Exercise and TZD Effects on Myocardial Substrate Metabolism and Function in HIV

运动和 TZD 对 HIV 心肌底物代谢和功能的影响

• 批准号: 7406025
• 负责人: WILLIAM Todd CADE
• 金额: $ 10.14万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7406025
• 关键词: 2,4-thiazolidinedione; Advisory Committees; Anti-Retroviral Agents; Award; Blood flow; Cardiac; Cardiovascular Diseases; Condition; Discipline of Nuclear Medicine; Environment; Equilibrium; Exercise; Faculty; Fatty acid glycerol esters; Functional disorder; Glucose; Goals; HIV; Heart; Image; Individual; Insulin; Insulin Resistance; Intervention; Left Ventricular Dysfunction; Left Ventricular Function; Mass Spectrum Analysis; Measurement; Measures; Mechanics; Mentors; Metabolic; Metabolism; Methodology; Myocardial; Peripheral; Phenotype; Positron-Emission Tomography; Radioisotopes; Randomized; Rate; Research; Research Training; Scientist; Standards of Weights and Measures; Testing; Thiazolidinediones; Tracer; Training; Two-Dimensional Doppler Echocardiography; Ultrasonography; Universities; Ventricular Function; Washington; career; impaired glucose tolerance; improved; oxidation; programs; stable isotope

This K-01.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, GETwill provide a greater improvement in LV function than TZD treatment. Results from this proposal are projected to demonstrate the efficacy of GETand TZD for the treatment of metabolically induced LVD in HIV-infected people. Hypotheses for this proposal will be tested through randomized, closely supervised, four-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.

这份K-01申请提出了一项为期5年的有指导的培训和研究计划，以发展以下方面的专业知识 测量、分析、解释和干预心肌底物代谢和 伴有代谢并发症(即葡萄糖受损)的HIV感染者的心功能异常 耐受性、脂肪再分布)。授课培训将包括心血管疾病、核疾病的课程 医学和心脏超声检查。这项建议的主要目的是测试两种胰岛素的效果- 致敏干预措施、心肺运动训练(GET)计划和噻唑烷二酮(TZD)， HIV感染者外周血和心肌基质代谢及左心功能的研究 糖耐量受损(HIV+IGT)。在HIV-IGT中，假设外周血细胞减少和 心肌葡萄糖利用和外周及心肌FFA氧化升高与左 心功能不全。此外，GET和TZD治疗均可通过以下途径改善心功能 心肌葡萄糖利用率的增加。最后，由于增加心肌血的相加作用 GET、GET治疗后左心功能的改善明显优于TZD治疗。结果来自 这项提案预计将证明GET和TZD在治疗代谢疾病方面的有效性 在HIV感染者中诱导LVD。这项提议的假设将通过随机、密切的 GET或TZD的监督治疗，为期四个月。心肌底物代谢、血流量和 在治疗前和治疗后立即测量心功能和外周基质代谢。 完成每一次干预。心肌底物代谢和血流量将通过 放射性同位素示踪方法学和正电子发射断层扫描(PET)成像，通过 标准二维和多普勒超声心动图和稳定同位素示踪剂的外周基质代谢 方法学和质谱学。候选人将接受特定的培训和指导，模范 导师和教职员工咨询委员会，并将得到华盛顿大学 优良的科研环境。这一奖项将有助于实现候选人的长期职业生涯 成为外周和心肌代谢领域的独立研究科学家的目标 HIV中的机械功能并发症。