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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23RR018379-03
Application #
6930482
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
2003-08-15
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
3
Fiscal Year
2005
Total Cost
$130,592
Indirect Cost
Name
University of Colorado Denver
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Ziegler, Thomas R; May, Addison K; Hebbar, Gautam et al. (2016) Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial. Ann Surg 263:646-55
Sufit, Alexandra; Weitzel, Lindsay B; Hamiel, Christine et al. (2012) Pharmacologically dosed oral glutamine reduces myocardial injury in patients undergoing cardiac surgery: a randomized pilot feasibility trial. JPEN J Parenter Enteral Nutr 36:556-61
Weitzel, Lindsay-Rae B; Wischmeyer, Paul E (2010) Glutamine in critical illness: the time has come, the time is now. Crit Care Clin 26:515-25, ix-x
Weitzel, Lindsay-Rae B; Mayles, William J; Sandoval, Paul A et al. (2009) Effects of pharmaconutrients on cellular dysfunction and the microcirculation in critical illness. Curr Opin Anaesthesiol 22:177-83
Singleton, Kristen D; Wischmeyer, Paul E (2008) Glutamine attenuates inflammation and NF-kappaB activation via Cullin-1 deneddylation. Biochem Biophys Res Commun 373:445-9
Singleton, Kristen D; Wischmeyer, Paul E (2007) Glutamine's protection against sepsis and lung injury is dependent on heat shock protein 70 expression. Am J Physiol Regul Integr Comp Physiol 292:R1839-45
Morrison, Angela L; Dinges, Martin; Singleton, Kristen D et al. (2006) Glutamine's protection against cellular injury is dependent on heat shock factor-1. Am J Physiol Cell Physiol 290:C1625-32
Singleton, Kristen D; Serkova, Natalie; Beckey, Virgina E et al. (2005) Glutamine attenuates lung injury and improves survival after sepsis: role of enhanced heat shock protein expression. Crit Care Med 33:1206-13
Ziegler, Thomas R; Ogden, Lorraine G; Singleton, Kristen D et al. (2005) Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med 31:1079-86
Singleton, Kristen D; Serkova, Natalie; Banerjee, Anirban et al. (2005) Glutamine attenuates endotoxin-induced lung metabolic dysfunction: potential role of enhanced heat shock protein 70. Nutrition 21:214-23