Electrophysiology of the atrioventricular junction: Implications for novel bioelectric antiarrhythmia therapies.

摘要

The atrioventricular junction (AVJ) of the heart is the crossroads of the cardiac conduction system which determines the delay between atrial and ventricular contraction. However its role in cardiac electrophysiology is not limited to slow conduction: it can also function as a pacemaker, filter, or an arrhythmogenic substrate. The complicated structure of the AVJ includes multiple myocardial cell types, unique cell-to-cell coupling, and discrete input pathways. AVJ pathology is clinically significant because AV nodal reentrant tachycardia (AVNRT) is the most common paroxysmal supraventricular tachycardia with over 90,000 cases per year, and AV block is a leading cause of pacemaker implantation. Despite its prominent role in cardiac electrophysiology, detailed understanding of many aspects of AVJ structure and function is lacking due to the inherent difficulty of relating specific functional phenomena to its complex structural heterogeneity.;In this dissertation, we developed a trimodal biophotonic imaging approach to correlate AVJ structure with function. Our approach used optical mapping with voltage-sensitive dyes to characterize electrophysiological function, optical coherence tomography to investigate intact structure, and molecular mapping with immunohistochemistry. With this approach, we characterized mechanisms of AV conduction, autonomic control, pacemaking properties, and the molecular characteristics of the rabbit AVJ. Our results indicated that the AV delay can be avoided through a particular pathway of the rabbit AVJ. Additional studies identified this pathway as a pacemaking region and characterized its autonomic control, innervation, and unique cell to cell coupling. Recent investigations translated our results from the rabbit to the human including the first instance of in vitro optical mapping of the human AVJ during normal rhythm and AVNRT. In the human, we identified two pathways by cell to cell coupling patterns. Our results in rabbit and human have many clinical implications. For instance, the pathways identified in the human AVJ could influence the treatment of AVNRT. Clinical pacing strategies could take advantage of the pacemaking and autonomic control present in the AVJ to enhance its pacemaking activity. Finally, the observation that excitation in a specific pathway of the AVJ can avoid the AV delay makes it a promising candidate for electronic or biological pacemaker implantation.