THE CHANGING PHARMACODYNAMICS OF METOCURINE IDENTIFY THE ONSET AND OFFSET OF CANINE GASTROCNEMIUS DISUSE ATROPHY

Background: Immobilization of skeletal muscle results in disuse atroph y and resistance to nondepolarizing muscle relaxants. We studied the p harmacodynamics of metocurine (MTC) to identify the development and re covery of disuse-related resistance to MTC. Methods: Nineteen dogs und erwent cast immobilization of a hind limb for as long as 3 weeks. Befo re, during, and after casting, dogs were intermittently anesthetized w ith thiamylal-N2O-fentanyl. The blood concentration of MTC and the cor responding degree of paralysis after a brief infusion were recorded an d were used to characterize the pharmacokinetics and pharmacodynamics of MTC. Results: Pharmacodynamic study of the response to MTC demonstr ated resistance by the 4th day of casting. The effect-site concentrati on associated with 50% paralysis of twitch increased after 3 weeks fro m approximately 250 to 750 ng/ml. After cast removal, resistance persi sted for 2 more weeks. Six weeks after cast removal, the effect-site c oncentration associated with 50% paralysis of twitch was normal in eve ry dog. Conclusions: Within the context of this study of immobilizatio n disuse atrophy, pharmacokinetic and pharmacodynamic characterization of antagonist responses can be used to infer muscle disuse-related ch anges in acetylcholine receptors.