Role of dihydropyridine calcium channel blockers in coronary bypass surgery using the radial artery graft

Aim. To assess the effect of a pharmacological protocol for the prevention of radial artery spasm, which is based on the systemic and local use of dihydropyridine calcium channel blockers, on the long-term outcomes of autoarterial coronary artery bypass grafting.Material and methods. According to the protocol, oral nifedipine at a dose of 5 mg/day is prescribed 3 days before surgery. Then, after the radial artery is isolated, the vessel is preserved in a solution of nifedipine (adalat) until it is used. After releasing the clamp from the aorta, a nifedipine (adalat) is infused intravenously at a dose of 0,63 mg/h. In the postoperative period, the infusion of nifedipine continues for 6 hours. In the future, patients are recommended to take dihydropyridine calcium channel blockers at a dose of 5 mg/day after discharge from the hospital.Results. The use of the pharmacological protocol (n=225) is associated with a lower number of major cardiovascular events (mortality, myocardial infarction, stroke) compared with the control group (n=230) (9,3% and 15,7%, p=0,031) during the 5-year follow-up. This result was achieved mainly by reducing the incidence of myocardial infarction (6,2% and 12,6%, p=0,018). Also, the use of the pharmacological protocol led to a decrease in repeated revascularizations (4,4% and 16,1%, p=0,0001) compared with the control group.Conclusion. The use of a pharmacological protocol for the prevention of radial artery spasm based on the systemic use of dihydropyridine calcium channel blockers improves the long-term outcomes of autoarterial coronary artery bypass grafting

From Normal to Obesity and Back: The Associations between Mitochondrial DNA Copy Number, Gender, and Body Mass Index.

Mitochondrial DNA (mtDNA) encodes core subunits of oxidative phosphorylation complexes and, as a result of intricate regulatory crosstalk between nuclear and mitochondrial genomes, the total number of mtDNA copies fits the requirements of each cell type. Deviations from the physiological number of mtDNA copies are expected to be deleterious and might cause some inherited diseases and normal ageing. We studied 46 obese patients with type 2 diabetes (T2DM) one year after a laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB). The results were compared with normal-weight patients without T2DM (control group 1) (body mass index (BMI) = 22.5 ± 3.01 kg/m <sup>2</sup> ) and patients with obesity without T2DM (control group 2) (BMI = 36 ± 3.45 kg/m <sup>2</sup> ). We detected an increase of mtDNA copy number in the cells of the buffy coat obtained from peripheral blood, sampled one year after bariatric surgery. We also found that average mtDNA copy number as well as its dynamics (before and after the surgery) are gender-specific. To the best of our knowledge, this is the first evidence for the restoration of mtDNA copy number in obese patients after LSG and RYGB

The role of Leu260Phe polymorphism of the receptor gene to GLP-1 incretin in the pathogenesis of diabetes type 2 diabetes with obesity

BACKGROUND: Glucagon-like peptide-1 (GLP-1) stimulates the proliferation of β-cells, enhances their resistance to apoptosis and increases glucose-dependent insulin secretion. AIMS: Study of the relationship of Leu260Phe polymorphism (rs1042044) of the GLP-1R gene with postprandial hormone production (C-peptide, insulin, ghrelin, GLP-1) in obese patients with type 2 diabetes. MATERIALS AND METHODS: A total of 174 patients, 82 patients with obesity with type 2 diabetes (BMI=40.4±14.3 kg/m2)and 92 conditionally healthy donors (BMI=22.6±2.7 kg/m2) were studied. The material for the study was venous blood taken on an empty stomach and 60 minutes after the test breakfast. Genotyping was performed by PCR using the sets for determining polymorphism (rs1042044) of the GLP-1R gene (Sintol) and the amplificator (CFX96 BioRad, USA). Plasma hormone levels were evaluated by flow fluorimetry (Bio-PlexProteinAssaySystem, Bio-Rad, USA) using commercial test systems (Bio-PlexProHumanDiabetes 10-Plex Assay, Bio-Rad, USA). Statistical analysis and graphs were obtained at R Statistical Software. RESULTS: A violation of postprandial production of GLP-1 and ghrelin after a test breakfast in obese patients with type 2 diabetes was found. A postprandial increase in C-peptide levels of 3.25[1.83;4.16] ng/ml and insulin 3048 [1978;4972] ng/ml in carriers of the CC genotype compared with carriers of the CA genotype in the group of patients with obesity with type 2 diabetes type In carriers of the CA genotype, there was a decrease in the C-peptide level of 2.21 [1.8;2.49] ng/ml and insulin 1462 [1146; 2304] ng/ml with a constant concentration of GLP-1. The postprandial level of ghrelin in carriers of the CA genotype of the Leu260Phe polymorphism increased to 118[96.1;157] ng/ml compared to carriers of the AA 98 genotype [86; 109] ng/ml. CONCLUSION: The presence of the CC genotype of the Leu260Phe polymorphism of the GLP-1 receptor gene is associated with an increase in postprandial plasma levels of C-peptide and insulin in obese patients with type 2 diabetes, and the CA genotype with a decrease in these indicators and an increase in ghrelin content

Adipokines in metabolic processes regulating during obesity treatment

Bariatric surgery serves as a model for the assessment of the relationship between body mass index (BMI) reduction and changes in adipokine production and for exploring the endocrine function of the pancreas in patients who do not have the proximal part of the small intestine. Aim.  of the study was to assess the biochemical parameters and plasma levels of adipokines [adiponectin, adipsin, leptin, plasminogen activator inhibitor (PAI-1), resistin and visfatin], insulin, C-peptide, ghrelin and incretins [glucose insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)] in patients with morbid obesity after surgery (gastric bypass) and therapeutic correction. Materials and methods. A total of 75 patients (34 men and 41 women; age range: 24?67 years) diagnosed as obese were divided into two groups according to the treatment they received. Biochemical analysis was performed to estimate carbohydrate and lipid metabolism rates and plasma levels of adipokines (adiponectin, adipsin, leptin, PAI-1, resistin, visfatin), insulin, C-peptide, ghrelin and incretins (GIP and GLP-1) using the flow fluorometry. Results. Surgical treatment of obesity resulted in a significant decrease in BMI (from 45.67?9.87 to 32.45?5.35 kg/m2,

CHEMERIN AS A POTENTIAL REGULATOR OF MITOCHONDRIAL QUALITY CONTROL IN OBESE PATIENTS

In obese patients, the relationship between the content of chemerin in blood plasma and the expression of genes TFAM, Drp1, MFN2, SOD, BAX, responsible for quality control of mitochondria, in insulin-dependent tissues (adipose tissue, liver) was revealed. The tissue-specific features of gene expression (TFAM, Drp1, MFN2, SOD, BAX), the number of mtDNA copies in the studied depots in obese patients were established. It has been proven that a change (decrease) in the number of mtDNA copies in insulin-dependent tissues can have a protective effect on mitochondria under conditions of increased oxidative stress. It was found that in patients without type 2 diabetes, an increase in chemerin production promotes the activation of the antioxidant system in the visceral adipose tissue but not in the liver. On the contrary, all obese patients with type 2 diabetes showed a decrease (compared with patients without type 2 diabetes) in the plasma level of chemerin. Thus, the low content of chemerin in the blood plasma in patients with type 2 diabetes mediates the formation of mitochondrial dysfunction in insulin-dependent tissues (adipose tissue, liver)

НЕКОТОРЫЕ АСПЕКТЫ АОРТОКОРОНАРНОГО ШУНТИРОВАНИЯ ПРИ ИНФАРКТЕ МИОКАРДА БЕЗ ПОДЪЕМА ST

HighlightsThe frequency of coronary artery bypass grafting in patients with non-ST-elevation myocardial infarction (NonSTEMI) in the Research Institute of Cardiology “Tomsk National Research Medical Center of the Russian Academy of Sciences” is equal to 10%, hospital mortality is 4.3%, which corresponds to the literature data. Patients with NonSTEMI who undergo coronary artery bypass grafting in cardiac surgery centers in Tomsk, Kemerovo and Chelyabinsk do not differ in main clinical and anamnestic characteristics. Patients with NonSTEMI who undergo CABG in cardiac surgery centers in Leipzig and Kiel (Germany), have a higher surgical risk compared with patients in Russian centers, while they are operated on much earlier than in Russian centers, and there are no statistically significant differences in hospital mortality between clinics. AbstractAim. To perform a comparative analysis of clinical and anamnestic characteristics and treatment outcomes in NonSTEMI patients who underwent CABG in 2020 at the Research Institute of Cardiology “Tomsk National Research Medical Center of the Russian Academy of Sciences” and in other domestic and foreign clinics.Methods. The retrospective study involved 23 NonSTEMI patients/ The patients clinical and anamnestic characteristics after CABG and the main outcome of treatment were analyzed. The obtained results were compared with the data of 4 other cardiac surgery clinics that were found in the literature.Results. The frequency of CABG in NonSTEMI patients is 10%, which corresponds to the literature data. The mean age of these patients was 64.8±8.4 years, LVEF – 55.5±9.2%, the risk according to the GRACE score – 4.9±5.6%, according to the EuroSCORE – 7.3±2.1%. There were no patients with cardiogenic shock or dialysis. The duration of hospitalization prior to surgery was 7.4±5.3 days. The hospital mortality was 4.3%. The clinical and anamnestic characteristics of NonSTEMI patients who underwent CABG surgery in the clinics of Tomsk, Kemerovo (n = 66), Chelyabinsk (n = 101), Leipzig (n = 758) and Kiel (n = 461) were compared. The characteristics of patients of the Russian clinics did not differ. It was found that in Russian clinics these patients were younger, and had less severe complications of the disease, and less severe comorbid diseases in comparison with patients of the German clinics. In particular, in the Russian clinics, CABG was not performed in patients with cardiogenic shock, unlike in the German clinics. At the same time, the German clinics conduct surgery on NonSTEMI patients much earlier than in the Russian clinics: only 10–20% of patients are operated on in the Russian clinics in the first 3 days of the disease, whereas in Leipzig – 42% of patients, and in Kiel almost all patients – on the first day of the disease; there were no statistically significant differences in hospital mortality between clinics.Conclusion. According to the results of the analysis, clinical and anamnestic characteristics of NonSTEMI patients who undergo CABG in Russian cardiac surgery centers (Tomsk, Kemerovo and Chelyabinsk) do not differ. Compared with the patients of the German cardiac surgery centers of Leipzig and Kiel, Russian patients have a lower surgical risk, they are operated on much later, there were no statistically significant differences in hospital mortality between clinics.Основные положенияЧастота выполнения аортокоронарного шунтирования при инфаркте миокарда без подъема сегмента ST в НИИ кардиологии Томского НИМЦ составляет 10%, госпитальная летальность – 4,3%, что соответствует данным литературы. По основным клинико-анамнестическим характеристикам больные инфарктом миокарда без подъема сегмента ST, получаемые аортокоронарное шунтирование в кардиохирургических центрах Томска, Кемерова и Челябинска, не различаются. Пациенты с инфарктом миокарда без подъема сегмента ST, которым АКШ проводят в кардиохирургических центрах Лейпцига и Киля (Германия), по сравнению с пациентами российских центров, имеют более высокий операционный риск, при этом их оперируют значительно раньше, чем в российских центрах, без статистически значимого различия в госпитальной летальности между клиниками. АбстрактЦель. Сравнительный анализ клинико-анамнестических характеристик и основных результатов лечения больных инфарктом миокарда без подъема сегмента ST (NonSTEMI), которым выполнили аортокоронарное шунтирование (АКШ) в 2020 г. в НИИ кардиологии Томского НИМЦ и других российских и зарубежных клиниках.Материалы и методы. Ретроспективно проанализированы клинико-анамнестические характеристики 23 больных NonSTEMI с выполненным АКШ. Проведено сравнение полученных результатов анализа с данными четырех других кардиохирургических клиник, представленными в литературе.Результаты. Частота выполнения АКШ при NonSTEMI в НИИ кардиологии Томского НИМЦ составляет 10%, что соответствует данным литературы. Средний возраст этих пациентов составил 64,8±8,4 года, фракция выброса левого желудочка – 55,5±9,2%, риск по шкале GRACE – 4,9±5,6%, по шкале EuroSCORE – 7,3±2,1%. Пациентов с кардиогенным шоком и на заместительной почечной терапии не было. Время от госпитализации до АКШ составило 7,4±5,3 дня. Госпитальная летальность зарегистрирована на уровне 4,3%. Проведено сравнение клинико-анамнестических характеристик больных NonSTEMI, которым выполнено АКШ в клиниках Томска (n = 23), Кемерова (n = 66), Челябинска (n = 101), Лейпцига (n = 758) и Киля (n = 461). Характеристики больных между российскими центрами не различаются. По сравнению с немецкими в российских клиниках больные более молодого возраста, с менее тяжелыми осложнениями и сопутствующей патологией. В частности, в российских кардиохирургических центрах, в отличие от немецких, не оперируют больных в состоянии кардиогенного шока. Кроме того, в немецких клиниках больных NonSTEMI оперируют значительно раньше: если в российских центрах в первые 3 дня заболевания вмешательству подвергаются только 10–20% пациентов, то в Лейпциге – 42%, при этом в Киле практически всех больных оперируют в первые сутки заболевания, без статистически значимого различия в госпитальной летальности между учреждениями.Заключение. По основным клинико-анамнестическим характеристикам больные NonSTEMI, подвергшиеся АКШ в российских кардиохирургических центрах (Томск, Кемерово и Челябинск), не различаются. По сравнению с пациентами немецких кардиохирургических центров (Лейпциг и Киль), российские пациенты имеют более низкий операционный риск, при этом им выполняют вмешательство значительно позже, без статистически значимого различия в госпитальной летальности между клиниками

HEPATIC SOD1 GENE EXPRESSION CHANGES IN THE NAFLD PATHOGENESIS IN OBESITY

Steatosis in the liver in obesity increases the work of mitochondria to utilize excess lipids. An overload of β-oxidation of fatty acids, the tricarboxylic acid cycle, and oxidative phosphorylation leads to a decrease in ATP and an increase in the formation of reactive oxygen species. Normally, mitochondria can efficiently remove elevated levels of reactive oxygen species using the cell's antioxidant system and metabolic adaptation to altered conditions. This study aimed to investigate the role of hepatic SOD expression in the pathogenesis of NAFLD in obesity. It was found that the level of SOD1 expression in the liver in obese patients with and without type 2 diabetes with a BMI > 40 kg/m2 was lower than in healthy donors. The copy number of mitochondrial DNA (mtDNA) in the liver in all obese patients was more than two times lower than in the control group. In the liver of obese patients without type 2 diabetes, the SOD1 protein level and the mtDNA copy number were interrelated and negatively correlated with the area of fatty inclusions. Thus, in obese patients, a decrease in antioxidant defense in the liver leads to the vulnerability of mitochondria, which, in turn, contributes to the progression of steatosis and insulin resistance