7-oxo-PgI 2 induced late appearing and long-lasting electrophysiological changes in the heart in situ of the rabbit, guinea-pig, dog and cat

Abstract

We have previously observed a long-lasting antiischemic and anti-arrhythmic effect induced by prostacyclin (PgI 2) or its stable analogue, 7-oxo-PgI 2-ephedrine salt in dogs subject to local myocardial ischemia. This protection appeared when the vasodilating and platelet aggregation inhibiting effect of PgI 2 or its analogue was over and persisted even 72 h after treatment. We have also found that short incubation with 7-oxo-PgI 2 may induce a long-lasting prolongation of the action potential duration and of the effective refractory period in the isolated rabbit papillary muscle preparation without affecting the membrane potential or the rate of rise of the action potential. Our present experiments have shown a 7-oxo-PgI 2 induced, dose-dependent prolongation of the ventricular functional refractory period in conscious rabbits and anesthetized dogs, as well as an increase of the QT interval in the ECG in both species and also in conscious guinea-pigs. In all three species 50 μg/kg i.m. dose proved to be optimal, evoking maximal effect 48 h after treatment. In conscious rabbits this pre-treatment prevented the train of non-stimulated extra beats induced by premature stimuli. Furthermore it also prevented widening of the QRS complex appearing in non-treated controls after programmed stimulation. Pre-treatment significantly increased electrical fibrillo-flutter thresholds in the auricles and ventricles of anesthetized cats. These electrophysiological changes seem to be closely related to the 7-oxo-PgI 2 induced, late appearing and long-lasting protection from ischemic and reperfusion arrhythmias.