Establishment of the Ex Vivo Lung Perfusion System for Application in the Small Animal Model

Background: For patients with end-stage lung disease, lung transplantation (LTx) remains the only life-saving therapy, but it is limited by the shortage of donor organs. Ex vivo perfusion (EVLP) is a new technique to expand the donor pool and significantly improve outcomes after LTx. In addition to LTx, it can also be used for surgical, regenerative and immunomodulatory approaches, as well as tumor and infection therapy. To further analyze this broad spectrum of EVLP applications, we established EVLP for the small animal model.

Methods: Twenty rat lungs (Lewis n = 10; F344 n = 10) were subjected to normothermic EVLP for 2 hours. A protective mode with mechanical ventilation and controlled perfusion was applied, using acellular STEEN (n = 10) or Perfadex Plus solution (n = 10). Ventilation and hemodynamics were monitored and blood gas analyses, cytokines, colloid oncotic pressures, metabolic and biochemical parameters of the perfusate and lung temperatures were determined at different time points. Finally, lung weight gain was quantified and histological examination was performed.

Results: Overall, no major significant differences were observed between the two rat strains. Monitoring of respiration and hemodynamics revealed stable values allowing sufficient perfusion and gas exchange capacity during normothermic EVLP. Other perfusate parameters (e.g. electrolytes, glucose, lactate) indicated constant conditions over time. Colloid oncotic pressure was significantly increased in the Perfadex Plus group, and weight gain was also significantly more pronounced in this group than in the STEEN group. Histological analysis showed intact lung architecture without infarcts.

Conclusion: We were able to demonstrate a stable, reproducible rat EVLP system that represents an attractive platform for further surgical, regenerative, immunomodulatory approaches as well as for tumor and infection therapy.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
13 February 2024