A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft

Michelle Mendiola Pla; Amy Evans; Franklin H. Lee; Yuting Chiang; Muath Bishawi; Andrew Vekstein; Lillian Kang; Diego Zapata; Ryan Gross; Alexis Carnes; Lynden E. Gault; Julie A. Balko; Desiree Bonadonna; Sam Ho; Paul Lezberg; Benjamin S. Bryner; Jacob N. Schroder; Carmelo A. Milano; Dawn E. Bowles

doi:10.3791/63114

A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft

Michelle Mendiola Pla, Amy Evans, Franklin H. Lee, Yuting Chiang, Muath Bishawi, Andrew Vekstein, Lillian Kang, Diego Zapata, Ryan Gross, Alexis Carnes, Lynden E. Gault, Julie A. Balko, Desiree Bonadonna, Sam Ho, Paul Lezberg, Benjamin S. Bryner, Jacob N. Schroder, Carmelo A. Milano^*, Dawn E. Bowles

^*Corresponding author for this work

Surgery, Cardiac Surgery Division

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intraabdominal position serves as an excellent model for assessing the effects of novel interventions and the immunopathology of graft rejection. This model additionally offers long-term survival for the pig, given that the graft is not required to maintain the recipient's circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.

Original language	English (US)
Article number	e63114
Journal	Journal of Visualized Experiments
Volume	2022
Issue number	180
DOIs	https://doi.org/10.3791/63114
State	Published - Feb 2022

ASJC Scopus subject areas

Neuroscience(all)
Chemical Engineering(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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10.3791/63114

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Pla, M. M., Evans, A., Lee, F. H., Chiang, Y., Bishawi, M., Vekstein, A., Kang, L., Zapata, D., Gross, R., Carnes, A., Gault, L. E., Balko, J. A., Bonadonna, D., Ho, S., Lezberg, P., Bryner, B. S., Schroder, J. N., Milano, C. A., & Bowles, D. E. (2022). A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft. Journal of Visualized Experiments, 2022(180), [e63114]. https://doi.org/10.3791/63114

@article{a0422fb97b1b46de9762f4fb50eef784,

title = "A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft",

abstract = "Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intraabdominal position serves as an excellent model for assessing the effects of novel interventions and the immunopathology of graft rejection. This model additionally offers long-term survival for the pig, given that the graft is not required to maintain the recipient's circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.",

author = "Pla, {Michelle Mendiola} and Amy Evans and Lee, {Franklin H.} and Yuting Chiang and Muath Bishawi and Andrew Vekstein and Lillian Kang and Diego Zapata and Ryan Gross and Alexis Carnes and Gault, {Lynden E.} and Balko, {Julie A.} and Desiree Bonadonna and Sam Ho and Paul Lezberg and Bryner, {Benjamin S.} and Schroder, {Jacob N.} and Milano, {Carmelo A.} and Bowles, {Dawn E.}",

note = "Funding Information: Paul Lezberg is employed by TransMedics, Inc. Carmelo Milano received a financial gift from TransMedics, Inc. to fund heterotopic heart transplant surgeries. Michelle Mendiola Pla is supported by T32HL007101. The other authors have no conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2022 JoVE Journal of Visualized Experiments.",

year = "2022",

month = feb,

doi = "10.3791/63114",

language = "English (US)",

volume = "2022",

journal = "Journal of Visualized Experiments",

issn = "1940-087X",

publisher = "MYJoVE Corporation",

number = "180",

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Pla, MM, Evans, A, Lee, FH, Chiang, Y, Bishawi, M, Vekstein, A, Kang, L, Zapata, D, Gross, R, Carnes, A, Gault, LE, Balko, JA, Bonadonna, D, Ho, S, Lezberg, P, Bryner, BS, Schroder, JN, Milano, CA & Bowles, DE 2022, 'A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft', Journal of Visualized Experiments, vol. 2022, no. 180, e63114. https://doi.org/10.3791/63114

TY - JOUR

T1 - A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft

AU - Pla, Michelle Mendiola

AU - Evans, Amy

AU - Lee, Franklin H.

AU - Chiang, Yuting

AU - Bishawi, Muath

AU - Vekstein, Andrew

AU - Kang, Lillian

AU - Zapata, Diego

AU - Gross, Ryan

AU - Carnes, Alexis

AU - Gault, Lynden E.

AU - Balko, Julie A.

AU - Bonadonna, Desiree

AU - Ho, Sam

AU - Lezberg, Paul

AU - Bryner, Benjamin S.

AU - Schroder, Jacob N.

AU - Milano, Carmelo A.

AU - Bowles, Dawn E.

N1 - Funding Information: Paul Lezberg is employed by TransMedics, Inc. Carmelo Milano received a financial gift from TransMedics, Inc. to fund heterotopic heart transplant surgeries. Michelle Mendiola Pla is supported by T32HL007101. The other authors have no conflicts of interest to declare. Publisher Copyright: © 2022 JoVE Journal of Visualized Experiments.

PY - 2022/2

Y1 - 2022/2

N2 - Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intraabdominal position serves as an excellent model for assessing the effects of novel interventions and the immunopathology of graft rejection. This model additionally offers long-term survival for the pig, given that the graft is not required to maintain the recipient's circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.

AB - Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intraabdominal position serves as an excellent model for assessing the effects of novel interventions and the immunopathology of graft rejection. This model additionally offers long-term survival for the pig, given that the graft is not required to maintain the recipient's circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.

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U2 - 10.3791/63114

DO - 10.3791/63114

M3 - Article

C2 - 35225284

AN - SCOPUS:85125429955

SN - 1940-087X

VL - 2022

JO - Journal of Visualized Experiments

JF - Journal of Visualized Experiments

IS - 180

M1 - e63114

ER -

A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft

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