Binge Drinking & Cigarette Smoking: A Rodent Model

喝到烂醉

• 批准号: 7295695
• 负责人: MARIANN R PIANO
• 金额: $ 17.71万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7295695
• 关键词: Adolescence; Adrenergic Agents; Adrenergic beta-Antagonists; Adult; Adverse effects; Affect; Alcohol consumption; Animal Model; Animals; Antioxidants; Arrhythmia; Atrial Function; Attenuated; Attitude; Behavior; Blood Pressure; Cardiac; Cardiovascular system; Cell Nucleus; Cells; Cessation of life; Cigarette; Conscious; Crista ampullaris; Development; Echocardiography; Electrocardiogram; Electron Microscopy; Electrons; Environmental Exposure; Ethanol; Experimental Models; Fetal Alcohol Syndrome; Functional disorder; Health; Heart Atrium; Heart Diseases; Heart Rate; Histology; Hypertrophy; Immune; Infarction; Intervention; Intoxication; Investigation; Kentucky; Left ventricular structure; Light; Measures; Medical; Metabolic Diseases; Methods; Microscopy; Mitochondria; Modeling; Monitor; Morbidity - disease rate; Morphology; Muscle Cells; Myocardial; Myocardial Infarction; Nicotine; Norepinephrine; Outcome; Oxygen Consumption; Pathology, Other; Pattern; Persons; Prevalence; Rattus; Research Institute; Research Personnel; Risk; Risk Factors; Rodent Model; Smoke; Smoking; Societies; Stress; Stroke; Structure; System; Testing; Thick; Time; Tissues; Tobacco; Tobacco use; United States; Universities; Ventricular; Ventricular Arrhythmia; Ventricular Premature Complexes; adrenergic; alcohol behavior; alcohol effect; alcohol misuse; alcohol related problem; alcohol research; binge drinking; cardiovascular risk factor; carvedilol; cigarette smoke-induced; cigarette smoking; cigarette smoking; college; design; drinking; electrical property; heart disease risk; heart function; heart rhythm; hemodynamics; male; model development; mortality; programs; psychologic; research study; social; sudden cardiac death; young adult

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.

描述（由申请人提供）：吸烟和暴饮暴食乙醇饮用与各种不良医疗后果有关。这些联合行为共存，在我们的社会中非常普遍。该修订后的R21提案的长期目标是开发一种乙醇暴饮暴食和香烟烟雾暴露的动物模型，以确定这些组合行为是否比单独使用任何一种物质更具有心脏毒性。假设尼古丁暴露（通过香烟烟）和暴饮暴食/弯曲乙醇消耗的组合将比单独使用的任何一种物质更具心脏毒性，这体现了心脏结构，心肌组织学，血液动力学和心电图变化的更大变化。 还假设这些不良反应将受到β-肾上腺素能阻断剂卡维迪尔的抑制。 用卡维醇进行的实验对于设计机械实验至关重要 RO1应用程序的一部分。这项研究的目的是：1）确定雄性大鼠在乙醇/香烟烟雾暴露的综合行为是否引起左心室结构/功能和心肌形态的更大变化，这是通过超声心动图和光和电子显微镜所评估的； 2）确定雄性大鼠是否乙醇/香烟烟雾暴露的联合行为会引起不同或更大的血液动力学变化（增加或降低血压和心脏速率）和心律变化（与任何药物相比3）为了确定β-肾上腺素能阻断剂是否为预防性施用的卡维地醇可为乙醇和吸烟引起的心脏结构和组织学变化的综合作用提供心脏保护。在两年期间，总共将使用74只动物。肯塔基大学烟草和健康研究所吸烟系统将用于使动物暴露于香烟中。重要的是，将使用一种放射性驱动器法来测量血压，心率并监测心电图。这允许在有意识的动物中测量这些重要参数。超声心动图将用于评估心脏结构。 在我们的社会中，尤其是在青春期和年轻人中，原发性烟草使用和暴饮暴食很普遍。这两种行为都与过早死亡有关。尽管这些行为极为普遍，但这些联合行为如何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是未知的。该模型将是酒精研究领域独有的，并且对于了解这些联合行为如何对长期健康和/或增加患者的心脏病或其他不良医学后果的重要性至关重要。

项目成果

Alcoholic cardiomyopathy: pathophysiologic insights.

• DOI: 10.1007/s12012-014-9252-4
• 发表时间: 2014-12
• 期刊: CARDIOVASCULAR TOXICOLOGY
• 影响因子: 3.2
• 作者: Piano, Mariann R.;Phillips, Shane A.
• 通讯作者: Phillips, Shane A.

20 Things You Didn't Know About Alcohol.

关于酒精你不知道的 20 件事。

• DOI: 10.1097/jcn.0b013e3182955274
• 发表时间: 2013
• 期刊: The Journal of cardiovascular nursing
• 作者: Piano,MariannR;Phillips,ShaneA
• 通讯作者: Phillips,ShaneA

Cigarette smoke-induced left ventricular remodelling is associated with activation of mitogen-activated protein kinases.

香烟烟雾引起的左心室重构与丝裂原激活蛋白激酶的激活有关。

• DOI: 10.1016/j.ejheart.2008.08.009
• 发表时间: 2008-11
• 期刊: EUROPEAN JOURNAL OF HEART FAILURE
• 影响因子: 18.2
• 作者: Gu, Lianzhi;Pandey, Vikas;Geenen, David L.;Chowdhury, Shamim A. K.;Piano, Mariann R.
• 通讯作者: Piano, Mariann R.