Effects of Antiplatelet Agents in the Prevention of Ventricular Tachyarrhythmias during Acute Myocardial Ischemia in the Rats

ABSTRACT

BACKGROUND: Aspirin, one of the antiplatelet agents, improves the survival rate after myocardial infarction. This beneficial effect is known to be obtained in part by the antiarrhythmic action of aspirin. It is not known whether other antiplatelet agents have such effects. This study was performed to compare the effects of aspirin, ticlopidine, and abciximab (platelet glycoprotein IIb/IIIa receptor antagonist) on the ischemia-induced arrhythmias with a rat model of cardiac regional ischemia. METHODS: Experiments were performed in 4 groups of rats. The 4 groups were as follows control, n=10aspirin-pretreated, 300 mg/kg po for 1 weekticlopidine-pretreated, 200 mg/kg po for 1 wkabciximab-pretreated, 2 mg/kg iv 10-20 minutes before experiment. The electrocardiogram and blood pressure were recorded during 20 minutes. The time to the onset of ST-segment elevation and ventricular tachyarrhythmias, frequency and incidence of ventricular tachyarrhythmias, and death rate were assessed during acute myocardial ischemia induced by ligation of proximal left anterior descending coronary artery in anesthetized rats. RESULTS: Platelet aggregations to ADP were significantly lower in aspirin (42.8%), ticlopidine (43.8%), and abciximab group (34.0%) than in control group (66.4%). The frequencies of sustained ventricular tachycardia (VT) were 6.8+/-3.6 in control, 3.6+/-3.8 aspirin, 4.7+/-3.7 ticlopidine, and 1.4+/-2.5 abciximab group. The frequency of sustained VT in the abciximab group was significantly lower than in control group. The incidences of ventricular arrhythmias for 20 min were 10/10 for VT and 8/10 for ventricular fibrillation (VF) in control group, 7/10 for VT and 3/10 for VF in aspirin group, 10/10 for VT and 3/10 for VF in ticlopidine group, and 5/10 for VT and 4/10 for VF in abciximab group. The incidences of cardiac death during 20 min were 8/10 in control group, 4/10 in aspirin group, 2/10 in ticlopidine group and 5/10 in abciximab group. The incidence of VT in the abciximab group was significantly lower than in control group, incidences of VF in the aspirin and ticlopidine groups were significantly lower than in control group, and death rate in ticlopidine group was significantly lower than in control group. CONCLUSION: The present study suggested that aspirin, ticlopidine, and abciximab could prevent ventricular tachycardia or ventricular fibrillation in a rat model of cardiac regional ischemia and their antiarrhythmic effects improve the survival rate.