Cardiac arrhythmogenesis and the isoelectric window
Description
Despite over a century of research the mechanisms underlying defibrillation failure remain unknown and the only available method of terminating life-threatening arrhythmia such as ventricular fibrillation (VF) is defibrillation by high-strength electrical shocks. Typically in larger hearts such as dogs, pigs, and sheep, a period of electrical quiescence has been observed following defibrillation shocks. This period of time, termed the isoelectric window (IW), is ended tens of milliseconds later, by the emergence of a global post-shock activation which can regenerate into VF. The mechanisms underlying the origination of this delayed post-shock activation are unknown and a hotly debated topic. This research investigates the mechanisms underlying this post-shock activation that ends the IW utilizing two investigative methodologies Optical mapping was used to test the hypothesis that graded responses rather than regenerative responses following a field shock were responsible for this post-shock activation. It was demonstrated that following a defibrillation shock, distributions of shock-induced graded responses at shock-end resulted in post-shock arrhythmia generation tens of milliseconds following shock-end. Additionally, the origination of these activations was examined focusing on the effects of the shock timing as well as shock polarity, and whether these post-shock activations emerged preferentially on the epi- or the endocardial surface The second part of this research used computational methods to investigate differences in electrical activity between the surfaces and within the depths of the model preparation as a possible mechanism underlying the generation of the post-shock activation that ends the IW. Using computational methods it was determined that differences in electrical activity induced by the shock between the surfaces and within the depths could underlie the origination of the postshock activation that ends the IW These findings elucidated two possible mechanisms underlying the origination of the post-shock activation that ends the IW following the defibrillation type shocks. Understanding the events occurring during the IW and leading up to the generation of these post-shock activations is vital to elucidating the mechanisms underlying defibrillation failure