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在心跳骤停后的供心器官中,线粒体和心功能的缺血再灌注损伤:一项实验研究。

Ischemia and reperfusion injury to mitochondria and cardiac function in donation after circulatory death hearts- an experimental study.

机构信息

Department of Surgery, Virginia Commonwealth University, Richmond, VA, United States of America.

Division of Cardiology, Department of Medicine, Virginia Commonwealth University, Richmond, VA, United States of America.

出版信息

PLoS One. 2020 Dec 28;15(12):e0243504. doi: 10.1371/journal.pone.0243504. eCollection 2020.

DOI:10.1371/journal.pone.0243504
PMID:33370296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7769461/
Abstract

The ultimate treatment for patients with end-stage heart failure is heart transplantation. The number of donor hearts which are primarily procured from donation after brain death (DBD) donors is limited, but donation after circulatory death (DCD) donor hearts can increase the heart donor pool. However, ischemia and reperfusion injuries associated with the DCD process causes myocardial damage, limiting the use of DCD hearts in transplantation. Addressing this problem is critical in the exploration of DCD hearts as suitable donor hearts for transplantation. In this study, rat hearts were procured following the control beating-heart donor (CBD) or DCD donation process. Changes in mitochondria and cardiac function from DCD hearts subjected to 25 or 35 minutes of ischemia followed by 60 minutes of reperfusion were compared to CBD hearts. Following ischemia, rates of oxidative phosphorylation and calcium retention capacity were progressively impaired in DCD hearts compared to CBD hearts. Reperfusion caused additional mitochondrial dysfunction in DCD hearts. Developed pressure, inotropy and lusitropy, were significantly reduced in DCD hearts compared to CBD hearts. We, therefore, suggest that interventional strategies targeted before the onset of ischemia and at reperfusion could protect mitochondria, thus potentially making DCD hearts suitable for heart transplantation.

摘要

对于终末期心力衰竭患者来说,最终的治疗方法是心脏移植。供体心脏的数量主要来源于脑死亡后的捐赠(DBD),但循环死亡后的捐赠(DCD)可以增加供体心脏池。然而,DCD 过程中与缺血再灌注损伤相关的心肌损伤限制了 DCD 心脏在移植中的应用。解决这个问题对于探索 DCD 心脏作为合适的移植供体心脏至关重要。在这项研究中,大鼠心脏通过控制跳动心脏供体(CBD)或 DCD 捐赠过程进行获取。比较了 DCD 心脏在缺血 25 或 35 分钟后再灌注 60 分钟与 CBD 心脏之间的线粒体和心脏功能变化。与 CBD 心脏相比,缺血后 DCD 心脏的氧化磷酸化和钙保留能力逐渐受损。再灌注导致 DCD 心脏中的线粒体功能进一步障碍。与 CBD 心脏相比,DCD 心脏的发展压力、变力性和顺应性显著降低。因此,我们建议在缺血发生前和再灌注时采取干预策略来保护线粒体,从而使 DCD 心脏有可能适合心脏移植。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a829/7769461/f11365c6cf70/pone.0243504.g007.jpg
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