Blood Cardioplegia Induction, Perfusion Storage and Graft Dysfunction in Cardiac Xenotransplantation.
cardiac preservation
cardiac xenotransplantation
graft dysfunction
heart failure
heart transplant
ventricular assist device (VAD)
xenotransplantation
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
15
02
2021
accepted:
18
05
2021
entrez:
28
6
2021
pubmed:
29
6
2021
medline:
26
10
2021
Statut:
epublish
Résumé
Perioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO Baboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO PCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L. Blood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.
Sections du résumé
Background
Perioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO
Methods
Baboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO
Results
PCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L.
Conclusion
Blood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.
Identifiants
pubmed: 34177906
doi: 10.3389/fimmu.2021.667093
pmc: PMC8220198
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
667093Subventions
Organisme : NIAID NIH HHS
ID : U19 AI090959
Pays : United States
Informations de copyright
Copyright © 2021 Goerlich, Griffith, Singh, Abdullah, Singireddy, Kolesnik, Lewis, Sentz, Tatarov, Hershfeld, Zhang, Strauss, Odonkor, Williams, Tabatabai, Bhutta, Ayares, Kaczorowski and Mohiuddin.
Déclaration de conflit d'intérêts
DA is employed by Revivicor, Inc., a subsidiary of United Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Am J Physiol. 1992 Dec;263(6 Pt 2):H1901-6
pubmed: 1282785
Am J Physiol Heart Circ Physiol. 2018 Dec 1;315(6):H1553-H1568
pubmed: 30168729
Xenotransplantation. 2015 Jul-Aug;22(4):310-6
pubmed: 26174749
Curr Opin Organ Transplant. 2012 Apr;17(2):148-54
pubmed: 22327911
Am J Transplant. 2020 Jan;20 Suppl s1:340-426
pubmed: 31898418
Ann Thorac Surg. 1999 May;67(5):1345-9
pubmed: 10355409
J Extra Corpor Technol. 2012 Sep;44(3):98-103
pubmed: 23198389
Circ Res. 2000 Nov 10;87(10):840-4
pubmed: 11073878
Nat Commun. 2016 Apr 05;7:11138
pubmed: 27045379
Transplant Proc. 1995 Oct;27(5):2863-5
pubmed: 7482947
Am J Transl Res. 2016 Feb 15;8(2):765-77
pubmed: 27158368
Ann Thorac Surg. 2020 May;109(5):1357-1361
pubmed: 31589847
J Extra Corpor Technol. 2016 Jun;48(2):P9-P14
pubmed: 27578906
Xenotransplantation. 2011 Jan-Feb;18(1):14-27
pubmed: 21342284
Int J Surg. 2015 Nov;23(Pt B):234-239
pubmed: 26318967
Heart Fail Rev. 2019 Sep;24(5):805-820
pubmed: 31020451
Nat Commun. 2020 Jun 12;11(1):2976
pubmed: 32532991
Sci Rep. 2020 Jul 1;10(1):10709
pubmed: 32612124
Scand Cardiovasc J. 2016 Jun;50(3):193-200
pubmed: 26882241
Nature. 2018 Dec;564(7736):430-433
pubmed: 30518863
Xenotransplantation. 2019 Mar;26(2):e12465
pubmed: 30290025
Xenotransplantation. 2021 Jan;28(1):e12636
pubmed: 32841431
Am J Pathol. 1990 Mar;136(3):491-5
pubmed: 2316621