Impact of Three Methods of Ischemic Preconditioning on Ischemia-Reperfusion Injury in a Pig Model of Liver Transplantation

Abstract

Background

Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion (I/R) injury.

Objectives

To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model.

Materials and methods

Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups: control, direct donor preconditioning, indirect preconditioning at the recipient, and direct donor with indirect recipient preconditioning. The recorded parameters were: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, warm and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0 h, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h post-reperfusion for the biochemical tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN (blood urea nitrogen), lactate, total and direct bilirubin. Histopathological examination of liver, gut, kidney, and lung fragments were performed, as well as molecular analyses for expression of the apoptosis-related BAX (pro-apoptotic) and Bcl-XL (anti-apoptotic) genes, eNOS (endothelial nitric oxide synthase) gene, and IL-6 gene related to inflammatory ischemia-reperfusion injury, using real-time polymerase chain reaction (RT-PCR).

Results

There were no differences between the groups regarding biochemical and histopathological parameters. We found a reduced ratio between the expression of the BAX gene and Bcl-XL in the livers of animals with IPC versus the control group.

Conclusions

DIPC, RIPC or a combination of both, produce beneficial effects at the molecular level without biochemical or histological changes.

Keywords:

• Experimental surgery
• hepatobiliary surgery
• ischemia-reperfusion
• preconditioning
• surgical technique
• pediatric surgery

This article is referred to by:

Ischemic Preconditioning in Liver Transplantation: Lost in Translation?

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The laboratory studies of the current investigation were supported by Fundação de Amparo a Pesquisa do Estado de São Paulo - (Research number 2014/25676-0).