Mechanical dyssynchrony (MD) affects left ventricular (LV) mechanics and coronary perfusion. To understand the multifactorial effects of MD, we developed a computational model that bi-directionally 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 to RA pacing measured in the same swine only when LV contractility is affected by flow alterations with a slope of 1.4 mmHg/ml² 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 (1) the loading conditions that further affect the coronary flow, which may explain some of the changes in , and (2) the coronary flow that reduces global contractility, which contributes to the reduction in LV pressure.

中文翻译：

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冠状动脉血流调节和心脏-冠状动脉耦合在与右心室起搏相关的机械不同步中的作用

机械不同步 (MD) 影响左心室 (LV) 力学和冠状动脉灌注。为了了解 MD 的多因素影响，我们开发了一个计算模型，该模型将体循环与 LV 和冠状动脉灌注与流量调节双向耦合。在该模型中，左前降支 (LAD) 和左回旋支 (LCX) 动脉中的冠状动脉血流会根据规定的线性 LV 收缩力-冠状动脉血流关系影响相应的区域收缩力。该模型通过对 LV 压力和容积的实验测量以及在调节和完全扩张条件下从猪在右心房 (RA) 起搏下获得的 LAD 和 LCX 流速波形进行校准。校准后的模型用于模拟 MD。该模型可以同时再现平均 LV 压力 (39.3%)、调节流量 (LAD: 7.9%; LCX 1.9%)、LAD 被动流量 (21.6%) 和 LCX 被动流量增加 (15.9%) 的降低。与 RA 起搏相比，这些变化与右室起搏相关²收缩流量关系。在敏感性分析中，该模型预测 LAD 和 LCX 的冠状动脉血流储备 (CFR) 会随着 LV 游离壁收缩延迟的增加而减少和增加。这些研究结果表明，与 MD 相关的异步激活影响（1）进一步影响冠状动脉血流的负荷条件，这可以解释 2 的一些变化，以及（2）降低整体收缩力的冠状动脉血流，这有助于减少LV 压力。