Mechanical restitution (MR) represents the time recovery of the heart muscle's ability to contract. Despite intensive research, some aspects of MR remain unclear. To describe MR in guinea pig cardiac muscle, we modified our published mathematical model of guinea pig ventricular cardiomyocyte and supplemented it with a description of cellular contraction. To achieve the best agreement between the model simulations and available experimental data, some model parameters were optimised. The model enables the simulation of the experimentally observed fast onset of recovery of action potential duration, L-type Ca2+ current amplitude, and isometric force. The performed simulations and analyses of model data showed that the high time constant of voltage-dependent inactivation of L-type Ca2+ channels used in previously published models (~ 600 ms at resting voltage) is not consistent with the initial steep rise of the MR curve in guinea pig cardiomyocytes. It also suggests that the adaptation rate of ryanodine receptors, which was set differently in the previous models, is fast (~ 100 s- 1). Finally, analysis of the effect of a 50% reduction in membrane currents on MR revealed a marked dependence on stimulation frequency. At 1 Hz, only the reduction of INaCa and INaK significantly affected the MR course.

Department of Physiology Faculty of Medicine Masaryk University Brno Kamenice 5 Brno 625 00 Czech Republic

Institute of Thermomechanics Czech Academy of Science Prague Czech Republic

Zobrazit více v PubMed

Giotti, A. Quantitative aspects and mechanisms of the relation between myocardial contraction and diastolic period. PubMed

Meijler, F. L.

Braveny, P. & Kruta, V. Dissociation de Deux facteurs: restitution et potentiation Dans l’action de l’intervalle Sur l’amplitude de La contraction du myocarde. PubMed

Allen, D. G., Jewell, B. R. & Wood, E. H. Studies of the contractility of mammalian myocardium at low rates of stimulation. PubMed PMC

Bravený, P., Sumbera, J. & Kruta, V. After-contractions and restitution of contractility in the isolated guinea-pig auricles. PubMed

Kruta, V. & Bravený, P. Potentiation of contractility in the heart muscle of the rat and some other mammals. PubMed

Kruta, V. & Bravený, P. Rate of restitution and self-regulation of contractility in mammalian heart muscle. PubMed

Kruta, V., Braveny, P., Hlavkova Stejskalova, J. & Husakova, B. Restoration of myocardial contractility and inotropic effects (ouabain, quinidine, tyramine, Theophylline and acetylcholine) in Guinea pigs and rats. PubMed

Edman, K. A. & Jóhannsson, M. The contractile state of rabbit papillary muscle in relation to stimulation frequency. PubMed PMC

Hoffman, B. F. & Cranefield, P. F. Paired-pulse stimulation of the heart. PubMed

Dumitrescu, C., Narayan, P., Cheng, Y., Efimov, I. R. & Altschuld, R. A. Phase I and phase II of short-term mechanical restitution in perfused rat left ventricles. PubMed

Liu, B., Wohlfart, B. & Johansson, B. W. Mechanical restitution at different temperatures in papillary-muscles from rabbit, rat and Hedgehog. PubMed

Bass, B. G. Enhanced contractility during relaxation of Cat papillary-muscle. PubMed

Bjornstad, H., Tande, P. M. & Refsum, H. Mechanisms for hypothermia-induced increase in contractile force studied by mechanical restitution and post-rest contractions in Guinea pig papillary muscle. PubMed

Wier, W. G. & Yue, D. T. Intracellular calcium transients underlying the short-term force-interval relationship in ferret ventricular myocardium. PubMed PMC

Dumitrescu, C. et al. Mechanical alternans and restitution in failing SHHF rat left ventricles. PubMed

Rice, J. J., Jafri, M. S. & Winslow, R. L. Modeling short-term interval-force relations in cardiac muscle. PubMed

Cortassa, S. et al. A computational model integrating electrophysiology, contraction, and mitochondrial bioenergetics in the ventricular myocyte. PubMed PMC

Pasek, M., Simurda, J., Orchard, C. H. & Christe, G. A model of the guinea-pig ventricular cardiac myocyte incorporating a transverse-axial tubular system. PubMed

Luo, C. & Rudy, Y. A dynamic model of the cardiac ventricular action-potential. I. Simulations of ionic currents and concentration changes. PubMed

Szigligeti, P. et al. Intracellular calcium and electrical restitution in mammalian cardiac cells. PubMed

Vornanen, M. & Shepherd, N. Restitution of contractility in single ventricular myocytes of Guinea pig heart. PubMed

Wang, W. et al. Reduced junctional Na PubMed PMC

Sher, A., Noble, P., Hinch, R., Gavaghan, D. & Noble, D. The role of the Na PubMed

Khokhlova, A., Balakina-Vikulova, N., Katsnelson, L., Iribe, G. & Solovyova, O. Transmural cellular heterogeneity in myocardial electromechanics. PubMed PMC

Pytkowski, B., Lewartowski, B., Prokopczuk, A., Zdanowski, K. & Lewandowska, K. Excitation-dependent and rest-dependent shifts of Ca in guinea-pig ventricular myocardium. PubMed

Kurihara, S. & Sakai, T. Effects of rapid cooling on mechanical and electrical responses in ventricular muscle of guinea-pig. PubMed PMC

Takagi, S. et al. Cold acclimation of Guinea pig depressed contraction of cardiac papillary muscle. PubMed

Alam, T., Qamar, S., Dixit, A. & Benaida, M. Genetic algorithm: reviews, implementations and applications.

Pásek, M. & Simurda, J. Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells. PubMed

Jafri, M., Rice, J. & Winslow, R. Cardiac Ca PubMed PMC

Dumitrescu, C. et al. Mechanical alternans and restitution in failing SHHF rat left ventricles. PubMed

Spencer, C., Morner, S., Noble, M. & Seed, W. Influences of stimulation frequency and temperature on interval-force relationships in guinea-pig papillary-muscles. PubMed

Cooper, I. C. & Fry, C. H. Mechanical restitution in isolated mammalian myocardium – species-differences and underlying mechanisms. PubMed

Valdivia, H., Kaplan, J., Ellisdavies, G. & Lederer, W. Rapid adaptation of cardiac Ryanodine receptors – modulation by Mg PubMed PMC

Yasui, K., Palade, P. & Györke, S. Negative control mechanism with features of adaptation controls Ca PubMed PMC

Kohajda, Z. et al. The effect of a novel highly selective inhibitor of the sodium/calcium exchanger (NCX) on cardiac arrhythmias in in vitro and in vivo experiments. PubMed PMC

Hegner, P. et al. SAR296968, a novel selective Na PubMed PMC

Pelat, M. et al. SAR340835, a novel selective Na PubMed

Ozdemir, S. et al. Pharmacological Inhibition of na/ca exchange results in increased cellular Ca PubMed

Bögeholz, N. et al. The effects of SEA0400 on Ca PubMed PMC

Altamirano, J. et al. The inotropic effect of cardioactive glycosides in ventricular myocytes requires Na PubMed PMC