Impact of intraischemic temperature on oxidative stress during hepatic reperfusion.
This study was designed to investigate the influence of intraischemic liver temperature on oxidative stress during postischemic normothermic reperfusion. In C57BL/6 mice, partial hepatic ischemia was induced for 90 min and intraischemic organ temperature adjusted to 4 degrees C, 15 degrees C, 26 degrees C, 32 degrees C, and 37 degrees C. As detected by electron spin-resonance spectroscopy, plasma/blood concentrations of hydroxyl and ascorbyl radicals were significantly increased in all groups after ischemia/reperfusion independent of the intraischemic temperature. In tissue, however, postischemic lipid peroxidation was attenuated after organ cooling down to 32 degrees C-26 degrees C and not detectable after ischemia at 15 degrees C-4 degrees C. mRNA expression of superoxide dismutase-1 and heme oxygenase-1, measured during reperfusion, was significantly elevated in the group at 37 degrees C as compared to the hypothermic groups at 4 degrees C-32 degrees C. The reduction of radical generation was associated with a prevention of adenosine monophosphate hydrolysis during ischemia in the hypothermic groups. In conclusion, ischemia-reperfusion-induced oxidative stress in the liver tissue is non-linearly-dependent on intraischemic temperature, whereas the plasma/blood concentration of radicals is not affected by organ cooling. Oxidative stress is reduced through mild hypothermia at 32 degrees C-26 degrees C and inhibited completely at 15 degrees C. Reduction of initial intracellular radical generation and prevention of secondary oxidant-induced tissue injury are possible mechanisms of this protection.
Khandoga
Andrej
A
Institute for Surgical Research, University of Munich, Munich, Germany. andrej.khandoga@icf.med.uni-muenchen.de
Enders
Georg
G
Luchting
Benjamin
B
Axmann
Stefan
S
Minor
Thomas
T
Nilsson
Ulf
U
Biberthaler
Peter
P
Krombach
Fritz
F
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D017665:Hydroxyl Radical; D007036:Hypothermia, Induced; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D013696:Temperature
D008565:Membrane Proteins; D012333:RNA, Messenger; D017665:Hydroxyl Radical; D000249:Adenosine Monophosphate; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D001205:Ascorbic Acid