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.
Hall
E D
ED
CNS Disease Research, Upjohn Company, Kalamazoo, MI 49001.
Yonkers
P A
PA
McCall
J M
JM
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008775:Methylprednisolone / Q000627:therapeutic use; D011281:Pregnatrienes / Q000627:therapeutic use*; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology
D008054:Lipid Peroxides; D011281:Pregnatrienes; D008775:Methylprednisolone; C053355:tirilazad