Androgens and Myocardial Relaxation in the Aging Heart

衰老心脏中的雄激素和心肌松弛

• 批准号: 7098100
• 负责人: THEODORE P ABRAHAM
• 金额: $ 11.99万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7098100
• 关键词: SDS polyacrylamide gel electrophoresis; aging; androgens; clinical research; clinical trials; dehydroepiandrosterone; digital imaging; echocardiography; heart circulation; heart function; heart imaging /visualization /scanning; hemodynamics; hormone regulation /control mechanism; hormone therapy; human old age (65+); human therapy evaluation; laboratory rat; muscle relaxation; myocardium disorder; statistics /biometry; testosterone; ultrasonography

DESCRIPTION (provided by applicant): This proposal seeks to support the career development of Theodore Abraham, M.D., an Assistant Professor of Internal Medicine at the Mayo Medical School. The applicant's career goal is to develop an independent, dynamic, translational research program, integrating innovative imaging modalities and muscle physiology, within a vibrant and stimulating scientific environment. The KO8 award would protect the applicant from clinical duties, such as staffing the echocardiography laboratory, and allow full time research. The applicant plans to strengthen ongoing clinical research, and enhance his expertise and gain independence in muscle physiology, endocrinology and aging, under the mentorship of senior, established investigators. The scientific goal of this proposal is to examine the role of testosterone in the development of age-related diastolic dysfunction. Aging is associated with diastolic dysfunction that results in significant morbidity and mortality in the elderly. Since testosterone levels decrease with age, it is hypothesized that testosterone deficiency forms the pathophysiologic basis for the development of diastolic dysfunction, and that testosterone replacement alleviates diastolic dysfunction in the elderly. Using innovative imaging techniques, the applicant has recently introduced novel concepts with obvious implications in age-related diastolic dysfunction. This proposal seeks to expand on these observations, and plans to: a) in the setting of a NIH funded, randomized, double-blind, placebo-controlled clinical study (applicant is the project leader for the cardiovascular component), test whether testosterone deficiency worsens, and replacement alleviates, diastolic dysfunction in the elderly; b) in the same setting, examine whether testosterone mediates diastolic function through regulation of peripheral hemodynamics; and c) in an animal model, explore possible underlying cellular mechanisms of testosterone-mediated diastolic dysfunction, specifically intracellular calcium regulation. The proposed experiments will generate significant new knowledge pertaining to age-related diastolic dysfunction, specifically with regard to the interactions between hormonal changes and ventricular mechanics. Most importantly, potential direct clinical benefits of this research include early detection, improved and novel therapy, and better clinical outcomes for age-related diastolic dysfunction.

描述（由申请人提供）：该提案旨在支持Mayo医学院内科医学助理教授Theodore Abraham的职业发展。申请人的职业目标是制定独立，动态的，转化的研究计划，将创新成像的方式和肌肉生理融合在充满活力和刺激的科学环境中。 KO8奖将保护申请人免受临床职责，例如超声心动图实验室的人员配备，并允许全职研究。申请人计划在高级研究人员的指导下加强正在进行的临床研究，并增强其专业知识并获得肌肉生理，内分泌学和衰老的独立性。该提案的科学目标是检查睾丸激素在与年龄相关的舒张功能障碍发展中的作用。衰老与舒张功能障碍有关，导致老年人的发病率和死亡率显着。由于睾丸激素水平随着年龄的增长而降低，因此假设睾丸激素缺乏症是舒张功能障碍发展的病理生理基础，并且睾丸激素的替代替代可以减轻老年人的舒张功能障碍。使用创新的成像技术，申请人最近引入了新颖的概念，对年龄相关的舒张功能障碍具有明显的影响。该提案旨在扩大这些观察结果，并计划：a）在NIH资助的，随机，双盲，安慰剂对照的临床研究（申请人是心血管成分的项目负责人）中，测试睾丸激素缺乏症的缺乏症和替代镇痛药是否降低，可替代的降低了抑郁症，在老年人中的可食用性降低了; b）在同一情况下，检查睾丸激素是否通过调节外周血流动力学介导舒张功能； c）在动物模型中，探索睾丸激素介导的舒张功能障碍，特别是细胞内钙调节的潜在细胞机制。提出的实验将产生与年龄相关的舒张功能障碍有关的重要新知识，特别是关于激素变化与心室力学之间的相互作用。最重要的是，这项研究的潜在直接临床益处包括早期检测，改进和新颖的治疗以及与年龄相关的舒张功能障碍的更好临床结果。