On the late antiischaemic action of the stable PgI2 analogue: 7-oxo-PgI2-Na and its possible mode of action.
Earlier we have shown in the dog model mimicking angina on effort a delayed antiischaemic effect of PgI2 and its stable analogue 7-oxo-PgI2-Na, appearing only when the drug induced marked vasodilatation was over [1]. In the present experiments we could show that the protective effect appears at a time when the blood pressure returned to normal and in addition the marked platelet aggregation inhibitory effect has also faded away. In the rat 7-oxo-PgI2 could substantially diminish vasopressine induced T-wave elevation in the ECG if given 2 hours before administration of vasopressin. In addition it could moderate the vasopressin induced metabolic changes appearing as diminution of the myocardial CP and ATP-level and increase of the myocardial lactate content. A similar metabolic protection was found in the heart of rats pretreated with 7-oxo-PgI2 2 hours before taking myocardial samples and exposing them for 1 minute to ischaemia by incubation in Ringer solution. It is concluded that a direct metabolic and hemodynamic effect could be at least partly responsible for the late antiischaemic effect of 7-oxo-PgI2. This effect was also present in the early phase of experimental myocardial infarction in conscious rats if animals were pretreated with 7-oxo-PgI2 2 hours before occlusion. However treatment did not increase survival rate and failed to reduce the incidence and severity of arrhythmias.
D000227:Adenine Nucleotides / Q000378:metabolism; D000787:Angina Pectoris / Q000188:drug therapy*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D011464:Epoprostenol / Q000627:therapeutic use* / Q000031:analogs & derivatives; D005260:Female; D006321:Heart / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology
D000227:Adenine Nucleotides; D007773:Lactates; D010725:Phosphocreatine; D014667:Vasopressins; C033705:7-oxoprostaglandin I2; D011464:Epoprostenol