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Non-ischemic Heart ...
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Critchley, William R.Manchester University NHS Foundation Trust,University of Manchester
(author)
Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-07-28
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Frontiers Media SA,2020
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LIBRIS-ID:oai:lup.lub.lu.se:1fa52ddd-d954-40c1-b6bf-4c6cd1b84d8b
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https://lup.lub.lu.se/record/1fa52ddd-d954-40c1-b6bf-4c6cd1b84d8bURI
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https://doi.org/10.3389/fimmu.2020.01621DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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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.
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Stone, John P.Manchester University NHS Foundation Trust,University of Manchester
(author)
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Liao, QiumingLund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital(Swepub:lu)thor-qli
(author)
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Qin, GuangqiLund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-ggq
(author)
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Risnes, Ivar
(author)
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Trafford, AndrewUniversity of Manchester
(author)
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Scott, HelgeUniversity of Oslo
(author)
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Sjöberg, TrygveLund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital(Swepub:lu)thor-tsj
(author)
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Steen, StigLund University,Lunds universitet,Hjärt- och lungtransplantation,Forskargrupper vid Lunds universitet,Heart and Lung transplantation,Lund University Research Groups,Skåne University Hospital(Swepub:lu)thor-sst
(author)
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Fildes, James E.Manchester University NHS Foundation Trust,University of Manchester
(author)
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Manchester University NHS Foundation TrustUniversity of Manchester
(creator_code:org_t)
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In:Frontiers in Immunology: Frontiers Media SA111664-3224
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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
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Risnes, Ivar
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Trafford, Andrew
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show more...
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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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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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