Research progress on preservation injury in donor lungs from donation after circulatory death_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LI Zeyu , WANG Yufei , WU Yongkun ,  GUO Zhanlin

Department of Thoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, P. R. China;

Corresponding?author：

GUO Zhanlin, Email: nmggzl0259@163.com

Keywords：

Donation after circulatory death; donor lung preservation; functional warm ischemia; mitochondrial homeostasis; controlled hypothermic storage; ex vivo lung perfusion; lung transplantation

DOI：

10.7507/1007-4848.202605028

Video：

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Abstract Full text Figures/Tables Video References Cited by

Donor lungs from donation after circulatory death (DCD) are an important supplementary source for expanding the donor pool in lung transplantation. Compared with donor lungs from donation after brain death (DBD), DCD donor lungs undergo hypoventilation, hypoxia, hypoperfusion, circulatory arrest, and functional warm ischemia after withdrawal of life-sustaining treatment. Consequently, varying degrees of pre-preservation injury may already be present before cold flushing and static hypothermic preservation and may further accumulate during preservation, rewarming, and reperfusion. Disruption of mitochondrial homeostasis may serve as a key link between these continuous injury phases and reperfusion vulnerability. The major mechanisms include impaired recovery of oxidative phosphorylation, metabolic reprogramming, increased reactive oxygen species generation, calcium dyshomeostasis, mitochondrial permeability transition pore opening, and dysregulation of mitochondrial dynamics and quality control. These alterations intersect with apoptosis, necroptosis, pyroptosis, ferroptosis, and other lytic cellular injury phenotypes. In recent years, controlled hypothermic storage at 10°C, ex vivo lung perfusion-based assessment and repair, optimization of procurement workflows, and metabolic interventions have provided new directions for DCD donor lung preservation and utilization. However, a substantial proportion of the available mechanistic evidence is derived from general donor lungs, marginal donor lungs, or models of lung ischemia-reperfusion injury and cannot be directly extrapolated to DCD lungs with different injury burdens. This review summarizes the continuous process of DCD donor lung preservation injury, mitochondrial homeostasis disruption, related cellular injury phenotypes, and preservation and dynamic assessment strategies. Evidence directly derived from DCD lungs is distinguished from lung transplantation-related evidence and cross-organ mechanistic references. These findings may inform donor-lung protection and optimization of lung transplantation workflows involving DCD donors.

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3. Van Raemdonck D, Keshavjee S, Levvey B, et al. Donation after circulatory death in lung transplantation: five-year follow-up from ISHLT Registry[J]. J Heart Lung Transplant, 2019, 38(12): 1235-1245.
4. Li SS, Funamoto M, Singh R, et al. Outcomes of donation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) lung transplantation[J]. J Heart Lung Transplant, 2025, 44(5): 721-733.
5. Sandiumenge A, Bello I, Coll-Torres E, et al. Systemic inflammation differences in brain-vs. circulatory-dead donors: impact on lung transplant recipients[J/OL]. Transpl Int, 2024, 37: 12512. DOI: 10.3389/ti.2024.12512.
6. Berzenji L, Hendriks JMH, Verleden SE, et al. Lung ischemia-reperfusion injury in lung transplant surgery: where do we stand[J/OL]. Antioxidants (Basel), 2025, 14(11): 1295. DOI: 10.3390/antiox14111295.
7. Paraskeva MA, Snell GI. Advances in lung transplantation: 60 years on[J]. Respirology, 2024, 29(6): 458-470.
8. Levvey BJ, Westall GP, Kotsimbos T, et al. Definitions of warm ischemic time when using controlled donation after cardiac death lung donors[J]. Transplantation, 2008, 86(12): 1702-1706.
9. Levvey B, Keshavjee S, Cypel M, et al. Influence of lung donor agonal and warm ischemic times on early mortality: analyses from the ISHLT DCD Lung Transplant Registry[J]. J Heart Lung Transplant, 2019, 38(1): 26-34.
10. Alzahrani A, Noda K, Chan EG, et al. The length of the warm ischemic interval in lung donation after circulatory death does not impact post-transplantation outcomes[J/OL]. JHLT Open, 2025, 8: 100244. DOI: 10.1016/j.jhlto.2025.100244.
11. Van Raemdonck D, Ceulemans LJ, Neyrinck A, et al. Donation after circulatory death in lung transplantation[J]. Thorac Surg Clin, 2022, 32(2): 153-165.
12. Cypel M, Levvey B, Van Raemdonck D, et al. International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report[J]. J Heart Lung Transplant, 2015, 34(10): 1278-1282.
13. Miyoshi K, Oto T, Otani S, et al. Effect of donor pre-mortem hypoxia and hypotension on graft function and start of warm ischemia in donation after cardiac death lung transplantation[J]. J Heart Lung Transplant, 2011, 30(4): 445-451.
14. Moreno P, González-García J, Ruíz-López E, et al. Lung transplantation in controlled donation after circulatory-determination-of-death using normothermic abdominal perfusion[J/OL]. Transpl Int, 2024, 37: 12659. DOI: 10.3389/ti.2024.12659.
15. Palleschi A, Zanella A, Sacchi M, et al. Uncontrolled donation after circulatory death lung transplantation program: clinical outcomes and perspectives for implementation[J]. Am J Transplant, 2026, 26: 1156-1167.
16. de Assis Ramos MM, dos Santos Pedroso L, Taira Ramos IY, et al. Effects of ventilation during warm ischemia in a rat lung perfusion model[J]. J Surg Res, 2026, 321: 107-117.
17. Campo-Ca?averal de la Cruz JL, Crowley Carrasco S, Tanaka S, et al. Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors[J]. Transpl Int, 2021, 34(12): 2609-2619.
18. Niikawa H, Sakota D, Kosaka R, et al. A whole-body cooling strategy in uncontrolled donation after circulatory death: insights from a porcine ex vivo lung perfusion model[J/OL]. Transplant Direct, 2026, 12(3): e1904. DOI: 10.1097/txd.0000000000001904.
19. Keshavamurthy S, Rodgers-Fischl P. Donation after circulatory death (DCD): lung procurement[J]. Indian J Thorac Cardiovasc Surg, 2021, 37(Suppl 3): 425-432.
20. Bello I, Palleschi A, Cypel M, et al. Unlocking the potential of uncontrolled DCD in lung transplantation: a review of 2 decades of experience[J/OL]. JHLT Open, 2025, 10: 100374. DOI: 10.1016/j.jhlto.2025.100374.
21. Inci I, Hillinger S, Schneiter D, et al. Lung transplantation with controlled donation after circulatory death donors[J]. Ann Thorac Cardiovasc Surg, 2018, 24(6): 296-302.
22. Levvey BJ, Snell GI. How do we expand the lung donor pool[J]. Curr Opin Pulm Med, 2024, 30(4): 398-404.
23. Ta HQ, Kuppusamy M, Sonkusare SK, et al. The endothelium: gatekeeper to lung ischemia-reperfusion injury[J/OL]. Respir Res, 2024, 25(1): 172. DOI: 10.1186/s12931-024-02776-4.
24. Van Slambrouck J, Loopmans S, Prisciandaro E, et al. The effect of rewarming ischemia on tissue transcriptome and metabolome signatures: a clinical observational study in lung transplantation[J]. J Heart Lung Transplant, 2025, 44(3): 437-447.
25. Baciu C, Shin J, Hsin M, et al. Altered purine metabolism at reperfusion affects clinical outcome in lung transplantation[J]. Thorax, 2023, 78(3): 249-257.
26. Wang A, Ali A, Baciu C, et al. Metabolomic studies reveal an organ-protective hibernation state in donor lungs preserved at 10°C[J]. J Thorac Cardiovasc Surg, 2025, 169(3): 796-810. e1.
27. Ribeiro RVP, Altarabsheh SE, Segamanasinghe DL, et al. Preconditioning donor lungs with lung-derived exosomes mitigates ischemia-reperfusion injury in a warm ischemia porcine DCD model[J]. J Heart Lung Transplant, 2025, 44(7): 1149-1160.
28. Duan L, Quan L, Zheng B, et al. Inflation using hydrogen improves donor lung quality by regulating mitochondrial function during cold ischemia phase[J/OL]. BMC Pulm Med, 2023, 23(1): 213. DOI: 10.1186/s12890-023-02504-6.
29. Liang L, Zhao Y, Wang A, et al. Metabolomic atlas of ischemia-reperfusion injury in human lung transplants: mitochondrial stress and primary graft dysfunction[J/OL]. Am J Transplant, 2026. Epub ahead of print. DOI: 10.1016/j.ajt.2026.04.007.
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