Name: A Preclinical Model of Orthotopic Heart Transplantation in Bama Miniature Pigs Using Biatrial Technique (Video) | JoVE Journal
Uploaded: 2025-06-13T13:45:00.000+00:00
Duration: 6 min 55 s
Description: Learn orthotopic heart transplantation using the biatrial technique in Bama miniature pigs. This preclinical model supports transplant immunology research and drug evaluation for clinical applications.

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5 minutes

This work was sponsored by the National Natural Science Fund for Distinguished Young Scholars of China (82125004; to Jiangping Song), Frontier Biotechnology Key Project of National Key R &#38; D Program of the Ministry of Science and Technology of China (2023YFC3404300; to Jiangping Song), Special Project of the Ministry of Science and Technology of China Supported by the State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences (2024GZZD-03; to Jiangping Song), and National Natural Science Foundation of China (82300464; to Yuan Chang)

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<li>Palliyaguru, D. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Fasting+blood+glucose+as+a+predictor+of+mortality%3A+Lost+in+translation%5BTitle%5D)+AND+%22Cell+Metab%22%5BJournal%5D)">Fasting blood glucose as a predictor of mortality: Lost in translation.</a> Cell Metab. 33 (11), 2189-2200.e3 (2021).</li>
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<li>Mendiola Pla, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+porcine+heterotopic+heart+transplantation+protocol+for+delivery+of+therapeutics+to+a+cardiac+allograft%5BTitle%5D)+AND+%22J+Vis+Exp%22%5BJournal%5D)">A porcine heterotopic heart transplantation protocol for delivery of therapeutics to a cardiac allograft.</a> J Vis Exp. (180), e63114(2022).</li>
</ol>

The authors have no conflicts of interest to declare.

The porcine heart orthotopic transplantation model is an effective experimental platform that simulates clinical heart transplantation15. The porcine heart shares many anatomical and physiological similarities with the human heart12. Therefore, this model has significant application value in studying various aspects of heart transplantation, particularly in heart protection, surgical procedures, and transplant immunology. However, despite these advantages, performing orthot...

Since the first heart transplant in 1967, significant advancements have been made in heart transplantation. However, in the past two decades, there have been few major breakthroughs in clinical practice. Core issues such as graft dysfunction, cardiac allograft vasculopathy (CAV), and long-term immune tolerance remain unresolved1,2,3,4. Despite numerous findings in basic research, these discoveries have been challenging to translate into clinical applications, leading to a stagnation in the progress of heart transplant treatments. Therefore, effectively evaluating new technologies and therapies has become a critical issue, which highlights the importance of animal models, especially appropriate preclinical models, in addressing these challenges.
While mouse models have been widely used in heart transplantation research, they have significant limitations due to anatomical and physiological differences from humans, making it difficult to fully replicate the clinical heart transplant procedure and postoperative immune responses. Moreover, the immune system is relatively different, which fails to adequately reflect the complex immune responses seen in large animal models5,6,7. Additionally, due to their small size, heart transplants in mice are limited to heterotopic transplants, which diverges from the clinical practice of orthotopic heart transplantation8,9,10,11. Therefore, the use of appropriate large animal models, particularly pigs, is crucial.
Pig models offer significant advantages in heart transplantation research, especially in orthotopic heart transplantation. The pig heart is anatomically similar to the human heart, and pigs exhibit immune responses and organ physiological functions that are much closer to those of humans, making them an ideal platform for heart transplantation studies. Furthermore, pig models provide more complex and detailed experimental data, enabling researchers to better evaluate new immunosuppressive strategies, cardiac protection methods, and long-term outcomes post-transplant12,13,14,15. While some studies have utilized abdominal heterotopic models in pigs, which avoid the use of cardiopulmonary bypass and reduce surgical complexity, they fail to fully replicate the clinical scenario of orthotopic heart transplantation16. Therefore, in this study, we have established a dual-atrium orthotopic heart transplantation model in Bama miniature pigs, providing a more clinically relevant experimental platform for advancing heart transplantation techniques.

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forceps</td><td>SureMed</td><td>GF04021-25</td><td>Donor Surgery</td></tr><tr><td>Atraumatic flat forceps</td><td>SureMed</td><td>GF04021-25</td><td>Recipient surgery</td></tr><tr><td>Atraumatic flat forceps</td><td>SureMed</td><td>GF04016-25</td><td>Recipient surgery</td></tr><tr><td>Balanced handle pen-style microsurgical forceps</td><td>Sinoview</td><td>FC12010-21</td><td>Donor Surgery</td></tr><tr><td>Balanced-handle pen-style microsurgical forceps</td><td>Sinoview</td><td>FC12010-21</td><td>Recipient surgery</td></tr><tr><td>Bama miniature pigs</td><td>Institute of Zoology, Chinese Academy of Sciences, Northern Large Animal Research Facility</td><td>-</td><td>Experimental animals</td></tr><tr><td>Belzer UW&amp;nbsp;Cold Storage Solution</td><td>Bridge to Life Ltd.</td><td>1000 ml/bag</td><td>Donor Surgery</td></tr><tr><td>Black-handle extreme-sharp scissors</td><td>Sinoview</td><td>SC35101-23UC</td><td>Donor Surgery</td></tr><tr><td>Black-handled extremely sharp scissors</td><td>Sinoview</td><td>SC35101-23UC</td><td>Recipient surgery</td></tr><tr><td>Blood gas analyzer</td><td>Ediagnosis</td><td>PT1000</td><td>Anesthesia and others</td></tr><tr><td>Cardiopulmonary bypass circuit</td><td>Medtronic</td><td>B-HL-159</td><td>Cardiopulmonary bypass</td></tr><tr><td>Central venous catheter</td><td>Baihe Medical</td><td>-</td><td>Anesthesia and others</td></tr><tr><td>Curved forceps</td><td>SureMed</td><td>GC01002-16</td><td>Donor Surgery</td></tr><tr><td>Curved forceps</td><td>SureMed</td><td>GC01002-12</td><td>Recipient surgery</td></tr><tr><td>Curved forceps</td><td>SureMed</td><td>GC01002-16</td><td>Recipient surgery</td></tr><tr><td>Disposable blood microembolus filter</td><td>Sansin</td><td>FAF-2</td><td>Cardiopulmonary bypass</td></tr><tr><td>Disposable blood reservoir filter</td><td>Sansin</td><td>FCR300K</td><td>Cardiopulmonary bypass</td></tr><tr><td>Disposable cardioplegia delivery 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injection</td><td>Kelun Pharmaceutical co.,Ltd</td><td>H20057816</td><td>Donor Surgery</td></tr><tr><td>Magnesium sulfate for injection</td><td>Zdjt Pharmaceutical co.,Ltd</td><td>H20051792</td><td>Donor Surgery</td></tr><tr><td>Medical electric sternum saw</td><td>Jingdong xiji</td><td>HF-X01</td><td>Donor Surgery</td></tr><tr><td>Medical sternum saw, electric sternum saw</td><td>Jingdong xiji</td><td>HF-X01</td><td>Recipient surgery</td></tr><tr><td>Medium basin</td><td>SureMed</td><td>-</td><td>Donor Surgery</td></tr><tr><td>Medium-sized sternum retractor</td><td>SureMed</td><td>GR04130-00</td><td>Recipient surgery</td></tr><tr><td>Modified St. Thomas Solution</td><td>Self-made</td><td>-</td><td>Anesthesia and others</td></tr><tr><td>Multiparameter monitor</td><td>Mindray</td><td>Benoversion N17</td><td>Anesthesia and others</td></tr><tr><td>Needle passer for purse-string sutures</td><td>SureMed</td><td>GR04074-00</td><td>Recipient surgery</td></tr><tr><td>Nerve and chordae 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forceps</td><td>Sinoview</td><td>FC25501-23S</td><td>Donor Surgery</td></tr><tr><td>Right-angle forceps</td><td>SureMed</td><td>GC01110-14</td><td>Donor Surgery</td></tr><tr><td>Right-angle forceps</td><td>SureMed</td><td>GC01089-18</td><td>Donor Surgery</td></tr><tr><td>Right-angled clamp</td><td>SureMed</td><td>GC01110-14</td><td>Recipient surgery</td></tr><tr><td>Right-angled clamp</td><td>SureMed</td><td>GC01089-18</td><td>Recipient surgery</td></tr><tr><td>Small basin</td><td>SureMed</td><td>-</td><td>Donor Surgery</td></tr><tr><td>Sodium acetate Ringer&#039;s injection</td><td>Duo Rui Pharmaceutical co.,Ltd</td><td>H20163331</td><td>Donor Surgery</td></tr><tr><td>Sodium bicarbonate injection</td><td>Kelun Pharmaceutical co.,Ltd</td><td>H20043739</td><td>Donor Surgery</td></tr><tr><td>Sternal retractor (medium size)</td><td>SureMed</td><td>GR04130-00</td><td>Donor Surgery</td></tr><tr><td>Straight forceps</td><td>SureMed</td><td>GC01001-12</td><td>Donor Surgery</td></tr><tr><td>Straight forceps</td><td>SureMed</td><td>GC01001-16</td><td>Donor Surgery</td></tr><tr><td>Straight forceps</td><td>SureMed</td><td>GC01001-12</td><td>Recipient surgery</td></tr><tr><td>Straight forceps</td><td>SureMed</td><td>GC01001-16</td><td>Recipient surgery</td></tr><tr><td>Suture 5-0 Prolene BB</td><td>Ethicon</td><td>-</td><td>Recipient surgery</td></tr><tr><td>Suture Prolene Blum 4-0 SH 36</td><td>Ethicon</td><td>-</td><td>Recipient surgery</td></tr><tr><td>Sutures 2-0 Prolene Blu M SH</td><td>Ethicon</td><td>-</td><td>Recipient surgery</td></tr><tr><td>Sutures BB 4-0 Prolene</td><td>Ethicon</td><td>-</td><td>Recipient surgery</td></tr><tr><td>Temperature probe</td><td>3M</td><td>-</td><td>Anesthesia and others</td></tr><tr><td>Tonsil forceps</td><td>SureMed</td><td>GC09009-20D</td><td>Donor Surgery</td></tr><tr><td>Tungsten carbide ring-handled needle holder</td><td>SureMed</td><td>GN01013-22K</td><td>Donor Surgery</td></tr><tr><td>Tungsten carbide ring-handled needle holder</td><td>SureMed</td><td>GN01013-22K</td><td>Recipient surgery</td></tr><tr><td>Tungsten carbide ring-handled needle holder</td><td>SureMed</td><td>GN01010-22K</td><td>Recipient surgery</td></tr><tr><td>UW Solution&amp;nbsp;</td><td>Belzer</td><td>-</td><td>Anesthesia and others</td></tr><tr><td>Venous cannula</td><td>Medtronic</td><td>28Fr, 32Fr</td><td>Cardiopulmonary bypass</td></tr><tr><td>Ventilator</td><td>Mindray</td><td>SV300</td><td>Anesthesia and others</td></tr><tr><td>Weighted pen-style needle holder</td><td>Sinoview</td><td>NH10400-23</td><td>Recipient surgery</td></tr></tbody></table>

a preclinical model of orthotopic heart transplantation in bama miniature pigs using biatrial technique

A Preclinical Model of Orthotopic Heart Transplantation in Bama Miniature Pigs Using Biatrial Technique

Although significant progress has been made in heart transplantation, issues such as graft preservation, primary graft dysfunction, cardiac allograft vasculopathy, and long-term immune tolerance remain unresolved. Due to anatomical size and immunological differences, mouse models are unable to effectively replicate clinical heart transplantation surgeries and immune responses. In contrast, pig models, which share more similarities with humans in terms of heart anatomy and immune response, are particularly suitable for orthotopic heart transplantation research. In this study, we established a biatrial orthotopic heart transplantation model in Bama miniature pigs. The transplanted hearts demonstrated prompt and robust contractility postoperatively without signs of elevated central venous pressure or other hemodynamic complications. Following a short period of intensive care unit monitoring, the pigs regained consciousness and resumed spontaneous feeding, indicating stable postoperative recovery. In summary, this model offers a clinically relevant experimental platform for evaluating new technologies and therapeutic approaches in the field of heart transplantation research.

Figure 1 illustrates the key procedural steps of orthotopic heart transplantation in pigs, including midline sternotomy, opening the pericardium to expose major blood vessels, aortic infusion of cardioplegic solution, cooling the heart with ice slush, and preserving the donor heart. A critical aspect highlighted is the management of the left azygos vein, which is a pivotal step in the transplantation procedure. For the donor heart, the left azygos vein should be ligated to prevent excessive ...

This study proposes a preclinical orthotopic heart transplantation model in Bama miniature pigs, utilizing the biatrial technique. The model is applicable for transplant immunology, drug evaluation, and surgical technique optimization, providing support for clinical heart transplantation applications.

Although significant progress has been made in heart transplantation, issues such as graft preservation, primary graft dysfunction, cardiac allograft ...

a-preclinical-model-orthotopic-heart-transplantation-bama-miniature

Research

JoVE Journal

Medicine

We describe a technique in which a section of the abdominal aorta from a mouse is transplanted orthotopically to just below the renal arteries in an allogeneic or syngeneic recipient.  This technique can be useful in studies in which transplantation of large arteries of uniform size is deemed advantageous.

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

Myocardial Infarction and Functional Outcome Assessment in Pigs

Here, we describe a pre-clinical large-animal (porcine) model of orthotopic heart transplantation that has been firmly established and utilized to investigate novel cardioprotective strategies.

A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation

We describe a sterile pericarditis model in minipigs to study atrial myopathy and atrial fibrillation (AF). We present surgical and anesthetic techniques, strategies for vascular access, and a protocol to study the inducibility of AF.

Sterile Pericarditis in Aachener Minipigs As a Model for Atrial Myopathy and Atrial Fibrillation

We present a protocol for utilizing a normothermic ex vivo sanguinous perfusion system for the delivery of therapeutics to an entire cardiac allograft in a porcine heterotopic heart transplant model.

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

The present protocol describes a step-by-step procedure to establish a minipig model of heart failure with preserved ejection fraction using descending aortic constriction. The methods for evaluating cardiac morphology, histology, and function of this disease model are also presented.

A Surgical Model of Heart Failure with Preserved Ejection Fraction in Tibetan Minipigs

This protocol describes a minimally invasive surgical procedure for ascending aortic banding in swine.

A Minimally Invasive Model of Aortic Stenosis in Swine

The protocol here describes a high-fidelity porcine model of heart transplantation following donation after circulatory death utilizing ex vivo perfusion of the allograft.

A High-Fidelity Porcine Model of Orthotopic Heart Transplantation Following Donation after Circulatory Death

This study presents a pre-clinical heterotopic abdominal heart xenotransplantation model using α-Gal knockout (GTKO) pigs and macaques. The model incorporates optimized recipient selection, vascular anastomosis techniques, and perioperative management strategies. It is suitable for evaluating novel immunosuppressive agents and provides a convenient platform for advancing heart xenotransplantation.

A Standardized Pig to Macaque Heterotopic Heart Xenotransplantation Model

This study presents a surgical method for subvalvular aortic valve structure intervention using targeted tissue cutting via a transaortic approach in normal Bama pigs.

A Surgical Method for Subvalvular Structure Intervention Through a Transaortic Approach in Normal Bama Pigs

Learn orthotopic heart transplantation using the biatrial technique in Bama miniature pigs. This preclinical model supports transplant immunology research and drug evaluation for clinical applications.

A Preclinical Model of Orthotopic Heart Transplantation in Bama Miniature Pigs Using Biatrial Technique

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