Perioperative Oxygenation, Endothelial Dysfunction, and Organ Injury in Cardiac Surgery

心脏手术中的围手术期氧合、内皮功能障碍和器官损伤

基本信息

批准号：
9763631
负责人：
Marcos G Lopez
金额：
$ 16.16万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9763631
关键词：
Academic Medical Centers Achievement Acute Renal Failure with Renal Papillary Necrosis Affect Arteries Atrial Fibrillation Award Biology Blood Vessels Brain Brain Injuries Cardiac Surgery procedures Cessation of life Clinical Research Clinical Trials Clinical Trials Design Coagulation Process Collaborations Conduct Clinical Trials Critical Illness Data Delirium Development E-Selectin Endothelium Enrollment F2-Isoprostanes Faculty Fatty acid glycerol esters Goals Harvest Hospitals Hyperbaric Oxygenation Hyperoxia Hypertension Immune Cell Activation Impairment Injury Injury to Kidney Investigation K-Series Research Career Programs Kidney Link Measurement Measures Mediating Mentors Mentorship Modeling Muscle Tonus Myography Nitric Oxide Operative Surgical Procedures Organ Organ failure Outcome Outcome Assessment Oxidative Stress Oxygen Parents Patient Recruitments Patient-Focused Outcomes Patients Perfusion Pericardial body location Perioperative Peripheral Physicians Physiological Plasma Plasminogen Activator Inhibitor 1 Postoperative Period Production Program Development Randomized Reactive Oxygen Species Reperfusion Injury Research Resistance Risk Route Sampling Scientist Sepsis Signal Transduction Smooth Muscle Techniques Testing Therapeutic Trials Tissues Training Translational Research arterial tonometry arteriole brachial artery career development data management design endothelial dysfunction experience improved innovation multidisciplinary novel therapeutics oxidative damage preclinical study programs prospective recruit research facility skills success tonometry

项目摘要

This career development award will provide training to Marcos Lopez, MD, MS and help him advance towards his long-term goal of becoming an independent physician-scientist testing hypotheses to reduce organ injury in surgical patients. Dr. Lopez is an anesthesiologist and intensivist at Vanderbilt University Medical Center (VUMC). He is establishing a research niche characterizing the contribution of endothelial dysfunction to perioperative brain and kidney injury. Dr. Lopez assembled a multidisciplinary mentorship committee to facilitate achievement of his goals. Primary mentor Frederic T. Billings IV MD, MSCI is an anesthesiologist and intensivist who conducts clinical trials to reduce kidney injury after cardiac surgery. Co-mentor David Harrison, MD, is a cardiologist and leader in the study of the endothelium. Co-mentor Pratik Pandharipande MD, MSCI, is an anesthesiologist, intensivist, and leader in the study of ICU delirium. Dr. Lopez will combine vascular biology training in the Harrison lab with perioperative clinical trial design and outcome assessments training from Drs. Billings and Pandharipande to achieve independence. VUMC is a tertiary academic hospital that prioritizes the development of physician-scientists like Dr. Lopez. Core research facilities, expert faculty renowned for collaboration, and research career development programs directly contribute to his success. Dr. Lopez's research will assess endothelium-mediated vascular reactivity prior to and following cardiac surgery in patients enrolled in an RCT of intraoperative oxygen treatment (R01GM112871; PI: Billings) to test the hypotheses that normoxia during cardiac surgery improves vascular reactivity compared to hyperoxia and that impaired vascular reactivity correlates with intraoperative oxidative stress (Aim 1), that vascular reactivity in arterioles dissected from the pericardial fat of normoxia-treated patients will be increased compared to hyperoxia-treated patients (Aim 2), and that endothelial dysfunction is associated with increased brain and kidney injury (Aim 3). The study benefits from the subject recruitment, randomization, sampling, and outcomes assessment of the parent trial but tests its own independent hypotheses, providing a route to scientific independence. Dr. Lopez will measure brachial artery flow-mediated dilation, peripheral artery tonometry, and plasma concentrations of plasminogen activator inhibitor-1 and E-selectin pre and postoperatively. He will measure vascular reactivity in pericardial fat arterioles at the end of surgery using wire myography. He will compare these data with oxygenation groups, markers of oxidative stress, and with measured brain and kidney injury to test his hypotheses. Dr. Lopez will gain experience recruiting patients into a clinical trial, prospectively collecting data, and managing a clinical research team. Dr. Lopez will progress to independence by completing career development training and this study. He will initiate a research program to reduce perioperative organ injury by targeting endothelial dysfunction.

该职业发展奖将为马里兰州马里兰州马科斯·洛佩兹（Marcos Lopez）提供培训，并帮助他进步朝着他成为独立医师科学家测试假设以减少器官的长期目标手术患者受伤。洛佩兹博士是范德比尔特大学医学的麻醉师和强化主义者中心（VUMC）。他正在建立一项研究，以表征内皮功能障碍的贡献围手术期的大脑和肾脏损伤。洛佩兹博士将一个多学科指导委员会汇集给促进实现他的目标。 MSCI的主要导师Frederic T. Billings IV MD是麻醉师和进行临床试验以减少心脏手术后肾脏损伤的强化主义者。联合官员大卫·哈里森（David Harrison），医学博士是内皮研究的心脏病专家和领导者。 MSCI的Co-Mentor Pratik Pandharipande医学博士是麻醉师，强化主义者和ICU del妄研究中的领导者。洛佩兹博士将结合血管围手术期临床试验设计和结果评估培训在哈里森实验室的生物学培训来自博士。 Billings和Pandharipande实现独立。 VUMC是一家三级学术医院优先考虑洛佩兹博士等医师科学家的发展。核心研究设施，专家教师以合作而闻名，研究职业发展计划直接为他的成功做出了贡献。洛佩兹博士的研究将在心脏之前和之后评估内皮介导的血管反应性参加术中氧气治疗RCT（R01GM112871; PI：Billings）的患者的手术以测试与高氧和高氧和障碍的血管反应性与术中氧化应激相关（AIM 1），即血管反应性与正常氧治疗患者的心包脂肪剖析的小动脉中，将增加高氧治疗的患者（AIM 2），并且内皮功能障碍与大脑和大脑增加有关肾脏受伤（目标3）。该研究受益于受试者的招聘，随机化，抽样和结果评估父母试验，但考验其自己的独立假设，提供了科学的途径独立。洛佩兹博士将测量臂动脉流介导的扩张，周围动脉渗透和纤溶酶原激活剂1和术后E-选择素的血浆浓度。他会的使用电线密闭手术结束时，在心包脂肪动脉中测量血管反应性。他会的将这些数据与氧合基团，氧化应激标记以及测量的大脑和肾脏进行比较受伤以检验他的假设。洛佩兹博士将获得招募患者的经验，前瞻性地收集数据并管理临床研究团队。洛佩兹博士将通过完成职业发展培训和这项研究来发展独立。他将启动一项研究计划，以靶向内皮功能障碍来减少围手术期的器官损伤。