ALCOHOL EFFECTS ON HEART FUNCTION--GENDER DIFFERENCES

描述（改编自研究者摘要）：长期 本研究的目的是了解心脏的变化， 结构和病理生理机制， 酒精性心脏病 这项调查的具体目的是： (1)在雄性和雌性大鼠中确定酒精诱导的 心脏结构变化（肥大和扩张/心肌病） 和（2）确定酒精诱导的发展是否 心肌病与心肌细胞的相应变化有关， 收缩和激活特定的血液动力学和神经内分泌 雄性和雌性大鼠的机制。 众所周知，慢性 饮酒会引起心肌功能的变化， 导致心肌病的发生 然而， 酒精诱发的心肌病的进展，特别是 心肌结构的变化如何与心肌收缩力的变化相关 功能和激活特定的神经体液或血液动力学 机制等 此外，还有许多研究记录了 酒精对男性心脏的不良影响，而酒精的影响 在女性心中的消费是相对未知的。 雄性和雌性Sprague-Dawley大鼠将接受Lieber- DeCarli酒精或对照饮食，而第三组将接受大鼠 周梁淑 动物将按照本方案饲养3和6个月。 将评估左心室大小和腔室扩张的变化 每隔4周进行超声心动图检查。 间接尾套法 将用于每隔2周测量血压。 动物 将在3个月和6个月时处死，以评估酒精含量- 引起心肌收缩力和形态学的变化。 评价 将进行后者的光学和电子显微镜检查， 将在分离的乳头肌中测量收缩性 准备. 同样在处死时，血浆肾素和血浆和 将测量组织血管紧张素转换酶（ACE）活性 分别使用放射免疫测定技术和荧光测定。 最后，所有上述变量将在乙醇饲养中重新检查， 和对照组动物在接受长期治疗后， ACE抑制剂或B-肾上腺素能阻滞剂。 的结果 这项研究将有助于更好地了解 酒精性心肌病及其治疗的合理开发 预防和治疗酒精性心肌病。

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.