非原位灌注期间供体心脏的功能评估：来自压力-容量环和表面超声心动图的见解
1Laboratory of Preclinical Research, Department of Research and Innovation,Groupe Hospitalier Paris Saint Joseph, 2Inserm UMR S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies, Marie Lannelongue Hospital,Groupe Hospitalier Paris Saint Joseph, 3Department of Cardiac Surgery,Marie Lannelongue Hospital
Summary
缺乏可靠的无创方法，用于在正常变温非 原位 心脏灌注（NESP）期间对供体心脏进行功能评估。我们在此描述了使用心外膜超声心动图和电导导管方法对心肌性能进行 异位 评估的方案。
Abstract
心脏移植仍然是晚期心力衰竭的金标准治疗。然而，目前的关键器官短缺导致越来越多的捐赠者心脏被分配，并具有扩展标准。这些边缘移植物与原发性移植失败的高风险相关，移植前的 异位 灌注可能有益。该技术允许使用温氧血液灌注和连续代谢监测来扩展器官保存。目前唯一可用于临床实践的NESP设备在卸载的非工作状态下灌注器官，这不允许对跳动的心脏进行功能评估。因此，我们开发了一种在工作模式下的NESP原始平台，可以调整左心室前负荷和后负荷。该方案应用于猪心。通过心内导尿术和表面超声心动图实现心脏的 离位 功能评估。除了对实验方案的描述外，我们在此报告了主要结果，以及与NESP期间获得压力 – 容量环和心肌功率相关的珍珠和陷阱。血流动力学发现与超声变量之间的相关性是主要兴趣，特别是对于移植前供体心脏的进一步康复。该协议旨在改善对供体心脏的评估，以增加供体库并降低原发性移植失败的发生率。
Introduction
心脏移植是晚期心力衰竭的金标准治疗，但受到当前器官短缺的限制1。越来越多的供体心脏具有扩展标准（年龄>45岁、心血管危险因素、长期低流量、继发于儿茶酚胺能危象的急性左心室功能障碍）被分配，原发性移植失败的风险增加2。此外，在控制循环死亡（DCD）后捐赠的心脏可能会出现继发于长期温缺血的心肌损伤3。因此，有必要在移植前对这些供体心脏进行更好的评估，特别是评估它们是否有资格进行心脏移植4，5。
常母异 位 灌注（NESP）使用温氧血液保存跳动的心脏。NESP的唯一市售设备将心脏保持在非工作状态（朗根道夫模式）。这种方法最初用于将移植物的保存扩大到冷缺血的关键4小时期之后6。该技术的另一个主要优点是根据灌注液中的乳酸浓度提供心肌活力的连续评估6。然而，迄今为止，这种生化评估从未与移植后的结果相关。同样，NESP的朗根多夫模式不允许在移植前对心脏进行血流动力学和功能评估。一些作者报道了NESP期间心内导管插入术对预测移植后心肌恢复的潜在益处7。
本报告旨在提供一种可重复的方法来评估NESP期间供体的心脏性能。我们修改了电路以允许工作模式灌注，从而通过心外膜超声心动图获取无创功能变量。心肌功指数是一个与负荷无关的变量，使用压力-应变环路记录。我们研究了心肌功与心内导尿获得的血流动力学变量之间的关系。
Protocol
本协议已获得当地动物实验伦理委员会和动物福利机构委员会（APAFIS#30483-2021031811339219 v1，法国巴黎萨克雷大学动物伦理委员会）的批准。动物按照美国国立卫生研究院制定的实验动物护理和使用指南和国家医学研究学会制定的实验动物护理原则进行处理。 注意：外科手术是在严格的无菌下进行的，使用与人类相同的技术。实验程序包括大白仔猪（45-60公斤），并在全身麻醉?…
Representative Results
我们在此描述了一种处于单心室工作状态的NESP方案，使用通常在临床实践中采用的改良心脏灌注模块，用于移植前供体心脏的Langendorff灌注。这种使用当前定制模块的NESP仔猪模型是在2019年开发的。电路的修改很小，因为大部分灌注回路被重新用于实验。模块的盖子提供了一层柔性和防水膜，在运输过程中保护心脏。它还允许在无菌环境中进行表面超声心动图检查。临床实践中混合血液和灌注液?…
Discussion
NESP协议中需要考虑一些关键步骤。对心脏进行 原位 初步评估仍然很重要，特别是考虑到主动脉瓣不应出现明显的主动脉瓣反流（2 级或以上）;否则，由于冠状动脉灌注受损和心肌缺血，在朗根多夫期间心脏的复苏将受到影响。朗根多夫灌注后启动WM是一项具有挑战性的操作，至少需要两个人来调节预负荷储液器的填充、泵流量、左心房压力和主动脉流出管。一旦达到乳酸的代谢有效心肌?…
Divulgations
The authors have nothing to disclose.
Acknowledgements
乔治·洛佩兹研究所， 利苏， 69380， 法国
克劳迪娅·拉塞尔达，通用电气医疗保健，法国布克
Materials
| 3T Heater Cooler System | Liva Nova, Châtillon, France | IM-00727 A | Extracorporeal Heater Cooler device |
| 4-0 polypropylene suture | Peters, bobigny, France | 20S15B | sutures |
| 5-0 polypropylene suture | Peters, bobigny, France | 20S10B | sutures |
| Adenosine | Efisciens BV, Rotterdam, Netherlands | 9088309 | Drugs for the ex-vivo perfusion |
| Adrenaline | Aguettant, Lyon, France | 600040 | Drugs for the ex-vivo perfusion |
| Atracurium | Pfizer Holding France, Paris, France | 582547 | Drugs for the induction of the anesthesia |
| DeltaStream | Fresenius Medical Care, L’Arbresle, France | MEH2C4024 | Extracorporeal blood pump |
| EKG epicardial electrodes | Cardinal Health LLC, Waukegan, Illinois, USA | 31050522 | EKG detection electrodes |
| External pacemaker | Medtronic Inc. Minneapolis, Minneapolis, USA | 5392 | Pacemaker device |
| Glucose 5% | B.Braun Melsungen AG, Melsungen, Germany | 3400891780017 | Drugs for the priming solution |
| Heart Perfusion Set, Organ Care System | Transmedics, Andover, MA, USA | Ref#1200 | Normothermic ex-vivo heart perfusion device |
| Intellivue MX550 | Philips Healthcare, Suresnes, France | NA | Permanent monitoring system |
| Istat 1 | Abbott, Chicago, Ill, USA | 714336-03O | Blood Analyzer machine |
| Labchart | AD Instruments Ltd, Paris, France | LabChart v8.1.21 | Pressure Volume loops aquisition software |
| Magnesium | Aguettant, Lyon, France | 564 780-6 | Drugs for the cardioplegia |
| Magnesium Sulfate | Aguettant, Lyon, France | 600111 | Drugs for the cardioplegia |
| Mannitol 20% | Macopharma, Mouvoux, France | 3400891694567.00 | Drugs for the cardioplegia |
| Methylprednisolone | Mylan S.A.S, Saint Priest, France | 400005623 | Drugs for the priming solution |
| Millar Conductance Catheter | AD Instruments Ltd, Paris, France | Ventri-Cath 507 | Pressure Volume loops conductance catheter |
| MWI software | General Electric Healthcare, Chicago, Ill, USA | NA | software used for the Ultrasound echocardiographic machine |
| Orotracheal probe | Smiths medical ASD, Inc., Minneapolis, Minneapolis, USA | 100/199/070 | probe for the intubation during anesthesia |
| Potassium chloride 10% | B.Braun Melsungen AG, Melsungen, Germany | 3400892691527.00 | Drugs for the cardioplegia |
| Propofol | Zoetis France, Malakoff, France | 8083511 | Drugs for the induction of the anesthesia |
| Quadrox-I small Adult Oxygenator | Getinge, Göteborg, Sweden | BE-HMO 50000 | Extracorporeal blood oxygenator |
| Ringer solution | B.Braun Melsungen AG, Melsungen, Germany | DKE2323 | Drugs for the cardioplegia |
| Sodium Bicarbonate | Laboratoire Renaudin, itxassou, France | 3701447 | Drugs for the cardioplegia |
| Sodium chloride | Aguettant, Lyon, France | 606726 | Drugs for the priming solution |
| Swan Ganz Catheter | Merit Medical, south jordan, utah, USA | 5041856 | Right pressure and cardiac output probe |
| Tiletamine | Virbac France, Carros, France | 3597132126021.00 | Drugs for the induction of the anesthesia |
| Transesophagus probe (3–8 MHz 6VT) | General Electric Healthcare, Chicago, Ill, USA | NA | Ultrasound echocardiographic transesophagus probe |
| Vivid E95 ultraSound Machine | General Electric Healthcare, Chicago, Ill, USA | NA | Ultrasound echocardiographic machine |
| Xylocaïne 2% | Aspen, Reuil-malmaison, France | 600550 | Drugs for the cardioplegia |
| Zolazepam | Virbac France, Carros, France | 3597132126021.00 | Drugs for the induction of the anesthesia |
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Citer Cet Article
Dang Van, S., Brunet, D., Akamkam, A., Decante, B., Guihaire, J. Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography. J. Vis. Exp. (188), e63945, doi:10.3791/63945 (2022).