Ischemic Postconditioning (IPostC) Protects Fibrotic and Cirrhotic Rat Livers after Warm Ischemia.

Julia Schewe,Doris Mayr,Max Schnurr,Simon Rothenfußer,Marie-Christine Makeschin,Jiang Zhang,Alexander L Gerbes,Ingrid Liss,Christian J Steib,Andrej Khandoga

doi:10.1155/2019/5683479

Abstract

Background Decreased organ function following liver resection is a major clinical issue. The practical method of ischemic postconditioning (IPostC) has been studied in heart diseases, but no data exist regarding fibrotic livers. Aims We aimed to determine whether IPostC could protect healthy, fibrotic, and cirrhotic livers from ischemia reperfusion injury (IRI). Methods Fibrosis was induced in male SD rats using bile duct ligation (BDL, 4 weeks), and cirrhosis was induced using thioacetamide (TAA, 18 weeks). Fibrosis and cirrhosis were histologically confirmed using HE and EvG staining. For healthy, fibrotic, and cirrhotic livers, isolated liver perfusion with 90 min of warm ischemia was performed in three groups (each with n=8): control, IPostC 8x20 sec, and IPostC 4x60 sec. additionally, healthy livers were investigated during a follow-up study. Lactate dehydrogenase (LDH) and thromboxane B2 (TXB2) in the perfusate, as well as bile flow (healthy/TAA) and portal perfusion pressure, were measured. Results LDH and TXB2 were reduced, and bile flow was increased by IPostC, mainly in total and in the late phase of reperfusion. The follow-up study showed that the perfusate derived from a postconditioned group had much less damaging potential than perfusate derived from the nonpostconditioned group. Conclusion IPostC following warm ischemia protects healthy, fibrotic, and cirrhotic livers against IRI. Reduced efflux of TXB2 is one possible mechanism for this effect of IPostC and increases sinusoidal microcirculation. These findings may help to improve organ function and recovery of patients after liver resection.

Highlights

Different pathological processes in liver tissue such as abscesses, cysts, or benign and malignant tumours necessitate partial resection of the liver
In Bile duct ligation EvG (BDL) livers, there was low to moderate fibrosis with septa in the area of bile duct proliferation and low to moderate inflammation with single cell necrosis, apoptosis, and mitoses
The aim of this study was to determine whether ischemic postconditioning (IPostC) could protect healthy, fibrotic, and cirrhotic livers from ischemia reperfusion injury (IRI) after 90 min of warm ischemia

Summary

Introduction

Different pathological processes in liver tissue such as abscesses, cysts, or benign and malignant tumours necessitate partial resection of the liver. Different methods have been investigated to reduce IRI after warm ischemia. A surgical method to protect the liver against IRI ischemic preconditioning (IPC) has been investigated. We aimed to determine whether IPostC could protect healthy, fibrotic, and cirrhotic livers from ischemia reperfusion injury (IRI). LDH and TXB2 were reduced, and bile flow was increased by IPostC, mainly in total and in the late phase of reperfusion. IPostC following warm ischemia protects healthy, fibrotic, and cirrhotic livers against IRI. Reduced efflux of TXB2 is one possible mechanism for this effect of IPostC and increases sinusoidal microcirculation. These findings may help to improve organ function and recovery of patients after liver resection

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