Dusica Djordjevic

Coordination Between Nitric Oxide and Superoxide Anion Radical During Progressive Exercise in Elite Soccer Players

Background: Exercise increases production of reactive oxygen and nitrogen species (RONS) via several mechanisms. Inter alia, increased blood flow during exercise exposes endothelial cells to shear stress, resulting in increased nitric oxide (NO) production. Increased oxygen consumption or hypoxia during exercise induces increased production of superoxide anion radical (O2-). Objective: This study investigates the effects of maximal progressive treadmill exercise test on time-course of peripheral blood NO and O2- production, as well as the effect of long-term training on NO bioavailability. Methods: Blood samples of 19 elite soccer players were gathered immediately before the test, during last 10 sec of every test stage, and during active recovery phases. Results: Significant increase (p<0.05) in NO production (estimated through nitrites (NO2-)), found between stage I (5.69 ± 1.32 nmol/ml) and basal values (5.36 ± 1.25 nmol/ml), was followed by the decrease in stage II (4.21 ± 0.42 nmol/ml) and production lower than basal to the end of the test. Significant increase (p<0.05) in O2- values was found between stage I (4.18 ± 0.77 nmol/ml) and resting values (4.01 ± 0.69 nmol/ml), and at stages V (4.24 ± 0.85 nmol/ml) and 1st phase of recovery (4.39 ± 0.92 nmol/ml). Conclusion: The regression lines of NO2- and O2- crossed at the level of anaerobic threshold, suggesting that anaerobic threshold could be of a crucial importance not only in the anaerobic and aerobic metabolism but in mechanisms of signal transductions as well. Long-term exercise increases NO bioavailability, and there is positive correlation between NO bioavailability and maximal oxygen uptake (VO2max).

Exercise-Induced Changes in Redox Status of Elite Karate Athletes

Regular training has been claimed to increase the activity of antioxidant enzymes and, consequently, augments the resistance to oxidative stress; however, large volumes of training performed by elite sportsmen could lead to a chronic oxidative stress state. The aim of our study was to assess the oxidative status of elite athletes at the beginning of the preparatory and the beginning of the competition training phases, so that the influence of three months of programmed physical activity on redox status could be determined. The chronic effects of exercise on the redox state of the athletes were compared to the effects of a single bout of karate training. Thirty elite karate athletes, 16-30 years old, were subjected to maximal graded exercise test to estimate their aerobic capacity; blood sampling was also performed to measure levels of superoxide anion radical (O₂⁻), hydrogen peroxide (H₂O₂), superoxide dismutase activity (SOD) and catalase activity (CAT). The only significant change after the three-month training process was found in the significantly decreased CAT activity (X ± SE: 7.95 ± 0.13 U/g Hb × 10³ in the preparatory period, 6.65 ± 0.28 U/g Hb × 10³ in the competition stage; P < 0.01). After a single karate training session, there was statistically significant decrease of O₂⁻(X ± SE: 32.7 ± 4.9 nmol/ml in the preparatory period, 24.5 ± 2.5 nmol/ml in the competition stage; P < 0.05) and increase of H₂O₂(X ± SE: 11.8 ± 1.0 nmol/ml in the preparatory period, 14.2 ± 0.9 nmol/ml in the competition stage; P < 0.01), as well as significant CAT increase (X ± SE: 6.6 ± 0.6 U/g Hb × 10³ in the preparatory period, 8.5 ± 0.5 U/g Hb × 10³ in the competition stage; P < 0.05). Although the three-month training process induced, at the first sight, negative changes in the redox state, expressed through the decrease in CAT activity, adequate response of the antioxidant system of our athletes to acute exercise was preserved.

Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension

AIM Тo examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension. METHODS Thirty healthy controls and 39 patients with clinically verified portal hypertension and increased vascular resistance participated in the study. Liver diameters, portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection. Cross-section area, portal flow and index of vascular resistance were calculated. In collected blood samples, superoxide anion radical (O(2) (-)), hydrogen peroxide (H(2)O(2)), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO(2) (-)) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. RESULTS Oxidative stress parameters changed significantly during the study. H(2)O(2) decreased at the end of study, probably via O(2) (-) mediated disassembling in Haber Weiss and Fenton reaction; O(2) (-) increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O(2) (-) and H(2)O(2) degradation products, like hydroxyl radical, initiated lipid peroxidation. Increased blood flow was to some extent lower in patients than in controls due to double paradoxes, flow velocity decreased, shear rate decreased significantly indicating non Newtonian characteristics of portal blood flow. CONCLUSION This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension.

Physical Activity for the Prevention of Cardiovascular Diseases

Abstract Over the last decade, the quantity and quality of scientific literature examining the relationship between physical activity (PA) and cardiovascular diseases (CVD) have significantly increased. Data from the literature now unequivocally show that physical inactivity is one of the major risk factors for CVD. It is believed that obesity, the prevalence of which has tripled over the last three decades, and physical inactivity among children are the main factors that will increase the prevalence of CVD in this century. The cardiovascular benefits of exercise are multifactorial and include important systemic effects on skeletal muscle, the peripheral vasculature, metabolism, and neurohumoral systems, as well as beneficial alterations within the myocardium itself. Thus, exercise does much more than change traditional risk factors, such as blood pressure, blood lipids, glucose tolerance and insulin resistance, metabolic syndrome, and overweight and obesity. Evidence from epidemiologic studies suggests that the preventive effects of PA may be achieved by 150 minutes of moderate PA a week, while increases in the intensity and volume of exercise lead to further health benefits. This dose–response gradient is curvilinear, with the largest gains from the first hour of weekly exercise. However, although much progress has been made in this field, existing studies performed on human subjects do not clearly show what type, intensity, and duration of exercise is most beneficial to cardiovascular fitness and metabolic optimization. Animal-based exercise studies may provide more information and help to elucidate the abilities of different training regimens to reduce the risk of CVD.

Oxidative Stress in Training, Overtraining and Detraining: from Experimental to Applied Research

Abstract According to the hormesis theory, the responses of biological systems to stressors in exercise training may be explained by a U-shaped curve with inactivity and overtraining as the two endpoints. Both of these endpoints decrease physiological functions. Markers of oxidative stress may be important parameters for biological monitoring of athletes. Numerous studies have shown that acute exercise has the potential to induce oxidative stress, but regular exposure to an increased level of prooxidants leads to upregulation of the endogenous antioxidative defence system (ADS) of an athlete. Studies that explored the redox state in athletes during the competitive season showed that the antioxidative status changes depending on the training load and training phase. During the training season, a state of fatigue known as overtraining may occur, which results from an excessive training load. Oxidative stress has been suggested as one of the causes of overtraining syndrome. Based on the existing studies, it can be said that a connection exists, but whether oxidative stress is a cause or a consequence of overtraining is yet to be clarified. Furthermore, detraining (training reduction or cessation) leads to a partial or complete loss of training-induced anatomical, physiological and performance adaptations; therefore, it seems reasonable to assume that changes in ADS are also reversible.

Anatomical Parameters of the Acetabulum in Heavy Vehicle Operators

Abstract It has been suggested that long-term exposure by heavy vehicle operators to whole-body vibration (WBV) may be related to an increased risk of pathological changes in the anatomical parameters of the hip. The aim of this study was to explore the difference in anatomical parameters of acetabulum in drivers of heavy vehicles (experimental group; n=60) and subjects who have not been exposed to WBV (control group; n=60). The anteroposterior radiographic view of the hips was used to measure the following parameters: the vertical centre edge (VCE), the ‘horizontal toit externe’ angle (HTE), the neck shaft angle (NSA) and the acetabular depth (AD). Compared with the control group, the mean VCE angle values and AD were signifi cantly lower, while the average HTE and NSA values were signifi cantly higher in the experimental group. This study supports the hypothesis that exposure to whole-body vibration during operation of a vehicle causes an increased risk of acetabular dysplasia.

[OP.7B.07] FIFTEEN-YEAR PROGNOSTIC SIGNIFICANCE OF ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: The aim of the study was to examine the predictive value of various electrocardiographic criteria for left ventricular hypertrophy (LVH) obtained at the beginning of the study in patients with essential arterial hypertension and echocardiographic LVH who were treated according to Guidelines, through a fifteen year follow-up period. Design and method: The study included 83 examined patients (53 male and 30 female; age 55.3 ± 8.1 years) with echocardiographic LVH. The LVH cutpoints were 134 g/m2 for male and 110 g/m2 for female patients. Electrocardiographic LVH was determined by Gubner–Ungerleider voltage, Lewis voltage, voltage of R wave in aVL lead, Lyon-Sokolow viltage, Cornell voltage and Cornell product, voltage RV6 and RV5 ratio, Romhilt-Estes score, Framingham criterion and Perugia criterion. Clinical and laboratory examinations, electrocardiography, echocardiography, exercise stress test, and 24-hours ambulatory blood pressure monitoring were carried out. Results: Average left ventricular mass index (LVMI) was 170.3 ± 31.6 g/m2, while the duration of hypertension was 12.1 ± 7.7 years. Adverse cardiovascular events occurred in 32 (38.5%) patients. At the beginning of the study, both groups, i.e. with and without adverse events, showed equal baseline characteristics, values of blood pressure and echocardiographic parameters. Positive Lyon-Sokolow score (17.6% vs. 47.3%; p < 0.05), Lewis voltage (9.8% vs. 21.9%; p < 0.05), Cornell voltage (15.7% vs. 37.5%; p < 0.05), and Cornell product (9.8% vs. 34.4%; p < 0.01) were more frequent in group with new cardiovascular events as compared to group without cardiovascular events. Multiple regression stepwise analyses separated Cornell product (standardized coefficient beta 0.303; p < 0.001) as compared to other criteria of hypertrophy after adjustments in terms of gender, age BMI and LVMI (model: R 0.303, R2 0.092, adjusted R square 0.081, standardized error of estimate 0.46951). Odd ratio for this criterion was 4.819 (95% CI 1.486–15.627). Conclusions: Patients with echocardiographic left ventricular hypertrophy who had positive Lewis voltage, Lyon-Sokolow voltage, Cornell voltage, and Cornell product showed worse fifteen-year outcome. The strongest predictor of cardiovascular events was positive result of Cornell product. Such patients should be recognized as early as possible, and treated more aggressively.

[PP.11.34] THE PREVALENCE OF METABOLIC SYNDROME IN PATIENTS WITH HYPERTENSION AND ITS IMPACT ON ASYMPTOMATIC CAROTID ATHEROSCLEROSIS

Objective: Increased cardiovascular risk in hypertensive patients might be partially attributable to metabolic disturbances. Carotid intima-media thickness (C-IMT) is a useful surrogate marker of early carotid atherosclerosis. Objective: To determine the prevalence of metabolic syndrome in patients with hypertension and its impact on asymptomatic carotid atherosclerosis. Design and method: The study included 391 subjects, divided into two groups. The first group consisted of patients with AH, n = 342 (age: 66,56 ± 09,52, female gender: 51%). Control group consisted of the examinees without AH, n = 49. For all patients there was determined: presence of risk factors for cardiovascular disease, SCORE risk, laboratory analyses, anthropometric measurements. MetS was diagnosed according to Adult Treatment Panel III criteria. The carotid artery intima-media thickness and carotid plaques were measured by B-mode ultrasound. Results: The prevalence of the MetS in the first group was 58% v.s.10% in the control group (p < 0,0001). The average number of components MetS was 2,76 ± 0.53 in first group (vs.1,30 ± 0.70 in control group, p < 0,0001). Hypertensive patients were divided into 2 groups according to the presence of MetS. Metabolic syndrome had 198 patients, there were no differences in age. Subjects with MetS had a higher average number of risk factors, SCORE risk, body mass index (p < 0,0001), serum acid level (p < 0,0001), more frequently had diabetes, hyperlipidemia and obesity (p < 0,0001). C-IMT were significantly higher in the group with MetS (0,91 ± 0,21 vs. 0,81 ± 0,17, p < 0,0001). The high C-IMC values (> = 0.90) were observed in 50,57% patients with MetS, p < 0,001. Patients with MetS had more frequently one or more carotid plaques (p = 0,04), higher average number of carotid plaques (p = 0,01) and percentage of stenosis (p = 0,01). In Mets group plaques were mostly fibrocalcified (30%), followed by fibrous (22%) and calcified, in non MetS group were mostly fibrous (36,6%). As the most important factors associated with carotid atherosclerosis multivariate regression analysis singled out age, number of components MetS (p = 0,002), serim acid level (p < 0,0001), hyperlipidemia (p = 0,035) and obesity (p = 0,03). Conclusions: Hypertensive patients in a significant percentage have metabolic syndrome. Our data suggest that MetS were independently associeted with subclinical carotid atherosclerosis in patients with hypertension.

[PP.01.19] PREDICTORS OF CARDIOVASCULAR EVENTS IN HYPERTENSIVE PATIENTS WITH HIGH CARDIOVASCULAR RISK

Objective: Hypertension is a major risk factor for cardiovascular events. Patients at high risk are particularly vulnerable and require adequate treatment and control. The treatment is complex and requires good control of blood pressure and all modifiable risk factors associated with the protection of target organ damage. The goal of this study is to determine which factors have predictive significance of cardiovascular events in patients with hypertension and high cardiovascular risk. Design and method: We studied 258 participants (60% females). Each participant underwent asymptomatic organ damage: 12-lead electrocardiogram examinations, two-dimensional and Doppler echocardiographs, Doppler sonography of the carotid arteries, and laboratory investigations were prospectively followed for fatal and non-fatal cardiovascular event and total mortality over a median of 7 years. Results: Mean age in the beginning of the study was 62.7 ± 9 years, body mass index of 28.9 ± 4. kg/m2, office blood pressure of 150.3 ± 20/87.6 ± 13 mmHg, left ventricular mass index (LVMI) of 129.8 ± 29 g/m2, carotid intima -media thickness (IMT) of 0.92 ± 0.2 mm. Diabetes mellitus (DM) was in 28% patients, mean total cholesterol 5.74 ± 1 mmol/l. At a follow-up, the incidence of non-fatal and fatal cardiovascular events was 18.2%, and total mortality was 4.7%. Major cardiovascular events were more common in men (p = 0.019) and were highly correlated with systolic blood pressure (SBP) at the beginning of the study (p = 0.038), with cholesterol at the beginning of the study(p = 0.019) and at the end of the study (p = 0.028), glucoses at the beginning of the study(p = 0.004), DM at the beginning (p = 0.001) and at the end (p = 0.006), LVMI (p < 0.001) and IMT (p < 0.001) at the beginning. Patients with a cardiovascular death were significantly older (p = 0.002), had higher SBP at the beginning (p = 0.017) and higher IMT (p = 0.017). During the study 7.4% of participants got cancer and its positive correlation with DM was determined at the end of the study (p = 0.002) and with IMT at the end of the study (p = 0.037). Conclusions: Main predictors of major cardiovascular events among patients with hypertension and high risk are: age, male sex, SBP, DM and IMT.

Correlations Between Clinical Parameters and Health-Related Quality of Life in Postmenopausal Osteoporotic Women

Abstract The purpose of this study was to assess the correlation between health-related quality of life (HRQoL) and clinically relevant osteodensitometric and biochemical parameters in postmenopausal osteoporotic women. Bone mineral density (BMD) and T scores of the lumbar vertebrae and femoral neck were assessed in 100 osteoporotic women (56 without previous fractures and 44 with previous fractures) using dual x-ray absorptiometry. The Fracture Risk Assessment Tool (FRAX) index for major osteoporotic and hip fractures was calculated based on demographic data and hip BMD. Venous blood samples were taken from each subject for biochemical analysis (serum calcium, phosphorus, alkaline phosphatase and vitamin D levels). HRQoL was assessed using the QUALEFFO-41 questionnaire (domains: Health perception, Pain, and Physical, Social and Mental function). Basic participant characteristics (age, menopause length, body mass index, smoking habits, hereditary tendency towards fracture, fracture history) correlated with some of the QUALEFFO-41 domains, but the correlation coefficients were low (r<0.3), except in the case of the correlation between Pain and fracture history (r=0.638). Of the six variables included in the multiple regression model, fracture history was shown to be the most significant predictor with respect to the following three QUALEFFO-41 domains: Pain (b=20.511), Social function (b=2.548) and Health perception (b=3.185). Correlation analysis showed that after adjustment for basic characteristics, BMD and T score of the femoral neck and Pain (r=0.331 and r=0.449, respectively), Social function (r=0.422 and r=0.419) and Health perception (r=0.434 for T score of the femoral neck) exhibited the strongest correlations. Vitamin D was negatively correlated with Mental function, while the other biochemical parameters exhibited variable correlations with the QUALEFFO- 41 domains (r≈0.2-0.5). Our study confirmed the previously established relationship between BMD of the femoral neck and HRQoL in patients with osteoporosis and demonstrated correlations between various blood bone metabolism parameters and HRQoL that have not been previously investigated.