Actions of Ketamine and Its Isomers on Contractility and Calcium Transients in Human Myocardium

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Abstract

Background

Ketamine has1 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 [micro sign]M, 360 [micro sign]M, and 730 [micro sign]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 force, maximal isotonic shortening amplitude, contractility, and relaxation increased by 12.5–22.4% after perfusion with s(+)-ketamine at the concentration of 73 [micro sign]M (P < 0.05). In contrast, no changes were seen after addition of 73 [micro sign]M R(-)-ketamine. The effect of racemic ketamine (73 [micro sign]M) was between that of the two isomers. At the highest concentration (730 [micro sign]M) 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 [micro sign]M) compared with the initial control. At higher concentrations (730 [micro sign]M) a direct negative inotropic action was observed after perfusion with ketamine and its isomers, which was accompanied by a decreased intracellular Ca2+ transient.

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