Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model

Dmitri Bezinover, Saravanan Ramamoorthy, Marek Postula, Gregory Weller, Saifeldin Mahmoud, Haresh Mani, Zakiyah Kadry, Tadahiro Uemura, Berend Mets, Bruce Spiess, Robert Brucklacher, Willard Freeman, Piotr K. Janicki

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. Materials and methods DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. Results Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. Conclusion Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

Original languageEnglish (US)
Pages (from-to)517-526
Number of pages10
JournalJournal of Surgical Research
Volume188
Issue number2
DOIs
StatePublished - May 15 2014

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Fluorocarbons
Ischemia
Perfusion
Transplants
Liver
Heart Arrest
Adenosine Diphosphate
Adenosine Triphosphate
Gene Expression
Emulsions
Caspase 3
Up-Regulation
Down-Regulation
Fats
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Bezinover, Dmitri ; Ramamoorthy, Saravanan ; Postula, Marek ; Weller, Gregory ; Mahmoud, Saifeldin ; Mani, Haresh ; Kadry, Zakiyah ; Uemura, Tadahiro ; Mets, Berend ; Spiess, Bruce ; Brucklacher, Robert ; Freeman, Willard ; Janicki, Piotr K. / Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model. In: Journal of Surgical Research. 2014 ; Vol. 188, No. 2. pp. 517-526.
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abstract = "Background Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. Materials and methods DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. Results Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. Conclusion Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.",
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Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model. / Bezinover, Dmitri; Ramamoorthy, Saravanan; Postula, Marek; Weller, Gregory; Mahmoud, Saifeldin; Mani, Haresh; Kadry, Zakiyah; Uemura, Tadahiro; Mets, Berend; Spiess, Bruce; Brucklacher, Robert; Freeman, Willard; Janicki, Piotr K.

In: Journal of Surgical Research, Vol. 188, No. 2, 15.05.2014, p. 517-526.

Research output: Contribution to journalArticle

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T1 - Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model

AU - Bezinover, Dmitri

AU - Ramamoorthy, Saravanan

AU - Postula, Marek

AU - Weller, Gregory

AU - Mahmoud, Saifeldin

AU - Mani, Haresh

AU - Kadry, Zakiyah

AU - Uemura, Tadahiro

AU - Mets, Berend

AU - Spiess, Bruce

AU - Brucklacher, Robert

AU - Freeman, Willard

AU - Janicki, Piotr K.

PY - 2014/5/15

Y1 - 2014/5/15

N2 - Background Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. Materials and methods DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. Results Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. Conclusion Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

AB - Background Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. Materials and methods DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. Results Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. Conclusion Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

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