Myocardial infarction and heart failure are leading causes of death worldwide, in large part because adult human myocardium has extremely limited regeneration capacity. Zebrafish are a powerful model for identifying new strategies for human cardiac repair because their hearts regenerate after relatively severe injuries. Zebrafish are also relatively scalable and compatible with many genetic tools. However, characterizing the regeneration process in live adult zebrafish hearts has proved challenging because adult fish are opaque, preventing live imaging in vivo. An alternative strategy is to explant and culture intact adult zebrafish hearts and investigate them ex vivo. However, explanted hearts maintained in conventional culture conditions experience rapid declines in morphology and physiology. To overcome these limitations, we designed and fabricated a fluidic device for culturing explanted adult zebrafish hearts with constant media perfusion that is also compatible with live imaging. We then compared the morphology and calcium activity of hearts cultured in the device, hearts cultured statically in dishes, and freshly explanted hearts. After one week of culture, hearts in the device experienced significantly less morphological degradation compared to hearts cultured in dishes. Hearts cultured in devices for one week also maintained capture rates similar to fresh hearts, unlike hearts cultured in dishes. We then cultured explanted injured hearts in the device and used live imaging techniques to continuously record the myocardial revascularization process over several days, demonstrating how our device is compatible with long-term live imaging and thereby enables unprecedented visual access to the multi-day process of adult zebrafish heart regeneration.

中文翻译：

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在流体装置中对正常和再生的成年斑马鱼心脏进行扩展培养和成像。

心肌梗塞和心力衰竭是全世界死亡的主要原因，很大程度上是因为成年人心肌的再生能力极其有限。斑马鱼是确定人类心脏修复新策略的强大模型，因为它们的心脏在相对严重的损伤后可以再生。斑马鱼的可扩展性也相对较高，并且与许多遗传工具兼容。然而，描述活体成年斑马鱼心脏的再生过程已被证明具有挑战性，因为成年斑马鱼是不透明的，妨碍了体内实时成像。另一种策略是外植和培养完整的成年斑马鱼心脏并进行离体研究。然而，在传统培养条件下维持的移植心脏的形态和生理学会迅速下降。为了克服这些限制，我们设计并制造了一种流体装置，用于培养外植的成年斑马鱼心脏，具有恒定的介质灌注，该装置也与实时成像兼容。然后，我们比较了在装置中培养的心脏、在培养皿中静态培养的心脏以及新鲜移植的心脏的形态和钙活性。培养一周后，与培养皿中培养的心脏相比，装置中的心脏经历的形态退化明显减少。与在培养皿中培养的心脏不同，在设备中培养一周的心脏也保持与新鲜心脏相似的捕获率。然后，我们在设备中培养移植的受伤心脏，并使用实时成像技术连续记录几天的心肌血运重建过程，展示了我们的设备如何与长期实时成像兼容，从而能够前所未有地直观地了解多天的心肌血运重建过程。成年斑马鱼心脏再生。