ALCOHOL EFFECTS ON HEART FUNCTION--GENDER DIFFERENCES

描述（改编自研究者摘要）：长期

DESCRIPTION (Adapted from the Investigator's Abstract): The long-term objective of this proposal is to understand the changes in cardiac structure and pathophysiological mechanisms that are associated with alcoholic heart disease. The specific aims of this investigation are: (1) to determine in male and female rats the evolution of alcohol-induced changes in cardiac structure (hypertrophy and dilation/cardiomyopathy) and (2) to determine if the development of alcohol-induced cardiomyopathy is associated with corresponding changes in myocardial contraction and activation of specific hemodynamic and neuroendocrine mechanisms in male and female rats. It is well established that chronic alcohol consumption produces functional changes in the myocardium which lead to the development of cardiomyopathy. However, little is known about the progression of alcohol-induced cardiomyopathy, specifically how changes in myocardial structure correlate to changes in contractile function and activation of specific neurohumoral or hemodynamic mechanisms. In addition, there have been many studies documenting the adverse effects of alcohol in male hearts, while the effects alcohol consumption in the female heart are relatively unknown. Male and female Sprague-Dawley rats will receive either the Lieber- DeCarli alcohol or control diet, while a third group will receive rat chow. Animals will be maintained on this protocol for 3 and 6 months. Changes in left ventricular size and chamber dilation will be assessed by echocardiography at 4 week intervals. The indirect tail-cuff method will be used to measure blood pressure at 2 week intervals. Animals will be sacrificed at 3 and 6 months in order to evaluate alcohol- induced changes in myocardial contractility and morphology. To evaluate the latter light and electron microscopy will be performed and changes in contractility will be measured in an isolated papillary muscle preparation. Also at the time of sacrifice, plasma renin and plasma and tissue angiotensin-converting enzyme (ACE) activity will be measured using a radioimmunoassay technique and fluorimetric assay, respectively. Finally, all of the above variables will be re-examined in ethanol-fed and control animals after they have received long-term therapy with either an ACE inhibitor or B-adrenergic blocker. The results of this study will lead to a better understanding of the pathophysiology of alcoholic cardiomyopathy and rational development of therapeutic innervations to prevent and treat alcohol-induced cardiomyopathy.