title: Further observations to confirm the arrhythmia mechanism-specific effects of flunarizine.
abstract: In conscious dogs with chronic atrioventricular (AV) block, we recently demonstrated that flunarizine is effective against ouabain-induced arrhythmias (triggered activity resulting from delayed afterdepolarizations, DADs) but fails to suppress spontaneous ventricular tachycardias (VT) occurring 24 h after left anterior descending coronary artery occlusion (abnormal automaticity). Neither does flunarizine affect normal automaticity, which suggests that flunarizine could be used as a clinical tool to recognize cardiac arrhythmias based on triggered activity. To elucidate further the arrhythmia mechanism-specific action of flunarizine, we investigated (a) its hemodynamic and electrophysiologic effects in 6 anesthetized dogs, (b) its ability to prevent pacing-induced VT 7 days after myocardial infarction (reentry) in 9 anesthetized animals, and (c) its effect on premature escape beats (PEBs) in 9 conscious dogs with chronic AV block. PEBs are probably caused by DADs. Flunarizine decreased systemic blood pressure (p less than 0.01), and left ventricular dP/dt (p less than 0.01), but did not affect AH or HV internal, QRS duration, QT time, or the effective refractory period of either AV node or right ventricle over a wide range of (paced) cycle lengths. Flunarizine decreased the inducibility of PEBs by 42% (p less than 0.01), but not that of the reentrant VT in any of the 6 inducible dogs. Therefore, we conclude that although flunarizine has no electrophysiologic effects in normal heart, it prevents induction of PEBs. The inability of flunarizine to prevent induction of reentrant VT confirms the mechanism-specific action of flunarizine against triggered activity.
authors.affiliation: Department of Cardiology, University Hospital, Maastricht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Vos
authors.forename: A P
authors.initials: AP
authors.lastname: Gorgels
authors.forename: J D
authors.initials: JD
authors.lastname: Leunissen
authors.forename: T
authors.initials: T
authors.lastname: van der Nagel
authors.forename: F J
authors.initials: FJ
authors.lastname: Halbertsma
authors.forename: H J
authors.initials: HJ
authors.lastname: Wellens
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D005117:Cardiac Complexes, Premature / Q000517:prevention & control; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005444:Flunarizine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D013610:Tachycardia / Q000517:prevention & control
chemical_list: D005444:Flunarizine