VENTRICULAR REMODELING IN AGED RATS

心肌梗死，特别是大面积和透壁性心肌梗死， 心室结构的改变涉及梗死和 非梗死心肌 这些被称为 "心室重构"影响心室性能和存活。 与年轻患者相比，老年患者的左心室 功能障碍和更差的长期存活率。 对此的解释是 不清楚然而，衰老大鼠和压力-和 老年大鼠容量超负荷提示代偿性心肌 足以使室壁应力正常化的肥大是主要决定因素 心室重塑和功能的影响 我们有初步的数据， 这表明，与年轻大鼠相比， 大面积梗塞有更多心室扩张和较少的肥大， 非梗塞心肌 这些数据支持我们的假设： "在老年大鼠中， 心肌导致广泛的重塑和左室功能恶化 心室功能" 该提案概述了一种改善心室功能的新方法 通过增加非梗死心肌的肥大。 的假设 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，以及 增加死亡率。 冠状动脉结扎心肌缺血模型 梗塞将用于8和18月龄的344 × BN大鼠。 一个月 梗死后，我们将检查整体心脏功能，并分析 左心室几何结构的解剖-形态学组成部分，以评估 室壁应力和重塑。 在非梗死区制造肥大 心肌，我们将使用抑制脂肪酸氧化或 刺激葡萄糖（乳酸盐）氧化。 第一个特工将是 十四烷基缩水甘油酸（TDGA），我们已经证明， 正常Sprague-Dawley大鼠的非梗死心肌肥大。 这种方法旨在改变心室重塑的过程 老年人梗死后。

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.