Comparison of Piroxicam, Meclofenamate, Ibuprofen, Aspirin, and Prostacyclin Efficacy in a Chronic Model of Cerebral Vasospasm

Abstract

Previous studies have suggested that certain prostanoids are mediators of the pathological features of subarachnoid hemorrhage (SAH) and that a reduced synthesis of prostacyclin in the vessel wall might also contribute to the cerebral vasospasm associated with this malady. The present study was performed, therefore, to ascertain whether known inhibitors of prostanoid synthesis would negate the changes that accompany the intracisternal administration of 4 ml of autogenous arterial blood to dogs and whether prostacyclin would lyse the vasospasm that is present 24 hours after this intrathecal blood. Nonsteroidal anti-inflammatory drugs (NSAIDs) were given intravenously to anesthetized dogs 30 minutes before and again 3 hours after the intracisternal injection of blood. The induced cerebral vasospasm was studied arteriographically for 1 hour after the intrathecal blood and again on the following day. Behavioral recovery of the animals was also evaluated on the day after the simulated hemorrhage. The results show that, as a group, NSAIDs significantly (P less than 0.001) reduced the occurrence of vasospasm and behavioral change associated with intrathecal blood. However, piroxicam was more efficacious than meclofenamate, ibuprofen, or aspirin in preventing both the vascular and the behavioral changes observed. This efficacy may be due to the long half-life of piroxicam and to known and unknown pharmacological differences among these compounds. On the other hand, prostacyclin infused via the vertebral artery failed to affect the vasospasm present 24 hours after intrathecal blood. The findings suggest that a suitable NSAID could provide clinical protection from the deleterious consequences of SAH.