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Mechanism‐Specific Antiarrhythmic Effects of the Potassium Channel Activator Levcromakalim Against Repolarization‐Dependent Tachycardias
Author(s) -
VOS MARC A.,
GORGELS ANTON P.M.,
LIPCSEI GYORGYI C.,
GROOT S.H. MARIEKE,
LEUNISSEN JET D.M.,
WELLENS HEIN J.J.
Publication year - 1994
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1994.tb01196.x
Subject(s) - medicine , potassium channel , repolarization , cardiology , potassium channel blocker , activator (genetics) , pharmacology , electrophysiology , receptor
Mechanism‐Specific Action of Levcromakalim. Introduction: The hypothesis that levcromakalim. a potassium channel (I K‐ATP .) activator with antihypertensive properties, has a mechanism‐specific antiarrhythmic action against repolarization‐dependent ventricular tachycardias (VTs) was tested in dogs. Methods and Results: A low dose of leveromakalim (0.01 mg/kg) was selected, which decreased blood pressure by 25% but had almost no electrophysiologic effect on AV nodal or ventricular conduction or effective refractory period. In dogs with chronic AV block, the antiarrhythmic action of this dose of levcromakalim was evaluated in three models of abnormal impulse formation: (I) dsotalol (2 mg/kg) induced torsades de pointes VT, initiated by early afterdepolarizations (EADs). (2) sustained ouabain‐induced VTs, which are dependent on delayed after depolarizations (DADs), and (3) VT occurring 24 hours after left anterior descending coronary artery occlusion, which are likely based on abnormal automaticity. Levcromakalim abolished d‐sotalol induced U waves, ventricular ectopic beats, and self‐terminating bouts of torsades de pointes. Induction of torsades de pointes by pacing was also completely prevented. The cycle length of the idioventricular rhythm, which was lengthened after d‐sotalol from 1490 ± 515 to 1700 ± 610 msec (P < 0.05), remained similar after levcromakalim (1655 ± 580 msec). The QT(U) duration, which was increased after d‐sotalol from 410 ± 55 to 550 ± 40 msec (P < 0.05), normalized to 405 ± 70 msec (P < 0.05). Lcvcromakulim did not suppress but rather enhanced ouabain‐induced VT by decreasing the cycle length slightly from 315 ± 35 to 290 ± 35 msec (P < 0.05). Pretreatment with a beta Mocker prevented this acceleration in rate. Finally, levcromakalim had no effect on VT 24 hours after infarction. Conclusion: A low dose of levcromakalim has specific antiarrhythmic properties against repolarization‐dependent arrhythmias, but it does not affect VTs based on other mechanisms of abnormal impulse formation.