CARDIOMYOPATHY IN DIABETES

糖尿病(DM)患者易患糖尿病 心力衰竭引起的死亡和发病率，特别是以下 心肌梗塞(MI)。这些观察结果表明， 研究证实存在糖尿病心肌病(DBCM)， 不依赖于大血管CAD。在实验DBCM中，多个 机械异常和可能的机制已被记录在案。 然而，DBCM在患者中的表现和机制并不是 很好理解。使用从慢性阻塞性肺疾病患者身上获得的心肌条 正在接受冠状动脉搭桥术的CAD和DM(CAD/DM)，我们有 最近表现出力-频率关系(FFR)的抑制 尽管基础心功能正常。这 冠心病/糖尿病患者的心肌异常相似，但没有那样严重 扩张型心肌病、二尖瓣返流和IS的观察 可被Forskolin逆转，表明其最接近的机制是 可能是兴奋收缩偶联的缺陷(S)。这 建议有三个目标，将在CAD/DM患者和CAD中进行 对照：1)描述体内是否存在In的对应物 冠心病/糖尿病患者FFR的体外抑制，2)系统研究 参与CAD/DM中的ECC，并确定已识别的缺陷是否会导致FFR 3)FFR/ECC异常与抑郁的相关性检验 糖尿病及其相关血管病变代谢效应的标记物 以便开始描述DBCM的上游机制。病人 将在佛蒙特大学和纽约大学招聘 医院-康奈尔医疗中心。我们将聘请一名综合的、 包括体内和体外测定的协作方法 FFR，ECC的体外定量和缺陷的评估 糖尿病心肌糖酵解和血管病变。我们的一个主要优势是 实验策略是相互关联的，在单个患者的基础上， 体外FFR抑制与其他感兴趣的变量之间的关系。我们的长- 学期计划是定义与碳水化合物代谢异常相关的步骤 和/或糖尿病中的血管病变到DBCM，并最终设计合理 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.