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

IntroductionPreclinically, 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.MethodsFive 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.ResultsPorcine 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.ConclusionNPV-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.