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Overcoming the Limits of Reconditioning: Seventeen Hours of EVLP With Successful Transplantation From Uncontrolled Circulatory Death Donor.

ABSTRACT:

Background

Uncontrolled donation after circulatory death (DCD) donors are an extraordinary resource to increase the number of lungs available for transplantation. However, the risk of the warm ischemia resulting from cardiac arrest to irreversibly damage the organs is considerable. Moreover, graft preservation issues and organizational problems often worsen the dangerous effects of warm ischemia. Ex vivo lung perfusion (EVLP) enables us to evaluate and recondition lungs whose functionality is doubtful, as well as to overcome the difficulties related to time and logistics.

Methods

We report the case of uncontrolled DCD lungs successfully treated with an exceptionally prolonged EVLP. Because the donor's blood count and liver biopsy showed signs of possible leukemia, EVLP was protracted up to 17 h while waiting for immunohistochemical analyses to rule out this diagnosis; eventually, the results came back negative, and the lungs were judged suitable for transplantation.

Results

The recipient was a 32-y-old male individual with cystic fibrosis, colonized by Pandoraea pnomenusa. Bilateral transplantation required central extracorporeal membrane oxygenation. The patient was extubated after 36 h and was discharged 21 d after the operation. Despite early recolonization by Pandoraea pnomenusa and airway complications requiring pneumatic dilatation, he is alive and has a satisfactory respiratory function 15 mo after transplantation.

Conclusions

Uncontrolled DCD represents a challenge due to both logistical issues and the complexity of graft evaluation before procurement. EVLP with cellular perfusate could be a valuable tool to overcome these limits. Nonetheless, caution should be exercised when interpreting the effects of this technique on airway healing.

SUBMITTER: Palleschi A

PROVIDER: S-EPMC8612888 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundWe set a model of brain death, donor management, and lung transplantation for studies on lung preservation and reconditioning before transplantation.MethodsTen pigs (39.7?±?5.9 Kg) were investigated. Five animals underwent brain death and were treated as organ donors; the lungs were then procured and cold stored (Ischemia). Five recipients underwent left lung transplantation and post-reperfusion follow-up (Graft). Cardiorespiratory and metabolic parameters were collected. Lung gene expression of cytokines (tumor necrosis factor alpha (TNF?), interleukin-1 beta (IL-1?), interleukin-6 (IL-6), interferon gamma (IFN?), high mobility group box-1 (HMGB-1)), chemokines (chemokine CC motif ligand-2 (CCL2-MCP-1), chemokine CXC motif ligand-10 (CXCL-10), interleukin-8 (IL-8)), and endothelial activation markers (endothelin-1 (EDN-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), selectin-E (SELE)) was assessed by real-time polymerase chain reaction (PCR).ResultsTachycardia and hypertension occurred during brain death induction; cardiac output rose, systemic vascular resistance dropped (P?<?0.05), and diabetes insipidus occurred. Lung-protective ventilation strategy was applied: 9 h after brain death induction, PaO2 was 192?±?12 mmHg at positive end-expiratory pressure (PEEP) 8.0?±?1.8 cmH2O and FiO2 of 40%; wet-to-dry ratio (W/D) was 5.8?±?0.5, and extravascular lung water (EVLW) was 359?±?80 mL. Procured lungs were cold-stored for 471?±?24 min (Ischemia) at the end of which W/D was 6.1?±?0.9. Left lungs were transplanted and reperfused (warm ischemia 98?±?14 min). Six hours after controlled reperfusion, PaO2 was 192?±?23 mmHg (PEEP 8.7?±?1.5 cmH2O, FiO2 40%), W/D was 5.6?±?0.4, and EVLW was 366?±?117 mL. Levels of IL-8 rose at the end of donor management (BD, P?<?0.05); CCL2-MCP-1, IL-8, HMGB-1, and SELE were significantly altered after reperfusion (Graft, P?<?0.05).ConclusionsWe have set a standardized, reproducible pig model resembling the entire process of organ donation that may be used as a platform to test in vivo and ex vivo strategies of donor lung optimization before transplantation.