Bistability and arrhythmogenesis in rapidly paced cardiac muscle: Experiments and modeling

Cardiac arrhythmias occur when the electrical rhythm and resulting contraction of the heart is abnormal. Arrhythmias can afflict the chambers of the heart that supply blood to the body, the ventricles, and the chambers of the heart that receive blood from the body, the atria. Ventricular arrhythmias can cause the heart to stop supplying blood to the body which can lead to sudden cardiac death. Hundreds of thousands of people die annually from sudden cardiac death. While less acutely deadly, atrial arrhythmias are highly undesirable as they can contribute to reduced cardiac output, embolisms, strokes, and decreased life expectancy. Millions of people have atrial arrhythmias at any given time. Clearly, there is tremendous incentive to investigate and understand cardiac arrhythmias.; This dissertation presents an anatomically and physiologically based model of the human right atrium that was used to assess the effects of pacing. The model was a two-dimensional surface existing in a three-dimensional space and included the superior vena cava, inferior vena cava, tricuspid valve, coronary sinus, crista terminalis, smooth muscle, pectinate muscle, and sinoatrial node. Electrical activation and propagation were modeled using the monodomain formulation. The model was discretized using the finite difference method and had 200,901 computational nodes.; In an effort to understand results seen experimentally in sheep, the model was exercised using a downsweep/upsweep pacing protocol whereby pacing period was decremented then incremented. The model reflected the experimental results in that 1:1/2:1 bistability in its response to the stimuli was observed and idiopathic waves were observed and found to be correlated with 1:1/2:1 bistability. The model demonstrated a clear link between bistability and formation of idiopathic waves. Furthermore, by including the entire atrium, the model was able to show the mechanisms of idiopathic wave initiation, maintenance, and termination.; All atrial structures played a role to varying degrees in idiopathic wave initiation, maintenance, and termination. The crista terminalis was the most involved. The model demonstrated that irregular behavior in the atrium is linked to bistability in the atrium and a fundamental cause of irregular behavior in the atrium is differences in the local electrical dynamics in the different atrial structures.; In the future, the model can be used to investigate other irregular behaviors and to test electrical and pharmacologic therapies for atrial arrhythmias. The research presented here has laid significant groundwork and provided a useful model, framework, and direction for future work.