title: The calcium channel antagonist, flunarizine, protects against ventricular fibrillation.
abstract: Elevations in intracellular calcium during myocardial ischemia have been implicated in the development of lethal cardiac arrhythmias. The calcium antagonist, flunarizine, has been shown to suppress the accumulation of intracellular calcium and has been proposed to protect against triggered activity due to calcium overload. Using 13 mongrel dogs with healed myocardial infarctions, ventricular fibrillation (VF) was induced by a 2 min coronary occlusion during exercise. This exercise plus ischemia test consistently induced VF during control (C, vehicle) presentations. Pretreatment with flunarizine (2.5 mg/kg i.v.) completely suppressed VF in all the animals (P less than 0.001 Chi-squared). Flunarizine (F) elicited significant (P less than 0.01 ANOVA) reductions in left ventricular (LV) systolic pressure (C 143.2 +/- 12.0 F 92.3 +/- 10.5 mm Hg), LVdP/dt max (C 4256 +/- 251.9, F 1784 +/- 297.2 mm Hg/s) and heart rate (C 118.8 +/- 7.4, F 104.7 +/- 9.0 beats/min). Since heart rate can contribute significantly to the development of VF, the exercise plus ischemia test was repeated with heart rate held constant with ventricular pacing (n = 3, 230.0 +/- 10 beats/min). Flunarizine pretreatment still prevented VF under these conditions.
authors.affiliation: Department of Physiology, Ohio State University, Columbus 43210-1218.
authors.forename: G E
authors.initials: GE
authors.lastname: Billman
mesh_terms: D000818:Animals; D004285:Dogs; D005444:Flunarizine / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000517:prevention & control*
chemical_list: D005444:Flunarizine