VENTRICULAR REMODELING IN AGED RATS

老年大鼠的心室重构

• 批准号: 2224212
• 负责人: Steven Goldman
• 金额: $ 16.22万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2224212
• 关键词: aging; cellular pathology; fatty acids; heart dimension /size; heart function; hemodynamics; laboratory rat; lactates; myocardial infarction; myosins; oxidation; stress; vasodilatation; ventricular hypertrophy

Myocardial infarction, especially if large and transmural, results in alterations in ventricular structure involving both the infarcted and noninfarcted myocardium. These alterations, which have been termed "ventricular remodeling," affect ventricular performance and survival. Compared to younger patients, the aged have more left ventricular dysfunction and worse long-term survival. The explanation for this is not clear. However, data in the senescent rat and in the pressure- and volume-overloaded aged rat suggest that compensatory myocardial hypertrophy sufficient to normalize wall stress is the major determinant of ventricular remodeling and function. We have preliminary data in aged rats which shows that, compared to younger rats, aged rats with the same size infarctions have more ventricular dilatation and less hypertrophy in the noninfarcted myocardium. These data support our hypothesis that: "In aged rats, inadequate compensatory hypertrophy of the noninfarcted myocardium results in extensive remodeling and deterioration in left ventricular function." This proposal outlines a novel approach to improving ventricular function by augmenting hypertrophy in the noninfarcted myocardium. The hypothesis is that this hypertrophy will reduce the extent of ventricular remodeling and its sequelae, i.e., ventricular dilatation, LV dysfunction, and increased mortality. The coronary artery ligation model of myocardial infarction will be used in 8 and 18 month old 344 X BN rats. One month after infarction, we will examine global cardiac function and analyze anatomic-morphologic components of left ventricular geometry to assess wall stress and remodeling. To create hypertrophy in the noninfarcted myocardium, we will use agents that inhibit fatty acid oxidation or that stimulate glucose (lactate) oxidation. The first agent will be tetradecylglycidic acid (TDGA), which we have shown will cause hypertrophy in the noninfarcted myocardium of normal Sprague-Dawley rats. This approach is designed to alter the process of ventricular remodeling post-infarction in the aged.

心肌梗塞，尤其是在大且透明膜的情况下导致的 涉及梗塞和的心室结构的改变 无刺的心肌。 这些变化已被称为 “心室重塑”，影响心室性能和生存。 与年轻患者相比，年龄较大的左心室 功能障碍和较差的长期生存。 对此的解释是 不清楚。但是，衰老大鼠以及压力和压力的数据 体积超过老年大鼠表明补偿性心肌 足以使壁应力归一化的肥大是主要的决定因素 心室重塑和功能。 我们有年龄的初步数据 大鼠表明，与年轻大鼠相比，年龄相同的大鼠 尺寸梗塞具有更多的心室扩张，而肥大则更少 非肉眼的心肌。 这些数据支持我们的假设： “在老年大鼠中，非肉眼的补偿性肥大不足 心肌导致左侧的大量重塑和恶化 心室功能。” 该建议概述了改善心室功能的新方法 通过增强非肉眼心肌中的肥大。 假设 是这种肥大会降低心室重塑的程度 及其后遗症，即心室扩张，LV功能障碍和 死亡率增加。 心肌的冠状动脉连接模型 梗塞将在8个月大的344 x BN大鼠中使用。 一个月 梗塞后，我们将检查全球心脏功能并进行分析 左心室几何形状的解剖学成分来评估 壁应力和重塑。 在非肉眼中创建肥大 心肌，我们将使用抑制脂肪酸氧化的药物或 刺激葡萄糖（乳酸）氧化。 第一个代理将是 四甲基甘油酸（TDGA），我们已经显示的会导致 正常的sprague-dawley大鼠的非肉眼心肌中的肥大。 这种方法旨在改变心室重塑的过程 老年人的界面。