TY - JOUR
T1 - Effects of the nonglucocorticoid 21-aminosteroid U74006F on acute cerebral hypoperfusion following experimental subarachnoid hemorrhage
AU - Hall, Edward D.
AU - Travis, Mark A.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1988/11
Y1 - 1988/11
N2 - The ability of the nonglucocorticoid 21-aminosteroid U74006F, a potent inhibitor of iron-dependent lipid peroxidation, to antagonize acute progressive cerebral hypoperfusion following experimental subarachnoid hemorrhage (SAH) was examined in chloralose-anesthetized cats. The SAH was produced by injection of 0.5 ml/kg of unheparinized autologous blood into the cisterna magna after prior withdrawal of an equivalent volume of cerebrospinal fluid. In untreated animals the SAH caused a progressive decline in caudate nuclear blood flow (CNBF) (-51.4% by 3 h) and an increase in intracranial pressure (ICP) (+18.5 mm Hg by 3 h). In comparison, in cats that received a 1 mg/kg iv dose of U74006F at 30 min after SAH, there was a complete prevention of the fall in CNBF and a significant attenuation of the rise in ICP. Furthermore, the drug reduced a concomitant fall in the mean arterial blood pressure and cerebral perfusion pressure. While not as effective as the 1 mg/kg dose, a 0.1 mg/kg dose also significantly attenuated the post-SAH fall in CNBF. These results supporte a role of lipid peroxidation in the acute pathophysiology of SAH and suggest that U74006F may be useful in the early treatment of this disorder.
AB - The ability of the nonglucocorticoid 21-aminosteroid U74006F, a potent inhibitor of iron-dependent lipid peroxidation, to antagonize acute progressive cerebral hypoperfusion following experimental subarachnoid hemorrhage (SAH) was examined in chloralose-anesthetized cats. The SAH was produced by injection of 0.5 ml/kg of unheparinized autologous blood into the cisterna magna after prior withdrawal of an equivalent volume of cerebrospinal fluid. In untreated animals the SAH caused a progressive decline in caudate nuclear blood flow (CNBF) (-51.4% by 3 h) and an increase in intracranial pressure (ICP) (+18.5 mm Hg by 3 h). In comparison, in cats that received a 1 mg/kg iv dose of U74006F at 30 min after SAH, there was a complete prevention of the fall in CNBF and a significant attenuation of the rise in ICP. Furthermore, the drug reduced a concomitant fall in the mean arterial blood pressure and cerebral perfusion pressure. While not as effective as the 1 mg/kg dose, a 0.1 mg/kg dose also significantly attenuated the post-SAH fall in CNBF. These results supporte a role of lipid peroxidation in the acute pathophysiology of SAH and suggest that U74006F may be useful in the early treatment of this disorder.
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U2 - 10.1016/0014-4886(88)90100-8
DO - 10.1016/0014-4886(88)90100-8
M3 - Article
C2 - 3181364
AN - SCOPUS:0023727576
SN - 0014-4886
VL - 102
SP - 244
EP - 248
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -