Canine gastrocnemius disuse atrophy: resistance to paralysis by dimethyl tubocurarine.
Ten dogs developed unilateral gastrocnemius disuse atrophy after unilateral hindlimb immobilization in a cast for 25 days. Dose-response curves to dimethyl tubocurarine (MTC) were determined during anesthesia with pentobarbital sodium-N2O. Bolus and continuous infusion increments of MTC every 30 min provided steady-state blood levels at each stage of paralysis. Both gastrocnemius tendons were sectioned and attached to transducers. Both sciatic nerves were stimulated every 30 min: 2 Hz for 2 s, a 15-s pause, 50 Hz for 2 s. Dose-response curves, computer calculated by nonlinear regression using a sigmoid maximal effect model of the Hill equation, were parallel for the data relating blocking of tetanus to dose of MTC. The 50% paralyzing dose (tetanus) for control vs. casted gastrocnemius muscle was 64 vs. 813 mg/kg; corresponding plasma concentrations were 0.12 vs. 2.0 micrograms/ml. Thus in vivo simultaneous tension measurements of both gastrocnemius muscles, one casted and one uncasted, demonstrated resistance to paralysis by MTC in muscle with disuse atrophy.
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D007103:Immobilization; D007866:Leg; D009133:Muscular Atrophy / Q000209:etiology / Q000503:physiopathology*; D010243:Paralysis / Q000139:chemically induced*; D014403:Tubocurarine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
C015836:dimethyltubocurarine; D014403:Tubocurarine