Impact of Normothermic Regional Perfusion During DCD Recovery on Lung Allograft Function: A Preclinical Study

Background: Normothermic regional perfusion (NRP) has been growing as a novel procurement strategy after circulatory death (donation after circulatory death (DCD)) in the context of heart transplantation. However, the impact of NRP on lung graft viability is largely unknown. We sought to determine lung function after thoraco-abdominal NRP (TA-NRP) in a clinically relevant porcine DCD model. Methods: Donor domestic pigs underwent hypoxic cardiac arrest to simulate DCD procurement and were randomly allocated to either 1-hour resuscitation on TA-NRP (n = 4) or direct lung procurement (direct procurement and perfusion (DPP), n = 4). All lungs were placed on ex-vivo lung perfusion (EVLP) and evaluated for 3 hours to assess functional outcome parameters and suitability for transplantation. Results: After 1 hour of TA-NRP, cardiopulmonary bypass was weaned, and mean systemic PaO2/fraction of inspired oxygen was 418 ± 76 mm Hg, which was comparable to baseline (467 ± 41, p = 0.41). No significant differences were seen between the groups during EVLP, except for a higher pulmonary artery pressure in the TA-NRP group at 3 hours of EVLP (19.7 ± 1.5 vs 14.7 ± 2.1 mm Hg, p = 0.02). Perfusate inflammatory cytokines levels of IL-6 and IL-8 were higher at the first hour of EVLP in the TA-NRP group; however, these differences were not sustained as levels were similar by the last hour of EVLP. There were no differences in histology, cytokines, or metabolic profile of the TA-NRP lungs compared to DPP. Conclusions: TA-NRP porcine lungs met functional criteria to proceed to transplantation and demonstrated no significant histological, cytokine, and metabolic differences when compared to DPP porcine lungs. This study highlights the value of considering TA-NRP lungs for transplant with well-established protocols.