Binge Alcohol Exposure in Adolescence Impairs Normal Heart Growth

Abstract

Background Approximately 1 in 6 adolescents report regular binge alcohol consumption, and we hypothesize it affects heart growth during this period. Methods and Results Adolescent, genetically diverse, male Wistar rats were gavaged with water or ethanol once per day for 6 days. In vivo structure and function were assessed before and after exposure. Binge alcohol exposure in adolescence significantly impaired normal cardiac growth but did not affect whole‐body growth during adolescence, therefore this pathology was specific to the heart. Binge rats also exhibited signs of accelerated pathological growth (concentric cellular hypertrophy and thickening of the myocardial wall), suggesting a global reorientation from physiologic to pathologic growth. Binge rats compensated for their smaller filling volumes by increasing systolic function and sympathetic stimulation. Consequently, binge alcohol exposure increased PKA (protein kinase A) phosphorylation of troponin I, inducing myofilament calcium desensitization. Binge alcohol also impaired in vivo relaxation and increased titin‐based cellular stiffness due to titin phosphorylation by PKCα (protein kinase C α). Mechanistically, alcohol inhibited extracellular signal‐related kinase activity, a nodal signaling kinase activating physiology hypertrophy. Thus, binge alcohol exposure depressed genes involved in growth. These cardiac structural alterations from binge alcohol exposure persisted through adolescence even after cessation of ethanol exposure. Conclusions Alcohol negatively impacts function in the adult heart, but the adolescent heart is substantially more sensitive to its effects. This difference is likely because adolescent binge alcohol impedes the normal rapid physiological growth and reorients it towards pathological hypertrophy. Many adolescents regularly binge alcohol, and here we report a novel pathological consequence as well as mechanisms involved.

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

“…Abstinence restored cardiac function back to a control level, and in some measures, exceeded control levels. A recent study showed that cardiac growth can be compromised by alcohol consumption in adolescent Wistar rats [35], which is consistent with our findings, though our mice were already in early adulthood. It is possible that alcohol consumption delayed the growth of their hearts, which rebounded after abstinence.…”

Simvastatin Significantly Reduced Alcohol-Induced Cardiac Damage in Adolescent Mice

“…Alcohol permeability is further implicated in the disruption of signalling processes, activation of apoptosis, and the loss of heart contraction [ 7 , 9 ]. Even acute alcohol exposure has been demonstrated to elicit haemodynamic changes (cardiac stress) leading to the enlargement of cardiomyocytes [ 7 , 33 , 36 ]. However, it must be noted that myocardial hypertrophy (which causes the thickening of the ventricular wall) may occur at the early stages of alcohol damage as a compensatory mechanism for the sarcoplasmic reticular dysfunction (arising from the effect of alcohol) [ 8 , 9 , 35 , 37 ].…”

“…A hindered repair mechanism promotes myocardial fibrosis [ 9 ] disrupting myocardial remodelling which is an essential contributor to the repair of ventricular wall damage [ 10 , 38 ]. The failure of remodelling after ventricular wall damage leads to ventricular dysfunction [ 10 ] characterized by a dilated left ventricle, a thin left ventricular wall, a disrupted myofibrillary architecture, and contractile dysfunction [ 33 , 35 , 36 ]. Ventricular dysfunction in alcoholics is also caused by the disruption of calcium ion homeostasis and its regulation by inhibiting endothelial nitric oxide synthase (eNOS) [ 38 – 40 ].…”

Postoperative acute heart failure in an 18-year-old McCune--Albright syndrome patient without preoperative cardiac morphology abnormality -- a case report and literature review

“…Firstly, long-term cAMP overload may induce myofilament calcium desensitization of the cardiac myocytes through increased protein kinase A. Therefore, the desensitized cardiac myocytes cannot respond effectively to the increased calcium influx to enhance the cardiac contractibility when the fluid load increases 21,22 . Secondly, long-term Ca 2+ overload may have a negative impact on the compliance of the heart due to the hypertrophied myocytes and increased myocardial contractility 23 .…”