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Role of coronary flow regulation and cardiac-coronary coupling in mechanical dyssynchrony associated with right ventricular pacing. Am J Physiol Heart Circ Physiol 2021 Mar 01;320(3):H1037-H1054



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-85102406585   5 Citations


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/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 CFR, and 2) the coronary flow that reduces global contractility, which contributes to the reduction in LV pressure.NEW & NOTEWORTHY 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.

Author List

Fan L, Namani R, Choy JS, Awakeem Y, Kassab GS, Lee LC


Lei Fan PhD Assistant Professor in the MU-MCW Department of Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cardiac Pacing, Artificial
Computer Simulation
Coronary Circulation
Disease Models, Animal
Models, Cardiovascular
Myocardial Contraction
Stroke Volume
Sus scrofa
Time Factors
Ventricular Dysfunction, Left
Ventricular Function, Left
Ventricular Function, Right
Ventricular Pressure