Abstract 140: Low-Dose Atorvastatin Improves Mortality and Inhibits Inflammatory Response to Endotoxin-Induced Shock in Rats
Background: Several investigations have demonstrated the beneficial effects of atorvastatin on septic shock in animal studies. However, our previous report has suggested that atorvastatin (10mg/kg/day) does not improve mortality in endotoxin-induced shock in rats. This finding suggested that high dose atorvastatin (10mg/kg/day) may have disadvantageous effects on endotoxic shock. The present study evaluated the dose-related effects of atorvastatin on mortality and inflammatory response in endotoxemic rats.
Methods: Forty-one male Sprague-Dawley rats were randomly assigned to one of the following three groups: control group (group C, n=14), no medication; medium dose group (group M, n=13), oral administration of atorvastatin (5mg/kg/day) for 5 days; low dose group (group L, n=14), oral administration of atorvastatin (2mg/kg/day) for 5 days. After that, all rats were anesthetized with pentobarbital i.p. Endotoxin-induced shock was induced by 15mg/kg of endotoxin i.v. Hemodynamics and arterial blood gases were recorded, and mortality rates were calculated for the 8-hr observation period and plasma cytokine concentration measurements were performed at 5hrs after shock.
Results: The mortality rates at 8hrs after endotoxin injection were 43%, 31%, and 7% for group C, M and L, respectively. The mortality rate in group L was significantly lower than that in group M and C. (P<0.05) There was no significant difference in mortality between group M and C. Lactate concentrations increased greater in group M and C than in group L. (P<0.001) As for hemodynamics, group M and C experienced a significant decrease in arterial blood pressure and heart rate measurements, compared with group L during experiment.(P<0.05)
Conclusions: The present study showed low dose atorvastatin improved mortality and inhibited inflammatory response to endotoxin-induced shock in rats. These findings suggest that low dose atorvastatin may have beneficial effects on septic patients.
- © 2011 by American Heart Association, Inc.