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

Abstract

Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.

Platelets and Cardiac Arrhythmia

“…Many of these substances can alter electrophysiological properties of the heart in various animal species, supporting the notion that activated platelets exert pro-arrhythmic effects (Figure 1; Hoffman et al, 1996, 1997; Flores et al, 1999). Conversely, platelet antagonists counteract ischemia-induced arrhythmias in animal studies (Wainwright et al, 1989; Ahn et al, 1999). …”

“…However, some evidence does exist for such an effect. Platelet antagonists effectively induced ventricular arrhythmias in models of ischemia by coronary ligation in rats (Ahn et al, 1999) and dogs (Moschos et al, 1978; Wainwright et al, 1989). In a dog model of regional ischemia, the threshold of epinephrine-induced VF was reduced after aspirin pre-treatment (Shehadeh et al, 2000).…”