ELECTROPHYSIOLOGIC CONSEQUENCES & REMODELING PREVENTION

电生理后果

• 批准号: 6391220
• 负责人: Jeffrey E Olgin
• 金额: $ 36.92万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391220
• 关键词: apoptosis; arrhythmia; cellular pathology; fibrosis; gene expression; genetically modified animals; heart cell; heart electrical activity; laboratory mouse; pathologic process; ventricular hypertrophy

Pathologic conditions in which electrical remodeling occurs and which are prone to ventricular and atrial arrhythmias are frequently associated with structural remodeling, such as fibrosis and hypertrophy. The presence of structural heart disease is the number one risk factor for sudden cardiac death due to ventricular arrhythmias. Most patients with structural disease prone to arrhythmias have hypertrophy and conditions with fibrosis, such as heart failure and ischemia. Similar, atrial fibrillation is associated with atrial hypertrophy and fibrosis both clinically and in several animal models. However, how this structural remodeling effects electrical remodeling or whether they are simply epiphenomenon is unknown. Since hypertrophy and fibrosis occur coincidentally in most pathologic conditions, the electrophysiologic effect of either alone, has not been well studied. Interventions aimed at blocking this pathologic structural remodeling may prevent electrical remodeling, ultimately rendering the heart resistant to fibrillation. We have recently identified several gene products which, when expressed in the myocardium of transgenic mice, block adverse structural remodeling. In particular two gene products we will study prevent the development of fibrosis and hypertrophy, respectively. We propose that the favorable effect of these gene products on structural remodeling will prevent electrical remodeling and serve to block the generation of a pro- arrhythmogenic substrate. We will test this hypothesis directly in the ventricles and atria of transgenic animals.

发生电重构的病理状况， 容易发生室性和房性心律失常， 结构重塑，如纤维化和肥大。 的存在 结构性心脏病是突发性心脏病的头号危险因素。 死于室性心律失常 大多数结构性疾病患者 容易发生心律失常的有肥大和纤维化的情况，如 心力衰竭和局部缺血。 心房纤颤的发生与 临床上和几种动物模型中的心房肥大和纤维化。 然而，这种结构重塑如何影响电重塑或 它们是否仅仅是附带现象尚不清楚。 由于肥大和 纤维化在大多数病理条件下同时发生， 电生理学效应的任何一个单独的，还没有得到很好的研究。 旨在阻断这种病理性结构重塑的干预措施可能 防止电重构，最终使心脏抵抗 纤维性颤动 我们最近发现了几种基因产物， 在转基因小鼠的心肌中表达， 重塑 特别是我们将研究的两种基因产物， 纤维化和肥大的发展。 我们建议 这些基因产物对结构重塑的有利作用将防止 电重塑，并用于阻止产生亲， 致炎底物。 我们将直接在 转基因动物的心室和心房。