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  Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation

Laengin, M., Reichart, B., Steen, S., Sjoeberg, T., Paskevicius, A., Liao, Q., et al. (2020). Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation. Xenotransplantation, e12636. doi:10.1111/xen.12636.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-1715-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-1716-7
Genre: Journal Article

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© 2020 The Authors. Open access funding enabled and organized by Projekt DEAL.

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 Creators:
Laengin, Matthias1, Author
Reichart, Bruno1, Author
Steen, Stig1, Author
Sjoeberg, Trygve1, Author
Paskevicius, Audrius1, Author
Liao, Qiuming1, Author
Qin, Guangqi1, Author
Mokelke, Maren1, Author
Mayr, Tanja1, Author
Radan, Julia1, Author
Issl, Lara1, Author
Buttgereit, Ines1, Author
Ying, Jiawei1, Author
Fresch, Ann Kathrin1, Author
Panelli, Alessandro1, Author
Egerer, Stefanie1, Author
Baehr, Andrea1, Author
Kessler, Barbara1, Author
Milusev, Anastasia1, Author
Sfriso, Riccardo1, Author
Rieben, Robert1, AuthorAyares, David1, AuthorMurray, Peter J.2, Author              Ellgass, Reinhard1, AuthorWalz, Christoph1, AuthorKlymiuk, Nikolai1, AuthorWolf, Eckhard1, AuthorAbicht, Jan-Michael1, AuthorBrenner, Paolo1, Author more..
Affiliations:
1external, ou_persistent22              
2Murray, Peter / Immunoregulation, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466696              

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Free keywords: INTERNATIONAL SOCIETY; LUNG TRANSPLANTATION; ACTIVATION; COAGULATION; MECHANISMS; EXPRESSION; ANTIBODIES; ISCHEMIA; REGISTRYResearch & Experimental Medicine; Transplantation; cardiac transplantation; heart preservation; perioperative cardiac xenograft dysfunction; xenotransplantation;
 Abstract: Background Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project. Methods Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1- KO/hCD46/hTBM) as donors and captive-bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non-ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin-containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti-non-Gal-antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient's kidney, liver and coagulation functions. Results In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti-non-Gal-antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi-organ failure in more than half of the xenotransplantation experiments. In contrast, cold non-ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long-term results after cardiac xenotransplantation.

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Language(s): eng - English
 Dates: 2020-08-25
 Publication Status: Published online
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000562259100001
DOI: 10.1111/xen.12636
 Degree: -

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Project name : -
Grant ID : TRR 127
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Funding organization : Deutsche Forschungsgemeinschaft, DFG

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Title: Xenotransplantation
Source Genre: Journal
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Publ. Info: 111 RIVER ST, HOBOKEN 07030-5774, NJ USA : WILEY
Pages: - Volume / Issue: - Sequence Number: e12636 Start / End Page: - Identifier: ISSN: 0908-665X