Name: functional assessment of the donor heart during ex situ perfusion: insights from pressure-volume loops and surface echocardiography
Uploaded: 2022-10-11T13:20:00
Description: Watch this Scientific Journal Video about Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography at JoVE.com

Georges Lopez Institute, Lissieu, 69380, France
Claudia Lacerda, General Electric Healthcare, Buc, France

The present protocol was approved by the local ethics committee on animal experiments and by the Institutional Committee on Animal Welfare (APAFIS#30483-2021031811339219 v1, Animals Ethics Committee of the University of Paris Saclay, France). Animals were treated in accordance with the Guidelines for the Care and Use of Laboratory Animals developed by the National Institute of Health and with the Principles of Laboratory Animal Care developed by the National Society for Medical Research.
NOTE:...

<ol>
	<li>Lund, L. 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=The+registry+of+the+international+society+for+heart+and+lung+transplantation:+thirty-second+official+adult+heart+transplantation+report-2015;+focus+theme:+early+graft+failure.">The registry of the international society for heart and lung transplantation: thirty-second official adult heart transplantation report-2015; focus theme: early graft failure.</a> Journal of Heart and Lung Transplant. 34 (10), 1244-1254 (2015).</li><li>. Annual report 2018 Eurotransplant International Foundation Available from: <a target="_blank" href="https://www.eurotransplant.org/cms/mediaobject.php?file=ET_Jaarv">https://www.eurotransplant.org/cms/mediaobject.php?file=ET_Jaarv</a> (2018)</li><li>Guglin, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+to+increase+the+utilization+of+donor+hearts.">How to increase the utilization of donor hearts.</a> Heart Failure Reviews. 20 (1), 95-105 (2015).</li><li>Tuttle-Newhall, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organ+donation+and+utilization+in+the+United+States:+1998-2007.">Organ donation and utilization in the United States: 1998-2007.</a> American Journal of Transplantation. 9 (4), 879-893 (2009).</li><li>Dronavalli, V. B., Banner, N. R., Bonser, R. S. <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+the+potential+heart+donor.">Assessment of the potential heart donor.</a> Journal of the American College of Cardiology. 56 (5), 352-361 (2010).</li><li>Reich, H. 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=Effects+of+older+donor+age+and+cold+ischemic+time+on+long-term+outcomes+of+heart+transplantation.">Effects of older donor age and cold ischemic time on long-term outcomes of heart transplantation.</a> Texas Heart Institute Journal. 45, 17-22 (2018).</li><li>Dhital, K. K., 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=Adult+heart+transplantation+with+distant+procurement+and+ex-vivo+preservation+of+donor+hearts+after+circulatory+death:+a+case+series.">Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.</a> The Lancet. 385 (9987), 2585-2591 (2015).</li><li>Garry, B. P., Bivens, H. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Seldinger+technique.">The Seldinger technique.</a> Journal of Cardiothoracic Anesthesia. 2 (3), 403 (1988).</li><li>Lang, R. M., 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=Recommendations+for+cardiac+chamber+quantification+by+echocardiography+in+adults:+an+update+from+the+American+Society+of+Echocardiography+and+the+European+Association+of+Cardiovascular+Imaging.">Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.</a> Journal of the American Society of Echocardiography. 28 (1), 1-39 (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+situ+heart+perfusion.">Assessment of donor heart viability during ex situ heart perfusion.</a> Canadian Journal of Physiology and Pharmacology. 93 (10), 893-901 (2015).</li><li>Hatami, 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=Myocardial+functional+decline+during+prolonged+ex+situ+heart+perfusion.">Myocardial functional decline during prolonged ex situ heart perfusion.</a> Annals of Thoracic Surgery. 108 (2), 499-507 (2021).</li><li>Hatami, 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=The+position+of+the+heart+during+normothermic+ex+situ+heart+perfusion+is+an+important+factor+in+preservation+and+recovery+of+myocardial+function.">The position of the heart during normothermic ex situ heart perfusion is an important factor in preservation and recovery of myocardial function.</a> American Society of Artificial Internal Organs Journal. 67 (11), 1222-1231 (2021).</li><li>Hatami, 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=Normothermic+ex+situ+heart+perfusion+in+working+mode:+assessment+of+cardiac+function+and+metabolism.">Normothermic ex situ heart perfusion in working mode: assessment of cardiac function and metabolism.</a> Journal of Visualized Experiments. (143), e58430 (2019).</li><li>Tchouta, 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=Twenty-four-hour+normothermic+perfusion+of+isolated+ex+situ+hearts+using+plasma+exchange.">Twenty-four-hour normothermic perfusion of isolated ex situ hearts using plasma exchange.</a> Journal of Thoracic and Cardiovascular Surgery. 164 (1), 128-138 (2020).</li><li>Ribeiro, R., 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=Comparing+donor+heart+assessment+strategies+during+ex+situ+heart+perfusion+to+better+estimate+posttransplant+cardiac+function.">Comparing donor heart assessment strategies during ex situ heart perfusion to better estimate posttransplant cardiac function.</a> Transplantation. 104 (9), 1890-1898 (2020).</li><li>Guihaire, 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=Are+pressure-volume+loops+relevant+for+hemodynamic+assessment+during+ex+vivo+heart+perfusion.">Are pressure-volume loops relevant for hemodynamic assessment during ex vivo heart perfusion.</a> Journal of Heart and Lung Transplantation. 39 (10), 1165-1166 (2020).</li><li>Hamed, 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=Serum+lactate+is+a+highly+sensitive+and+specific+predictor+of+post+cardiac+transplant+outcomes+using+the+Organ+Care+System.">Serum lactate is a highly sensitive and specific predictor of post cardiac transplant outcomes using the Organ Care System.</a> Journal of Heart and Lung Transplantation. 28 (2), 71 (2009).</li></ol>

There are some critical steps to consider in the NESP protocol. In situ preliminary assessment of the heart remained important, especially considering the aortic valve that should not present with significant aortic regurgitation (grade 2 or more); otherwise, the resuscitation of the heart will be compromised during the Langendorff period because of impaired coronary perfusion and myocardial ischemia. The initiation of the WM after Langendorff perfusion was a challenging maneuver, requiring at least two persons ...

Heart transplantation is the gold standard treatment for advanced heart failure, but is limited by current organ shortage1. A growing number of donor hearts with extended criteria (age &gt;45 years, cardiovascular risk factors, prolonged low flow, acute left ventricular dysfunction secondary to catecholaminergic storm) are allocated with an increased risk of primary graft failure2. Moreover, hearts donated after controlled circulatory death (DCD) may be presented with myocardial injury secondary to prolonged warm ischemia3. Therefore, there is a need for a better assessment of these donor hearts before transplantation, especially to evaluate their eligibility for heart transplantation4,5. 
Normothermic ex situ perfusion (NESP) preserves the beating heart using warm oxygenated blood. The only commercially available device for NESP preserves the heart in a non-working state (Langendorff mode). This approach was initially applied to expand the preservation of the graft beyond the critical 4 h period of cold ischemia6. Another major advantage of this technology is to provide continuous assessment of myocardial viability based on lactate concentration in the perfusate6. However, this biochemical assessment has never been correlated with post-transplant outcomes to date. Similarly, Langendorff mode for NESP does not allow for hemodynamic and functional evaluation of the heart prior to transplantation. Some authors have reported the potential benefit of intracardiac catheterization during NESP to predict myocardial recovery after transplantation7.
The present report aims to provide a reproducible methodology to evaluate donor heart performance during NESP. We modified the circuit to allow for working mode perfusion and, therefore, for the acquisition of noninvasive functional variables with epicardial echocardiography. Myocardial work index, a load-independent variable, was recorded using pressure-strain loops. We investigated the relationships between myocardial work and hemodynamic variables obtained from intracardiac conductance catheterization.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3T Heater Cooler System</td>
			<td>Liva Nova, Ch&#226;tillon, France</td>
			<td>IM-00727 A</td>
			<td>Extracorporeal Heater Cooler device</td>
		</tr>
		<tr>
			<td>4-0 polypropylene suture</td>
			<td>Peters, bobigny, France</td>
			<td>20S15B</td>
			<td>sutures</td>
		</tr>
		<tr>
			<td>5-0 polypropylene suture</td>
			<td>Peters, bobigny, France</td>
			<td>20S10B</td>
			<td>sutures</td>
		</tr>
		<tr>
			<td>Adenosine</td>
			<td>Efisciens BV, Rotterdam, Netherlands</td>
			<td>9088309</td>
			<td>Drugs for the ex-vivo perfusion</td>
		</tr>
		<tr>
			<td>Adrenaline</td>
			<td>Aguettant, Lyon, France</td>
			<td>600040</td>
			<td>Drugs for the ex-vivo perfusion</td>
		</tr>
		<tr>
			<td>Atracurium</td>
			<td>Pfizer Holding France, Paris, France</td>
			<td>582547</td>
			<td>Drugs for the induction of the anesthesia</td>
		</tr>
		<tr>
			<td>DeltaStream</td>
			<td>Fresenius Medical Care, L&#8217;Arbresle, France</td>
			<td>MEH2C4024</td>
			<td>Extracorporeal blood pump</td>
		</tr>
		<tr>
			<td>EKG epicardial electrodes</td>
			<td>Cardinal Health LLC, Waukegan, Illinois, USA</td>
			<td>31050522</td>
			<td>EKG detection electrodes</td>
		</tr>
		<tr>
			<td>External pacemaker</td>
			<td>Medtronic Inc. Minneapolis, Minneapolis, USA</td>
			<td>5392</td>
			<td>Pacemaker device</td>
		</tr>
		<tr>
			<td>Glucose 5%</td>
			<td>B.Braun Melsungen AG, Melsungen, Germany</td>
			<td>3400891780017</td>
			<td>Drugs for the priming solution</td>
		</tr>
		<tr>
			<td>Heart Perfusion Set, Organ Care System</td>
			<td>Transmedics, Andover, MA, USA</td>
			<td>Ref#1200</td>
			<td>Normothermic ex-vivo heart perfusion device</td>
		</tr>
		<tr>
			<td>Intellivue MX550</td>
			<td>Philips Healthcare, Suresnes, France</td>
			<td>NA</td>
			<td>Permanent monitoring system</td>
		</tr>
		<tr>
			<td>Istat 1</td>
			<td>Abbott, Chicago, Ill, USA</td>
			<td>714336-03O</td>
			<td>Blood Analyzer machine</td>
		</tr>
		<tr>
			<td>Labchart</td>
			<td>AD Instruments Ltd, Paris, France</td>
			<td>LabChart&#160;v8.1.21</td>
			<td>Pressure Volume loops aquisition software</td>
		</tr>
		<tr>
			<td>Magnesium</td>
			<td>Aguettant, Lyon, France</td>
			<td>564 780-6</td>
			<td>Drugs for the cardioplegia</td>
		</tr>
		<tr>
			<td>Magnesium Sulfate</td>
			<td>Aguettant, Lyon, France</td>
			<td>600111</td>
			<td>Drugs for the cardioplegia</td>
		</tr>
		<tr>
			<td>Mannitol 20%</td>
			<td>Macopharma, Mouvoux, France</td>
			<td>3400891694567.00</td>
			<td>Drugs for the cardioplegia</td>
		</tr>
		<tr>
			<td>Methylprednisolone</td>
			<td>Mylan S.A.S, Saint Priest, France</td>
			<td>400005623</td>
			<td>Drugs for the priming solution</td>
		</tr>
		<tr>
			<td>Millar Conductance Catheter</td>
			<td>AD Instruments Ltd, Paris, France</td>
			<td>Ventri-Cath 507</td>
			<td>Pressure Volume loops conductance catheter</td>
		</tr>
		<tr>
			<td>MWI software</td>
			<td>General Electric Healthcare, Chicago, Ill, USA</td>
			<td>NA</td>
			<td>software used for the Ultrasound echocardiographic machine</td>
		</tr>
		<tr>
			<td>Orotracheal probe</td>
			<td>Smiths medical ASD, Inc., Minneapolis, Minneapolis, USA</td>
			<td>100/199/070</td>
			<td>probe for the intubation during anesthesia</td>
		</tr>
		<tr>
			<td>Potassium chloride 10%</td>
			<td>B.Braun Melsungen AG, Melsungen, Germany</td>
			<td>3400892691527.00</td>
			<td>Drugs for the cardioplegia</td>
		</tr>
		<tr>
			<td>Propofol</td>
			<td>Zoetis France, Malakoff, France</td>
			<td>8083511</td>
			<td>Drugs for the induction of the anesthesia</td>
		</tr>
		<tr>
			<td>Quadrox-I small Adult Oxygenator</td>
			<td>Getinge, G&#246;teborg, Sweden</td>
			<td>BE-HMO 50000</td>
			<td>Extracorporeal blood oxygenator</td>
		</tr>
		<tr>
			<td>Ringer solution</td>
			<td>B.Braun Melsungen AG, Melsungen, Germany</td>
			<td>DKE2323</td>
			<td>Drugs for the cardioplegia</td>
		</tr>
		<tr>
			<td>Sodium Bicarbonate</td>
			<td>Laboratoire Renaudin, itxassou, France</td>
			<td>3701447</td>
			<td>Drugs for the cardioplegia</td>
		</tr>
		<tr>
			<td>Sodium chloride</td>
			<td>Aguettant, Lyon, France</td>
			<td>606726</td>
			<td>Drugs for the priming solution</td>
		</tr>
		<tr>
			<td>Swan Ganz Catheter</td>
			<td>Merit Medical, south jordan, utah, USA</td>
			<td>5041856</td>
			<td>Right pressure and cardiac output probe</td>
		</tr>
		<tr>
			<td>Tiletamine</td>
			<td>Virbac France, Carros, France</td>
			<td>3597132126021.00</td>
			<td>Drugs for the induction of the anesthesia</td>
		</tr>
		<tr>
			<td>Transesophagus probe (3&#8211;8 MHz 6VT)</td>
			<td>General Electric Healthcare, Chicago, Ill, USA</td>
			<td>NA</td>
			<td>Ultrasound echocardiographic transesophagus probe</td>
		</tr>
		<tr>
			<td>Vivid E95 ultraSound Machine</td>
			<td>General Electric Healthcare, Chicago, Ill, USA</td>
			<td>NA</td>
			<td>Ultrasound echocardiographic machine</td>
		</tr>
		<tr>
			<td>Xyloca&#239;ne 2%</td>
			<td>Aspen, Reuil-malmaison, France</td>
			<td>600550</td>
			<td>Drugs for the cardioplegia</td>
		</tr>
		<tr>
			<td>Zolazepam</td>
			<td>Virbac France, Carros, France</td>
			<td>3597132126021.00</td>
			<td>Drugs for the induction of the anesthesia</td>
		</tr>
	</tbody>
</table>

functional assessment of the donor heart during ex situ perfusion: insights from pressure-volume loops and surface echocardiography

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the allocation of a growing number of donor hearts with extended criteria. These marginal grafts are associated with a high risk of primary graft failure and may benefit from ex situ perfusion before transplant. This technology allows for extended organ preservation using warm oxygenated blood perfusion with continuous metabolic monitoring. The only NESP device currently available for clinical practice perfuses the organ in an unloaded non-working state, which does not allow for functional assessment of the beating heart. We therefore developed an original platform of NESP in working mode conditions with adjustment of left ventricular preload and afterload. This protocol was applied in porcine hearts. Ex situ functional assessment of the heart was achieved with intracardiac conductance catheterization and surface echocardiography. Along with a description of the experimental protocol, we herein report the main results, as well as pearls and pitfalls associated with the acquisition of pressure-volume loops and myocardial power during NESP. Correlations between hemodynamic findings and ultrasound variables are of major interest, especially for further rehabilitation of donor hearts before transplantation. This protocol aims to improve the assessment of donor hearts to both increase the donor pool and reduce the incidence of primary graft failure.

We herein described a NESP protocol in a monoventricular working state, using a modified heart perfusion module usually employed in clinical practice for Langendorff perfusion of the donor heart before transplantation. This piglet model of NESP using the present custom module was developed in 2019. The modifications of the circuit were minor, as most of the perfusion circuit was re-used for experiments. The cap of the module provided a flexible and waterproof membrane to protect the heart during transportation. It also a...

Watch this Scientific Journal Video about Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography at JoVE.com

Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography

A reliable noninvasive approach for functional assessment of the donor heart during normothermic ex situ heart perfusion (NESP) is lacking. We herein describe a protocol for ex situ assessment of myocardial performance using the epicardial echocardiography and conductance catheter method.

Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the ...

Research

JoVE Journal

Medicine

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts

Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage, Assessment, and Repair of Marginal Liver Grafts

The success of liver transplantation has resulted in a dramatic organ shortage. In most transplant regions 20-30% of patients on the waiting list for ...

Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

Method of Isolated Ex Vivo Lung Perfusion in a Rat Model: Lessons Learned from Developing a Rat EVLP Program

The number of acceptable donor lungs available for lung transplantation is severely limited due to poor quality. Ex-Vivo Lung Perfusion (EVLP) has allowed ...

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these ...

Ex Situ Normothermic Machine Perfusion of Donor Livers

Ex Situ Normothermic Machine Perfusion of Donor Livers

In contrast to conventional static cold preservation (0-4 &#176;C), ex situ machine perfusion may provide better preservation of donor livers. Continuous ...

Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any ...

Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism

The current standard method for organ preservation (cold storage, CS), exposes the heart to a period of cold ischemia that limits the safe preservation ...

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...