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.
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