Protection against postischemic spinal cord injury using a new 21-aminosteroid.
Ischemic spinal cord injury following repair of the thoracoabdominal aorta is an unpredictable and devastating complication. Recently, a new class of agents has been developed, the 21-aminosteroids, which have been demonstrated to reduce ischemic neurologic injury in several animal models. We performed this study to determine if the 21-aminosteroid U-74006F exerted a protective effect in a rabbit model of spinal cord ischemia. Nineteen New Zealand rabbits were anesthetized and then subjected to 25 min of temporary infrarenal aortic occlusion. Nine rabbits were given 3.0 mg/kg U-74006F iv 10 min prior to clamping the aorta, followed by 0.75 mg/kg every hour for 6 hr beginning 1 hr after the clamp was removed. Ten rabbits received equivalent doses of an aqueous buffered vehicle. The rabbits were neurologically graded upon awakening and then daily using the following scale: grade 0 = complete paralysis, grade 1 = partial deficit, grade 2 = normal. In the U-74006F-treated group, five animals were normal, one had a partial deficit, and three were paraplegic. In the vehicle group, only one animal was normal and nine were paraplegic. The difference between the mean neurologic grading scores of the two groups was statistically significant (P = 0.013). It is believed that U-74006F acts at the cell membrane level during reperfusion by inhibiting lipid peroxidation and lipid hydrolysis. Our data suggest that this agent may significantly reduce the incidence of postischemic spinal cord injury following temporary aortic occlusion.
Fowl
R J
RJ
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267.
Patterson
R B
RB
Gewirtz
R J
RJ
Anderson
D K
DK
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D007511:Ischemia / Q000150:complications* / Q000503:physiopathology; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D010243:Paralysis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011281:Pregnatrienes / Q000627:therapeutic use*; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply*
D008054:Lipid Peroxides; D011281:Pregnatrienes; C053355:tirilazad