title: Hepatic ischemia-reperfusion injury modification during liver surgery in rats: pretreatment with nifedipine or misoprostol.
abstract: The aim of the study was to determine if pretreatment with misoprostol (a prostaglandin analogue) or nifedipine (a calcium antagonist), know protectants of the whole liver, would ameliorate the ischemia-reperfusion injury (IRI) of resected liver associated with vascular occlusion. Male Wistar rats were allocated to 5 groups (n = 20 each group): sham-operated, liver resection only, liver resection plus pretreatment with 0.1 mg/kg misoprostol, 10 mg/kg, or 2 mg/kg nifedipine during the 3 days before IRI with liver resection. Fifteen percent of the liver was made ischemic by 30-minute continuous vascular occlusion, and the remaining 85% nonischemic liver was resected. The model was designed to have survival of the rats so that liver function could be studied over 3 weeks. Seventeen of 20 control resection rats survived indicating a suitable model for study. The bilirubin level was reduced by 25% on postoperative days 3 through 23 with misoprostol. The serum alanine aminotransferase (ALT) peak was significantly lower on day 1 with misoprostol and high-dose nifedipine (both reduced to half the control resection value). There was a modest but significant reduction of serum alkaline phosphatase (SAP) for low-dose nifedipine on days 1, 2, and 23. Prothrombin had a lower peak and lower values on days 1 through 4 with misoprostol. Liver histological changes were minor, being cytoplasmic vacuolization only, and was slightly more marked in the nifedipine groups. Preoperative misoprostol 0.1 mg/kg and nifedipine 10 mg/kg each ameliorate the IRI associated with liver resection, as measured by liver function tests. Different aspects of liver function were altered by the different agents. These results justify initiating a trial for human liver resections.
authors.affiliation: Department of Surgery, Austin Hospital, Melbourne, Australia.
authors.forename: K J
authors.initials: KJ
authors.lastname: Hardy
authors.forename: S
authors.initials: S
authors.lastname: Tancheroen
authors.forename: A
authors.initials: A
authors.lastname: Shulkes
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006498:Hepatectomy; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000601:surgery*; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D016595:Misoprostol / Q000627:therapeutic use*; D009543:Nifedipine / Q000627:therapeutic use*; D009929:Organ Size; D010120:Oxytocics / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D002121:Calcium Channel Blockers; D010120:Oxytocics; D016595:Misoprostol; D009543:Nifedipine