We examined the effects of the
heparin ion-pair complex
ITF 1300 on
ventricular fibrillation (VF) and other arrhythmias elicited by regional
ischemia and by reperfusion in isolated rat hearts (n = 12 per group). During 30-min
ischemia, 1, 3, and 10 mg/L
ITF 1300 reduced the incidence of VF concentration dependently, with complete abolition of VF at the highest concentration (p < 0.05). Similar but weaker effects were observed for other arrhythmias [
ventricular tachycardia (VT) and salvos]. Reperfusion-induced arrhythmias (elicited after 10- or 30-min regional
ischemia) were affected similarly, with complete abolition of VF at the highest
drug concentration (p < 0.05). Coronary blood flow (CBF), recovery of CBF during reperfusion, and occluded zone sizes were little affected (p = NS).
ITF 1300 caused concentration-dependent
bradycardia, PR interval widening, and QT widening. In further studies, we examined the roles of these changes in mediating the antiarrhythmic effects. Left atrial pacing at a rate close to control rate (300 beats/min) abolished the antiarrhythmic effects of
ITF 1300 and the QT widening, indicating that
bradycardia and QT widening were important in mediating the antiarrhythmic effects. Doubling the
calcium concentration in the perfusion
solution prevented ITF 1300-induced PR widening, indicating that
calcium antagonist activity probably mediated the
drug's effects on this variable. However, the antiarrhythmic effect of
ITF 1300 was not affected by high
calcium perfusion.
ITF 1300 is an effective antiarrhythmic agent in a model of
ischemic heart disease. Its effects are mediated primarily by heart rate-dependent QT widening and were not related to possible
calcium antagonist activity.