Transmural heterogeneity in the mechanical and electrical properties of cardiomyocytes. Experimental study and modeling

Supported by the Russia Foundation for Basic Research (14-01-00885, 14-01-31134), by Presidium of the Ural Branch of the Russian Academy of Sciences (12-M-14-2009, 12-П-4-1067) by Ural Federal University (Act 211 Government of the Russian Federation #02.A03.21.0006) and by JREX Fellowship for young researchers

Integrative Modeling of Electrical Properties of Pacemaker Cardiac Cells

This work represents modeling of electrical properties of pacemaker (sinus) cardiac cells. Special attention is paid to electrical potential arising from transmembrane current of Na{+}, K{+} and Ca{2+} ions. This potential is calculated using the NaCaX model. In this respect, molar concentration of ions in the intercellular space which is calculated on the basis of the GENTEX model is essential. Combined use of two different models allows referring this approach to integrative modeling

Methods for investigating the mechanical properties of isolated subendocardial and subepicardial cells ffom mouse heart

Supported by the Russia Foundation for Basic Research (14-01-00885, 14-01-31134, 13-04-00365) and JSPS KAKENHI2628212

Rotational Activity Around an Obstacle in 2d Cardiac Tissue in Presence of Cellular Heterogeneity

Waves of electrical excitation rotating around an obstacle is one of the important mechanisms of dangerous cardiac arrhythmias occurring in the heart damaged by a post-infarction scar. Such a scar is also surrounded by the region of heterogeneity called a gray zone. In this paper, we perform the first comprehensive numerical study of various regimes of wave rotation around an obstacle surrounded by a gray zone. We use the TP06 cellular ionic model for human cardiomyocytes and study how the period and the pattern of wave rotation depend on the radius of a circular obstacle and the width of a circular gray zone. Our main conclusions are the following. The wave rotation regimes can be subdivided into three main classes: (1) functional rotation, (2) scar rotation and the newly found (3) gray zone rotation regimes. In the scar rotation regime, the wave rotates around the obstacle, while in the gray zone regime, the wave rotates around the gray zone. As a result, the period of rotation is determined by the perimeter of the scar, or gray zone perimeter correspondingly. The transition from the scar to the gray rotation regimes can be determined from the minimal period principle, formulated in this paper. We have also observed additional regimes associated with two types of dynamical instabilities which may affect or not affect the period of rota-tion. The results of this study can help to identify the factors determining the period of arrhythmias in post-infarction patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.A.V.P., P.K., D.M., A.D. and O.S. were funded by the Russian Foundation for Basic Research (№ 18-29-13008). The work of P.K., D.M., A.D. and O.S. was carried out within the framework of the IIF UrB RAS theme No AAAA-A21-121012090093-0

Period of Arrhythmia Anchored Around an Infarction Scar in an Anatomical Model of the Human Ventricles

Rotating nonlinear waves of excitation in the heart cause dangerous cardiac arrhythmias. Frequently, ventricular arrhythmias occur as a result of myocardial infarction and are associated with rotation of the waves around a post-infarction scar. In this paper, we perform a detailed in silico analysis of scroll waves in an anatomical model of the human ventricles with a generic model of the infarction scar surrounded by the gray zone with modified properties of the myocardial tissue. Our model includes a realistic description of the heart shape, anisotropy of cardiac tissue and a detailed description of the electrical activity in human ventricular cells by a TP06 ionic model. We vary the size of the scar and gray zone and analyze the dependence of the rotation period on the injury dimensions. Two main regimes of wave scrolling are observed: the scar rotation, when the wave rotates around the scar, and the gray zone rotation, when the wave rotates around the boundary of the gray zone and normal tissue. The transition from the gray zone to the scar rotation occurs for the width of gray zone above 10–20 mm, depending on the perimeter of the scar. We compare our results with simulations in 2D and show that 3D anisotropy reduces the period of rotation. We finally use a model with a realistic shape of the scar and show that our approach predicts correctly the period of the arrhythmia. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.A.V.P., P.K., D.M., A.D., and O.S. was funded by the Russian Foundation for Basic Research (№ 18-29-13008). P.K., D.M., A.D., and O.S. work was carried out within the framework of the IIF UrB RAS theme No AAAA-A21-121012090093-0

Impact of inter-ventricular lead distance on cardiac resynchronization therapy outcomes

Cardiac resynchronization therapy (CRT) has been shown as an essential treatment of patients with heart failure, leading to improvements in symptoms, left ventricular (LV) function, and survival. However, up to 30% of appropriately selected patients remain non-responders to CRT. The aim of our study was to test a hypothesis on the impact of lead positioning in the ventricular walls on CRT response in patients with advanced chronic heart failure with and without pre-operative inter and intra-ventricular myocardial dyssynchrony. We examined 53 guideline-selected CRT candidates. Response to CRT was defined in 6 months after implantation of CRT devices. All patients underwent standard and Doppler echocardiography for assessment of LV function and mechanical dyssynchrony. Individual right ventricular (RV) and LV lead tip position, inter-lead distance, and the horizontal and vertical components were measured on the radiograph images with using an automated custom made software Our results showed that the RLV inter-lead distance is an essential parameter correlated with the CRT outcomes. A logistic model comprising the RLV inter-lead distance with parameters of dyssynchrony demonstrated a high predictive power for odds of CRT success. © 2017 IEEE Computer Society. All rights reserved.Research was supported by Act 211 Government of the Russian Federation, agreement № 02.A03.21.0006 and Program of the RAS Presidium #I.33П

Influence of sanatorium treatment with thermotherapy on the adaptive capacity of hard-working people

370 apparently healthy men aged 27 to 35 with considerable mental and physical burden were examined at the sanatorium. They were divided into two groups depending on the duration of rehabilitation. Group 1 consisted of 226 men with rehabilitation period from 18 to 21 days. Group 2 comprised 144 men with rehabilitation period from 10 to 14 days. Each group was subdivided into three subgroups: A, B and C. Patients of Group 1 subgroup A visited cryochamber, patients of Group 1 subgroup B visited infrared sauna, and patients of Group 1 subgroup C visited vibration sauna every second day. Patients of Group 2 subgroups A, B and C had the same procedures every day. Dynamic indicators of nonspecific adaptive response, hemodynamics, vascular adrenergic reactivity of skin, blood coagulation system, lipid and carbohydrate metabolism of all patients were studied. The results allowed us to conclude that all therapeutic complexes could be used in the restoration of adaptive capacity of hard-working people. Cryotherapy performed every second day was the most effective

Metabolic Correction of Primary Hemostasis in the Acute Phase of Traumatic Brain Injury

The aim of the study was to investigate the effect of ethylmethylhydroxypyridine on the ultrastructural alterations in endothelial cells of liver sinusoidal capillaries (SC) and primary hemostasis in the acute phase of traumatic brain injury (TBI).Materials and methods. Ultrastructural endothelial cell changes were studied in 36 female outbred rats in the acute phase of TBI using electron microscopy, and the platelet count was determined using a blood analyzer. The experimental group (n=18) animals received intraperitoneal injections of ethylmethylhydroxypyridine at the dose of 8.0 mg/kg per day for 12 days, and the control group (n=18) rats were administered with normal saline solution at the same dose.Results. Administration of ethylmethylhydroxypyridine in the early post TBI period reduced microvilli damage in endothelial, hepatic and stellate cells in the Disse space, whereas in the control group a significant decrease of these cells counts was detected. In contrast to the control group, the experimental group animals did not demonstrate thrombocytopenia on the days 1, 3, and 7 after injury. There was a significant increase in the platelet count compared with the baseline values, which was highest on day 12 after injury.Conclusion. Intraperitoneal administration of ethylmethylhydroxypyridine in rats in early post TBI period inhibited the TBI-associated damaging effect of secondary factors on liver sinusoid endothelial cells and platelet consumption

Метаболическая коррекция сосудисто-тромбоцитарного звена системы гемостаза в остром периоде черепно-мозговой травмы у крыс

The aim of the study was to investigate the effect of ethylmethylhydroxypyridine on the ultrastructural alterations in endothelial cells of liver sinusoidal capillaries (SC) and primary hemostasis in the acute phase of traumatic brain injury (TBI).Materials and methods. Ultrastructural endothelial cell changes were studied in 36 female outbred rats in the acute phase of TBI using electron microscopy, and the platelet count was determined using a blood analyzer. The experimental group (n=18) animals received intraperitoneal injections of ethylmethylhydroxypyridine at the dose of 8.0 mg/kg per day for 12 days, and the control group (n=18) rats were administered with normal saline solution at the same dose.Results. Administration of ethylmethylhydroxypyridine in the early post TBI period reduced microvilli damage in endothelial, hepatic and stellate cells in the Disse space, whereas in the control group a significant decrease of these cells counts was detected. In contrast to the control group, the experimental group animals did not demonstrate thrombocytopenia on the days 1, 3, and 7 after injury. There was a significant increase in the platelet count compared with the baseline values, which was highest on day 12 after injury.Conclusion. Intraperitoneal administration of ethylmethylhydroxypyridine in rats in early post TBI period inhibited the TBI-associated damaging effect of secondary factors on liver sinusoid endothelial cells and platelet consumption.Цель исследования — изучить влияние этилметилгидроксипиридина на ультраструктурные изменения эндотелиоцитов синусоидных капилляров (СК) печени и сосудисто-тромбоцитарное звено системы гемостаза в остром периоде черепно-мозговой травмы (ЧМТ).Материалы и методы. В посттравматическом периоде (ПТП) ЧМТ на 36 аутбредных крысах-самках исследовали динамику изменения ультраструктуры эндотелиоцитов СК печени методом электронной микроскопии и определяли количество тромбоцитов на гемоанализаторе. В течение 12 сут. в опытной группе (n=18) животным внутрибрюшинно вводили этилметилгидроксипиридин в дозе 8,0 мг/кг массы тела в сутки, а в контрольной группе (n=18) — физиологический раствор натрия хлорида в том же объеме.Результаты. Введение этилметилгидроксипиридина в ПТП уменьшало повреждение микроворсинок эндотелиоцитов, гепатоцитов и звездчатых ретикулоэндотелиоцитов в пространстве Диссе, тогда как в контрольной группе в этот период обнаруживали их выраженную редукцию. В отличие от контрольной группы, у животных опытной группы не выявили тромбоцитопению в 1-, 3- и 7-е сутки после травмы, отметили статистически значимое увеличение числа тромбоцитов, относительно исходных данных, достигшее наибольшей величины к 12-м суткам после травмы.Заключение. Внутрибрюшинное введение этилметилгидроксипиридина крысам в раннем ПТП сдерживало повреждающее действие формирующихся после ЧМТ вторичных факторов на эндотелиоциты синусоидов печени и потребление тромбоцитов

Anatomical Model of Rat Ventricles to Study Cardiac Arrhythmias under Infarction Injury

Species-specific computer models of the heart are a novel powerful tool in studies of life-threatening cardiac arrhythmias. Here, we develop such a model aimed at studying infarction injury in a rat heart, the most common experimental system to investigate the effects of myocardial damage. We updated the Gattoni2016 cellular ionic model by fitting its parameters to experimental data using a population modeling approach. Using four selected cellular models, we studied 2D spiral wave dynamics and found that they include meandering and break-up. Then, using an anatomically realistic ventricular geometry and fiber orientation in the rat heart, we built a model with a postinfarction scar to study the electrophysiological effects of myocardial damage. A post-infarction scar was simulated as an inexcitable obstacle surrounded by a border zone with modified cardiomyocyte properties. For cellular models, we studied the rotation of scroll waves and found that, depending on the model, we can observe different types of dynamics: anchoring, self-termination or stable rotation of the scroll wave. The observed arrhythmia characteristics coincide with those measured in the experiment. The developed model can be used to study arrhythmia in rat hearts with myocardial damage from ischemia reperfusion and to examine the possible arrhythmogenic effects of various experimental interventions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.This study has been supported by a grant from the Ministry of Science and Higher Education of the Russian Federation (agreement № 075-15-2020-800)