Effect of preoperative interventions on outcome following liver resection in a rat model of cirrhosis.
OBJECTIVE
High morbidity and mortality rates in cirrhotic patients undergoing resections for hepatocellular malignancies underscore the need for identifying a therapy that will decrease fibrosis or enhance hepatic regenerative activity in the perioperative period. Thus, in the present study, 104 carbon tetrachloride-induced cirrhotic rats received either saline (untreated cirrhotic controls) or one of the following agents that have been reported to decrease hepatic fibrosis or increase hepatic regeneration; pentoxifylline, ciprofloxacin or a traditional Chinese herbal remedy (TCHR). Twelve additional rats served as healthy, non-cirrhotic controls.


METHODS
Treatments were administered daily by gavage for 4 weeks followed by a 70% partial hepatectomy. Hepatic fibrosis was documented at the time of surgery by computer-assisted quantitation of collagen content. Liver function and hepatic regenerative activity were documented 24 h post partial hepatectomy by serum bilirubin determinations and a combination of 3[H]-Thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) quantitation, respectively.


RESULTS
Compared to untreated cirrhotic controls (8.1 +/- 0.7%), fibrosis was significantly reduced in the pentoxifylline- and ciprofloxacin-treated groups (4.6 +/- 0.2%, p<0.005 and 5.5 +/- 0.6%, p<0.05) but unchanged in the TCHR-treated group (6.6 +/- 11.0%). Post-operatively, total serum bilirubin levels were lower in the pentoxifylline (1.40 +/- 0.15 mg/dl,p<0.01) and ciprofloxacin (1.87 +/- 0.25 mg/dl, p<0.05)-treated groups, but unchanged in the TCHR group (2.20 +/- 0.45 mg/dl), when compared to untreated cirrhotic controls (3.00 +/- 0.37 mg/dl). Hepatic regenerative activity was also significantly improved in the pentoxifylline-treated group (17.8 +/- 2.2 versus 9.9 +/- 1.9 DPM/microg DNA in untreated cirrhotic controls, p<0.05), but unchanged in the ciprofloxacin (16.1 +/- 1.8 DPM/microg DNA) and TCHR (10.9 +/- 1.2 DPM/microg DNA)-treated groups. PCNA protein determinations were in keeping with the 3[H]-Thymidine results


CONCLUSIONS
Pre-operative pentoxifylline holds promise as a useful therapeutic intervention for patients with cirrhosis requiring hepatic resection.
Moser
M
M
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Zhang
M
M
Gong
Y
Y
Johnson
J
J
Kneteman
N
N
Minuk
G Y
GY
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002939:Ciprofloxacin / Q000627:therapeutic use*; D003936:Diagnosis, Computer-Assisted; D005355:Fibrosis; D008099:Liver / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008106:Liver Cirrhosis, Experimental / Q000473:pathology / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D008115:Liver Regeneration; D008297:Male; D008516:Medicine, Chinese Traditional; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011300:Preoperative Care; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D013936:Thymidine / Q000378:metabolism
D000890:Anti-Infective Agents; D010726:Phosphodiesterase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D002939:Ciprofloxacin; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D010431:Pentoxifylline; D013936:Thymidine