Effects of new 21-aminosteroid tirilazad mesylate (U74006F) on chronic cerebral vasospasm in a "two-hemorrhage" model of beagle dogs.

The present work aimed at examining the effect of tirilazad mesylate (U74006F), a newly developed lipid peroxidation inhibitor, on the intraluminal narrowing of basilar artery subjected to subarachnoid hemorrhage (SAH) in beagle dogs. In Experiment 1, an intravenous bolus injection of either vehicle or U74006F (0.5, 1.5 and 3.0 mg/kg) was repeated every 8 hours after an induction of the first SAH until the animals were killed. A dose of 0.5 mg/kg of U74006F provided the greatest beneficial effect. In Experiment 2, an intravenous infusion of 100 ml of saline containing either vehicle or U74006F (0.3 and 1.0 mg/kg) was given in the same time schedule as in Experiment 1. Post-SAH treatment of U74006F, at a dosage of approximately 0.5 mg/kg, showed a beneficial effect by infusion as well as by bolus administration. The present study demonstrates that U74006F has an ability to prevent chronic vasospasm in the canine SAH model.