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Multiscale Modeling of Cardiac Cellular Energetics

机译:心肌细胞能量的多尺度建模

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Inducing abnormal routes of cardiac excitation results in predictable changes in regional blood flows and metabolism. In LBBB, glucose uptake and flow are both reduced in the septal region, similar to the situation in dogs paced at the right ventricular outflow tract, when the septum is activated early, shorten rapidly against low left ventricular (LV) pressure, and blood flow to the interventricular septum diminishes, while flow increases in the later-activated LV free wall. A mathematical model has been developed to explain this set of phenomena, attempting to minimize the model in order to identify the key characteristics governing the observed responses. The specific objective is to provide a logical, quantitatively appropriate representation of the linked events: (1) local blood flow and substrate and oxygen supply, (2) local fatty acid and glucose metabolism, (3) ATP generation by gly-colysis and oxidative phosphorylation, (4) ATP utilization by hydrolysis at the cross bridge, by ion pumps, and for cell maintenance, (5) the processes of excitation-contraction coupling, and (6) feedback regulation of blood flow. We attempt to explain the observations in a simplified representation of these events using a common parameter set for two regions linked in tandem, but activating them separately with a time delay representing the time for excitation to spread from septum to free wall. The early activation of one cell stretches the other, so that the first cell has diminished oxygen requirements and the second, increased, as seen in the intact heart. Integrative modeling of cardiac energy metabolism, capillary-tissue substrate exchange, and local blood flow regulation provides an overall representation of the data in a quantitative fashion, an approach in accord with the goals for physiome projects.
机译:诱导心脏激发异常途径导致区域血流和新陈代谢的可预测变化。在LBBB中,隔膜区域的葡萄糖摄取和流动均降低,类似于在右心室流出道上的狗的情况,当清沉早期激活时,迅速缩短低左心室(LV)压力,血流到间隔的隔膜减少,而流动在后来活化的LV自由壁中增加。已经开发了一种数学模型来解释这组现象,试图最小化模型,以便确定观察到的响应的关键特征。具体目的是提供链接事件的逻辑,定量适当的表示:(1)局部血流和基材和氧气供应,(2)局部脂肪酸和葡萄糖代谢,(3)通过Gly-沉淀和氧化产生ATP磷酸化,(4)通过离子泵,通过离子泵和电池维护,(5)激发收缩耦合的过程,(6)血流反馈调节的血流反馈调节。我们试图使用串联链接的两个区域的公共参数设置在这些事件的简化表示中解释观察,但是用表示激励时间从隔膜传播到自由墙的时间的时间延迟来分开激活它们。一种细胞的早期活化延伸另一个细胞,使得第一电池减少氧要求和第二细胞,增加,如完整的心脏所示。心能新陈代谢,毛细管 - 组织基础交换和局部血流调节的一致性建模提供了以定量方式的总体表示,这是一种符合物理项目的目标的方法。

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