The Effects of Oxygen-Derived Free-Radical Scavengers During Normothermic Ex-Situ Heart Perfusion.

IF 3.1 3区医学 Q2 ENGINEERING, BIOMEDICAL ASAIO Journal Pub Date : 2024-09-01 Epub Date: 2024-03-08 DOI:10.1097/MAT.0000000000002176

Xiao Qi, Sanaz Hatami, Sabin Bozso, Xiuhua Wang, Bruno Saleme, Jayan Nagendran, Evangelos Michelakis, Gopinath Sutendra, Darren H Freed

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Abstract

Oxidative stress occurs during ex-situ heart perfusion (ESHP) and may negatively affect functional preservation of the heart. We sought to assess the status of key antioxidant enzymes during ESHP, and the effects of augmenting these antioxidants on the attenuation of oxidative stress and improvement of myocardial and endothelial preservation in ESHP. Porcine hearts were perfused for 6 hours with oxygen-derived free-radical scavengers polyethylene glycol (PEG)-catalase or PEG-superoxide dismutase (SOD) or with naive perfusate (control). The oxidative stress-related modifications were determined in the myocardium and coronary vasculature, and contractile function, injury, and endothelial integrity were compared between the groups. The activity of key antioxidant enzymes decreased and adding catalase and SOD restored the enzyme activity. Cardiac function and endothelial integrity were preserved better with restored catalase activity. Catalase and SOD both decreased myocardial injury and catalase reduced ROS production and oxidative modification of proteins in the myocardium and coronary vasculature. The activity of antioxidant enzymes decrease in ESHP. Catalase may improve the preservation of cardiac function and endothelial integrity during ESHP. While catalase and SOD may both exert cardioprotective effects, unbalanced SOD and catalase activity may paradoxically increase the production of reactive species during ESHP.

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常温离体心脏灌注过程中氧自由基清除剂的作用

原位心脏灌注（ESHP）过程中会产生氧化应激，可能会对心脏功能的保存产生负面影响。我们试图评估 ESHP 期间关键抗氧化酶的状态，以及增强这些抗氧化剂对减轻氧化应激和改善 ESHP 中心肌和内皮保存的影响。用氧源性自由基清除剂聚乙二醇（PEG）-催化酶或聚乙二醇-超氧化物歧化酶（SOD）或纯净灌流液（对照组）灌注猪心 6 小时。测定了心肌和冠状动脉血管中与氧化应激相关的改变，并比较了各组之间的收缩功能、损伤和内皮完整性。关键抗氧化酶的活性降低，而添加过氧化氢酶和 SOD 后酶活性得到恢复。过氧化氢酶活性恢复后，心脏功能和内皮完整性得到了更好的保护。过氧化氢酶和 SOD 都减轻了心肌损伤，过氧化氢酶减少了 ROS 的产生以及心肌和冠状血管中蛋白质的氧化修饰。ESHP 中抗氧化酶的活性降低。过氧化氢酶可改善 ESHP 期间心脏功能和内皮完整性的保护。虽然过氧化氢酶和 SOD 都能起到保护心脏的作用，但如果 SOD 和过氧化氢酶的活性不平衡，可能会增加 ESHP 期间活性物质的产生。

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来源期刊

ASAIO Journal 医学-工程：生物医学

CiteScore

6.60

自引率

7.10%

发文量

651

审稿时长

4-8 weeks

期刊介绍： ASAIO Journal is in the forefront of artificial organ research and development. On the cutting edge of innovative technology, it features peer-reviewed articles of the highest quality that describe research, development, the most recent advances in the design of artificial organ devices and findings from initial testing. Bimonthly, the ASAIO Journal features state-of-the-art investigations, laboratory and clinical trials, and discussions and opinions from experts around the world. The official publication of the American Society for Artificial Internal Organs.