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Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation
- Source :
- Liver Transplantation. 22:1573-1583
- Publication Year :
- 2016
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2016.
-
Abstract
- Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti-inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied. This was compared with a perfused control group (group 2) where livers (n = 5) were perfused at 37°C without anti-inflammatory agents, similar to the setup used in current European clinical trials, and to a control group preserved with static cold storage (group 3). During 3-day follow-up, markers of reperfusion injury, bile duct injury, and liver function were examined. Aspartate aminotransferase (AST) levels during perfusion were significantly lower in the study versus control group at 1 hour (52 ± 6 versus 162 ± 86 U/L; P = 0.01), 2 hours (43 ± 5 versus 191 ± 111 U/L; P = 0.008), and 3 hours (24 ± 16 versus 218 ± 121 U/L; P = 0.009). During perfusion, group 1 versus group 2 had reduced interleukin (IL) 6, tumor necrosis factor α, and galactosidase levels and increased IL10 levels. After transplantation, group 1 had lower AST peak levels compared with group 2 and group 3 (1400 ± 653 versus 2097 ± 1071 versus 1747 ± 842 U/L; P = 0.47) without reaching significance. Bilirubin levels were significantly lower in group 1 versus group 2 at day 1 (3.6 ± 1.5 versus 6.60 ± 1.5 μmol/L; P = 0.02) and 3 (2 ± 1.1 versus 9.7 ± 7.6 μmol/L; P = 0.01). A trend toward decreased hyaluronic acid, as a marker of improved endothelial cell function, was observed at 1, 3, and 5 hours after reperfusion in group 1 versus group 2. Only 1 early death occurred in each group (80% survival). In conclusion, addition of anti-inflammatory strategies further improves warm perfused preservation. Liver Transplantation 22 1573-1583 2016 AASLD.
- Subjects :
- Male
Methyl Ethers
medicine.medical_specialty
Swine
medicine.medical_treatment
Sus scrofa
Anti-Inflammatory Agents
Urology
Cold storage
030230 surgery
Liver transplantation
Sevoflurane
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Aspartate Aminotransferases
Alprostadil
Hyaluronic Acid
Biliary Tract
Transplantation
Hepatology
business.industry
Cold Ischemia
Temperature
Endothelial Cells
Bilirubin
Organ Preservation
Allografts
medicine.disease
Acetylcysteine
Liver Transplantation
Perfusion
Liver
Reperfusion Injury
Models, Animal
Tissue and Organ Harvesting
Cytokines
030211 gastroenterology & hepatology
Surgery
Liver function
Inflammation Mediators
business
Reperfusion injury
Ex vivo
medicine.drug
Subjects
Details
- ISSN :
- 15276473 and 15276465
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Liver Transplantation
- Accession number :
- edsair.doi.dedup.....586043b127eb86b91f1e3a41e89efd18