Impact of three methods of ischemic preconditioning on ischemia-reperfusion injury in a pig model of liver transplantation

Autor: Daniel de Albuquerque Rangel Moreira, Caroline Silvério Faria, Josiane de Oliveira Gonçalves, Alessandra Matheus da Silva, Alcione Sanches de Alexandre, Ana Cristina Aoun Tannuri, Raimundo Renato Nunes Guimarães, Suellen Serafini, Jose Luiz Figueiredo, Uenis Tannuri, Vitor Ribeiro Paes, Alessandro Rodrigo Belon
Rok vydání: 2020
Předmět:
DOI: 10.21203/rs.3.rs-19511/v3
Popis: Background. Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion injury. Aims. To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model. Methods. Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups according to the procedures applied: direct donor preconditioning; indirect preconditioning at the recipient and a group with direct donor and indirect recipient preconditioning. The following parameters were recorded: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, hot and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0h, 1h, 3h, 6h, 12h, 18h, and 24h post-reperfusion and the following biochemical tests were performed: 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 pro-apoptotic BAX gene and the expression of the anti-apoptotic Bcl gene in the livers of animals with IPC versus the control group. Conclusions. DIPC, RIPC or a combination of both produce local beneficial effects only at the molecular level but do not translate into biochemical or histological changes.
Databáze: OpenAIRE