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Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation.

Publication ,  Journal Article
Goldaracena, N; Echeverri, J; Spetzler, VN; Kaths, JM; Barbas, AS; Louis, KS; Adeyi, OA; Grant, DR; Selzner, N; Selzner, M
Published in: Liver Transpl
November 2016

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.

Duke Scholars

Published In

Liver Transpl

DOI

EISSN

1527-6473

Publication Date

November 2016

Volume

22

Issue

11

Start / End Page

1573 / 1583

Location

United States

Related Subject Headings

  • Tissue and Organ Harvesting
  • Temperature
  • Swine
  • Sus scrofa
  • Surgery
  • Sevoflurane
  • Reperfusion Injury
  • Perfusion
  • Organ Preservation
  • Models, Animal
 

Citation

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Goldaracena, N., Echeverri, J., Spetzler, V. N., Kaths, J. M., Barbas, A. S., Louis, K. S., … Selzner, M. (2016). Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation. Liver Transpl, 22(11), 1573–1583. https://doi.org/10.1002/lt.24603
Goldaracena, Nicolas, Juan Echeverri, Vinzent N. Spetzler, Johan M. Kaths, Andrew S. Barbas, Kristine S. Louis, Oyedele A. Adeyi, David R. Grant, Nazia Selzner, and Markus Selzner. “Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation.Liver Transpl 22, no. 11 (November 2016): 1573–83. https://doi.org/10.1002/lt.24603.
Goldaracena N, Echeverri J, Spetzler VN, Kaths JM, Barbas AS, Louis KS, et al. Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation. Liver Transpl. 2016 Nov;22(11):1573–83.
Goldaracena, Nicolas, et al. “Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation.Liver Transpl, vol. 22, no. 11, Nov. 2016, pp. 1573–83. Pubmed, doi:10.1002/lt.24603.
Goldaracena N, Echeverri J, Spetzler VN, Kaths JM, Barbas AS, Louis KS, Adeyi OA, Grant DR, Selzner N, Selzner M. Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation. Liver Transpl. 2016 Nov;22(11):1573–1583.
Journal cover image

Published In

Liver Transpl

DOI

EISSN

1527-6473

Publication Date

November 2016

Volume

22

Issue

11

Start / End Page

1573 / 1583

Location

United States

Related Subject Headings

  • Tissue and Organ Harvesting
  • Temperature
  • Swine
  • Sus scrofa
  • Surgery
  • Sevoflurane
  • Reperfusion Injury
  • Perfusion
  • Organ Preservation
  • Models, Animal