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

: 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.