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Electromechanical and atrial and ventricular antiarrhythmic actions of CIJ ‐3‐2 F , a novel benzyl‐furoquinoline vasodilator in rat heart
Author(s) -
Chang GwoJyh,
Yeh YungHsin,
Lin TsungPin,
Chang ChiJen,
Chen WeiJan
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12752
Subject(s) - medicine , cardiology , refractory period , ventricle , chemistry , purkinje fibers , vasodilation , electrophysiology
Background and Purpose This study was designed to examine the antiarrhythmic efficacy and the underlying mechanisms of the benzyl‐furoquinoline vasodilator, CIJ ‐3‐2 F , in rat cardiac preparations. Experimental Approach Conduction electrograms and left ventricular pressure were determined in L angendorff‐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 ‐3‐2 F prolonged sinus cycle length, QT interval, W enckebach cycle length, atrio‐ H is bundle and H is bundle‐ventricular conduction intervals, refractory periods in atrium, AV node, H is‐ P urkinje system and ventricle, and also increased left ventricular pressure. CIJ ‐3‐2 F 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 ‐3‐2 F decreased upstroke velocity and prolonged duration of the action potential. In ventricular myocytes, CIJ ‐3‐2 F moderately increased the amplitude of [ Ca 2+ ] i transients and cell shortening. CIJ ‐3‐2 F inhibited the transient outward K + current ( I to ) ( IC 50 = 4.4 μ M ) with accelerated inactivation, a slower rate of recovery from inactivation and use‐dependency. CIJ ‐3‐2 F also suppressed the steady‐state outward K + current ( I ss , IC 50 = 3.6 μ M , maximum inhibition = 65.7%) and both the inward Na + current ( I Na , IC 50 = 2.8 μ M ) and L ‐type Ca 2+ current ( I Ca,L , IC 50 = 4.9 μ M , maximum inhibition = 69.4%). Conclusions and Implications CIJ ‐3‐2 F blocked Na + and I to channels and, to some extent, also blocked Ca 2+ and I ss channels, modifying cardiac electromechanical function. These effects are likely to underlie its antiarrhythmic properties.