Negative Pressure Ventilation Ex-Situ Lung Perfusion Preserves Porcine and Human Lungs for 36-Hours

IF 1.9 4区医学 Q2 SURGERY Clinical Transplantation Pub Date : 2025-01-17 DOI:10.1111/ctr.70083

Keir Forgie, Sayed Himmat, Katie Du, Alynne Ribano, Abeline Watkins, Nicholas M. Fialka, Sanaz Hatami, Mubashir Khan, Xiuhua Wang, Ryan Edgar, Katie-Marie Buswell-Zuk, Darren H. Freed, Jayan Nagendran

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Abstract

Introduction

Preclinically, 24-hour continuous Ex-Situ Lung Perfusion (ESLP) is the longest duration achieved in large animal models and rejected human lungs. Here, we present our 36-hour Negative Pressure Ventilation (NPV)-ESLP protocol applied to porcine and rejected human lungs.

Methods

Five sets of donor domestic pig lungs (45-55 kg) underwent 36-hour NPV-ESLP. Two sets of clinically rejected human lungs were preserved on 36-hour NPV-ESLP. Graft function was assessed via physiologic parameters, edema formation, and cytokine profiles.

Results

Porcine and human lung function was stable with mean partial pressure of oxygen divided by the fraction of inspired oxygen (PaO2/FiO2; PF) ratios throughout preservation of 473±11.79 and 554.7±13.26, respectively (mean±standard error of the mean). In porcine lungs, mean compliance (Cdyn) during ESLP was 33.96±2.18, pulmonary artery pressure (PAP) 13.03±0.53, and pulmonary vascular resistance (PVR) 481.20 ±21.86. In human lungs, mean Cdyn was 82.68±3.54, PAP 6.00±0.33, and PVR 184.00±9.71. Average percentage weight-gain was 34.47±13.22 in porcine lungs and 116.3±6.65 in rejected human lungs.

Conclusion

NPV-ESLP can preserve porcine lungs and human lungs for 36-hours with acceptable physiologic function. Greater weight-gain in the human lungs is likely due to prolonged ischemic time prior to ESLP and use of an acellular perfusate. Continuous 36-hour NPV-ESLP could support therapies for endothelial protection and mitigate fluid accumulation.

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负压通气离体肺灌注保存猪和人肺36小时。

临床前，24小时连续离体肺灌注（ESLP）是在大型动物模型和排斥的人肺中实现的最长持续时间。在这里，我们提出了36小时负压通气(NPV)-ESLP方案，适用于猪和排斥的人肺。方法：5组供体家猪肺（45 ~ 55 kg）行36小时NPV-ESLP。两组临床排斥的人肺在NPV-ESLP上保存36小时。通过生理参数、水肿形成和细胞因子谱评估移植物功能。结果：猪和人肺功能稳定，平均氧分压除以吸入氧分数(PaO2/FiO2；PF)在整个保存过程中的比值分别为473±11.79和554.7±13.26（平均值±标准误差）。猪肺ESLP期间的平均顺应性（Cdyn）为33.96±2.18，肺动脉压（PAP）为13.03±0.53，肺血管阻力（PVR）为481.20±21.86。人肺平均Cdyn为82.68±3.54，PAP为6.00±0.33，PVR为184.00±9.71。猪肺的平均增重百分比为34.47±13.22，人肺的平均增重百分比为116.3±6.65。结论：NPV-ESLP可保存猪肺和人肺36小时，并具有良好的生理功能。人体肺部更大的体重增加可能是由于ESLP前缺血时间延长和使用脱细胞灌注所致。连续36小时的NPV-ESLP可以支持内皮保护和减轻液体积聚的治疗。

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来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.