Modeling And Simulation Of Biological Pacemaker In Human Ventricle

The heart is one of the important organs of the human body,providing power for the circulation of the blood.Once the disfunction occures,often leading to serious diseases,of which,sinus node dysfunction,atrioventricular block and other cardiac conduction diseases are of high incidence,causing chest tightness,syncope and even sudden death.The best way to treat these diseases is to implant eletronic pacemakers.However,there are many disadvantages which can not be ignored,such as infections,surgery to repalce the battery and so on,though the pacemakers are able to greatly improve the quality of life of patients.As a result,the more advanced pacemakers are expected to take place of the electronic ones;and as the leading-edge,biological pacemaker is considered to have the potential to overcome the drawbacks of the electronic ones.Nevertheless,the bio-experiments are always time-consuming,laborious and expensive.With the help of the cross advantages of computer and mathematics,the computatiomal models are established in the dissertation to explore the pacing mechanism and pathogenic risk of the biological pacemaker at mutiple scales from single cell to tissue,which could provide theoretical guidance for the development and early clinical application of the biological pacemaker.The main content and contributions are summarize as follows:Firstly,the nonlinear dynamics theory is applied to analyze the pacing mechanism of the single cell,finding the transmembrane currents which would influence the pacing;make the single cell pacing by adjusting the dependent currents to provide the basis for generating biological pacemaker.Under normal conditions,the ventricular work cells are non-pace-making,which could only make one full action potential once receive the threshold stimulus from the sinoatrial node and then keep in the resting state.The cells could not generate electronic exciation automatically,maintaining the constant voltage,until the next treshold stimulus comes.By the nonlinear dynamic analysis,combined with the experimenal verification,the consitions to make the cell pacing could be found.In tradition,many conditions are continually tried manually to find the reasonable ones to make the cell pacing;and with the use of nonlinear dynamic theory,the conditions could be achived by calculations.Secondly,when the single cells are set to pace,the effect of the change on the ventricular function is discussed before the pacemaker is generated.The results demonstate that the pacing ability of the ventricular tissue increases and the sinus rhythm is weakened when the cells in large area have the pacing capability.Meanwhile,the electrical conduction velocity reduced in the ventricle,leading to long QT interval,more likely to cause reentrant wave and inducing arrhythmia.Therefore,it should be avoided to simply increase the number of the automatic cells to improve the capability of the biological pacemaker.Thirdly,the effect of electrical isolation(insulation)between the pacemaker and the ventricular tissue on the driving ability of the biological pacemaker is investigated.The driving ability could be enhanced by simply increasing the automatic cells,however,which may induce arrhythmia.As a consequence,a large part of the contact area is set insulating beween the pacemaker and the ventricular tissue,and the rest is keep electrically conductive.The results show that only a small amount of automatic cells could ensure the pacemaker ’s robust pacing.Therefore,the eletrical isolation could be one important way to generate biological pacemaker.At last,the effect of uncoupling(weak elctrical coupling)between the pacing cells on the driving ability of the pacemaker is investigated.Too many pacing cells may induce arrhythmia;the reasonable pacemaker could be generated by electrical isolation,however,which is difficult to operate in bio-experiments.As a result,the anisotropic electrical conduction equations is derivated and a pacemaker model is established to study the enhancing effect of weak coupling on the driving capability of the pacemaker.The results indicate that for the pacemaker consisting of constant cells,the driving ability is enhanced as the coupling weakens.The pacemaker could drive the ventricular tissue robustly only by a small mount of automatic cells,when the coupling is weakened.As result,the weak coupling is one more reasonable method to generate biological pacemaker.