Table 3.
Experimental and clinical studies of machine perfusion of extended criteria donor lung grafts.
| Studies | Model | Primary graft condition, N | MP time (h) | Results and immunological aspects |
|---|---|---|---|---|
| ANIMAL STUDIES | ||||
| Nakajima et al. (81) | Canine HMP after SCS vs. SCS alone followed by 4 h machine reperfusion | DCD; N = 5/group WIT: 4 h CIT: 12 vs. 14 h |
2 | Short-term HMP could resuscitate ischemically damaged DCD lungs and ameliorate IRI. HMP significantly decreased oxidative damage and the production of pro-inflammatory cytokines after reperfusion compared with SCS |
| Mulloy et al. (82) | Porcine NMP vs. SCS vs. SCS + NMP with Tx. Perfusate supplemented with adenosine A2A receptor agonist |
DCD; N = 5/group WIT: 60 min CIT: 4 h (SCS group) |
4 | The adenosine A2A receptor agonist exerts anti-inflammatory effects and reduces IRI when administered to DCD donor lungs during MP |
| Stone et al. (83) | Mice NMP ± A2A receptor agonist vs. SCS without Tx | DCD; N = 10–12/group WIT: 1 h CIT: 1 h |
1 | MP modulates pro-inflammatory genes and reduces pulmonary dysfunction, edema, pro-inflammatory cytokines, and neutrophil numbers in DCD lungs, which are further reduced by A2A receptor agonism |
| Stone et al. (9) | Porcine NMP vs. SCS with Tx | DCD; N = 12 WIT: 65 min CIT: 2 h |
3 | NMP resulted in reduction of donor leukocyte transfer into the recipient, and recipient T cell infiltration of the donor lung was significantly diminished |
| HUMAN STUDIES | ||||
| Stone et al. (36) | NMP without Tx | DCD; N = 7 WIT: 65 min CIT: 3 h |
2 | NMP showed the capacity to remove donor dendritic cell generating non-classical monocytes from graft |
| Nakajima et al. (35) | NMP ± broad-spectrum antibiotic without Tx | DBD with clinically diagnosed lung infection; N = 15 CIT: ~10 h |
12 | The results demonstrated that treatment with antibiotics significantly reduced bronchoalveolar lavage bacterial counts and inflammatory injury by decreasing endotoxin levels and key inflammatory mediators (TNF-α, IL-1β, MIP-1α, MIP-1β) |
| Nakajima et al. (84) | NMP ± MSCs with Tx |
N = 6/group CIT: 24 h |
12 | The administration of MSCs ameliorated ischemic injury in donor lungs during NMP and attenuated the subsequent IRI after Tx |
CIT, cold ischemia time; ECD, extended criteria donor; DCD, donation after circulatory death; HMP, hypothermic MP; IL, interleukin; IRI, ischemia–reperfusion injury; MIP, macrophage inflammatory protein; MP, machine perfusion; MSCs, mesenchymal stromal cells; NMP, normothermic MP; SCS, static cold storage; TNF, tumor necrosis factor; Tx, transplantation; WIT, warm ischemia time; DBD, donor after brain death.