VENTRICULAR REMODELING IN AGED RATS

心肌梗死，尤其是如果大面积和跨壁心肌梗死，会导致 梗死区和非梗死区的室壁结构改变 非梗死性心肌。这些变化被称为 “心脏重塑”会影响心脏的性能和存活率。 与年轻患者相比，老年人有更多的左心室 功能障碍和较差的长期存活率。对此的解释是 不清楚。然而，在衰老大鼠和压力中的数据-和 容量超负荷老年大鼠提示代偿性心肌 足以使壁应力正常化的肥厚是主要的决定因素 心脏重塑和功能的关系。我们有老年人的初步数据 这表明，与年轻大鼠相比，老年大鼠具有相同的 面积较大的梗塞有更多的脑室扩张和较少的肥厚。 非梗死性心肌。这些数据支持我们的假设： 在老年大鼠中，非梗死区的代偿性肥厚不足 心肌导致左心室广泛重构和恶化 心功能。“ 这项建议概述了一种改善心功能的新方法。 通过增加非梗死区心肌的肥厚。假说 这种肥厚会降低心脏重塑的程度 及其后遗症，即脑室扩张，左心功能不全，以及 死亡率上升。心肌梗死冠脉结扎模型的建立 在8月龄和18月龄的344只X-BN大鼠中使用脑梗塞。一个月 脑梗塞后，我们将检查整体心功能并分析 用于评价左心室几何形态的解剖形态成分 墙体应力和重塑。在非梗死区制造肥厚 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。第一个特工将是 十四烷基缩水甘油酸(TDGA)，我们已经证明它会导致 正常SD大鼠非梗死区心肌肥厚。 这种方法旨在改变心脏重塑的过程。 老年人脑梗塞后。

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.