The effect of trimetazidine on liver regeneration after partial hepatectomy under hepatic blood inflow occlusion.
OBJECTIVE
It has been shown that hepatic blood inflow occlusion impairs liver regeneration. Our aim in this study was to investigate the effect of trimetazidine, known as an anti-ischemic and anti-oxidant agent, on liver regeneration after hepatic blood inflow occlusion.


METHODS
Sprague-Dawley rats were randomized into three groups. Rats in group 1 underwent 65% hepatectomy. Rats in group 2 and 3 were subjected to 15 minutes of hepatic blood inflow occlusion during 65% hepatectomy. Rats were treated with saline (in group 1 and 2) or trimetazidine (in group 3) 30 minutes before operation. Serum level of aspartate transaminase, wet to dry liver weight ratio, and liver injury score in light microscopy were studied for the evaluation of liver injury. Liver regeneration was evaluated by PCNA-labeling index (the percentage of hepatocytes staining for proliferating cell nuclear antigen), mitotic index (the percentage of mitotic hepatocytes), and liver regeneration rate (the percentage of initial liver weight).


RESULTS
Rats in group 2 and 3 had significantly higher serum aspartate transaminase level, wet to dry liver weight ratio and injury score than those in group 1 on day 1 posthepatectomy. Except for serum aspartate transaminase level on day 4, these parameters were significantly higher in group 2 than in group 1 and 3 on day 1 and 4. PCNA-labeling index and mitotic index were significantly less in group 2 and 3 than in group 1 on day 1. In contrast to liver regeneration rate, both indices in group 2 were significantly less than those in group 3 on day 1. There were no differences in regeneration parameters between the groups on day 4. Survival rate was significantly higher in group 3 than in group 2.


CONCLUSIONS
Fifteen minutes of hepatic blood inflow occlusion caused an injury in the remnant liver, impaired liver regeneration, and decreased survival rate after partial hepatectomy. However, pretreatment with trimetazidine reduced liver injury, and improved liver regeneration and survival rate. For situations where hepatic blood inflow occlusion is planned in major liver resection, trimetazidine pretreatment would be useful strategy to improve postoperative outcome.
Kaya
Yavuz
Y
Department of Surgery, Celal Bayar University, Faculty of Medicine, Manisa, Turkey. ydakaya@hotmail.com
Coskun
Teoman
T
Aral
Erinc
E
Erkasap
Nilüfer
N
Var
Ahmet
A
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D006498:Hepatectomy; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D018809:Proliferating Cell Nuclear Antigen; D014665:Vasodilator Agents; D001219:Aspartate Aminotransferases; D014292:Trimetazidine