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 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 postreperfusion and the following biochemical tests were performed: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN, 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 apoptosisrelated 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. BackgroundPrimary graft dysfunction due to ischemia-reperfusion (I/R) injury is one of the most serious complications of liver transplantation. 1,2 Ischemic preconditioning (IPC) is an important approach to reduce the harmful effects of this process. It consists of producing brief periods of ischemia followed by brief periods of reperfusion prior to the prolonged ischemic insult, which should induce greater

Effects of local and remote ischemic postconditioning methods on ischemiareperfusion injury in a young animal model of acute mesenteric ischemia

“…Also, we observed that the differences among the groups are more notable at the gene expression level, secondarily at the histological level, and less evident at the histomorphometric level. This might occur because gene expression changes are more precocious and precede morphological changes at the tissue level, as we found in a previous investigation from our group 16 .…”

“…As an initial consideration, it may emphasize that the different modalities of IPC are impractical procedures that may further increase the already high complexity of transplantation surgery. This conclusion was based on a sequence of experimental investigations performed in a pig model of liver transplantation in which it was demonstrated that direct, remote ischemic preconditioning or a combination of both, produce beneficial effects only at the molecular level, without any biochemical or histological advantages 15,16 . These studies led to the conclusion that the benefits' procedures are not consistent and may not be applied to liver transplantation in humans.…”

Protective role of remote ischemic conditioning in renal transplantation and partial nephrectomy: A systematic review and meta-analysis of randomized controlled trials

“…For example, RIC may promote the production of some active substances (opioids, adenosine, bradykinin and stromal cell-derived factor-1, etc.) and accelerate their entry into the blood, thus activating neural networks and acting on the target organs of the human body ( 38 , 39 ). In addition, RIC may also activate antiapoptotic ( 40 ), antioedema ( 41 ), and anti-inflammatory signalling pathways ( 42 ), improve microvascular endothelial function ( 43 ), and affect the transcription of related genes and mitochondrial respiratory function ( 44 , 45 ), thereby reducing the impact of I/R injury.…”

NGAL in the Development of Acute Kidney Injury in a Murine Model of Remote Ischaemic Preconditioning and Liver Ischaemia Reperfusion

“…The underlying mechanisms of protection remain poorly understood but involve neural, humoral and systemic pathways and include a downregulation of oxidative stress and upregulation of protective pathways within the transplant organ [19]. Whilst experimental animal models have provided promising results, there has been limited translation into clinical practice [20][21][22][23][24].…”