Dexmedetomidine and clonidine inhibit ventricular tachyarrhythmias in a rabbit model of acquired long QT syndrome.
BACKGROUND
Agents with α-2 adrenoreceptor (AR) agonistic action have reportedly suppressed tachyarrhythmias.


RESULTS
We hypothesized that α-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 α-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 (1μg·kg(-1)·min(-1): 5/12 [P<0.01 vs. control]) or with clonidine (33.3μg·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 α-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.
The 4th Department of Internal Medicine, Teikyo University School of Medicine, Mizonokuchi Hospital, 3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki 213-8507, Japan. tsutsui@med.teikyo-u.ac.jp
Kenta
K
Tsutsui
Noriyuki
N
Hayami
Tomoyuki
T
Kunishima
Anna
A
Sugiura
Takashi
T
Mikamo
Kenta
K
Kanamori
Noboru
N
Yamagishi
Satoshi
S
Yamagishi
Hidenori
H
Watanabe
Kosuke
K
Ajiki
Yuji
Y
Murakawa
D058646:Adrenergic alpha-1 Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008729:Methoxamine / Q000009:adverse effects / Q000494:pharmacology; D011744:Pyrimidinones / Q000009:adverse effects / Q000494:pharmacology; D011817:Rabbits; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant; D020927:Dexmedetomidine; D008729:Methoxamine; D003000:Clonidine