| Title | Differential effects of anesthetics on endotoxin-induced liver injury. | | Author(s) | Suliburk JW, Gonzalez EA, Kennison SD, Helmer KS, Mercer DW | | Institution | Department of Surgery, The University of Texas Medical School at Houston, Houston, Texas, USA. | | Source | J Trauma 2005 Apr; 58(4):711-6; discussion 716-7. | | MeSH | Anesthetics
Animals
Comparative Study
Female
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Isoflurane
Ketamine
Lipopolysaccharides
Liver
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Oxidative Stress
Rats
Rats, Sprague-Dawley
Research Support, U.S. Gov't, P.H.S.
Sepsis
| | 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. Upregulation 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 15824646 |
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