Endothelin-Converting Enzyme 1 and Vascular Endothelial Growth Factor as Potential Biomarkers during Ex Vivo Lung Perfusion with Prolonged Hypothermic Lung-Sparing

内皮素转换酶 1 和血管内皮生长因子作为长期低温肺保留体外肺灌注过程中的潜在生物标志物

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作者:Claudia Hernández-Jiménez, J Raúl Olmos-Zúñiga, Matilde Baltazares-Lipp, Rogelio Jasso-Victoria, Adrián Polo-Jerez, María Teresa Pérez-López, Luis Florentino Vázquez-Justiniano, Néstor Emmanuel Díaz-Martínez, Miguel Gaxiola-Gaxiola, Laura Romero-Romero, Axel Edmundo Guzmán-Cedillo, Mario Enrique Bal

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.

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