在脑死亡供体猪模型中，供体循环因子和体外心脏灌注中的循环因子均与心脏恢复相关。

Circulating factors, in both donor and ex-situ heart perfusion, correlate with heart recovery in a pig model of DCD.

作者信息

Graf Selianne, Egle Manuel, Sanz Maria-Nieves, Segiser Adrian, Clavier Alexia, Arnold Maria, Gsponer Didier, Bartkevics Maris, Kadner Alexander, Siepe Matthias, Vermathen Peter, Longnus Sarah

机构信息

Department of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.

Department of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, University of Bern, Bern, Switzerland.

出版信息

J Heart Lung Transplant. 2025 Jan;44(1):92-101. doi: 10.1016/j.healun.2024.08.016. Epub 2024 Sep 7.

DOI:10.1016/j.healun.2024.08.016

PMID:39251114

Abstract

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.

摘要

背景

心脏移植采用循环死亡后器官捐献及体外心脏灌注可带来良好的结果并提高移植率。然而，需要改进移植物评估技术以确保移植物的有效利用。因此，我们研究了原位和体外循环因子作为心脏移植物质量潜在生物标志物的情况。

方法

在麻醉的雄性猪中模拟循环死亡，设置0、10、20或30分钟的热缺血时间。取出心脏并在无负荷模式下进行3小时的体外灌注，随后进行1小时的左心室负荷，以评估心脏恢复情况（结果）。使用标准生化技术或核磁共振波谱对多个供体血液和体外灌注液样本进行生物标志物评估。

结果

供体及体外心脏灌注10分钟时的循环肾上腺素与心脏恢复呈负相关（均p<0.05）。我们确定了几种用于心脏移植物质量的新的潜在生物标志物，这些标志物可通过核磁共振波谱快速且同时进行测量。在无负荷体外心脏灌注的多个时间点，灌注液中丙酮、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水平（均p<0.05）与结果显著相关；最佳时间点为60分钟。