Fan Lei, Namani Ravi, Choy Jenny S, Awakeem Yousif, Kassab Ghassan S, Lee Lik Chuan
Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan.
California Medical Innovation Institute, San Diego, California.
Am J Physiol Heart Circ Physiol. 2021 Mar 1;320(3):H1037-H1054. doi: 10.1152/ajpheart.00549.2020. Epub 2020 Dec 24.
Mechanical dyssynchrony (MD) affects left ventricular (LV) mechanics and coronary perfusion. To understand the multifactorial effects of MD, we developed a computational model that bidirectionally couples the systemic circulation with the LV and coronary perfusion with flow regulation. In the model, coronary flow in the left anterior descending (LAD) and left circumflex (LCX) arteries affects the corresponding regional contractility based on a prescribed linear LV contractility-coronary flow relationship. The model is calibrated with experimental measurements of LV pressure and volume, as well as LAD and LCX flow rate waveforms acquired under regulated and fully dilated conditions from a swine under right atrial (RA) pacing. The calibrated model is applied to simulate MD. The model can simultaneously reproduce the reduction in mean LV pressure (39.3%), regulated flow (LAD: 7.9%; LCX: 1.9%), LAD passive flow (21.6%), and increase in LCX passive flow (15.9%). These changes are associated with right ventricular pacing compared with RA pacing measured in the same swine only when LV contractility is affected by flow alterations with a slope of 1.4 mmHg/mL in a contractility-flow relationship. In sensitivity analyses, the model predicts that coronary flow reserve (CFR) decreases and increases in the LAD and LCX with increasing delay in LV free wall contraction. These findings suggest that asynchronous activation associated with MD impacts ) the loading conditions that further affect the coronary flow, which may explain some of the changes in CFR, and ) the coronary flow that reduces global contractility, which contributes to the reduction in LV pressure. A computational model that couples the systemic circulation of the left ventricular (LV) and coronary perfusion with flow regulation is developed to study the effects of mechanical dyssynchrony. The delayed contraction in the LV free wall with respect to the septum has a significant effect on LV function and coronary flow reserve.
机械性不同步（MD）会影响左心室（LV）力学和冠状动脉灌注。为了解MD的多因素影响，我们开发了一种计算模型，该模型将体循环与LV双向耦合，并将冠状动脉灌注与血流调节耦合。在该模型中，基于规定的线性LV收缩性-冠状动脉血流关系，左前降支（LAD）和左旋支（LCX）动脉中的冠状动脉血流会影响相应区域的收缩性。该模型通过LV压力和容积的实验测量值以及在右心房（RA）起搏下从猪身上在调节状态和完全扩张状态下获取的LAD和LCX血流速率波形进行校准。校准后的模型用于模拟MD。该模型可以同时再现LV平均压力降低（39.3%）、调节血流（LAD：7.9%；LCX：1.9%）、LAD被动血流降低（21.6%）以及LCX被动血流增加（15.9%）。仅当LV收缩性受血流改变影响且收缩性-血流关系斜率为1.4 mmHg/mL时，与在同一头猪中测量的RA起搏相比，这些变化与右心室起搏相关。在敏感性分析中，该模型预测随着LV游离壁收缩延迟增加，LAD和LCX中的冠状动脉血流储备（CFR）会降低和增加。这些发现表明，与MD相关的异步激活会影响：）进一步影响冠状动脉血流的负荷条件，这可能解释了CFR的一些变化；以及）降低整体收缩性的冠状动脉血流，这导致LV压力降低。开发了一种将左心室（LV）体循环与冠状动脉灌注及血流调节耦合的计算模型，以研究机械性不同步的影响。LV游离壁相对于室间隔的延迟收缩对LV功能和冠状动脉血流储备有显著影响。
