Neural elements behind the hepatoprotection of remote perconditioning.

Abstract

BACKGROUND: The ability of remote ischemic perconditioning (RIPER) to protect the liver from ischemic-reperfusion (IR) injury has been reported before; however, the mechanism behind the positive effects of RIPER remains unrevealed. Therefore, we aimed to investigate the potential role of neural elements to transfer protective signals evoked by perconditioning. MATERIALS AND METHODS: Male Wistar rats were randomly allocated into six groups (sham, IR, RIPER +/- denervation; n = 7 per group). Half of the animals underwent left femoral and sciatic nerve resection. In IR and RIPER groups, normothermic, partial (70%) liver ischemia lasting for 60 min was induced; parallel animals in the RIPER groups received perconditioning treatment (4x5-5 min IR, left femoral artery clamping). Hepatic microcirculation and systemic blood pressure were monitored during the first postischemic hour. After 24 h of reperfusion, liver samples were taken for histology and redox-state analysis. Automated image analysis software was used for necrosis quantification. Serum alanine aminotransferase, aspartate aminotransferase, and bilirubin levels were measured. RESULTS: Microcirculation and blood pressure showed significant improvement during reperfusion after perconditioning. This phenomenon was completely abolished by nerve resection (P < 0.05; RIPER versus IR, IR + denervation, and RIPER + denervation). Results of necrosis quantification showed similar pattern. Besides noncharacteristic changes in aspartate aminotransferase levels, alanine aminotransferase values were significantly lower (P < 0.05) in the RIPER group compared with the other IR groups. Mild but significant alterations were observed in liver function assessed by total bilirubin levels. Further supporting results were obtained from analysis of redox homeostasis. CONCLUSIONS: Perconditioning was able to reduce liver IR injury in our model via a mechanism most probably involving interorgan neural pathways.