The role of the Frank-Starling law in the transduction of cellular work to whole organ pump function: a computational modeling analysis.
The role of the Frank-Starling law in the transduction of cellular work to whole organ pump function: a computational modeling analysis.
复制标题
DOI：
10.1371/journal.pcbi.1000371
复制
发表时间：
2009-04
影响因子：
4.3
通讯作者：
Smith NP
中科院分区：
文献类型：
--
作者：
Niederer SA;Smith NP
我们建立了一个室温下大鼠左心室多尺度生物物理力学模型。该模型已被应用于调查的相对作用的细胞尺度长度依赖性调节器的张力产生的转导工作从细胞到整个器官泵功能。具体而言，通过在不存在这些反馈机制中的每一个的情况下进行模拟，预测了张力的长度依赖性Ca 2+敏感性（Ca 50）、细丝重叠张力依赖性、张力的速度依赖性以及Ca 2+与肌钙蛋白C的张力依赖性结合对功和应力的有效转导以及应变均匀性的度量的作用。长度依赖性Ca_（50）和细丝重叠构成了Frank-Starling定律，被认为是功的有效转导的两个主要调节因子。在没有Frank-Starling机制的情况下分析纤维速度场表明，在没有细丝重叠效应的情况下，工作的转导效率降低是由收缩后缩短增加引起的，而在没有长度依赖性Ca 50的情况下，效率降低是由应变的区域分布的反转引起的。心脏通过跨越多个空间和时间尺度的复杂反馈回路网络实现有效的协调收缩。计算硬件和数值技术的进步使我们能够开始通过使用计算模型来分析这种反馈系统。应用这种方法，我们已经集成了广泛的实验数据到一个共同的和一致的建模框架，代表心脏电气和机械系统。我们已经使用这个模型来研究反馈回路如何调节心脏收缩。这些结果表明，在细胞水平上，来自肌肉长度对张力产生的反馈是心肌在整个器官水平上收缩的效率的重要控制机制。除了测试这一特定的假设，本研究中开发的模型提供了一个框架，将这项工作扩展到调查重要的病理条件，如心力衰竭和缺血性心脏病。
We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca2+ sensitivity of tension (Ca50), filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca2+ to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca50 and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca50 was caused by an inversion in the regional distribution of strain. The heart achieves an efficient coordinated contraction via a complex web of feedback loops that span multiple spatial and temporal scales. Advances in computational hardware and numerical techniques now allow us to begin to analyse this feedback system through the use of computational models. Applying this approach, we have integrated a wide range of experimental data into a common and consistent modelling framework representing the cardiac electrical and mechanical systems. We have used this model to investigate how feedback loops regulate heart contraction. These results show that feedback from muscle length on tension generation at the cellular level is an important control mechanism of the efficiency with which the heart muscle contracts at the whole organ level. In addition to testing this specific hypothesis, the model developed in this study provides a framework for extending this work to investigating important pathological conditions such as heart failure and ischemic heart disease.
登录
查看更多内容
DOI：
10.1152/ajpheart.1998.275.5.h1879
发表时间：
1998-11-01
影响因子：
4.8
作者：
DeAnda, A;Komeda, M;Miller, DC
通讯作者：
Miller, DC
影响因子：
--
作者：
FANN, JI;SARRIS, GE;MILLER, DC
通讯作者：
MILLER, DC
DOI：
10.1098/rspb.1938.0050
发表时间：
1938-10-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Hill, AV
通讯作者：
Hill, AV
DOI：
10.1152/ajpheart.00577.2005
发表时间：
2006-04-01
影响因子：
4.8
作者：
Connelly, KA;Prior, DL;Gilbert, RE
通讯作者：
Gilbert, RE
影响因子：
20.1
作者：
HANSEN, DE;DAUGHTERS, GT;MILLER, DC
通讯作者：
MILLER, DC