7-oxo-PGI2 induced late protective action from arrhythmias due to local myocardial ischemia

In our earlier experiments administration of the stable PGI2 analogue: 7-oxo-PGI2-ephedrine salt to dogs resulted in a late appearing and long-lasting protection from coronary ligation induced ischemia and subsequent postocclusion and reperfusion arrhythmias. Objective of the present study was to evaluate the extent and duration of antiischemic and antiarrhythmic action induced by a single dose 50 micrograms/kg i.m. 7-oxo-PGI2 in dogs subjected to myocardial ischemia evoked by left anterior descending coronary (LAD) ligation at different intervals (2, 6, 24, 48, 72 hours and 2 weeks) after treatment. In the 2 weeks prolonged treatment group treatment started with 50 micrograms/kg i.m. dose, followed every third day by administration of 25 micrograms/kg 7-oxo-PGI2. After anesthesia and thoracotomy the electrophysiological parameters (SCL, CSNRT, AFRP, VFRP and A-V ERP) were determined by means of computer controlled programmed electrical stimulation. Then the animals were subjected to LAD occlusion for 25 min and subsequent reperfusion. 7-oxo-PGI2 pretreatment considerably protected against myocardial ischemia, i.e. there was a marked reduction in ST-segment elevation, the number of ES and the incidence of VF. The maximal antiischemic action and the most striking reduction in ventricular arrhythmias could be observed 48 hours after a single dose of 7-oxo-PGI2 and also after prolonged treatment of two weeks. In this latter group CSNRT showed the most expressed prolongation, however, AFRP and to lesser degree VFRP was also prolonged.