Effect of digitalis on central demyelinative conduction block in vivo.
In searching for agents effective in treating multiple sclerosis, we studied the effect of a short-acting digitalis, ouabain, on conduction block in an animal model of central nervous system demyelination. The electrogenic sodium/potassium pump, which digitalis specifically inhibits, is responsible for part of the resting membrane potential and also the activity-related membrane hyperpolarization following high-frequency impulses. The latter causes intermittent conduction block in demyelinated fibers. Therefore, digitalis might be expected to reverse demyelinative conduction blocks by reducing the threshold at the blocking node. Somatosensory evoked potentials were monitored in 11 rats with spinal cord demyelination before and after systemic administration of ouabain (0.1-0.6 mg or 0.21-1.58 mg/kg IP). In all rats, slowed conduction velocity of the compound action potential through the lesion was significantly reversed, and failure to transmit high-frequency impulses was improved upon. The amplitude of the cortical somatosensory evoked potentials also increased significantly. Digitalis is a promising therapeutic agent for trial in patients with multiple sclerosis.
Kaji
R
R
Department of Neurology, University of Pennsylvania, Philadelphia.
Sumner
A J
AJ
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D008297:Male; D009103:Multiple Sclerosis / Q000503:physiopathology*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013003:Somatosensory Cortex / Q000503:physiopathology; D013116:Spinal Cord / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects*; D013979:Tibial Nerve / Q000503:physiopathology
D010042:Ouabain