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Effects of Omecamtiv Mecarbil on the Tension–Length Loop and Work in Right Ventricular Trabeculae from Rats with Pulmonary Heart Failure

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Abstract

Omecamtiv mecarbil (OM) is a selective cardiac myosin activator. We studied the effects of OM on the characteristics of contractility under mechanical loads of right ventricular trabeculae in control group rats and rats with monocrotaline-induced pulmonary heart failure. Right ventricular hypertrophy was accompanied by an increase in phosphorylation of cardiac myosin-binding protein C (cMyBP-C), troponin T, and troponin I and a decrease in phosphorylation of myosin regulatory light chain. We studied the OM effect in concentrations of 0.2 µM and 1 µM on the “tension–length” loop and the work amount in the intact trabeculae obtained in a physiological contraction mode. To study the OM effect on actin-myosin interaction we analyzed the dependence of the sliding velocities of F-actin and native thin filaments over myosin in an in vitro motility assay on the OM concentrations. The OM effects on the characteristics of contraction of trabeculae from control rats and rats with pulmonary heart failure were different. In the intact rats, OM dose-dependently reduced the work amount of rat trabeculae, but in the rats with pulmonary heart failure, 0.2 µM OM increased it by 8.5 ± 8.7% (p < 0.05, U-test) at 0.5 P/P 0. These differences in the OM effects are explained by an increase in phosphorylation of cMyBP-C and TnI during right ventricular hypertrophy.

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Funding

This work was supported by IIF UrB RAS theme no. 122022200089-4. This work was performed using the equipment of the Shared Research Center of Scientific Equipment SRC IIP UrB RAS.

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  1. Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russia

    A. Balakin, R. Lisin, D. Kuznetsov, A. Kochurova, E. Mukhlynina, D. Shchepkin, G. Kopylova & Yu. Protsenko

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Contributions

Y.P. conceptualized the work; A.B., R.L., and D.K. performed experiments with intact trabeculae and analyzed data; E.M. performed histological analysis; A.K., D.S., and G.K. performed in vitro motility experiments and analyzed data; A.B., D.S., G.K., and Y.P. wrote the manuscript; all authors read and approved the manuscript.

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Correspondence to A. Balakin.

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Balakin, A., Lisin, R., Kuznetsov, D. et al. Effects of Omecamtiv Mecarbil on the Tension–Length Loop and Work in Right Ventricular Trabeculae from Rats with Pulmonary Heart Failure. J Evol Biochem Phys 59, 1182–1194 (2023). https://doi.org/10.1134/S0022093023040130

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