption 93,94.
Pharmacological treatment for alcohol use disorder
As pointed out before, the current accepted definition of ACM probably underestimates the number of women affected by the disease. Alcohol affects heart function and is dependent on the quantity of alcohol that the heart is exposed to. Women typically have a lower BMI than men, and therefore the same alcohol exposure can be achieved with lower alcohol intake. Finally, it is worth stressing that a large majority of studies on the physiopathology and prognosis of ACM were conducted some years ago, prior to the development of our current understanding regarding the role of genetics in DCM67. According to recent data, a genetic form of DCM could be present in up to 50% of idiopathic DCM cases, and other specific forms of DCM such as peripartum cardiomyopathy have been shown to have a genetic basis in a significant number of cases68.
Acknowledgments
Activation of PKCɛ may protect the myocardium against ischemia–reperfusion injury by stimulating the opening of mitochondrial =https://ecosoberhouse.com/ ATP-sensitive potassium channels. This in turn prevents the opening of the mitochondrial permeability transition pore (Walker et al. 2013). In Munich, the annual consumption of beer reached 245 l per capita and year in the last quarter of the 19th century. In 1884, the pathologist and veterinarian Otto von Bollinger (Fig. 2a) described the “Munich beer heart” with fibrosis, hypertrophy, and fatty degeneration in postmortem cardiac tissue of alcoholics who consumed an estimated average of 432 liters of beer per year (Fig. 2b; 23). At that time every 10th necropsy in men at the Munich pathology institute named cardiac dilatation and fatty degeneration as “Bierherz” being its underlying cause.
- In 1819 the Irish physician Dr. Samuel Black, who had a special interest in angina pectoris described what is probably the first commentary pertinent to the ”French Paradox“ 91.
- Caution for anticoagulation is warranted due to the problems of noncompliance, trauma, and overdosage especially in hepatic dysfunction.
- Notably, in patients with a history of chronic alcohol consumption complicated by significant myocardial dysfunction and chronic malnutrition, re-feeding syndrome may increase the cardiac dysfunction.
- New therapeutic strategies for AC are being developed with the support of animal models.
In addition, ethanol is an immunosuppressive drug that is pro-inflammatory and pro-oncogenic 14,15,16,17. It has been said that ethanol is the “perfect drug” because of its pleasant effects but damaging long-term effect 1,6. It is distributed worldwide, with easy social access, and is pleasant when consumed, with positive sensations of welfare, but its negative effects, which include depressive and damaging noxious health effects, are reserved for Substance abuse later. Ethanol is one of the most addictive drugs for humans, with high physical and psychological addiction potential 7.
Direct toxic effect of ethanol
Daily alcohol consumption of 80 g per day or more for more than 5 years significantly increases the risk, however not all chronic alcohol users will develop Alcohol-induced cardiomyopathy. The proportion of cardiomyopathy cases attributable to alcohol abuse has ranged from 23 to 40 percent (Piano and Phillips 2014). Recently, Guzzo-Merello and colleagues (2015) reported that, among 282 patients with a dilated cardiomyopathy phenotype, 33 percent had ACM.
