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

The 4-aminopyridine (4-AP)-sensitive transient outward current (Ito) has been reported to play an important role in the ischemia- or high [Ca2+]o-induced reentrant ventricular arrhythmias. However, the role of 4-AP sensitive Ito in reperfusion arrhythmia remains unknown. Rat hearts were perfused with Tyrode solution (control), and treated with 0.5 micromol/L verapamil, 1 micromol/L glibenclamide, 10 micromol/L E-4031 or 2 mmol/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 pointes (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 Ito is required for the occurrence of reperfusion Tdp or VF in the present model.