The effects of two cardiomyopathy-associated mutations in regulatory sarcomere protein tropomyosin (Tpm) on heart function were studied with a new multiscale model of the cardiovascular system (CVS). They were a Tpm mutation, Ile284Val, associated with hypertrophic cardiomyopathy (HCM), and an Asp230Asn one associated with dilated cardiomyopathy (DCM). When the molecular and cell-level changes in the Ca2+ regulation of cardiac muscle caused by these mutations were introduced into the myocardial model of the left ventricle (LV) while the LV shape remained the same as in the model of the normal heart, the cardiac output and arterial blood pressure reduced. Simulations of LV hypertrophy in the case of the Ile284Val mutation and LV dilatation in the case of the Asp230Asn mutation demonstrated that the LV remodeling partially recovered the stroke volume and arterial blood pressure, confirming that both hypertrophy and dilatation help to preserve the LV function. The possible effects of changes in passive myocardial stiffness in the model according to data reported for HCM and DCM hearts were also simulated. The results of the simulations showed that the end-systolic pressure–volume relation that is often used to characterize heart contractility strongly depends on heart geometry and cannot be used as a characteristic of myocardial contractility.

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This article deals with the negative impact of slag dumps and sludge collectors on the environment. The development of measures to prevent, reduce (limit), compensate and eliminate potential and actual damage caused by sludge collectors of the surrounding natural environment is a highly important issue. It was also revealed that the current legislation of the Russian Federation does not account for the amount of economic damage caused to the recipient objects by environmental pollution and as a separate component of damage to atmospheric air and soils. Therefore, it is suggested to make additional changes to the order of Rostekhnadzor No. 120 “On approval of the methodology for determining the amount of harm that may be caused to life and health of individuals, property of individuals and legal entities as a result of an accident of a hydraulic structure (except for shipping and port hydraulic structures)”.

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