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

Background. Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic preconditioning (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery.Methods. An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies.Results. 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection.Conclusions. Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC.

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

10.21203/rs.3.rs-19511/v1 ◽

2020 ◽

Author(s):

Alessandro Rodrigo Belon ◽

Ana Cristina Aoun Tannuri ◽

Daniel Albuquerque Moreira ◽

Alessandra Matheus Silva ◽

Suellen Serafini ◽

...

Keyword(s):

Liver Transplantation ◽

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Histopathological Examination ◽

Ischemia Reperfusion ◽

Weight Ratio ◽

Control Group ◽

Gamma Glutamyl Transferase ◽

Glutamyl Transferase

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 post-reperfusion 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 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.

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

10.21203/rs.3.rs-19511/v3 ◽

2020 ◽

Author(s):

Alessandro Rodrigo Belon ◽

Ana Cristina Aoun Tannuri ◽

Daniel Albuquerque Moreira ◽

Jose Luiz Figueiredo ◽

Alessandra Matheus Silva ◽

...

Keyword(s):

Liver Transplantation ◽

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Histopathological Examination ◽

Ischemia Reperfusion ◽

Weight Ratio ◽

Control Group ◽

Gamma Glutamyl Transferase ◽

Glutamyl Transferase

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 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.

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Impact of combined ischemic preconditioning and remote ischemic perconditioning on ischemia-reperfusion injury after liver transplantation

Scientific Reports ◽

10.1038/s41598-018-36365-5 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 2

Author(s):

Ding-yang Li ◽

Wen-tao Liu ◽

Guang-yi Wang ◽

Xiao-ju Shi

Keyword(s):

Liver Transplantation ◽

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Remote Ischemic Perconditioning

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

10.21203/rs.3.rs-19511/v2 ◽

2020 ◽

Author(s):

Alessandro Rodrigo Belon ◽

Ana Cristina Aoun Tannuri ◽

Daniel Albuquerque Moreira ◽

Alessandra Matheus Silva ◽

Suellen Serafini ◽

...

Keyword(s):

Liver Transplantation ◽

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Histopathological Examination ◽

Ischemia Reperfusion ◽

Weight Ratio ◽

Control Group ◽

Gamma Glutamyl Transferase ◽

Glutamyl Transferase

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 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.

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Effect of remote ischemic preconditioning on hepatic ischemia-reperfusion injury in patients undergoing liver resection: a randomized controlled trial

Minerva Anestesiologica ◽

10.23736/s0375-9393.19.13838-2 ◽

2020 ◽

Vol 86 (3) ◽

Cited By ~ 1

Author(s):

Guilin Wu ◽

Mo Chen ◽

Xiaoqiang Wang ◽

Erliang Kong ◽

Weifeng Yu ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Liver Resection ◽

Reperfusion Injury ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Controlled Trial ◽

Hepatic Ischemia ◽

Randomized Controlled ◽

Hepatic Ischemia Reperfusion

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Ischemic Preconditioning for Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Visceral Medicine ◽

10.1159/000516608 ◽

2021 ◽

pp. 1-8

Author(s):

Lina Jakubauskiene ◽

Matas Jakubauskas ◽

Philipp Stiegler ◽

Bettina Leber ◽

Peter Schemmer ◽

...

Keyword(s):

Liver Transplantation ◽

Mortality Rate ◽

Randomized Controlled Trials ◽

Ischemic Preconditioning ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Meta Analysis ◽

Graft Loss ◽

Controlled Trials ◽

Randomized Controlled

Background: In recent decades, liver transplantation (LTx) has increased the survival and quality of life of patients with end-stage organ failure. Unfortunately, LTx is limited due to the shortage of donors. A lot of effort is put into finding new ways to reduce ischemia-reperfusion injury (IRI) in liver grafts to increase the number of suitable organs procured from expanded-criteria donors (ECD). The aim of this study was to systematically review the literature reporting LTx outcomes when using ischemic preconditioning (IPC) or remote ischemic preconditioning (RIPC) to reduce IRI in liver grafts. Methods: A literature search was performed in the MEDLINE, Web of Science, and EMBASE databases. The following combination was used: “Liver” OR “Liver Transplantation” AND “Ischemic preconditioning” OR “occlusion” OR “clamping” OR “Pringle.” The following outcome data were retrieved: the rates of graft primary nonfunction (PNF), retransplantation, graft loss, and mortality; stay in hospital and the intensive care unit; and postoperative serum liver damage parameters. Results: The initial search retrieved 4,522 potentially relevant studies. After evaluating 17 full-text articles, a total of 9 randomized controlled trials (RCTs) were included (7 IPC and 2 RIPC studies) in the qualitative synthesis; the meta-analysis was only performed on the data from the IPC studies. RIPC studies had considerable methodological differences. The meta-analysis revealed the beneficial effect of IPC when comparing postoperative aspartate aminotransferase (AST) corresponding to a statistically lower mortality rate in the IPC group (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.27–0.98; p = 0.04). Conclusion: IPC lowers postoperative AST levels and reduces the mortality rate; however, data on the benefits of RIPC are lacking.

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