The Effect of Prostaglandin E1 on Pulmonoplegia before and after Ex Vivo Lung Perfusion

Purpose The lungs on ex vivo lung perfusion (EVLP) are kept under suboptimal condition in terms of graft preservation and their status can be compromised against cold ischemia (CI) after EVLP. Prostaglandin E1 (PG) is routinely used for pulmonoplegia against CI in clinical practice, however not used after EVLP. In this study, we investigated the effect of PG on graft preservation for the lungs before and after EVLP. Methods Lewis rats lungs were procured with cold Perfadex and were assigned for 4 different preservation groups: 1) 8h CI, 2) 8h CI with PG, 3) 2h EVLP + 6h CI and 4) 2h EVLP + 6h CI with PG. Lungs in group 3 and 4 were subjected to normothermic EVLP for 2h then kept under 4°C for 6h. PG (30 μg) was intravenously administered into grafts at graft procurement for group 2 and those at 2h EVLP for group 4. After preservation, left lungs in all groups were transplanted orthotopically using cuff technique in syngeneic rats and evaluated 2h after reperfusion. Results The lungs treated with PG on procurement showed better graft function after transplant following 8h CI than those without PG. Also, less inflammation and less endothelial barrier damage were found in PG treated lung tissue than control. However, the lungs treated with PG after EVLP showed worse posttransplant graft quality compared to those with no treatment after EVLP, although there was no difference in EVLP data. Further analysis showed PG depleted energy in the tissue after EVLP. Conclusion Lungs can obtain CI tolerance via a PG-induced protection mechanism that appears to be supported by cellular energy production. Importantly, PG may be unsuitable for post-EVLP pulmonoplegia due to disrupted cellular metabolic environment.