Dissecting Heart Failure mechanisms by integrating in vivo and in vitro data within customised in silico models

心力衰竭（HF）是由心脏定义的？由于左心室（LV）收缩和舒张功能下降，患者泵血能力下降。随着心脏病发作后生存率的提高和英国的扩张？在老年人群中，HF正迅速成为一种流行病，造成显著的死亡率和发病率负担。最近，新的实验技术的力量已经为HF临床综合征的机制之谜贡献了几个新的部分。然而，尽管做出了这些努力，我们对这一重要过程的了解仍然是零散的，阻碍了确定治疗干预的强有力目标。计算心脏生理学的学科提供了一个令人兴奋的方法来解决这个问题，通过定量描述心脏的生理行为，使用数学和计算模型。这种模型的发展表现出捕捉复杂和多因素因果关系的能力，这些因果关系将潜在的病理生理机制联系起来。此外，心脏是一个集成模型的最先进的例子，因此代表了令人兴奋的工具，重点是，在HF的情况下，在一个重要的diseases.Combining这种计算技术与最先进的体内和体外实验技术，我们的目标是同化多个数据集，以测试我们的理解HF机制在一个一致的模型。我们的初步实验测量表明，在HF中，单个心脏细胞可以继续正常收缩，然而，这是它们在心脏组织中连接方式的变化，这可能对收缩产生不利影响。应用我们的综合实验和计算方法，我们将能够测试这一假设，并在这样做时，为这种疾病的新治疗策略的发展指明了一个潜在的全新方向。

Heart Failure (HF) is defined by the heart?s reduced ability to pump blood due to a drop in left ventricular (LV) systolic and diastolic function. With the improved survival after a heart attack and the expansion of the U.K.?s elderly population, HF is rapidly becoming an epidemic accounting for a significant mortality and morbidity burden. Recently, the strength of new experimental techniques has contributed several new pieces to the mechanistic puzzle that underpins the clinical syndrome of HF. Despite these efforts, however, our knowledge of this important process remains fragmented, hampering the identification of robust targets for therapeutic intervention. The discipline of computational cardiac physiology offers an exciting approach to address this issue by quantitatively describing the physiological behavior of the heart using mathematical and computational models. The development of such models presents the ability capture the complex and multi-factorial cause and effect relationships which link underlying patho-physiological mechanisms. Furthermore, the heart is arguable the most advanced example of an integrated model and as such represents exciting tool with which to focus, in the case of HF, on an important disease.Combining this computational technology with state of the art in-vivo and in-vitro experimental techniques we aim to assimilate multiple data sets to test our understanding of HF mechanisms within a consistent model. Our preliminary experimental measurements indicate that in HF individual cardiac cells may continue to contract normally, however, it is a change in the way they are connected in heart tissue which may be adversely affecting contraction. Applying our integrated experimental and computational approach we will be able to test this hypothesis and in doing so indicate a potentially brand new direction for the development of new treatment strategies for this disease.