Da Silveira Cavalcante Luciana, Tessier Shannon N
Center for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 2114, USA.
Shriners Hospitals for Children, Boston, MA 2114, USA.
J Cardiovasc Dev Dis. 2021 Apr 8;8(4):39. doi: 10.3390/jcdd8040039.
Heart transplantation became a reality at the end of the 1960s as a life-saving option for patients with end-stage heart failure. Static cold storage (SCS) at 4-6 °C has remained the standard for heart preservation for decades. However, SCS only allows for short-term storage that precludes optimal matching programs, requires emergency surgeries, and results in the unnecessary discard of organs. Among the alternatives seeking to extend ex vivo lifespan and mitigate the shortage of organs are sub-zero or machine perfusion modalities. Sub-zero approaches aim to prolong cold ischemia tolerance by deepening metabolic stasis, while machine perfusion aims to support metabolism through the continuous delivery of oxygen and nutrients. Each of these approaches hold promise; however, complex barriers must be overcome before their potential can be fully realized. We suggest that one barrier facing all experimental efforts to extend ex vivo lifespan are limited research tools. Mammalian models are usually the first choice due to translational aspects, yet experimentation can be restricted by expertise, time, and resources. Instead, there are instances when smaller vertebrate models, like the zebrafish, could fill critical experimental gaps in the field. Taken together, this review provides a summary of the current gold standard for heart preservation as well as new technologies in ex vivo lifespan extension. Furthermore, we describe how existing tools in zebrafish research, including isolated organ, cell specific and functional assays, as well as molecular tools, could complement and elevate heart preservation research.
心脏移植在20世纪60年代末成为现实，成为终末期心力衰竭患者的一种挽救生命的选择。几十年来，4-6℃的静态冷藏（SCS）一直是心脏保存的标准方法。然而，SCS只允许短期保存，这排除了优化匹配程序，需要进行急诊手术，并导致器官被不必要地丢弃。在试图延长体外寿命和缓解器官短缺的替代方法中，有零下保存或机器灌注方式。零下保存方法旨在通过加深代谢停滞来延长冷缺血耐受性，而机器灌注旨在通过持续输送氧气和营养物质来支持新陈代谢。这些方法都有前景；然而，在其潜力得到充分实现之前，必须克服复杂的障碍。我们认为，所有延长体外寿命的实验努力面临的一个障碍是研究工具有限。由于转化方面的原因，哺乳动物模型通常是首选，但实验可能会受到专业知识、时间和资源的限制。相反，在某些情况下，较小的脊椎动物模型，如斑马鱼，可以填补该领域关键的实验空白。综上所述，本综述总结了目前心脏保存的金标准以及延长体外寿命的新技术。此外，我们描述了斑马鱼研究中的现有工具，包括离体器官、细胞特异性和功能测定以及分子工具，如何能够补充和提升心脏保存研究。
