Effect of the 21-aminosteroid U-74006F on cerebral vasospasm following subarachnoid hemorrhage.
The purpose of this study was to use a new 21-aminosteroid (U-74006F) with in vitro antioxidant and antilipolytic properties as a pharmacological probe to assess the role of lipid hydrolysis and peroxidation in a rabbit model of subarachnoid hemorrhage (SAH)-induced vasospasm. Cerebral angiograms were performed on 15 rabbits. Eighteen hours later, 1 cc/kg of autologous blood was infused into the cisterna magna of all 15 animals. Six rabbits received no treatment, six received U-74006F starting 30 minutes after SAH, and three rabbits received the vehicle for U-74006F starting 30 minutes after SAH. At 72 hours post-SAH, a second angiogram was obtained. Digital subtraction angiographic techniques were used to measure the diameter of and contrast material flow through the basilar artery. At 72 hours post-SAH, vasospasm was evident in all untreated and vehicle-treated rabbits. The diameter of and the flow through the basilar artery were significantly reduced 42.3% +/- 6.6% and 46.8% +/- 5.8%, respectively, below pre-SAH levels (means +/- standard error of the means). Treatment with U-74006F eliminated the SAH-induced vasospasm; in treated animals, both the flow through and the diameter of the basilar arteries were at pre-SAH levels. These findings indicate that: 1) membrane lipid changes (that is, hydrolysis with eicosanoid production and/or peroxidation) contribute to the chronic vasospasm resulting from SAH, and 2) U-74006F prevents the SAH-induced chronic vasospasm in this model by limiting these pathological membrane events.
Zuccarello
M
M
Cincinnati Veterans Administration Medical Center, Ohio.
Marsch
J T
JT
Schmitt
G
G
Woodward
J
J
Anderson
D K
DK
D000818:Animals; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D008297:Male; D011281:Pregnatrienes / Q000627:therapeutic use*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013382:Subtraction Technique
D008054:Lipid Peroxides; D011281:Pregnatrienes; C053355:tirilazad