EFFECTS OF ASTEMIZOLE ON VENTRICULAR ACTIVATION DELAY AND RT INTERVALS IN A CANINE MYOCARDIAL-INFARCTION MODEL

In order to clarify the arrhythmogenic effects of nonsedating antihist amines, we examined the effects of astemizole, a nonsedating antihista mine, on ventricular activation and RT intervals in a canine myocardia l infarction model. Myocardial infarction was produced by two-stage li gation of the left anterior descending coronary artery in dogs. Seven days after ligation, bipolar electrodes were sutured on the ventricula r surface of the infarcted and normal zones to apply an electrical sti mulation or record the ventricular activation. an electrical stimulati on with coupling intervals between 300 and 140 ms was applied on the v entricular surface of the normal zone during atrial pacing, and the ve ntricular activation delay was measured. The effect of astemizole on t he RT interval was also determined during atrial pacing, sinus rhythm or after premature stimulation, The ventricular activation delay incre ased after astemizole at doses of 0.3 to 3 mg/kg in the infarcted and at 3 mg/kg in the normal zones, and the effect of astemizole was great er in the infarcted zone. Astemizole increased the RT interval in the normal zone to a greater extent at a long coupling interval. The incre ase in the RT interval was greater in the infarcted zone compared with that in the normal zone, In conclusion, astemizole increased the acti vation delay in the infarcted zone, probably through prolongation of t he repolarization time, and its effect on the activation delay may be arrhythmogenic.