ALCOHOL EFFECTS ON HEART FUNCTION--GENDER DIFFERENCES

酒精对心脏功能的影响——性别差异

• 批准号: 2748459
• 负责人: MARIANN R PIANO
• 金额: $ 9.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2748459
• 关键词: ACE inhibitors; alcoholic beverage consumption; beta antiadrenergic agent; echocardiography; enzyme activity; ethanol; gender difference; heart enlargement; heart function; histopathology; laboratory rat; muscle contraction; myocardium disorder; neurotransmitters; peptidyl dipeptidase A; radioimmunoassay; renin; toxicology

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.

描述（根据调查员的摘要改编）：长期 该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。 这项调查的具体目的是： （1）确定雄性和雌性大鼠酒精引起的演变 心脏结构的变化（肥大和扩张/心肌病） （2）确定酒精诱导的发展是否 心肌病与心肌的相应变化有关 特定血流动力学和神经内分泌的收缩和激活 男性和雌性大鼠的机制。 慢性病已经很好 饮酒会在心肌中产生功能变化 导致心肌病的发展。 但是，鲜为人知 关于酒精引起的心肌病的进展，特别是 心肌结构的变化与收缩变化如何相关 特定神经肿瘤或血流动力学的功能和激活 机制。 此外，还有许多研究记录了 酒精对雄性心脏的不利影响，而饮酒的效果 女性心脏的消费相对未知。 雄性和女性Sprague-Dawley老鼠将获得Lieber- decarli酒精或对照饮食，而第三组将接受老鼠 周。 动物将在该方案上维持3和6个月。 将评估左心室大小和腔室扩张的变化 通过超声心动图以4周的间隔进行。 间接尾扣法 将使用2周的间隔来测量血压。 动物 将在3和6个月处牺牲，以评估酒精 - 诱导心肌收缩和形态的变化。 评估 后一种光和电子显微镜将进行并改变 收缩力将以孤立的乳头肌肉进行测量 准备。 同样在牺牲时，血浆肾素和血浆以及 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法。 最后，以上所有变量将在乙醇喂养中重新检查 并控制动物在接受长期治疗后 ACE抑制剂或B-肾上腺素能阻滞剂。 结果的结果 研究将使人们更好地了解 酒精性心肌病和治疗的合理发展 预防和治疗酒精引起的心肌病的神经。