Abstract
Background: The liver is both a source and a target of inflammatory and anti-inflammatory mediators during sepsis. The oxidative stress proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are upregulated in the liver during sepsis but have opposite roles. Up-regulation of HO-1 has hepatoprotective effects, whereas iNOS has injurious effects to the liver. Although recent studies indicate that ketamine anesthesia has anti-inflammatory effects during sepsis, the effects of other anesthetics are unknown. We hypothesized that ketamine, but not isoflurane, would attenuate lipopolysaccharide (LPS)-induced liver injury through differential modulation of iNOS and HO-1. Methods: Adult rats were given no anesthesia (saline), continuous isoflurane inhalation, or intraperitoneal ketamine (70 mg/ kg). One hour later, saline or LPS (20 mg/kg intraperitoneally) was given for 5 hours. Rats were killed, serum prepared for determination of hepatocellular enzymes, and the liver assessed for iNOS and HO-1 by Western immunoblot. Results: LPS significantly increased serum aspartate aminotransferase levels, iNOS, and HO-1 immunoreactivity in the liver. Ketamine but not isoflurane attenuated LPS-induced liver injury, upregulated HO-1, and downregulated iNOS. Conclusion: These data indicate that anesthetics differ in their effects on the liver in a rat model of sepsis with LPS. Ketamine has hepatoprotective effects against LPS-induced liver injury that appear to be mediated, at least in part, by differential modulation of the oxidative stress proteins iNOS and HO-1. Thus, ketamine may be the anesthetic agent of choice for septic patients requiring anesthesia.
Original language | English (US) |
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Pages (from-to) | 711-717 |
Number of pages | 7 |
Journal | Journal of Trauma - Injury, Infection and Critical Care |
Volume | 58 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2005 |
Externally published | Yes |
Keywords
- Anesthesia
- Heme oxygenase-1 (HO-1)
- Inducible nitric oxide synthase (iNOS)
- Isoflurane
- Ketamine
- Lipopolysaccharide (LPS)
ASJC Scopus subject areas
- Surgery
- Critical Care and Intensive Care Medicine