EFFECT OF MILD HYPOTHERMIA AND THE 21-AMINOSTEROID U-74389G ON NEUROLOGIC AND HISTOPATHOLOGIC OUTCOME AFTER TRANSIENT SPINAL-CORD ISCHEMIA IN THE RABBIT

Mild hypothermia and the 21-aminosteroids have both been neuroprotecti ve In several models of cerebral ischemia. In this study we compared t he effects of mild hypothermia and the 21-aminosteroid U-74389G, alone and in combination on neurologic and histopathologic outcome after te mporary spinal cord ischemia. Ferry male anaesthetized New Zealand whi te rabbits were randomized to four groups (n = 10): (a) normothermia ( control); (b) U-74389G (3 mg/kg intravenously [i.v.] before aortic occ lusion, 1.5 mg/kg i.v. and 10 mg/kg intraperitoneally after occlusion) ; (c) mild hypothermia (4 degrees C epidural temperature decrease); an d (d) mild hypothermia combined with U-74389G. Spinal cord ischemia wa s produced by 40 min of infrarenal aortic balloon occlusion. Forty-eig ht hours after the procedure, the neurologic status of the animals was assessed (Tarlov score) and the animals were killed for histologic ev aluation. In the normothermic control group, eight of 10 animals becam e paraplegic. There was a significant reduction of the incidence of pa raplegia and overall neurologic deficits and a significant improved Ta rlov score in the mild hypothermic group (one animal paraplegic) and i n the group with both mild hypothermia and U-74389G (two animals with a mild paraparesis). The histopathologic scares showed significantly l ess damage in both hypothermic groups. In group 2, U-74389G administra tion did not improve neurologic or histopathologic outcomes. The resul ts of the current study demonstrate that a slight decrease of intraisc hemic spinal cord temperature significantly improved neurologic and hi stopathologic outcomes after experimental spinal cord ischemia. Protec tion by the 21-aminosteroid at normothermic conditions, or additional protection when U-74389G was added to mild hypothermia, could not be d emonstrated.