Kunst G, Martin E, Graf B M, Hagl S, Vahl C F
Department of Anesthesiology, University of Heidelberg, Germany.
Anesthesiology. 1999 May;90(5):1363-71. doi: 10.1097/00000542-199905000-00021.
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.
Right auricular myocardial strips obtained during open heart surgery were exposed to increasing concentrations (73 microM, 360 microM, and 730 microM) 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.
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 microM (P < 0.05). In contrast, no changes were seen after addition of 73 microM R(-)-ketamine. The effect of racemic ketamine (73 microM) was between that of the two isomers. At the highest concentration (730 microM) 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).
In contrast to R(-)-ketamine, S(+)-ketamine increased isometric force, isotonic shortening, contractility, and relaxation at low concentrations (73 microM) compared with the initial control. At higher concentrations (730 microM) a direct negative inotropic action was observed after perfusion with ketamine and its isomers, which was accompanied by a decreased intracellular Ca2+ transient.
氯胺酮对心肌具有种属依赖性的变力作用。作者的目的是研究氯胺酮及其异构体对人心脏的直接变力作用和相应的细胞内Ca2+瞬变。
在心脏直视手术中获取右心耳心肌条，将其暴露于外消旋氯胺酮（n = 12）、S(+)-氯胺酮（n = 12）或R(-)-氯胺酮（n = 11）的浓度递增（73微摩尔/升、360微摩尔/升和730微摩尔/升）溶液中。评估等长力、等张缩短、收缩性、舒张以及达到最大等张和等长力的时间。每组中的十条肌肉条加载钙敏荧光染料FURA-2/AM以同时测量钙瞬变。
与初始对照最大等长收缩力相比，在灌注浓度为73微摩尔/升的S(+)-氯胺酮后，最大等张缩短幅度、收缩性和舒张增加了12.5 - 22.4%（P < 0.05）。相比之下，添加73微摩尔/升的R(-)-氯胺酮后未见变化。外消旋氯胺酮（73微摩尔/升）的作用介于两种异构体之间。在最高浓度（730微摩尔/升）时，氯胺酮及其异构体使最大等长收缩力、最大缩短幅度、收缩性和舒张降低了26.8 - 57.4%（P < = 0.05），同时细胞内钙瞬变显著降低（降低21.0 - 32.2%，P < 0.05）。
与R(-)-氯胺酮相比，低浓度（73微摩尔/升）的S(+)-氯胺酮与初始对照相比增加了等长力、等张缩短、收缩性和舒张。在较高浓度（730微摩尔/升）时，灌注氯胺酮及其异构体后观察到直接的负性变力作用，同时细胞内Ca2+瞬变降低。
