Effect of ketamine HCl on norepinephrine disposition in isolated ferret ventricular myocardium

DJ Cook, PR Housmans and DK Rorie

Department of Anesthesiology, Mayo Foundation, Rochester, Minnesota.

The purpose of this study was to determine if ketamine altered the release or disposition of norepinephrine at adrenergic nerve terminals in isolated ferret myocardium. In superfused right ventricular strips, the effect of ketamine on norepinephrine release and uptake was determined. Dihydroxyphenylglycol, the intraneuronally derived metabolite of norepinephrine, served as an index of neuronal uptake and was also measured in superfusate. Pharmacological manipulation of selective aspects of adrenergic transmission with corticosterone, yohimbine, clorgyline and desmethylimipramine allowed the primary site of action of ketamine to be established. Quantitation of tissue norepinephrine content after the experiments provided another means to evaluate ketamine's effect on norepinephrine release as well as to estimate the density of adrenergic innervation in ferret myocardium. Norepinephrine and dihydroxyphenylglycol were quantitated by high- pressure liquid chromatography with electrochemical detection. Ketamine increased norepinephrine overflow and decreased the efflux of dihydroxyphenylglycol in isolated myocardium. Studies in the presence of the clorgyline suggest that ketamine does not increase norepinephrine overflow by means of monoamine oxidase inhibition, and studies in the presence of desmethylimipramine and corticosterone indicate that ketamine does not augment norepinephrine release. Quantitation of tissue norepinephrine content demonstrates that ketamine does not cause depletion of myocardial catecholamines. The ketamine-induced increase in norepinephrine overflow and the observed decrease in dihydroxyphenylglycol production suggest that inhibition of the neuronal uptake of norepinephrine is the primary mechanism of ketamine's effect in isolated myocardium.

Volume 261, Issue 1, pp. 101-107, 04/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics

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