Evaluation of 10°C as the Optimal Storage Temperature for Injured Donor Lungs in a Large Animal Transplant Model

Purpose

Recent work has challenged cold static storage at 4°C to remain the standard for donor lung preservation (Ali A, Science Tr Med 2021). However, this was performed using ideal lungs, not reflecting the clinical reality of donor lungs with underlying injury.

Methods

In Yorkshire pigs, a moderate degree of lung injury was induced by instillation of gastric juice (5ml/segment). Donor lungs (n=5/group) were then procured and blindly randomized to storage at 4°C or at 10°C for 12 hours. A third group included minimal cold storage at 4°C. A left lung transplant was performed followed by 4 hours of functional assessment (Fig. 1A). Tissue biopsies and plasma were collected to evaluate mitochondrial health and metabolic mechanisms. Finally, histological samples were obtained to measure the degree of lung injury and cell death.

Results

During reperfusion, lungs stored at 10°C showed significantly better oxygenation when compared to 4°C demonstrated via selective pulmonary vein gases (Fig 1B, 2h, P = 0.027; 3h, P = 0.008; 4h, P = 0.004) and exclusion of the contralateral native lung (Fig 1C, 343 ± 43 vs 128 ± 76 mmHg, P = 0.04). This group also tended to better dynamic compliances (Fig 1D, P = 0.06). Post-reperfusion tissue showed lower levels of IL-1β (Fig 1E, P = 0.026). Circulating cell-free mtDNA within the recipient plasma was significantly lower for lungs stored at 10°C in comparison to those stored with minimal periods (Fig 1F, P = 0.048). Histology revealed lower signs of acute lung injury (Fig 1G, P = 0.036) and significantly less apoptotic cell death (Fig 1H, P = 0.048) in the 10°C group vs 4°C. In general, storage of lungs at 10°C showed a tendency to improved graft quality, even when compared to minimal cold ischemia.

Conclusion

We demonstrate 10°C to be a superior storage condition in the setting of injured donor lungs. Interestingly, prolonged preservation at 10°C led to better outcomes even when compared to short ischemia. This could be due to reparative process occurring with enhanced mitochondrial health.