Influence of Activation Time on Hemodynamic Parameters: a Simulation Study

Abstract

Ventricular activation time (AT [ms]) is the time required to activate the ventricle electrically. The in uences of AT on hemodynamics are of interest in clinical studies on methods for improving left ventricle (LV) function. However, the cardiovascular system is a dynamic system, in which many parameters are interrelated with each other, and teasing out the causality of the effects of AT within the system experimentally is dif cult. In this research, we focused on analyzing the effects of changing AT on hemodynamics using a hemodynamic model by incorporating a cardiac tissue model into an LV geometric model within a circulation model. The cardiac tissue model is constructed by connecting 10 cardiac cellular contraction models in the ber direction. In our cardiac tissue model, AT is represented by adding a constant delay time, δ delay [ms], to the starting times of calcium transients between adjacent contraction models. Thus, AT becomes δ delay × 9 [ms]. Simulations were performed under two conditions: normal AT (99 [ms], physiological); and prolonged AT (207 [ms], pathological). AT prolongation caused slight decreases in stroke volume (SV [mL]) and ejection fraction (EF [%]) by 2.10% and 6.00%, respectively, since both LV end-systolic and LV end-diastolic volumes increased by similar amounts. Maximum elastance (E max [mmHg/mL]) decreased by 15.4%. The maximum rate of LV pressure rise (max dp/dt [mmHg/ms]) decreased markedly by 43.7% at longer AT. The cellular mechanisms underlying changes in half sarcomere length were analyzed individually in 10 cells. Even though hemodynamic parameters did not change signi cantly, we concluded that large differences in cell behaviors existed.

Mathematical Analysis of Left Ventricular Elastance with respect to Afterload Change During Ejection Phase

“…To simplify the mathematical analysis, we simplified the hemodynamic model proposed by Utaki et al [49, 45] for two points. First, LV wall thickness was fixed at a constant length, and second, the relation between the LV internal radius ( R l,v ) and LV volume ( V l,v ) was simplified to linear.…”

“…In this research, a simplified hemodynamic model proposed by our group [49, 45] was used for mathematical analysis. The model was constructed from a circulation model, a LV geometry model, and a muscle contraction model.…”

“…Utaki et al [49, 45] used the following reported data to define the relation between R ιυ and L . Rodriguez et al [31] also measured the time course of canine LV sarcomere length.…”

Mathematical analysis of left ventricular elastance with respect to afterload change during ejection phase

“…In this research, a simplified hemodynamic model proposed by our group [ 24 , 25 ] was used for mathematical analysis. The model was constructed from a circulation model, a LV geometry model, and a muscle contraction model.…”

“…Utaki et al [ 24 , 25 ] used the following reported data to define the relation between R lv and L . Rodriguez et al [ 31 ] measured the time course of canine LV sarcomere length, and Sabbah et al measured the time course of the canine LV internal diameter [ 32 ].…”