Comparative study of lung preconditioning protocols in donors after circulatory arrest: an experimental rabbit model

Objective: to perform a comparative analysis of donor lung preconditioning protocols in donors after circulatory arrest, followed by normothermic ex vivo lung perfusion (EVLP), using two approaches: topical lung cooling and continued artificial ventilation after circulatory arrest.

Materials and methods. The study was conducted on male Grey Giant rabbits weighing 4.5–5.0 kg (n = 20). Group 1: Donor lung preconditioning after circulatory arrest using topical cooling (n = 10). Group 2: Donor lung preconditioning after circulatory arrest with continued artificial ventilation in protective modes (n = 10). To evaluate the viability and functional state of donor lungs following preconditioning and cold preservation, both groups underwent normothermic EVLP. Assessments included lactate concentration, perfusate gas composition, endoscopic evaluation of the tracheobronchial tree, and subsequent morphological examination.

Results. After 60 minutes of cold preservation, all grafts demonstrated satisfactory gas exchange function during normothermic EVLP. In Group 1 (topical cooling), the oxygenation index (OI) at 60 minutes was 552 (461–599) and increased to 558 (462–603) at 120 minutes. In Group 2 (continuous artifi cial ventilation), OI was 358 (343–368) at 60 minutes, with a tendency to increase to 374 (349–395) at 120 minutes. The difference between the groups was statistically signifi cant (p = 0.000). Lactate levels in both groups showed an upward trend, with a mean value of 6.99 ± 0.81, and no statistically significant intergroup differences were observed (p > 0.05).

Conclusion. The study demonstrates the potential advantages of using topical cooling as part of the donor lung preconditioning protocol after cessation of eff ective circulation, employing a dextran40-based preservation solution at all stages. This approach may increase the number of donor lungs suitable for transplantation.

1. Valapour M, Lehr CJ, Skeans MA, Smith JM, Uccellini K, Lehman R et al. OPTN/SRTR 2017 Annual Data Report: Lung. Am J Transplant. 2019 Feb; 19 Suppl 2: 404–484. doi: 10.1111/ajt.15279.

2. Cypel M, Sato M, Yildirim E, Karolak W, Chen F, Yeung J et al. Initial experience with lung donation after cardiocirculatory death in Canada. J Heart Lung Transplant. 2009 Aug; 28 (8): 753–758. doi: 10.1016/j.healun.2009.05.009.

3. Van Raemdonck D, Ceulemans LJ, Neyrinck A, Levvey B, Snell GI. Donation After Circulatory Death in lung transplantation. Thorac Surg Clin. 2022 May; 32 (2): 153–165. doi: 10.1016/j.thorsurg.2021.11.002.

4. Inci I, Hillinger S, Schneiter D, Opitz I, Schuurmans M, Benden C, Weder W. Lung Transplantation with Controlled Donation after Circulatory Death Donors. Ann Thorac Cardiovasc Surg. 2018 Dec 20; 24 (6): 296–302. doi: 10.5761/atcs.oa.18-00098.

5. Erasmus ME, Verschuuren EA, Nijkamp DM, Vermeyden JW, van der Bij W. Lung transplantation from nonheparinized category III non-heart-beating donors. A single-centre report. Transplantation. 2010 Feb 27; 89 (4): 452–457. doi: 10.1097/TP.0b013e3181c46a74.

6. Cypel M, Levvey B, Van Raemdonck D, Erasmus M, Dark J, Love R et al. International Society for Heart and Lung Transplantation. International Society for Heart and Lung Transplantation Donation After Circulatory Death Registry Report. J Heart Lung Transplant. 2015 Oct; 34 (10): 1278–1282. doi: 10.1016/j.healun.2015.08.015.

7. Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med. 2011 Apr 14; 364 (15): 1431–1440. doi: 10.1056/NEJMoa1014597.

8. Spratt JR, Mattison LM, Iaizzo PA, Meyer C, Brown RZ, Iles T et al. Lung transplant after prolonged ex vivo lung perfusion: predictors of allograft function in swine. Transpl Int. 2018 Dec; 31 (12): 1405–1417. doi: 10.1111/tri.13315.

9. Gomez-de-Antonio D, Campo-Cañaveral JL, Crowley S, Valdivia D, Cordoba M, Moradiellos J et al. Clinical lung transplantation from uncontrolled non-heart-beating donors revisited. J Heart Lung Transplant. 2012 Apr; 31 (4): 349–353. doi: 10.1016/j.healun.2011.12.007.

10. De Antonio DG, Marcos R, Laporta R, Mora G, García-Gallo C, Gámez P et al. Results of clinical lung transplant from uncontrolled non-heart-beating donors. J Heart Lung Transplant. 2007 May; 26 (5): 529–534. doi: 10.1016/j.healun.2007.01.028.

11. Rodríguez DA, Del Río F, Fuentes ME, Naranjo S, Moradiellos J, Gómez D et al. Trasplante de pulmón con donantes no controlados a corazón parado. Factores pronósticos dependientes del donante y evolución inmediata postrasplante [Lung transplantation with uncontrolled non-heart-beating donors. Transplantation. Donor prognostic factor and immediate evolution post transplant]. Arch Bronconeumol. 2011 Aug; 47 (8): 403–409. Spanish. doi: 10.1016/j.arbres.2011.04.009.

12. Palleschi A, Zanella A, Citerio G, Musso V, Rosso L, Tosi D et al. Lung Transplantation From Controlled and Uncontrolled Donation After Circulatory Death (DCD) Donors With Long Ischemic Times Managed by Simple Normothermic Ventilation and Ex-Vivo Lung Perfusion Assessment. Transpl Int. 2023 Feb 8; 36: 10690. doi: 10.3389/ti.2023.10690.

13. Valenza F, Citerio G, Palleschi A, Vargiolu A, Fakhr BS, Confalonieri A et al. Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion. Am J Transplant. 2016 Apr; 16 (4): 1312–1318. doi: 10.1111/ajt.13612.

14. Gautier SV, Pashkov IV, Bogdanov VK, Oleshkevich DO, Bondarenko DM, Mozheiko NP et al. Normothermic ex vivo lung perfusion using a developed solution followed by orthotopic left lung transplantation (experimental study). Russian Journal of Transplantology and Artificial Organs. 2023; 25 (2): 158–166. https://doi.org/10.15825/1995-1191-2023-2-158-166.

15. Gautier SV, Tsirulnikova OM, Pashkov IV, Oleshkevich DO, Filatov IA, Bogdanov VK et al. Normothermic ex vivoperfusion of isolated lungs in an experiment using a russian-made perfusion system. Russian Journal of Transplantology and Artificial Organs. 2022; 24 (2): 94–101. https://doi.org/10.15825/1995-1191-2022-2-94101.

16. Schroder JN, Patel CB, DeVore AD, Bryner BS, Casalinova S, Shah A et al. Transplantation outcomes with donor hearts after circulatory death. N Engl J Med. 2023 Jun 8; 388 (23): 2121–2131. doi: 10.1056/NEJMoa2212438.

17. Alzahrani A, Noda K, Chan EG, Ryan JP, Furukawa M, Sanchez PG. The length of the warm ischemic interval in lung donation after circulatory death does not impact post-transplantation outcomes. JHLT Open. 2025 Mar 11; 8: 100244. doi: 10.1016/j.jhlto.2025.100244.