In vivo cardiac electrophysiologic and antiarrhythmic effects of an isoquinoline IKur blocker, ISQ-1, in rat, dog, and nonhuman primate.
J Cardiovasc Pharmacol
; 49(4): 236-45, 2007 Apr.
Article
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| MEDLINE
| ID: mdl-17438409
ABSTRACT
The cardiac electrophysiologic effects of ISQ-1, an isoquinolinone I(Kur) blocker, were characterized in vivo. In rat, ISQ-1 elicited maximal 33% to 36% increases in atrial and ventricular refractoriness at a plasma concentration of 11.5 microM. In African green monkey, ISQ-1 increased atrial refractory period (maximal 17% at plasma concentration up to 20 microM) with no effect on ventricular refractory period or ECG QTc. Likewise in dog, ISQ-1 increased atrial refractory period (maximal 16% at plasma concentration up to 2 microM) with no effect on ventricular refractory period or QTc. In contrast, studies with ibutilide in nonhuman primate and dog demonstrated concomitant increases in atrial and ventricular refractoriness and QTc. Additionally, in a dog model of atrial flutter, ISQ-1 terminated ongoing flutter at doses (2.5 +/- 0.5 mg/kg IV) that selectively prolonged atrial refractoriness (13% increase), whereas flutter termination with ibutilide occurred at doses that increased both atrial and ventricular refractoriness as well as QTc. Of note, the cardiac electrophysiologic profiles displayed by ISQ-1 in these species were similar to those reported previously by our lab with a structurally distinct I(Kur) blocker. Taken together, these results further support the inhibition of I(Kur) as an approach to terminate atrial arrhythmia.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arritmias Cardíacas
/
Primates
/
Técnicas Electrofisiológicas Cardíacas
/
Bloqueadores de los Canales de Potasio
/
Isoquinolinas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos