Glutamine restores myocardial cytochrome C oxidase activity and improves cardiac function during experimental sepsis.
Glutamine restores myocardial cytochrome C oxidase activity and improves cardiac function during experimental sepsis.
复制标题
DOI：
10.1177/0148607110383040
复制
发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Portia Groening;Zhishan Huang;E. L. La Gamma;R. Levy
中科院分区：
文献类型：
--
作者：
Portia Groening;Zhishan Huang;E. L. La Gamma;R. Levy
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.
