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>
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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.

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	<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>
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</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 ...

Hemodynamic assessment of the heart during isolated Ex situ perfusion is poorly described. This protocol provides a method to evaluate Ex situ cardiac performances in working mode. Our approach co compares invasive PV loop technique to epicardial echocardiography for functional assessment of their heart during isolated Ex situ perfusion.This approach requires a team experience in Ex situ heart perfusion, along with involvement of a cardiologist trained for transoeosphageal echocardiography. A major concerns in heart transplantation is the risk of primary graft failure. Our approach using epicardial echocardiography provides an assessment of the heart before transplant during Ex situ perfusion.This non-invasive method could be written applied during Ex situ heart perfusion prior to transplant. Begin by placing four zero polypropylene sutures on the right atrium and on the ascending aorta of the anesthetized animal to secure cannulation with tourniquets. Infuse heparin and carefully dissect the aortic root.Then insert a double staged venous cannula in the right atrium for blood collection and a single lumen cannula in the ascending aorta for cardioplegia infusion. After isolating the superior and inferior vena cava connect the venous cannula to a blood collecting bag containing 10, 000 units of unfractionated heparin. Place the piglet body in the Trendelenberg position to improve blood drainage into the collecting bag.Proceed to heart procurement keeping two centimeters of the pulmonary trunk along with the left atrium posterior wall. Place the heart in a four degree Celsius saline solution and separate the ascending aorta from the pulmonary trunk. Verify that the aortic valve and the coronary ostea are not injured.Insert four pledged four zero polypropylene stitches, five millimeters below the distal section of the ascending aorta and insert the infusion cannula into the aorta. Tighten a hose clamp around the aorta to secure the cannula. Insert a drainage cannula into the pulmonary trunk and secure it with a three zero polypropylene running suture.Close the inferior and superior vena cava with five zero polypropylene running sutures. Close the left atrium posterior wall with a four zero polypropylene running suture. Insert a left vent cannula through the posterior wall of the left atrium and snare a tourniquet around.Insert a preloaded cannula into the left atrial appendage and snare a tourniquet around. Decrease the pump flow to 200 milliliters per minute. Connect the heart to the aortic connector after de-airing the connector.Adjust the aortic pressure to 30 millimeters of mercury at room temperature. During resuscitation, perform a smooth cardiac massage until a sinus rhythm is restored. Slowly increase the pump flow within 15 to 25 minutes by steps of 50 milliliters per minute to achieve an aortic pressure of 65 millimeters of mercury.At the same time, increase the profused temperature by steps of two to four degrees Celsius to reach 37 degrees Celsius. Once the required aortic pressure and profuse a temperature is reached deliver an electric shock at five joules if needed and repeat until the sinus rhythm is restored. Secure an epicardial electrode to the right ventricular posterior wall and connect to an external pacemaker.Then connect the pulmonary cannula to the coronary flow line. Open the preload line and adjust the pump flow to ensure stable filling of the preload reservoir. Open the aortic afterload line and clamp the main line of the circuit used for Langandorf perfusion.The afterload reservoir will be progressively filled up. Ensure the drainage of the reservoir by an overflow line which brings the profused back to the main reservoir of the circuit. Initiate the infusion of dobutamine at 0.04 milligrams per minute.Then remove the vent. Clean the seven French pigtail conductance catheter with saline solution and connect it to the hardware interface. Gently push the catheter into the introducer 8 French sheath previously inserted through the left atrium roof to be aligned with the mitral valve.Stop epicardial pacing of the heart to avoid interference with the conductance signal. Record data in a steady state when the signal is stabilized. Select a series of 10 consecutive loops and open the analysis software.To obtain the end systolic and end diastolic pressure volume relation, record the signal during preload occlusion. Gradually clamp the atrial profusion line until preload reduction is effective. Then slowly release the clamp.After placing a sterile drape around the heart apply the probe to the upper wall of the left atrium and manually rotate the transducer until a four chamber view is obtained. Then run the ultrasound probe monitor to obtain three and two chamber views. To assess the MWI proceed to the acquisition of four, three, and two chamber views and record simultaneous arterial pressure.Assess the global longitudinal strain using these views and open MWI software. Use the invasive blood pressure detected by the external sensor on the perfusion circuit using loop acquisition. Manually notify the software of the exact opening and closing times of the aortic and mitral valves.Echocardiographic assessment during working mode perfusion was performed in the custom setup. All three left ventricular views were obtained at any time point in all experiments. Mean left ventricular ejection fraction global longitudinal strain and M W I was approximately 40.8%minus 8.0%and 65 millimeters of mercury respectively.Hemodynamic parameters were assessed by either conductance catheter or surface echocardiography during work mode perfusion. During the work mode perfusion a significant decrease was observed in M W I over time in all experiments. A similar decrease was observed in the cardiac output and other parameters related to the end systolic pressure volume relationship.The echocardiographic probe has to be located on the roof of the left atrium. Stable requisition of at least three to six myocardial cycles must be performed correctly. A metabolic assessment of the myocardial tissue and the endothelial function would bring a complimentary evaluation of the heart graft during ex situ heart perfusion to optimize perfusion settings.

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