Dataset Information

Electromechanical and atrial and ventricular antiarrhythmic actions of CIJ-3-2F, a novel benzyl-furoquinoline vasodilator in rat heart.

ABSTRACT:

Background and purpose

This study was designed to examine the antiarrhythmic efficacy and the underlying mechanisms of the benzyl-furoquinoline vasodilator, CIJ-3-2F, in rat cardiac preparations.

Experimental approach

Conduction electrograms and left ventricular pressure were determined in Langendorff-perfused hearts. Action potentials were assessed with microelectrode techniques, calcium transients by fura-2 fluorescence and ionic currents by whole-cell patch-clamp techniques.

Key results

In isolated hearts, CIJ-3-2F prolonged sinus cycle length, QT interval, Wenckebach cycle length, atrio-His bundle and His bundle-ventricular conduction intervals, refractory periods in atrium, AV node, His-Purkinje system and ventricle, and also increased left ventricular pressure. CIJ-3-2F reduced the incidences of both ischaemic and reperfusion-induced ventricular arrhythmias and prevented the induction of atrial tachyarrhythmias. In both atrial and papillary muscles, CIJ-3-2F decreased upstroke velocity and prolonged duration of the action potential. In ventricular myocytes, CIJ-3-2F moderately increased the amplitude of [Ca(2+)]i transients and cell shortening. CIJ-3-2F inhibited the transient outward K(+) current (Ito ) (IC?? = 4.4??M) with accelerated inactivation, a slower rate of recovery from inactivation and use-dependency. CIJ-3-2F also suppressed the steady-state outward K(+) current (Iss , IC?? = 3.6??M, maximum inhibition = 65.7%) and both the inward Na(+) current (INa , IC?? = 2.8??M) and L-type Ca(2+) current (ICa,L , IC?? = 4.9??M, maximum inhibition = 69.4%).

Conclusions and implications

CIJ-3-2F blocked Na(+) and Ito channels and, to some extent, also blocked Ca(2+) and Iss channels, modifying cardiac electromechanical function. These effects are likely to underlie its antiarrhythmic properties.

SUBMITTER: Chang GJ

PROVIDER: S-EPMC4128053 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Electromechanical and atrial and ventricular antiarrhythmic actions of CIJ-3-2F, a novel benzyl-furoquinoline vasodilator in rat heart.

Chang Gwo-Jyh GJ Yeh Yung-Hsin YH Lin Tsung-Pin TP Chang Chi-Jen CJ Chen Wei-Jan WJ

British journal of pharmacology 20140801 16

<h4>Background and purpose</h4>This study was designed to examine the antiarrhythmic efficacy and the underlying mechanisms of the benzyl-furoquinoline vasodilator, CIJ-3-2F, in rat cardiac preparations.<h4>Experimental approach</h4>Conduction electrograms and left ventricular pressure were determined in Langendorff-perfused hearts. Action potentials were assessed with microelectrode techniques, calcium transients by fura-2 fluorescence and ionic currents by whole-cell patch-clamp techniques.<h4 ...[more]

PMID: 24820856

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Dataset Information

Electromechanical and atrial and ventricular antiarrhythmic actions of CIJ-3-2F, a novel benzyl-furoquinoline vasodilator in rat heart.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Electromechanical and atrial and ventricular antiarrhythmic actions of CIJ-3-2F, a novel benzyl-furoquinoline vasodilator in rat heart.

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