IMPROVING NITRIC OXIDE-DERIVED OXIDANTS USING TOSIGLITAZONE IN NON-DIABETIC D

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：探讨罗格列酮治疗非糖尿病扩张型心肌病的安全性和有效性。我们假设，在这些患者中，罗格列酮是安全的，可以减少一氧化氮(NO)衍生的应激，从而改善内皮功能障碍、左心室功能和代谢参数。 背景：胰岛素抵抗在扩张型心肌病中更为普遍，可能与内皮功能障碍有关。氧化应激和炎症的增加可能在心力衰竭的病理生理学以及硝基酪氨酸等非衍生氧化剂中发挥作用。噻唑烷二酮类药物(TZD)是直接改善胰岛素敏感性和内皮功能的胰岛素增敏剂。然而，关于这些药物的安全性和有效性的信息很少。 研究设计：该研究将是一项双盲、随机、安慰剂对照试验。来自心力衰竭诊所的慢性稳定型心力衰竭患者将被筛查。60名患者将被随机分为罗格列酮和安慰剂两组。随访时间分别为6周、3个月和6个月。主要终点是确定血清硝基酪氨酸水平的绝对和相对变化。 意义：胰岛素抵抗作为心力衰竭患者新的治疗靶点的潜力具有广泛的意义。通过改善内皮功能障碍的药物逆转胰岛素抵抗，可能通过改善心肌灌注和存活而显著延缓疾病的进展。我们相信，针对胰岛素抵抗综合征的药物治疗可能在我们未来的管理和预防策略中发挥重要作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aim: The principal aim is to investigate the safety and efficacy of rosiglitazone in patients with non-diabetic dilated cardiomyopathy. We hypothesize that in these patients, rosiglitazone is safe and can reduce nitric oxide (NO) derived stress thereby improving endothelial dysfunction, left ventricular performance, and metabolic parameters. Background: Insulin resistance is more prevalent in dilated cardiomyopathy and may be related to endothelial dysfunction. Increased oxidant stress and inflammation may have been shown to play a role in the pathophysiology of heart failure as well as NO-derived oxidants such as nitrotyrosine. Thiazolidinediones (TZDs) are insulin-sensitizing agents that directly improve insulin sensitivity and endothelial function. However, there is a paucity of information regarding the safety and efficacy of these agents. Study Design: The study will be a double-blind, randomized, placebo-control trial. Patients from the Heart Failure clinic with chronic stable heart failure will be screened. 60 patients will be randomized to receive either rosiglitazone versus placebo. Follow-up will be conducted at 6-week, 3-month and 6-month. The primary endpoint is to determine the absolute and relative changes in serum nitrotyrosine levels. Significance: The potential for insulin resistance as a novel therapeutic target in patients with heart failure has broad implications. Pharmacologic reversal of insulin resistance via improvement of endothelial dysfunction may significantly delay disease progression by improving myocardial perfusion and viability. We believe that pharmacological therapy targeting the insulin resistance syndrome may play an important role in our future management and prevention strategies.