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 antihistamines, we examined the effects of astemizole, a nonsedating antihistamine, on ventricular activation and RT intervals in a canine myocardial infarction model. Myocardial infarction was produced by two-stage ligation of the left anterior descending coronary artery in dogs. Seven days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted and normal zones to apply an electrical stimulation or record the ventricular activation. An electrical stimulation with coupling intervals between 300 and 140 ms was applied on the ventricular surface of the normal zone during atrial pacing, and the ventricular activation delay was measured. The effect of astemizole on the RT interval was also determined during atrial pacing, sinus rhythm or after premature stimulation. The ventricular activation delay increased 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 greater in the infarcted zone. Astemizole increased the RT interval in the normal zone to a greater extent at a long coupling interval. The increase in the RT interval was greater in the infarcted zone compared with that in the normal zone. In conclusion, astemizole increased the activation delay in the infarcted zone, probably through prolongation of the repolarization time, and its effect on the activation delay may be arrhythmogenic.
Nishimoto
M
M
Department of Clinical Pharmacology, Hamamatsu University School of Medicine, Japan.
Hashimoto
H
H
Ohmura
T
T
Ikeda
Y
Y
Watanabe
S
S
Ohashi
K
K
Umemura
K
K
Nakashima
M
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D016589:Astemizole / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy*; D018754:Ventricular Dysfunction / Q000188:drug therapy*
D006634:Histamine H1 Antagonists; D016589:Astemizole