EFFECTS OF ANAESTHETIC PRECONDITIONING WITH SEVOFLURANE IN WARM LIVER ISCHEMIA/REPERFUSION INJURY IN RATS

Abstract

Background: Preconditioning is a therapeutic strategy aimed to increase ischemic tissue tolerance against ischemia/reperfusion (IR) injury. Recentstudies demonstrated that volatile anaesthetics may improve postischemic recovery by an ischemic preconditioning-like mechanism. We hypothesized that pharmacological preconditioning with sevoflurane may reduce the hepatocellular damage in a rat model of warm liver IR. Methods: Ten Wistar rats under mechanical ventilation were divided into 2 groups of 5 animals: I) IR: rats subjected to 45 min of warm liver ischemia of the left and median lobes, followed by resection of the non-ischemic lobes at early reperfusion; and II) SEVO+IR: rats were exposed to sevoflurane 2.5% for 15 min, followed by washout during 5 min, before IR. The carotid artery was cannulated for mean arterial pressure (MAP) monitoring. The mean portal venous flow (MPF) was assessed by perivascular flowprobe. MAP and MPF were recorded at baseline, pre reperfusion and 4 hours post-reperfusion. Liver transaminases, creatinine, pH, bicarbonate (BIC) and base excess (BE), potassium (K), glucose and lactate were measured at 4 hours post-reperfusion. Results: AST and ALT were decreased in SEVO+IR group (10.056 ± 5.830 and 8.586 ± 5.296 U/L) compared to IR group (16.890 ± 1.630 and 13.418 ± 1.088 U/L), P < 0.05. BIC, BE and K were increased in SEVO+IR group (12.42 ± 4.39, -14.72 ± 4.46 mmol/l and 6.3 ± 0.9 mEq/dl) compared to IR (6.70 ± 3.32, -20.48 ± 4.22 mmol/l and 4.7 ± 0.7 mEq/dl), P< 0.05. MAP at 4 hours post-reperfusion was decreased in SEVO+IR group (65 ± 24 mmHg) compared to IR (93 ± 14 mmHg), P < 0.05. There were no differences in MPF, creatinine, glucose and lactate. Glucose tended to be higher and lactate lower in SEVO+IR group (54.0 ± 22.7 and 42.8 ± 18.6 mg/dl) compared to IR (35.0 ± 18.4 and 66.8 ± 25.9 mg/dl). Conclusions: In liver IR, sevoflurane preconditioning reduced hepatocellular injury demonstrated by lower levels of transaminases. Despite the lower mean arterial pressure presented in sevoflurane treated animals, no detrimental effect was observed in portal venous flow, hepatic metabolism and renal function. This study highlight the need for clarifying the mechanisms of sevoflurane preconditioning, and if there is additional hepatoprotection against cold IR injury.