Cardiovascular Response to Intraneural Right Vagus Nerve Stimulation in Adult Minipig.

OBJECTIVE: This study explored intraneural stimulation of the right thoracic vagus nerve (VN) in sexually mature male minipigs to modulate safe heart rate and blood pressure response. MATERIAL AND METHODS: We employed an intraneural electrode designed for the VN of pigs to perform VN stimulation (VNS). This was delivered using different numbers of contacts on the electrode and different stimulation parameters (amplitude, frequency, and pulse width), identifying the most suitable stimulation configuration. All the parameter ranges had been selected from a computational cardiovascular system model. RESULTS: Clinically relevant responses were observed when stimulating with low current intensities and relatively low frequencies delivered with a single contact. Selecting a biphasic, charge-balanced square wave for VNS with a current amplitude of 500 µA, frequency of 10 Hz, and pulse width of 200 µs, we obtained heart rate reduction of 7.67 ± 5.19 beats per minute, systolic pressure reduction of 5.75 ± 2.59 mmHg, and diastolic pressure reduction of 3.39 ± 1.44 mmHg. CONCLUSION: Heart rate modulation was obtained without inducing any observable adverse effects, underlining the high selectivity of the intraneural approach.

Age and work duration do not predict burnout in firefighters.

BACKGROUND: The aim of this study was to ascertain the prevalence of burnout in Kazakhstan firefighters with regard to position and to identify predictors of faster burnout in order to plan future preventive strategies. METHODS: Data on demographics, lifestyle, fatigue (Fatigue Severity Scale (FSS)), SF-8 health-related quality of life (HRQL) and Maslach Burnout Inventory (MBI) emotional exhaustion (EX), cynicism (CY) and professional efficacy (PE) were obtained from 604 (94% men, median age 27 (interquartile range (IQR) 12) years) firefighters from all 18 fire departments of the city of Almaty. Associations between predictors and burnout EX, CY and PE dimensions were tested using multivariate logistic regression analyses. RESULTS: Burnout scores were low in this sample, including EX (0.6; IQR 1.55), CY (1.2; IQR 1.8) and PE (4.8; IQR 2.4). The highest median EX score (1.5 (IQR 2.0)) was in managers as opposed to the lowest in drivers (0.4 (IQR 1.4)), (p < 0.01). The greatest CY difference was between managers (2.1 (IQR 2.2)) and trainees (0.4 (IQR 1.1)) (p < 0.001). Age, work duration, education or fatigue were not associated with EX or CY in adjusted models. Better HRQL predicted lower EX and CY burnout, whereas alcohol never-use and language barrier predicted high CY. Male sex and no university degree predicted high PE burnout. CONCLUSIONS: Firefighting managers are at risk for higher burnout, irrespective of age and work duration, and the targeted intervention to combat burnout should include better uniform, mitigation of language barrier, general health improvement and less alcohol.

Prevalence and patient awareness of inflammatory bowel disease in Kazakhstan: a cross-sectional study.

BACKGROUND/AIMS: There has been a paucity of published data on the epidemiology of inflammatory bowel disease (IBD) in Central Asia and Kazakhstan. Therefore, we aimed to study IBD prevalence and patient awareness among adults in Kazakhstan. METHODS: The cross-sectional study was carried out among subjects of both sexes aged 18 years and older using IBD Alert Questionnaire (CalproQuest), single fecal calprotectin test, and endoscopy with biopsy to verify IBD from January to December 2017, across regions of Kazakhstan. All participants were included in the study after providing informed consent. RESULTS: Out of 115,556 subjects, there were 128 confirmed IBD cases, in which 36 Crohn's disease (CD) and 92 ulcerative colitis (UC) cases identified. The age and sex-adjusted IBD prevalence were 113.9 (95% confidence interval [CI], 69.0-158.9) per 100,000 population. The age- and sex-adjusted prevalence for UC were 84.4 (95% CI, 44.8-123.9) and for CD were 29.5 (95% CI, 8.2-50.9) per 100,000 population. CONCLUSIONS: This is the first report on the prevalence of IBD with a verified diagnosis in the Central Asia and could be used to better plan and allocate healthcare resources for IBD management program.

Occupational burnout and lifestyle in Kazakhstan cardiologists.

BACKGROUND: No data exist in the published literature on burnout in physicians from Central Asia. The aim of this analysis was to assess burnout prevalence in doctors and nurses of a cardiological hospital in Almaty, Kazakhstan and ascertain whether smoking, alcohol and physical activity may predict job-associated burnout. METHODS: The staff of the City Cardiological Centre of Almaty (N = 259, 82% females) filled in the questionnaire with the questions on demographics, lifestyle, including smoking, alcohol and physical activity, as well as fatigue (using Fatigue Severity Scale (FSS)) and burnout using Maslach Burnout Inventory (MBI) Human Services Survey for Medical Personnel. We compared the scores of emotional exhaustion (EE), depersonalization (DP) and personal accomplishment (PA) between doctors and nurses. RESULTS: We found significant differences in the smoking prevalence, alcohol use and regular physical activity, but no mean scores of burnout between men and women. High DP was prevalent in 52% doctors and 45% nurses, whereas high EE was found in 32 and 26% and PA in 16 and 32%, accordingly. In contrast with EE and DP, PA score was greater in nurses (median 38, interquartile range (IQR) 17) compared to doctors (median 41, IQR 9). Age, sex, work duration, smoking or physical activity could not predict higher burnout, whereas FSS score was associated with higher burnout of all dimensions (p < 0.05), and never-alcohol could predict higher PA burnout (p < 0.05). CONCLUSIONS: In Kazakhstan cardiologists, high prevalence of DP burnout should target specific preventive strategies and the association of alcohol use with PA needs further deeper insight.

Prevalence of supplement use in recreationally active Kazakhstan university students.

BACKGROUND: Little is known about the supplements use and recreational sport practices in Kazakhstan university students. Therefore, the aim of this study was to ascertain supplements use prevalence and their predictors in this population. METHODS: Cross-sectional survey of both undergraduate and graduate level students was completed in 2017 et al.-Farabi Kazakh National University, the largest higher institution in the country, from almost all Schools. A 45-item questionnaire was used to record physical activity, supplements use, lifestyle attributes (smoking, alcohol, sleep, etc.) and eating habits, and adjusted regression models were used to verify predictors of supplements use. RESULTS: Of the entire sample of 889 students (70% females), 526 (59%) were practicing recreational physical activity (RPA), and walking, jogging and track and field was the most popular activity type (38%). N = 151 (29%) students reported the use of any supplement (31% in men and 27% in women), whereas the most popular supplement type were vitamins. Supplement use was most prevalent in swimmers (55%). Age (odds ratio (OR) 1.19 (95% confidence interval (CI) 1.04-1.37), use of fitness tracker (OR 6.26 (95% CI 3.90-10.03)) and low-fat diet (OR 1.95 (95% CI 1.23-3.10)), but not income predicted supplements use in adjusted models. CONCLUSIONS: With more than half of students exercising regularly, only less than one-third use supplements with a very strong association with fitness tracker use.

Gene silencing of endothelial von Willebrand Factor attenuates angiotensin II-induced endothelin-1 expression in porcine aortic endothelial cells.

Expression of endothelin (ET)-1 is increased in endothelial cells exposed to angiotensin II (Ang II), leading to endothelial dysfunction and cardiovascular disorders. Since von Willebrand Factor (vWF) blockade improves endothelial function in coronary patients, we hypothesized that targeting endothelial vWF with short interference RNA (siRNA) prevents Ang II-induced ET-1 upregulation. Nearly 65 ± 2% silencing of vWF in porcine aortic endothelial cells (PAOECs) was achieved with vWF-specific siRNA without affecting cell viability and growth. While showing ET-1 similar to wild type cells at rest, vWF-silenced cells did not present ET-1 upregulation during exposure to Ang II (100 nM/24 h), preserving levels of endothelial nitric oxide synthase activity similar to wild type. vWF silencing prevented AngII-induced increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity and superoxide anion (O2-) levels, known triggers of ET-1 expression. Moreover, no increase in O2- or ET-1 levels was found in silenced cells treated with AngII or NOX-agonist phorbol ester (PMA 5 nM/48 h). Finally, vWF was required for overexpression of NOX4 and NOX2 in response to AngII and PMA. In conclusion, endothelial vWF knockdown prevented Ang II-induced ET-1 upregulation through attenuation of NOX-mediated O2- production. Our findings reveal a new role of vWF in preventing of Ang II-induced endothelial dysfunction.

Pantoprazole significantly interferes with antiplatelet effect of clopidogrel: results of a pilot randomized trial.

BACKGROUND: The CYP2C19*2 polymorphism is significantly associated with residual platelet reactivity (RPR) and maybe a major confounding factor in studies evaluating pharmacological interactions with clopidogrel. OBJECTIVES: We sought to evaluate the influence of a proton pump inhibitor (PPI), pantoprazole, indicated as relatively less influent than other PPIs, on the antiplatelet effect of clopidogrel, considering a stratification of the population for the presence of cytochrome 2C19*2 polymorphism. METHODS: 105 patients with ST elevation myocardial infarction (STEMI), treated with percutaneous coronary angioplasty (PCI) and who received dual antiplatelet therapy, were randomized between pantoprazole (n=54) or ranitidine (n=51). RPR was evaluated by Platelet Function Analyzer-100 (PFA-100) with collagen-epinephrine (CEPI) and collagene-ADP (CADP) cartridges and by light transmitted aggregometry with 10 µM adenosin diphosphate (ADP) and 1mM arachidonic acid (AA), on 5 (T0) and 30 (T1) days after PCI. RESULTS: Demographic, clinical and procedural data and the prevalence of CYP2C19*2 polymorphism were similar between the two groups. Not statistically differences were observed for CEPI-CT and for the maximal aggregation (MA) values with AA stimulus at both times. We observed a significant increase in MA values with ADP in PPI group at T0 (p=0.01) and T1 (p=0.03). At the multiple regression analysis PPI use remained significantly associated with ADP-MA both at T0 (p=0.05) and T1 (p=0.03). CONCLUSIONS: This is the first documentation in a randomized trial, after correction for the bias of CYP2C19*2 polymorphism, that pantoprazole increases the ADP-MA in patients treated with dual antiplatelet therapy.

Impact of acute changes of left ventricular contractility on the transvalvular impedance: validation study by pressure-volume loop analysis in healthy pigs.

BACKGROUND: The real-time and continuous assessment of left ventricular (LV) myocardial contractility through an implanted device is a clinically relevant goal. Transvalvular impedance (TVI) is an impedentiometric signal detected in the right cardiac chambers that changes during stroke volume fluctuations in patients. However, the relationship between TVI signals and LV contractility has not been proven. We investigated whether TVI signals predict changes of LV inotropic state during clinically relevant loading and inotropic conditions in swine normal heart. METHODS: The assessment of RVTVI signals was performed in anesthetized adult healthy anesthetized pigs (n = 6) instrumented for measurement of aortic and LV pressure, dP/dtmax and LV volumes. Myocardial contractility was assessed with the slope (Ees) of the LV end systolic pressure-volume relationship. Effective arterial elastance (Ea) and stroke work (SW) were determined from the LV pressure-volume loops. Pigs were studied at rest (baseline), after transient mechanical preload reduction and afterload increase, after 10-min of low dose dobutamine infusion (LDDS, 10 ug/kg/min, i.v), and esmolol administration (ESMO, bolus of 500 µg and continuous infusion of 100 µg·kg-1·min-1). RESULTS: We detected a significant relationship between ESTVI and dP/dtmax during LDDS and ESMO administration. In addition, the fluctuations of ESTVI were significantly related to changes of the Ees during afterload increase, LDDS and ESMO infusion. CONCLUSIONS: ESTVI signal detected in right cardiac chamber is significantly affected by acute changes in cardiac mechanical activity and is able to predict acute changes of LV inotropic state in normal heart.