On the 7-oxo-PgI2 induced lasting protection against ouabain arrhythmias in anesthetized guinea pigs

In our earlier experiments prolonged administration of the stable PgI2 analogue: 7-oxo-PgI2 ephedrine salt to dogs afforded a long-lasting protection against coronary occlusion induced ischemia as well as against postocclusion and reperfusion arrhythmias. In the present experiments we wanted to clear, whether this prolonged protective action is present in other types of arrhythmia, which are not due to ischemia. The ouabain-arrhythmia seemed to be suitable for elucidation of this question. Therefore guinea pigs were pretreated with 50 micrograms/kg i.p. 7-oxo-PgI2 and 24, 48, 72 and 96 hrs after treatment anesthetized with 35 mg/kg sodium pentobarbitone. To prevent ouabain bradycardia, 0.4 mg/kg atropine was administered i.p. Ouabain was applied by intermittent infusion technique i.e. an initial infusion for 5 minutes of a total dose of 60 micrograms/kg into the right jugular vein was followed after a 25 minutes interval by infusions of 30 micrograms/kg for 2.5 minutes every 10 minutes until cardiac arrest. The ouabain induced rhythm disturbances appeared in the following order: Anomalies in T wave morphology, ventricular or nodal extrasystoles, atrio-ventricular and intraventricular conduction disturbances, ventricular tachycardia, ventricular fibrillation and finally cardiac arrest. If 50 micrograms/kg i.p. 7-oxo-PgI2 was given to ouabain-intoxicated animals at the appearance of the first extrasystole a transient aggravation of this arrhythmia developed. In 7-oxo-PgI2 pretreated animals the total amount of ouabain necessary to induced rhythm disturbances was markedly elevated, the appearance of the various arrhythmias significantly delayed. Maximal protective effects were seen 48 hrs after the administration of 50 micrograms/kg 7-oxo-PgI2.