456: Preclinical Orthotopic Cardiac Xenotransplantation

McGregor, Christopher G.A.; Byrne, Guerard W.; Vlašín, M.; Walker, Randall C.; Tazelaar, Henry D.; Davies, William R.; Chandrasekaran, Krishnaswamy; Oehler, Elise A.; Boilson, Barry A.; Wiseman, BS; Logan, John S.

doi:10.1016/j.healun.2008.11.463

Cited by 11 publications

(14 citation statements)

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“…In contrast, CC has generally not been reported after orthotopic cardiac xenotransplantation in the context of conventional immunosuppression despite the requirement for cardiopulmonary bypass, which is known to activate platelets. The general absence of post‐operative CC in orthotopic xenotransplantation may be affected by the need for full anti‐coagulation at the time of the transplant and/or the higher flow rate of blood through the graft throughout the post‐operative course.…”

Section: Coagulation and Graft Failuresupporting

confidence: 73%

“…C in Reference ) shows vascular antibody deposition with occasional diffuse fibrin deposits. There is however minimal platelet thrombi, vascular congestion, complement deposition, or thrombosis . It seems likely that severity of PCXD is affected by heightened porcine sensitivity to ischemia–reperfusion injury and the effects of acute anti‐non‐Gal antibody‐mediated injury.…”

Section: Orthotopic Cardiac Xenotransplantationmentioning

confidence: 99%

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Histopathologic insights into the mechanism of anti‐non‐Gal antibody‐mediated pig cardiac xenograft rejection

Byrne

Azimzadeh

Ezzelarab

et al. 2013

Xenotransplantation

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The histopathology of cardiac xenograft rejection has evolved over the last 20 years with the development of new modalities for limiting antibody-mediated injury, advancing regimens for immune suppression, and an ever-widening variety of new donor genetics. These new technologies have helped us progress from what was once an overwhelming anti-Gal-mediated hyperacute rejection to a more protracted anti-Gal-mediated vascular rejection, to what is now a more complex manifestation of nonGal humoral rejection and coagulation dysregulation. This review summarizes the changing histopathology of Gal and nonGal-mediated cardiac xenograft rejection and discusses the contributions of immune-mediated injury, species-specific immune-independent factors, transplant and therapeutic procedures, and donor genetics to the overall mechanism(s) of cardiac xenograft rejection.

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Section: Coagulation and Graft Failuresupporting

confidence: 73%

Section: Orthotopic Cardiac Xenotransplantationmentioning

confidence: 99%

Histopathologic insights into the mechanism of anti‐non‐Gal antibody‐mediated pig cardiac xenograft rejection

Byrne

Azimzadeh

Ezzelarab

et al. 2013

Xenotransplantation

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“…Replicating this level of survival in a life-supporting oCXTx model is now clearly the primary objective in the field. There have been relatively few life supporting oCXTx reports [35–42] as this is a far more complex and demanding procedure. These studies have used GT+:hCRP donor hearts, with and without Gal-polymers to block anti-Gal antibody, and GTKO:hCRP donor hearts.…”

Section: Life-supporting Functional Cardiac Xenotransplantationmentioning

confidence: 99%

Current status of pig heart xenotransplantation

Mohiuddin

Reichart

Byrne

et al. 2015

International Journal of Surgery

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Significant progress in understanding and overcoming cardiac xenograft rejection using a clinically relevant large animal pig-to-baboon model has accelerated in recent years. This advancement is based on improved immune suppression, which attained more effective regulation of B lymphocytes and possibly newer donor genetics. These improvements have enhanced heterotopic cardiac xenograft survival from a few weeks to over 2 years, achieved intrathoracic heterotopic cardiac xenograft survival of 50 days and orthotopic survival of 57 days. This encouraging progress has rekindled interest in xenotransplantation research and refocused efforts on preclinical orthotopic cardiac xenotransplantation.

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“…1 Survival after life-supporting heterotopic thoracic pig-to-baboon heart transplantations is up to 50 days, 2 and graft survival in orthotopic xenotransplantations exceeds 1 month in only a limited number of experiments. 3,4 As reported by Byrne, 5 many experiments fail during the intraoperative and early postoperative periods due to perioperative cardiac xenograft dysfunction (PCXD). The outcome of life-supporting pig-to-baboon cardiac xenotransplantations is thus highly dependent on hemodynamic parameters during these two phases of the experiment.…”

Section: Introductionmentioning

confidence: 96%