- Poster presentation
- Open Access
Hyperglycemia in a rat CLP model of sepsis is associated with mitochondrial uncoupling
© BioMed Central Ltd 2006
- Published: 21 March 2006
- Liver Mitochondrion
- Mitochondrial Respiratory Chain
- Oxygen Electrode
- Cecal Ligation
Tight glucose control was shown to greatly improve the morbidity and mortality of septic ICU patients . The mechanism by which hyperglycemia is detrimental is not clearly understood.
Hyperglycemia is associated with hepatic dysfunction of the mitochondrial respiratory chain (MRC).
Male Sprague-Dawley rats, 250–400 g, were used. We followed glucose levels in rats made septic by cecal ligation and perforation (CLP) over time (tail puncturing). We also evaluated MRC in isolated liver mitochondria at different time-points post-CLP. Enzymatic activities of MRC complexes I-IV were measured by spectrophotometry and respiration was measured by an oxygen electrode with glutamate + malate as substrates. The respiratory control ratio (RCR), calculated as the ratio of oxygen uptake in the presence and absence of ADP, served as an indicator for coupling. Sham laparotomy rats served as controls.
This rat CLP model of sepsis, in its early hours, mimics human septic hyperglycemia. Impaired function of a septic rat's liver mitochondria (markedly decreased coupling and moderately decreased MRC activities) is evident following the time-period of hyperglycemia in this model.