Optimizing pulsatility during cardiopulmonary bypass to reduce acute kidney injury

优化体外循环期间的搏动以减少急性肾损伤

• 批准号: 10674015
• 负责人: Nathan Clendenen
• 金额: $ 18.11万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674015
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Address; Arginine; Benefits and Risks; Biology; Biometry; Blood Vessels; Blood flow; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cardiovascular Diseases; Clinical; Clinical Trials; Clinical Trials Design; Clinical Trials Network; Colorado; Control Groups; Critical Illness; Data; Dedications; Development; Development Plans; Emergency Medicine; Endothelial Cells; Endothelium; Enrollment; Environment; Erythrocytes; Funding; Future; Glycocalyx; Goals; Health; Heart and Lung machine; Hemolysis; Hour; Impairment; Incidence; Injury to Kidney; Intervention; Intra-Aortic Balloon Pumping; Kidney; Kidney Diseases; Lactate Dehydrogenase; Measures; Mechanics; Medical center; Mentors; Mentorship; Metabolic Pathway; Methodology; Microscopy; Monitor; Morbidity - disease rate; Nitric Oxide; Operative Surgical Procedures; Organ; Outcome; Participant; Pathway interactions; Patient-Focused Outcomes; Patients; Perfusion; Persons; Phase; Physicians; Plasma; Postoperative Period; Procedures; Pulsatile Flow; Qualifying; Randomized, Controlled Trials; Research; Resources; Risk; Risk Reduction; Role; Stress; Structure; TIMP2 gene; Testing; Thick; Thinness; Training; United States; Universities; Work; biomedical referral center; career development; cell injury; clinical implementation; clinical practice; cohort; design; efficacy evaluation; endothelial dysfunction; experience; hemodynamics; improved; improved outcome; innovation; metabolomics; mortality; mortality risk; organ injury; patient subsets; phase III trial; preservation; prevent; prospective; response; risk minimization; risk/benefit ratio; single-cell RNA sequencing; transcriptomics; trial comparing; urinary; ventricular assist device

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.

项目总结/文摘

项目成果

Hyperoxemia During Cardiac Surgery Is Associated With Postoperative Pulmonary Complications.

• DOI: 10.1097/cce.0000000000000878
• 发表时间: 2023-03
• 期刊: Critical care explorations
• 作者: Douin DJ;Pattee J;Scott B;Fernandez-Bustamante A;Prin M;Eckle T;Ginde AA;Clendenen N
• 通讯作者: Clendenen N

Year in Review 2022: Noteworthy Literature in Cardiac Anesthesiology.

• DOI: 10.1177/10892532231173074
• 发表时间: 2023-06
• 期刊: SEMINARS IN CARDIOTHORACIC AND VASCULAR ANESTHESIA
• 影响因子: 1.4
• 作者: Christensen, Elijah;Morabito, Joseph;Kowalsky, Markus;Tsai, John-Paul;Rooke, Douglas;Clendenen, Nathan
• 通讯作者: Clendenen, Nathan

Challenging Paradigms and Trusting Evidence: New Approaches to Perioperative Care.

具有挑战性的范式和可信的证据：围手术期护理的新方法。

• DOI: 10.1177/10892532221138170
• 发表时间: 2022
• 期刊: Seminars in cardiothoracic and vascular anesthesia
• 影响因子: 1.4
• 作者: Prin,Meghan;Clendenen,Nathan;Lum,Hillary;Kertai,MiklosD;Abrams,BenjaminA
• 通讯作者: Abrams,BenjaminA

Year in Review 2020: Noteworthy Literature in Cardiothoracic Anesthesiology.

• DOI: 10.1177/10892532211013614
• 发表时间: 2021-06
• 期刊: SEMINARS IN CARDIOTHORACIC AND VASCULAR ANESTHESIA
• 影响因子: 1.4
• 作者: Clendenen, Nathan;Ahlgren, Bryan;Robitaille, Mark J.;Christensen, Elijah;Morabito, Joseph;Grae, Lyndsey;Lyman, Matthew;Weitzel, Nathaen
• 通讯作者: Weitzel, Nathaen