Targeting atrioventricular differences in ion channel properties for terminating acute atrial fibrillation in pigs

Pandit, S.V. et al. (2011) Targeting atrioventricular differences in ion channel properties for terminating acute atrial fibrillation in pigs. Cardiovascular Research, 89(4), pp. 843-851. (doi: 10.1093/cvr/cvq359) (PMID:21076156) (PMCID:PMC3306132)

Abstract

<p><b>Aims</b> The goal was to terminate atrial fibrillation (AF) by targeting atrio-ventricular differences in ionic properties.</p> <p><b>Methods</b> Optical mapping was used to record electrical activity during carbachol (0.25-0.5 µM) induced AF in pig hearts. The atrial specific current, /_Kur, was blocked with 100 µM 4-aminopyridine (4-AP) or 0.5 µM DPO-1. Hearts in AF and ventricular fibrillation (VF) were also subjected to increasing levels of extracellular K+ ([K+]o:6-12mM), compared to controls (4mM). We hypothesized that due to the more negative steady-state half inactivation voltage for the atrial Na+ current, /_Na, compared to the ventricle, AF would terminate before VF in hyperkalemia. Mathematical models were used to interpret experimental findings. Results. /_Kur block did not terminate AF in a majority of the experiments (6/9 with 4-AP; ¾ with DPO-1). AF terminated in mild hyperkalemia ([K+]o≤10.0 mM; <i>N</i>=8). In contrast, only 2/5 VF episodes terminated at the maximum ([K+]o: 12 mM [K+]o. /_Kur block did not terminate a simulated rotor in cholinergic AF because its contribution to repolarization was dwarfed by the large magnitude of the acetylcholine-activated K+ current (/_K,ACh). Simulations showed that the lesser availability of the atrial Na+ current at depolarized potentials, and a smaller atrial tissue size compared to the ventricle, could partly explain the earlier termination of AF compared to VF during hyperkalemia.</p> <p><b>Conclusions</b> /_Kur is an ineffective antiarrhythmic drug target in cholinergic AF. Manipulating Na+ current “availability” might represent a viable anti-arrhythmic strategy in AF.</p>

• Item Type: Articles
• Additional Information: <a href="http://dx.doi.org/10.1093/cvr/cvr194"><b>Corrigendum: Cardiovascular Research 92(2):358</b></a>
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Workman, Dr Antony
• Authors: Pandit, S.V., Zlochiver, S., Filgueiras-Rama, D., Mironov, S., Yamazaki, M., Ennis, S.R., Noujaim, S.F., Workman, A.J., Berenfeld, O., Kalifa, J., and Jalife, J.
• Subjects: Q Science > QP Physiology
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Cardiovascular Research
• Journal Abbr.: Cardiovasc Res.
• Publisher: Oxford University Press
• ISSN: 0008-6363
• ISSN (Online): 1755-3245
• Published Online: 13 November 2010