TY - JOUR
T1 - Early Experience With Preclinical Perioperative Cardiac Xenograft Dysfunction in a Single Program
AU - DiChiacchio, Laura
AU - Singh, Avneesh
AU - Lewis, Billeta
AU - Zhang, Tianshu
AU - Hardy, Naomi
AU - Pasrija, Chetan
AU - Morales, David
AU - Odonkor, Patrick
AU - Strauss, Erik
AU - Williams, Brittney
AU - Deatrick, Kristopher B.
AU - Kaczorowski, David J.
AU - Ayares, David
AU - Griffith, Bartley P.
AU - Bartlett, Stephen T.
AU - Mohiuddin, Muhammad M.
N1 - Funding Information:
This study was supported by funding from United Therapeutics, Inc, and a grant from National Institute of Allergy and Infectious Disease and National Institutes of Health (5U19090959-10).
Funding Information:
This study was supported by funding from United Therapeutics , Inc, and a grant from National Institute of Allergy and Infectious Disease and National Institutes of Health ( 5U19090959-10 ).
Publisher Copyright:
© 2020 The Society of Thoracic Surgeons
PY - 2020/5
Y1 - 2020/5
N2 - Background: Perioperative cardiac xenograft dysfunction (PCXD) was described by McGregor and colleagues as a major barrier to the translation of heterotopic cardiac xenotransplantation into the orthotopic position. It is characterized by graft dysfunction in the absence of rejection within 24 to 48 hours of transplantation. We describe our experience with PCXD at a single program. Methods: Orthotopic transplantation of genetically engineered pig hearts was performed in 6 healthy baboons. The immunosuppression regimen included induction by anti-CD20 monoclonal antibodies (mAb), thymoglobulin, cobra venom factor, and anti-CD40 mAb, and maintenance with anti-CD40 mAb, mycophenolate mofetil, and tapering doses of steroids. Telemetry was used to assess graft function. Extracorporeal membrane oxygenation was used to support 1 recipient. A full human clinical transplantation team was involved in these experiments and the procedure was performed by skilled transplantation surgeons. Results: A maximal survival of 40 hours was achieved in these experiments. The surgical procedures were uneventful, and all hearts were weaned from cardiopulmonary bypass without issue. Support with inotropes and vasopressors was generally required after separation from cardiopulmonary bypass. The cardiac xenografts performed well immediately, but within the first several hours they required increasing support and ultimately resulted in arrest despite maximal interventions. All hearts were explanted immediately; histology showed no signs of rejection. Conclusions: Despite excellent surgical technique, uneventful weaning from cardiopulmonary bypass, and adequate initial function, orthotopic cardiac xenografts slowly fail within 24 to 48 hours without evidence of rejection. Modification of preservation techniques and minimizing donor organ ischemic time may be able to ameliorate PCXD.
AB - Background: Perioperative cardiac xenograft dysfunction (PCXD) was described by McGregor and colleagues as a major barrier to the translation of heterotopic cardiac xenotransplantation into the orthotopic position. It is characterized by graft dysfunction in the absence of rejection within 24 to 48 hours of transplantation. We describe our experience with PCXD at a single program. Methods: Orthotopic transplantation of genetically engineered pig hearts was performed in 6 healthy baboons. The immunosuppression regimen included induction by anti-CD20 monoclonal antibodies (mAb), thymoglobulin, cobra venom factor, and anti-CD40 mAb, and maintenance with anti-CD40 mAb, mycophenolate mofetil, and tapering doses of steroids. Telemetry was used to assess graft function. Extracorporeal membrane oxygenation was used to support 1 recipient. A full human clinical transplantation team was involved in these experiments and the procedure was performed by skilled transplantation surgeons. Results: A maximal survival of 40 hours was achieved in these experiments. The surgical procedures were uneventful, and all hearts were weaned from cardiopulmonary bypass without issue. Support with inotropes and vasopressors was generally required after separation from cardiopulmonary bypass. The cardiac xenografts performed well immediately, but within the first several hours they required increasing support and ultimately resulted in arrest despite maximal interventions. All hearts were explanted immediately; histology showed no signs of rejection. Conclusions: Despite excellent surgical technique, uneventful weaning from cardiopulmonary bypass, and adequate initial function, orthotopic cardiac xenografts slowly fail within 24 to 48 hours without evidence of rejection. Modification of preservation techniques and minimizing donor organ ischemic time may be able to ameliorate PCXD.
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U2 - 10.1016/j.athoracsur.2019.08.090
DO - 10.1016/j.athoracsur.2019.08.090
M3 - Article
C2 - 31589847
AN - SCOPUS:85079790482
SN - 0003-4975
VL - 109
SP - 1357
EP - 1361
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 5
ER -