Glutamine's role in cardioprotection from cardiac bypass

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导师研究职业发展奖将有助于Wischmeyer博士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方面的知识，从而促进他的研究技能和经验的增长。这项建议中提出的学习目标，再加上他的导师罗伯特·埃克尔博士的支持，以及麻醉系、外科系和加州大学临床科学培训计划内的关键环境，将推动Wischmeyers博士在组织损伤和危重疾病的临床应用方面取得进展，成为独立的研究方向。这项提案的具体目的将扩展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)损伤具有保护作用。本建议旨在通过一项随机对照临床试验，评估术前口服谷氨酰胺对体外循环下择期冠状动脉旁路移植术(CABG)患者的影响。为试验确定了四个近期目标： 1)测定谷氨酰胺对心肌组织损伤的影响。收集粪便和血浆进行肌钙蛋白、肌钙蛋白同工酶检测。2)测定谷氨酰胺对人心房组织热休克蛋白含量的影响。右心耳组织取自冠状动脉旁路移植术患者，分析热休克蛋白72和27的含量(Western分析)。3)测定谷氨酰胺对人心房组织代谢指标的增强作用。右心耳组织将从接受冠状动脉搭桥术的患者身上获取，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)确定谷氨酰胺对术后心功能和整体患者预后的影响。将收集有关心功能(心输出量)、心律失常的发生、是否需要血管加压治疗、术后机械通气时间、ICU住院时间以及生存趋势的数据。

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.