Acute and chronic exposure to ethanol (ETOH) is associated with electrophysiologic anomalies and contractile depression. Chronic alcoholism, in many instances, leads to the development of a specific cardiomyopathy. However, the exact mechanism of this self-induced pathology is poorly understood. Prolonged alcohol use alone can myocardial dysfunction but, its deleterious effects can be exoerbated by other diseases or behavior that occur independent of (hypertension, smoking and diabetes) secondary (malnutrition and cirrhosis), to alcoholism. Considerable epidemiological and clinical data indicate that chronic alcohol abuse is prevalent in urban communities as is essential hypertension. However, little is known regarding the effects of long-term ETOH consumption on cardiac electromechanical function in hypertensive patients with underlying cardiovascular disease particularly with regard to : dose and concentration of ETOH, duration of intake, experimental species and conditions. Ethanol, alone, exerts concentration-dependent effects on electromechanical properties of myocardial tissue. Low concentrations of ETOH enhance, whereas higher concentrations depress both automaticity and contractile force of cardiac muscle. High concentrations of ETOH also reduces the action potential duration of isolated cardiac fibers which may generate spontaneous arrhythmias, both atrial and ventricular. Recent studies suggest that ETOH-induced alterations in cardiac function may be attributed to biochemical, metabolic and ultrastructural changes in cardiomyocytes. However, the mechanism underlying myocardial dysfunction remain only partially understood. Acetaldehyde (ACA) and tetrahydroisoquinoline alkaloids (TIQ's), condensation products of ACA and biogenic amines, are two substances that may in part mediate ETOH-induced myocardial dysfunction. Thus, the long-term objective of this proposal is to determine the acute and chronic effects of ETOH exposure on myocardial electromechanical function using a hypertensive animal model. In addition, role of acetaldehyde and TIQ's in mediating the deleterious effects of ETOH on the functional properties of myocardial tissue will also be investigated. Using the spontaneously hypertensive rat model (SHR) the acute and chronic effects of ethanol, acetaldehyde and tetrahydropapaveroline on: 1) the automaticity and membrane potentials of the isolated sinus node; 2) electromechanical function of isolated ventricular papillary muscle and; 3) calcium mobilization in individual cardiomyocytes will be studied.
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