[Contribution of cooperative mechanisms of the thin filament activation to the myocardium contractile function. Assessment by a mathematical model].

We applied a mathematical model to compare the contributions to the myocardium mechanical activity of two a priori feasible variants of the cooperative effect of myosin cross-bridges on the calcium activation of sarcomere thin filaments. One of these variants implies that cross-bridge cooperative influence on the troponin C affinity to calcium is localized within the same functional cluster A7TmTn where the cross-bridge is attached. The second variant is based on the assumption that cross-bridges may affect the affinity of troponin C to calcium in other functional clusters A7TmTn as well (so that the nearer to the cross-bridge a cluster lies, the stronger the cross-bridge affects the affinity of CaTnC complex in this cluster). Each of these two variants and its contribution to the active mechanical performance of the heart muscle during the contraction-relaxation cycle were alternatively assessed in the model. It was found that only the second variant correctly simulates the mechanical activity of the muscle. Thus, the modeling suggests that just this variant of the cooperativity seems to be more feasible.

[Mechanisms of electromechanical function disturbances in cardiomyocytes overloaded with calcium. The theoretical study].

Arrhythmias and mechanical disturbances are simulated in a mathematical model of cardiomyocyte electromechanical activity. The simulated pattern is similar to that observed for acute heart failure associated with calcium overloading of myocardium cells. Special attention was paid to the calcium overloading resulting from the reduced Na+,K+ pump activity. In the framework of the model, it was shown that mechanical factors could promote arrhythmia initiation when the pump activity reduced. Different approaches to electrical and mechanical function restoration during acute heart failure associated with calcium overloading were suggested and analyzed in the model.

[Modeling of mechanoelectric coupling in cardiomyocytes in norm and pathology].

We developed mathematical models of the electromechanical function of cardiomyocytes and the simplest mechanically heterogeneous myocardial systems, muscle duplexes. By means of these models we studied the contribution of mechanoelectric feedbacks to the contractile activity of the myocardium in norm and pathology. In particular, we simulated and clarified the effects of mechanical conditions on both the form and the duration of the action potential during contractions. From this standpoint different kinds of myocardium mechanical heterogeneity were analyzed. As we have established, the latter can play both a positive and a negative role, depending on the distribution of mechanical nonuniformity and the sequence of activation of heterogeneous myocardium system elements. By means of the same models, we studied the contribution of mechanical factors to the arrhythmogenicity in the case of the cardiomyocyte calcium overload caused by the attenuation of the sodium-potassium pump and outlined the ways for correcting the contractile function in these disturbances.