4-Aminopyridine Inhibits the Occurrence of Ventricular Fibrillation but not Ventricular Tachycardia in the Reperfused, Isolated Rat Heart

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The 4-aminopyridine (4-AP)-sensitive transient outward current (I_<to>) has been reported to play an important role in the ischemia- or high [Ca^<2+>]_o-induced reentrant ventricular arrhythmias. However, the role of 4-AP sensitive I_<to> in reperfusion arrhythmia remains unknown. Rat hearts were perfused with Tyrode solution (control), and treated with 0.5μmol/L verapamil, 1μmol/L glibenclamide, 10μmol/L E-4031 or 2mmol/L 4-AP. After a 10-min perfusion, hearts were subjected to 30-min global ischemia followed by 10-min reperfusion. The effects of the ion-channel blockers on the incidence of ventricular tachycardia (VT), torsades de points (Tdp) and ventricular fibrillation (VF) during the reperfusion period were investigated. Verapamil and 4-AP abolished VF and Tdp. The incidence of VT was also attenuated by verapamil, but not by 4-AP. Glibenclamide and E-4031 (a blocker of a rapidly activating component of delayed rectifier K^+ current) did not affect the incidence of those tachyarrhythmias. Accordingly, (1) the underlying mechanism of VF or Tdp is different from that of VT, and (2) 4-AP sensitive I_<to> is required for the occurrence of reperfusion Tdp or VF in the present model.
社団法人日本循環器学会の論文
2000-07-20