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Glutamine restores myocardial cytochrome C oxidase activity and improves cardiac function during experimental sepsis.
MedLine Citation:
PMID:  21378254     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND: Cardiac dysfunction occurs commonly in sepsis. Impaired mitochondrial function is a potential cause of sepsis-associated myocardial depression. Cytochrome oxidase (COX), the terminal oxidase of the electron transport chain, is inhibited in the septic heart. Glutamine (GLN) increases Krebs cycle intermediates and supports oxidative phosphorylation. Exogenous GLN has been shown to restore myocardial adenosine triphosphate levels and cardiac function following ischemia-reperfusion injury. The authors hypothesize that exogenous GLN will abrogate sepsis-induced myocardial COX inhibition and improve sepsis-associated myocardial depression.
METHODS: Under general anesthesia, male Sprague-Dawley rats underwent cecal ligation and double puncture (CLP) or sham operation. At the time of operation, rats underwent intraperitoneal injection of either GLN (0.75 g/kg) or an equal volume of saline. Twenty-four hours after the procedure, animals were killed, cardiac ventricles harvested, and mitochondria isolated. Steady-state COX kinetic activity was measured and normalized to citrate synthase activity. Steady-state levels of COX subunit I protein were determined with immunoblot analysis. Cardiac function was assessed using an isolated rat heart preparation. Five animals per group were evaluated. Significance was determined with analysis of variance and post hoc Tukey test.
RESULTS: CLP significantly decreased myocardial COX activity, oxygen consumption, left ventricular pressure (LVP), and pressure developed during isovolumic contraction (+dP/dt) and relaxation (-dP/dt). GLN restored COX activity to sham levels, significantly increased myocardial oxygen extraction and consumption, increased LVP toward sham values, and increased ±dP/dt by >30% following CLP. Conclusion: The beneficial effects of GLN therapy during sepsis may be in part due to restoration of oxidative phosphorylation and abrogation of sepsis-associated myocardial depression.
Authors:
Portia Groening; Zhishan Huang; Edmund Frances La Gamma; Richard J Levy
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  JPEN. Journal of parenteral and enteral nutrition     Volume:  35     ISSN:  0148-6071     ISO Abbreviation:  JPEN J Parenter Enteral Nutr     Publication Date:    2011 Mar-Apr
Date Detail:
Created Date:  2011-03-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804134     Medline TA:  JPEN J Parenter Enteral Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  249-54     Citation Subset:  IM    
Affiliation:
Division of Newborn Medicine, Maria Fareri Children's Hospital of Westchester Medical Center, New York Medical College, Valhalla, New York.
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