The Effect of Ketamine on Catecholamine Metabolism in the Isolated Perfused Rat Heart

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Abstract
The effects of ketamine infusion on the uptake and release of norepinephrine and on formation of deaminated metabolites in the isolated, perfused rat heart were studied. Hearts were removed from animals during light ether anesthesia, transferred to a modified Langendorff perfusing apparatus, and perfused with Krebs-Ringer solution containing various doses of ketamine and 200 µg/ml of DL-norepinephrine—14C. Norepinephrine uptake was determined after perfusion for 1, 2, 4, 6, and 20 minutes. At the end of each period the ketaminetreated hearts contained less DL-norepinephrine—14C per gram of heart tissue than control hearts. The reduction was proportional to the dose of ketamine. On an equal-dose basis, ketamine was approximately 80 per cent as effective as cocaine in blocking the uptake of norepinephrine. Norepinephrine release was determined after perfusing hearts for 4 minutes with perfusate containing 200 µg/ml of DL-norepinephrine—14C, then perfusing with solution containing ketamine but free of norepinephrine for 20 minutes. After 10 minutes of perfusion a decrease in myocardial DL-norepinephrine began to appear, and at 20 minutes the decrease was significant. Ketamine infusion did not alter myocardial levels of intracellular deaminated metabolites of norepinephrine, indicating that the effects of ketamine are primarily membrane-related. The results of this study suggest that the sympathomimetic-like effects of ketamine seen in both man and animals may be due to inhibition of the reuptake processes for endogenously released norepinephrine.

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