Glutamine's role in cardioprotection from cardiac bypass

点击翻译按钮获取中文摘要

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.