DISCORDANT PROLONGATION OF THE REFRACTORY PERIOD AND REPOLARIZATION TIME BY A CLASS-III AGENT, E4031, IN THE HEALING PHASE OF MYOCARDIAL-INFARCTION

Susceptibility to reentrant tachyarrhythmias and the antiarrhythmic ef ficacy of class III agents are related more to the duration of the ref ractory period (ERP) than to the repolarization time (RT). We measured both ERP and RT in a canine model of healing myocardial infarction, a nd evaluated the effect of a class III agent (E4031) on these paramete rs and on the inducibility of ventricular tachyarrhythmias. ERP and RT on the unipolar electrogram were measured at several cycle lengths in the normal (NZ) and infarct zones (IZ), respectively, in 10 canine my ocardial infarction models and extrastimulation was used to induce ven tricular arrhythmias. Measurements were repeated after E4031 administr ation. At baseline, both ERP and RT were significantly longer in IZ th an in NZ with ERP/RT ratio also higher in IZ. This ratio tended to inc rease at longer cycle lengths. E4031 increased ERP and RT both in NZ a nd IZ at all cycle lengths, but increased the ERP/RT ratio predominant ly in IZ. E4031 prevented induction of sustained VT or VF, which was i nducible in 3 out of 10 dogs at baseline, although it facilitated indu ction of VF in I dog with no baseline arrhythmia. By increasing the ER P/RT ratio, class III drugs may shorten the relative refractory period in IZ at the expense of a greater ERP difference created between NZ a nd IZ.