The development of alcohol-induced cardiac dysfunction in the rat.

Abstract

Hemodynamic, contractile and energetic functions of isolated working hearts from ethanol-fed and control rats were studied to determine the time course of cardiac dysfunction development during long-term consumption of alcohol. Hearts from fasted, 24 hr withdrawn rats were studied after 2, 4, 7 and 11 months consuming ethanol as 38% of daily calories in a nutritionally-adequate liquid diet. After 2 months, the right ventricle of the alcoholic rat hearts was significantly enlarged; left ventricular weight was not significantly different from control and there was little evidence that left ventricular function was compromised. After 4 months and 7 months, there was biventricular cardiomegaly and evidence of reduced left ventricular function in the alcoholics, although altered sensitivity to the positive inotropic agent, dobutamine, was not evident in those hearts. After 11 months, cardiac output, stroke work, and peak power of the alcoholic rat hearts were significantly depressed, the responsiveness of the left ventricle to dobutamine was diminished, and both ventricles were enlarged compared to controls. Cardiac function during early withdrawal was studied in rats that had consumed alcohol for 14-16 months. Hearts from non-fasted rats at 0 hr of withdrawal exhibited diminished responsiveness to dobutamine compared to controls; at 24 hr and 72 hr of withdrawal no differences between alcoholic and control rat heart dobutamine responsiveness were observed. The data indicated that: (a) cardiomegaly, beginning with right ventricular enlargement, was an early indicator of alcohol's cardiac effects in rats; (b) left ventricular enlargement of the alcoholic rat hearts was associated with basal left ventricular dysfunction; and (c) evidence of cardiac subsensitivity to dobutamine, which is characteristic of this alcoholic rat model, depended on the nutritional status and withdrawal state of the rat at the time that the heart was excised for study.