Protective effect of ischemic preconditioning against intermittent warm-ischemia-induced liver injury.
BACKGROUND
Although ischemic preconditioning (IPC) has been reported to protect the liver from injury when subjected to continuous hepatic ischemia, whether IPC protects rat livers against ischemia-reperfusion (I/R) injury after intermittent ischemia has not been elucidated.


METHODS
Five groups of Wistar rats were subjected to intermittent hepatic ischemia (I) comprising 15-min ischemia and 5-min reperfusion three times with or without prior IPC (10-min ischemia and 10-min reperfusion), 45-min continuous ischemia (C) with or without IPC, and sham operation. Serum transaminase and lactic acid levels, hepatic tissue energy charges, and hepatic blood perfusion were measured after reperfusion. Plasma tumor necrosis factor-alpha (TNF-alpha) levels were determined after reperfusion for 120 min. Histological and apoptotic findings were evaluated after reperfusion for 180 min.


RESULTS
IPC significantly reduced serum transaminase levels after continuous and intermittent ischemia (IPC + C, 1107 vs C, 2684 IU/l; IPC + I, 708 vs I, 1859 IU/l). After hepatic ischemia without IPC, apoptosis and necrosis with increased plasma TNF-alpha levels were observed. IPC protected livers from injury by interfering with the increase in plasma TNF-alpha (IPC + I, 27.6 vs I, 64.8 pg/ml; IPC + C, 21.6 vs C, 49.3 pg/ml). This resulted in the attenuation of hepatic necrosis after continuous ischemia and significantly reduced necrosis and apoptosis after intermittent ischemia.


CONCLUSIONS
IPC exerts a greater protective effect against hepatic I/R injury after intermittent hepatic ischemia than after continuous hepatic ischemia.
Iwasaki
Yoshimi
Y
Department of Gastroenterological Surgery, Dokkyo University School of Medicine, 321-0293 Tochigi, Japan. yiwasaki@dokkyomed.ac.jp
Tagaya
Nobumi
N
Hattori
Yoshiyuki
Y
Yamaguchi
Keiichiro
K
Kubota
Keiichi
K
D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D004734:Energy Metabolism; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology; D006358:Hot Temperature; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D019194:Ischemic Preconditioning; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008102:Liver Circulation; D008297:Male; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D001219:Aspartate Aminotransferases