CARDIOMYOPATHY IN DIABETES

糖尿病（DM）患者的以下疾病发病率很高 心力衰竭导致的死亡和发病，尤其是 心肌梗死（MI）。 这些观察结果表明， 研究证实存在糖尿病性心肌病（DBCM）， 与大血管CAD无关。在实验DBCM中，多个 机械异常和潜在机制已被记录。 然而，DBCM在患者中的表现和机制并不清楚。 很好理解。使用从患有心脏病的患者中获得的心肌条， 接受冠状动脉旁路移植术的CAD和DM（CAD/DM），我们 最近显示出力-频率关系（FFR）的抑制 尽管基础心室功能正常 这 冠心病/糖尿病的心肌异常与冠心病/糖尿病的心肌异常相似，但不如冠心病/糖尿病严重。 在扩张型心肌病和二尖瓣返流中观察到， 可逆的毛喉素，表明其近似机制是 可能是兴奋-收缩偶联（ECC）中的缺陷。 这 建议有三个目标，在CAD/DM患者和CAD中进行 对照：1）描述是否存在体内对应物， CAD/DM中的体外FFR抑制，2）系统研究过程 参与CAD/DM中的ECC，并确定识别出的缺陷是否会导致FFR 抑郁症，和3）测试异常FFR/ECC与 糖尿病代谢效应和相关血管病变的标志物 以便开始表征DBCM的上游机制。 患者 将同时在佛蒙特大学和纽约 医院-康奈尔医疗中心。 我们将采用一个综合的， 合作方法，包括体内和体外测定 血流储备分数、ECC的体外定量和 糖尿病心肌糖酵解和血管病变。 我们的一个主要优势 实验策略是，在个体患者的基础上， 与其他感兴趣变量的体外FFR抑制。 我们长久以来- 长期计划是明确糖代谢异常的步骤 和/或血管病变，并最终设计合理性 治疗。

Patients with diabetes mellitus (DM) are subject to a high incidence of death and morbidity due to heart failure, especially following myocardial infarction (MI). These observations suggested and subsequent studies confirmed the presence of a diabetic cardiomyopathy (DBCM), indepenent of macrovascular CAD. In experimental DBCM, multiple mechanial abnormalities and potential mechanisms have been documented. However, the manifestations and mechanisms of DBCM in patients are not well understood. Using strips of myocardium obtained from patients with CAD and DM (CAD/DM) undergoing coronary bypass grafting, we have recently shown depression of the force-frequency relationship (FFR despite the fact that basal ventricular function was normal. This myocardial abnormality in CAD/DM is similar but less severe than that observed in dilated cardiomyopathy and mitral regurgitation and is reversible by forskolin, indicating that its proximate mechanism is likely a defect(s) in excitation-contraction coupling (ECC). This proposal has three aims, to be undertaken in CAD/DM patients and CAD controls: 1) delineate whether there is an in vivo counterpart of in vitro FFR depression in CAD/DM, 2) systematically study the processes involved in ECC in CAD/DM and determine if identified defects cause FFR depression, and 3) test for correlations between abnormal FFR/ECC and markers of both the metabolic effects of DM and associated vasculopathy in order to begin to characterize upstream mechanisms of DBCM. Patients will be recruited at both the University of Vermont and the New York Hospital-Cornell Medical Center. We will employ an integrated, collaborative approach including in vivo and in vitro determination of the FFR, in vitro quantification of ECC, and assessment of defects in glycolysis and vasculopathy in DM myocardium. A major strength of our experimental strategy is correlation, on an individual patient basis, of in vitro FFR depression with other variables of interest. Our long- term plan is to define the steps linkin abnormal carbohydrate metabolism and/or vasculopathy in DM to DBCM and ultimately design rational treatments.