Hiromasa Utaki’s research while affiliated with Ritsumeikan University and other places

Ventricular activation time (AT [ms]) is the time required to activate the ventricle electrically. The influences 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 difficult. 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 fiber direction. In our cardiac tissue model, AT is represented by adding a constant delay time, δdelay [ms], to the starting times of calcium transients between adjacent contraction models. Thus, AT becomes δdelay × 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 (Emax [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 significantly, we concluded that large differences in cell behaviors existed.

Scale parameters are used to combine two or more models in different scales into one integrative model. One of the crucial issues in the research field of biosimulation in hemodynamics is how to determine the scale parameters in comprehensive hemodynamic models comprising a cardiac cellular contraction model and a circulation model. In this report, we propose a method for determining the scale parameters using mathematical equations derived from the shape of the left ventricle (LV), which is assumed to be a hemisphere. In this method, we derived five equations with seven unknown scale parameters. By using measured values of hemodynamic parameters such as the end-systolic and end-diastolic pressures and LV volume, we successfully determined seven scale parameters to reproduce pathological data of progressive hypertension in Dahl salt-sensitive rats. From the results, we found that accompanying the progression of hypertension, the active contraction force at end-diastole first increase by 54%, followed by 93% increase of the passive elastic force. We also successfully reproduced normal human physiological hemodynamics.