7-oxo-PGI2 induced late appearing and long lasting antiischaemic and antiarrhythmic action in dogs.
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 ischaemia as well as from postocclusion and reperfusion arrhythmias. Objective of the present study was to evaluate the extent and duration of antiischaemic and antiarrhythmic action induced by a single dose 50 ug/kg i.m. 7-oxo-PGI2 in dogs subjected to myocardial ischaemia evoked by left anterior descending coronary artery (LAD) ligation at different intervals (2, 6, 24, 48, 72 hours and 2 weeks) after treatment. After anaesthesia and thoracotomy the electrophysiological parameters - sinus cycle length (SCL), corrected sinus node recovery time (CSNRT), atrial and ventricular functional refractory period (AFRP, VFRP), and atrio-ventricular effective refractory period (A-V ERP) - were determined by means of computer controlled programmed electrical stimulation. Then the animals were subjected to LAD occlusion for 25 minutes and subsequent reperfusion. 7-oxo-PGI2 pretreatment considerably protected against myocardial ischaemia i.e. there was significant reduction in ST-segment elevation, the number of extrasystoles (ES) and the incidence of ventricular fibrillation (VF). The antiischaemic action started 2 or 6 hours after the drug administration, however, the maximal protection - indicated by the diminution of ischaemic epicardial ST-segment elevation - as well as the most striking reduction in postocclusion and reperfusion arrhythmias could be observed 48 hours after the single dose of 7-oxo-PGI2 and in case of two weeks treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Végh
A
A
Department of Pharmacology, Szent-Györgyi Albert University Medical School, Szeged, Hungary.
Udvary
E
E
Szekeres
L
L
Szilvássy
Z
Z
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004809:Ephedrine / Q000031:analogs & derivatives / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D012016:Reference Values
D000889:Anti-Arrhythmia Agents; C053676:7-oxo-prostaglandin I2-ephedrine; D011464:Epoprostenol; D004809:Ephedrine