Differential effects of anesthetics on endotoxin-induced liver injury.
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.


CONCLUSIONS
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.
Suliburk
James W
JW
Department of Surgery, The University of Texas Medical School at Houston, Houston, Texas, USA.
Gonzalez
Ernest A
EA
Kennison
Sasha D
SD
Helmer
Kenneth S
KS
Mercer
David W
DW
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007530:Isoflurane / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism*
D000777:Anesthetics; D008070:Lipopolysaccharides; D007649:Ketamine; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1