The Effects of Ethanol on the Heart: Alcoholic Cardiomyopathy

Abstract

Alcoholic-dilated Cardiomyopathy (ACM) is the most prevalent form of ethanol-induced heart damage. Ethanol induces ACM in a dose-dependent manner, independently of nutrition, vitamin, or electrolyte disturbances. It has synergistic effects with other heart risk factors. ACM produces a progressive reduction in myocardial contractility and heart chamber dilatation, leading to heart failure episodes and arrhythmias. Pathologically, ethanol induces myocytolysis, apoptosis, and necrosis of myocytes, with repair mechanisms causing hypertrophy and interstitial fibrosis. Myocyte ethanol targets include changes in membrane composition, receptors, ion channels, intracellular [Ca²⁺] transients, and structural proteins, and disrupt sarcomere contractility. Cardiac remodeling tries to compensate for this damage, establishing a balance between aggression and defense mechanisms. The final process of ACM is the result of dosage and individual predisposition. The ACM prognosis depends on the degree of persistent ethanol intake. Abstinence is the preferred goal, although controlled drinking may still improve cardiac function. New strategies are addressed to decrease myocyte hypertrophy and interstitial fibrosis and try to improve myocyte regeneration, minimizing ethanol-related cardiac damage. Growth factors and cardiomyokines are relevant molecules that may modify this process. Cardiac transplantation is the final measure in end-stage ACM but is limited to those subjects able to achieve abstinence.

Keywords: alcohol; alcoholic cardiomyopathy; ethanol; heart damage.

Figure 1

Different effects of ethanol on cardiomyocyte organelles. (Adapted form Nature 451; 929–936, 2008). Cardiac myocytes are excitable cells with complex signaling and contractile structures and are highly sensitive to the toxic effect of alcohol on: (1) plasma membrane composition and permeability, signaling, and activation of apoptosis; (2) L-Type Ca²⁺ channel activity; (3) Na⁺/K⁺ ATPase channel activity; (4) Na⁺/Ca²⁺ exchanger activity; (5) Na⁺ channel currents; (6) K⁺ channel currents; (7) ryanodine Ca²⁺ release; (8) sarcomere Ca²⁺ sensitivity, excitation–contraction coupling, myofibrillary structure, and protein expression; (9) several aspects of mitochondrial function, including respiratory complex activities; (10) cytoskeletal structure; (11) nuclear regulation of transcription; (12) ribosomal protein synthesis; (13) desmosomal contacts; (14) connexin channel communication; (15) sarcoglycan complex interactions.

Figure 2

Histological lesions in the subclinical and clinical periods of human alcoholic cardiomyopathy. Left ventricle apical biopsy. Semithin section. Toluidine blue staining x 400 magnification. Left: Subclinical period with slight signs of myocytolysis, disarray, and myocyte hypertrophy (arrows). Right: End-stage clinical period with myocyte loss, diffuse interstitial fibrosis and intense nuclear and myocyte hypertrophy (white arrows).