U74006F, a novel 21-aminosteroid, is an inhibitor of
iron-dependent lipid peroxidation that is devoid of
glucocorticoid and
mineralocorticoid side effects. The efficacy of
U74006F in reducing
cerebral infarct size was investigated in a rabbit model of thromboembolic
stroke. Each animal received either
U74006F (3.0 mg/kg immediately before and 2 hr after embolization, n = 8) or vehicle control (n = 10). Hematocrit, mean arterial pressure, PCO2, PO2, and pH were measured and controlled both before and after the administration of an autologous clot into one internal carotid artery. Regional cerebral blood flow (in ml/100 g/min, mean +/- SEM) measured by
hydrogen clearance was similar in both groups, being reduced from 68.2 +/- 9.6 to 5.2 +/- 1.9 in the control group immediately after clot embolization and from 73.3 +/- 14.9 to 7.0 +/- 1.7 in the
U74006F group. Four hours after embolization the brain was harvested and
cerebral infarct size was determined using the triphenyl-tetrazolium
chloride technique (% hemisphere, mean +/- SEM). In the U74006F-treated group, the
infarct size was significantly reduced (P < 0.05) to 14.8 +/- 6.4 from a control value of 36.0 +/- 6.4. Additionally, cerebral blood flow values after embolization were consistently higher in the
U74006F group, although the differences were not statistically significant. This data suggests that the 21-aminosteroid
U74006F may have a protective effect in
cerebral ischemia.