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）： 主要研究者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。 接受指导的以患者为导向的研究职业发展奖将促进Wischmeyer博士的调查技能和经验的增长，通过扩大他在临床研究设计和在人类研究中使用分子和代谢分析技术的知识。 本提案中规定的学习目标，加上他的导师Robert Eckel博士的支持，以及UC麻醉学系，外科系和临床科学培训计划中的关键环境，将促进Wischmeyers博士发展到独立的调查线，将营养应用于组织损伤和危重病的临床状态。 该提案的具体目标将扩展Wischmeyer博士先前的临床前研究，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。本提案旨在通过一项随机对照临床试验，评价术前口服GLN对采用心肺转流术的择期冠状动脉旁路移植术（CABG）患者的影响。 确定了试验的四个近期目标： 1)测定GLN对心肌组织损伤的影响。 将采集合并液和血浆，并进行肌钙蛋白、CKMB分析。 2)测定谷氨酰胺对人心房组织热休克蛋白含量的影响。从接受CABG手术的患者中采集右心耳组织，并分析热休克蛋白72和27的含量（Western分析）。 3)确定GLN对增强人心房组织代谢指标的影响。 将从接受CABG手术的患者中采集右心耳组织，并进行组织代谢磁共振波谱（MRS）分析。 这些测量将包括组织ATP、ATP/ADP比值、NAD/NADH含量、乳酸盐、谷氨酰胺、谷氨酸盐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结局的影响。 将收集关于心功能（心输出量）、心律失常发生率、血管加压药治疗需求、术后通气时间、ICU住院时间和生存趋势的数据。