Dec 4, 2008

Moderate hypothermia prevents cardiac arrest-mediated suppression of drug metabolism and induction of interleukin-6 in rats

Critical Care Medicine
Michael A TortoriciSamuel M Poloyac


Therapeutic hypothermia is being clinically used to reduce neurologic deficits after cardiac arrest (CA). Patients receiving hypothermia after CA receive a wide-array of medications. During hypothermia, drug metabolism is markedly reduced. Little, however, is known about the impact of hypothermia on drug metabolism after rewarming. The objective of this study was to examine the effect of CA and hypothermia on the functional regulation of two major drug metabolizing cytochrome P450 (CYP) isoforms. Laboratory investigation. University pharmacy school and animal research facility. Thirty-six male Sprague-Dawley rats. Hypothermia was induced via surface cooling in a rat CA model and maintained for 3 hrs. Animals were killed at 5 or 24 hrs and liver was analyzed for hepatic activity and mRNA expression of CYP3A2 and CYP2E1. Plasma interleukin-6 (IL-6) concentrations were determined. The effect of IL-6 on pregnane X receptor-mediated transcription of the rat CYP3A2 promoter was evaluated via luciferase reporter in HepG2 cells. At 24 hrs after CA a decrease in CYP3A2 and CYP2E1 activity was observed, 55.7% +/- 12.8% and 46.8% +/- 29.7% of control, respectively (p < 0.01). CA decreased CYP3A2 mRNA (p < 0.05), but not CYP2E1 mRNA. Expre...Continue Reading

  • References34
  • Citations12


  • References34
  • Citations12


Mentioned in this Paper

Neurologic Manifestations
Enzymes, antithrombotic
Cytochrome P450
CYP2E1 gene
Xenobiotic Monooxygenases
Cytochrome P450 3A
Rats, Sprague-Dawley
Cytochrome P-450 CYP2E1

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