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[强心苷与非苷类强心剂对心肌收缩蛋白系统的变力作用的比较疗效及分子机制差异]

[The comparative efficacy and differences in the molecular mechanism of the inotropic action of cardiac glycosides and nonglycoside cardiotropic agents on the contractile protein system of the myocardium].

作者信息

Karsanov N V, Kipshidze N N, Sukoian G V, Guchua Z I, Tatulashvili D R, Karsanov V N, Iarovaia E V, Magaldadze V A, Turmanauli G S

出版信息

Eksp Klin Farmakol. 1996 May-Jun;59(3):28-33.

PMID:8974579
Abstract

The in vitro study on an isolated system of myocardial contractile proteins determined optimal concentrations of the positive inotropic action and biological activity ranges of beta-methyldigoxin (beta-MD), strophanthin K, K-strophantozide, beta-acetyldigoxin (beta-AD), milrinone, and amrinone. Optimal concentrations of the beta-MD and strophanthin K (10(-2) and 10(-6) M, respectively) significantly increased qualitatively and quantitatively the economy and thermodynamic efficiency, altered the energy transformation in the contractile protein system under the isometric contraction, whereas the beta-AD produced only the quantitative effect. However, the beta-MD and strophanthin K at concentrations exceeding the optimal one by one order lost the ability to produce the qualitative effect, retaining only the quantitative one in the actomyosin ensemble. The strophanthin K significantly increased the economy of a single actomyosin ensemble in the force generation phase and the beta-MD in the tension maintenance phase. Unlike the strophanthin K, the beta-MD did not slow down (did not worsen) the relaxation process. This provides grounds to conclude that the beta-MD produces most favorable effect on the energy transformation by myocardial contractile proteins.

摘要

对心肌收缩蛋白分离系统进行的体外研究确定了β-甲基地高辛(β-MD)、毒毛花苷K、毒毛花苷K苷、β-乙酰地高辛(β-AD)、米力农和氨力农正性肌力作用的最佳浓度以及生物活性范围。β-MD和毒毛花苷K的最佳浓度(分别为10^(-2)和10^(-6) M)在定性和定量方面均显著提高了经济性和热力学效率,改变了等长收缩下收缩蛋白系统中的能量转换,而β-AD仅产生定量效应。然而,β-MD和毒毛花苷K的浓度超过最佳浓度一个数量级时,失去了产生定性效应的能力,在肌动球蛋白总体中仅保留了定量效应。毒毛花苷K在力产生阶段显著提高了单个肌动球蛋白总体的经济性,而β-MD在张力维持阶段有此作用。与毒毛花苷K不同,β-MD不会减缓(不会恶化)舒张过程。这为得出β-MD对心肌收缩蛋白的能量转换产生最有利影响这一结论提供了依据。

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