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

Background Ketamine has a species-dependent inotropic effect on myocardium, The authors' aim was to investigate the direct inotropic effect and the co rresponding intracellular Ca2+ transients of ketamine and its isomers on hu man myocardium. Methods: Right auricular myocardial strips obtained during open heart surge ry were exposed to increasing concentrations (73 mu M, 360 mu M, and 750 mu M) 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 forc e, maximal isotonic shortening amplitude, contractility, and relaxation inc reased by 12.5-22.4% after perfusion with S(+)-ketamine at the concentratio n of 73 mu M (P < 0.05), In contrast, no changes were seen after addition o f 73 mu M R(-)-ketamine, The effect of racemic ketamine (73 mu M) was betwe en that of the two isomers. At the highest concentration (730 mu M) ketamin e and its isomers decreased maximal isometric developed force, maximal shor tening amplitude, contractility, and relaxation by 26.8-57.4% CP < 0.05), a ccompanied 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 isometri c force, isotonic shortening, contractility, and relaxation at low concentr ations (73 mu M) compared with the initial control. At higher concentration s (730 mu M) a direct negative inotropic action was observed after perfusio n with ketamine and its isomers, which was accompanied by a decreased intra cellular Ca2+ transient.