Isoflurane attenuates early neutrophil-independent hypoxia-reoxygenation injuries in the reperfused liver in fasted rats.
BACKGROUND
Ischemia-hypoxia followed by reperfusion and reoxygenation injures cells and organs. Previous studies have indicated that isoflurane may protect organs from ischemia-reperfusion or hypoxia-reoxygenation. This study investigated the ability of isoflurane to protect the liver from hypoxia-reoxygenation injury and the mechanisms of this phenomenon.


METHODS
The isolated liver was perfused at a constant pressure of 12 cm H2O with a modified Krebs-Ringer-bicarbonate solution saturated with a 95% oxygen/5% carbon dioxide gas mixture. Hypoxic perfusion produced by decreasing the oxygen concentration in the gas mixture to 10% was followed by perfusion at 95% oxygen for 60 min. Viability of the liver was assessed by lactate dehydrogenase release from the liver. Isoflurane at 0.5, 1, and 2 minimum alveolar concentration was administered to assess the effect of isoflurane on hypoxia-reperfusion injury. To determine the effect of isoflurane on extracellular generation of superoxide in the liver, the reduction of ferricytochrome c with or without superoxide dismutase was measured.


RESULTS
Lactate dehydrogenase release was transiently but dramatically increased by reoxygenation and significantly attenuated by 1 and 2 minimum alveolar concentration of isoflurane. Suppression of Kupffer cells with gadolinium chloride also attenuated the lactate dehydrogenase release. Isoflurane significantly reduced the superoxide generation on reperfusion.


CONCLUSIONS
The results show that isoflurane protected the liver from an early reoxygenation injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory effects of isoflurane on the injury may involve suppression of extracellular superoxide generation during reoxygenation.
Kon
S
S
Department of Anesthesiology, Kimitsu Chuo Hospital, Chiba, Japan.
Imai
M
M
Inaba
H
H
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D050260:Carbohydrate Metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D005215:Fasting; D007530:Isoflurane / Q000494:pharmacology*; D007728:Kupffer Cells / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism
D018685:Anesthetics, Inhalation; D003574:Cytochrome c Group; D013481:Superoxides; D007530:Isoflurane; D007770:L-Lactate Dehydrogenase