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)
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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, /<sub>Kur</sub>, 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, /<sub>Na</sub>, compared to the ventricle, AF would terminate before VF in hyperkalemia. Mathematical models were used to interpret experimental findings. Results. /<sub>Kur</sub> 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. /<sub>Kur</sub> 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 (/<sub>K,ACh</sub>). 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> /<sub>Kur</sub> 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 |
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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 |
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