Perfusate Biomarkers of DCD Cardiac Graft Quality Identified With Proteomics: Studies in an Isolated Rat Heart Model.

IF 5.3 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2024-10-31 DOI:10.1097/TP.0000000000005241

Alexia Clavier, Maria Arnold, Adrian Segiser, Natalia Méndez-Carmona, Rahel Wyss, Manfred Heller, Anne-Christine Uldry, Matthias Siepe, Sarah Longnus

{"title":"Perfusate Biomarkers of DCD Cardiac Graft Quality Identified With Proteomics: Studies in an Isolated Rat Heart Model.","authors":"Alexia Clavier, Maria Arnold, Adrian Segiser, Natalia Méndez-Carmona, Rahel Wyss, Manfred Heller, Anne-Christine Uldry, Matthias Siepe, Sarah Longnus","doi":"10.1097/TP.0000000000005241","DOIUrl":null,"url":null,"abstract":"Background: Heart transplantation with donation after circulatory death (DCD) enhances cardiac graft availability, but exposes hearts to potentially damaging conditions, such as warm ischemia. Normothermic machine perfusion (NMP), used for graft transportation, allows biomarker determination in perfusate. Using our isolated, rat heart model of DCD, we evaluated potent.Methods: Isolated, perfused adult male Wistar rat hearts (n = 5/group) underwent different warm ischemic durations to simulate DCD, followed by reperfusion to simulate NMP. Perfusate samples were collected after 10 min reperfusion, and proteins were analyzed using mass spectrometry. Cardiac recovery was evaluated after 60 min reperfusion. The relationship between perfusate proteins and cardiac recovery was investigated.Results: Cardiac recovery decreased with increasing ischemic duration. Principal component analysis of perfusate proteins demonstrated segregation by ischemic group. Several proteins demonstrated an On-Off pattern, and correlated with key outcome measurements. Other proteins were released by all hearts and were confirmed as predictors of cardiac recovery, for example, heat shock protein 70 and valosin-containing protein (area under the curve [AUC] = 0.962-0.968, respectively; P < 0.05 for all). Additionally, proteins such as glycogen phosphorylase, muscle associated (AUC = 0.9632; P < 0.05) showed potential as novel biomarkers for evaluating cardiac graft quality, unlike lactate release after 10 min of reperfusion (AUC = 0.60).Conclusions: Multiple perfusate proteins, such as heat shock protein 70, valosin-containing protein, or glycogen phosphorylase, muscle associated, released during early reperfusion are promising as biomarkers for assessing graft quality during NMP. Perfusate proteins, as biomarkers, offer the possibility of both rapid immune detection and out-of-hospital implementation, and may provide valuable information about graft quality, especially when profiled with serial sampling during NMP.","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/TP.0000000000005241","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Heart transplantation with donation after circulatory death (DCD) enhances cardiac graft availability, but exposes hearts to potentially damaging conditions, such as warm ischemia. Normothermic machine perfusion (NMP), used for graft transportation, allows biomarker determination in perfusate. Using our isolated, rat heart model of DCD, we evaluated potent.

Methods: Isolated, perfused adult male Wistar rat hearts (n = 5/group) underwent different warm ischemic durations to simulate DCD, followed by reperfusion to simulate NMP. Perfusate samples were collected after 10 min reperfusion, and proteins were analyzed using mass spectrometry. Cardiac recovery was evaluated after 60 min reperfusion. The relationship between perfusate proteins and cardiac recovery was investigated.

Results: Cardiac recovery decreased with increasing ischemic duration. Principal component analysis of perfusate proteins demonstrated segregation by ischemic group. Several proteins demonstrated an On-Off pattern, and correlated with key outcome measurements. Other proteins were released by all hearts and were confirmed as predictors of cardiac recovery, for example, heat shock protein 70 and valosin-containing protein (area under the curve [AUC] = 0.962-0.968, respectively; P < 0.05 for all). Additionally, proteins such as glycogen phosphorylase, muscle associated (AUC = 0.9632; P < 0.05) showed potential as novel biomarkers for evaluating cardiac graft quality, unlike lactate release after 10 min of reperfusion (AUC = 0.60).

Conclusions: Multiple perfusate proteins, such as heat shock protein 70, valosin-containing protein, or glycogen phosphorylase, muscle associated, released during early reperfusion are promising as biomarkers for assessing graft quality during NMP. Perfusate proteins, as biomarkers, offer the possibility of both rapid immune detection and out-of-hospital implementation, and may provide valuable information about graft quality, especially when profiled with serial sampling during NMP.

查看原文本刊更多论文

用蛋白质组学鉴定 DCD 心脏移植质量的灌注液生物标志物：孤立大鼠心脏模型研究。

背景：循环死亡后捐献（DCD）的心脏移植提高了心脏移植物的可用性，但会使心脏暴露于潜在的破坏性条件下，如温暖缺血。用于移植物运输的常温机器灌注（NMP）可以测定灌注液中的生物标志物。我们利用大鼠离体心脏模型对 DCD 的有效性进行了评估：离体灌注的成年雄性 Wistar 大鼠心脏（n = 5/组）经历不同的温缺血持续时间以模拟 DCD，然后再灌注以模拟 NMP。再灌注 10 分钟后收集灌注液样本，并使用质谱分析蛋白质。再灌注 60 分钟后评估心脏恢复情况。研究了灌注液蛋白质与心脏恢复之间的关系：结果：心脏恢复能力随着缺血时间的延长而下降。灌流液蛋白质的主成分分析表明，缺血组存在分离现象。有几种蛋白质显示出一种 "开-关 "模式，并与主要的结果测量相关。其他蛋白则是所有心脏都释放的，并被证实是心脏恢复的预测因子，例如热休克蛋白 70 和含缬氨肽蛋白（曲线下面积 [AUC] = 0.962-0.968，分别为 0.962、0.968 和 0.968）：再灌注早期释放的多种灌注液蛋白，如热休克蛋白 70、含缬氨酸蛋白或糖原磷酸化酶、肌肉相关蛋白，有望成为评估 NMP 期间移植物质量的生物标记物。灌注液蛋白作为生物标记物，既能进行快速免疫检测，又能在院外实施，还能提供有关移植物质量的宝贵信息，尤其是在 NMP 期间通过连续采样进行分析时。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.