We would like to thank Melanie Borie, Caroline Landry, Henry Aceros and Ahmed Menaouar for their precious help and support.

The institutional animal care and use committee of the Centre de Recherche du Centre Hospitalier de l&#39;Universit&#233; de Montr&#233;al (CRCHUM) approved all experimental protocols, and animals were treated in compliance with the Guide for the Care and Use of Laboratory Animals. For this protocol, 3-4-month-old Large White male or female pigs weighing 50-60 kg was used. Animal size can vary according to the investigators&#39; experimental goals.
1. Animal preparation and anesthetic in...

<ol>
	<li>Yusen, R. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Registry+of+the+International+Society+for+Heart+and+Lung+Transplantation:+thirty-third+adult+heart+transplantation+report-2016;+focus+theme:+primary+diagnostic+indications+for+transplant.">The Registry of the International Society for Heart and Lung Transplantation: thirty-third adult heart transplantation report-2016; focus theme: primary diagnostic indications for transplant.</a> The Journal of Heart and Lung Transplantation: the Official Publication of the International Society for Heart Transplantation. 35 (10), 1170-1184 (2016).</li><li>Hornby, K., Ross, H., Keshavjee, S., Rao, V., Shemie, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Non-utilization+of+hearts+and+lungs+after+consent+for+donation:+a+Canadian+multicentre+study.">Non-utilization of hearts and lungs after consent for donation: a Canadian multicentre study.</a> Canadian Journal of Anaesthesia. 53 (8), 831-837 (2006).</li><li>Messer, S. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+assessment+and+transplantation+of+the+donor+heart+after+circulatory+death.">Functional assessment and transplantation of the donor heart after circulatory death.</a> The Journal of Heart and Lung Transplantation: the Official Publication of the International Society for Heart Transplantation. 35 (12), 1443-1452 (2016).</li><li>Messer, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Outcome+after+heart+transplantation+from+donation+after+circulatory-determined+death+donors.">Outcome after heart transplantation from donation after circulatory-determined death donors.</a> The Journal of Heart and Lung Transplantation: the Official Publication of the International Society for Heart Transplantation. 36 (12), 1311-1318 (2017).</li><li>Dhital, K. K., Chew, H. C., Macdonald, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Donation+after+circulatory+death+heart+transplantation.">Donation after circulatory death heart transplantation.</a> Current Opinion in Organ Transplantation. 22 (3), 189-197 (2017).</li><li>Ardehali, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ex-vivo+perfusion+of+donor+hearts+for+human+heart+transplantation+(PROCEED+II):+a+prospective,+open-label,+multicentre,+randomised+non-inferiority+trial.">Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.</a> The Lancet. 385 (9987), 2577-2584 (2015).</li><li>White, C. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+donor+heart+viability+during+ex+vivo+heart+perfusion.">Assessment of donor heart viability during ex vivo heart perfusion.</a> Canadian Journal of Physiology and Pharmacology. 93 (10), 893-901 (2015).</li><li>Xin, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+multi-mode+perfusion+system+for+ex+vivo+heart+perfusion+study.">A new multi-mode perfusion system for ex vivo heart perfusion study.</a> Journal of Medical Systems. 42 (2), 25 (2017).</li><li>Robinson, N., et al., Iaizzo, P. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Handbook of Cardiac Anatomy, Physiology, and Devices. , 469-491 (2015).</li><li>Swindle, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Swine in the Laboratory: Surgery, Anesthesia, Imaging, and Experimental Techniques. , (2007).</li><li>Nasir, B. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=HSP90+inhibitor+improves+lung+protection+in+porcine+model+of+donation+after+circulatory+arrest.">HSP90 inhibitor improves lung protection in porcine model of donation after circulatory arrest.</a> The Annals of Thoracic Surgery. 110 (6), 1861-1868 (2020).</li><li>Aceros, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+heat+shock+protein+90+inhibitor+improves+cardiac+recovery+in+a+rodent+model+of+donation+after+circulatory+death.">Novel heat shock protein 90 inhibitor improves cardiac recovery in a rodent model of donation after circulatory death.</a> The Journal of Thoracic and Cardiovascular Surgery. 163 (2), 187-197 (2022).</li><li>Der Sarkissian, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heat+shock+protein+90+inhibition+and+multi-target+approach+to+maximize+cardioprotection+in+ischaemic+injury.">Heat shock protein 90 inhibition and multi-target approach to maximize cardioprotection in ischaemic injury.</a> British Journal of Pharmacology. 177 (15), 3378-3388 (2020).</li><li>Aceros, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Celastrol-type+HSP90+modulators+allow+for+potent+cardioprotective+effects.">Celastrol-type HSP90 modulators allow for potent cardioprotective effects.</a> Life Sciences. 227, 8-19 (2019).</li><li>Aceros, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pre-clinical+model+of+cardiac+donation+after+circulatory+death.">Pre-clinical model of cardiac donation after circulatory death.</a> Journal of Visualized Experiments. (150), e59789 (2019).</li><li>Der Sarkissian, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Celastrol+protects+ischaemic+myocardium+through+a+heat+shock+response+with+up-regulation+of+haeme+oxygenase-1.">Celastrol protects ischaemic myocardium through a heat shock response with up-regulation of haeme oxygenase-1.</a> British Journal of Pharmacology. 171 (23), 5265-5279 (2014).</li></ol>

The authors have nothing to disclose.

This manuscript describes a large-animal model donation after circulatory death (DCD) followed by thoracoabdominal normothermic regional perfusion. In this experiment, the heart is reperfused for a minimum of 30 min and a maximum of 3 h before it is weaned off from the ECMO circuit. The heart is then functioning on its own for 2 h which allows for valuable cardiac assessment on the short term. Therefore, the major limitation of this protocol is the short-term follow-up; however, a long-term assessment would be resource-i...

Over 300,000 individuals die in North America each year of heart failure (HF); cardiac transplantation remains the only treatment option for some of these patients with end stage disease1. Historically, the exclusive source for heart transplantation was donor hearts obtained after neurological determination of death (NDD), but even then, only around 40% were adequate for transplantation2. Between 15% to 20% of patients die while waiting for a heart donation, with shortage of donor hearts being one of the reasons that creates a discrepancy between the hearts available and the hearts needed2. In order to increase the organ donor pool, one important consideration is the use of hearts donated after circulatory death (DCD)3. There is reluctance to use DCD hearts because these organs are invariably submitted to a period of unprotected (warm) ischemia after cessation of blood circulation and may sustain irreversible damage. Although reports for successful DCD heart transplantation with excellent early outcomes do exist4,5, there is a need to develop a validated assessment method to determine if these hearts are usable and to potentially predict their post-transplant performance6,7. To limit ischemic periods of DCD hearts and to continuously monitor them during storage and transportation, ex situ heart perfusion systems were developed8. However, this technology relies on complex machines with perfusion equipment, and has a high upfront cost without any guarantee that the procured organ will be suitable for transplantation. A novel protocol for DCD heart transplantation based on normothermic regional perfusion (NRP) was proposed by Messer et al3. This technique involves restoring myocardial perfusion while the heart is still in the donor and excluding cerebral circulation. It allows a functional assessment in situ before procurement3.
When using large-animal models, the porcine heart is one of the preferred platforms to perform cardiac surgical research considering its anatomical similarity to the human heart. However, some important factors in porcine hearts should be considered when using this model. For example, porcine cardiac tissue is very fragile and friable and is prone to tears, especially in the pulmonary artery and the right atrium9. Another important factor to consider is that the porcine heart is very sensitive to ischemia and prone to arrhythmias, which is why antiarrhythmics should be administered routinely to every animal before the experiment; nevertheless, it is still considered an appropriate model for the study of acute ischemia in heart transplantation9.
This manuscript describes a large-animal (porcine) model of donation after circulatory death followed by thoracoabdominal normothermic regional perfusion that closely simulates the clinical scenario in heart transplantation and has the potential to facilitate novel therapeutic studies and strategies for translational research.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Amiodarone</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Angiocath 20G</td>
			<td>BD</td>
			<td>381704</td>
			<td></td>
		</tr>
		<tr>
			<td>Atropine 0.4 mg/mL</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Biomedicus Centrifugal Pump</td>
			<td>Medtronic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cardioplegia Solution (Del Nido)</td>
			<td>in-house made</td>
			<td></td>
			<td>Another solution can be used at the discretion of the researcher</td>
		</tr>
		<tr>
			<td>Cautery Pencil</td>
			<td>Covidien</td>
			<td>E2515H</td>
			<td></td>
		</tr>
		<tr>
			<td>Central Venous Catheter double-lumen</td>
			<td>Cook Medical</td>
			<td>C-UDLM-501J-LSC</td>
			<td></td>
		</tr>
		<tr>
			<td>Central Venous Sheath Introducer 7 Fr</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Conductance Catheter</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>CPB pack</td>
			<td>Medtronic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>DLP Aortic Root Cannula</td>
			<td>Medtronic</td>
			<td>12218</td>
			<td></td>
		</tr>
		<tr>
			<td>DLP double-stage venous cannula (29 or 37 F)</td>
			<td>Medtronic</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Dobutamine</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Dopamine</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Electrode Polyhesive</td>
			<td>Covidien</td>
			<td>E7507</td>
			<td></td>
		</tr>
		<tr>
			<td>EOPA Arterial Cannula (17 or 21 F)</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Epinephrine</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>O2 Face Mask</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Gloves, Nitrile, Medium</td>
			<td>Fischer</td>
			<td>27-058-52</td>
			<td></td>
		</tr>
		<tr>
			<td>Heparin 1000 IU/mL</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Inhaled Isofurane</td>
			<td></td>
			<td></td>
			<td>Provided by the institution&#39;s animal facility</td>
		</tr>
		<tr>
			<td>Jelco 16 or 18 G catheter</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ketamine inj. 50 mL vial (100 mg/mL)</td>
			<td>Health Canada</td>
			<td></td>
			<td>Health Canada approval is required</td>
		</tr>
		<tr>
			<td>Lidocaine/Xylocaine 1%</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Magnesium Sulfate 5 g/10 mL</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Midazolam inj. 10 mL vial (5 mg/mL)</td>
			<td>Health Canada</td>
			<td></td>
			<td>Health Canada approval is required</td>
		</tr>
		<tr>
			<td>MPS Quest delivery disposable pack</td>
			<td>Quest Medical</td>
			<td>5001102-AS</td>
			<td></td>
		</tr>
		<tr>
			<td>Norepinephrine</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Normal Saline (NaCl 0.9%) 1L bag</td>
			<td>Baxter</td>
			<td>JB1324</td>
			<td></td>
		</tr>
		<tr>
			<td>Pipette Tips 1 mL</td>
			<td>Fisherbrand</td>
			<td>02-707-405</td>
			<td></td>
		</tr>
		<tr>
			<td>Propofol 1 mg/mL</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Rocuronium</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Set Admin Prim NF PB W/ Checkvalve</td>
			<td>Smith Medical</td>
			<td>21-0442-25</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium Bicarbonate (NaOH) 8.4%</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Sofsil 0 wax coated</td>
			<td>Covidien</td>
			<td>S316</td>
			<td></td>
		</tr>
		<tr>
			<td>Solumedrol 500 mg/5 mL</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
		<tr>
			<td>Suction Tip</td>
			<td>Covidien</td>
			<td>8888501023</td>
			<td></td>
		</tr>
		<tr>
			<td>Suction Tubing 1/4&#39;&#39; x 120&#39;&#39;</td>
			<td>Med-Rx</td>
			<td>70-8120</td>
			<td></td>
		</tr>
		<tr>
			<td>Suture 3.0 Prolene Blu M SH</td>
			<td>Ethicon</td>
			<td>8523H</td>
			<td></td>
		</tr>
		<tr>
			<td>Suture 5.0 Prolene BB</td>
			<td>Ethicon</td>
			<td>8580H</td>
			<td></td>
		</tr>
		<tr>
			<td>Suture Prolene Blum 4-0 SH 36</td>
			<td>Ethicon</td>
			<td>8521H</td>
			<td></td>
		</tr>
		<tr>
			<td>Suture BB 4.0 Prolene</td>
			<td>Ethicon</td>
			<td>8881H</td>
			<td></td>
		</tr>
		<tr>
			<td>Tracheal Tube, 6.5 mm</td>
			<td>Mallinckrodt</td>
			<td>86449</td>
			<td></td>
		</tr>
		<tr>
			<td>Vasopressin</td>
			<td></td>
			<td></td>
			<td>As available in the institution</td>
		</tr>
	</tbody>
</table>

large-animal model of donation after circulatory death and normothermic regional perfusion for cardiac assessment

The increase in demand for cardiac transplantation throughout the years has fueled interest in donation after circulatory death (DCD) to expand the organ donor pool. However, the DCD process is associated with the risk of cardiac tissue injury due to the inevitable period of warm ischemia. Normothermic regional perfusion (NRP) allows for an in situ organ assessment, allowing the procurement of hearts determined to be viable. Here, we describe a clinically relevant large-animal model of DCD followed by NRP. Circulatory death is established in anesthetized pigs by stopping mechanical ventilation. After a preset warm ischemia period, an extracorporeal membrane oxygenator (ECMO) is used for a NRP period lasting at least 30 min. During this reperfusion period, the model allows the collection of various myocardial biopsies and blood samples for initial cardiac evaluation. Once NRP is weaned, biochemical, hemodynamic, and echocardiographic assessments of cardiac function and metabolism can be performed before organ procurement. This protocol closely simulates the clinical scenario previously described for DCD and NRP in heart transplantation and has the potential to facilitate studies aimed at decreasing ischemia-reperfusion injury and enhance cardiac functional preservation and recovery.

This preclinical model has been successfully used in our institution for multiple experiments. First, we demonstrated that DCD hearts, initially reperfused with NRP, demonstrated similar functional recovery following transplantation when compared to conventional beating heart donation preserved with cold storage. Further, we have used this protocol to show that cardiac functional assessment following NRP was predictive of post-transplantation recovery. Finally, we have also studied the effects of NRP on cerebral perfusio...

Watch this Scientific Journal Video about Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment at JoVE.com

Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment

The protocol describes a large-animal (porcine) model of donation after circulatory death, followed by thoracoabdominal normothermic regional perfusion that closely simulates the clinical scenario in heart transplantation, and has the potential to facilitate therapeutic studies and strategies.

The increase in demand for cardiac transplantation throughout the years has fueled interest in donation after circulatory death (DCD) to expand the organ ...

This protocol describes a large animal model of donation after circulatory death followed by thoracoabdominal normothermic regional perfusion that precisely mimics the clinical heart transplantation. This could be used to evaluate potential strategies in translational research. The main advantage of this protocol is that it provides a suitable preclinical model for cardiac transplantation given the anatomical and surgical techniques similarities between the boar swine and the human hearts.Begin by using a cautery pen to perform a midline incision on an anesthetized animal from the mid cervical region to the xiphoid. Then, divide the subcutaneous fat, layer by layer, along the midline using electrocautery to reach the peristernum. After cutting around the sternal notch, use a finger to retract and sweep soft tissues from under the sternum.Open the sternum with a bone saw, ensuring that the sternum is completely divided, while being careful with the vein beneath the upper part of the sternal bone. Then, cauterize the sternum or apply bone wax to ensure adequate hemostasis. Next, using electrocautery, dissect and remove the thymus by lifting it from the pericardium and cauterize the vessels that supply the thymus from the aorta and the superior vena cava to prevent bleeding.Carefully cut the pericardium open with cautery. While cutting, insert fingers under the pericardium to avoid injury to the heart. Then, administer 300 units per kilogram of heparin intravenously to achieve systemic anticoagulation.If the test is available, ensure the activated clotting time is more than 300 seconds. Administer a bolus of three milligrams per kilogram propofol intravenously. Then, stop mechanical ventilation and disconnect the endotracheal tube.Monitor arterial pressure and peripheral oxygen saturation. When systolic pressure is less than 50 millimeters of mercury, start functional warm ischemia time. Establish circulatory arrest when there is asystole and an absence of arterial pulsatility.After the withdrawal of life sustaining therapies and confirmation of death, retract the right ventricle outflow tract inferiorly, the pulmonary artery to the left and the aorta to the right. Then, carefully dissect the aorta pulmonary space using cautery. Apply a large cross clamp over the supraaortic vessels to avoid and exclude cerebral perfusion.Next, using the Metzenbaum and right angle forceps, dissect delicately between the superior vena cava and the innominate artery and between the inferior vena cava and pericardium. And circle the superior and inferior vena cava using an umbilical tape or a simple zero silk suture and secure them with a tourniquet. Using a 3-0 suture, place two concentric purse-string sutures on the distal ascending aorta adventitia, avoiding full thickness sutures.Then, place a purse-string suture on the right atrium before securing all sutures with a tourniquet. Next, set up and prime the normothermic regional perfusion system. Then, cannulate the aorta using a 17 to 21 French arterial cannula and secure it in place by tightening the tourniquet, holding the purse-string suture.Create a five millimeter incision at the center of the purse-string on the right atrium and dilate it using a small angled instrument, like a right angle or snap. Cover the incision with a finger to avoid excessive bleeding. Next, use a double stage venous cannula to cannulate the right atrium.Then, secure the cannula by tightening the purse-string sutures using a tourniquet. Connect the cannulas to the venous line of the normothermic regional perfusion circuit using a half to three over eight inch connector, ensuring complete de-airing to avoid an airlock in the system. Ensuring that a minimum of 15 minutes has passed between the declaration of death and the initiation of normothermic regional perfusion to encompass the time needed in clinical practice preparation, draping and having access to the heart.15 minutes after starting functional warm ischemia time, initiate the normothermic regional perfusion and adjust flow rates progressively to reach a perfusion index of 2.5 liters per minute per square meter. Restart mechanical ventilation with a 50%fraction of inspired oxygen and six milliliters per kilogram tidal volume. When weaning off criteria are met, stop normothermic regional perfusion.Remove the cannula from the right atrium and quickly tighten the purse-string suture to minimize blood loss. Secure the suture with knots. Then follow the same procedure to remove the aortic cannula.Analyze cardiac function through echocardiography using a standard transesophageal probe and a transthoracic probe placed directly on the heart. Representative results of cardiac function demonstrated a significant decline in heart function following donation after circulatory death. However, these organs demonstrated similar functional recovery post transplantation when compared to conventionally transplanted hearts.Cerebral oximetry measurements during normothermic regional perfusion with the supraaortic vessels clamped confirmed the absence of adequate cerebral perfusion, while lung compliance measurements during normothermic regional perfusion and after weaning from support shown no significant change from baseline. The development of this technique introduced the importance of assessing the transplantability of other organs like the lungs, the kidneys, and the liver in the context of donation after circulatory death and normothermic regional perfusion.

large-animal-model-donation-after-circulatory-death-normothermic

Research

JoVE Journal

Medicine

1.5K visualizações.  Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM). Este protocolo descreve um modelo animal de grande porte de doação após morte circulatória seguida de perfusão regional normotérmica toracoabdominal que mimetiza com precisão o transplante cardíaco clínico. Isso poderia ser usado para avaliar potenciais estratégias em pesquisa translacional. A principal vantagem deste protocolo é que ele fornece um modelo pré-clínico adequado para transplante cardíaco, dadas as semelhanças das técnicas anatômicas e cirúrgicas entre os coraç...