Research Of The Effect Of Myocardial Cell Membrane Channel Currents On Ventricular Arrhythmia And Its Regulation

For years, the experimental research in the biomedical field showsthat the electrophysiological activity of mammal`s heart ventricle isaccomplished by many kinds of ion currents(such as sodium ion,potassium ion, calcium ion etc.) which distribute in the ventricle cellmembrane. Because of these ions to participate, a delicate balance couldbe maintained among different types of ion current, and the ventriclenormal electrophysiological activity could be accomplished; However,the ventricle electrophysiological activity is also affected by the changesof the internal and external environment of the cell. Taking the humanventricle as an example, hypokalemia, electrolyte disturbance, drugpoisoning, severe hypoxia, ischemia, organic heart disease and so on.These symptoms could cause the abnormal ion concentration inside andoutside the cell, affect the ventricular electrophysiological activity,significantly reduce the ventricular action potential duration, and producerapid ventricular rate, leading to a rapid heartbeat, engender theventricular arrhythmia, such as ventricular tachycardia, ventricular flutterand ventricular fibrillation and other symptoms, seriously affect thehuman life. Ventricular as the main conduction organizations of the heartconduction system, and it plays a decisive role on ventricular arrhythmia. Experimental study in vitro reveals that potassium ion current plays animportant role in the treatment of ventricular arrhythmias.So it has an important reference significance and reference value forbiomedicine study about the simulation of potassium ion current onventricular electrophysiological activity under the condition of ventriculararrhythmia. By using the model of canine ventricular, we have discussedthe effect of appropriately or excessively inhibited the potassium currenton ventricular cell under the condition of ventricular arrhythmia, andstudied the controlling of later sodium current and extracellular sodiumion concentration on ventricular arrhythmia symptoms which induced byexcessively inhibited the potassium current.The first chapter of this paper introduced concerned basic thoughtand knowledge, including control quantities and kinetic problems, ionchannels, ventricular tissue physiological activities, etc.The second chapter presentated the model of canine ventricular,potassium current multiple factor λ is introduced and the relevantformula is described. After the simulation, we have learned the effect ofappropriately or excessively blocking potassium ion channel currents onventricular arrhythmia; At the same time, the early afterdepolarization(early after depolarization; EAD) internal mechanismcaused by excessively suppress potassium current was further analysised.The results show that if the potassium current blocked appropriately (adjust the parameter λ>0.67, block potassium current less than43%),ventricular arrhythmia could be reduced and even be eliminated thephenomenon of arrhythmia. However, if the potassium current inhibitedexcessively (adjust parameter λ <0.67), for example, if λ=0.1, lead toEAD, increase the symptomatic of ventricular arrhythmia.At the last chapter, we investigated the effect on EAD by regulatedthe late sodium current and extracellular sodium ion concentration. In theoriginal model, we introduced the parametersλ NaL(multiple factors oflate sodium current),λ Nao(multiple factors of extracellular sodium ionconcentration), the parameter λ=0.1was fixed, and make the system atthe symptoms of EAD, then regulated the parametersλ NaLandλ Nao, theparameters ofλ NaL、λ Naorange are0.1~1.0, respectively; then thevarious parameters whether eliminate the phenomenon of EAD wereanalysised. According to the results, when the late sodium current wasblocked reached to80%(ifλ NaL=0.2), could significantly eliminate thephenomenon of EAD. Ranolazine is a specific drug blocking late sodiumcurrent(Its scope of effective treatment is2~6μ mol L, in canineventricular cellsIC50=6μmol L), ifλ NaL=0.2, This data is far beyond thescope of its effective treatment; If reduced extracellular sodium ionconcentration, when regulated the parameterλ Nao=0.55, EAD could beeliminated very well, but extracellular sodium ion concentration reducedtoo much, may cause other diseases; By blocking late sodium current and reducing the extracellular sodium ion concentration at the same time,EAD could be eliminated, blocking the late sodium current in the range ofits effective treatment, ranolazine could play its specific drug role, anddecreasing the extracellular sodium ion concentration in the physiologicalallowed range, also; In order to reflect the EAD could be well eliminatedby regulating late sodium and extracellular sodium ion concentration atthe same time, We introduce a concept of the discrete of ventricularrepolarization (Beat-to-beat variability of repolarization, BVR).Combining BVR, the reasonable range of control late sodium current andextracellular sodium concentration was given. The results show that,when EAD occurs, we may be able to reduce or eliminate the negativeeffects by adjusting the late sodium current and the extracellular sodiumconcentration, as well as other methods.