Simulation Study Of Cardiac Pathological Electrophysiology With Virtual Heart Mode

Heart disease is currently the leading cause of death in the worldwide,and the incidence and death rate are still in the rising stage.Therefore,the research on cardiac physiology and pathology has been widely concerned by scholars at home and abroad.The use of virtual heart model to simulate various physiological mechanisms of the heart is an effective aid to current clinical methods.The modeling and simulation of virtual heart is an extremely complex system work,which integrates many disciplines such as cytology,biochemistry,anatomy,genetic engineering,computer science,mathematics,and physics theory.By modeling and simulating the shape and function of the heart,virtual heart reproduces the characteristics of electrophysiology,mechanics and hemodynamics properties of the heart under physiological and pathological conditions.The advantage of the virtual heart is that it can quantitatively and visually study the dynamic behavior of the heart and various parameters.It is also very convenient to study how the physiological and pathological changes of the heart at the microscopic cellular level develop into a macroscopic heart change,then contributing to the improvement of the diagnosis and treatment of heart diseases and the development of innovative drugs.In addition,the virtual heart can be repeatedly simulated on research issues,the test results are reproducible,and there are no medical ethics restrictions,which is difficult to achieve in clinical human and animal experiments.In this thesis,the research work mainly focuses on the construction of the virtual heart model and the simulation of cardiac electrophysiology under normal and pathological conditions.The research content mainly includes the following aspects:Based on the image data of human heart(scanned by spiral computer tomography)provided by Zhujiang Hospital of Southern Medical University,combined with the knowledge of the anatomy of the heart,a three-dimensional data model of the human whole heart with a fine anatomical structure was successfully constructed.According to the electrophysiological characteristics of different cardiomyocytes,the action potential model of various cardiomyocytes was constructed based on the ion channel level.Fully considering the conduction pathway of the real heart and the excitation diffusion anisotropy of the myocardium fiber rotation,the excitatory diffusion equation was used to simulate the conduction process of cardiac myocytes.Then based on the male virtual human torso model,the distribution of the cardiac electric field and body surface potential was simulated,and 12-lead electrocardiogram was calculated.The virtual heart was then applied to the simulation study of various heart diseases.The excitation sequence maps and 12-lead electrocardiogram under various pathological conditions were compared with normal case.First,a coupled myocyte-fibroblast model was used to investigate the effects of atrial fibrosis at cellular and human atrial levels.The results show that the fibrosis can modify action potential morphology of human atrial myocyte,slow down wave propagation and has rate adaptation.These caused the atrial electrical heterogeneity.The fibrosis alone was sufficient to cause arrhythmia,induce re-entry wave,result in low amplitude and wide P waves at normal heart rate while significant prolonged and inverse P waves at high heart rate.These symptoms will aggravate with the level of fibrosis increased.Our simulations demonstrated that fibrosis is the substrate of atrial arrhythmia thereby may be a potential target in treatment of atrial arrhythmia.The understanding of the ECG changes could provide some references for clinical diagnosis.Second,by bolcoking four right to left atrial conduction pathways(including Bachmann bundle(BB),posteriorly in the vicinity of the right pulmonary veins(VRPV),transseptal fibers in the fossa ovalis(FO)and muscular bundles on the inferior atrial surface near the coronary sinus(CS)),we investigated the effects of inter atrial block(IAB)with various conduction pathways block combinations.The results showed that single pathway block could not make P wave morphology satisfy the typical diagnostic criteria of IAB.Both BB and VRPV pathways play the important roles in IAB.The importance of the four conduction pathways follows as BB,VRPV,FO and CS(i.e.the superior pathway was more important than the inferior pathway).Although single inferior pathway play subordinate role in the inter-atrial conduction,their combination with other pathway could produce more severe IAB.The simulation results are consistent with the clinical experimental data,and can effectively explain the mechanism of the clinical pacing treatment.This provides a good mutual evidence and provides guidance for future clinical research.Finally,the ventricular excitation delay induced by left anterior fascicular block(LAFB)and slow conduction velocity in the left ventricle anterior wall(LVAW)was simulated.The results showed that conduction delay in LVAW could produce typical ECG waveforms similar to LAFB.The presences of decreased amplitude and prolonged duration of QRS are good indicators of conduction delay in LVAW.In view of their different pathological mechanisms,effective differentiation in diagnosis will play a positive role in treatment.The simulation results achieved the intended purpose of the study,indicating that our model can truly reproduce the various physiological and pathological electrical characteristics of the heart,and can assist in the analysis of the mechanism of heart disease and give guidance.The work of this thesis is very useful for the further study of cardiac pathological mechanisms and clinical treatments.