High frequency ultrasound for echocardiography in small animals

点击翻译按钮获取中文摘要

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.