Exercise /TZD Effects on Myocardial Substrate Metabolism

描述（由申请人提供）： 该K 01申请提出了一项为期5年的指导培训和研究计划，以发展测量、分析和解释以及干预患有代谢并发症（即葡萄糖耐量受损、脂肪再分布）的HIV感染者的心肌基质代谢和心室功能异常的专业知识。教学培训将包括心血管疾病，核医学和心脏超声检查的课程。本提案的主要目的是测试两种胰岛素增敏干预措施，心肺运动训练（GET）计划和噻唑烷二酮（TZD），对外周和心肌底物代谢和左心室功能的影响，在HIV感染的个体与糖耐量受损（HIV+IGT）。在HIV-IGT中，假设外周和心肌葡萄糖利用减少以及外周和心肌FFA氧化升高与左心室功能障碍相关。此外，GET和TZD治疗都将通过增加心肌葡萄糖利用来改善心室功能。最后，由于GET后心肌血流量增加的叠加效应，GET将比TZD治疗更大程度地改善LV功能。该提案的结果预计将证明GET和TZD治疗HIV感染者代谢诱导的LVD的疗效。这项建议的假设将通过随机，密切监督，我们一个月的治疗要么GET或TZD进行测试。在每次干预之前和完成之后立即测量心肌底物代谢、血流量和心室功能以及外周底物代谢。将通过放射性同位素示踪方法和正电子发射断层扫描（PET）成像测量心肌底物代谢和血流量，通过标准2-D和多普勒超声心动图测量心室功能，通过稳定同位素示踪方法和质谱法测量外周底物代谢。候选人将接受模范导师和教师咨询委员会的具体培训和指导，并将获得华盛顿大学优秀研究环境的全力支持。该奖项将有助于实现候选人的长期职业目标，成为HIV外周和心肌代谢和机械功能并发症领域的独立研究科学家。

DESCRIPTION (provided by applicant): This K01 application proposes a 5-year mentored training and research plan to develop expertise in measurement, analysis and interpretation of, and interventions for, myocardial substrate metabolism and ventricular function abnormalities in HIV-infected people with metabolic complications (i.e. impaired glucose tolerance, fat redistribution). Didactic training will include coursework in cardiovascular diseases, nuclear medicine, and cardiac sonography. The primary aim of this proposal is to test the effects of two insulin sensitizing interventions, a cardiorespiratory exercise training (GET) program and a thiazolidinedione (TZD), on peripheral and myocardial substrate metabolism and left ventricular function in HIV-infected individuals with impaired glucose tolerance (HIV+IGT). In HIV-IGT, it is hypothesized that reduced peripheral and myocardial glucose utilization and elevated peripheral and myocardial FFA oxidation is associated with left ventricular dysfunction. Furthermore, both GET and TZD treatment will improve ventricular function through an increase of myocardial glucose utilization. Lastly, due to an additive effect of increased myocardial blood flow following GET, GET will provide a greater improvement in LV function than TZD treatment. Results from this proposal are projected to demonstrate the efficacy of GET and TZD for the treatment of metabolically induced LVD in HIV-infected people. Hypotheses for this proposal will be tested through randomized, closely supervised, our-month treatments of either GET or TZD. Myocardial substrate metabolism, blood flow and ventricular function and peripheral substrate metabolism will be measured before and immediately following completion of each intervention. Myocardial substrate metabolism and blood flow will be measured by radioisotope tracer methodology and Positron Emission Tomography (PET) imaging, ventricular function by standard 2-D and Doppler echocardiography, and peripheral substrate metabolism by stable-isotope tracer methodology and mass spectrometry. The candidate will receive specific training and guidance by exemplary mentors and a faculty advisory committee and will receive the full support of Washington University's outstanding research environment. This award will assist in accomplishing the candidate's long-term career goal of becoming an independent research scientist in the field of peripheral and myocardial metabolic and mechanical function complications in HIV.