Overcoming perioperative inflammation as a hurdle for successful preclinical orthotopic cardiac xenogeneic transplantations - particular in regard of the mandatory use of heart-lung machines.
heart-lung machine
orthotopic heart transplantation
perioperative inflammation
xenotransplantation
Journal
Xenotransplantation
ISSN: 1399-3089
Titre abrégé: Xenotransplantation
Pays: Denmark
ID NLM: 9438793
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
19
12
2021
received:
27
10
2021
accepted:
28
04
2022
pubmed:
27
5
2022
medline:
24
6
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
After orthotopic cardiac xenotransplantation, the combination of both the inflammatory responses to the exposure of a recipient to the xenogeneic organ and the use of cardiopulmonary bypass has been assumed to cause detrimental side effects. These have been described not only to affect the transplanted organ (heart) itself, but also the recipient's lungs. In this article, we summarize how these possible detrimental processes can be minimized or even avoided. Data from eight pig-to-baboon orthotopic cardiac xenotransplantation experiments were analyzed with a special focus on early (within the first week) postoperative organ dysfunction and systemic inflammatory responses. Non-ischemic heart preservation and the careful management of the heart-lung machine were deemed essential to guarantee not only the immediate function of the transplanted xenogeneic organ but also the prompt recovery of the recipient. After weaning from cardiopulmonary bypass, very low catecholamine amounts were needed to ensure an adequate pump function and cardiac output. Central venous oxygen saturation and serum lactate levels remained within normal ranges. All animals were successfully weaned from ventilation within the first postoperative hours. Serum parameters of the transplants and native kidneys and livers were initially slightly elevated or always normal, as were hemoglobin, LDH, and platelet measurements. Markers of systemic inflammation, C-reactive protein, and IL-6 were slightly elevated, but the reactions caused no lasting damage. Consistent short-term and long-term results were achieved after orthotopic cardiac pig-to-baboon transplantation without detrimental inflammatory responses or signs of multiorgan failure. In comparison to allogeneic procedures, non-ischemic heart preservation was important for successful immediate organ function, as was the management of the heart-lung machine. Thus, we believe that genetically modified porcine hearts are ready for use in the clinical setting.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12749Informations de copyright
© 2022 The Authors. Xenotransplantation published by John Wiley & Sons Ltd.
Références
Thompson CP, Jagdale A, Walcott G, et al. A perspective on the potential detrimental role of inflammation in pig orthotopic heart xenotransplantation. Xenotransplantation. 2021;28(4):e12687.
Gibbon JH Jr. The maintenance of life during experimental occlusion of the pulmonary artery followed by survival. Surg Gynec Obst. 1939;69:602-614.
Gibbon JH Jr. Application of a mechanical heart and lung apparatus to cardiac surgery. Minn Med. 1954;37(3):171-185.
Kirklin JW, Dushane JW, Patrick RT, et al. Intracardiac surgery with the aid of a mechanical pump-oxygenator system (gibbon type): report of eight cases. Proc Staff Meet Mayo Clin. 1955;30(10):201-206.
Dewall RA, Gott VL, Lillehei CW, et al. A simple, expendable, artificial oxygenator for open heart surgery. Surg Clin North Am. 1956:1025-1034.
Lillehei CW, Dewall RA, Read RC, Warden HE, Varco RL. Direct vision intracardiac surgery in man using a simple, disposable artificial oxygenator. Dis Chest. 1956;29(1):1-8.
Iwahashi H, Yuri K, Nosé Y. Development of the oxygenator: past, present, and future. J Artif Organs. 2004;7(3):111-120.
Kirklin JW, Barrat-Boyes G. Cardiac Surgery. 1st ed. Whiley and Sons; 1986: 44-74.
Kirklin JW, Barrat-Boyes G. Cardiac Surgery. 2 ed. Churchill Livingstone; 1993: 73-128.
Kouchoukos NT, Kirklin JW, Barrat-Boyes G. Kirklin/Barrat-Boyes - Cardiac Surgery. 4 ed. Churchill Livingstone; 2003: 79-130.
Mavroudis C, Backer CL. Pediatr Cardiay Surg. 2003: 171-222.
Novitzky D, Cooper DK, Human PA, Reichart B, Zuhdi N. Triiodothyronine therapy for heart donor and recipient. J Heart Transplant. 1988;7(5):370-376.
Mohiuddin MM, Reichart B, Byrne GW, McGregor CGA. Current status of pig heart xenotransplantation. Int J Surg. 2015;23(Pt B):234-239.
Längin M, Mayr T, Reichart B, et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature. 2018;564(7736):430-433.
Reichart B, Längin M, Radan J, et al. Pig-to-non-human primate heart transplantation: the final step toward clinical xenotransplantation?. J Heart Lung Transplant. 2020;39(8):751-757.
Längin M, Reichart B, Steen S, et al. Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation. Xenotransplantation. 2021;28(1):e12636.
Steen S, Paskevicius A, Liao Q, Sjöberg T. Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours. Scand Cardiovasc J. 2016;50(3):193-200.
Lower RR, Shumway NE. Studies on orthotopic homotransplantation of the canine heart. Surg Forum. 1960;11:18-19.
Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008;112(10):3959-3964.
Iwase H, Yamamoto T, Cooper DKC. Episodes of hypovolemia/dehydration in baboons with pig kidney transplants: a new syndrome of clinical importance?. Xenotransplantation. 2019;26(2):e12472.