EFFECTS OF ASTEMIZOLE ON VENTRICULAR ACTIVATION, EFFECTIVE REFRACTORYPERIODS, RT INTERVALS, AND PROGRAMMED STIMULATION-INDUCED VENTRICULARARRHYTHMIAS IN DOG HEARTS WITH MYOCARDIAL-INFARCTION

To clarify the mechanisms of enhanced cardiotoxic effects of astemizol e in ischemic hearts, we examined the effects of astemizole on ventric ular activation, effective refractory periods (ERPs), RT intervals, an d incidence of programmed electrical stimulation (PES)-induced ventric ular arrhythmias in the dog heart after myocardial infarction, Myocard ial infarction was produced by the two-stage ligation of left anterior descending coronary artery in dogs, At 7 days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted a nd the normal zones for applying an electrical stimulation or recordin g the ventricular activation. Ventricular-activation delay was measure d in a premature excitation, which was produced by a stimulation at a coupling interval between 300 and 140 ms on the ventricular surface of the normal zone. The ERP and the RT interval were determined during a trial pacing. The ventricular-activation delay increased after astemiz ole at doses of 0.3-3 mg/kg in the infarcted zone and at 3 mg/kg in th e normal zone. Astemizole at doses of 0.3-3 mg/kg significantly prolon ged the ERP to a greater extent in the infarcted zone than in the norm al zone, and thus a dispersion of ERP between normal and infarcted zon es increased. The RT interval in the normal zone significantly increas ed after astemizole to a greater extent at a long coupling interval. T he RT interval in the infarcted zone also increased after astemizole a t doses of 0.1-3 mg/kg to a greater extent than that in the normal zon e. Astemizole at doses of 0.3-3 mg/kg increased the incidence of PES-i nduced ventricular arrhythmias. In conclusion enhanced cardiotoxic eff ects of astemizole in ischemic hearts may be caused by increased activ ation delay in the ischemic regions and increased ERP dispersion in th e ventricle.