Caballero-Marcos Aránzazu, Rodríguez-Bachiller Luis, Baroja-Mazo Alberto, Morales Álvaro, Fernández-Cáceres Paloma, Fernández-Martínez María, DíazFontenla Fernando, Velasco Enrique, Fernández-Yunquera Ainhoa, Díaz-Zorita Benjamin, Cortese Sergio, Pérez-Peña José María, Colón-Rodríguez Arturo, Romero-Cristóbal Mario, Asencio José Manuel, Bañares Rafael, López-Baena José Ángel, Salcedo-Plaza Magdalena
Hepatology and Liver Transplantation Unit, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Transplant Direct. 2024 Nov 14;10(12):e1728. doi: 10.1097/TXD.0000000000001728. eCollection 2024 Dec.
A comprehensive mechanistic assessment of normothermic machine perfusion (NMP) is an essential step toward identifying biomarkers to assess liver viability. Although some studies have evaluated the effect of NMP on inflammation markers, there are other key pathological mechanisms involved in ischemia/reperfusion injury (IRI) that have not yet been evaluated.
Eight human donor livers preserved by NMP were included to analyze IRI during preservation. Concentrations of several biomarkers involved in different biological processes of IRI were measured in the perfusate.
Perfusate levels of intercellular adhesion molecule 1, P-selectin, vascular cell adhesion molecule 1, metalloproteinase with thrombospondin motif type 1, member 13, phospholipase A2 group VII, and syndecan-1 progressively increased during NMP. Noteworthy, perfusate lactate levels showed a strong correlation with C-X-C motif chemokine ligand 10 ( = 0.001), intercellular adhesion molecule 1 ( = 0.01), and urokinase plasminogen activator ( = 0.001).
Perfusate lactate correlates with the main underlying biological mechanisms occurring in the NMP environment. Moreover, several IRI biomarkers accumulate during NMP, which may limit the extent of the benefits of this technology.
对常温机器灌注(NMP)进行全面的机制评估是识别评估肝脏活力生物标志物的关键一步。尽管一些研究已经评估了NMP对炎症标志物的影响,但缺血/再灌注损伤(IRI)中涉及的其他关键病理机制尚未得到评估。
纳入8个通过NMP保存的人类供体肝脏,分析保存期间的IRI。在灌注液中测量了参与IRI不同生物学过程的几种生物标志物的浓度。
在NMP期间,细胞间粘附分子1、P选择素、血管细胞粘附分子1、含血小板反应蛋白基序的金属蛋白酶1型成员13、磷脂酶A2第VII组和多功能蛋白聚糖1的灌注液水平逐渐升高。值得注意的是,灌注液乳酸水平与C-X-C基序趋化因子配体10(r = 0.001)、细胞间粘附分子1(r = 0.01)和尿激酶型纤溶酶原激活剂(r = 0.001)呈强相关。
灌注液乳酸与NMP环境中发生的主要潜在生物学机制相关。此外,几种IRI生物标志物在NMP期间积累,这可能会限制该技术的受益程度。