Differences in the response of Sprague-Dawley and Lewis rats to bezafibrate: The hypolipidemic effect and the induction of peroxisomal enzymes

The effects of bezafibrate administered at 10 and 50 mg/kg/day for 7 days to male Sprague-Dawley (SD) and Lewis rats were investigated in order to determine the interrelation between the changes in serum and hepatic lipid contents and activities of selected peroxisomal, microsomal and mitochondrial enzymes in the two rat strains. In both strains, bezafibrate effectively reduced serum and hepatic lipids, increased the liver weight, induced a proliferation of peroxisomes, and selectively elevated the activities of carnitine acetyltransferase and of the enzymes of the peroxisomal -oxidation system. Moreover, immunoblotting revealed that the drug specifically enhanced the concentration of only those peroxisomal enzymes involved in fatty acid -oxidation. The data obtained demonstrate that although the responses initiated by bezafibrate are qualitatively similar in both strains, they differ in their magnitude in a dose-dependent manner, with the Lewis strain exhibiting a more pronounced response than the SD rats. These results show that dose-dependent strain differences as well as the generally known species differences should be taken into account in pharmacological and toxicological evaluations of fibrates in rodents. Furthermore, generalization and extrapolation from rodent studies should be treated with great caution.     

Therapeutic Hypothermia Following Emergent Coronary Artery Bypass Grafting After Failed Percutaneous Coronary Intervention in a Comatose Post-Cardiac Arrest Patient

We report the case of 60-yr-old female in which therapeutic hypothermia (TH) was successfully induced maintaining the target temperature of 34℃ for 12 hr despite a risk of hypothermia-induced coagulation abnormalities following an emergent coronary artery bypass grafting (CABG) due to failed percutaneous coronary intervention, who suffered a cardiac arrest. Emergent CABG may be a relative contraindication for TH in post-cardiac arrest patients because hypothermia may increase the risk of infection and bleeding. However, the possibility of an improved neurologic outcome outweighs the risk of bleeding, although major surgery may be a relative contraindication for TH.