Attenuation of hemorrhagic shock by the non-glucocorticoid 21-aminosteroid U74006F.

The ability of the novel non-glucocorticoid 21-aminosteroid U74006F to protect against the development of hemorrhagic shock was examined in pentobarbital-anesthetized cats. The animals were hemorrhaged to a mean arterial blood pressure (MAP) of 45-50 mm Hg where they were held for 2 h. At the end of the hemorrhage period, either vehicle, a 30 mg/kg dose of methylprednisolone sodium succinate, or a 10 mg/kg dose of U74006F was administered i.v. followed by reinfusion of the shed blood. In vehicle-treated animals, there was a progressive post-reinfusion decline in the MAP over the subsequent 2 h. In the methylprednisolone-treated cats, the post-reinfusion decrease in the MAP was only slightly and not significantly better. In contrast, U74006F administration resulted in a significant maintenance of the MAP. These results suggest that U74006F may be efficacious for the attenuation of hemorrhagic shock and superior to conventional high dose glucocorticoid therapy in that context.