Studies on Heart. XXII. Inhibitory Effect of an Atrial Peptide (AAP) on Several Drug-induced Arrhythmias in Vivo

Abstract

The effect of an atrial peptide, Gly-Pro-4Hyp-Gly-Ala-Gly (AAP), on several druginduced arrhythmias in anesthetized dogs, rats and mice was investigated together with its effect on the related functions. AAP (10 mg/kg, i.v.) significantly reversed the persistent arrhythmias consisting of atrio-ventricular (A-V) block, ectopic beat and/or ventricular tachycardia induced by aconitine pretreatment, to normal sinus rhythm for a while, and evidently prevented development of ventricular fibrillation in dogs and rats. AAP (10, 25 mg/kg, i.v.) significantly prolonged the time until onset of A-V block or ectopic beat and the time until onset of ventricular tachycardia induced by aconitine infusion in mice. This peptide (10 mg/kg, i.v.) significantly prolonged the onset time of A-V block or ectopic beat induced by CaCl₂ infusion and the time until ventricular fibrillation induced by ouabain infusion in mice, and significantly shortened the duration of arrhythmia induced by ADP in rats, but did not affect the mouse epinephrine-induced arrhythmia. The peptide (25 mg/kg, i.v.) was found to prolong significantly the QTc interval and to have no effect on the PQ interval, heart rate, respiratory rate and blood pressure in dogs. AAP (1 g/kg. i.v., i.p. and p.o.) did not show the acute toxicity in mice. AAP was a chemically new type of antiarrhythmic substance with very little side effect and low toxicity, possessing the action intensity almost equal to quinidine.