Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population

Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). the purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF <= 40%, peak (V) over dot O-2 <= 20 ml.kg(-1).min(-1) were divided into two groups: untrained (UT, n = 13, 57 +/- 3 years) and exercise trained (ET, n = 13, 49 +/- 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. the gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. the gain and time delay of ABRMSNA were unchanged in the ET patients. in contrast, the gain of ABRMSNA was significantly reduced [3.5 +/- 0.7 vs. 1.8 +/- 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 +/- 0.8 vs. 7.9 +/- 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao ZerbiniCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Heart, Lung, and Blood InstituteUniv São Paulo, Sch Med, Heart Inst InCor, São Paulo, BrazilUniv São Paulo, Sch Phys Educ & Sport, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilUniv Calif Los Angeles, David Geffen Sch Med, Dept Med Cardiol & Physiol, Los Angeles, CA 90095 USAUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilFAPESP: 2010/50048-1FAPESP: 140643/2009-5FAPESP: 2013/07651-7CNPq: 142366/2009-9CNPq: 301867/2010-0CNPq: 308068/2011-4FAPESP: 2013/15651-7National Heart, Lung, and Blood Institute: RO1-HL084525Web of Scienc

The Impact of Obstructive Sleep Apnea on Metabolic and Inflammatory Markers in Consecutive Patients with Metabolic Syndrome

Background: Obstructive Sleep Apnea (OSA) is tightly linked to some components of Metabolic Syndrome (MetS). However, most of the evidence evaluated individual components of the MetS or patients with a diagnosis of OSA that were referred for sleep studies due to sleep complaints. Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS. Methodology/Principal Findings: We studied 152 consecutive patients (age 48 +/- 9 years, body mass index 32.3 +/- 3.4 Kg/m(2)) newly diagnosed with MetS (Adult Treatment Panel III). All participants underwent standard polysomnography irrespective of sleep complaints, and laboratory measurements (glucose, lipid profile, uric acid and C-reactive protein). The prevalence of OSA (apnea-hypopnea index >= 15 events per hour of sleep) was 60.5%. Patients with OSA exhibited significantly higher levels of blood pressure, glucose, triglycerides, cholesterol, LDL, cholesterol/HDL ratio, triglycerides/HDL ratio, uric acid and C-reactive protein than patients without OSA. OSA was independently associated with 2 MetS criteria: triglycerides: OR: 3.26 (1.47-7.21) and glucose: OR: 2.31 (1.12-4.80). OSA was also independently associated with increased cholesterol/HDL ratio: OR: 2.38 (1.08-5.24), uric acid: OR: 4.19 (1.70-10.35) and C-reactive protein: OR: 6.10 (2.64-14.11). Indices of sleep apnea severity, apnea-hypopnea index and minimum oxygen saturation, were independently associated with increased levels of triglycerides, glucose as well as cholesterol/HDL ratio, uric acid and C-reactive protein. Excessive daytime sleepiness had no effect on the metabolic and inflammatory parameters. Conclusions/Significance: Unrecognized OSA is common in consecutive patients with MetS. OSA may contribute to metabolic dysregulation and systemic inflammation in patients with MetS, regardless of symptoms of daytime sleepiness.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[200032/2009-7]Fundacao Zerbini, BrazilNational Sleep Foundation/American Lung Association Pickwick[SF-78568 N]National Institutes of Health (NIH)[HL07534]National Institutes of Health (NIH)[R01 HL80105]National Institutes of Health (NIH)[5P50HL084945]American Heart Association[0765293U](BSF) United States Israel Binational Science Foundation[2005265

Understanding Novel Superconductors with Ab Initio Calculations

This chapter gives an overview of the progress in the field of computational superconductivity. Following the MgB2 discovery (2001), there has been an impressive acceleration in the development of methods based on Density Functional Theory to compute the critical temperature and other physical properties of actual superconductors from first-principles. State-of-the-art ab-initio methods have reached predictive accuracy for conventional (phonon-mediated) superconductors, and substantial progress is being made also for unconventional superconductors. The aim of this chapter is to give an overview of the existing computational methods for superconductivity, and present selected examples of material discoveries that exemplify the main advancements.Comment: 38 pages, 10 figures, Contribution to Springer Handbook of Materials Modellin

Valsalva maneuver unveils central baroreflex dysfunction with altered blood pressure control in persons with a history of mild traumatic brain injury

BACKGROUND: Patients with a history of mild TBI (post-mTBI-patients) have an unexplained increase in long-term mortality which might be related to central autonomic dysregulation (CAD). We investigated whether standardized baroreflex-loading, induced by a Valsalva maneuver (VM), unveils CAD in otherwise healthy post-mTBI-patients. METHODS: In 29 healthy persons (31.3 ± 12.2 years; 9 women) and 25 post-mTBI-patients (35.0 ± 13.2 years, 7 women, 4–98 months post-injury), we monitored respiration (RESP), RR-intervals (RRI) and systolic blood pressure (BP) at rest and during three VMs. At rest, we calculated parameters of total autonomic modulation [RRI-coefficient-of-variation (CV), RRI-standard-deviation (RRI-SD), RRI-total-powers], of sympathetic [RRI-low-frequency-powers (LF), BP-LF-powers] and parasympathetic modulation [square-root-of-mean-squared-differences-of-successive-RRIs (RMSSD), RRI-high-frequency-powers (HF)], the index of sympatho-vagal balance (RRI LF/HF-ratios), and baroreflex sensitivity (BRS). We calculated Valsalva-ratios (VR) and times from lowest to highest RRIs after strain (VR-time) as indices of parasympathetic activation, intervals from highest systolic BP-values after strain-release to the time when systolic BP had fallen by 90 % of the differences between peak-phase-IV-BP and baseline-BP (90 %-BP-normalization-times), and velocities of BP-normalization (90 %-BP-normalization-velocities) as indices of sympathetic withdrawal. We compared patient- and control-parameters before and during VM (Mann-Whitney-U-tests or t-tests; significance: P < 0.05). RESULTS: At rest, RRI-CVs, RRI-SDs, RRI-total-powers, RRI-LF-powers, BP-LF-powers, RRI-RMSSDs, RRI-HF-powers, and BRS were lower in patients than controls. During VMs, 90 %-BP-normalization-times were longer, and 90 %-BP-normalization-velocities were lower in patients than controls (P < 0.05). CONCLUSIONS: Reduced autonomic modulation at rest and delayed BP-decrease after VM-induced baroreflex-loading indicate subtle CAD with altered baroreflex adjustment to challenge. More severe autonomic challenge might trigger more prominent cardiovascular dysregulation and thus contribute to increased mortality risk in post-mTBI-patients

Depression and cardiovascular autonomic control: a matter of vagus and sexparadox

Depression is a well-established stress-related risk factor for several diseases, mainly for those with cardiovas-cular outcomes. The mechanisms that link depression disorders with cardiovascular diseases (CVD) includedysfunctions of the autonomic nervous system. Heart rate variability analysis is a widely-used non-invasivemethod that can simultaneously quantify the activity of the two branches of cardiac autonomic neural controland provide insights about their pathophysiological alterations. Recent scientific literature suggests that sexinfluences the relationship between depressive symptoms and cardiac autonomic dysfunction. Moreover, a fewstudies highlight a possible sex paradox: depressed women, despite a greater vagal tone, experience a higher riskof adverse cardiovascular events than depressed men. Although there are striking sex differences in the incidenceof depression, scanty data on this topic are available. Lastly, studies on the heart-brain axis bidirectionality andthe role of sex are fundamental not only to clarify the biological bases of depression-CVD comorbidity, but also todevelop alternative therapies, where vagus nerve appears to be a promising target of non-invasive neuromo-dulation techniques

Depression and cardiovascular autonomic control: a matter of vagus and sex paradox

Depression is a well-established stress-related risk factor for several diseases, mainly for those with cardiovascular outcomes. The mechanisms that link depression disorders with cardiovascular diseases (CVD) include dysfunctions of the autonomic nervous system. Heart rate variability analysis is a widely-used non-invasive method that can simultaneously quantify the activity of the two branches of cardiac autonomic neural control and provide insights about their pathophysiological alterations. Recent scientific literature suggests that sex influences the relationship between depressive symptoms and cardiac autonomic dysfunction. Moreover, a few studies highlight a possible sex paradox: depressed women, despite a greater vagal tone, experience a higher risk of adverse cardiovascular events than depressed men. Although there are striking sex differences in the incidence of depression, scanty data on this topic are available. Lastly, studies on the heart-brain axis bidirectionality and the role of sex are fundamental not only to clarify the biological bases of depression-CVD comorbidity, but also to develop alternative therapies, where vagus nerve appears to be a promising target of non-invasive neuromodulation techniques

Cardiac autonomic responses to nociceptive stimuli in patients with chronic disorders of consciousness

Objectives: Patients with chronic disorders of consciousness (DOC) may show alterations of autonomic function; however, in this clinical population, no data are available on the specific effects of nociceptive stimuli on cardiac autonomic control. Thus, we aimed at investigating the effects of a noxious stimulation on heart rate variability (HRV) in a population of patients with chronic DOC, taking into account different states of consciousness (vegetative state/unresponsive wakefulness syndrome, VS/UWS and minimally conscious state, MCS). Methods: We enrolled twenty-four DOC patients (VS/UWS, n = 12 and MCS, n = 12). ECG and respiration were recorded during baseline, immediately after the nociceptive stimulus and, finally, during the recovery period. Linear and nonlinear HRV measures were used to evaluate the cardiac autonomic control. Results: In DOC patients, nonlinear HRV analysis showed that nociceptive stimuli are able to elicit a change of autonomic function characterized by an increased sympathetic and a reduced vagal modulation. A significant reduction of autonomic complexity has also been detected. More interestingly, VS/UWS patients showed a less complex dynamics compared to MCS patients. Conclusions: Cardiac autonomic responses are able to significantly differentiate the autonomic function between VS/UWS and MCS patients. Significance: Nonlinear HRV analysis may represent a useful tool to characterize the cardiac autonomic responses to nociceptive stimuli in a chronic DOC population

Complement and contact system activation in acute congestive heart failure patients

Recent experimental data indicate a pathogenic role of complement activation in congestive heart failure (CHF). The aim of this study was to evaluate contact and complement systems activation in patients hospitalized for an acute episode of CHF. Forty-two of 80 consecutive patients admitted at our hospital with confirmed diagnosis of acute CHF were enrolled. They underwent blood sampling within 24 h from admission (T0) and at clinical stability (T1). Patients were stratified for ejection fraction (EF) based on echocardiographic test. We measured plasma levels of C3, C4, sC5b-9 and cleaved high molecular weight kininogen (contact activation marker). At T1, C3 levels increased significantly compared to T0 (97 \ub1 2 versus 104 \ub1 3% of total pooled plasma, P < 0\ub701). Classifying patients according to EF, only patients with preserved EF presented a significant increase of C3 from T0 to T1 (99 \ub1 3 versus 108 \ub1 4%, P = 0\ub703). When the sample was stratified according to clinical outcome, C3 (98 \ub1 3 versus 104 \ub1 4%, P = 0\ub703) and sC5b-9 levels (204 \ub1 10 versus 230 \ub1 11 ng/ml, P = 0\ub703) were increased in patients who had positive outcome after hospitalization. CHF patients with preserved EF and positive outcome after hospitalization showed higher levels of sC5b-9 in the T1 period compared with T0 (211 \ub1 14 versus 243 \ub1 14 ng/ml, P = 0\ub704). Our results suggest that the complement system reacts differently if CHF occurs with preserved or reduced EF. This finding is interesting if we consider the difference in epidemiology, pathogenesis and possible therapeutic approaches of these two clinical entities