Abstract 5286: Human AV Junctional Pacemaker Shift Due to Cholinergic and Adrenergic Stimulations: Optical Imaging with a Novel Long Wavelength Voltage-Sensitive Dye

Abstract

It is well known that under different physiological and pathologic conditions, the atrioventricular junction (AVJ) may become the pacemaker of the heart. However, unlike the well-characterized AVJ pacemaker in animal models, autonomic control of the human AVJ pacemaker has not been studied. Explanted human hearts with different types of cardiomyopathy (n=7) were obtained at the time of cardiac transplantation and perfused with cardioplegic solution. The AVJ was cannulated, isolated from the rest of the heart, immobilized with the excitation-contraction uncoupler blebbistatin (10 μmol/L) and optically mapped using the infrared voltage sensitive dye di-ANBDQBS. Imaging was conducted with 100x100 CMOS camera from endocardial field of view ranging 24x24 to 36x36mm 2 , which allowed to simultaneously map right side of intratrial and intraventricular septa, coronary sinus (CS) and His bundle regions. In control, we found AVJ rhythm of 31+/−15 bpm (2409+/−1264 ms) in all human preparations which originated in compact AV node (N-region, n=4) and/or region between AV node and His bundle (NH-region, n=3). Isoproternol (Iso, 1 μM) induced AVJ rhythm acceleration up to 68+/−12 bpm (913+/−192 ms), temporary pacemaker shift to CS region (n=2) and improved conduction in both slow and fast pathways, which induced reentrant arrhythmias in 3/5 preparations. Acetylcholine (ACh, 1–3 μM) slowed rhythm to 21+/−6 bpm (3130+/−1146 ms) and conduction in both pathways up to complete block, and induced temporary pacemaker shift to CS region in 3/4 preparations. Moreover, we found bifocal activation in 3/4 preparation when two main pacemakers (CS and compact AV node) worked asynchronously with different frequencies, accompanied by the exit block from AV node. We showed by high-resolution optical mapping for the first time that unlike in animal models (rabbit and rat) in isolated coronary perfused human AVJ leading pacemaker localized mostly in the N- or NH-regions. Beta-adrenergic (Iso) and cholinergic (ACh) stimulations of AVJ can significantly accelerate or slow rhythm and conduction, as well as induced pacemaker shift to CS, and result in reentrant arrhythmias. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).