Hepatic ischemia-reperfusion injury modification during liver surgery in rats: pretreatment with nifedipine or misoprostol.
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.
Hardy
K J
KJ
Department of Surgery, Austin Hospital, Melbourne, Australia.
Tancheroen
S
S
Shulkes
A
A
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*
D002121:Calcium Channel Blockers; D010120:Oxytocics; D016595:Misoprostol; D009543:Nifedipine