Circulatory-dead donor lungs: evaluation of different management strategies
Circulatory-dead donor lungs: evaluation of different management strategies
Lung transplantation remains the final therapeutic option for patients with end-stage pulmonary disease; however, its wider application is limited by the ongoing shortage of suitable donor organs. In this setting, lungs retrieved from donors after circulatory death (DCD) represent a relevant strategy to expand the donor pool. Nevertheless, DCD lungs are inevitably subjected to a period of warm ischemia (WI), which predisposes the graft to ischemia–reperfusion injury and may negatively affect post-transplant outcomes. Improving the safe use of DCD lungs therefore requires a better understanding of injury mechanisms and the evaluation of targeted management strategies.
This thesis of Mayara Munhoz De Assis Ramos aimed to investigate different approaches to optimise the quality of DCD donor lungs. A systematic review was first conducted to characterise experimental rat models of DCD lung donation, focusing on methodological aspects such as the method of circulatory arrest, duration of WI, and perfusion strategies. The review revealed considerable heterogeneity between models, particularly regarding the agonal phase and cause of death, raising concerns about reproducibility and clinical relevance. In addition, no studies incorporated in situ lung perfusion, with most relying solely on ex vivo techniques.
The following experimental studies in small and large animal models evaluated the effects of ventilation initiated immediately after circulatory arrest and maintained during WI. In both models, ventilation during WI failed to provide functional benefit and was associated with increased apoptotic activity and upregulation of inflammatory genes. These findings suggest that the absence of ventilation, as observed in uncontrolled DCD donors, does not necessarily compromise lung viability.
Finally, given recognised sex-related differences in IRI and the reported protective effects of estrogens, the therapeutic potential of 17β-estradiol (E2), including potential nano-based delivery systems, was assessed. The E2 treatment was tested through DCD lung preservation. Although modest histological improvements and increased VEGF expression were observed in rat models, E2 did not improve functional or metabolic parameters in a sheep ex vivo lung perfusion model, nor did it consistently modulate inflammatory or apoptotic pathways. Overall, these results support refinement of DCD donor management strategies and highlight the central role of ex vivo lung perfusion for graft evaluation and reconditioning.