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

这个职业发展奖将提供培训马科斯洛佩斯，医学博士，MS和帮助他前进 朝着他的长期目标，成为一个独立的物理学家，科学家测试假设，以减少器官 手术患者的损伤。洛佩斯博士是范德比尔特大学医学院的麻醉师和重症监护医师 中心（VUMC）。他正在建立一个研究利基， 围手术期脑和肾损伤洛佩斯博士组建了一个多学科指导委员会， 帮助实现他的目标。导师Frederic T. Billings IV MD，MSCI是一名麻醉师， 进行临床试验以减少心脏手术后肾损伤的重症监护医师。共同导师大卫哈里森， 是一位心脏病专家，也是内皮研究的领导者。共同导师Pratik Pandharipande医学博士，MSCI， 是一名麻醉师、重症监护医师和ICU谵妄研究的领导者。洛佩斯医生会将联合收割机 哈里森实验室的生物学培训，包括围手术期临床试验设计和结局评估培训 从比林斯博士和潘达里潘德博士那里获得独立VUMC是一家三级学术医院， 优先培养像洛佩斯博士这样的医学科学家。核心研究设施，专家教师 他以合作和研究职业发展计划而闻名，这直接促成了他的成功。 洛佩斯博士的研究将评估心脏移植前后内皮介导的血管反应性。 在入组术中氧疗RCT（R 01 GM 112871; PI：Billings）的患者中进行手术， 与高氧相比，心脏手术期间常氧可改善血管反应性的假设， 受损的血管反应性与术中氧化应激相关（目的1）， 在从常氧治疗患者的心包脂肪解剖的小动脉中， 高氧治疗的患者（目的2），内皮功能障碍与脑和 肾损伤（目的3）。研究受益于受试者招募、随机化、采样和结局 母试验的评估，但测试自己的独立假设，提供了一个科学的途径， 独立洛佩斯医生将测量肱动脉血流介导的扩张，外周动脉张力测定， 血浆纤溶酶原激活物抑制物-1和E-选择素浓度。他将 在手术结束时使用钢丝肌造影术测量心包脂肪小动脉中的血管反应性。他将 将这些数据与氧合组、氧化应激标志物以及测量的脑和肾进行比较 以检验他的假设。洛佩斯博士将获得招募患者参加临床试验的经验， 收集数据和管理临床研究团队。 洛佩斯博士将通过完成职业发展培训和本研究实现独立。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。

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.