A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury.

A practical approach to remote ischemic preconditioning and ischemic preconditioning against myocardial ischemia/reperfusion injury.
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DOI:
10.14440/jbm.2016.149
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发表时间:
2016-01-01
期刊:
Journal of biological methods
影响因子:
--
通讯作者:
Rassaf, Tienush
Rassaf, Tienush
中科院分区:
其他
文献类型:
--
作者:
Totzeck, Matthias;Hendgen-Cotta, Ulrike B;Rassaf, Tienush

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尽管临床实践中迫切需要,但针对心肌缺血/再灌注损伤的心脏保护治疗方法仍有待建立。远程缺血预处理(remote ischemic preconditioning,rIPC)和缺血预处理(ischemic preconditioning,IPC)是一种有前途的工具,包括三个方面:保护信号的产生、信号向靶器官的传递以及对传递信号的反应,从而导致心脏保护。然而,鉴于最近的科学进步,关于潜在信号的功效出现了许多争议。我们在这里显示的信号级联的产生rIPC以及IPC在体内心肌缺血/再灌注损伤的小鼠模型中使用高度可重复的方法的方法。这是通过利用与临床环境兼容的易于应用的预处理策略来实现的。我们描述了使用激光多普勒灌注成像来真实的实时监测灌注停止和恢复的方法。预处理对心脏功能的影响也可以使用超声或磁共振成像方法进行评估。在细胞水平上,我们证实了如何组织损伤可以使用梗死面积的组织学评估结合免疫组化评估在一个单一的标本的两个方面进行监测。最后,我们概述了rIPC相关信号如何通过体液(血液)隔室中的信号保守转移到靶细胞。这一汇编的实验方案,包括预处理方案的临床设置应证明有用的初学者和专家在心肌梗死领域,提供信息的详细程序以及故障排除指南。
Although urgently needed in clinical practice, a cardioprotective therapeutic approach against myocardial ischemia/ reperfusion injury remains to be established. Remote ischemic preconditioning (rIPC) and ischemic preconditioning (IPC) represent promising tools comprising three entities: the generation of a protective signal, the transfer of the signal to the target organ, and the response to the transferred signal resulting in cardioprotection. However, in light of recent scientific advances, many controversies arise regarding the efficacy of the underlying signaling. We here show methods for the generation of the signaling cascade by rIPC as well as IPC in a mouse model for in vivo myocardial ischemia/ reperfusion injury using highly reproducible approaches. This is accomplished by taking advantage of easily applicable preconditioning strategies compatible with the clinical setting. We describe methods for using laser Doppler perfusion imaging to monitor the cessation and recovery of perfusion in real time. The effects of preconditioning on cardiac function can also be assessed using ultrasound or magnetic resonance imaging approaches. On a cellular level, we confirm how tissue injury can be monitored using histological assessment of infarct size in conjunction with immunohistochemistry to assess both aspects in a single specimen. Finally, we outline, how the rIPC-associated signaling can be transferred to the target cell via conservation of the signal in the humoral (blood) compartment. This compilation of experimental protocols including a conditioning regimen comparable to the clinical setting should proof useful to both beginners and experts in the field of myocardial infarction, supplying information for the detailed procedures as well as troubleshooting guides.