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Non-ischemic Heart ...
Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation
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- Critchley, William R. (author)
- Manchester University NHS Foundation Trust,University of Manchester
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- Stone, John P. (author)
- Manchester University NHS Foundation Trust,University of Manchester
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- Liao, Qiuming (author)
- Lund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital
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- Qin, Guangqi (author)
- Lund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital
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Risnes, Ivar (author)
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- Trafford, Andrew (author)
- University of Manchester
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- Scott, Helge (author)
- University of Oslo
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- Sjöberg, Trygve (author)
- Lund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital
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- Steen, Stig (author)
- Lund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital
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- Fildes, James E. (author)
- Manchester University NHS Foundation Trust,University of Manchester
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(creator_code:org_t)
- 2020-07-28
- 2020
- English.
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Abstract
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- Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation. Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint. Results: Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci. Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- acute rejection
- heart preservation
- heart transplantation
- hypothermic cardioplegic ex vivo heart perfusion
- passenger leukocytes
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Critchley, Willi ...
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Stone, John P.
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Liao, Qiuming
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Qin, Guangqi
-
Risnes, Ivar
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Trafford, Andrew
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show more...
-
Scott, Helge
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Sjöberg, Trygve
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Steen, Stig
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Fildes, James E.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Frontiers in Imm ...
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Lund University