Abstract
Lung transplantation requires optimization of donor's organ use through ex vivo lung perfusion (EVLP) to avoid primary graft dysfunction. Biomarkers can aid in organ selection by providing early evidence of suboptimal lungs during EVLP and thus avoid high-risk transplantations. However, predictive biomarkers of pulmonary graft function such as endothelin-converting enzyme (ECE-1) and vascular endothelial growth factor (VEGF) have not been described under EVLP with standard prolonged hypothermic preservation, which are relevant in situations where lung procurement is difficult or far from the transplantation site. Therefore, this study is aimed at quantifying ECE-1 and VEGF, as well as determining their association with hemodynamic, gasometric, and mechanical ventilatory parameters in a swine model of EVLP with standard prolonged hypothermic preservation. Using a protocol with either immediate (I-) or delayed (D-) initiation of EVLP, ECE-1 levels over time were found to remain constant in both study groups (p > 0.05 RM-ANOVA), while the VEGF protein was higher after prolonged preservation, but it decreased throughout EVLP (p > 0.05 RM-ANOVA). Likewise, hemodynamic, gasometric, mechanical ventilatory, and histological parameters had a tendency to better results after 12 hours of hypothermic preservation in the delayed infusion group.
Highlights
Lung transplantation (LTx) is the last resort treatment for patients with severe chronic lung disease
PaCO2 I-ex vivo lung perfusion (EVLP) (19:58 ± 6:99) and delayed initiation of EVLP (D-EVLP) (25:20 ± 5:58) levels did not vary over time (p = 0:964), nor amongst groups (p = 0:551)
The evaluation of immediate EVLP (I-EVLP) and D-EVLP groups was similar; even though I-EVLP presented a rise in the wet-dry weight ratio and lightly augmented histological findings, and oxygenation capacity in both groups was maintained at above-expected values for EVLP lungs [22, 23]
Summary
Lung transplantation (LTx) is the last resort treatment for patients with severe chronic lung disease. LTx requires optimal utilization of available donors and the optimization of donor’s organ use This has led to the emergence of ex vivo lung perfusion (EVLP) as a tool for evaluation, preservation, and reconditioning of the donor’s lung prior to transplantation [2], since it allows the evaluation of lungs under continuous physiological monitoring, reconditioning lungs with fluid removal, and intervention/engineering of lungs with intense therapy during extended preservation. Endothelial dysfunction is manifested by the activation of endothelial biomarkers such as endothelin (ET) and vascular endothelial growth factor (VEGF), which could lead to reduced graft survival after brain death In these circumstances, biomarkers can aid in organ selection by providing early evidence of suboptimal lungs during EVLP and avoid high-risk transplantations [4, 5].
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