Correlation between attenuation of posttraumatic spinal cord ischemia and preservation of tissue vitamin E by the 21-aminosteroid U74006F: evidence for an in vivo antioxidant mechanism.

In the present study, the ability of U74006F, the 21-aminosteroid inhibitor of lipid peroxidation, to attenuate posttraumatic spinal cord ischemia has been examined in cats following a moderately severe compression injury. Moreover, in an attempt to assess whether U74006F is affecting in vivo posttraumatic lipid peroxidation, the effect of the compound on injury-induced spinal tissue vitamin E depletion was also studied. Following an initial 10 min postinjury hyperperfusion (+45%), spinal cord blood flow (SCBF) returned to the preinjury level at 30 min before entering a phase of progressive hypoperfusion, which reached -42.0 +/- 4.5% by 4 h postinjury in the vehicle-treated animals. In animals that received 30 min postinjury U74006F i.v. doses of 1.0, 3.0, or 10 mg/kg (plus 0.5, 1.5, and 5.0 mg/kg maintenance doses at 2.5 h.), the SCBF decline was reduced to -23.1%, -22.9%, and -26.1%, respectively (p less than 0.05 vs. vehicle at all three doses). A 0.3 mg/kg dose did not reduce the posttraumatic fall in SCBF. In vehicle-treated cats, the vitamin E content of the injured cord segment was reduced by 78.9% at 4 h postinjury in comparison to cord samples from uninjured vehicle-treated cats. In contrast, the same doses of U74006F (1.0, 3.0, and 10 mg/kg) that attenuated posttraumatic ischemia also significantly reduced the depletion of cord vitamin E. The lowest U74006F dosage (0.3 mg/kg), which failed to affect posttraumatic ischemia development, also had no effect on spinal cord vitamin E content.(ABSTRACT TRUNCATED AT 250 WORDS)