Optimizing pulsatility during cardiopulmonary bypass to reduce acute kidney injury

项目摘要/摘要 该提案的长期目标是确定搏动性在体外循环(CPB)中的作用。 用于保护心脏手术后的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，让他们活得更长、更有成就感， 但如果手术并发急性肾损伤(AKI)，死亡率会增加10倍。克伦德宁博士是 一位心胸麻醉师致力于改善心脏手术后的临床结果 K23计划旨在为他提供必要的结构化指导和培训，使其成为 在旨在改善患者结果的创新临床试验方面处于领先地位。他已经开发出一种协作性的 由Adit Ginde博士领导的导师小组，他是一名急诊医生，也是一家大型 有3000名参与者参加的Petal网络临床试验，由专家Sarah Faubel博士提供共同指导 在肾脏疾病研究方面，Kristen Jablonski Nowak博士是公认的内皮功能领导者。 方法学顾问包括亚历克斯·凯泽博士(生物统计学)和克里·莫罗博士(血管生物学)。这 Proposal利用成熟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，包括心脏手术的第三转诊中心 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宁博士能够解决 降低心脏手术后发病率和死亡率的关键障碍与适应性临床试验比较 搏动性与非搏动性体外循环心脏手术后急性心肌梗死的发生率。他将通过以下方式实现这一点 脉冲式体外循环对术后内皮功能影响的前瞻性观察 队列(目标1)，确定心脏手术后内皮功能障碍和肾损伤的时间 相同的队列(目标2)，并确定CPB期间脉搏的最佳水平和疗效，以预防AKI 适应性无缝IIa/IIb期临床试验(目标3)。这些具体目标需要克伦德宁博士开发 评估临床内皮功能和AKI风险以及设计和完成适应性临床的专业知识 审判。他将通过一个有重点的职业发展计划来实现这一点，其中包括临床试验设计方面的课程 生物统计学和结构化训练一起评估内皮功能，以衡量体外循环的效果。 拟议项目的完成将提供必要的指导、培训和所需的经验 使Clendenen博士成为心脏手术后改善预后的适应性临床试验的领导者。

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.