title: Tachyphylaxis to local anesthetics does not result from reduced drug effectiveness at the nerve itself.
abstract: Possible development of tachyphylaxis to local anesthetics in the nerve itself (time-dependent change in axonal conduction properties) was studied in the aortic nerve of eight rabbits anesthetized with urethane. The nerve was immersed in Tyrode solution with or without bupivacaine at pH 7.4 and 38 degrees C in a trough molded from the surrounding tissues. After control measurements the nerve was exposed to increasing bupivacaine concentrations until complete nerve block at minimal blocking concentration. Subsequently, bupivacaine concentrations were reduced and kept constant for 4 h (partial block). Finally, intact nerve function was confirmed after bupivacaine washout with Tyrode solution. For quantification total nerve activity was recorded continuously and related to drug concentrations. Two findings argue against the occurrence of tachyphylaxis at the nerve itself: 1) nerve activity decreased rather than increased over time in the presence of constant bupivacaine concentrations during partial block; and 2) for the same bupivacaine concentration, nerve activity during partial block was always lower than during the initial blocking experiments. Thus, drug effectiveness increased rather than decreased over time, which cannot be reconciled with the theory that tachyphylaxis might be mediated by changes in axonal conduction properties.
authors.affiliation: Department of Experimental Anesthesiology, University of Duesseldorf.
authors.forename: P
authors.initials: P
authors.lastname: Lipfert
authors.forename: H
authors.initials: H
authors.lastname: Holthusen
authors.forename: J O
authors.initials: JO
authors.lastname: Arndt
mesh_terms: D000779:Anesthetics, Local; D000818:Animals; D001011:Aorta / Q000294:innervation*; D002045:Bupivacaine / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D009407:Nerve Block; D009431:Neural Conduction / Q000187:drug effects*; D011817:Rabbits; D013618:Tachyphylaxis
chemical_list: D000779:Anesthetics, Local; D002045:Bupivacaine