Normothermic ex vivo lung perfusion using a developed solution followed by orthotopic left lung transplantation (experimental study)

I. Pashkov, S. Gautier, V. Bogdanov, D. Oleshkevich, D. M. Bondarenko, N. Mozheiko, N. S. Bunenkov, N. V. Grudinin
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Abstract

The continued unavailability of adequate organs for transplantation to meet the existing demand has resulted in a major challenge in transplantology. This is especially felt in lung transplantation (LTx). LTx is the only effective method of treatment for patients with end-stage lung diseases. Normothermic ex vivo lung perfusion (EVLP) has been proposed to increase the number of donor organs suitable for transplant – EVLP has proven itself in a number of clinical trials. The ability to restore suboptimal donor lungs, previously considered unsuitable for transplantation, can improve organ functionality, and thus increase the number of lung transplants. However, widespread implementation of ex vivo perfusion is associated with high financial costs for consumables and perfusate.Objective: to test the developed solution on an ex vivo lung perfusion model, followed by orthotopic LT under experimental conditions.Materials and methods. The experiment included lung explantation stages, static hypothermic storage, EVLP and orthotopic left LTx. Perfusion was performed in a closed perfusion system. We used our own made human albumin-based perfusion solution as perfusate. Perfusion lasted for 2 hours, and evaluation was carried out every 30 minutes. In all cases, static hypothermic storage after perfusion lasted for 4 hours. The orthotopic single-lung transplantation procedure was performed using assisted circulation, supplemented by membrane oxygenation. Postoperative follow-up was 2 hours, after which the experimental animal was euthanized.Results. Respiratory index before lung explantation was 310 ± 40 mmHg. The PaO2/FiO2 ratio had positive growth dynamics throughout the entire EVLP procedure. Oxygenation index was 437 ± 25 mm Hg after 120 minutes of perfusion. Throughout the entire EVLP procedure, there was a steady decrease in pulmonary vascular resistance (PVR). Initial PVR was 300 ± 100 dyn×s/cm5; throughout the EVLP, PVR tended to fall, reaching 38,5 ± 12 dyn×s/cm5 at the end of perfusion.Conclusion. A safe and effective EVLP using our perfusate is possible. The developed orthotopic left lung transplantation protocol under circulatory support conditions, supplemented by membrane oxygenation, showed it is efficient and reliable.
体外正常肺灌注后左肺原位移植(实验研究)
由于仍然没有足够的移植器官来满足现有的需求,这对移植学造成了重大挑战。这在肺移植(LTx)中尤其明显。LTx是终末期肺部疾病患者唯一有效的治疗方法。常温离体肺灌注(EVLP)已被提出用于增加适合移植的供体器官数量,EVLP已在许多临床试验中得到证明。先前被认为不适合移植的次优供体肺的恢复能力可以改善器官功能,从而增加肺移植的数量。然而,体外灌注的广泛实施与耗材和灌注液的高财务成本有关。目的:在离体肺灌注模型上验证所研制的溶液,并在实验条件下进行原位肝移植。材料和方法。实验包括肺移植阶段、静态低温储存、EVLP和原位左LTx。灌注在封闭的灌注系统中进行。我们用自己研制的人白蛋白基灌注液作为灌注液。灌注2小时,每30分钟评估一次。所有病例均在灌注后静置低温保存4小时。原位单肺移植手术采用辅助循环,辅以膜氧合。术后随访2小时,对实验动物实施安乐死。肺移植前呼吸指数为310±40 mmHg。在整个EVLP过程中,PaO2/FiO2比率呈正增长动态。灌注120 min后氧合指数为437±25 mm Hg。在整个EVLP过程中,肺血管阻力(PVR)稳步下降。初始PVR为300±100 dyn×s/cm5;在整个EVLP过程中,PVR呈下降趋势,灌注结束时PVR达到38.5±12 dyn×s/cm5。使用我们的灌注液进行安全有效的EVLP是可能的。在循环支持条件下发展的原位左肺移植方案,辅以膜氧合,证明是有效和可靠的。
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