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

• 批准号: 10242134
• 负责人: Marcos G Lopez
• 金额: $ 16.02万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 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/10242134
• 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; Hyperoxia; Hypertension; Impairment; Injury to Kidney; Investigation; K-Series Research Career Programs; Link; Measurement; Measures; Mediating; Mentors; Mentorship; Modeling; Muscle Tonus; Myography; Nitric Oxide; Operative Surgical Procedures; 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; immune activation; improved; innovation; multidisciplinary; normoxia; novel therapeutics; organ injury; oxidative damage; preclinical study; programs; prospective; recruit; research facility; skills; success; tonometry; vascular injury

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科斯·洛佩兹医学博士和硕士提供培训，并帮助他晋升 他的长期目标是成为一名独立的内科医生-科学家，测试减少器官的假说 外科病人的损伤。洛佩兹博士是范德比尔特大学医学院的麻醉师和重症医生 中心(VUMC)。他正在建立一个研究利基，以表征内皮功能障碍的贡献 到围手术期的脑和肾损伤。洛佩兹博士召集了一个多学科指导委员会 促进他的目标的实现。主要导师Frederic T.Billings IV医学博士，MSCI是一名麻醉师和 进行临床试验以减少心脏手术后肾脏损伤的强化医师。共同导师大卫·哈里森， 他是一位心脏病专家，也是内皮研究领域的领导者。共同导师Patik Pandharipande MD，MSCI， 是一位麻醉学家、重症监护学家，也是ICU精神错乱研究的领导者。洛佩兹博士将结合血管 哈里森实验室的生物学培训与围手术期临床试验设计和结果评估培训 从比林斯博士和Pandharipande博士那里获得独立。VUMC是一家三级学院医院， 优先发展像洛佩兹博士这样的内科科学家。核心研究设施、专家教员 以合作而闻名，研究和职业发展计划直接为他的成功做出贡献。 洛佩兹博士的研究将评估心脏手术前后内皮介导的血管反应性 参加RCT术中氧气治疗(R01GM112871；PI：Billings)的患者的手术测试 心脏手术期间常氧可改善血管反应性的假说与高氧和 血管反应性受损与术中氧化应激(目标1)相关，即血管反应性 与正常氧治疗的患者相比，常氧治疗患者的心包脂肪中分离出的小动脉将增加 高氧治疗患者(AIM 2)，内皮功能障碍与大脑和 肾损伤(目标3)。研究受益于受试者的招募、随机化、抽样和结果 父母试验的评估，但检验自己的独立假设，提供了一条科学的途径 独立。洛佩兹博士将测量肱动脉血流介导的扩张，外周动脉眼压测量，以及 术前、术后血浆纤溶酶原激活物抑制物-1和E-选择素水平。他会的 在手术结束时，使用肌丝造影术测量心包脂肪小动脉的血管反应性。他会的 将这些数据与氧合组、氧化应激标志物以及测量的大脑和肾脏进行比较 以检验他的假设。洛佩兹博士将获得招募病人参加临床试验的经验 收集数据，管理临床研究团队。 通过完成职业发展培训和这项研究，洛佩兹博士将逐步走向独立。他 将启动一项研究计划，通过靶向内皮功能障碍来减少围手术期器官损伤。