Binge Drinking & Cigarette Smoking: A Rodent Model

描述（由申请人提供）：吸烟和酗酒与各种不良医学后果独立相关。这些综合行为并存，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酒精狂饮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更具有心脏毒性。据推测，尼古丁暴露（通过吸烟）和酗酒/酗酒酒精消费的组合将比单独使用任何一种物质更具有心脏毒性，例如心脏结构，心肌细胞组织学，血流动力学和心电图变化的更显着变化。也有假设认为这些不良反应会被卡维地洛（一种β -肾上腺素能阻滞剂）所抑制。用卡维地洛进行的实验对于设计机械实验将是至关重要的

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.