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

这个子项目是众多研究子项目之一

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.