POSTREPOLARIZATION REFRACTORINESS VERSUS CONDUCTION SLOWING CAUSED BYCLASS-I ANTIARRHYTHMIC DRUGS - ANTIARRHYTHMIC AND PROARRHYTHMIC EFFECTS

Background-Conduction block may be both antiarrhythmic and proarrhythm ic. Drug-induced postrepolarization refractoriness (PRR) may prevent p remature excitation and tachyarrhythmia induction. The effects of prop afenone and procainamide on these parameters, and their antiarrhythmic or proarrhythmic consequences, were investigated. Methods and Results -In 11 isolated Langendorff-perfused rabbit hearts, monophasic action potentials (MAPs) were recorded simultaneously from six to seven diffe rent right and left ventricular sites, along with a volume-conducted E GG. All recordings were used to discern ventricular tachycardia (VT) o r ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5) or l0-second burst stimulation at 25 to 200 Hz at baseline an d after addition of procainamide (20 mu mol/L) or propafenone (1 mu mo l/L) to the perfusate, MAPs were analyzed for action potential duratio n at 90% repolarization (APD,,), conduction times (CT) between the pac ing site and the other MAPs, and PRR (effective refractory period-APD( 90)=PRR) and related to the induction of VT or VF. During steady-state pacing, procainamide and propafenone prolonged APD(90) by 12% and 14% , respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing , whereas propafenone slowed mean CT by up to 400% (P<0.001 versus bas eline and procainamide). Wavelength was not changed significantly by p rocainamide but was shortened fourfold by propafenone at S5. Both drug s produced PRR, which was associated with a 70% decrease in VF inducib ility with procainamide and elimination of VF with propafenone. Despit e this protection from VF, monomorphic VT was induced with propafenone in 57% of burst stimulations. Conclusions-Drug-induced PRR protects a gainst VF induction. Propafenone promotes slow monomorphic VT, probabl y by use-dependent conduction slowing and wavelength shortening.