I.V. BOLUS ADMINISTRATION OF SUBCONVULSIVE DOSES OF LIGNOCAINE TO CONSCIOUS SHEEP: RELATIONSHIPS BETWEEN MYOCARDIAL PHARMACOKINETICS AND PHARMACODYNAMICS

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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.

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