Dexmedetomidine and Clonidine Inhibit Ventricular Tachyarrhythmias in a Rabbit Model of Acquired Long QT Syndrome

Background: Agents with a-2 adrenoreceptor (AR) agonistic action have reportedly suppressed tachyarrhythmias. Methods and Results: We hypothesized that a-2 AR agonists would have an inhibitory effect on abnormal repolarization-related ventricular tachyarrhythmias (VTs). To test this hypothesis, the effects of 2 clinically available a-2 AR agonists (dexmedetomidine and clonidine) on the occurrence of VTs were assessed in a methoxamine-sensitized rabbit model of acquired long QT syndrome (Study 1: n=45). In control rabbits, administration of methoxamine and nifekalant almost invariably caused VTs (14/15). In contrast, incidence of VT significantly decreased during the treatment with dexmedetomidine (1 mu g.kg(-1).min(-1): 5/12 [P<0.01 vs. control]) or with clonidine (33.3 mu g.kg(-1).min(-1): 10/18 [P<0.01]). To verify that VTs in this animal model are triggered by early afterdepolarization (EAD), the monophasic action potential on the left ventricular surface was recorded in 28 open-chest rabbits (Study 2). EAD-like hump was less frequently detected during treatment with clonidine or dexmedetomidine (2/14) than in saline-treated rabbits (9/10, P<0.005). Presence of a hump was significantly related to the advent of VTs (P<0.05). Conclusions: Agents with a-2 AR agonistic action have an inhibitory effect on VTs in a rabbit model of long QT syndrome. Alpha-2 AR agonists, especially dexmedetomidine, may be a therapeutic choice for abnormal repolarization-related VTs that are resistant to conventional treatment. (Circ J 2012; 76: 2343-2347)