Timing of ischaemia/reperfusion before hepatectomy without inflow occlusion determines liver damage in rats: role of heat shock protein 70.
BACKGROUND
Living donor hepatectomies in liver transplantation are usually performed without inflow occlusion. We hypothesized that selective ischaemia/reperfusion (SIR) before partial hepatectomy (PH) without inflow occlusion might exert a hepatoprotective effect.


METHODS
In the SIR groups, rats were subjected to a selective 30-min ischaemia to the liver that remained after PH, followed by various durations of reperfusion before 70% PH without inflow occlusion. The control group underwent 70% PH alone.


RESULTS
As assessed by serum aspartate and alanine aminotransferase levels, 30-min reperfusion was highly protective against liver injury compared with 10-min reperfusion, showing the same levels as that of the control group. After PH in the 10-min reperfusion group, apoptotic cells were significantly higher and the 7-day survival rate was significantly lower than that of the 30-min reperfusion group and the control group. In the 30-min reperfusion group, the expression of heat shock protein 70 (HSP70) was significantly higher than that in the 10-min reperfusion group, while apoptosis was improved to the levels of the control group. In the SIR groups, liver regeneration was significantly enhanced, with markedly increased levels of interleukin 6 (IL-6) compared with the control group.


CONCLUSIONS
The timing of SIR before PH without inflow occlusion seemed to be the most important factor for determining liver damage and survival in the context of HSP70 production, while high levels of IL-6 appear to be associated with liver regeneration after PH. The procedure of SIR before PH is not recommended because the SIR groups did not overcome the control group.
Nakamura
Ikuo
I
Department of Hepatobiliary Pancreatic Surgery, Mie University Hospital, Mie, Japan. ikuo.n@clin.medic.mie-u.ac.jp
Isaji
Shuji
S
Yamagiwa
Kentaro
K
Hamada
Takashi
T
Uemoto
Shinji
S
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006498:Hepatectomy / Q000379:methods*; D015850:Interleukin-6 / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008115:Liver Regeneration; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha