title: Electromechanical and atrial and ventricular antiarrhythmic actions of CIJ-3-2F, a novel benzyl-furoquinoline vasodilator in rat heart.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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 ) (IC₅₀ = 4.4 μM) 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 , IC₅₀ = 3.6 μM, maximum inhibition = 65.7%) and both the inward Na(+) current (INa , IC₅₀ = 2.8 μM) and L-type Ca(2+) current (ICa,L , IC₅₀ = 4.9 μM, maximum inhibition = 69.4%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate Institute of Clinical Medicinal Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Gwo-Jyh
authors.initials: GJ
authors.lastname: Chang
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Yeh
authors.forename: Tsung-Pin
authors.initials: TP
authors.lastname: Lin
authors.forename: Chi-Jen
authors.initials: CJ
authors.lastname: Chang
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D011804:Quinolines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; C550028:N-(2-fluoro-benzyl)-7-bromo-2,3,4,9-tetrahydrofuro(2,3-b)quinoline-3,4-dione; D011804:Quinolines; D014665:Vasodilator Agents; D002118:Calcium