Correlation of methylprednisolone levels in cat spinal cord with its effects on (Na+ + K+)-ATPase, lipid peroxidation, and alpha motor neuron function.
Large intravenous doses of methylprednisolone sodium succinate are associated with biochemical and electrophysiological effects in the cat spinal cord which may be of therapeutic value in the treatment of spinal cord injury. The potentially beneficial effects of large doses of the glucocorticoid include: 1) an enhancement of spinal cord (Na + + K+)-ATPase activity; 2) an attenuation of lipid peroxide formation; 3) a hyperpolarization of motor neuron resting membrane potentials; and 4) an accelerated impulse conduction along the myelinated portion of the motor axon. Each of these is apparent with spinal cord tissue levels of methylprednisolone around 1.3 micrograms/gm wet weight, which are rapidly obtained following a single intravenous dose of 30 mg/kg. The half-life of methylprednisolone in cat spinal cord following a single intravenous administration, as well as the duration of its pharmacological actions, is roughly 3 hours. The data suggest that, in order to be of therapeutic value in the treatment of acute spinal cord trauma, early intervention with high-dose intravenous methylprednisolone (30 to 40 mg/kg) is necessary, followed by intravenous maintenance dosing of 15 to 20 mg/kg every 2 to 3 hours. The rationale and duration for this regimen are discussed.
D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008775:Methylprednisolone / Q000031:analogs & derivatives*; D008776:Methylprednisolone Hemisuccinate / Q000378:metabolism / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology; D013119:Spinal Cord Injuries / Q000188:drug therapy
D008054:Lipid Peroxides; D008315:Malondialdehyde; D008776:Methylprednisolone Hemisuccinate; D000254:Sodium-Potassium-Exchanging ATPase; D008775:Methylprednisolone