Yuriy V Egorov1,2, Vladislav S Kuz'min1,3,2, Alexey V Glukhov1,2, Leonid V Rosenshtraukh1,2. 1. Laboratory of Heart Electrophysiology, Cardiology Research Centre, Moscow, Russian Federation, Russia. 2. Department of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College, London, UK. 3. Pirogov Russian National Research Medical University (RNRMU), Moscow, Russian Federation.
Abstract
INTRODUCTION: Despite the importance of neurogenic initiation of rapid firing from pulmonary veins (PVs), the mechanism of autonomic modulation of electrophysiological properties of the PV myocardium to form a substrate for atrial arrhythmia remains poorly understood. METHODS AND RESULTS: A 2-microelectrode technique was used to characterize electrophysiological properties of rat PV myocardium and to explore PV arrhythmogenesis, at baseline, during electrical stimulation and/or under autonomic modulation. PV myocardium was characterized by prolonged action potential duration (APD), high degree of APD alternans, and spontaneous depolarizations. Autonomic stimulation resulted in significantly enhanced APD dispersion within the PV, which dynamically changed over time and was associated with intra-PV and atria-PV conduction blocks and could lead to spontaneous fibrillation-like high-frequency activity. In the distal part of the PV we found an unexcitable area that was characterized by depolarized resting potential (-50 ± 4 mV vs. -75 ± 2 mV vs. PV mouth, P < 0.01). This region could be activated during autonomic stimulation or fast pacing that led to multiple conduction discontinuities (uni- and bi-directional conduction blocks, Wenckebach periodicity, electrotonic modulation conduction block, echo phenomenon) in 17/23 preparations, including those occurring under norepinephrine superfusion (14/17) and during pacing frequency changes (3/17). PV echoes (unstable reentrant circuits) were found in 8/23 preparations. In some experiments, several types of conduction abnormalities were observed. CONCLUSION: The PV myocardium demonstrates distinct electrophysiological characteristics, which could be considerably exaggerated by electrical stimulation and/or autonomic nervous system to dynamically form a functional substrate to support re-entry as well as focal activity.
INTRODUCTION: Despite the importance of neurogenic initiation of rapid firing from pulmonary veins (PVs), the mechanism of autonomic modulation of electrophysiological properties of the PV myocardium to form a substrate for atrial arrhythmia remains poorly understood. METHODS AND RESULTS: A 2-microelectrode technique was used to characterize electrophysiological properties of rat PV myocardium and to explore PV arrhythmogenesis, at baseline, during electrical stimulation and/or under autonomic modulation. PV myocardium was characterized by prolonged action potential duration (APD), high degree of APD alternans, and spontaneous depolarizations. Autonomic stimulation resulted in significantly enhanced APD dispersion within the PV, which dynamically changed over time and was associated with intra-PV and atria-PV conduction blocks and could lead to spontaneous fibrillation-like high-frequency activity. In the distal part of the PV we found an unexcitable area that was characterized by depolarized resting potential (-50 ± 4 mV vs. -75 ± 2 mV vs. PV mouth, P < 0.01). This region could be activated during autonomic stimulation or fast pacing that led to multiple conduction discontinuities (uni- and bi-directional conduction blocks, Wenckebach periodicity, electrotonic modulation conduction block, echo phenomenon) in 17/23 preparations, including those occurring under norepinephrine superfusion (14/17) and during pacing frequency changes (3/17). PV echoes (unstable reentrant circuits) were found in 8/23 preparations. In some experiments, several types of conduction abnormalities were observed. CONCLUSION: The PV myocardium demonstrates distinct electrophysiological characteristics, which could be considerably exaggerated by electrical stimulation and/or autonomic nervous system to dynamically form a functional substrate to support re-entry as well as focal activity.
Authors: Yuriy V Egorov; Di Lang; Leonid Tyan; Daniel Turner; Evi Lim; Zachary D Piro; Jonathan J Hernandez; Rylie Lodin; Rose Wang; Eric G Schmuck; Amish N Raval; Carter J Ralphe; Timothy J Kamp; Leonid V Rosenshtraukh; Alexey V Glukhov Journal: J Am Heart Assoc Date: 2019-10-10 Impact factor: 5.501
Authors: Andrew P Holmes; Ting Y Yu; Samantha Tull; Fahima Syeda; Stefan M Kuhlmann; Sian-Marie O'Brien; Pushpa Patel; Keith L Brain; Davor Pavlovic; Nigel A Brown; Larissa Fabritz; Paulus Kirchhof Journal: PLoS One Date: 2016-05-05 Impact factor: 3.240