? It is well known that enhanced heat shock protein-70 (HSP-70) expression can protect cells and tissues from injury. Further, HSP-70 expression can improve survival in experimental models of critical illness. However, clinical application of these findings has not occurred, as known enhancers of HSP-70 are not safe for human administration. Thus, this very powerful tool, that could possibly significantly improve outcome in critically ill patients, has yet to be clinically applied. Our laboratory has shown that the amino acid glutamine (GLN) can enhance HSP-70 expression in tissues of stressed animals. This expression is correlated with improved survival following experimental models of critical illness. In a small initial trial of critically ill patients we demonstrated GLN could enhance serum HSP-70 levels after one-week of therapy. The effect of GLN on tissue HSP-70 expression and its potential to improve outcomes in patients is unknown. We propose three Specific Aims. The first examines GLN's effect on serum and cellular HSP-70 expression in healthy volunteers following a heat stress. This trial will assess if HSP-70 can be pre-induced to improve outcomes prior to a stressful event, such as surgery. The second Specific Aim will be to assess GLN's effect on serum and cellular HSP-70 expression in critical illness. The third Specific Aim will examine the effect of potentially enhanced HSP-70 expression on clinical outcomes. We believe this study will demonstrate that GLN is the first clinically viable enhancer of HSP-70 expression. The potential for such an agent to reduce morbidity/mortality in surgical and critical illness is significant. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
5R03DK073035-02
Application #
7282449
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (M4))
Program Officer
Miles, Carolyn
Project Start
2006-09-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$149,534
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
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