Jianyin Lu

An approximation model of myocardial crossbridge for weak coupling calculation of left ventricle model and circulation model

It is necessary to use complicated myocardial cell model and heart model to evaluate the regional energy production and consumption which leads to the unrealistic computational time. In this research, a left ventricle (LV) simulation model was constructed which includes accurate myocardial cell model. In order to simulate the model in realistic time, we introduced an approximation model of the crossbridge model which can be calculated with weak coupling calculation. The LV model was combined with a circulation model to validate the proposed model by calculating the hemodynamics parameters and ventricular energetics indices. The ESPVR (End Systolic Pressure Volume Relation) showed linear relation, and also the PVA - ATP consumption relation showed linear relation which are widely known as the physiological characteristics of mammalian hearts. From these results, we can say that the model can be used as a model for physiological simulation experiments which are related to the ventricular energetics.

The Influence of Activation Time on Contraction Force of Myocardial Tissue: a Simulation Study

The efficiency of heart pump function greatly depends on synchronized contraction of myocardial muscle. In this work, contraction simulation of an excitable ventricular tissue cable was constructed to study the influence of excitation patterns on tissue contraction. The tissue cable is composed of elements which contract when excited by an external stimulus. In each calculation step, contraction force of each element is determined by a ventricular cell model. The mechanical deformation is then solved by finite element method and states of cells are updated accordingly. Several factors such as the starting position of the stimulation signal and the conduction velocity of gap-junctions affect contraction behavior. Simulation results show that the activation time, i.e. the time period the stimulation signal needs to spread over the tissue, is a dominant parameter for determining tissue contraction force. Contraction force of myocardial tissue increases monotonically with a decrease in activation time. This result suggests that minimization of activation time might be important for achieving effective tissue contraction

Strong Coupling System for the LV Motion Simulation in a Distributed Simulation Environment

A system where model parts can be easily exchanged and modified is of great advantage, especially in a combination of models such as an electrophysiological cell model and a mechanical model to a more complex left ventricular (LV) motion model. The use of a distributed simulation environment is straightforward because each simulation model is calculated by an existing user-friendly simulator. However, the weak coupling calculation usually used in a distributed environment reduces the accuracy of the simulation and results in an unstable simulation of the LV motion. To overcome this problem, we have developed a strong coupling simulation system for the distributed simulation environment. Simulation results for a myocardial tissue and a simple LV shape model are presented to elucidate the effectiveness of our system

Infant Circulation Model based on the Electrophysiological Cell Model

It is important to use a myocardial cell model to evaluate the effects of the drugs to the hemodynamic parameters. We developed an infant circulation model which incorporates an accurate myocardial cell model including a beta adrenergic system. The beta adrenergic system is essential mechanism for reproducing the response of baroreflex control system. The parameters of the published adult human circulation model were modified to fit the infant hemodynamic values. The guinea pig myocardial cell model was introduced to the circulation model whose baseline heart rate is close to that of an infant. The presented model is in good agreement with results obtained in physiological experiments.

A model for simulation of infant cardiovascular response to orthostatic stress

We developed an infant circulation model which incorporates an accurate myocardial cell model including a beta adrenergic system. The beta adrenergic system is essential for the response reproduction of the baroreflex control system. The proposed model was constructed by modifying the parameters of a human adult circulation model with the aid of a guinea pig myocardial cell model, whose baseline heart rate is close to that of an infant. The presented model is in good agreement with results obtained in physiological experiments.

Fast Drug Action Solving from Cardiac Action Potential by Model Fitting in A Sampled Parameter Space

Model-based predictive approaches have been receiving increasing attention as a valuable tool to reduce cost in drug development. In this work, a model-fltting-based approach for solving drug actions using cardiac action potential recordings is investigated. Contribution of major ion currents in cardiac membrane excitation has been intensively studied. Cardiac cell models nowadays reproduce APs very precisely. Giving a test AP, the activities of involved ion channels can be determined by fitting the cell model to reproduce the test AP. Using experimental APs recordings both before and after drug dose, drug actions can be estimated by changes in channel activity. Due to the high computational cost in calculating cardiac models, a fast approach using only pre- calculated sample set is proposed. The searching strategy in the sampled space is divided into two steps: in the first step, the sample of best similarity comparing with the test AP is selected; then response surface approximation using the neighboring samples is followed and the estimation value is obtained by the approximated surface. This approach showed quite good estimation accuracy for a large number of simulation tests. Experiments using animal AP recordings from drug dose trials were also exemplified in which case the ICaL inhibition effect of nifedipine [10] was correctly discovered.

In silico drug action estimation from cardiac action potentials by model fitting in a sampled parameter space

Model-based predictive approaches have been receiving increasing attention as a valuable tool to reduce high development cost in drug discovery. Recently developed cardiac cell models are integrated with major ion channels and capable of reproducing action potentials (AP) precisely. In this work, a model-fitting-based approach for estimating drug action from cardiac AP recordings is investigated. Giving a test AP, the activities of involved ion channels can be determined by fitting the cell model to reproduce the test AP. Using experimental APs recordings both before and after drug dose, drug actions can be estimated by changes in activity of corresponding ion channels. Localgradient-based optimization methods are too time-consuming due to the high computational cost of cardiac cell models. A fast approach using only pre-calculated samples to improve computational efficiency is addressed. The searching strategy in the sampled space is divided into two steps: in the first step, the sample of best similarity comparing with the test AP is selected; then response surface approximation using the neighboring samples is followed and the estimation value is obtained by the approximated surface. This approach showed quite good estimation accuracy for a large number of simulation tests. Also results for animal AP recordings from drug dose trials were exemplified in which case the ICaL inhibition effect of Nifedipine and IKr inhibition effect of E4031 were correctly discovered.

Stress distribution in a rotationally symmetric and a measurement based left ventricular shape model.

We evaluated the stress distribution in a geometrical shape model and a shape model obtained from human heart using two different fiber orientations. For both orientation models, the results showed large differences of the stress distributions between the mathematical shape model and the measurement based shape model. These results suggest that stress distribution is highly dependent on the model geometry and the usage of a measurement based shape model is important for the evaluation of the left ventricular (LV) wall stress distribution. This fact may have some influences on the reported homogeneity of stress distribution with anatomical fiber orientation model that uses mathematical shape model

Reproducing Nonlinear Force Velocity Relation of Myocardial Tissue by a Nonlinear Parallel Elastic Component

To realize precise simulation of the left ventricular motion, it is important to utilize an accurate myocardial tissue model which can reproduce various characteristics of myocardial tissue contraction. In this study, we show that the nonlinear characteristics of the passive myocardial tissue property is the essential nature of the nonlinear force-velocity relation and present a formulation for hyperelastic physiological tissue property. Experimental results of our myocardial tissue simulation with the hyperelastic material property proposed are in good agreement with the reported force-velocity relation of real tissue