Binge Drinking & Cigarette Smoking: A Rodent Model

描述(由申请人提供)：吸烟和酗酒已经独立地与各种不利的医疗后果有关。这些组合行为并存，在我们的社会中非常普遍。这项修订后的R21提案的长期目标是建立一种酗酒和吸烟暴露的动物模型，以确定这些联合行为是否比单独使用任何一种物质对心脏的毒性更大。据推测，尼古丁暴露(通过香烟烟雾)和酗酒/酗酒的组合比单独使用任何一种物质对心脏的毒性都更大，表现为心脏结构、心肌细胞组织学、血流动力学和心电图的更显著变化。还假设这些不良反应将被β-肾上腺素能阻滞剂卡维地洛抑制。使用卡维地洛进行的实验将是设计机械实验的关键 RO1应用程序的一部分。本研究的目的是：1)通过超声心动图和光镜和电子显微镜观察，确定在雄性大鼠中，酒精/香烟烟雾联合暴露引起的左心室结构/功能和心肌细胞形态的改变是否比任何一种药物单独作用更大：2)在雄性大鼠中，酒精/香烟烟雾联合暴露引起的血流动力学改变(血压和心率升高或降低)和心律改变(室性早搏、房性和室性心律失常)是否与单独使用任何一种药物相比不同或更大；3)为了确定预防性应用β-肾上腺素能阻滞剂卡维地洛对酒精和香烟引起的心脏结构和组织学改变的联合作用是否具有心脏保护作用。在两年的时间里，总共将使用74只动物。肯塔基大学烟草与健康研究所吸烟暴露系统将被用来让动物暴露在香烟烟雾中。重要的是，将使用无线电遥测方法测量血压、心率和监测心电图。这使得这些重要的参数可以在有意识的动物身上进行测量。超声心动图将被用来评估心脏结构。主要吸烟和酗酒在我们的社会中很普遍，特别是在青春期和年轻人中。这两种行为都与过早死亡有关。尽管这些行为非常普遍，但这些联合行为如何可能对心脏的结构和功能产生不利影响，甚至影响长期健康结果，目前尚不清楚。这一模型将是酒精研究领域独一无二的，对于了解这些组合行为可能如何对长期健康产生负面影响和/或增加一个人患心脏病或其他不利医疗后果的风险至关重要。

DESCRIPTION (provided by applicant): Cigarette smoking and binge ethanol drinking have been independently associated with a variety of adverse medical consequences. These combined behaviors coexist and are very prevalent in our society. The longterm objective of this revised R21 proposal is to develop an animal model of ethanol binge drinking and cigarette smoke exposure in order to determine if these combined behaviors are more cardiotoxic than either substance alone. It is hypothesized that the combination of nicotine exposure (via cigarette smoke) and binge/bender ethanol consumption will be more cardiotoxic than either substance alone, exemplified by more significant changes in cardiac structure, myocyte histology, hemodynamics and electrocardiogram changes. It is also hypothesized that these adverse effects will be inhibited by carvedilol, a beta-adrenergic blocker. Experiments conducted with carvedilol will be critical for designing mechanistic experiments that would be part of an RO1 application. The aims of this investigation are: 1) To determine in male rats if the combined behaviors of ethanol/cigarette smoke exposure elicit greater changes in left ventricular structure/function and myocyte morphology as assessed by echocardiography and light and electron microscopy, compared to either agent alone; 2) To determine in male rats if the combined behaviors of ethanol/cigarette smoke exposure elicit different or greater hemodynamic changes (increased or decreased blood pressure and heart rate) and cardiac rhythm changes (premature ventricular contractions, atrial and ventricular arrhythmias) compared to either agent alone; 3) To determine if the beta-adrenergic blocker, carvedilol administered prophylactically will provide cardioprotection against the combined effects of ethanol and cigarette smokinginduced cardiac structural and histological changes. A total of 74 animals will be used over the two-year period. The University of Kentucky Tobacco and Health Research Institute smoking exposure system will be used to expose animals to cigarette smoke. Importantly, a radiotelemetry method will be used to measure blood pressure, heart rate and to monitor the electrocardiogram. This allows for these important parameters to be measured in conscious animals. Echocardiography will be used to evaluate cardiac structure. Primary tobacco use and binge alcohol drinking are prevalent in our society, especially among adolescence and young adults. Both behaviors are associated with premature death. Despite the extreme prevalence of these behaviors, how these combined behaviors might adversely affect the structure and function of the heart or even impact long-term health outcomes are unknown. This model will be unique to the field of alcohol research and critical for understanding how these combined behaviors might negatively influence long-term health and/or increase a person's for heart disease or other adverse medical consequences.