Mentored Patient-Oriented Research Career Development Award

指导以患者为中心的研究职业发展奖

• 批准号: 6930482
• 负责人: PAUL E WISCHMEYER
• 金额: $ 13.06万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930482
• 关键词: atrium; cardiovascular disorder therapy; clinical research; clinical trials; coronary bypass; creatine phosphate; cytoprotection; diet therapy; dietary supplements; glutamine; heart /lung bypass; heart function; heat shock proteins; human subject; human therapy evaluation; magnetic resonance imaging; metabolism; myocardial ischemia /hypoxia; nutrition related tag; patient oriented research; plasma; troponin; western blottings

DESCRIPTION (provided by applicant): The Principal Investigator, Dr. Wischmeyer has the long-term goal of pursuing independent clinical investigation in the field of nutritional pharmacology. Receipt of a Mentored Patient-Oriented Research Career Development Award will facilitate the growth of Dr. Wischmeyer's investigative skills and experience by expanding his knowledge of clinical research design and the use of molecular and metabolic assay techniques in human research. The learning objectives set out in this proposal, combined with the support of his mentor, Dr. Robert Eckel and the critical environment within the Department of Anesthesiology, the Department of Surgery, and the Training Program in Clinical Sciences at the UC, will foster Dr. Wischmeyers's progression to independent lines of investigation into the clinical applications of nutrition to clinical states of tissue injury and critical illness. The specific aims of this proposal will extend previous pre-clinical research by Dr. Wischmeyer demonstrating a protective effect of the amino acid glutamine (GLN) on myocardial ischemia/reperfusion (I/R) injury. This proposal aims to evaluate in a randomized, controlled clinical trial the effect of pre-operatively administered, oral GLN on patients undergoing elective coronary artery bypass grafting (CABG) in which cardiopulmonary bypass is employed. Four immediate goals for the trial are defined: 1) Determine the effect of GLN on myocardial tissue injury. Comary effluent and plasma will be collected and analyzed for troponin, CKMB analysis. 2) Determine the effect of GLN on human atrial tissue heat shock protein content. Right atrial appendage tissue will be harvested from patients undergoing CABG surgery and analyzed for heat shock protein 72 and 27 content (Western analysis). 3) Determine the effect of GLN on enhancement of measures of metabolism in human atrial tissue. Right atrial appendage tissue will be harvested from patients undergoing CABG surgery and analyzed for tissue metabolism magnetic resonance spectroscopy (MRS). These measurements will include tissue ATP, ATP/ADP ratio, NAD/NADH content, lactate, glutamine, glutamate, and reduced glutathione content. 4) Determine the effect of GLN on post-operative cardiac function and overall patient outcomes. Data will be collected on cardiac function (cardiac output), occurrence of arrhythmias, need for vasopressor therapy, length of post-operative ventilation, ICU stay; and survival trends.

描述（由申请人提供）： 首席研究员 Wischmeyer 博士的长期目标是在营养药理学领域进行独立的临床研究。 获得以患者为导向的研究职业发展奖将通过扩展 Wischmeyer 博士在临床研究设计以及在人类研究中使用分子和代谢测定技术的知识，促进他的研究技能和经验的增长。 该提案中提出的学习目标，加上他的导师 Robert Eckel 博士的支持以及加州大学麻醉学系、外科系和临床科学培训项目内的关键环境，将培养 Dr. Robert Eckel 博士。 Wischmeyers 对营养在组织损伤和危重疾病临床状态中的临床应用进行独立研究。 该提案的具体目标将扩展 Wischmeyer 博士之前的临床前研究，证明氨基酸谷氨酰胺 (GLN) 对心肌缺血/再灌注 (I/R) 损伤的保护作用。该提案旨在通过一项随机对照临床试验评估术前口服 GLN 对接受体外循环的选择性冠状动脉旁路移植术 (CABG) 患者的影响。 该试验确定了四个近期目标： 1)确定GLN对心肌组织损伤的作用。 将收集并分析香豆流出物和血浆以进行肌钙蛋白、CKMB 分析。 2)测定GLN对人心房组织热休克蛋白含量的影响。将从接受 CABG 手术的患者身上采集右心耳组织，并分析热休克蛋白 72 和 27 的含量（Western 分析）。 3) 确定 GLN 对增强人体心房组织代谢指标的影响。 将从接受 CABG 手术的患者身上采集右心耳组织，并进行组织代谢磁共振波谱 (MRS) 分析。 这些测量包括组织 ATP、ATP/ADP 比率、NAD/NADH 含量、乳酸、谷氨酰胺、谷氨酸和还原型谷胱甘肽含量。 4) 确定 GLN 对术后心功能和患者总体预后的影响。 将收集有关心功能（心输出量）、心律失常的发生、血管加压治疗的需要、术后通气时间、ICU 住院时间的数据；和生存趋势。