TY - JOUR
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.
N1 - Funding Information:
The authors would like to acknowledge the use of resources of the Genome Sciences Facility at Penn State College of Medicine for completion of the project. The authors are grateful for the assistance of Victor Ruiz-Velasco, PhD, Associate Professor of Anesthesiology, Neural and Behavioral Science, and Pharmacology for help in performing this study. The study was partially supported by a Grant from Sanguine Corporation and Starter Grant from the Department of Anesthesiology at the Penn State Milton S. Hershey Medical Center, Penn State College of Medicine . There was no funding received from any other organizations. Author contributions: D.B.: conceiving and designing the study, collecting the data, analyzing and interpreting the data, writing the manuscript, providing critical revisions that are important for the intellectual content, approving the final version of the manuscript; S.R.: collecting the data, writing the manuscript, approving the final version of the manuscript; M.P.: collecting the data, analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; G.W.: analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; S.M.: collecting the data, writing the manuscript, approving the final version of the manuscript; H.M.: collecting the data, writing the manuscript, approving the final version of the manuscript; Z.K.: analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; T.U.: analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; B.M.: analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; B.S.: analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; R.B.: analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; W.F.: analyzing and interpreting the data, writing the manuscript, approving the final version of the manuscript; and P.K.J.: conceiving and designing the study, analyzing and interpreting the data, writing the manuscript, providing critical revisions that are important for the intellectual content, approving the final version of the manuscript.
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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U2 - 10.1016/j.jss.2014.01.045
DO - 10.1016/j.jss.2014.01.045
M3 - Article
C2 - 24582069
AN - SCOPUS:84898833192
SN - 0022-4804
VL - 188
SP - 517
EP - 526
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -