Division of Anesthesia and Intensive Care, Department of Surgical Sciences, University of Torino, Torino (Italy).
Division of Anesthesia and Intensive Care, Department of Surgical Sciences, University of Torino, Torino (Italy).
J Heart Lung Transplant. 2019 Mar;38(3):267-276. doi: 10.1016/j.healun.2018.12.015. Epub 2018 Dec 20.
Lung metabolism during ex vivo lung perfusion (EVLP) is increasingly studied. Microdialysis (MD) allows metabolic monitoring by sampling parenchymal interstitial fluid. This study investigated lung metabolism using MD during EVLP and evaluated whether microdialysate metabolites could improve selection and discriminate outcome of donor lungs.
MD monitoring was used during 14 clinical EVLP procedures. Paired microdialysate and perfusate samples were analyzed for glucose, lactate, pyruvate, glutamate, and the lactate/pyruvate (L/P) ratio, and values that best discriminated an unfavorable outcome were determined. Outcome was defined as unfavorable (lungs not transplanted or transplanted with primary graft dysfunction at 72 hours ≥ 2) or favorable (lungs transplanted with primary graft dysfunction < 2).
Microdialysate markers and the perfusate L/P ratio could discriminate unfavorable outcome with sensitivity and specificity of 0.85 and 0.81 for MD glutamate > 18.4 μmol/liter, 0.81 and 0.74 for MD lactate > 685 μmol/liter, 0.92 and 0.75 for MD glucose > 530 μmol/liter, 0.85 and 0.65 for MD pyruvate > 25 μmol/liter, and 0.73 and 0.67 for perfusate L/P ratio > 24.17. All microdialysate markers, perfusate and microdialysate L/P ratio, and perfusate lactate discriminated outcome when we limited analysis only to transplanted lungs.
We report the use of MD to evaluate lung metabolism during clinical EVLP, demonstrating that MD metabolites can contribute to selection of reconditioned lungs and discriminate early outcome after transplantation. Furthermore, glutamate as a marker of lung injury during EVLP is proposed and could hence be used as a potential target for future therapies.
体外肺灌注（EVLP）期间的肺代谢越来越受到关注。微透析（MD）通过取样肺实质间质液来进行代谢监测。本研究通过 EVLP 期间的 MD 研究了肺代谢，并评估了微透析液代谢物是否可以改善供体肺的选择和区分预后。
在 14 例临床 EVLP 过程中使用 MD 监测。对配对的微透析液和灌注液样本进行葡萄糖、乳酸、丙酮酸、谷氨酸和乳酸/丙酮酸（L/P）比值分析，并确定最佳区分不良结果的指标。结果定义为不良（未移植或移植后 72 小时原发性移植物功能障碍≥2）或良好（原发性移植物功能障碍<2）。
微透析液标志物和灌注液 L/P 比值可以区分不良预后，MD 谷氨酸>18.4μmol/L 的灵敏度和特异性分别为 0.85 和 0.81，MD 乳酸>685μmol/L 的灵敏度和特异性分别为 0.81 和 0.74，MD 葡萄糖>530μmol/L 的灵敏度和特异性分别为 0.92 和 0.75，MD 丙酮酸>25μmol/L 的灵敏度和特异性分别为 0.85 和 0.65，灌注液 L/P 比值>24.17 的灵敏度和特异性分别为 0.73 和 0.67。当我们仅分析已移植的肺时，所有微透析液标志物、灌注液和微透析液 L/P 比值以及灌注液乳酸都可以区分预后。
我们报告了使用 MD 评估临床 EVLP 期间的肺代谢，表明 MD 代谢物可以为再充氧肺的选择和移植后早期结果的区分提供帮助。此外，提出了 EVLP 期间肺损伤的标志物谷氨酸，因此可以作为未来治疗的潜在靶点。
