Mitochondrial calcium uniporter structure and function in different types of muscle tissues in health and disease
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01.10.2019 |
Tarasova N.
Vishnyakova P.
Logashina Y.
Elchaninov A.
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International Journal of Molecular Sciences |
10.3390/ijms20194823 |
1 |
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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Calcium ions (Ca2+) influx to mitochondrial matrix is crucial for the life of a cell. Mitochondrial calcium uniporter (mtCU) is a protein complex which consists of the pore-forming subunit (MCU) and several regulatory subunits. MtCU is the main contributor to inward Ca2+ currents through the inner mitochondrial membrane. Extensive investigations of mtCU involvement into normal and pathological molecular pathways started from the moment of discovery of its molecular components. A crucial role of mtCU in the control of these pathways is now recognized in both health and disease. In particular, impairments of mtCU function have been demonstrated for cardiovascular and skeletal muscle-associated pathologies. This review summarizes the current state of knowledge on mtCU structure, regulation, and function in different types of muscle tissues in health and disease.
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Heart phantom with electrical properties of heart muscle tissue
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01.09.2018 |
Korn L.
Lyra S.
Rüschen D.
Pugovkin A.
Telyshev D.
Leonhardt S.
Walter M.
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Current Directions in Biomedical Engineering |
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© 2018 Leonie Korn et al. The weakened heart is supported by a left ventricular assist device (LVAD) to supply the heart muscle with oxygenated blood. In case the heart muscle recovers during LVAD therapy, the patient has to be weaned from the device. To date, there is no adequate method to detect heart muscle recovery in LVAD therapy. In order to establish a novel method based on the measurement of electric conductivity, this study presents a silicone model of a ventricle mock-up to simulate the electrical properties of cardiac muscle tissue. Previously, it has been shown that the electrical properties of myocardial tissue change during ischemia, so that these changes are a possible estimate for measuring the condition of myocardial tissue. To this purpose, this study presents a casting process for a ventricle model and describes the materials used to imitate the electrical properties of the heart muscle to obtain conductive material. Initial results showed that the higher the carbon concentration in the silicone, the higher the conductivity of the silicone samples. The measurements were performed at different frequencies and the samples were analyzed for homogenization.
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Risk stratification of sudden death and selection criteria for the implantation of defibrillators in patients with cardiomyopathies (dilated, arrhythmogenic right ventricular, noncompact myocardium)
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01.01.2018 |
Blagova O.
Lutokhina Y.
Varionchik N.
Solovyeva E.
Bukaeva A.
Shestak G.
Polyak
Nedostup A.
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Clinical and Experimental Surgery |
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0 |
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© 2018 GEOTAR Media. All rights reserved. Aim: to value the significance of various predictors of sudden cardiac death (SCD) and clarify the selection criteria for implantation of cardioverter-defibrillators in patients with cardiomyopathies [dilated (DCM), arrhythmogenic right ventricular (ARVC), left ventricular noncompaction (LVNC)]. Material and methods. 220 patients with DCM syndrome were observed, 151 men, average age 47.5±12.5 years [mean left ventricular end-diastolic dimension (LV EDD) 6.5 [6.0, 7.1] cm, LV EF 30.3±10.1%], 50 patients with ARVC (definite diagnosis in 26 patients, probable in 13, possible in 11), 20 men, average age 38.1±14.6 years and 108 patients with a definite diagnosis of LVNC, 63 men, average age 45.4±14.8 years [mean LV ejection fraction (LF EV) 38.4±14.4%, LV EDD 5.9±0.8 cm]. The average follow-up periods were 16 [6, 37], 13.5 [4, 34] and 14 [3, 5, 36.0] months accordingly. The decision to implant the ICD / CRT-D was taken individually. The endpoints of the study were overall mortality, SCD, death + transplantation, appropriate defibrillators shocks and the "shocks + SCD". Results. The overall mortality in DCM, ARVC, and LVNC was 19.1%, 14.0% and 14.8%. It was mainly determined by terminal heart failure; SCD was recorded in 2.7%, 4.0% and 2.8%. Cardioverter-defibrillators were implanted in 66 (30%) patients with DCM (37 ICD, 29 CRT-D, 93.9% as the primary prevention of SCD), in 13 (26%) patients with ARVC (only ICD, primary prevention in 32,1%) and in 33 (30,6%) patients with LVNC (24 ICD, 9 CRTD, primary prevention in 88,1%). The frequency of appropriate shocks was 18.2% (15.0% in the primary prevention group and 50.0% in the secondary group) in patients with DCM syndrome, 69.2% (33.3% and 80.0% %) in ARVC, and 27.2% in LVNC (22.2% and 50.0%). The primary (genetic) nature of DCM (RR 1.58, OR 10.93), stable VT (RR 18, OR 26.5), and unstable VT (RR 1.43), a low QRS voltage (RR 1.75, OR 1.98), absence of LV hypertrophy signs on the ECG (RR 1.37, OR 2.56) were identified as criteria for selection for the implantation of a defibrillators in patients with DCM syndrome. In the patients with ARVC, these were a stable VT/VF and syncope (RR 4.75, OR 19), male sex (RR 1.25, OR 2), the low QRS voltage (RR 2.2, OR 10.5), chronic heart failure (OR 2.4, OR 8.0), the size of RV 2.85 cm (RR 1.55, OR 3.5), LV EDD> 5.5 cm (RR 2.1, OR 16, 7). In patients with LVNC the criteria were a stable VT/ VF, the presence of myocarditis (RR 3.3, OR 6.3), more than 500 PVBs per day (RR 3.3, OR 4.9), the low QRS voltage (RR 1,1, ОR 1,1), the follow up more than one year (RR 1,5, ОR 1,8). EF is not a statistically significant predictor of appropriate defibrillators shocks. Conclusions. In patients with various cardiomyopathies, which are accompanied by a high risk of SCD, the implantation of a cardioverter-defibrillators is an effective method of preventing SCD, including primary prevention. Due to adequate use of cardioverter-defibrillators in patients with DCM, ARVC and LVNC implanted in view of conventional and additional indications established in the study, mortality is determined primarily not by SCD, but terminal heart failure. Isolated myocarditis as the cause of DCM syndrome is not accompanied by a high risk of SCD, but its adherence to genetic cardiomyopathy determines the high risk of SCD.
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Risk factors for diastolic left ventricular myocardial dysfunction in patients with chronic kidney disease
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01.01.2018 |
Rudenko T.
Kamyshova E.
Vasilyeva M.
Bobkova I.
Solomakhina N.
Shvetsov M.
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Terapevticheskii Arkhiv |
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0 |
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© 2018 Media Sphera Publishing Group.All Rights Reserved. Purpose of the study. To examine the frequency and risk factors for the development of diastolic dysfunction (DD) of the left ventricle (LV) of the heart in patients with chronic kidney disease (CKD). Materials and methods. The study included 225 patients with stage I-CKD of non-diabetic etiology (median age 47.0 years, 50.2% of women). Depending on the degree of decrease in the glomerular filtration rate (GFR), all patients were divided into 3 groups. Group 1 (n=70) consisted of patients with GFR 89-45 ml / min / 1.73 m2, group 2 (n=120) - patients with GFR 44-15 ml / min / 1.73 m2, group 3 (n=35) - patients with GFR <15 mL / min / 1.73 m2. The control group includes persons without CKD. All patients underwent general clinical examination and transthoracic echocardiography; in 86 patients the level of cystatin C in the blood serum was determined. Results. Hypertrophy of the left ventricle (LVH) of the heart was detected in 87 (38.7%) of 225 patients with CKD. Hypertrophic type (type I) of myocardial DD is diagnosed in 90 (41.4%) of 225 patients with CKD. The incidence of myocardial left ventricular dysfunction of the 1st type increased with a decrease in GFR, amounting to 30, 40 and 60% in groups 1, 2 and 3, respectively. The systolic function of the left ventricular myocardium was preserved. Patients with DD were older, they had a higher body mass index (BMI), a more pronounced decrease in GFR, a higher level of fibrinogen. They were more likely to have LVH. The level of cystatin C as the kidney function worsened, but when comparing the mean levels of cystatin C in patients with the presence / absence of DD in the groups isolated depending on the stage of CKD, no statistically significant differences were found. According to the multivariate analysis, the independent predictor of DD was the age (odds ratio 1.106, 95% confidence interval 1.051-1.157, p=0.00001). The conclusion. DD of the myocardium of the LV is detected on average in 40% of patients with CKD, the frequency of its development increases with the progression of renal dysfunction. The development of DD is influenced by traditional factors of cardiovascular risk (age, BMI), as well as the decline in GFR and closely related structural remodeling of LV myocardium.
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N-terminal propeptide of collagen type III as a proposed marker of myocardial fibrosis in type 2 diabetes
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01.01.2018 |
Drapkina O.
Gegenava B.
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Cardiovascular Therapy and Prevention (Russian Federation) |
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© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. To evaluate the role of N-terminal procollagen type III propeptide (P3NP) as a proposed marker of myocardial fibrosis in type 2 diabetes (DM2) patients. Material and methods. In the study, 2 groups of patients participated: with DM2 and non-DM2 (both n=32). All patients underwent clinical and laboratory assessment, including P3NP, electrocardiography, echocardiography. Statistics was done with Mann-Whitney criteria and Spearman correlation. Results. The level P3NP is significantly higher in DM2 patients (р<0,00001). In DM2 patients, the level of P3NP significantly correlates with increased myocardial mass of the left ventricle (р=0,00026) and myocardial mass index of the left ventricle (р=0,03685). Conclusion. Echo- and electrocardiographic signs characteristic for myocardial fibrosis (mass increase, voltage decline) in DM2 patients are concomitant with the increase of P3NP. Significant correlation of P3NP and the size of myocardium makes it to propose P3NP as one of possible markers of myocardial fibrosis in DM2 persons.
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Clinical types (classification) of the right ventricle arrhythmogenic dysplasia: Specifics of diagnostics and management
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01.01.2018 |
Lutokhina Y.
Blagova V.
Nedostup V.
Shestak G.
Zaklyazminskaya V.
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Russian Journal of Cardiology |
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© 2018, Silicea-Poligraf. All rights reserved. Aim. To classify established clinical types of the right ventricle arrhythmogenic dysplasia (RVAD) taken a variety of genetic and inflammatory mechanisms, and to analyze the specifics of differential diagnostics and management of the respective types. Material and methods. Main group consisted of 50 patients with evident (n=26), probable (n=13) and possible (n=11) RVAD diagnosis, mean age 38,1±14,6 y. o., males — 20 (40%), follow up time 13,5 [4; 34] months. Comparison group consisted of 58 patients with some of the RVAD criteria insufficient for evident diagnosis. All patients underwent ECG, Holter ECG 24 hours, EchoCG; in the main group additionally — DNA-diagnostics (n=46), cardiac MRI (n=44), high definition ECG (n=16), endomyocardial biopsy of the RV (n=2), autopsy (n=2). In comparison group, MRI was done in 32 patients, biopsy to 7, and in 1 case — autopsy. Results. Based upon the clinical data and specifics of the disease course, 4 types of established clinical RVAD were selected, that do not tend to overlap: latent arrhythmic (50% patients), manifest arrhythmic (20%), RVAD with predominant biventricular chronic heart failure (CHF, 16%), and RVAD with non-compaction left ventricle myocardium (14%). The development of one or another type is based on genetic factors, as on comorbid myocarditis (in percent in the following, respectively). In diagnostics of the latent arrhythmic type (frequent right ventricle extrasystoly, VE and/or non-sustained right ventricular tachicardia, VT) the key role played female sex, syncopes in anamnesis (16%), family history of sudden death (12%), ECG-criteria and positive results of DNA diagnostics (24%). For manifest arrhythmic type (sustained VT) — sudden death family anamnesis (in 20%), MRI-criteria (enlarged RV with lower EF), ECG-criteria and positive DNA tests (50%). For RVAD with progressing CHF — sustained VT (50%), syncopes (37,5%), predominance of RV failure with its severely reduced EF (25,7±15,0%), major MRI-and ECG-criteria, decreased QRS-voltage and positive DNA test (38%). Comorbidity of RVAD and non-compaction myocardium differ by frequent VE, aggressive VT (57,1%), syncope (42,9%) and CHF with significantly lower than in DCMP EF LV. Mortality rate in I-IV types was, respectively, 0%, 10%, 25%, 14,3%, and relevant shocks in 8 of 13 (61,5%) patients with ICD. Conclusion. It is worthy to use the proposed RVAD classification in clinical practice to define the spectrum of diagnostical and management events and assess the individual patient prognosis.
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Myocarditis as a legitimate phenomenon in non-compaction myocardium: Diagnostics, management and influence on outcomes
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01.01.2018 |
Blagova O.
Pavlenko V.
Varionchik N.
Nedostup V.
Sedov V.
Kogan
Zaydenov V.
Kupriyanova G.
Donnikov
Kadochnikova V.
Gagarina N.
Mershina
Sinitsyn V.
Polyak
Zaklyazminskaya V.
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Russian Journal of Cardiology |
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2 |
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© 2018, Silicea-Poligraf. All rights reserved. Aim. To evaluate the prevalence of myocarditis in adult patients with non-compaction myocardium (NCM) of the left ventricle (LV), and its influence on the disease course, results of treatment and outcomes. Material and methods. To the study, 103 adult patients included, with NCM, 61 males, mean age 45,6±14,9 y. o. (from 18 to 78). Mean end diastolic LV size was 6,0±0,8 сm, EF LV 38,8±14,5%. Diagnosis of NCM had been done by echocardiography, multispiral computed tomography (n=81) and magnetic resonance tomography (n=39). DNA-diagnostics was performed by NGS method with further Senger sequencing. Pathogenic mutations were found in 9% of patients in the genes MYH7, MyBPC3, LAMP2, DES, DSP, TTN. The investigation also included anticardiac antibodies, genome of cardiotropic viruses by PCR, coronary arteriography (n=26), scintigraphy (n=25). Morphological assessment of the myocardium was done in 19 patients (12 endomyocardial biopsies), 1 intraoperation biopsy, 3 explanted hearts, incl. 2 after biopsy, and 5 autopsies. Mean follow-up 12 [2; 32] months. Results. Myocarditis was found in 53,4%, incl. virus-positive in 32,7% of those, with morphology done for 19 patients (active myocarditis in 10, borderline in 6; with minimal signs of activeness in 3). Viral genome in myocardium found in 8 patients (42,1%). The prevalence of myocarditis 44,4% in an arrhythmic variant of NCM, 12,5% in chronic ischemic, 57,5% in dilation cardiomyopathy, 50,0% in NCM patients with other cardiomyopathies. Special cases were acute/subacute myocarditis in NCM (10,7% of all), acute necrosis (infarction) in 4,9%. Comorbidity with myocarditis in NCM led to significantly more severe LV dysfunction (CHF FC 2 [1; 3] v 1,75 [0; 2], p<0,01, EF 33,8±13,5 v 44,7±13,6%, p<0,001), more prevalent non-sustained ventricular tachycardia (67,3% v 29,3%, p<0,01), proper shocks (38,9% v 0, p<0,05), deaths (16,4 and 4,2%, OR 5,75, 95% CI 1,21-27,43, p<0,05) and transplantation (7,3% v 2,1%, p>0,05). Only in myocarditis patients, as a result of basis (antiviral, immune suppression) and cardiotropic therapy there was significant increase of EF (in acute myocarditis from 25,4±7,9 to 38,6±9,5%, p<0,01), decrease of LV size and pulmonary systolic pressure. Conclusion. Myocarditis is typical phenomenon developing in patients with the primary, i. e. genetically verified NCM. The nature of myocarditis in NCM varies (primary infectious-autoimmune, secondary as a response on genetic/ischemic damage of cardiomyocytes), however regardless of this, it leads to significant worsening of structural and functional parameters, increase of the life-threatening arrhythmias rate, and outcomes (death + transplantation, proper shocks), demanding for active basic therapy.
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