Abstract | BACKGROUND: METHODS AND RESULTS:
Pinacidil, an I(K- ATP) channel opener, was administered in increasing concentrations (50-100 microM) in 48 Langendorff-perfused rabbit hearts and led to a significant reduction of action potential duration and QT interval, thereby mimicking SQTS. Eight simultaneously recorded monophasic action potentials demonstrated an increase in dispersion of repolarization, especially between the left and the right ventricle. During programmed ventricular stimulation with up to two extrastimuli, pinacidil significantly increased the inducibility of ventricular fibrillation (1 heart under baseline conditions, 29 hearts during pinacidil administration; P = 0.0001). Additional treatment with the I(Kr) blocker sotalol (100 microM) and the class I antiarrhythmic drugs flecainide (2 microM) and quinidine (0.5 microM) randomly assigned to three groups of 16 hearts led to prolongation of repolarization as well as refractory period. Sotalol or flecainide did not reduce the rate of inducibility of ventricular fibrillation significantly (P = 0.63; P = 0.219). However, quinidine reduced the inducibility of ventricular fibrillation by 73% (P = 0.008). The antiarrhythmic potential of quinidine was associated with a significantly greater prolongation of MAP duration, refractoriness, and postrepolarization refractoriness (PRR) as compared with sotalol and flecainide. Moreover, quinidine, in contrast to sotalol and flecainide, reduced dispersion of repolarization. CONCLUSION:
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Authors | Peter Milberg, Regina Tegelkamp, Nani Osada, Rainer Schimpf, Christian Wolpert, Günter Breithardt, Martin Borggrefe, Lars Eckardt |
Journal | Journal of cardiovascular electrophysiology
(J Cardiovasc Electrophysiol)
Vol. 18
Issue 6
Pg. 658-64
(Jun 2007)
ISSN: 1540-8167 [Electronic] United States |
PMID | 17521304
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Arrhythmia Agents
- Vasodilator Agents
- Pinacidil
- Sotalol
- Quinidine
- Flecainide
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Topics |
- Action Potentials
(drug effects)
- Animals
- Anti-Arrhythmia Agents
(pharmacology)
- Arrhythmias, Cardiac
(chemically induced, diagnosis, drug therapy)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Electrocardiography
- Electrophysiologic Techniques, Cardiac
- Flecainide
(pharmacology)
- Heart Conduction System
(drug effects)
- In Vitro Techniques
- Pinacidil
- Quinidine
(pharmacology)
- Rabbits
- Random Allocation
- Refractory Period, Electrophysiological
(drug effects)
- Sotalol
(pharmacology)
- Vasodilator Agents
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