Preconditioning by sevoflurane metabolite hexafluoro-2-propanol decreases liver ischemia reperfusion injury: preliminary results

Abstract

Liver ischemia-reperfusion (IR) injury is still a significant cause of complications after liver resection and transplantation. Sevoflurane has been demonstrated to decrease IR injury. Objective: To investigate if preconditioning with the sevoflurane metabolite hexafluoro-2-propanol (HFIP) decreases liver normothermic IR injury. Methods: Rats anaesthetised with ketamine+xylazine were submitted to 30min of partial warm liver ischemia alone (Control group; n=8), or preconditioned with HFIP 67mg/kg through intravenous infusion, 10 min prior to ischemia (HFIP group; n=8). Immediately after reperfusion non-ischemic right and caudate lobes were resected, allowing evaluation global IR liver injury. Blood samples were acquired at 4h after reperfusion. Results: HFIP group showed significantly decreased levels of AST (2,336±809UI/L) and ALT (2,251±768UI/L) compared to Control group (4,859±3,053UI/L and 4,484±2,678UI/L, respectively). Ionized calcium and potassium levels were significantly increased in HFIP (5.256±0.7mg/dL and 6.813±0.645mEq/L, respectively) compared to Control group (4.773±0.256 and 6.086±0.422, respectively). Base excess, bicarbonate, lactate, chloride and glucose levels in HFIP group were not significantly different from Control. Conclusions: In experimental warm liver IR injury, sevoflurane metabolite HFIP maybe related to the non-anaesthetic effects of sevoflurane in promoting liver protection. This is suggested by the marked decrease in liver transaminases in the model of IR liver injury. Ionic imbalance of serum potassium and calcium maybe related to increased intracellular release with possible changes in cellular membrane potential. It is possible that HFIP co-administration with sevoflurane anaesthesia can increase liver protection effects in clinical situations such us liver transplantation. Care must be taken to the patient potassium levels monitoring.