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Computer Model of the Canine Ventricle

犬心室的计算机模型

基本信息

批准号：
7151190
负责人：
Robert F Gilmour
金额：
$ 61.14万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-12-15 至 2009-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7151190
关键词：
3-Dimensional Action Potentials Address Adrenergic Agents Agonist Algorithms Anatomic Models Apical Arrhythmia Behavior Buffers Calcium Calmodulin Canis familiaris Cardiac Cardiac Myocytes Cell model Code Complex Computer Simulation Condition Data Data Analyses Development Diagnosis Disease Effectiveness of Interventions Electric Countershock Elements Evaluation Fiber Genes Heart Heterogeneity Hodgkin Disease Imagery Individual Laboratories Left Left ventricular structure M cell Measurement Measures Methods Modeling Morbidity - disease rate Muscle Cells Pathway interactions Pharmaceutical Preparations Phase Physiological Play Potassium Publishing Rate Research Personnel Right ventricular structure Role Running Sarcoplasmic Reticulum Science Secondary to Series Signal Pathway Signal Transduction Sodium Sudden Death Supercomputing System Tachyarrhythmias Tachycardia Techniques Technology Testing United States Universities Update Ventricular Ventricular Fibrillation Ventricular Tachycardia Writing adrenergic cell type computer program cost drug discovery drug testing heart electrical activity heart rhythm improved indium arsenide innovation markov model mortality novel parallel computer prevent programs simulation time use tool uptake

项目摘要

DESCRIPTION (provided by applicant): Sudden death secondary to ventricular fibrillation (VF) remains a leading cause of mortality in the US. Therapy for VF has been largely ineffectual, principally because the underlying mechanisms for VF are not well understood and probing for potential mechanisms has been hindered by the inability to precisely modify specific ionic currents. To address these issues, we propose to develop a data-driven computer model of the electrical behavior of the canine ventricle. Specifically, we will: 1) Experimentally characterize IKr, ICa, IK1, INaCa, and the late sodium current INa in myocytes obtained from specific regions of the ventricles. These particular currents will be studied because they play a significant role in repolarization. They will be measured using action potentials recorded at rapid pacing rates as the command waveforms, to replicate current behavior during a tachyarrhythmias. 2) Develop deterministic Hodgkin-Huxley and Markov models for each ionic current for each anatomical region using the time series and steady state current data obtained under Specific Aim 1. Optimization routines will be used to determine unknown parameters in the models by comparing the model current to experimental data. 3) Incorporate the models of the individual currents into computer models of region-specific single canine ventricular myocytes. Models of left and right ventricular epicardial, midmyocardial and endocardial myocytes of basal and apical origin and of right and left ventricular Purkinje myocytes will be developed. 4) Incorporate the single cell models into a 3-D computer model of the canine ventricle using a modified version of the phase field method. The model will be written using a portable parallel version of the code and run on a parallel computer and multi-node clusters. Initially, the model will consist of the left ventricle, with epicardial, midmyocardial and endocardial layers. More detailed anatomical models subsequently will be constructed to include the His-Purkinje system and the right ventricle. 5) Use the 3-D model to test candidate hypotheses for the development of VF. The initial test will determine whether suppressing dynamic electrical heterogeneity prevents VF. The computer model of ventricular electrical function we propose will provide an invaluable tool for drug discovery and the evaluation of algorithms for anti-tachycardia and anti-fibrillatory pacing and defibrillation. As such, the model is expected to have a significant impact on the diagnosis and treatment of lethal heart rhythm disorders.

描述（由申请人提供）：