DIABETES MELLITUS: EFFECT ON MYOCARDIAL INFARCTION

心肌梗死是糖尿病死亡的主要原因， 糖尿病患者似乎对心脏缺血特别敏感。 糖尿病大鼠心肌缺血敏感性增加的机制 将在01-03年度进行定义和测量。随后，我将 尝试确定它们是否被更改的类型和程度 在本提案的04-05年间控制糖尿病。胰腺B细胞 细胞毒素四氧嘧啶将用于兔糖尿病的诱导。一个 将建立轻度、慢性糖尿病兔群体，在其中没有 生存需要治疗。这是轻度糖尿病不治疗组 将与年龄匹配的非糖尿病组进行比较，以确定 未经治疗的轻度糖尿病增加心肌对缺血的敏感性 受伤。然后将未治疗的轻度糖尿病组与轻度糖尿病组进行比较 糖尿病组接受胰岛素治疗后确定是否治疗轻度 糖尿病影响心肌对缺血的敏感性。类似 比较更严重的胰岛素依赖型糖尿病患者 组相对于非糖尿病对照组和胰岛素依赖组之间 血糖维持在“差”或“紧”的糖尿病组 对照组采用不同的胰岛素方案。跟随冠状动脉 结扎，将测量缺血和继发性脑梗塞的面积 并在糖尿病组和非糖尿病组进行比较。此外，并行 随后将评估各组左心功能的变化。 梗塞，包括a)收缩，b)舒张期顺应性，c) 心肌的三磷酸腺苷水平，产生磷酸盐，甘油三酯，乳酸，水肿， 和钙，d)冠状动脉血管扩张功能，和e) 代谢-机械耦合效率。创面的愈合与修复 心肌梗死后1至60天将通过以下方法进行评估 测量对脑室破裂的抵抗力、疤痕大小、厚度和 弹性，以及由活动定义的活动修复量 胶原蛋白合成的关键酶--脯氨酸羟基酶和赖氨酸氧化酶 由胶原和弹性蛋白含量、胶原类型和交联度决定。

Myocardial infarction is the leading of death in diabetes mellitus, and diabetics appear to be particularly sensitive to cardiac ischemia. Mechanisms of this increased ischemic sensitivity in the diabetic myocardium will be defined and measured during years 01-03. Subsequently, I will attempt to determine whether they are altered by the type and degree of diabetic control during years 04-05 of this proposal. The pancreatic B-cell cytotoxin alloxan will be used in rabbits to induce diabetes mellitus. A rabbit colony with mild, chronic diabetes will be established in which no treatment is required for survival. This mild diabetic - no treatment group will be compared to an age-matched non-diabetic group to determine if untreated mild diabetes increases myocardial sensitivity to ischemic injury. The mild diabetic untreated group will then be compared to mild diabetic groups treated with insulin to determine if treatment of mild diabetes affects the myocardial sensitivity to ischemia. Similar comparisons will be made between a more severe, insulin-dependent diabetic group relative to a non-diabetic control group and between insulin-dependent diabetic groups which are maintained in either "poor" or "tight" glycemic control with different insulin regimens. Following coronary artery ligation, the area of ischemia and subsequent infarction will be measured and compared in the diabetic and non-diabetic groups. In addition, parallel groups will be assessed for changes in left ventricular function following infarction, including a) contractility, b) diastolic compliance, c) myocardial levels of ATP, creating phosphate, triglyceride, lactate, edema, and calcium, d) coronary arterial vasodilatory function, and e) metabolic-mechanical coupling efficiency. Healing and repair of the infarcted myocardium will be assessed from 1 to 60 days post-infarction by measuring resistance to ventricular rupture, scar size, thickness and elasticity, and the amount of active repair as defined by activity of the key collagen synthetic enzymes prolyl hydroxylase and lysyk oxidase as well as by collagen and elastin content and collagen type and cross-link density.