Numerical modelling of myocardial infarction in multivessel coronary lesion. II.~Patterns of formation of large-scale damages and structures

O. F. Voropaeva ; Ch. A. Tsgoev

Matematičeskaâ biologiâ i bioinformatika, Tome 19 (2024), pp. 497-532.

Résumé

In this work, the basic mechanisms of myocardial infarction development during its inflammatory phase have been studied using mathematical modelling methods. Complex scenarios associated with multivessel lesions of the coronary bed and variability in baseline indicators of the innate immune system state have been considered. Special attention is paid to methodological issues related to the analysis of the effectiveness of the algorithm for approximate solutions of nonlinear initial-boundary value problems and setting up computational experiments under conditions close to the conditions of laboratory experiments in the field of interest. A numerical analysis was performed of several of the most common variants in laboratory practice of the formation of a large lesion in the left ventricle of the mouse heart, caused by the spatiotemporal heterogeneity of the properties of the environment, the immune reaction and ischemic myocardial damage, including recurrent infarction. The main attention is on the following aspects: – analysis of the mechanism of formation of large-scale infarct damages with an extensive core covering almost the entire infarct focus, or with a relatively small core, and assessment of the role of inflammation in these processes; – analysis of current scenarios of structure formation and the role of nonlinear dynamic structures of demarcation inflammation in the formation of a large but highly structured focus. The obtained data allow us to conclude that there is sufficient conservatism during infarction, evidenced by the basic patterns of the inflammatory phase revealed during modeling. The variability of heart attack scenarios manifests itself as a “memory”-effect about the initial data. We observe the “memory”-effect only at a biologically significant time interval, but we also note a general tendency to switch to the usual scenario of inflammation in large-focal infarction, which eliminates the peculiarities of the initial and individual conditions. The role of inflammation has been investigated in the context of a wave process in which spatial localization and the interaction of density and concentration waves can determine the main features of myocardial damage. In particular, within the framework of the adopted mathematical model, the conditions under which the formation of local zones with a relatively low or, conversely, high level of damage is possible have been described. In our work, we have established a significant interdependence between the formation of quasi-stationary structures and the intensity of the immune response. The high probability of developing severe or even terminal myocardial infarction may be due to the high level of immune system factors, in particular, monocytes-macrophages or cytokines in the reinfarction heart.

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