High frequency ultrasound for echocardiography in small animals

通过对斑马鱼和豹纹壁虎的研究，我们可以了解到很多脊椎动物的心脏是如何工作的，或者受伤后心脏是如何再生的。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，斑马鱼的心脏与人类的心脏有许多相似之处。斑马鱼也很小，发育很快。因此，研究斑马鱼比研究包括老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改变它们的DNA。这意味着有可能操纵心脏中存在的蛋白质，从而更多地了解整个器官的功能。有趣的是，斑马鱼和豹纹壁虎的心肌在受损后都有再生能力。就像在人体组织中发生的那样，受伤后会出现疤痕，但随着新肌肉的生长，疤痕会消失。因此，没有损伤的迹象，心脏继续工作。了解这是如何发生的，对于治疗包括人类在内的哺乳动物心脏损伤具有重要的潜力。然而，当试图研究斑马鱼和壁虎的心脏如何工作时，一个挑战是它们的体积很小。这阻止了使用标准工具，如插入心脏的探针，来测量力的产生。然而，现在有可能利用一种称为高频超声心动图的技术，对斑马鱼和壁虎的心脏在活体动物体内的功能进行成像。因此，我们可以测量血液流经心脏的速率，每次跳动可以泵出的血液量，以及每次跳动时心脏收缩的程度。损伤后心脏形态或形状的变化，以及心脏再生过程中的变化，也可以被描述为特征。因此，现在有可能具体量化斑马鱼和壁虎心脏的功能或形态变化，这些变化是实验操作的结果。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)损伤后再生过程中心功能发生了怎样的变化？3)与人类遗传性心脏病相关的蛋白质突变对斑马鱼心脏功能的影响是什么？4)是否有可能通过改变特定蛋白质的氨基酸序列来增加心脏的强度？这些问题将为了解脊椎动物心脏对生理压力源或心脏损伤的反应能力，以及调节心脏工作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遗传性心脏突变损害心脏功能的患者的心脏功能。

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.