Delayed antiischemic effect of prostaglandin I2 and of a new stable prostaglandin I2 analogue, 7-oxo-prostacyclin-Na, in experimental model angina in dogs.

ABSTRACT

Therapeutic application of prostaglandin I2 (PGI2) is rendered difficult by its instability. The 7-oxo-derivative synthesized by Kovács et al. [8] proved to be stable in aqueous solution. Both drugs were tested in experimental model angina in anesthetized thoracotomized dogs with critical stenosis of the left anterior descending coronary artery, in which drug-induced reduction of ischemic ST-segment elevation evoked by frequency loading was estimated [10]. Both drugs markedly reduced blood pressure (BP) even if given by intravenous infusion for 60 min in a total dose of 20 micrograms/kg for PGI2 and 250 micrograms/kg for 7-oxo-PGI2-Na. BP returned to normal soon after infusion and did not substantially change. After a latency of 90-120 min, a 40-50% reduction of ischemia-induced ST-segment elevation appeared in the epi-, endo-, and intramyocardial ECG. Intracoronary infusion of PGI2 in 1 microgram/kg and 7-oxo-PGI2-Na in 25 micrograms/kg total dose minimized systemic actions, but a delayed protective effect appeared, due probably to some nonvasoactive metabolite of these substances. Although both substances exert a potent platelet-aggregation-inhibiting action, serial ex vivo determination of ADP aggregation at different times has shown a dissociation of antiaggregatory action from the protection, this dissociation reaching its maximum when antiaggregatory action was already over.