ALCOHOL EFFECTS ON HEART FUNCTION--GENDER DIFFERENCES

描述(改编自《调查者摘要》)：长期 这项建议的目的是了解心脏的变化 与之相关的结构和病理生理机制 酒精性心脏病。本次调查的具体目的是： (1)在雄性和雌性大鼠中确定酒精诱导的进化 心脏结构改变(肥大和扩张/心肌病) 以及(2)确定酒精是否会导致 心肌病与心肌细胞的相应变化有关 特定血流动力学和神经内分泌的收缩和激活 雄性和雌性大鼠的机制。众所周知，慢性病 饮酒会导致心肌功能改变，从而 导致心肌病的发展。然而，人们对此知之甚少 关于酒精性心肌病的进展，特别是 心肌结构的变化如何与收缩功能的变化相关 特异性神经体液或血流动力学的功能和激活 机械装置。此外，已经有许多研究记录了 酒精对男性心脏的不良影响，而酒精的影响 消费在女性心中是比较鲜为人知的。 雄性和雌性Spraogue-Dawley大鼠将接受利伯- DeCarli酒精或对照饮食，而第三组将接受大鼠 周先生。动物将在这个方案中维持3到6个月。 将评估左心室大小和心腔扩张的变化。 超声心动图检查间隔4周。间接尾袖法 将用于每隔2周测量一次血压。动物 将在3个月和6个月时被牺牲以评估酒精含量- 引起心肌收缩性能和形态的改变。评估 后一种光学显微镜和电子显微镜将被进行和改变 将在分离的乳头肌中测量收缩能力 准备工作。同样在牺牲的时候，血浆肾素和血浆 将测量组织血管紧张素转换酶(ACE)活性 分别使用放射免疫分析技术和荧光分析技术。 最后，在以乙醇为燃料的情况下，将重新检查上述所有变量 并在动物接受了长期的治疗后控制动物 血管紧张素转换酶抑制剂或B-肾上腺素能阻滞剂。这样做的结果 研究将有助于更好地了解脑血管疾病的病理生理学。 酒精性心肌病与合理开发治疗药物 预防和治疗酒精性心肌病的神经作用。

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.