High frequency ultrasound for echocardiography in small animals

高频超声用于小动物超声心动图检查

• 批准号: RTI-2019-00235
• 负责人: Gillis, Todd
• 金额: $ 10.92万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=651912
• 关键词: frequency; ultrasound; echocardiography; small; animals

There is much that can be learned of how the vertebrate heart works, or can regenerate following injury, by studying zebrafish and leopard geckos. One reason why zebrafish are becoming an important animal for studying how the heart works is that at the cellular level, there are many similarities between their hearts and that of humans. Zebrafish are also quite small, and develop rapidly. As a result, it is more cost effective to study zebrafish than many other species, including mice. Finally, there are many tools that have been developed to study zebrafish and to mutate their DNA. This means that it is possible to manipulate the proteins present in the heart so as to learn more of how the whole organ functions. Interestingly, both zebrafish and leopard geckos have the capacity to regrow heart muscle after it has been damaged. As occurs in human tissues, a scar appears after injury but this disappears as new muscle grows. As a result, there is no sign of the injury and the heart continues to function. Understanding how this occurs has significant potential in treating cardiac damage in mammalian hearts including those from humans. However, one challenge when trying to study how the hearts of zebrafish and geckos work, is their very small size. This prevents the use of standard tools, such as probes inserted into the heart, to measure force generation. However, it is now possible to image the heart of zebrafish and geckos while it is functioning inside a live animal using a technique called high frequency echocardiography. As a result, we can make measurements of the rate of blood flow through the heart, the amount of blood that can be pumped per beat, and how much the heart contracts during each beat. Changes to the morphology, or shape, of the heart that occurs following injury, and while the heart is regenerating, can also be characterized. As a result, it is now possible to specifically quantify changes in the function or morphology of zebrafish hearts and gecko hearts that occur as the result of an experimental manipulation. The specific questions that will be addressed using this instrument are: 1) How does the heart respond to a physiological stressor such as low temperature? 2) How does cardiac function change during the process of regeneration following injury? 3) What are the consequences of protein mutations, linked to inherited cardiac diseases in humans, on the function of the zebrafish heart? 4) Is it possible to increase the strength of the heart by changing the amino acid sequence of specific proteins? These questions will provide fundamental insight into the ability of the vertebrate heart to respond to physiological stressors, or cardiac injury, and of the molecular mechanisms responsible for regulating how it works. Such knowledge will help develop new strategies, or treatments, to improve cardiac function after a heart attack or in patients with an inherited heart mutation that impairs cardiac function.

通过研究斑马鱼和豹壁虎，可以了解到很多关于脊椎动物心脏如何工作或受伤后如何再生的信息。斑马鱼成为研究心脏如何工作的重要动物的一个原因是，在细胞水平上，它们的心脏与人类的心脏有许多相似之处。斑马鱼也很小，但发育迅速。因此，研究斑马鱼比包括小鼠在内的许多其他物种更具成本效益。最后，已经开发了许多工具来研究斑马鱼并使其DNA突变。 这意味着可以操纵心脏中存在的蛋白质，以便更多地了解整个器官的功能。有趣的是，斑马鱼和豹纹壁虎都有在心肌受损后再生的能力。 就像人体组织一样，受伤后会出现疤痕，但随着新肌肉的生长，疤痕就会消失。 因此，没有受伤的迹象，心脏继续发挥功能。 了解这是如何发生的，在治疗哺乳动物心脏（包括人类心脏）的心脏损伤方面具有重要的潜力。然而，当试图研究斑马鱼和壁虎的心脏如何工作时，一个挑战是它们的尺寸非常小。这阻止了标准工具的使用，例如插入心脏的探针，以测量力的产生。然而，现在可以使用一种称为高频超声心动图的技术来成像斑马鱼和壁虎的心脏，同时它在活体动物体内发挥作用。因此，我们可以测量通过心脏的血流速度，每次心跳可以泵出的血液量，以及每次心跳期间心脏收缩的程度。也可以表征在损伤后以及在心脏再生时发生的心脏形态或形状的变化。因此，现在可以具体量化实验操作导致的斑马鱼心脏和壁虎心脏的功能或形态变化。使用该仪器将解决的具体问题是：1）心脏如何对生理应激源（如低温）作出反应？2)在损伤后的再生过程中，心脏功能如何变化？3)与人类遗传性心脏病有关的蛋白质突变对斑马鱼心脏功能有什么影响？4)有没有可能通过改变特定蛋白质的氨基酸序列来增加心脏的力量？这些问题将为脊椎动物心脏对生理应激或心脏损伤的反应能力以及负责调节其工作方式的分子机制提供基本的见解。这些知识将有助于开发新的策略或治疗方法，以改善心脏病发作后或患有损害心脏功能的遗传性心脏突变的患者的心脏功能。