anthopleurin-a and Arrhythmias--Cardiac

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.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Bradycardia; Dogs; Intercellular Signaling Peptides and Proteins; Lidocaine; Papillary Muscles; Peptides; Pericardium; Purkinje Fibers; Tachycardia, Supraventricular