Polymorphic
ventricular tachyarrhythmias occurred spontaneously during
bradycardia in dogs given the inotropic
polypeptide anthopleurin-A (AP-A). The
arrhythmia was investigated in in vitro and in vivo experiments. In in vitro experiments, AP-A (50 micrograms/l) produced
bradycardia-dependent prolongation of action potential duration that was more pronounced in Purkinje than in muscle fibers. Only Purkinje fibers developed early afterdepolarizations (EAD) and triggered activity. These effects could be abolished by rapid pacing,
lidocaine (4 mg/l), or
tetrodotoxin (1 mg/l). In vivo experiments were conducted in anesthetized healthy dogs with simultaneous recording of surface ECG, monophasic action potentials from the endocardial and epicardial surface of the left ventricle by contact
electrode catheter technique, and transmembrane action potentials from the epicardial surface of the left ventricle with a floating
microelectrode technique. AP-A in a dose comparable to that used in vitro (4 micrograms/kg, i.v. bolus) resulted in
bradycardia-dependent marked prolongation of both monophasic and transmembrane action potentials. An EAD gradually appeared on both recordings but was more marked in endocardial monophasic action potentials. Eventually, a premature ventricular depolarization arose from or very close to the peak of the EAD. The prolongation of action potentials was associated with similar prolongation of the QTU interval in surface ECG, and in some experiments, the EAD corresponded to a distinct prominent U wave. A ventricular premature depolarization arose from the U or TU complex and initiated polymorphic
ventricular tachyarrhythmias that terminated spontaneously or degenerated into
ventricular fibrillation. These effects were reversed by rapid pacing or
lidocaine (1 mg/kg). The present study provides evidence in support of the hypothesis that AP-A-induced
ventricular tachyarrhythmias are due to
bradycardia-dependent EAD and triggered activity.