Effects of new chemically and metabolically stable prostacyclin analogues (iloprost and ZK 96480) on early consequences of a transient cerebral oligemia, in the rat.

Transient incomplete cerebral ischemia (oligemia) has been obtained in rats by associating mild systemic hypotension with bilateral carotid artery occlusion for 60 min. Continuous i.v drug administration for 3 days, performed with Alzet osmotic minipumps so that to deliver 167 ng.kg-1.min-1 Iloprost, 5 ng.kg-1.min-1 ZK 96480 or their respective vehicle, started 1 hour post-oligemia. Both compounds which are stable prostacyclin analogues reduced the edematous reaction and the post-oligemic accumulation of calcium in the brain tissue but above all they improved, mainly ZK 96480, the learning capacity of injured animals. These results indicate that regarding its therapeutic effect toward early consequences of a transient cerebral oligemia, ZK 96480 has the same profile as Iloprost at a dose 20-fold lower. Thus, these data encourage further clinical studies, in ischemic stroke, in which PGI2 and Iloprost have been shown promising.