Biventricular Interaction During Acute Left Ventricular Ischemia in Mice: A Combined In-Vivo and In-Silico Approach.

Biventricular Interaction During Acute Left Ventricular Ischemia in Mice: A Combined In-Vivo and In-Silico Approach.
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DOI:
10.1007/s10439-023-03293-z
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发表时间:
2023-11
影响因子:
3.8
通讯作者:
Chesler, N. C.
Chesler, N. C.
中科院分区:
工程技术2区
文献类型:
--
作者:
Colebank, M. J.;Taylor, R.;Hacker, T. A.;Chesler, N. C.

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计算模型为整合和连接多个时空尺度提供了一种有效的范式。然而,这些模型难以参数化并与实验数据相匹配。数据收集和模型分析方面的最新进展有助于克服这一限制。在这里,我们将多尺度双心室相互作用模型与左心室缺血前后的小鼠数据结合起来。灵敏度分析用于确定对压力和体积预测影响最大的参数。有影响的模型参数子集在基线时被校准为双心室压力-容积环路数据(n = 3)。每只小鼠进行左冠状动脉前降支结扎,在此过程中记录分数缩短和右心室压力-容积动力学的变化。使用校准的模型,我们模拟急性左室缺血,并在基线和模拟缺血时对比输出。我们的基线模拟与左室和右室数据一致,我们在缺血期间的预测补充了记录的左室数据和先前对心肌梗死期间左室功能的研究。我们表明,具有双心室机械相互作用和系统级心血管动力学的模型可以定量地再现体内数据,并定性地匹配先前左室缺血动物研究的结果。在线版本包含补充材料,可在10.1007/s10439-023-03293-z获得。
Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure–volume loop data (n = 3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure–volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems-level cardiovascular dynamics can quantitatively reproduce in-vivo data and qualitatively match prior findings from animal studies on LV ischemia. The online version contains supplementary material available at 10.1007/s10439-023-03293-z.
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