title: IV bolus administration of subconvulsive doses of lignocaine to conscious sheep: relationships between myocardial pharmacokinetics and pharmacodynamics.
abstract: We have studied relationships between the time-courses of lignocaine concentrations in arterial and coronary sinus blood and myocardial tissue, and negative inotropic effects on the myocardium, after i.v. bolus administration of 50-, 75- or 100-mg doses of lignocaine to conscious, chronically instrumented sheep. Peak arterial and coronary sinus blood lignocaine concentrations occurred 26-38 s before and 29-78 s after the maximum decreases in myocardial contractility, respectively. Peak myocardial concentrations occurred simultaneously with the maximum decreases in myocardial contractility, except for the 100-mg doses. Anti-clockwise hysteresis occurred only between arterial blood lignocaine concentrations and the negative inotropic effect. It was concluded that, after short-term i.v. administration, only the myocardial concentrations of lignocaine were in pseudoequilibrium with the negative inotropic effects of the lignocaine on the myocardium.
authors.affiliation: Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, Australia.
authors.forename: Y F
authors.initials: YF
authors.lastname: Huang
authors.forename: R N
authors.initials: RN
authors.lastname: Upton
authors.forename: W B
authors.initials: WB
authors.lastname: Runciman
mesh_terms: D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D012756:Sheep; D013997:Time Factors
chemical_list: D008012:Lidocaine