BACKGROUND Heart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality. METHODS Circulatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 minutes. Hearts were explanted and underwent ex-situ perfusion for 3 hours in an unloaded mode, followed by left ventricular loading for 1 hour, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy. RESULTS Circulating adrenaline, both in the donor and at 10 minutes ex-situ heart perfusion, negatively correlated with cardiac recovery (p < 0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p < 0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 minutes. CONCLUSIONS In heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.

中文翻译：

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供体和非原位心脏灌注中的循环因子与 DCD 猪模型中的心脏恢复相关。


背景 循环死亡和非原位心脏灌注后捐献的心脏移植可提供出色的结果并提高移植率。然而，需要改进的移植物评估技术以确保移植物的有效利用。因此，我们研究了原位和非原位循环因子作为心脏移植物质量的潜在生物标志物。方法 在温缺血持续时间为 0 、 10 、 20 或 30 分钟的麻醉雄性猪中模拟循环死亡。心脏被移植并以空负荷模式进行 3 小时的异位灌注，然后进行左心室负荷 1 小时，以评估心脏恢复 （结果）。使用多个供体血液和非原位灌注液样品通过标准生化技术或核磁共振波谱进行生物标志物评估。结果 循环肾上腺素，无论是在供体中还是在 10 分钟非原位心脏灌注时，都与心脏恢复呈负相关 （p < 0.05）。我们确定了几种新的心脏移植物质量的潜在生物标志物，这些生物标志物可以用核磁共振波谱快速同时测量。在空负荷非原位心脏灌注期间的多个时间点，丙酮、甜菜碱、肌酸、肌酐、富马酸盐、次黄嘌呤、乳酸、丙酮酸和琥珀酸盐的灌注液水平 （p < 0.05 对于所有人） 与结果显著相关;最佳时间点为 60 分钟。结论 循环死亡后心脏捐献中，循环肾上腺素水平对心脏移植物评估有价值。核磁共振波谱特别有趣，因为它可以在短时间内测量多种代谢物。 改进的生物标志物可能允许更高的精度，从而更好地支持关于移植适宜性的临床决策。