Optimized cellular perfusate increases lung viability ex vivo and extends the duration of ex vivo lung perfusion.

BACKGROUND

Ex vivo lung perfusion (EVLP) has emerged as a strategy to assess and extend preservation of donor lungs prior to transplantation. However, due to progressive deterioration of the graft, current protocols limit EVLP duration to 10-12 h. We developed an optimized cellular perfusate, DEVOL solution, designed to support multi-day EVLP and evaluated its performance against standard TransMedics OCS perfusate.

METHODS

Porcine lungs were procured, flushed with OCS solution, and perfused using either STANDARD (n=5) or DEVOL (n=5) perfusate supplemented with washed red blood cells. Physiological parameters, perfusate biomarkers, histology, and transcriptomics were assessed throughout extended perfusion. A lung tissue culture system was employed to investigate procurement flush perfusate reperfusion-related cytokine release.

RESULTS

DEVOL-perfused lungs exhibited increased median perfusion survival time compared with STANDARD (36 vs. 12 h). Improved viability was associated with reduced edema and lower endothelial injury markers (PECAM-1, syndecan-1). DEVOL lungs demonstrated transient early rises in pulmonary vascular resistance and IL-10, as well as sustained elevations in IL-17, without evidence of increased tissue injury. Mathematical simulation and cell culture experiments suggest this phenomenon is due in part to rapid calcium influx into DEVOL-perfused lungs following calcium-free OCS flush during procurement.

CONCLUSION

DEVOL perfusate markedly prolongs lung viability during EVLP compared to standard, commercially available perfusate by maintaining oncotic and osmotic balance. Ongoing studies will dissect the contribution of individual DEVOL components to extended perfusion and integrate additional EVLP parameters to elucidate mechanisms underlying late graft failure observed in this study.