The role of mechano-electric feedback in cardiac arrhythmogenesis and defibrillation
Description
In both physiological and pathological processes, cardiac electrical and mechanical activities are inseparably connected and affect each other via excitation-contraction coupling (ECC) and mechano-electric feedback (MEF). While ECC has been extensively studied, there is only limited information on cardiac MEF. The study presented here investigates the role of MEF in cardiac arrhythmia induction and termination through computational simulations In the study, we investigated the role of mechanical impact in the induction and maintenance of arrhythmia, the mechanism of arrhythmia termination by precordial thump and effect of mechano-electrical feedback on the defibrillation efficacy. Our results showed that mechanical impact to the chest may induce a life-threatening arrhythmia, the phenomena called commotio cordis. The timing of impact was suggested to be critical; synchronization of impact with R wave of the ECG was found most vulnerable. Exploration of the underlying mechanisms showed that a class of novel stretch-activated ionic channels (SAC) play an important role in the process, especially the most commonly reported type of nonselective SAC. In the other hand, in the present thesis, we demonstrated that precordial thump is able to terminate arrhythmia if given before the development of ischemia. Otherwise the success rate will be lower. The reason for this was proposed as the sensitized KATP channels to mechanical stimulation under the myocardial ischemia. Activation of cation non-selective SAC explained the success of termination of arrhythmias by precordial thump As the first two studies were external mechanical stimulation, the third project was internal mechanical stimulation, which was conducted with two different computational models: a 2D tissue model and a 3D realistic rabbit model. Our results showed that SAC opening induced by chronic ventricular dilatation contribute partly to the experimentally observed increase of defibrillation threshold (DFT) and arrhythmogenesis. Opening of SAC could cause stretch triggered arrhythmias or lead to earlier repolarization and larger spatial heterogeneity in repolarization, depending on the reversal potential of these channels In conclusion, the findings of the research have important implications for the future study of mechanoelectric feedback and may have clinical applications in the improvement of preventing and manipulating cardiac arrhythmia