Peripheral Limitations in Pulmonary Hypertension and Effects of Muscle Training

肺动脉高压的外周局限性和肌肉训练的影响

• 批准号: 10661187
• 负责人: Yogesh Nellore Vilambi Reddy
• 金额: $ 16.77万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-10 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10661187
• 关键词: Accelerometer; Address; Adopted; Aerobic Exercise; Affect; Aftercare; Age; Award; Biology; Biopsy; Biostatistical Methods; Blood Vessels; Blood flow; Blood gas; Body mass index; Cardiac Output; Cardiovascular Abnormalities; Cardiovascular system; Clinic; Clinical; Clinical Trials; Complement; Consumption; Data; Educational Intervention; Exercise; Exercise Physiology; Exercise Tolerance; Exertion; Extensor; Femur; Functional disorder; Funding; Goals; Grant; Heart; Heart Rate; Heart failure; Impairment; Individual; Intervention; K-Series Research Career Programs; Knee; Knowledge; Left; Leg; Life; Lung; Magnetic Resonance Imaging; Measurement; Measures; Medicine; Mentors; Mentorship; Methods; Mitochondria; Monitor; Muscle; Muscle Mitochondria; Outcome; Oxidative Stress; Oxygen; Participant; Patient Care; Patient Outcomes Assessments; Patients; Performance; Peripheral; Persons; Physiology; Positioning Attribute; Production; Pulmonary Hypertension; Quality of life; Questionnaires; Randomized; Reporting; Research Personnel; Residual state; Respiration; Role; Scientist; Skeletal Muscle; Supination; Surveys; Symptoms; Techniques; Therapeutic; Thermodilution; Time; Training; United States National Institutes of Health; Vasodilator Agents; Walking; Woman; Work; clinically significant; comparison control; exercise capacity; exercise intolerance; exercise program; exercise training; exhaustion; experience; fitbit; hemodynamics; improved; indexing; mathematical model; multidisciplinary; muscle form; novel; primary endpoint; professor; pulmonary arterial hypertension; pulmonary vascular disorder; quadriceps muscle; randomized trial; randomized, clinical trials; recruit; right ventricular failure; sedentary; sex; skills; standard of care; targeted treatment; time use; translational clinical trial; week trial

PROJECT SUMMARY/ABSTRACT Dr. Yogesh Reddy, MBBS, MSc, is an Assistant Professor in the Department of Cardiovascular Medicine at Mayo Clinic. Dr. Reddy is seeking a Mentored Career Development Award to develop the training required to study the contribution of skeletal muscle abnormalities to exercise performance in patients with Pulmonary Arterial Hypertension (PAH). Dr. Reddy has received extensive training in pulmonary vascular hemodynamics in PAH during his previous training under the T32 grant, providing necessary skills and experience to study the central cardiovascular abnormalities that drive exercise intolerance in PAH. While therapies targeted to these central limitations have markedly improved clinical outcomes in PAH, a wide therapeutic gap remains, as nearly 90% of patients report significant residual symptoms even after treatment with pulmonary vasoactive therapy. Preliminary studies have suggested that peripheral abnormalities in skeletal muscle may contribute to the exercise intolerance of patients with PAH, but no study has yet used gold standard methods to measure skeletal muscle oxygen (O2) utilization during exertion in PAH. To fill this knowledge gap and build new skills in the characterization of peripheral deficits in PAH, Dr. Reddy proposes to: 1) determine the independent role of skeletal muscle and mitochondrial O2 transport abnormalities in exercise performance in PAH compared to controls, and 2) perform a randomized clinical trial of isolated quadriceps (knee-extension) based training to assess its effect on peripheral O2 transport and whole-body exercise performance in PAH. In this proposal, Dr. Reddy is seeking the primary mentorship of Dr. Barry Borlaug, an experienced, NIH-funded investigator with expertise in exercise physiology in pulmonary hypertension, who has a proven track record of successfully mentoring junior investigators. The mentorship team supervised by Dr. Borlaug includes multidisciplinary experts who will provide necessary advanced training in the fields of mitochondrial biology (Dr. Sreekumaran Nair), leg blood flow quantification and exercise training interventions (Dr. Thomas Olson), iterative mathematical modeling and biostatistical methods (Dr. Rickey Carter), patient reported outcomes (Dr. Shannon Dunlay) and clinical trials in PAH (Dr. Robert Frantz). As a result of the training proposed, Dr. Reddy will obtain the skills necessary to: 1) comprehensively evaluate mitochondrial and peripheral O2 transfer physiology during exertion, and 2) conduct randomized trials of an exercise-based intervention. The advanced training obtained during this award in skeletal muscle biology and exercise physiology will greatly complement the skills he has already obtained characterizing central hemodynamic abnormalities in PAH, uniquely positioning him to succeed as an independently-funded clinician scientist focused on the pathophysiology and treatment of exercise intolerance in PAH, understanding and investigating the problem “from all angles”. The data derived and expertise gained will form the basis for a competitive R01 application centered on novel treatments targeting peripheral deficits for patients with PAH.

项目摘要/摘要 MSC MBBS的Yogesh Reddy博士是心血管医学系的助理教授 梅奥诊所。 Reddy博士正在寻求指导的职业发展奖，以开发所需的培训 研究骨骼肌肉异常对肺部患者锻炼性能的贡献 动脉高血压（PAH）。 Reddy博士接受了肺血管血流动力学的广泛培训 在PAH在T32 Grant的先前培训期间，提供了必要的技能和经验来研究 中央心血管异常，这些异常在PAH中驱动运动。而疗法针对这些 中心局限性明显改善了PAH的临床结果，仍然存在较大的治疗差异，因为几乎 即使在接受肺血管活性疗法治疗后，有90％的患者也会报告显着的残留症状。 初步研究表明，骨骼肌的外围异常可能有助于 PAH患者的运动摄入率，但尚未使用黄金标准方法来测量骨骼 PAH努力期间的肌肉氧（O2）利用。填补这一知识差距并建立新技能 PAH中周围缺陷的表征，Reddy博士提案至：1）确定独立作用 与 对照和2）对孤立的股四头肌（膝关节扩张）训练进行随机临床试验 评估其对PAH中周围O2运输和全身运动表现的影响。在此提案中，博士 雷迪（Reddy）正在寻求Barry Borlaug博士的主要心态 在肺动脉高压中运动生理学专业知识，他的良好记录成功地记录了 心理初级调查员。 Borlaug博士监督的Mentalship团队包括多学科专家 谁将在线粒体生物学（Sreekumaran Nair博士）的领域提供必要的高级培训 血流定量和运动训练干预措施（托马斯·奥尔森博士），迭代数学建模 和生物统计学方法（Rickey Carter博士），患者报告的结果（Shannon Dunlay博士）和临床试验 在PAH（Robert Frantz博士）。由于提出了培训，Reddy博士将获得所需的技能：1） 全面评估劳累过程中的线粒体和周围O2转移生理，以及2） 基于运动干预的随机试验。该奖项在骨骼中获得的高级培训 肌肉生物学和运动生理学将大大完成他已经获得的特征的技能 PAH中心血流动力学异常，独特地定位他成为独立资金的成功 临床科学家专注于PAH的病理生理学和运动摄入术的治疗 并“从各个角度”调查问题。得出的数据和获得的专业知识将构成 竞争性的R01应用以针对周围的新型治疗方法定义了PAH患者。