Heparin accelerates liver regeneration following portal branch ligation in normal and cirrhotic rats with increased plasma hepatocyte growth factor levels.
OBJECTIVE
Heparin is widely used as a general anticoagulant, and has been recently reported to elevate plasma hepatocyte growth factor (HGF) levels by releasing HGF sequestrated in the extracellular matrix. Therefore, we investigated the effects of heparin administration on liver regeneration following portal branch ligation (PBL) in normal and cirrhotic rats.


METHODS
Dimethylnitrosamine-induced cirrhotic rats and control rats underwent portal ligation of the left lateral and median branches, followed by intraperitoneal heparin injections, every 12 h. To examine the feasibility of an extensive hepatectomy in the cirrhotic livers, cirrhotic rats with or without heparin treatment underwent resection of occluded lobes at 72 h after the PBL.


RESULTS
Heparin injections significantly augmented liver regeneration after PBL in both normal and cirrhotic rats, following an increase in hepatocellular DNA synthesis at 24 h after the PBL. The plasma HGF concentrations were elevated by heparin treatment in both groups. In addition, heparin administration dramatically improved the survival rate after an extensive hepatectomy in the cirrhotic rats.


CONCLUSIONS
Heparin treatment significantly accelerated liver regeneration following the PBL, with an increase in the plasma HGF levels in both normal and cirrhotic rats. Heparin administration may make an extensive hepatectomy clinically feasible even for cirrhotic livers.
Nakao
Teizo
T
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Arii
Shigeki
S
Kaido
Toshimi
T
Mori
Akira
A
Murata
Toru
T
Matsumori
Akira
A
Imamura
Masayuki
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000097:blood*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D011168:Portal System; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D017228:Hepatocyte Growth Factor; D006493:Heparin