Protection by cyclosporine a against normothermic liver ischemia- reperfusion in pigs

Denise L. Travis, Renata Fabia, George G. Netto, Bo S. Husberg, Robert M. Goldstein, Goran B. Klintmalm, Marlon F. Levy

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Cyclosporine A (CYA) is primarily utilized as an immunosuppressant, but its mechanisms of action (including decreased neutrophilic free radical production and stabilization of mitochondrial and lysosomal membranes) may have beneficial effects in ischemia and reperfusion (IR) injury. This study was undertaken to examine the effect of CYA pretreatment on porcine liver histopathologic changes and enzymatic release caused by ischemia and reperfusion. Materials and methods. CYA was administered orally for 4 days prior to surgery in two doses (10 or 20 mg/kg) while controls received only the control vehicle. Pigs were then exposed to 4 h of hepatic ischemia followed by 2 h of reperfusion. Results. Significant decreases in AST levels compared to controls were seen in high dose CYA pigs at the end of ischemia and at 30-min intervals during the reperfusion period. Controls exhibited necrotic hepatocytes and severe inflammatory cell infiltration, while high dose CYA animals demonstrated mild inflammatory cell infiltrates. Controls had decreased survival-20% did not survive reperfusion. Conclusions. This study indicates that CYA may be useful in decreasing initial damage resulting from warm hepatic IR injury.

Original languageEnglish (US)
Pages (from-to)116-126
Number of pages11
JournalJournal of Surgical Research
Volume75
Issue number2
DOIs
StatePublished - Mar 1998

Keywords

  • Cyclosporine A
  • Ischemia/reperfusion injury
  • Liver perfusion

ASJC Scopus subject areas

  • Surgery

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