Optimizing pulsatility during cardiopulmonary bypass to reduce acute kidney injury

项目总结/摘要 该提案的长期目标是确定搏动在体外循环（CPB）期间的作用 用于心脏手术后保护内皮功能和防止器官损伤。40多万人 每年在美国接受心脏手术，使他们活得更长，更充实， 但如果手术并发急性肾损伤（阿基），死亡率会增加10倍。克伦德南医生是 一位心胸麻醉师，致力于改善心脏手术后的临床结局， K23提案旨在为他提供成为一名 创新临床试验的领导者，旨在改善患者的治疗效果。他建立了一个合作 导师团队由Adit Ginde博士领导，他是一名急诊医学医师和一家大型 PETAL网络临床试验，有3,000名参与者，由专家Sarah Faubel博士提供共同指导 和Kristen Jablonski Nowak博士，内皮功能领域公认的领导者。 方法学顾问包括Alex Kaizer博士（生物统计学）和Kerrie Moreau博士（血管生物学）。这 提案利用了已建立的指导团队的集体专业知识和独特的环境， 科罗拉多大学安舒茨医学中心，该中心包括一个心脏外科三级转诊中心 在一所大型公立研究型大学的背景下。这些充足的资源将使克伦德南博士能够解决 降低心脏手术后发病率和死亡率的关键障碍， 采用脉动式CPB与非脉动式CPB的心脏手术后阿基的发生率。他将通过 在一项前瞻性观察中确定脉动式CPB对术后内皮功能的影响 队列（目的1），确定心脏手术后内皮功能障碍和肾损伤的时间， 同一队列（目标2），并确定CPB期间脉动的最佳水平和有效性，以预防阿基， 适应性无缝IIa/IIb期临床试验（Aim 3）。这些具体目标要求克伦德南博士开发 在评估临床内皮功能和阿基风险以及设计和完成适应性临床 审判他将通过一个有重点的职业发展计划来实现这一目标，包括临床试验设计课程 和生物统计学以及评估内皮功能的结构化培训，以衡量CPB的效果。 完成拟议项目将提供必要的指导、培训和经验， 使Clendenen博士成为适应性临床试验的领导者，以改善心脏手术后的结果。

PROJECT SUMMARY/ABSTRACT The long term goal of the proposal is to determine the role of pulsatility during cardiopulmonary bypass (CPB) for preserving endothelial function and preventing organ injury after cardiac surgery. More than 400,000 people undergo cardiac surgery in the United States each year which allows them to live longer and more fulfilling lives, but if the surgery is complicated by acute kidney injury (AKI) mortality increases up to 10-fold. Dr. Clendenen is a Cardiothoracic Anesthesiologist dedicated to improving clinical outcomes after cardiac procedures and this K23 proposal is designed to provide him with the structured mentorship and training necessary to become a leader in innovative clinical trials designed to improve patient outcomes. He has developed a collaborative mentorship team led by Dr. Adit Ginde who is an Emergency Medicine Physician and national PI for a large PETAL network clinical trial with 3,000 participants, with co-mentorship provided by Dr. Sarah Faubel, an expert in renal disease research, and Dr. Kristen Jablonski Nowak, a recognized leader in endothelial function. Methodological advisors include Dr. Alex Kaizer (Biostatistics) and Dr. Kerrie Moreau (Vascular Biology). This proposal leverages the collective expertise of an established mentorship team and the unique environment at the University of Colorado Anschutz Medical Center that incorporates a tertiary referral center for cardiac surgery in the setting of a large public research University. These ample resources will allow Dr. Clendenen to address key barriers to reducing morbidity and mortality after cardiac surgery with an adaptive clinical trial comparing the incidence of AKI after cardiac surgery with pulsatile versus non-pulsatile CPB. He will accomplish this by determining the effect of pulsatile CPB on post-operative endothelial function in a prospective observational cohort (Aim 1), determining the timing of endothelial dysfunction and renal injury after cardiac surgery in the same cohort (Aim 2), and determining the optimal level and efficacy of pulsatility during CPB to prevent AKI with an adaptive seamless phase IIa/IIb clinical trial (Aim 3). These specific aims require Dr. Clendenen to develop expertise in assessing clinical endothelial function and AKI risk and designing and completing an adaptive clinical trial. He will accomplish this with a focused career development plan including coursework on clinical trial design and biostatistics alongside structured training in assessing endothelial function to measure the effects of CPB. Completion of the proposed project will provide the necessary mentorship, training, and experience required to allow Dr. Clendenen to become a leader in adaptive clinical trials to improve outcomes after cardiac surgery.