Ibutilide: enhanced defibrillation via plateau sodium current activation.
Reductions in current and energy requirements for defibrillation have previously been ascribed to type III antiarrhythmic agents that block outward potassium conductance. This study investigated the effect on defibrillation of ibutilide, a type III antiarrhythmic agent that prolongs action potential duration by activating the sodium component of the plateau inward current. Pentobarbital-anesthetized dogs were subjected to serial episodes of ventricular fibrillation lasting 10 s. In protocol I, current and energy defibrillation requirements were determined via an interactive approach after bolus injections of saline placebo and ibutilide (0.1 mg/kg i.v.). In protocol II, a current dose-response method was utilized in which four shocks each at current doses of 0.7, 0.8, 0.9, and 1.0 x an estimated defibrillation threshold were administered before and after ibutilide (0.075 mg/kg bolus; 0.00125 mg.kg-1 x min-1 i.v.). In protocol I, current and energy values associated with defibrillation measured 10.9 +/- 4.5 A and 16.0 +/- 11.9 J for ibutilide compared with 14.1 +/- 5.6 A and 27.7 +/- 17.7 J for placebo, respectively (n = 9, P < 0.005). In protocol II, ibutilide significantly shifted the current doses associated with 50% successful defibrillation from 14.8 +/- 3.7 to 8.9 +/- 2.0 A (n = 6, P < 0.05). Eight of 15 animals given ibutilide exhibited one or more episodes of spontaneous defibrillation. Ibutilide significantly (P < 0.05) increased ventricular effective refractory period (+23.4%), and both preventricular fibrillation and postdefibrillation monophasic action potential duration at 90% repolarization (+21.7% and +23.3%, n = 9, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Cardiology, Veterans Affairs Medical Center, Long Beach 90822.
R C
RC
Wesley
F
F
Farkhani
D
D
Morgan
D
D
Zimmerman
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007275:Injections, Intravenous; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D013449:Sulfonamides; C067192:ibutilide