Effect of Prolonged Alcohol Administration on Calcium Transport in Heart Muscle of the Dog

Abstract

The effect of prolonged administration of alcohol on calcium binding and uptake by sarcoplasmic reticulum and mitochondria and on respiratory function of mitochondria was investigated in heart muscle of dogs. Dogs were paired and maintained with and without alcohol for 6 months; alcohol was administered by adding it to drinking water and food with vitamin supplements. Measurements were made after alcohol had been temporarily withheld for 2 days. Prolonged alcohol ingestion resulted in a decline in calcium binding and uptake by sarcoplasmic reticulum and mitochondria, suggesting a diminished affinity of the reticular and mitochondrial membranes for calcium ions. The endogenous calcium content of mitochondria and sarcoplasmic reticulum decreased. Prolonged alcohol administration failed to alter cardiac contractility, although contraction and relaxation tended to diminish following the administration of angiotensin. The results illustrate that one link in the regulation of the state of contraction or relaxation involving myofibrillar calcium transport is weakened in dogs maintained on alcohol for prolonged periods of time. KEY WORDScalcium binding and uptake mitochondrial respiration sarcoplasmic reticulum alcohol and cardiac contractility excitation-contraction coupling

Alcoholic Cardiomyopathy: Pathophysiologic Insights

“…These effects include: myocyte loss and disarray (18), sarcoplasmic reticulum dysfunction (19–21) and changes in intracellular Ca 2+ handling (22), depressed/disturbed mitochondrial function (20,23,25,26), decreased myofibrillar ATPase activity (25,27), decreased myofibrillar calcium sensitivity (28), contractile protein fragmentation and disarray (11, 29, 30) and fatty acid accumulation within intracellular organelles (31–33). Accumulation of reactive oxygen species (ROS) can induce changes in intracellular organelles or processes through lipid peroxidation and/or other chemical modifications of structural proteins, cytoskeletal proteins, transport proteins, and enzymes (34).…”

Angiotensin II Type 1 Receptor Blockade Prevents Alcoholic Cardiomyopathy

“…1,2 However, the experimental evaluation of cardiac contractile performance as alcoholism progresses has been difficult in the past due to the lack of animal models that more closely resemble or mimic the human condition in terms of the amount and pattern of alcohol consumption. 2,[17][18][19] Although acute alcohol consumption has been demonstrated to have a direct cardiodepressant effect, 20 chronic alcohol intake has been variably reported to have no direct effect 21,22 or to impair LV performance. 18,19 Previous investigations with dogs administered alcohol for 6 months 21 or longer 19 demonstrated a clear impairment of LV relaxation and diastolic filling and an abnormal response to angiotensin infusion, which is consistent with our findings.…”

Mechanism of myocardial contractile depression by clinical concentrations of ethanol. A study in ferret papillary muscles.

“…This effect occurs in normals, alcoholics, and patients with dilated cardiomyopathy, and almost certainly has a different mechanism from the cardiomyopathy induced by longterm ethanol consumption (7)(8)(9)(10)(11)(12)(13)(14). Most studies of isolated myocardium have sought to explain these acute and reversible changes in the force of contraction by using pharmacologic concentrations of ethanol in the 1% (by volume) range (see reference 12).…”