Attenuation of postischemic cerebral hypoperfusion by the 21-aminosteroid U74006F.
The ability of the nonglucocorticoid 21-aminosteroid U74006F, a potent inhibitor of iron-dependent lipid peroxidation, to antagonize progressive brain hypoperfusion after a 5-minute episode of global brain ischemia was examined in alpha-chloralose-anesthetized cats. Immediately after a 5-minute episode of near-total tourniquet-induced brain ischemia, cortical blood flow returned to normal or above normal. Thereafter, cortical blood flow fell progressively to a level 71.7% below normal by 3 hours after ischemia. In contrast, in cats that received 1 mg/kg i.v. U74006F 15 minutes after the ischemic episode, cortical blood flow remained significantly greater than that seen in vehicle-treated cats. At 3 hours, cortical blood flow had declined by only 45.7% (p less than 0.04 compared with vehicle). In addition, U74006F treatment significantly improved postischemic maintenance of blood pressure and recovery of somatosensory evoked potentials and reduced postischemic arterial blood acidosis. U74006F had no effect on cortical blood flow, somatosensory evoked potentials, or blood pressure in nonischemic cats. Our results suggest that U74006F may be useful in the early treatment of global cerebral ischemia.
Hall
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Central Nervous System Diseases Research Unit, Upjohn Company, Kalamazoo, Michigan 49001.
Yonkers
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D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D011281:Pregnatrienes / Q000627:therapeutic use*; D012016:Reference Values
D011281:Pregnatrienes; C053355:tirilazad