Actions of ketamine and its isomers on contractility and calcium transients in human myocardium

Abstract

Background: Ketamine has a species-dependent inotropic effect on myocardium. The authors' aim was to investigate the direct inotropic effect and the corresponding intracellular Ca2+ transients of ketamine and its isomers on human myocardium. Methods: Right auricular myocardial strips obtained during open heart surgery were exposed to increasing concentrations (73 μM, 360 μM, and 730 μM) of racemic ketamine (n = 12), S(+)-ketamine (n = 12), or R(-)-ketamine (n = 11). Isometric force, isotonic shortening, contractility, relaxation, and time to maximal isotonic and isometric force were assessed. Ten muscle strips in each group were loaded with the calcium- sensitive fluorescent dye FURA-2/AM for simultaneous measurements of calcium transients. Results: Compared with the initial control maximal isometric developed force, maximal isotonic shortening amplitude, contractility, and relaxation increased by 12.5-22.4% after perfusion with S(+)-ketamine at the concentration of 73 μM (P < 0.05). In contrast, no changes were seen after addition of 73 μM R(-)-ketamine. The effect of racemic ketamine (73 μM) was between that of the two isomers. At the highest concentration (730 μM) ketamine and its isomers decreased maximal isometric developed force, maximal shortening amplitude, contractility, and relaxation by 26.8-57.4% (P < 0.05), accompanied by a significant decrease of the intracellular calcium transient (by 21.0-32.2%, P < 0.05). Conclusions: In contrast to R(-)-ketamine, S(+)- ketamine increased isometric force, isotonic shortening, contractility, and relaxation at low concentrations (73 μM) compared with the initial control. At higher concentrations (730 μM) a direct negative inotropic action was observed after perfusion with ketamine and its isomers, which was accompanied by a decreased intracellular Ca2+ transient.