Trimigno Alessia, Zhao Jifang, Michaud William A, Paneitz Dane C, Chukwudi Chijioke, D'Alessandro David A, Lewis Greg D, Minie Nathan F, Catricala Joseph P, Vincent Douglas E, Lopera Higuita Manuela, Bolger-Chen Maya, Tessier Shannon N, Li Selena, O'Day Elizabeth M, Osho Asishana A, Rabi S Alireza
Olaris, Inc., Framingham, MA.
Division of Cardiac Surgery, Corrigan Minehan Heart Center, Massachusetts General Hospital, Corrigan Minehan Heart Center, Boston, MA.
Transplant Direct. 2024 Aug 29;10(9):e1704. doi: 10.1097/TXD.0000000000001704. eCollection 2024 Sep.
The number of patients waiting for heart transplant far exceeds the number of hearts available. Donation after circulatory death (DCD) combined with machine perfusion can increase the number of transplantable hearts by as much as 48%. Emerging studies also suggest machine perfusion could enable allograft "reconditioning" to optimize outcomes. However, a detailed understanding of the energetic substrates and metabolic changes during perfusion is lacking.
Metabolites were analyzed using 1-dimensional H and 2-dimensional C-H heteronuclear spectrum quantum correlation nuclear magnetic resonance spectroscopy on serial perfusate samples (N = 98) from 32 DCD hearts that were successfully transplanted. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test for significant differences in metabolite resonances during perfusion and network analysis was used to uncover altered metabolic pathways.
Metabolite differences were observed comparing baseline perfusate to samples from hearts at time points 1-2, 3-4, and 5-6 h of perfusion and all pairwise combinations. Among the most significant changes observed were a steady decrease in fatty acids and succinate and an increase in amino acids, especially alanine, glutamine, and glycine. This core set of metabolites was also altered in a DCD porcine model perfused with a nonblood-based perfusate.
Temporal metabolic changes were identified during ex vivo perfusion of DCD hearts. Fatty acids, which are normally the predominant myocardial energy source, are rapidly depleted, while amino acids such as alanine, glutamine, and glycine increase. We also noted depletion of ketone, β-hydroxybutyric acid, which is known to have cardioprotective properties. Collectively, these results suggest a shift in energy substrates and provide a basis to design optimal preservation techniques during perfusion.
等待心脏移植的患者数量远远超过可获得的心脏数量。循环死亡后捐赠（DCD）联合机器灌注可使可移植心脏数量增加多达48%。新出现的研究还表明，机器灌注可使同种异体移植物“修复”以优化结果。然而，目前缺乏对灌注过程中能量底物和代谢变化的详细了解。
使用一维氢谱和二维碳-氢异核谱量子相关核磁共振波谱对32例成功移植的DCD心脏的系列灌注液样本（N = 98）进行代谢物分析。采用Wilcoxon符号秩检验和Kruskal-Wallis检验来检测灌注过程中代谢物共振的显著差异，并使用网络分析来揭示代谢途径的改变。
将基线灌注液与灌注1 - 2小时、3 - 4小时和5 - 6小时时心脏的样本以及所有成对组合进行比较，观察到代谢物存在差异。观察到的最显著变化包括脂肪酸和琥珀酸稳步减少，氨基酸增加，尤其是丙氨酸、谷氨酰胺和甘氨酸。在灌注非血液基灌注液的DCD猪模型中，这组核心代谢物也发生了改变。
在DCD心脏的体外灌注过程中确定了时间性代谢变化。通常作为心肌主要能量来源的脂肪酸迅速消耗，而丙氨酸、谷氨酰胺和甘氨酸等氨基酸增加。我们还注意到具有心脏保护特性的酮体β-羟基丁酸减少。总体而言，这些结果表明能量底物发生了转变，并为设计灌注过程中的最佳保存技术提供了依据。
