Effect of Mechanical Circulatory Support on Exercise Capacity in Heart Failure

机械循环支持对心力衰竭患者运动能力的影响

• 批准号: 9338298
• 负责人: William Cornwell
• 金额: $ 17万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9338298
• 关键词: Acetylene; Active Learning; Affect; Age; Artificial Heart; Autonomic nervous system; Award; Biological Neural Networks; Biomedical Engineering; Blood; Blood Pressure; Blood flow; Brain; Cardiac Output; Cardiopulmonary; Cardiovascular Physiology; Cardiovascular system; Cerebrovascular Physiology; Clinical; Clinical Sciences; Control Groups; Data; Development; Development Plans; Devices; Disease; Ensure; Environment; Environmental Medicine; Exercise; Exercise Physiology; Exercise stress test; Funding; Future Generations; Goals; Heart; Heart Rate; Heart failure; Human body; Individual; Institutes; Institution; International; Intervention; Laboratory Research; Left ventricular structure; Life; Mechanics; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Methods; Morbidity - disease rate; Muscle; Nerve; Operating System; Operative Surgical Procedures; Outcome; Oxygen; Patient Schedules; Patients; Performance; Physiology; Population; Positioning Attribute; Procedures; Process; Program Development; Public Health; Publications; Publishing; Qi; Quality of life; Recovery; Reflex action; Reporting; Research; Research Personnel; Resources; Rest; Risk; Savings; Skeletal Muscle; Symptoms; Teacher Professional Development; Technology; Testing; Texas; Time; Training; Translational Research; United States; United States National Institutes of Health; Universities; Ventricular Function; Work; ascending aorta; base; career; career development; exercise capacity; exercise intervention; exercise rehabilitation; experience; functional disability; hemodynamics; implantation; improved; interest; left ventricular assist device; mortality; next generation; novel strategies; patient population; programs; public health relevance; reduce symptoms; relating to nervous system; response; skills; success; symposium; therapy design; uptake

 DESCRIPTION (provided by applicant): My career goal is to become an independent NIH-funded RO1 investigator contributing to advancements in mechanical circulatory support ("mechanical hearts") for patients with advanced heart failure. My work to date has focused on the impact of continuous-flow (CF) left ventricular assist devices (LVADs), a type of mechanical heart, on cerebrovascular physiology, sympathetic neural activity and blood pressure. This work has led to several presentations at national conferences, first-author publications that are either published or in review and research awards. However, there are two immediate research goals that are necessary for my own career development and to advance the field, including: 1) acquire new skills in the assessment of the cardiovascular and autonomic nervous system; and 2) extend my research program from the study of the cardiovascular system and CF-LVAD interactions under resting conditions, to dynamic conditions during exercise. To accomplish these goals, I have assembled a rigorous career development plan with experiential learning, opportunities to gain proficiency in procedures that I can incorporate into my research program, formal coursework to obtain a Master in Clinical Science degree, and oversight from mentors and advisors who are international experts in their respective fields. I will continue my successful mentored relationship with Dr. Benjamin Levine, who will serve as my primary mentor, Dr. Mark H. Drazner, who will serve as my co-mentor, as well as Drs Qi Fu and Jere Mitchell, who will continue to serve as research advisors. In addition, I will form a new collaborative relationship with Dr. Murray Esler, an international expert in cardiovascular and exercise physiology, with expertise in assessment of the autonomic nervous system. My long term goal is to understand how the cardiovascular system operates in the presence of a CF-LVAD. The objectives of this proposal are to determine how CF-LVADs impact exercise pressor reflexes and to identify the factor(s) which determine exercise capacity in advanced heart failure patients with these devices. Here, I will test the central hypothesis that exercise pressor reflexe improve following CF-LVAD implantation and that the primary determinant of exercise capacity is contractility of the left ventricle. The objectives of this proposal will be accomplished by pursuing two specific aims: 1) Determine the effect of a CF-LVAD on exercise pressor reflex in heart failure patients; and 2) Define the primary determinant(s) of exercise capacity in heart failure patients prior to and following CF-LVAD implantation. Results delivered from these specific aims will provide major contributions to the field and inform development of novel strategies to improve quality of life and survival in this unique patient population, and contribut to refinements in device technology, such that future-generation LVADs can modulate flow during exercise, similar to the normal heart. The proposed research will be conducted at the University of Texas Southwestern Medical Center (UTSW) and the Institute of Exercise and Environmental Medicine (IEEM) in Dallas, Texas. UTSW provides extraordinary translational research opportunities and faculty development programs, while the IEEM houses a world- renowned physiology research laboratory. I will have complete access to all resources available at these two institutions that will ensure my success during this K23 award period and that my career goals are achieved. Based on my training to date, mentored research experience and institutional environment, I believe that I am uniquely positioned to accomplish all objectives outlined in this career development project. This success will ensure that I transition into an independent RO1 funded investigator with expertise in cardiovascular and exercise physiology in patients with advanced heart failure, with a unique skillset in assessment of the autonomic nervous system, which few researchers possess.

 描述（由申请人提供）：我的职业目标是成为一名独立的NIH资助的RO 1研究员，为晚期心力衰竭患者的机械循环支持（“机械心脏”）做出贡献。迄今为止，我的工作主要集中在连续流（CF）左心室辅助装置（LVAD）（一种机械心脏）对脑血管生理学、交感神经活动和血压的影响。这项工作已导致在国家会议上的几个介绍，第一作者出版物， 发表或在评论和研究奖。然而，有两个直接的研究目标是必要的，我自己的职业发展和推进该领域，包括：1）获得心血管和自主神经系统的评估新技能;和2）扩展我的研究计划从心血管系统的研究和CF-LVAD在静息条件下的相互作用，在运动过程中的动态条件。为了实现这些目标，我已经制定了一个严格的职业发展计划，包括体验式学习，有机会熟练掌握我可以纳入我的研究计划的程序，正式的课程以获得临床科学硕士学位，以及导师和顾问的监督，他们是各自领域的国际专家。我将继续我与本杰明·莱文博士的成功的指导关系，他将担任我的主要导师，马克·H。Drazner博士，他将担任我的共同导师，以及Qi Fu博士和Jere Mitchell博士，他们将继续担任研究顾问。此外，我将与Murray Esler博士建立新的合作关系，他是心血管和运动生理学的国际专家，在自主神经系统评估方面具有专长。我的长期目标是了解心血管系统在CF-LVAD存在下如何运作。本提案的目的是确定CF-LVAD如何影响运动升压反射，并确定决定使用这些器械的晚期心力衰竭患者运动能力的因素。在这里，我将检验中心假设，即CF-LVAD植入后运动加压反射改善，运动能力的主要决定因素是左心室的收缩力。本提案的目的将通过追求两个特定目标来实现：1）确定CF-LVAD对心力衰竭患者运动升压反射的影响; 2）定义CF-LVAD植入前后心力衰竭患者运动能力的主要决定因素。这些特定目标的结果将为该领域做出重大贡献，并为开发新策略提供信息，以提高这一独特患者人群的生活质量和生存率，并有助于改进器械技术，使下一代LVAD可以在运动期间调节血流，类似于正常心脏。这项拟议中的研究将在德克萨斯大学西南医学中心（UTSW）和德克萨斯州达拉斯的运动与环境医学研究所（IEEM）进行。UTSW提供非凡的转化研究机会和教师发展计划，而IEEM拥有世界知名的生理学研究实验室。我将完全获得这两个机构的所有可用资源，这将确保我在K23奖期间取得成功，并实现我的职业目标。根据我迄今为止的培训，指导研究经验和机构环境，我相信我处于独特的地位，可以完成这个职业发展项目中列出的所有目标。这一成功将确保我过渡到一个独立的RO 1资助的研究者，在心血管和运动生理学的专业知识，在先进的心脏衰竭患者，具有独特的技能，在自主神经系统的评估，这是很少有研究人员拥有。