Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord.
A method was developed for administering intrathecal pharmacotherapy in a rat model of spinal cord injury. The effects of intrathecal administration of nimodipine on spinal cord blood flow (SCBF) and evoked potentials (EPs) were measured in the normal and injured spinal cord. It had previously been shown that systemic nimodipine caused severe hypotension after spinal cord injury. After baseline SCBF and EPs, 15 uninjured rats were blindly allocated to one of three groups: one placebo group (n = 5); and two groups with intrathecal nimodipine, 0.05 mg/kg (n = 5), or 0.2 mg/kg (n = 5). Ten other rats received a 35 g acute clip compression injury of the spinal cord for 1 minute and, were allocated to one of two groups: placebo (n = 5); and intrathecal nimodipine 0.05 mg/kg (n = 5) given 60 min after injury. In the uninjured groups, neither 0.05 nor 0.2 mg/kg of nimodipine increased SCBF during, or 30 min after, intrathecal infusion. However, the mean arterial blood pressure (MABP) decreased significantly to 69.73.1% after the infusion of 0.2 mg/kg nimodipine and did not recover by 98 min. In all three groups of uninjured rats, the amplitude of the cerebellar EP was decreased 30 min after infusion. After spinal cord injury, there were significant decreases in MABP, SCBF and EP amplitude in both placebo and treatment groups, but there was no therapeutic benefit from nimodipine. Thus, intrathecal infusion of nimodipine did not prevent the hypotension encountered with systemic administration and exerted no beneficial effect on SCBF or EPs after acute spinal cord injury.
Canadian Paraplegic Association Spinal Cord Research Laboratory, Division of Neurosurgery, Toronto, Ontario, Canada.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D005071:Evoked Potentials / Q000187:drug effects*; D007278:Injections, Spinal; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D009553:Nimodipine