ELECTROPHYSIOLOGIC CONSEQUENCES & REMODELING PREVENTION

发生电重构的病理条件，以及 容易发生室性和房性心律失常经常与 结构重塑，如纤维化和肥大。.的存在 结构性心脏病是突发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 易发生心律失常的肥大和纤维化的情况，如 心力衰竭和缺血。类似的，心房颤动与 在临床和几种动物模型中都存在心房肥大和纤维化。 然而，这种结构重建如何影响电气重建或 它们是否只是偶然现象还不得而知。由于肥厚和 纤维化在大多数病理条件下都是巧合发生的， 单独的电生理效应还没有得到很好的研究。 旨在阻止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 纤颤。我们最近发现了几种基因产品，当 在转基因小鼠的心肌中表达，阻断不利结构 改建。特别是我们将研究的两种基因产品，可以预防 分别发展为纤维化和肥大。我们建议， 这些基因产物对结构重塑的有利作用将防止 电气重塑和服务，以阻止产生亲- 致心律失常的底物。我们将直接在 转基因动物的脑室和心房。

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.