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  1. Reproducibility of adenosine stress cardiovascular magnetic resonance in multi-vessel symptomatic coronary artery disease

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    Feneley Michael P

    2010-07-01

    Full Text Available Abstract Purpose First-pass perfusion cardiovascular magnetic resonance (CMR is increasingly being utilized in both clinical practice and research. However, the reproducibility of this technique remains incompletely evaluated, particularly in patients with severe coronary artery disease (CAD. The purpose of this study was to determine the inter-study reproducibility of adenosine stress CMR in patients with symptomatic multi-vessel CAD and those at low risk for CAD. Methods Twenty patients (10 with CAD, 10 low risk CAD underwent two CMR scans 8 ± 2 days apart. Basal, mid and apical left ventricular short axis slices were acquired using gadolinium 0.05 mmol/kg at peak stress (adenosine, 140 μ/kg/min, 4 min and rest. Myocardial perfusion was evaluated qualitatively by assessing the number of ischemic segments, and semi-quantitatively by determining the myocardial perfusion reserve index (MPRi using a normalized upslope method. Inter-study and observer reproducibility were assessed--the latter being defined by the coefficient of variation (CoV, which was calculated from the standard deviation of the differences of the measurements, divided by the mean. Additionally, the percentage of myocardial segments with perfect agreement and inter- and intra-observer MPRi correlation between studies, were also determined. Results The CoV for the number of ischemic segments was 31% with a mean difference of -0.15 ± 0.88 segments and 91% perfect agreement between studies. MPRi was lower in patients with CAD (1.13 ± 0.21 compared to those with low risk CAD (1.59 ± 0.58, p = 0.02. The reproducibility of MPRi was 19% with no significant difference between patients with CAD and those with low risk CAD (p = 0.850. Observer reproducibility for MPRi was high: inter-observer CoV 9%, r = 0.93 and intra-observer CoV 5%, r = 0.94. For trials using perfusion CMR as an endpoint, an estimated sample size of 12 subjects would be required to detect a two-segment change in

  2. Diagnostic Accuracy of Adenosine Stress Cardiovascular Magnetic Resonance Following Acute ST-segment Elevation Myocardial Infarction Post Primary Angioplasty

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    Wong Dennis TL

    2011-10-01

    Full Text Available Abstract Background Adenosine stress cardiovascular magnetic resonance (CMR has been proven an effective tool in detection of reversible ischemia. Limited evidence is available regarding its accuracy in the setting of acute coronary syndromes, particularly in evaluating the significance of non-culprit vessel ischaemia. Adenosine stress CMR and recent advances in semi-quantitative image analysis may prove effective in this area. We sought to determine the diagnostic accuracy of semi-quantitative versus visual assessment of adenosine stress CMR in detecting ischemia in non-culprit territory vessels early after primary percutaneous coronary intervention (PCI for ST-segment elevation myocardial infarction (STEMI. Methods Patients were prospectively enrolled in a CMR imaging protocol with rest and adenosine stress perfusion, viability and cardiac functional assessment 3 days after successful primary-PCI for STEMI. Three short axis slices each divided into 6 segments on first pass adenosine perfusion were visually and semi-quantitatively analysed. Diagnostic accuracy of both methods was compared with non-culprit territory vessels utilising quantitative coronary angiography (QCA with significant stenosis defined as ≥70%. Results Fifty patients (age 59 ± 12 years admitted with STEMI were evaluated. All subjects tolerated the adenosine stress CMR imaging protocol with no significant complications. The cohort consisted of 41% anterior and 59% non anterior infarctions. There were a total of 100 non-culprit territory vessels, identified on QCA. The diagnostic accuracy of semi-quantitative analysis was 96% with sensitivity of 99%, specificity of 67%, positive predictive value (PPV of 97% and negative predictive value (NPV of 86%. Visual analysis had a diagnostic accuracy of 93% with sensitivity of 96%, specificity of 50%, PPV of 97% and NPV of 43%. Conclusion Adenosine stress CMR allows accurate detection of non-culprit territory stenosis in patients

  3. Effects of adenosine and regadenoson on hemodynamics measured using cardiovascular magnetic resonance imaging

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    Thomas, Dustin M.; Minor, Matthew R.; Aden, James K.; Lisanti, Christopher J.; Steel, Kevin E.

    2017-01-01

    Background Adenosine or regadenoson vasodilator stress cardiovascular magnetic resonance (CMR) is an effective non-invasive strategy for evaluating symptomatic coronary artery disease. Vasodilator injection typically precedes ventricular functional sequences to efficiently reduce overall scanning times, though the effects of vasodilators on CMR-derived ventricular volumes and function are unknown. Methods We prospectively enrolled 25 healthy subjects to undergo consecutive adenosine and regad...

  4. Regulation of Cardiovascular Development by Adenosine and Adenosine-Mediated Embryo Protection

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    Rivkees, Scott A; Wendler, Christopher C.

    2012-01-01

    Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists include the methlyxanthines caffeine and theophylline. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). We examined how adenosine acts via A1ARs to influence embryo development.

  5. Erythrocyte adenosine transport. A rapid screening test for cardiovascular drugs.

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    Yeung, P K; Mosher, S J; Li, R; Farmer, P S; Klassen, G A; Pollak, P T; McMullen, M; Ferrier, G

    1993-11-01

    An erythrocyte (RBC) model based on whole blood was used to investigate the effect of cardiovascular drugs on the uptake of adenosine in vitro. Fresh whole blood obtained from healthy volunteers was allowed to equilibrate with various concentrations (5-1000 microM) of a tested agent. (2-3H)-Adenosine was used as a substrate, and the reaction was terminated after 2 sec of incubation at room temperature by rapid addition of a "Stopping Solution" which was a mixture of erythro-9-(2-hydroxy-3-nonyl)adenine, dipyridamole, and EDTA. The mixture was centrifuged (1760 g, 4 degrees C, 10 min), and the radioactivity of an aliquot of the supernatant was determined by a scintillation counter. The results showed that dipyridamole was the most potent agent tested (IC50 = 0.2 microM). Amongst the calcium antagonists studied, isradipine was most potent, followed by verapamil, clentiazem, diltiazem, and then nifedipine. The racemates of two metabolites of diltiazem, MX and MB, were more potent than the parent drug. The antiarrhythmic agents, amiodarone and sotalol, the two new lipid peroxidation inhibitors, U-74389F and U-78517F, and the anxiolytic agent, alprazolam, were as active as verapamil. The beta-receptor antagonist propranolol and the angiotensin converting enzyme (ACE) inhibitor, enalapril, were practically inactive. In addition, the model was stereoselective such that the S(-)-enantiomer of verapamil was considerably more potent than the R(+)-antipote, whereas d(+)-sotalol was practically inactive compared to racemic sotalol.

  6. Effects of adenosine and regadenoson on hemodynamics measured using cardiovascular magnetic resonance imaging.

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    Thomas, Dustin M; Minor, Matthew R; Aden, James K; Lisanti, Christopher J; Steel, Kevin E

    2017-12-04

    Adenosine or regadenoson vasodilator stress cardiovascular magnetic resonance (CMR) is an effective non-invasive strategy for evaluating symptomatic coronary artery disease. Vasodilator injection typically precedes ventricular functional sequences to efficiently reduce overall scanning times, though the effects of vasodilators on CMR-derived ventricular volumes and function are unknown. We prospectively enrolled 25 healthy subjects to undergo consecutive adenosine and regadenoson administration. Short axis CINE datasets were obtained on a 1.5 T scanner following adenosine (140mcg/kg/min IV for 6 min) and regadenoson (0.4 mg IV over 10 s) at baseline, immediately following administration, at 5 min intervals up to 15 min. Hemodynamic response, bi-ventricular volumes and ejection fractions were determined at each time point. Peak heart rate was observed early following administration of both adenosine and regadenoson. Heart rate returned to baseline by 10 min post-adenosine while remaining elevated at 15 min post-regadenoson (p = 0.0015). Left ventricular (LV) ejection fraction (LVEF) increased immediately following both vasodilators (p regadenoson remained increased at 10 min (p = 0.003) and 15 min (p = 0.0015) with a mean LVEF increase at 15 min of 4.2 ± 1.3%. Regadenoson resulted in a similar magnitude reduction in both LV end-diastolic volume index (LVEDVi) and LV end-systolic volume index (LVESVi) at 15 min whereas LVESVi resolved at 15 min following adenosine and LVEDVi remained below baseline values (p = 0.52). Regadenoson and adenosine have significant and prolonged impact on ventricular volumes and LVEF. In patients undergoing vasodilator stress CMR where ventricular volumes and LVEF are critical components to patient care, ventricular functional sequences should be performed prior to vasodilator use or consider the use of aminophylline in the setting of regadenoson. Additionally, heart rate resolution itself is not an

  7. Targeting adenosine receptors in the development of cardiovascular therapeutics.

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    Riksen, N.P.; Rongen, G.A.P.J.M.

    2012-01-01

    Adenosine receptor stimulation has negative inotropic and dromotropic actions, reduces cardiac ischemia-reperfusion injury and remodeling, and prevents cardiac arrhythmias. In the vasculature, adenosine modulates vascular tone, reduces infiltration of inflammatory cells and generation of foam cells,

  8. Low-dose adenosine stress echocardiography: Detection of myocardial viability

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    Nedeljkovic Milan

    2003-06-01

    Full Text Available Abstract Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

  9. Development of coronary vasospasm during adenosine-stress myocardial perfusion CT imaging

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    Nam, Jeong Gu; Choi, Seong Hoon; Kang, Byeong Seong; Bang, Min Aeo; Kwon, Woon Jeong [Dept. of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of)

    2015-06-15

    Adenosine is a short-acting coronary vasodilator, and it is widely used during pharmacological stress myocardial perfusion imaging. It has a well-established safety profile, and most of its side effects are known to be mild and transient. Until now, coronary vasospasm has been rarely reported as a side effect of adenosine during or after adenosine stress test. This study reports a case of coronary vasospasm which was documented on stress myocardial perfusion CT imaging during adenosine stress test.

  10. Stress and atherosclerotic cardiovascular disease.

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    Inoue, Nobutaka

    2014-01-01

    Recent major advances in medical science have introduced a wide variety of treatments against atherosclerosis-based cardiovascular diseases, which has led to a significant reduction in mortality associated with these diseases. However, atherosclerosis-based cardiovascular disease remains a leading cause of death. Furthermore, progress in medical science has demonstrated the pathogenesis of cardiovascular disease to be complicated, with a wide variety of underlying factors. Among these factors, stress is thought to be pivotal. Several types of stress are involved in the development of cardiovascular disease, including oxidative stress, mental stress, hemodynamic stress and social stress. Accumulating evidence indicates that traditional risk factors for atherosclerosis, including diabetes, hyperlipidemia, hypertension and smoking, induce oxidative stress in the vasculature. Oxidative stress is implicated in the pathogenesis of endothelial dysfunction, atherogenesis, hypertension and remodeling of blood vessels. Meanwhile, mental stress is a well-known major contributor to the development of cardiovascular disease. The cardiovascular system is constantly exposed to hemodynamic stress by the blood flow and/or pulsation, and hemodynamic stress exerts profound effects on the biology of vascular cells and cardiomyocytes. In addition, social stress, such as that due to a lack of social support, poverty or living alone, has a negative impact on the incidence of cardiovascular disease. Furthermore, there are interactions between mental, oxidative and hemodynamic stress. The production of reactive oxygen species is increased under high levels of mental stress in close association with oxidative stress. These stress responses and their interactions play central roles in the pathogenesis of atherosclerosis-based cardiovascular disease. Accordingly, the pathophysiological and clinical implications of stress are discussed in this article.

  11. Regadenoson and adenosine are equivalent vasodilators and are superior than dipyridamole- a study of first pass quantitative perfusion cardiovascular magnetic resonance.

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    Vasu, Sujethra; Bandettini, W Patricia; Hsu, Li-Yueh; Kellman, Peter; Leung, Steve; Mancini, Christine; Shanbhag, Sujata M; Wilson, Joel; Booker, Oscar Julian; Arai, Andrew E

    2013-09-24

    Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There are few comparative studies of the vasodilator properties of regadenoson, adenosine and dipyridamole in humans. The specific aim of this study was to determine the relative potency of these three vasodilators by quantifying stress and rest myocardial perfusion in humans using cardiovascular magnetic resonance (CMR). Fifteen healthy normal volunteers, with Framingham score less than 1% underwent vasodilator stress testing with regadenoson (400 μg bolus), dipyridamole (0.56 mg/kg) and adenosine (140 μg /kg/min) on separate days. Rest perfusion imaging was performed initially. Twenty minutes later, stress imaging was performed at peak vasodilation, i.e. 70 seconds after regadenoson, 4 minutes after dipyridamole infusion and between 3-4 minutes of the adenosine infusion. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution. Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 μl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 μl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs

  12. Caffeine intake inverts the effect of adenosine on myocardial perfusion during stress as measured by T1 mapping

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    Kuijpers, Dirkjan; Prakken, Niek H.; Vliegenthart, Rozemarijn; van Dijkman, Paul R. M.; Van der Harst, Pim; Oudkerk, Matthijs

    2016-01-01

    Caffeine intake before adenosine stress myocardial perfusion imaging may cause false negative findings. We hypothesized that the antagonistic effect of caffeine can be measured by T1 relaxation times in rest and adenosine stress cardiac magnetic resonance imaging (CMR), as T1 mapping techniques are sensitive to changes in myocardial blood volume. We prospectively analyzed 105 consecutive patients with adenosine stress perfusion CMR on a 1.5-T MRI system. Rest and stress T1 mapping was perform...

  13. Comparison of the Safety of Adenosine and Regadenoson in Patients Undergoing Outpatient Cardiac Stress Testing.

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    Brink, Heidi L; Dickerson, Jennifer A; Stephens, Julie A; Pickworth, Kerry K

    2015-12-01

    To compare the adverse effect profiles of adenosine and regadenoson in patients undergoing outpatient cardiac stress testing. Single-center retrospective cohort study. Two outpatient clinics, both of which are part of a single tertiary academic medical health system; one clinic exclusively used adenosine for cardiac stress testing, and the other clinic exclusively used regadenoson. A total of 489 patients who underwent an outpatient cardiac stress test between January 1, 2014, and December 31, 2014; of those patients, 254 received adenosine and 235 received regadenoson. Baseline characteristics were similar between groups, except for chronic kidney disease (pregadenoson groups. A significantly higher proportion of patients who were given regadenoson during cardiac stress testing experienced at least one adverse effect compared with patients who underwent an adenosine stress test (79.6% vs 31.5%, pregadenoson experienced a significantly higher occurrence of arrhythmia (30.6% vs 16.1%, pregadenoson based on the average wholesale price. Among patients undergoing an outpatient pharmacologic stress test, the use of adenosine was associated with a lower occurrence of adverse effects and lower rate of a rescue agent use and may provide a potential medication cost savings opportunity compared with regadenoson. © 2015 Pharmacotherapy Publications, Inc.

  14. Adenosine-diphosphate (ADP) receptor antagonists for the prevention of cardiovascular disease in type 2 diabetes mellitus (Review)

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    Valentine, N.; Laar, F.A. van de; Driel, M.L. van

    2012-01-01

    BACKGROUND: Cardiovascular disease (CVD) is the most prevalent complication of type 2 diabetes with an estimated 65% of people with type 2 diabetes dying from a cause related to atherosclerosis. Adenosine-diphosphate (ADP) receptor antagonists like clopidogrel, ticlopidine, prasugrel and ticagrelor

  15. Caffeine intake inverts the effect of adenosine on myocardial perfusion during stress as measured by T1 mapping

    NARCIS (Netherlands)

    Kuijpers, Dirkjan; Prakken, Niek H.; Vliegenthart, Rozemarijn; van Dijkman, Paul R. M.; van der Harst, Pim; Oudkerk, Matthijs

    2016-01-01

    Caffeine intake before adenosine stress myocardial perfusion imaging may cause false negative findings. We hypothesized that the antagonistic effect of caffeine can be measured by T1 relaxation times in rest and adenosine stress cardiac magnetic resonance imaging (CMR), as T1 mapping techniques are

  16. Splenic Switch-off: A Tool to Assess Stress Adequacy in Adenosine Perfusion Cardiac MR Imaging.

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    Manisty, Charlotte; Ripley, David P; Herrey, Anna S; Captur, Gabriella; Wong, Timothy C; Petersen, Steffen E; Plein, Sven; Peebles, Charles; Schelbert, Erik B; Greenwood, John P; Moon, James C

    2015-09-01

    To investigate the pharmacology and potential clinical utility of splenic switch-off to identify understress in adenosine perfusion cardiac magnetic resonance (MR) imaging. Splenic switch-off was assessed in perfusion cardiac MR examinations from 100 patients (mean age, 62 years [age range, 18-87 years]) by using three stress agents (adenosine, dobutamine, and regadenoson) in three different institutions, with appropriate ethical permissions. In addition, 100 negative adenosine images from the Clinical Evaluation of MR Imaging in Coronary Heart Disease (CE-MARC) trial (35 false and 65 true negative; mean age, 59 years [age range, 40-73 years]) were assessed to ascertain the clinical utility of the sign to detect likely pharmacologic understress. Differences in splenic perfusion were compared by using Wilcoxon signed rank or Wilcoxon rank sum tests, and true-negative and false-negative findings in CE-MARC groups were compared by using the Fisher exact test. The spleen was visible in 99% (198 of 200) of examinations and interobserver agreement in the visual grading of splenic switch-off was excellent (κ = 0.92). Visually, splenic switch-off occurred in 90% of adenosine studies, but never in dobutamine or regadenoson studies. Semiquantitative assessments supported these observations: peak signal intensity was 78% less with adenosine than at rest (P regadenoson (4% reduction; P = .08). Calculated peak splenic divided by myocardial signal intensity (peak splenic/myocardial signal intensity) differed between stress agents (adenosine median, 0.34; dobutamine median, 1.34; regadenoson median, 1.13; P adenosine is a new, simple observation that identifies understressed patients who are at risk for false-negative findings on perfusion MR images. These data suggest that almost 10% of all patients may be understressed, and that repeat examination of individuals with failed splenic switch-off may significantly improve test sensitivity.

  17. Oxidative stress in cardiovascular diseases

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    Shyamal K Goswami

    2015-01-01

    Full Text Available Oxidative stress caused by various oxygen containing free radicals and reactive species (collectively called "Reactive Oxygen Species" or ROS has long been attributed to cardiovascular diseases. In human body, major oxidizing species are super oxide, hydrogen peroxide, hydroxyl radical, peroxy nitrite etc. ROS are produced from distinct cellular sources, enzymatic and non-enzymatic; have specific physicochemical properties and often have specific cellular targets. Although early studies in nineteen sixties and seventies highlighted the deleterious effects of these species, later it was established that they also act as physiological modulators of cellular functions and diseases occur only when ROS production is deregulated. One of the major sources of cellular ROS is Nicotinamide adenine dinucleotide phosphate oxidases (Noxes that are expressed in almost all cell types. Superoxide and hydrogen peroxide generated from them under various conditions act as signal transducers. Due to their immense importance in cellular physiology, various Nox inhibitors are now being developed as therapeutics. Another free radical of importance in cardiovascular system is nitric oxide (a reactive nitrogen species generated from nitric oxide synthase(s. It plays a critical role in cardiac function and its dysregulated generation along with superoxide leads to the formation of peroxynitrite a highly deleterious agent. Despite overwhelming evidences of association between increased level of ROS and cardiovascular diseases, antioxidant therapies using vitamins and omega 3 fatty acids have largely been unsuccessful till date. Also, there are major discrepancies between studies with laboratory animals and human trials. It thus appears that the biology of ROS is far complex than anticipated before. A comprehensive understanding of the redox biology of diseases is thus needed for developing targeted therapeutics.

  18. Adenosine Stress Induced Left Bundle Branch Block During Technetium-99m Tetrofosmin Myocardial Perfusion Imaging.

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    Jayanthi, Mohan Roop; Sasikumar, Arun; Gorla, Arun Kumar Reddy; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2017-01-01

    The occurrence of left bundle branch block (LBBB) in electrocardiogram during exercise testing is a relatively rare finding. The incidence of LBBB during exercise testing ranges from 0.5% to 1.1%. The mechanism of exercise-induced LBBB (EI-LBBB) is poorly understood, but ischemia is a proposed etiology. Stress myocardial perfusion imaging (MPI) can be useful in patients with EI-LBBB to rule out coronary artery disease. Adenosine vasodilator stress is the preferred mode of stress in patients with LBBB for performing stress-MPI. Here we present an interesting case of adenosine-induced LBBB during stress-MPI in a 67-year-old female patient with normal coronary angiography.

  19. Genetic influences on cardiovascular stress reactivity

    NARCIS (Netherlands)

    Wu, Ting; Snieder, Harold; de Geus, Eco

    Individual differences in the cardiovascular response to stress play a central role in the reactivity hypothesis linking frequent exposure to psychosocial stress to adverse outcomes in cardiovascular health. To assess the importance of genetic factors, a meta-analysis was performed on all published

  20. Delayed heart rate recovery after adenosine stress testing with supplemental arm exercise predicts mortality.

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    Akutsu, Yasushi; Gregory, Shawn A; Kardan, Arash; Zervos, Gerasimos D; Thomas, Gregory S; Gewirtz, Henry; Yasuda, Tsunehiro

    2009-01-01

    Delayed heart rate (HR) recovery after treadmill exercise testing predicts mortality. Patients with suspected ischemic heart disease who cannot perform adequate treadmill exercise are typically evaluated with pharmacological stress myocardial perfusion imaging (MPI) studies, but little prognostic significance has been attributed to the hemodynamic response to vasodilator stress testing with low-level exercise. We hypothesized that a delay in HR recovery after adenosine stress testing with arm exercise is associated with increased mortality. Technetium 99m-Sestamibi MPI was performed in 1,455 consecutive patients (70 +/- 12 years, 50.2% men) with adenosine stress and supplemental arm exercise. HRs were recorded at rest, continuously during infusion, and then 5 minutes post-infusion. Delayed HR recovery was defined as a decline of mortality (16.5% vs 5.3% in those with normal HR recovery, P testing with arm exercise is a readily available and powerful predictor of all-cause mortality.

  1. Specificity of the stress electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin.

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    Hart, C Y; Miller, T D; Hodge, D O; Gibbons, R J

    2000-12-01

    In patients taking digoxin, the exercise electrocardiogram has a lower specificity for detecting coronary artery disease. However, the effect of digoxin on adenosine-induced ST-segment depression is unknown. The purpose of this study was to evaluate the specificity of the electrocardiogram during adenosine myocardial perfusion imaging in patients taking digoxin. Between May 1991 and September 1997, patients (n = 99) taking digoxin who underwent adenosine stress imaging with thallium-201 or technetium-99m sestamibi and coronary angiography within 3 months were retrospectively identified. Exclusion criteria included prior myocardial infarction, coronary artery angioplasty or bypass surgery, left bundle branch block, paced ventricular rhythm, or significant valvular disease. Twelve-lead electrocardiograms were visually interpreted at baseline, during adenosine infusion, and during the recovery period. The stress electrocardiogram was considered positive if there was > or =1 mm additional horizontal or downsloping ST-segment depression or elevation 0.08 seconds after the J-point compared with the baseline tracing. ST-segment depression and/or elevation occurred in 24 of 99 patients. There were only 2 false-positive stress electrocardiograms, yielding a specificity of 87% and positive predictive value of 92%. All 8 patients with > or =2 mm ST segment depression had multivessel disease by coronary angiography. ST-segment depression or elevation during adenosine myocardial perfusion imaging in patients taking digoxin is highly specific for coronary artery disease. Marked (> or =2 mm) ST-segment depression and/or ST-segment elevation is associated with a high likelihood of multivessel disease.

  2. Maintaining methylation activities during salt stress. The involvement of adenosine kinase.

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    Weretilnyk, E A; Alexander, K J; Drebenstedt, M; Snider, J D; Summers, P S; Moffatt, B A

    2001-02-01

    Synthesis of the compatible osmolyte Gly betaine is increased in salt-stressed spinach (Spinacia oleracea). Gly betaine arises by oxidation of choline from phosphocholine. Phosphocholine is synthesized in the cytosol by three successive S-adenosyl-Met-dependent N-methylations of phosphoethanolamine. With each transmethylation, a molecule of S-adenosylhomo-Cys (SAH) is produced, a potent inhibitor of S-adenosyl-Met-dependent methyltransferases. We examined two enzymes involved in SAH metabolism: SAH hydrolase (SAHH) catabolizes SAH to adenosine plus homo-Cys and adenosine kinase (ADK) converts adenosine to adenosine monophosphate. In vitro SAHH and ADK activities increased incrementally in extracts from leaves of spinach plants subjected to successively higher levels of salt stress and these changes reflected increased levels of SAHH and ADK protein and transcripts. Another Gly betaine accumulator, sugar beet (Beta vulgaris), also showed salt-responsive increases in SAHH and ADK activities and protein whereas tobacco (Nicotiana tabacum) and canola (Brassica napus), which do not accumulate Gly betaine, did not show comparable changes in these enzymes. In spinach, subcellular localization positions SAHH and ADK in the cytosol with the phospho-base N-methyltransferase activities. Because SAHH activity is inhibited by its products, we propose that ADK is not a stress-responsive enzyme per se, but plays a pivotal role in sustaining transmethylation reactions in general by serving as a coarse metabolic control to reduce the cellular concentration of free adenosine. In support of this model, we grew Arabidopsis under a short-day photoperiod that promotes secondary cell wall development and found both ADK activity and transcript levels to increase severalfold.

  3. Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease.

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    Levelt, Eylem; Piechnik, Stefan K; Liu, Alexander; Wijesurendra, Rohan S; Mahmod, Masliza; Ariga, Rina; Francis, Jane M; Greiser, Andreas; Clarke, Kieran; Neubauer, Stefan; Ferreira, Vanessa M; Karamitsos, Theodoros D

    2017-10-25

    Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention.

  4. Role of adipokinetic hormone and adenosine in the anti-stress response in Drosophila melanogaster.

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    Zemanová, Milada; Stašková, Tereza; Kodrík, Dalibor

    2016-01-01

    The role of adipokinetic hormone (AKH) and adenosine in the anti-stress response was studied in Drosophila melanogaster larvae and adults carrying a mutation in the Akh gene (Akh(1)), the adenosine receptor gene (AdoR(1)), or in both of these genes (Akh(1) AdoR(1) double mutant). Stress was induced by starvation or by the addition of an oxidative stressor paraquat (PQ) to food. Mortality tests revealed that the Akh(1) mutant was the most resistant to starvation, while the AdoR(1) mutant was the most sensitive. Conversely, the Akh(1) AdoR(1) double mutant was more sensitive to PQ toxicity than either of the single mutants. Administration of PQ significantly increased the Drome-AKH level in w(1118) and AdoR(1) larvae; however, this was not accompanied by a simultaneous increase in Akh gene expression. In contrast, PQ significantly increased the expression of the glutathione S-transferase D1 (GstD1) gene. The presence of both a functional adenosine receptor and AKH seem to be important for the proper control of GstD1 gene expression under oxidative stress, however, the latter appears to play more dominant role. On the other hand, differences in glutathione S-transferase (GST) activity among the strains, and between untreated and PQ-treated groups were minimal. In addition, the glutathione level was significantly lower in all untreated AKH- or AdoR-deficient mutant flies as compared with the untreated control w(1118) flies and further declined following treatment with PQ. All oxidative stress characteristics modified by mutations in Akh gene were restored or even improved by 'rescue' mutation in flies which ectopically express Akh. Thus, the results of the present study demonstrate the important roles of AKH and adenosine in the anti-stress response elicited by PQ in a D. melanogaster model, and provide the first evidence for the involvement of adenosine in the anti-oxidative stress response in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography.

    Science.gov (United States)

    Blankstein, Ron; Shturman, Leon D; Rogers, Ian S; Rocha-Filho, Jose A; Okada, David R; Sarwar, Ammar; Soni, Anand V; Bezerra, Hiram; Ghoshhajra, Brian B; Petranovic, Milena; Loureiro, Ricardo; Feuchtner, Gudrun; Gewirtz, Henry; Hoffmann, Udo; Mamuya, Wilfred S; Brady, Thomas J; Cury, Ricardo C

    2009-09-15

    This study sought to determine the feasibility of performing a comprehensive cardiac computed tomographic (CT) examination incorporating stress and rest myocardial perfusion imaging together with coronary computed tomography angiography (CTA). Although cardiac CT can identify coronary stenosis, very little data exist on the ability to detect stress-induced myocardial perfusion defects in humans. Thirty-four patients who had a nuclear stress test and invasive angiography were included in the study. Dual-source computed tomography (DSCT) was performed as follows: 1) stress CT: contrast-enhanced scan during adenosine infusion; 2) rest CT: contrast-enhanced scan using prospective triggering; and 3) delayed scan: acquired 7 min after rest CT. Images for CTA, computed tomography perfusion (CTP), and single-photon emission computed tomography (SPECT) were each read by 2 independent blinded readers. The DSCT protocol was successfully completed for 33 of 34 subjects (average age 61.4 +/- 10.7 years; 82% male; body mass index 30.4 +/- 5 kg/m(2)) with an average radiation dose of 12.7 mSv. On a per-vessel basis, CTP alone had a sensitivity of 79% and a specificity of 80% for the detection of stenosis > or =50%, whereas SPECT myocardial perfusion imaging had a sensitivity of 67% and a specificity of 83%. For the detection of vessels with > or =50% stenosis with a corresponding SPECT perfusion abnormality, CTP had a sensitivity of 93% and a specificity of 74%. The CTA during adenosine infusion had a per-vessel sensitivity of 96%, specificity of 73%, and negative predictive value of 98% for the detection of stenosis > or =70%. Adenosine stress CT can identify stress-induced myocardial perfusion defects with diagnostic accuracy comparable to SPECT, with similar radiation dose and with the advantage of providing information on coronary stenosis.

  6. Cardiac displacement during13N-Ammonia myocardial perfusion PET/CT: comparison between adenosine and regadenoson induced stress.

    Science.gov (United States)

    Vleeming, Elise; Lazarenko, Sergiy; van der Zant, Friso; Pan, Xiao-Bo; Declerck, Jerome; Wondergem, Maurits; Knol, Remco

    2017-12-22

    In this study, differences are investigated in cardiac displacement during adenosine stress versus regadenoson stress in 13 N-Ammonia( 13 NH 3 ) MP PET/CT scans. A total of 61 MP PET/CTs were acquired using either adenosine (n=30) or regadenoson (n=31) as a stressor. For both groups, cardiac displacement during rest and stress was measured three-dimensionally, relative to either a fixed reference frame or the previous frame, in each 1-minute frame of a list-mode PET acquisition of 25 minutes. All stress scans were additionally evaluated for the presence of motion artifacts. Also, patient tolerability and occurrence of various side effects were compared between groups. Significantly larger cardiac displacement during stress was detected in the adenosine group as compared to the regadenoson group, reflected by both maximal cardiac displacement (p=0.022) and mean cardiac displacement (p=0.001). The duration of the movement was typically shorter in the regadenoson group. Frames with cardiac displacement ≥5 mm were observed nearly twice as frequent when using adenosine instead of regadenoson. The displacement during regadenoson stress is of lower amplitude and lasts shorter, and may therefore contribute to the lower incidence of motion artifacts on regadenoson compared to adenosine induced stress PET/CT scans. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  7. [Is stress cardiovascular magnetic resonance really useful to detect ischemia and predict events in patients with different cardiovascular risk profile?

    Science.gov (United States)

    Esteban-Fernández, Alberto; Coma-Canella, Isabel; Bastarrika, Gorka; Barba-Cosials, Joaquín; Azcárate-Agüero, Pedro M

    The aim of this study was to evaluate the diagnostic and prognostic usefulness of stress cardiovascular magnetic resonance (stress CMR) in patients with different cardiovascular risk profile and to assess if the degree of hypoperfusion is important to guide clinical decisions. We included patients submitted to adenosine stress CMR to rule out myocardial ischemia. We evaluated its diagnostic accuracy with likelihood ratio (LR) and its prognostic value with survival curves and a Cox regression model. 295 patients were studied. The positive LR was 3.40 and the negative one 0.47. The maximal usefulness of the test was found in patients without previous ischemic cardiomyopathy (positive LR 4.85), patients with atypical chest pain (positive LR 8.56), patients with low or intermediate cardiovascular risk (positive LR 3.87) and those with moderate or severe hypoperfusion (positive LR 8.63). Sixty cardiovascular major events were registered. The best survival prognosis was found in patients with a negative result (p=0.001) or mild hypoperfusion (p=0.038). In the multivariate analysis, a moderate or severe hypoperfusion increased cardiovascular event probability (HR=2.2; IC 95% 1.26-3.92), with no differences between a mild positive and a negative result (HR=0.93; IC 95% 0.38-2.28). Stress CMR was specially useful in patients with low or intermediate cardiovascular risk, patients with atypical chest pain, patients without previous ischemic cardiomyopathy and those with moderate or severe hypoperfusion. Hypoperfusion degree was the main issue factor to guide clinical decisions. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Caffeine intake inverts the effect of adenosine on myocardial perfusion during stress as measured by T1 mapping.

    Science.gov (United States)

    Kuijpers, Dirkjan; Prakken, Niek H; Vliegenthart, Rozemarijn; van Dijkman, Paul R M; van der Harst, Pim; Oudkerk, Matthijs

    2016-10-01

    Caffeine intake before adenosine stress myocardial perfusion imaging may cause false negative findings. We hypothesized that the antagonistic effect of caffeine can be measured by T1 relaxation times in rest and adenosine stress cardiac magnetic resonance imaging (CMR), as T1 mapping techniques are sensitive to changes in myocardial blood volume. We prospectively analyzed 105 consecutive patients with adenosine stress perfusion CMR on a 1.5-T MRI system. Rest and stress T1 mapping was performed using Modified Look-Locker Inversion recovery. T1 reactivity was defined as difference in T1rest and T1stress (∆T1). Fifteen patients drank coffee within 4 h of CMR (8H caffeine group). Comparison was made to patients without self-reported coffee intake: 50 with normal CMR (control group), 18 with myocardial ischemia, and 12 with myocardial infarction. The national review board approved the study; all patients gave written informed consent. The T1 of -7.8 % (T1rest 975 ± 42 ms, T1stress 898 ± 51 ms, p 8H caffeine group showed reduced T1 reactivity (1.8 %; T1rest 979 ms, T1stress 997 ms) compared to the controls (4.3 %; T1rest 977 ± 40 ms, T1stress 1018 ± 40 ms), p infarcted myocardium showed minimal T1 reactivity (0.2 and 0.3 %, respectively). Caffeine intake inverts the adenosine effect during stress perfusion CMR as measured by T1 mapping. T1 reactivity can assess the adequacy of adenosine-induced stress in perfusion CMR.

  9. Comparison of dual-source 64-slice adenosine stress CT perfusion with stress-gated SPECT-MPI for evaluation of left ventricular function and volumes.

    Science.gov (United States)

    Uthamalingam, Shanmugam; Gurm, Gagandeep S; Sidhu, Manavjot S; Verdini, Daniel J; Vorasettakarnkij, Yongkasem; Engel, Leif-Christopher; Blankstein, Ron; Mamuya, Wilfred S; Hoffman, Udo; Brady, Thomas J; Cury, Ricardo C; Ghoshhajra, Brian B

    2012-01-01

    Evaluation of left ventricular (LV) volumes and ejection fraction (LVEF) represent important components of pharmacologic stress imaging with either myocardial CT perfusion (CTP) or gated single-photon emission CT (SPECT) myocardial perfusion imaging (SPECT-MPI). We compared measurements of left ventricular function and volumes obtained with CTP and SPECT-MPI. Forty-seven patients (mean age, 62 ± 11 years; male, n = 39) underwent stress CTP and SPECT-MPI. LVEF (in %), end-systolic volume (ESV; in mL), and end-diastolic volume (EDV; in mL) derived from stress CTP images were compared with SPECT-MPI. Stress CTP was in good agreement with SPECT-MPI for quantification of LVEF (r = 0.91), EDV (r = 0.75), and ESV (r = 0.83; all P stress CTP (66% ± 17%) was similar to SPECT-MPI (64% ± 15%). Similar values were also derived for mean EDV (123 ± 30 mL vs 120 ± 34 mL) and ESV (44 ± 28 mL vs 51 ± 34 mL) for CTP and SPECT-MPI, respectively. Good agreement was also shown between both techniques for the assessment of regional wall motion with identical wall motion scores in 95.3% of the segments (κ = 0.79). LVEF and LV volume parameters as determined by dual-source 64-slice adenosine stress CTP show a high correlation with values obtained with stress-gated SPECT-MPI. Copyright © 2012 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  10. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yosuke Kayama

    2015-10-01

    Full Text Available Cardiovascular disease (CVD is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM. DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD, cardiac hypertrophy, and heart failure (HF. HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS. ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

  11. Prognostic value of normal regadenoson stress perfusion cardiovascular magnetic resonance.

    Science.gov (United States)

    Freed, Benjamin H; Narang, Akhil; Bhave, Nicole M; Czobor, Peter; Mor-Avi, Victor; Zaran, Emily R; Turner, Kristen M; Cavanaugh, Kevin P; Chandra, Sonal; Tanaka, Sara M; Davidson, Michael H; Lang, Roberto M; Patel, Amit R

    2013-12-21

    Regadenoson is a vasodilator stress agent that selectively activates the A2A receptor. Compared to adenosine, regadenoson is easier to administer and results in fewer side effects. Although extensively studied in patients undergoing nuclear perfusion imaging (MPI), its use for perfusion cardiovascular magnetic resonance (CMR) is not well described. The aim of this study was to determine the prognostic value of a normal regadenoson perfusion CMR in patients with known or suspected coronary artery disease. Patients with known or suspected coronary artery disease were prospectively enrolled to receive perfusion CMR (Philips 1.5 T) with regadenoson. Three short-axis slices of the left ventricle (LV) were obtained during first pass of contrast using a hybrid GRE-EPI pulse sequence (0.075 mmol/kg Gadolinium-DTPA-BMA at 4 ml/sec). Imaging was performed 1 minute after injection of regadenoson (0.4 mg) and repeated 15 minutes after reversal of hyperemia with aminophylline (125 mg). Perfusion defects were documented if they persisted for ≥ 2 frames after peak enhancement of the LV cavity. CMR was considered abnormal if there was a resting wall motion abnormality, decreased LVEF (Regadenoson perfusion CMR provides high confidence for excellent prognosis in patients with normal perfusion.

  12. Editing of Cellular Self-RNAs by Adenosine Deaminase ADAR1 Suppresses Innate Immune Stress Responses.

    Science.gov (United States)

    George, Cyril X; Ramaswami, Gokul; Li, Jin Billy; Samuel, Charles E

    2016-03-18

    Adenosine deaminases acting on double-stranded RNA (ADARs) catalyze the deamination of adenosine (A) to produce inosine (I) in double-stranded (ds) RNA structures, a process known as A-to-I RNA editing. dsRNA is an important trigger of innate immune responses, including interferon (IFN) production and action. We examined the role of A-to-I RNA editing by two ADARs, ADAR1 and ADAR2, in the sensing of self-RNA in the absence of pathogen infection, leading to activation of IFN-induced, RNA-mediated responses in mouse embryo fibroblasts. IFN treatment of Adar1(-/-) cells lacking both the p110 constitutive and p150 IFN-inducible ADAR1 proteins induced formation of stress granules, whereas neither wild-type (WT) nor Adar2(-/-) cells displayed a comparable stress granule response following IFN treatment. Phosphorylation of protein synthesis initiation factor eIF2α at serine 51 was increased in IFN-treated Adar1(-/-) cells but not in either WT or Adar2(-/-) cells following IFN treatment. Analysis by deep sequencing of mouse exonic loci containing A-to-I-editing sites revealed that the majority of editing in mouse embryo fibroblasts was carried out by ADAR1. IFN treatment increased editing in both WT and Adar2(-/-) cells but not in either Adar1(-/-) or Adar1(-/-) (p150) cells or Stat1(-/-) or Stat2(-/-) cells. Hyper-edited sites found in predicted duplex structures showed strand bias of editing for some RNAs. These results implicate ADAR1 p150 as the major A-to-I editor in mouse embryo fibroblasts, acting as a feedback suppressor of innate immune responses otherwise triggered by self-RNAs possessing regions of double-stranded character. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Inter-observer variability of visual analysis of "stress"-only adenosine first-pass myocardial perfusion imaging in relation to clinical experience and reading criteria

    NARCIS (Netherlands)

    Lubbers, D. D.; Kuijpers, D.; Bodewes, R.; Kappert, P.; Kerkhof, M.; van Ooijen, P. M. A.; Oudkerk, M.

    To assess the inter-observer agreement of adenosine "stress"-only visual analysis of perfusion MR images in relation to experience and reading criteria. 106 adenosine perfusion MR examinations out of 350, 46 consecutive positive examinations and 60 randomly selected negative examinations were

  14. Toward a causal model of cardiovascular responses to stress and the development of cardiovascular disease.

    Science.gov (United States)

    Schwartz, Amy R; Gerin, William; Davidson, Karina W; Pickering, Thomas G; Brosschot, Jos F; Thayer, Julian F; Christenfeld, Nicholas; Linden, Wolfgang

    2003-01-01

    Cardiovascular reactivity is hypothesized to mediate the relationship between stress and cardiovascular disease. We describe three considerations that are crucial for a causal model of cardiovascular responses to stress: the need for laboratory-life generalizability, the role of interactions between environmental exposures and individual response predispositions, and the importance of the duration of both stressor exposure and cardiovascular responding. We illustrate current understanding of stress-cardiovascular disease relationships with examples from the human and animal psychophysiology, epidemiology, and genetics literature. In a causal model of reactivity, the usefulness of laboratory assessment rests on the assumption that laboratory-based cardiovascular reactivity predicts responses in the natural environment. We find only limited generalizability and suggest that cardiovascular responses to stress can be better understood when examined in the natural environment. The interaction of individual response predispositions and stressor exposures contributes to the development and progression of cardiovascular disease; stress-disease relationships could therefore be better understood if predispositions and exposures were assessed simultaneously in interactive models. Cardiovascular responses to stress are likely to be most deleterious when responses are prolonged. Responses may vary in their magnitude, frequency, and duration; however, reactivity captures only response magnitude. The assessment of anticipatory and recovery measures, with response magnitude, may therefore lead to a more useful model of the stress-disease relationship. A causal model of cardiovascular responses to stress should generalize to the real world, assess interactions between individual predispositions and environmental exposures, and focus on sustained pathogenic exposures and responses.

  15. Adenosine-diphosphate (ADP) receptor antagonists for the prevention of cardiovascular disease in type 2 diabetes mellitus.

    Science.gov (United States)

    Valentine, Nyoli; Van de Laar, Floris A; van Driel, Mieke L

    2012-11-14

    Cardiovascular disease (CVD) is the most prevalent complication of type 2 diabetes with an estimated 65% of people with type 2 diabetes dying from a cause related to atherosclerosis. Adenosine-diphosphate (ADP) receptor antagonists like clopidogrel, ticlopidine, prasugrel and ticagrelor impair platelet aggregation and fibrinogen-mediated platelet cross-linking and may be effective in preventing CVD. To assess the effects of adenosine-diphosphate (ADP) receptor antagonists for the prevention of cardiovascular disease in type 2 diabetes mellitus. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (issue 2, 2011), MEDLINE (until April 2011) and EMBASE (until May 2011). We also performed a manual search, checking references of original articles and pertinent reviews to identify additional studies. Randomised controlled trials comparing an ADP receptor antagonist with another antiplatelet agent or placebo for a minimum of 12 months in patients with diabetes. In particular, we looked for trials assessing clinical cardiovascular outcomes. Two review authors extracted data for studies which fulfilled the inclusion criteria, using standard data extraction templates. We sought additional unpublished information and data from the principal investigators of all included studies. Eight studies with a total of 21,379 patients with diabetes were included. Three included studies investigated ticlopidine compared to aspirin or placebo. Five included studies investigated clopidogrel compared to aspirin or a combination of aspirin and dipyridamole, or compared clopidogrel in combination with aspirin to aspirin alone. All trials included patients with previous CVD except the CHARISMA trial which included patients with multiple risk factors for coronary artery disease. Overall the risk of bias of the trials was low. The mean duration of follow-up ranged from 365 days to 913 days.Data for diabetes patients on all-cause mortality, vascular

  16. Effects of caffeine intake prior to stress cardiac magnetic resonance perfusion imaging on regadenoson- versus adenosine-induced hyperemia as measured by T1 mapping.

    Science.gov (United States)

    van Dijk, R; Kuijpers, D; Kaandorp, T A M; van Dijkman, P R M; Vliegenthart, R; van der Harst, P; Oudkerk, M

    2017-11-01

    The antagonistic effects of caffeine on adenosine receptors are a possible cause of false-negative stress perfusion imaging. The purpose of this study was to determine the effects of coffee intake regadenoson- versus adenosine-induced hyperemia as measured with T1-mapping. 98 consecutive patients with suspected coronary artery disease referred for either adenosine or regadenoson perfusion CMR were included in this analysis. Twenty-four patients reported coffee consumption regadenoson); 74 patients reported no coffee intake (50 patients with adenosine, and 24 patients with regadenoson). T1 mapping was performed using a modified look-locker inversion recovery sequence. T1 reactivity was determined by subtracting T1 rest from T1 stress . T1 rest , T1 stress , and T1 reactivity in patients referred for regadenoson perfusion CMR were not significantly different when comparing patients with regadenoson perfusion CMR (p regadenoson perfusion CMR has no effect on stress-induced hyperemia as measured with T1 mapping.

  17. Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases.

    Science.gov (United States)

    Matsuda, Morihiro; Shimomura, Iichiro

    2014-03-01

    The recent increase in populations with obesity is a worldwide social problem, and the enhanced susceptibility of obese people to metabolic and cardiovascular diseases has become a growing health threat. An understanding of the molecular basis for obesity-associated disease development is required to prevent these diseases. Many studies have revealed that the mechanism involves various bioactive molecules that are released from adipose tissues and designated as adipocytokines/adipokines. Adiponectin is an adipocytokine that exerts insulin-sensitizing effects in the liver and skeletal muscle via adenosine monophosphate-activated protein kinase and proliferator-activated receptor α activation. Additionally, adiponectin can suppress atherosclerosis development in vascular walls via various anti-inflammatory effects. In contrast, oxidative stress is a harmful factor that systemically increases during obesity and promotes the development of diabetes, atherosclerosis, and various other diseases. In obese mice, oxidative stress is enhanced in adipose tissue before diabetes development, but not in the liver, skeletal muscle, and aorta, suggesting that in obesity, adipose tissue may be a major source of reactive oxygen species (ROS). ROS suppress adiponectin production in adipocytes. Treatment of obese mice with anti-oxidative agents improves insulin resistance and restores adiponectin production. Recent studies have demonstrated that adiponectin protects against oxidative stress-induced damage in the vascular endothelium and myocardium. Thus, decreased circulating adiponectin levels and increased oxidative stress, which are closely linked to each other, should be deeply involved in obesity-associated metabolic and cardiovascular disease pathogenesis.

  18. Cardiovascular drift during heat stress: implications for exercise prescription.

    Science.gov (United States)

    Wingo, Jonathan E; Ganio, Matthew S; Cureton, Kirk J

    2012-04-01

    Cardiovascular drift, the progressive increase in heart rate and decrease in stroke volume that begins after approximately 10 min of prolonged moderate-intensity exercise, is associated with decreased maximal oxygen uptake, particularly during heat stress. Consequently, the increased heart rate reflects an increased relative metabolic intensity during prolonged exercise in the heat when cardiovascular drift occurs, which has implications for exercise prescription.

  19. Post-traumatic stress disorder and cardiovascular disease.

    Science.gov (United States)

    Edmondson, Donald; von Känel, Roland

    2017-04-01

    In this paper, a first in a Series of two, we look at the evidence for an association of post-traumatic stress disorder with incident cardiovascular disease risk and the mechanisms that might cause this association, as well as the prevalence of post-traumatic stress disorder due to cardiovascular disease events and its associated prognostic risk. We discuss research done after the publication of previous relevant systematic reviews, and survey currently funded research from the two most active funders in the field: the National Institutes of Health and the US Veterans Administration. We conclude that post-traumatic stress disorder is a risk factor for incident cardiovascular disease, and a common psychiatric consequence of cardiovascular disease events that might worsen the prognosis of the cardiovascular disease. There are many candidate mechanisms for the link between post-traumatic stress disorder and cardiovascular disease, and several ongoing studies could soon point to the most important behavioural and physiological mechanisms to target in early phase intervention development. Similarly, targets are emerging for individual and environmental interventions that might offset the risk of post-traumatic stress disorder after cardiovascular disease events. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Stress in university students and cardiovascular response to academic stressors

    OpenAIRE

    Guimarães, Teresa; Silva, Ana Patrícia; Monteiro, Iolanda; Gomes, Rui

    2014-01-01

    Introduction: University students are frequently exposed to events that can cause stress and anxiety, producing elevated cardiovascular responses. Repeated exposure to academic stress has implications to students’ success and well-being and may contribute to the development of long-term health problems. Objective: To identify stress levels and coping strategies in university students and assess the impact of stress experience in heart rate variability (HRV). Methods: 17 university students, 1...

  1. Adenosine-stress dynamic real-time myocardial perfusion CT and adenosine-stress first-pass dual-energy myocardial perfusion CT for the assessment of acute chest pain: Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Weininger, Markus [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, SC (United States); Ramachandra, Ashok [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Fink, Christian [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University (Germany); Rowe, Garrett W.; Costello, Philip [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Henzler, Thomas [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University (Germany)

    2012-12-15

    Purpose: Recent innovations in CT enable the evolution from mere morphologic imaging to dynamic and functional testing. We describe our initial experience performing myocardial stress perfusion CT in a clinical population with acute chest pain. Methods and materials: Myocardial stress perfusion CT was performed on twenty consecutive patients (15 men, 5 women; mean age 65 ± 8 years) who presented with acute chest pain and were clinically referred for stress/rest SPECT and cardiac MRI. Prior to CT each patient was randomly assigned either to Group A or to Group B in a consecutive order (10 patients per group). Group A underwent adenosine-stress dynamic real-time myocardial perfusion CT using a novel “shuttle” mode on a 2nd generation dual-source CT. Group B underwent adenosine-stress first-pass dual-energy myocardial perfusion CT using the same CT scanner in dual-energy mode. Two experienced observers visually analyzed all CT perfusion studies. CT findings were compared with MRI and SPECT. Results: In Group A 149/170 myocardial segments (88%) could be evaluated. Real-time perfusion CT (versus SPECT) had 86% (84%) sensitivity, 98% (92%) specificity, 94% (88%) positive predictive value, and 96% (92%) negative predictive value in comparison with perfusion MRI for the detection of myocardial perfusion defects. In Group B all myocardial segments were available for analysis. Compared with MRI, dual-energy myocardial perfusion CT (versus SPECT) had 93% (94%) sensitivity, 99% (98%) specificity, 92% (88%) positive predictive value, and 96% (94%) negative predictive value for detecting hypoperfused myocardial segments. Conclusion: Our results suggest the clinical feasibility of myocardial perfusion CT imaging in patients with acute chest pain. Compared to MRI and SPECT both, dynamic real-time perfusion CT and first-pass dual-energy perfusion CT showed good agreement for the detection of myocardial perfusion defects.

  2. Effects of caffeine intake prior to stress cardiac magnetic resonance perfusion imaging on regadenoson- versus adenosine-induced hyperemia as measured by T1 mapping

    NARCIS (Netherlands)

    van Dijk, R; Kuijpers, D; Kaandorp, T A M; van Dijkman, P R M; Vliegenthart, R; van der Harst, P; Oudkerk, M

    2017-01-01

    The antagonistic effects of caffeine on adenosine receptors are a possible cause of false-negative stress perfusion imaging. The purpose of this study was to determine the effects of coffee intake <4 h prior to stress perfusion cardiac magnetic resonance imaging (CMR) in regadenoson- versus

  3. Prenatal stress alters cardiovascular responses in adult rats

    Science.gov (United States)

    Igosheva, N; Klimova, O; Anishchenko, T; Glover, V

    2004-01-01

    Environmental factors in early life are clearly established risk factors for cardiovascular disease in later life. Most studies have focused on nutritional programming and analysed basal cardiovascular parameters rather than responses. In the present study we have investigated whether prenatal stress has long-term effects on cardiovascular responses in adult offspring. Female pregnant Sprague-Dawley rats were subjected to stress three times daily from day 15 to day 21 of gestation. Litters from stressed and control females were cross-fostered at birth to control for mothering effects. When the offspring were 6 months old, blood pressure was measured in the conscious rats through implanted catheters at rest, during restraint stress and during recovery. Basal haemodynamic parameters were similar in the different groups but the pattern of cardiovascular responses during stress and recovery differed markedly between prenatally stressed (PS) and control animals. PS rats had higher and longer-lasting systolic arterial pressure elevations to restraint stress than control animals. They also showed elevated systolic and diastolic blood pressure values during the recovery phase. PS rats demonstrated a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, and showed more prolonged heart rate responses to acute stress and delayed recovery than controls. There was no effect of prenatal stress on baroreflex regulation of heart rate. PS females showed a greater increase in systolic arterial pressure and blood pressure variability and delayed heart rate recovery following return to the home cage then did PS males. These findings demonstrate for the first time that prenatal stress can induce long-term, sex-related changes in the sensitivity of the cardiovascular system to subsequent stress. PMID:15034122

  4. Adenosine stress high-pitch 128-slice dual-source myocardial computed tomography perfusion for imaging of reversible myocardial ischemia: comparison with magnetic resonance imaging.

    Science.gov (United States)

    Feuchtner, Gudrun; Goetti, Robert; Plass, André; Wieser, Monika; Scheffel, Hans; Wyss, Christophe; Stolzmann, Paul; Donati, Olivio; Schnabl, Johannes; Falk, Volkmar; Alkadhi, Hatem; Leschka, Sebastian; Cury, Ricardo C

    2011-09-01

    Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR). Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64 ± 10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate 63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv. Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.

  5. The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

    Science.gov (United States)

    Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Sun, Tao

    2014-01-01

    Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol. PMID:25143940

  6. Endoplasmic Reticulum Stress-Related Inflammation and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Tomomi Gotoh

    2011-01-01

    Full Text Available The endoplasmic reticulum (ER is the site of synthesis and maturation of proteins designed for secretion or for localization on the cell membrane. Various types of stress from both inside and outside cells disturb ER function, thus causing unfolded or misfolded proteins to accumulate in the ER. To improve and maintain the ER functions against such stresses, the ER stress response pathway is activated. However, when the stress is prolonged or severe, apoptosis pathways are activated to remove damaged cells. It was recently reported that the ER stress pathway is also involved in the inflammatory response, whereby inflammation induces ER stress, and ER stress induces an inflammatory response. Therefore, the ER stress response pathway is involved in various diseases, including cardiovascular diseases such as atherosclerosis and ischemic diseases, in various ways. The ER stress pathway may represent a novel target for the treatment of these diseases.

  7. The integrated stress response system in cardiovascular disease.

    Science.gov (United States)

    Santos-Ribeiro, Diana; Godinas, Laurent; Pilette, Charles; Perros, Frédéric

    2018-02-27

    The integrated stress response system represents an ancillary, extremely conserved signalling pathway present in virtually all eukaryotic cells, which plays an important part in the pathophysiology of several disorders such as cancer and neurodegeneration. However, its role in the cardiovascular system remains largely elusive. Hence, this review aims to acknowledge recent findings regarding the action of the eIF2α kinases in the cardiovascular system and their role in the pathophysiology of related disorders. Copyright © 2018. Published by Elsevier Ltd.

  8. Angiographic correlations of patients with small vessel disease diagnosed by adenosine-stress cardiac magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Scheck Roland

    2008-01-01

    Full Text Available Abstract Cardiac magnetic resonance imaging (CMR with adenosine-stress myocardial perfusion is gaining importance for the detection and quantification of coronary artery disease (CAD. However, there is little knowledge about patients with CMR-detected ischemia, but having no relevant stenosis as seen on coronary angiography (CA. The aims of our study were to characterize these patients by CMR and CA and evaluate correlations and potential reasons for the ischemic findings. 73 patients with an indication for CA were first scanned on a 1.5T whole-body CMR-scanner including adenosine-stress first-pass perfusion. The images were analyzed by two independent investigators for myocardial perfusion which was classified as subendocardial ischemia (n = 22, no perfusion deficit (n = 27, control 1, or more than subendocardial ischemia (n = 24, control 2. All patients underwent CA, and a highly significant correlation between the classification of CMR perfusion deficit and the degree of coronary luminal narrowing was found. For quantification of coronary blood flow, corrected Thrombolysis in Myocardial Infarction (TIMI frame count (TFC was evaluated for the left anterior descending (LAD, circumflex (LCX and right coronary artery (RCA. The main result was that corrected TFC in all coronaries was significantly increased in study patients compared to both control 1 and to control 2 patients. Study patients had hypertension or diabetes more often than control 1 patients. In conclusion, patients with CMR detected subendocardial ischemia have prolonged coronary blood flow. In connection with normal resting flow values in CAD, this supports the hypothesis of underlying coronary microvascular impairment. CMR stress perfusion differentiates non-invasively between this entity and relevant CAD.

  9. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress.

    Science.gov (United States)

    Kaster, Manuella P; Machado, Nuno J; Silva, Henrique B; Nunes, Ana; Ardais, Ana Paula; Santana, Magda; Baqi, Younis; Müller, Christa E; Rodrigues, Ana Lúcia S; Porciúncula, Lisiane O; Chen, Jiang Fan; Tomé, Ângelo R; Agostinho, Paula; Canas, Paula M; Cunha, Rodrigo A

    2015-06-23

    The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine A2A receptor (A2AR) antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection. Therefore we tested the ability of A2AR to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression. CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance. These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of A2AR in glutamatergic terminals in the hippocampus. Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective A2AR antagonist KW6002 (3 mg/kg, p.o.); (iii) global A2AR deletion; and (iv) selective A2AR deletion in forebrain neurons. Notably, A2AR blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the A2AR antagonist SCH58261 (0.1 mg/kg, i.p.) reversed the mood and synaptic dysfunction caused by CUS. These results herald a key role for synaptic A2AR in the control of chronic stress-induced modifications and suggest A2AR as candidate targets to alleviate the consequences of chronic stress on brain function.

  10. Qualitative and quantitative assessment of adenosine triphosphate stress whole-heart dynamic myocardial perfusion imaging using 256-slice computed tomography.

    Directory of Open Access Journals (Sweden)

    Akira Kurata

    Full Text Available BACKGROUND: The aim of this study was to investigate the correlation of the qualitative transmural extent of hypoperfusion areas (HPA using stress dynamic whole-heart computed tomography perfusion (CTP imaging by 256-slice CT with CTP-derived myocardial blood flow (MBF for the estimation of the severity of coronary artery stenosis. METHODS AND RESULTS: Eleven patients underwent adenosine triphosphate (0.16 mg/kg/min, 5 min stress dynamic CTP by 256-slice CT (coverage: 8 cm, 0.27 s/rotation, and 9 of the 11 patients underwent coronary angiography (CAG. Stress dynamic CTP (whole-heart datasets over 30 consecutive heart beats in systole without spatial and temporal gaps was acquired with prospective ECG gating (effective radiation dose: 10.4 mSv. The extent of HPAs was visually graded using a 3-point score (normal, subendocardial, transmural. MBF (ml/100g/min was measured by deconvolution. Differences in MBF (mean ± standard error according to HPA and CAG results were evaluated. In 27 regions (3 major coronary territories in 9 patients, 11 coronary stenoses (> 50% reduction in diameter were observed. In 353 myocardial segments, HPA was significantly related to MBF (P 70%], 119 ± 69. CONCLUSION: The qualitative transmural extent of HPA using stress whole-heart dynamic CTP imaging by 256-slice CT exhibits a good correlation with quantitative CTP-derived MBF and may aid in assessing the hemodynamic significance of coronary artery disease.

  11. Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Jorge G. Farías

    2017-09-01

    Full Text Available Oxidative stress (OS refers to the imbalance between the generation of reactive oxygen species (ROS and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia–reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs.

  12. Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress.

    Science.gov (United States)

    Farías, Jorge G; Molina, Víctor M; Carrasco, Rodrigo A; Zepeda, Andrea B; Figueroa, Elías; Letelier, Pablo; Castillo, Rodrigo L

    2017-09-01

    Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia-reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs.

  13. Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress

    Science.gov (United States)

    Molina, Víctor M.; Carrasco, Rodrigo A.; Figueroa, Elías; Letelier, Pablo; Castillo, Rodrigo L.

    2017-01-01

    Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia–reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs. PMID:28862654

  14. Effects of Diesel Exhaust on Cardiovascular Function and Oxidative Stress.

    Science.gov (United States)

    Wilson, Simon J; Miller, Mark R; Newby, David E

    2017-07-14

    Air pollution is a major global health concern with particulate matter (PM) being especially associated with increases in cardiovascular morbidity and mortality. Diesel exhaust emissions are a particularly rich source of the smallest sizes of PM ("fine" and "ultrafine") in urban environments, and it is these particles that are believed to be the most detrimental to cardiovascular health. Recent Advances: Controlled exposure studies to diesel exhaust in animals and man demonstrate alterations in blood pressure, heart rate, vascular tone, endothelial function, myocardial perfusion, thrombosis, atherogenesis, and plaque stability. Oxidative stress has emerged as a highly plausible pathobiological mechanism by which inhalation of diesel exhaust PM leads to multiple facets of cardiovascular dysfunction. Diesel exhaust inhalation promotes oxidative stress in several biological compartments that can be directly associated with adverse cardiovascular effects. Further studies with more sensitive and specific in vivo human markers of oxidative stress are required to determine if targeting oxidative stress pathways involved in the actions of diesel exhaust PM could be of therapeutic value. Antioxid. Redox Signal. 00, 000-000.

  15. Associations between life stress and subclinical cardiovascular disease are partly mediated by depressive and anxiety symptoms

    NARCIS (Netherlands)

    Bomhof-Roordink, Hanna; Seldenrijk, Adrie; van Hout, Hein P. J.; van Marwijk, Harm W. J.; Diamant, Michaela; Penninx, Brenda W. J. H.

    Background: Stress experienced during childhood or adulthood has been associated with cardiovascular disease (CVD), but it is not clear whether associations are already prevalent on a subclinical cardiovascular level. This study investigates associations between indicators of life stress and

  16. Stress and coping among cardiovascular nurses: a survey in Brazil.

    Science.gov (United States)

    Bianchi, Estela Regina Ferraz

    2004-01-01

    Cardiovascular nurses are frequently involved in critical patient care, providing support to patients and their families. The goals of this study were to survey a representative sample of cardiovascular nurses, describe ways of coping, and identify sources of stress in the hospital setting. A descriptive and correlational survey design was used. A self-completed questionnaire was distributed to 76 nurses from a cardiovascular hospital in São Paulo City, Brazil. The measures were the Nursing Stress Evaluation Questionnaire (NSEQ) by Bianchi and Ways of Coping Questionnaire (WCOQ) by Folkman and Lazarus. A high response rate of 76.3% was achieved. The results identified work conditions as the major source of stress for nurses and use of positive reappraisal, self-controlling skills, and social support to cope with job stress. Nurses are using coping strategies based on personal resources but the use of organizational strategies is encouraged to improve life quality. Mental health nurses could play an essential role in preventive stress management programs for hospital nurses.

  17. Selective attenuation of norepinephrine release and stress-induced heart rate increase by partial adenosine A1 agonism.

    Directory of Open Access Journals (Sweden)

    Lorenz Bott-Flügel

    Full Text Available The release of the neurotransmitter norepinephrine (NE is modulated by presynaptic adenosine receptors. In the present study we investigated the effect of a partial activation of this feedback mechanism. We hypothesized that partial agonism would have differential effects on NE release in isolated hearts as well as on heart rate in vivo depending on the genetic background and baseline sympathetic activity. In isolated perfused hearts of Wistar and Spontaneously Hypertensive Rats (SHR, NE release was induced by electrical stimulation under control conditions (S1, and with capadenoson 6 · 10(-8 M (30 µg/l, 6 · 10(-7 M (300 µg/l or 2-chloro-N(6-cyclopentyladenosine (CCPA 10(-6 M (S2. Under control conditions (S1, NE release was significantly higher in SHR hearts compared to Wistar (766+/-87 pmol/g vs. 173+/-18 pmol/g, p<0.01. Capadenoson led to a concentration-dependent decrease of the stimulation-induced NE release in SHR (S2/S1  =  0.90 ± 0.08 with capadenoson 6 · 10(-8 M, 0.54 ± 0.02 with 6 · 10(-7 M, but not in Wistar hearts (S2/S1  =  1.05 ± 0.12 with 6 · 10(-8 M, 1.03 ± 0.09 with 6 · 10(-7 M. CCPA reduced NE release to a similar degree in hearts from both strains. In vivo capadenoson did not alter resting heart rate in Wistar rats or SHR. Restraint stress induced a significantly greater increase of heart rate in SHR than in Wistar rats. Capadenoson blunted this stress-induced tachycardia by 45% in SHR, but not in Wistar rats. Using a [(35S]GTPγS assay we demonstrated that capadenoson is a partial agonist compared to the full agonist CCPA (74+/-2% A(1-receptor stimulation. These results suggest that partial adenosine A(1-agonism dampens stress-induced tachycardia selectively in rats susceptible to strong increases in sympathetic activity, most likely due to a presynaptic attenuation of NE release.

  18. Adenosine A

    National Research Council Canada - National Science Library

    Vallon, Volker; Schroth, Jana; Satriano, Joseph; Blantz, Roland C; Thomson, Scott C; Rieg, Timo

    2009-01-01

    ...'). Here, experiments were performed in adenosine A receptor knockout mice (A R-/-), which lack an immediate TGF response, to determine whether A Rs are essential for early diabetic hyperfiltration and the salt paradox. Methods...

  19. [Cardiovascular risk factors and life and occupational stress among policemen].

    Science.gov (United States)

    Czaja-Miturai, Izabela; Merecz-Kot, Dorota; Szymczak, Wieslaw; Bortkiewicz, Alicja

    2013-01-01

    Several studies have shown an association between work-related stress and risk factors for cardiovascular disease. ever, only a few studies concerned the police. The aim of this study was to assess the relationship between the general and work-related stress, and the functioning of the circulatory system in the police staff. The study group consisted of 126 policemen (aged 37.8 +/- 7.3 years), with average employment duration of 14.4 +/- 7 years. The study comprised the assessment of health status based on the medical examination and medical history of identified diseases, cardiovascular risk factors and symptoms, dietary habits, physical activity, intake of drugs, data on the family history, determinations of serum total cholesterol, HDL and LDL fractions, triglycerides, and fasting glycemia . The stress level was assessed using the Questionnaire for the Subjective Assessment of Work and Perceived Stress Scale. On medical examination hypertension was found in 36% of the people under study. Chest discomfort was reported by 60% of the subjects. Average body mass index (BMI), serum cholesterol and LDI, were elevated (22.7 +/- 4.1, 222.6 +/- 41.7 mg/dl and 142.7 +/- 39.7 mg/dl, respectively). Mean triglyceride, HDL fraction and fasting glucose levels were normal in the whole group. The levels of general and occupational stress were 34.914.8 and 128.0+33.3, respectively, being higher than in other occupational groups. In the group with the highest level of stress, there were significantly more people with circulatory problems (81%), drinking strong alcohol at least once a week (27%), working in a 3-shift system (40.5%) and working overtime (44%). The results show that the police are a group at high risk of developing cardiovascular diseases due to work-related stress.

  20. HYPOTHESIS ON CELLULAR ATP DEPLETION AND ADENOSINE RELEASE AS CAUSES OF HEART-FAILURE AND VASODILATATION IN CARDIOVASCULAR BERIBERI

    NARCIS (Netherlands)

    Bakker, sjl; LEUNISSEN, KML

    Cardiovascular beriberi is a syndrome caused by thiamine deficiency and characterized by systemic vasodilatation, heart failure and lactic acidosis. The occurrence of heart failure and vasodilatation is yet unexplained: neither theoretical nor experimental data are known. In this article, it is

  1. Bivariate genetic modeling of cardiovascular stress reactivity: Does stress uncover genetic variance?

    NARCIS (Netherlands)

    de Geus, E.J.C.; Kupper, H.M.; Boomsma, D.I.; Snieder, H.

    2007-01-01

    OBJECTIVE: To test the existence of gene-by-stress interaction by assessing cardiovascular stress reactivity in monozygotic and dizygotic twins. METHODS: We studied 160 adolescent (mean age 16.7 ± 2.0 years; range 13-22 years) and 212 middle-aged twin pairs (mean age 44.2 ± 6.7 years; range 34-63

  2. Bivariate genetic modeling of cardiovascular stress reactivity : Does stress uncover genetic variance?

    NARCIS (Netherlands)

    De Geus, Eco J. C.; Kupper, Nina; Boomsma, Dorret I.; Snieder, Harold

    Objective: To test the existence of gene-by-stress interaction by assessing cardiovascular stress reactivity in monozygotic and dizygotic twins. Methods: We studied 160 adolescent (mean age 16.7 +/- 2.0 years; range 13-22 years) and 212 middle-aged twin pairs (mean age 44.2 +/- 6.7 years; range

  3. [Civilization stress, cardiovascular risk, evidence-based medicine, guidelines].

    Science.gov (United States)

    Simon, Kornél

    2009-05-10

    Cardiovascular diseases have the pole-position on the list of morbidity and mortality statistics. Despite the great advances have been made in management of cardiovascular diseases, prevalence of these disorders increases worldwide, and even younger and younger ages are threatened. This phenomenon is strongly related to obesity and type 2 diabetes pandemic, which shows an unequivocal association with expansion of modernized life-style. The pathomechanism proposed to have central role is the chronic stress induced by civilized life-conduct. The authors criticizes the everyday practice suggested for management of cardiovascular diseases, focusing on normalization of cardiovascular risk factors, instead of fighting against the primary cause ie. chronic stress. There is growing evidence, that achieving the target values defined in guide-lines will not necessarily result in improvement of patient related clinical outcomes. The statistical approach generally practiced in randomized clinical trials is primarily striving for the drug-sale, instead of discovering novel pathophysiological relations. Pharmaceutical industry having decisive role in research and patient-care is mainly interested in profit-sharing, therefore patients' interest can not be optimally realized, and costs are unnecessarily augmented. Separation of patient-, and business-oriented medical care is an ethical question of fundamental importance.

  4. Cardiovascular Complications in CKD Patients: Role of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Elvira O. Gosmanova

    2011-01-01

    Full Text Available Starting with the early stages, patients with chronic kidney disease (CKD experience higher burden of cardiovascular disease (CVD. Moreover, CVD complications are the major cause of mortality in CKD patients as compared with complications from chronic kidney failure. While traditional CVD risk factors, including diabetes, hypertension, hyperlipidemia, obesity, physical inactivity, may be more prevalent among CKD patients, these factors seem to underestimate the accelerated cardiovascular disease in the CKD population. Search for additional biomarkers that could explain the enhanced CVD risk in CKD patients has gained increasing importance. Although it is unlikely that any single nontraditional risk factor would fully account for the increased CVD risk in individuals with CKD, oxidative stress appears to play a central role in the development and progression of CVD and its complications. We will review the data that support the contribution of oxidative stress in the pathogenesis of CVD in patients with chronic kidney failure.

  5. Stress in Obesity and Associated Metabolic and Cardiovascular Disorders

    Science.gov (United States)

    Holvoet, Paul

    2012-01-01

    Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity. PMID:24278677

  6. Work stress and cardiovascular disease: a life course perspective.

    Science.gov (United States)

    Li, Jian; Loerbroks, Adrian; Bosma, Hans; Angerer, Peter

    2016-05-25

    Individuals in employment experience stress at work, and numerous epidemiological studies have documented its negative health effects, particularly on cardiovascular disease (CVD). Although evidence on the various interrelationships between work stress and CVD has been accumulated, those observations have not yet been conceptualized in terms of a life course perspective. Using the chain of risk model, we would like to propose a theoretical model incorporating six steps: (1) work stress increases the risk of incident CVD in healthy workers. (2) Among those whose work ability is not fully and permanently damaged, work stress acts as a determinant of the process of return to work after CVD onset. (3) CVD patients experience higher work stress after return to work. (4) Work stress increases the risk of recurrent CVD in workers with prior CVD. (5) CVD patients who fully lose their work ability transit to disability retirement. (6) Disability retirees due to CVD have an elevated risk of CVD mortality. The life course perspective might facilitate an in-depth understanding of the diverse interrelationships between work stress and CVD, thereby leading to work stress management interventions at each period of the lifespan and three-level prevention of CVD.

  7. Adenosine Stress and Rest T1 Mapping Can Differentiate Between Ischemic, Infarcted, Remote, and Normal Myocardium Without the Need for Gadolinium Contrast Agents.

    Science.gov (United States)

    Liu, Alexander; Wijesurendra, Rohan S; Francis, Jane M; Robson, Matthew D; Neubauer, Stefan; Piechnik, Stefan K; Ferreira, Vanessa M

    2016-01-01

    The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial blood flow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] on first-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954 ± 19 ms at 1.5-T; 1,189 ± 34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2 ± 0.5% at 1.5-T; 6.3 ± 1.1% at 3.0-T; all p Infarcted myocardium showed the highest resting T1 of all tissue classes (1,442 ± 84 ms), without significant T1 reactivity (0.2 ± 1.5%). Ischemic myocardium showed elevated resting T1 compared to normal (987 ± 17 ms; p T1 reactivity (0.2 ± 0.8%). Remote myocardium, although having comparable resting T1 to normal (955 ± 17 ms; p = 0.92), showed blunted T1 reactivity (3.9 ± 0.6%; p T1 mapping at rest and

  8. Adenosine stress and rest T1 mapping can differentiate between ischemic, infarcted, remote, and normal myocardium without the need for gadolinium contrast agents.

    OpenAIRE

    Liu, Alexander; Wijesurendra, Rohan S; Francis, Jane M; Robson, Matthew D; Neubauer, Stefan; Piechnik, Stefan K; Ferreira, Vanessa M

    2015-01-01

    Objectives The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. Background In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial bloodflow. T1 mapping using cardiac magne...

  9. Cardiovascular Stress During Inpatient Spinal Cord Injury Rehabilitation.

    Science.gov (United States)

    Zbogar, Dominik; Eng, Janice J; Noble, Jeremy W; Miller, William C; Krassioukov, Andrei V; Verrier, Mary C

    2017-12-01

    (1) To measure the amount of cardiovascular stress, self-reported physical activity, and accelerometry-measured physical activity by individuals with spinal cord injury (SCI) during physical therapy (PT) and occupational therapy (OT); and (2) to investigate the relations between these measures. Observational study. Two inpatient SCI rehabilitation centers. Patients with SCI (N=87) were recruited from consecutive admissions to rehabilitation. Not applicable. Heart rate was recorded by a Holter monitor, whereas physical activity was captured by self-report (Physical Activity Recall Assessment for People with SCI questionnaire) and real-time wrist accelerometry during a total of 334 PT and OT inpatient sessions. Differences between individuals with paraplegia and tetraplegia were assessed via Mann-Whitney U tests. Spearman correlations were used to explore the relation between measurements of physical activity and heart rate. Time spent at a heart rate within a cardiovascular training zone (≥40% heart rate reserve) was low and did not exceed a median of 5 minutes. In contrast, individuals reported at least 60 minutes of higher-intensity time during therapy. There was a low but statistically significant correlation between all measures. The cardiovascular stress incurred by individuals with SCI during inpatient PT and OT sessions is low and not sufficient to obtain a cardiovascular training effect to optimize their neurologic, cardiovascular, or musculoskeletal health; this represents a lost opportunity to maximize rehabilitation. Self-reported minutes of higher-intensity physical activity do not reflect actual time spent at a higher intensity measured objectively via a heart rate monitor. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. Cardiovascular risk factors and life and occupational stress among policemen

    Directory of Open Access Journals (Sweden)

    Izabela Czaja-Mitura

    2013-06-01

    Full Text Available Background: Several studies have shown an association between work-related stress and risk factors for cardiovascular disease. However, only a few studies concerned the police. The aim of this study was to assess the relationship between the general and work-related stress, and the functioning of the circulatory system in the police staff. Material and Methods: The study group consisted of 126 policemen (aged 37.8±7.3 years, with average employment duration of 14.4±7 years. The study comprised the assessment of health status based on the medical examination and medical history of identified diseases, cardiovascular risk factors and symptoms, dietary habits, physical activity, intake of drugs, data on the family history, determinations of serum total cholesterol, HDL and LDL fractions, triglycerides, and fasting glycemia. The stress level was assessed using the Questionnaire for the Subjective Assessment of Work and Perceived Stress Scale. Results: On medical examination hypertension was found in 36% of the people under study. Chest discomfort was reported by 60% of the subjects. Average body mass index (BMI, serum cholesterol and LDL were elevated (22.7±4.1, 222.6±41.7 mg/dl and 142.7±39.7 mg/dl, respectively. Mean triglyceride, HDL fraction and fasting glucose levels were normal in the whole group. The levels of general and occupational stress were 34.9±4.8 and 128.0±33.3, respectively, being higher than in other occupational groups. In the group with the highest level of stress, there were significantly more people with circulatory problems (81%, drinking strong alcohol at least once a week (27%, working in a 3-shift system (40.5% and working overtime (44%. Conclusions: The results show that the police are a group at high risk of developing cardiovascular diseases due to work-related stress. Med Pr 2013;64(3:335–348

  11. [Perceived stress and cardiovascular disease mortality. The Ohsaki Cohort Study].

    Science.gov (United States)

    Kowata, Emi; Hozawa, Atsushi; Kakizaki, Masako; Tomata, Yasutake; Nagai, Masato; Sugawara, Yumi; Kuriyama, Shinichi; Tsuji, Ichiro

    2012-02-01

    Previous studies have indicated that stress can affect the circulatory system. Although prospective studies have examined the association between perceived stress and cardiovascular disease (CVD) mortality, the results are still controversial. The purpose of the present study was to elucidate the relationship with stratified analyses by alcohol intake category and smoking status. The prospective Ohsaki Cohort Study covered all National Health Insurance beneficiaries aged 40 to 79 years living in the precinct of Ohsaki Public Health Center, Miyagi, Japan. A total of 45,293 Japanese (21,552 men and 23,741 women), without a history of cancer, ischemic heart disease or stroke, and who answered all items related to stress level at the baseline in 1994, were followed prospectively. Over 12 years of follow-up, 1,751 deaths from CVD occurred (994 men and 757 women). We used Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for CVD mortality according to the perceived stress categories. The low stress category was used as the reference in all analyses. Perceived stress demonstrated a significant positive association with CVD mortality for men; the multivariate adjusted HR for high versus low stress was 1.43 (95% CI: 1.19, 1.87, P = 0.006). No significant relationship was noted for women. With current smokers, perceived high stress versus low had a pronounced association for both men (HR = 1.76, 95% CI: 1.28, 2.41, P = 0.001) and women (HR = 1.61, 95% CI: 1.20, 2.16, P = 0.004), and a similar tendency was noted for current drinking (HR = 1.56, 95% CI: 1.16, 2.09, P = 0.006, HR = 1.42, 95% CI: 1.08, 1.87, P = 0.001). Additionally, for both smoking and drinking men, those reporting high stress had 2 times the risk of CVD mortality of their low stress counterparts (P for trend stress with smoking for CVD mortality was of borderline statistical significance only for men (P for interaction = 0.04). The results suggest that the

  12. Work Stress as a Risk Factor for Cardiovascular Disease.

    Science.gov (United States)

    Kivimäki, Mika; Kawachi, Ichiro

    2015-09-01

    The role of psychosocial work stress as a risk factor for chronic disease has been the subject of considerable debate. Many researchers argue in support of a causal connection while others remain skeptical and have argued that the effect on specific health conditions is either negligible or confounded. This review of evidence from over 600,000 men and women from 27 cohort studies in Europe, the USA and Japan suggests that work stressors, such as job strain and long working hours, are associated with a moderately elevated risk of incident coronary heart disease and stroke. The excess risk for exposed individuals is 10-40 % compared with those free of such stressors. Differences between men and women, younger versus older employees and workers from different socioeconomic backgrounds appear to be small, indicating that the association is robust. Meta-analyses of a wider range of health outcomes show additionally an association between work stress and type 2 diabetes, though not with common cancers or chronic obstructive pulmonary disease, suggesting outcome specificity. Few studies have addressed whether mitigation of work stressors would reduce the risk of cardiovascular disease. In view of the limited interventional evidence on benefits, harms and cost-effectiveness, definitive recommendations have not been made (e.g. by the US Preventive Services Taskforce) for the primary prevention of cardiovascular disease via workplace stress reduction. Nevertheless, governments are already launching healthy workplace campaigns, and preventing excessive work stress is a legal obligation in several countries. Promoting awareness of the link between stress and health among both employers and workers is an important component of workplace health promotion.

  13. Diagnostic accuracy of combined coronary angiography and adenosine stress myocardial perfusion imaging using 320-detector computed tomography: pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Nasis, Arthur; Ko, Brian S.; Leung, Michael C.; Antonis, Paul R.; Wong, Dennis T.; Kyi, Leo; Cameron, James D.; Meredith, Ian T.; Seneviratne, Sujith K. [Southern Health and Monash University, Monash Cardiovascular Research Centre, Monash Heart, Department of Medicine Monash Medical Centre (MMC), Melbourne (Australia); Nandurkar, Dee; Troupis, John M. [MMC, Southern Health, Department of Diagnostic Imaging, Melbourne (Australia)

    2013-07-15

    To determine the diagnostic accuracy of combined 320-detector row computed tomography coronary angiography (CTA) and adenosine stress CT myocardial perfusion imaging (CTP) in detecting perfusion abnormalities caused by obstructive coronary artery disease (CAD). Twenty patients with suspected CAD who underwent initial investigation with single-photon-emission computed tomography myocardial perfusion imaging (SPECT-MPI) were recruited and underwent prospectively-gated 320-detector CTA/CTP and invasive angiography. Two blinded cardiologists evaluated invasive angiography images quantitatively (QCA). A blinded nuclear physician analysed SPECT-MPI images for fixed and reversible perfusion defects. Two blinded cardiologists assessed CTA/CTP studies qualitatively. Vessels/territories with both >50 % stenosis on QCA and corresponding perfusion defect on SPECT-MPI were defined as ischaemic and formed the reference standard. All patients completed the CTA/CTP protocol with diagnostic image quality. Of 60 vessels/territories, 17 (28 %) were ischaemic according to QCA/SPECT-MPI criteria. Sensitivity, specificity, PPV, NPV and area under the ROC curve for CTA/CTP was 94 %, 98 %, 94 %, 98 % and 0.96 (P < 0.001) on a per-vessel/territory basis. Mean CTA/CTP radiation dose was 9.2 {+-} 7.4 mSv compared with 13.2 {+-} 2.2 mSv for SPECT-MPI (P < 0.001). Combined 320-detector CTA/CTP is accurate in identifying obstructive CAD causing perfusion abnormalities compared with combined QCA/SPECT-MPI, achieved with lower radiation dose than SPECT-MPI. (orig.)

  14. Comparison of the prognostic value of regadenoson and adenosine myocardial perfusion imaging.

    Science.gov (United States)

    Farzaneh-Far, Afshin; Shaw, Linda K; Dunning, Allison; Oldan, Jorge D; O'Connor, Christopher M; Borges-Neto, Salvador

    2015-08-01

    Regadenoson is now widely used in single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). However, the prognostic value of abnormal stress perfusion findings with regadenoson vs adenosine are unclear. The aim of this study was to evaluate the prognostic value of regadenoson SPECT and to compare it to that of adenosine SPECT. 3698 consecutive patients undergoing either adenosine or regadenoson SPECT were assessed at 1 year for the endpoints of cardiovascular death and a composite endpoint of cardiovascular death or MI. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for agent was used to account for differences in baseline characteristics. Patients undergoing adenosine SPECT MPI had a significantly higher prevalence of smoking history, diabetes, hypertension, and prior myocardial infarction (P regadenoson SPECT MPI is a significant predictor of events and provides incremental prognostic information beyond basic clinical variables. We have shown for the first time that use of regadenoson vs adenosine as stress agent does not modify the prognostic significance of SSS. Similar findings were seen with SDS.

  15. Sleep restriction undermines cardiovascular adaptation during stress, contingent on emotional stability.

    Science.gov (United States)

    Lü, Wei; Hughes, Brian M; Howard, Siobhán; James, Jack E

    2017-12-12

    Sleep loss is associated with increased cardiovascular disease, but physiological mechanisms accounting for this relationship are largely unknown. One possible mechanism is that sleep restriction exerts effects on cardiovascular stress responses, and that these effects vary between individuals. Emotional stability (ES) is a personality trait pertinent to sleep restriction and stress responding. However, no study to date has explored how ES and sleep-restriction interactively affect cardiovascular stress responses or processes of adaptation during stress. The present study sought to investigate the association between ES and impact of sleep restriction on cardiovascular function during stress, with particular regard to the trajectory of cardiovascular function change across time. Ninety female university students completed a laboratory vigilance stress task while undergoing continuous cardiovascular (SBP, DBP, HR, SV, CO, TPR) monitoring, after either a night of partial sleep restriction (40% of habitual sleep duration) or a full night's rest. Individuals high in ES showed stable and adaptive cardiovascular (SBP, SV, CO) responses throughout stress exposure, regardless of sleep. In contrast, individuals low in ES exhibited cardiovascular adaptation during stress exposure while rested, but disrupted adaption while sleep-restricted. These findings suggest that sleep-restriction undermines healthful cardiovascular adaptation to stress for individuals low in ES. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Risks of cardiovascular diseases evolvement and occupational stress

    Directory of Open Access Journals (Sweden)

    Z.F. Gimaeva

    2017-03-01

    Full Text Available Our aim was to study how significant psychosocial factors are in occupational stress and cardiovascular diseases evolvement in workers employed at petrochemical production; we also intended to work out a set of preventive measures. Our hygienic and social-psychological research enabled us to detect factors causing stress evolvement in workers employed at petrochemical production. These factors included chemical impact, noise, unfavorable microclimate, labor hardness and labor intensity. High level of risk for their own lives and responsibility for safety of others, as well as work under time deficiency conditions with increased responsibility for the final results, were the most significant psychosocial factors for workers. In the course of questioning we detected that 74 % machine operators, 63 % tool men working with controllers and automatic devices, and 57 % repairmen mentioned having stress at work. Here 38 % workers gave a subjective estimation of their professional activity as having apparent "stress nature". The questioning revealed that 48 % workers with various occupations had increased parameters as per anxiety scale (HADS; 23 % workers had increased parameters as per depressions scale (HADS. Primary hypertension was the most widely spread nosologic form among chronic non-infectious diseases; it was found in 46.1 % operators and in 45.2 % repairmen dealing with processing stations repair. 30.1 % tool men working with controllers and automatic devices had average occupational causation of primary hypertension by production factors. We detected direct relation between hyperlipidemia and age and working period. We created foundation for preventive measures and worked out a program aimed at increasing resistance to stress at corporate and individual level. It will provide significant social effect and later on economic one. To overcome social stress we need to create safe working conditions at workplaces and to increase labor motivation

  17. Social identity influences stress appraisals and cardiovascular reactions to acute stress exposure.

    Science.gov (United States)

    Gallagher, Stephen; Meaney, Sarah; Muldoon, Orla T

    2014-09-01

    This study tested a recent theoretical development in stress research to see whether group membership influenced cardiovascular reactions following exposure to acute stress. Participants (N = 104) were exposed to a message in which a maths test was described as stressful or challenging by an ingroup member (a student) or outgroup member (a stress disorder sufferer). Systolic blood pressure and diastolic blood pressure(DBP) and heart rate (HR) were monitored throughout a standard reactivity study. As expected, a significant interaction was found; relative to those who were told that the task was challenging, ingroup members reported more stress and had higher DBP and HR reactivity when told by an ingroup member that the maths task was stressful; task information did not have the same effect for outgroup members. These results indicate that informational support is not constant but varies as a function of group membership. Finally, this recent development in stress research may prove useful for those interested in investigating the interactions between social, psychological and physiological processes underlying health disparities. What is already known on this subject? Stress is a common risk factor for hypertension and coronary heart disease. Social support has been found to reduce cardiovascular reactions to acute psychological stress. The influence of social support on stress varies as a consequence of social identity. What does this study add? The social group that one belongs to influences how one appraises and responds to stress. Social identity provides a useful framework for understanding how social processes are associated with health disparities. © 2013 The British Psychological Society.

  18. Chronic stress impacts the cardiovascular system: animal models and clinical outcomes.

    Science.gov (United States)

    Golbidi, Saeid; Frisbee, Jefferson C; Laher, Ismail

    2015-06-15

    Psychological stresses are associated with cardiovascular diseases to the extent that cardiovascular diseases are among the most important group of psychosomatic diseases. The longstanding association between stress and cardiovascular disease exists despite a large ambiguity about the underlying mechanisms. An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies. Copyright © 2015 the American Physiological Society.

  19. Adenosine-stress low-dose single-scan CT myocardial perfusion imaging using a 128-slice dual-source CT: a comparison with fractional flow reserve.

    Science.gov (United States)

    Choo, Ki Seok; Hwangbo, Lee; Kim, June Hong; Park, Yong Hyun; Kim, Jeong Su; Kim, Jun; Chun, Kook Jin; Jeong, Dong Wook; Lim, Soo Jin

    2013-05-01

    Coronary CT angiography (CCTA) allows accurate evaluation of coronary artery stenosis but has limitations in information on hemodynamic significance of stenotic lesions. To determine the feasibility of adenosine-stress low-dose single-scan CT myocardial perfusion imaging (MPI) using a 128-slice dual-source CT scanner for the diagnosis of hemodynamically significant coronary artery stenosis as defined by fractional flow reserve (FFR). This study was proved by the Institutional Review Board and informed consent was obtained from the patients before enrollment in the study. Ninety-seven patients with chest pain and low-to-intermediate pretest probability of coronary artery disease were prospectively enrolled. Adenosine-stress CCTA using ECG-correlated maximum tube current modulation (Mindose(®)) with 128-slice dual-source CT was performed in all 97 patients. In 37 patients (38.1%; 28 men, nine women; mean age, 61.7 ± 20.5 years; mean heart rate, 74.6 ± 2.8 bpm) with significant stenosis at CCTA (lumen diameter reduction >50%), FFR was performed after CCTA, as a reference standard for the evaluation of myocardial perfusion. FFR value ≤0.75 was considered as positive. CTMPI and CCTA were read by two experienced radiologists with consensus, respectively. The effective radiation dose of adenosine-stress single-scan CTMPI was 4.63 ± 2.57 mSv. Compared with FFR, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying significant coronary stenoses were 93.1%, 82.7%, 75.0%, and 95.6%, respectively, on CCTA and 93.1%, 90.3%, 84.4%, and 95.9%, respectively, on CTMPI. On combined CCTA and CTMPI, sensitivity, specificity, PPV, and NPV were 93.1%, 94.2%, 90.0%, and 96.0%, respectively. Adenosine-stress low-dose single scan CTMPI using a 128-slice dual-source CT can provide complementary information on the hemodynamical significance of coronary artery stenosis as well as anatomical information of coronary arteries.

  20. Occupational status and job stress in relation to cardiovascular stress reactivity in Japanese workers

    Directory of Open Access Journals (Sweden)

    Kumi Hirokawa

    2016-12-01

    Full Text Available This study aimed to investigate the effects of occupational status and job stress factors on cardiovascular stress reactivity in Japanese workers. In this baseline assessment between 2001 and 2009 in Osaka, Japan, we examined 928 healthy Japanese employees (330 men, 598 women from two occupational statuses: managers/professionals and general workers. A brief job stress questionnaire was used to evaluate job stress levels. Systolic and diastolic blood pressure (SBP, DBP, heart rate, heart rate variability (high-frequency [HF], low-frequency [LF], LF/HF], and peripheral blood flow were measured at rest and during two stressful tasks. Changes in stress reactivity were calculated as the difference between the measured variables during the tasks and the rest period. Men showed inverse associations between quantitative job overload and DBP, heart rate, and LF/HF, between physical demands and blood pressure (SBP, DBP, and between a poor physical environment and HF. Men also had positive associations between qualitative job overload and heart rate, and between physical demands and peripheral blood flow (all p < 0.05. Women showed inverse associations between qualitative job overload and SBP, and showed positive associations between qualitative job overload and peripheral blood flow, and between a poor physical environment and SBP (all p < 0.05. When stratified by occupational status, significant associations between job stress and changes in stress reactivity were observed in male managers/professionals and female general workers (p < 0.05. Job stress levels are associated with changes in cardiovascular stress reactivity in men and women. Occupational status may modify these associations.

  1. Long-term moderate exercise accelerates the recovery of stress-evoked cardiovascular responses.

    Science.gov (United States)

    Hsu, Yuan-Chang; Tsai, Sheng-Feng; Yu, Lung; Chuang, Jih-Ing; Wu, Fong-Sen; Jen, Chauying J; Kuo, Yu-Min

    2016-01-01

    Psychological stress is an important global health problem. It is well documented that stress increases the incidences of various cardiovascular disorders. Regular exercise is known to reduce resting blood pressure (BP) and heart rate (HR). This study was designed to clarify the effects of long-term exercise on stress-evoked cardiovascular responses and to emphasize post-stress recovery effects. Male Wistar rats underwent 8 weeks of moderate treadmill training, with cardiovascular responses, autonomic nervous system activities and local Fos reactivity changes in the cardiovascular regulation center were monitored before, during and after immobilization stress. A spectral analysis of cardiovascular parameters was used to examine autonomic nervous activities. We found that long-term exercise (i) lowered resting BP, HR and sympathetic activity, but increased resting parasympathetic activity and baroreflex sensitivity (BRS); (ii) accelerated post-stress recovery of stress-evoked cardiovascular and sympathetic responses along with increased BRS and (iii) accelerated post-stress recovery of stress-evoked neuron activations in the paraventricular nucleus, but delayed it in the nucleus of the tractus solitarius. We conclude that, in rats, long-term exercise accelerated recovery of stress-evoked cardiovascular responses differentially altering hypothalamic and medullar neuron activities.

  2. Myocardial perfusion imaging laboratory efficiency with the use of regadenoson compared to adenosine and dipyridamole.

    Science.gov (United States)

    Friedman, Michelle; Spalding, James; Kothari, Smita; Wu, You; Gatt, Elyse; Boulanger, Luke

    2013-01-01

    Adenosine, dipyridamole, and regadenoson are pharmacologic stress agents used in myocardial perfusion imaging (MPI), to diagnose and monitor coronary artery disease. Clinical studies suggest that regadenoson has pharmacologic properties that simplify the MPI procedure through availability to a wider range of patients and easier administrative requirements. This study assesses the operational advantages and laboratory efficiency associated with the use of regadenoson compared to adenosine and dipyridamole. A web-based survey of 141 nuclear medicine technologists working in US-based cardiovascular imaging laboratories from June-July 2009. Descriptive statistics measured the adenosine, dipyridamole, and regadenoson cohorts. Bivariate analyses compared the overall and staff-specific time to conduct an MPI test. The site-specific sub-groups were defined by hospital vs non-hospital setting, hours of operation, number of SPECT cameras, and number of full-time equivalent staff, including nurses, nuclear technologists, physicians, and nurse practitioners/physician assistants. The total time to conduct an MPI test was shortest with regadenoson 156 (46) min compared to adenosine and dipyridamole 182 (63) and 191 (61) min, respectively. Time from regadenoson administration to the start of the imaging session, including dose calculation and infusion time, was 14.2 min less than adenosine, and 12.0 min less than dipyridamole. The time to manage adverse events was shortest if it occurred with regadenoson compared to adenosine and dipyridamole, with minor exceptions. Due to the nature of survey implementation, possible recall bias may limit the results. Some differences in procedures times may be attributable to differences in laboratories' protocols. Overall time savings and time savings stratified by operational ability (number of staff, number of SPECT cameras, hours of operation) translate to a more efficient utilization of laboratory resources when using regadenoson

  3. Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: a possible role for plasticity in adenosine receptors

    Science.gov (United States)

    Clark, Peter J.; Ghasem, Parsa R.; Mika, Agnieszka; Day, Heidi E.; Herrera, Jonathan J.; Greenwood, Benjamin N.; Fleshner, Monika

    2014-01-01

    Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was two-fold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance. PMID:25017571

  4. Nuclear stress test

    Science.gov (United States)

    ... Persantine stress test; Thallium stress test; Stress test - nuclear; Adenosine stress test; Regadenoson stress test; CAD - nuclear stress; Coronary artery disease - nuclear stress; Angina - nuclear ...

  5. Perceived stress correlates with disturbed sleep: a link connecting stress and cardiovascular disease.

    Science.gov (United States)

    Kashani, Mariam; Eliasson, Arn; Vernalis, Marina

    2012-01-01

    The association between stress and cardiovascular disease (CVD) risk is becoming established. A mechanistic link clarifying the intermediate steps between the experience of stress and the development of CVD would support this association. We sought to examine the role of perceived stress as a factor associated with disturbed sleep with the goal of providing an explanation for the stress-CVD connection. We performed a cross-sectional analysis of data recorded by subjects at entry to our CVD prevention program. Data collection included questionnaire surveys, anthropometrics, and a CVD-relevant laboratory panel. Of 350 consecutively enrolled subjects (mean age 54.4 ± 12.4 [SD] years, 138 men, 39%), 165 (47%) scored above the mean for stress measures. These high-stress subjects displayed an increased cardiovascular risk profile including elevated body mass index (mean ± SD 31.1 ± 5.9 vs. 29.0 ± 5.9, r(s) = 0.175), increased waist circumference (102 ± 17 cm vs. 98 ± 14, r(s) = 0.135), and elevated high-sensitivity serum C-reactive protein (0.384 mg/dl vs. 0.356, r(s) = 0.109). High-stress subjects also demonstrated greater daytime sleepiness (Epworth Sleepiness Scale: 10.4 ± 5.0 vs. 7.8 ± 4.8, r(s) sleep quality (Pittsburgh Sleep Quality Index: 8.5 ± 4.4 vs. 5.9 ± 4.0, r(s) = 0.416), and shorter sleep duration (20 min less/24 h, r(s) = negative 0.177) with a higher risk for sleep apnea (60% at high risk vs. 40%, p = 0.003) than low-stress subjects. High stress was associated with significant disturbances in sleep duration and sleep quality. Stress levels also correlated with daytime consequences of disturbed sleep. The stress-sleep connection may be an important mechanistic mediator of the association between stress and CVD.

  6. The effects of chronic candesartan treatment on cardiac and hepatic adenosine monophosphate-activated protein kinase in rats submitted to surgical stress.

    Science.gov (United States)

    Ribeiro-Oliveira, Antônio; Marques, Mirna B; Vilas-Boas, Walkiria W; Guimarães, Jonas; Coimbra, Cândido C; Anjos, Allan P; Fóscolo, Rodrigo B; Santos, Robson; Thomas, Julia D; Igreja, Suzana M; Kola, Blerina; Grossman, Ashley B; Korbonits, Márta

    2015-09-01

    adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor, and it has recently been suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating the AMPK system. This study aimed to evaluate the effects of candesartan, an angiotensin II receptor blocker, on cardiac and hepatic AMPK activity basally as well as after surgical stress under general anesthesia. Male Wistar rats were treated with 5 mg/kg/day candesartan in their drinking water for two weeks. Levels of cardiac and hepatic AMPK activity were determined, using a kinase activity assay, basally and after surgical stress under general anesthesia. Chronic administration of candesartan increased hepatic AMPK activity approximately 4 times (pcandesartan decreased AMPK activity in both liver and heart after surgical stress under anesthesia (pcandesartan treatment may stimulate AMPK activity in certain organs such as the liver, when combined with surgical stress under anesthesia it inhibits pathways regulating AMPK activity. © The Author(s) 2013.

  7. A comparative study of cardiovascular stress during different swimming strokes.

    Science.gov (United States)

    Gupta, S; Goswami, A

    2001-04-01

    The study was aimed: (i) to compare maximum heart rate during exhaustive running (HRmasr) and swimming (HRmaxs), (ii) to compare heart rate (HR) in various modes of swimming-front crawl (FC), butterfly (BF), breast stroke (BRS) and back stroke (BS). HRmaxr (192.3 +/- 4.9 beats/min) of the swimmers (N = 7) was higher, although not significantly (P < 0.05), than their HRmaxs (183.7 +/- 3.8). Peak HR of the swimmers in FC, BF, BRS and BS (each of 100 m distance) were 179.9 +/- 7.2, 180.3 +/- 7, 178.6 +/- 6.2 and 177.3 +/- 5.4 beats/min respectively. Average HR in the respective events were 167.3 +/- 15.8, 166.6 +/- 14.1, 163.3 +/- 13.5 and 165.8 +/- 14.6 beats/min. Differences were not significant between any two modes, either in peak HR or mean HR. The results conclude that: (i) maximum HR in swimming is approximately 8 beats/min lower than maximal running and (ii) when the effort is maximum, cardiovascular stress remains unaltered in different swimming modes.

  8. [Cardiovascular resistance to orthostatic stress in athletes after aerobic exercise].

    Science.gov (United States)

    Mel'nikov, A A; Popov, S G; Vikulov, A D

    2014-01-01

    In the paper cardiovascular resistance to orthostatic stress in the athletes in the two-hour recovery period after prolonged aerobic exercise was investigated. The reaction of the cardiac (stroke volume and cardiac output) and peripheral blood volumes in the lower and upper limbs, abdominal and neck regions in response to the tilt-test before and during two hours after exercise (30 min, heart rate = 156 +/- 8 beats/min) was determined by impedance method: It is found that: (1) at baseline distribution of blood flow in favor of the neck-region in response to the tilt-test, in spite of the decrease in cardiac output, was more efficient in athletes, that was due to a large decrease in blood flow to the lower extremities, and increased blood flow in the neck region; (2) after exercise it was established symptoms of potential orthostatic intolerance: postural hypotension and tachycardia, reduced peripheral pulse blood volume, expressed in a standing position, and reduced effectiveness of the distribution of blood flow in the direction of the neck region; (3) the abilityto effectively distribute blood flow in favor of the neck region in athletes after exercise remained elevated, which was due to a large decrease in blood flow in the abdominal region at the beginning, and in the lower limbs at the end of the recovery period.

  9. Adenosine-stress dynamic myocardial perfusion imaging with second-generation dual-source CT: comparison with conventional catheter coronary angiography and SPECT nuclear myocardial perfusion imaging.

    Science.gov (United States)

    Wang, Yining; Qin, Ling; Shi, Ximin; Zeng, Yong; Jing, Hongli; Schoepf, U Joseph; Jin, Zhengyu

    2012-03-01

    The purpose of this article is to evaluate the feasibility of adenosine-stress dynamic myocardial perfusion imaging (MPI) with 128-MDCT dual-source CT for detecting myocardial ischemia in comparison with conventional catheter coronary angiography and nuclear MPI. Thirty patients (21 men and nine women; mean [± SD] age, 59.2 ± 7.6 years) prospectively underwent a combined stress CT perfusion and CT angiography (CTA) examination. Complete time-attenuation curves of the myocardium were acquired with prospectively ECG-triggered axial images at two alternating positions. Myocardial blood flow (MBF) was quantified according to dynamic CT perfusion, and MBF values of normal and abnormal segments were compared. Findings on CT perfusion were compared with those for stress and rest SPECT. Perfusion defects according to CT were correlated to flow-obstructing stenosis detected on CTA and catheter coronary angiography. On stress CT perfusion, 19 patients (63%) and 83 of 504 segments (16%) had perfusion abnormalities. There was a significant difference in MBF values between normal (142.9 ± 30.6 mL/100 mL/min) and hypoperfused (90.0 ± 22.8 mL/100 mL/min) segments (p stress CT perfusion detects myocardial perfusion defects in good correlation with nuclear MPI. CT perfusion combined with CTA improves the diagnostic accuracy for identifying flow-obstructing stenosis compared with CTA alone.

  10. Individual differences in the locus coeruleus-norepinephrine system: Relevance to stress-induced cardiovascular vulnerability.

    Science.gov (United States)

    Wood, Christopher S; Valentino, Rita J; Wood, Susan K

    2017-04-01

    Repeated exposure to psychosocial stress is a robust sympathomimetic stressor and as such has adverse effects on cardiovascular health. While the neurocircuitry involved remains unclear, the physiological and anatomical characteristics of the locus coeruleus (LC)-norepinephrine (NE) system suggest that it is poised to contribute to stress-induced cardiovascular vulnerability. A major theme throughout is to review studies that shed light on the role that the LC may play in individual differences in vulnerability to social stress-induced cardiovascular dysfunction. Recent findings are discussed that support a unique plasticity in afferent regulation of the LC, resulting in either excitatory or inhibitory input to the LC during establishment of different stress coping strategies. This contrasting regulation of the LC by either afferent regulation, or distinct differences in stress-induced neuroinflammation would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The goal of this review is to highlight recent developments in the interplay between the LC-NE and cardiovascular systems during repeated stress in an effort to advance therapeutic treatments for the development of stress-induced cardiovascular vulnerability. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Cardiovascular disease-induced thermal responses during passive heat stress: an integrated computational study.

    Science.gov (United States)

    Zhang, Xiancheng; Noda, Shigeho; Himeno, Ryutaro; Liu, Hao

    2016-11-01

    The cardiovascular system plays a crucial role in human thermoregulation; cardiovascular diseases may lead to significantly degrading the thermoregulation ability for patients during exposure to heat stress. To evaluate the thermal responses of patients with common chronic cardiovascular diseases, we here propose an integrated computational model by coupling a two-node thermoregulation model with a closed-loop, multi-compartment, lumped-parameter cardiovascular model. This bioheat transfer model is validated, capable to predict cardiovascular functions and thermal responses under varying environmental conditions. Our results demonstrate that the cardiovascular disease-induced reduction in cardiac output and skin blood flow causes extra elevation in core temperature during hyperthermic challenges. In addition, a combination of aging, obesity, and cardiovascular diseases shows a pronounced increase in core temperature during heat exposure, which implies that such combined effect may increase the risk of heat-related morbidity and mortality. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. The role of affect and rumination in cardiovascular recovery from stress

    NARCIS (Netherlands)

    Radstaak, M.; Geurts, S.A.E.; Brosschot, J.F.; Cillessen, A.H.N.; Kompier, M.A.J.

    2011-01-01

    This study examined the psychological processes that may impede or facilitate cardiovascular recovery. It was hypothesized that cardiovascular recovery would be hampered by negative affect and rumination, and facilitated by positive affect. In an experimental study, stress was elicited by exposing

  13. Metabolic and cardiovascular adjustments during psychological stress and carotid artery intima-media thickness in youth

    Science.gov (United States)

    Objective: Cardiovascular reactivity is associated with carotid artery intima-media thickness as early as childhood. Excess cardiovascular responses relative to the metabolic demand during psychological stress have been proposed as a mechanism for this association. It is not known whether measure...

  14. Work stress and risk of cardiovascular mortality: prospective cohort study of industrial employees

    National Research Council Canada - National Science Library

    Kivimäki, Mika; Leino-Arjas, Päivi; Luukkonen, Ritva; Riihimäi, Hilkka; Vahtera, Jussi; Kirjonen, Juhani

    2002-01-01

    Abstract Objective: To examine the association between work stress, according to the job strain model and the effort-reward imbalance model, and the risk of death from cardiovascular disease. Design...

  15. Physical versus psychological social stress in male rats reveals distinct cardiovascular, inflammatory and behavioral consequences.

    Science.gov (United States)

    Finnell, Julie E; Lombard, Calliandra M; Padi, Akhila R; Moffitt, Casey M; Wilson, L Britt; Wood, Christopher S; Wood, Susan K

    2017-01-01

    Repeated exposure to social stress can precipitate the development of psychosocial disorders including depression and comorbid cardiovascular disease. While a major component of social stress often encompasses physical interactions, purely psychological stressors (i.e. witnessing a traumatic event) also fall under the scope of social stress. The current study determined whether the acute stress response and susceptibility to stress-related consequences differed based on whether the stressor consisted of physical versus purely psychological social stress. Using a modified resident-intruder paradigm, male rats were either directly exposed to repeated social defeat stress (intruder) or witnessed a male rat being defeated. Cardiovascular parameters, behavioral anhedonia, and inflammatory cytokines in plasma and the stress-sensitive locus coeruleus were compared between intruder, witness, and control rats. Surprisingly intruders and witnesses exhibited nearly identical increases in mean arterial pressure and heart rate during acute and repeated stress exposures, yet only intruders exhibited stress-induced arrhythmias. Furthermore, re-exposure to the stress environment in the absence of the resident produced robust pressor and tachycardic responses in both stress conditions indicating the robust and enduring nature of social stress. In contrast, the long-term consequences of these stressors were distinct. Intruders were characterized by enhanced inflammatory sensitivity in plasma, while witnesses were characterized by the emergence of depressive-like anhedonia, transient increases in systolic blood pressure and plasma levels of tissue inhibitor of metalloproteinase. The current study highlights that while the acute cardiovascular responses to stress were identical between intruders and witnesses, these stressors produced distinct differences in the enduring consequences to stress, suggesting that witness stress may be more likely to produce long-term cardiovascular

  16. Construction of deletion mutants in the phosphotransferase transport system and adenosine triphosphate-binding cassette transporters in Listeria monocytogenes and analysis of their growth under different stress conditions

    Directory of Open Access Journals (Sweden)

    Marina Ceruso

    2013-10-01

    Full Text Available Functional genomics approaches enable us to investigate the biochemical, cellular, and physiological properties of each gene product and are nowadays applied to enhance food safety by understanding microbial stress responses in food and host-pathogen interactions. Listeria monocytogenes is a food-borne pathogen that causes listeriosis and is difficult to eliminate this pathogen since it can survive under multiple stress conditions such as low pH and low temperature. Detailed studies are needed to determine its mode of action and to understand the mechanisms that protect the pathogen when it is subjected to stress. In this study, deletion mutants of phosphotransferase transport system genes (PTS and adenosine triphosphate(ATP-binding cassette transporters (ABC of Listeria monocytogenes F2365 were created using molecular techniques. These mutants and the wild-type were tested under different stress conditions, such as in solutions with different NaCl concentration, pH value and for nisin resistance. Results demonstrate that the behaviour of these deletion mutants is different from the wild type. In particular, deleted genes may be involved in L. monocytogenes resistance to nisin and to acid and salt concentrations. Functional genomics research on L. monocytogenes allows a better understanding of the genes related to stress responses and this knowledge may help in intervention strategies to control this food-borne pathogen. Furthermore, specific gene markers can be used to identify and subtype L. monocytogenes. Thus, future development of this study will focus on additional functional analyses of important stress response-related genes, as well as on methods for rapid and sensitive detection of L. monocytogenes such as using DNA microarrays.

  17. Neuroinflammation at the interface of depression and cardiovascular disease: Evidence from rodent models of social stress

    Directory of Open Access Journals (Sweden)

    Julie E. Finnell

    2016-10-01

    Full Text Available A large body of evidence has emerged linking stressful experiences, particularly from one's social environment, with psychiatric disorders. However, vast individual differences emerge in susceptibility to developing stress-related pathology which may be due to distinct differences in the inflammatory response to social stress. Furthermore, depression is an independent risk factor for cardiovascular disease, another inflammatory-related disease, and results in increased mortality in depressed patients. This review is focused on discussing evidence for stress exposure resulting in persistent or sensitized inflammation in one individual while this response is lacking in others. Particular focus will be directed towards reviewing the literature underlying the impact that neuroinflammation has on neurotransmitters and neuropeptides that could be involved in the pathogenesis of comorbid depression and cardiovascular disease. Finally, the theme throughout the review will be to explore the notion that stress-induced inflammation is a key player in the high rate of comorbidity between psychosocial disorders and cardiovascular disease.

  18. Dobutamine stress cardiovascular magnetic resonance at 3 Tesla

    Directory of Open Access Journals (Sweden)

    Klein C

    2008-10-01

    Full Text Available Abstract Purpose The assessment of inducible wall motion abnormalities during high-dose dobutamine-stress cardiovascular magnetic resonance (DCMR is well established for the identification of myocardial ischemia at 1.5 Tesla. Its feasibility at higher field strengths has not been reported. The present study was performed to prospectively determine the feasibility and diagnostic accuracy of DCMR at 3 Tesla for depicting hemodynamically significant coronary artery stenosis (≥ 50% diameter stenosis in patients with suspected or known coronary artery disease (CAD. Materials and methods Thirty consecutive patients (6 women (66 ± 9.3 years were scheduled for DCMR between January and May 2007 for detection of coronary artery disease. Patients were examined with a Philips Achieva 3 Tesla system (Philips Healthcare, Best, The Netherlands, using a spoiled gradient echo cine sequence. Technical parameters were: spatial resolution 2 × 2 × 8 mm3, 30 heart phases, spoiled gradient echo TR/TE: 4.5/2.6 msec, flip angle 15°. Images were acquired at rest and stress in accordance with a standardized high-dose dobutamine-atropine protocol during short breath-holds in three short and three long-axis views. Dobutamine was administered using a standard protocol (10 μg increments every 3 minutes up to 40 μg dobutamine/kg body weight/minute plus atropine if required to reach target heart rate. The study protocol included administration of 0.1 mmol/kg/body weight Gd-DTPA before the cine images at rest were acquired to improve the image quality. The examination was terminated if new or worsening wall-motion abnormalities or chest pain occurred or when > 85% of age-predicted maximum heart rate was reached. Myocardial ischemia was defined as new onset of wall-motion abnormality in at least one segment. In addition, late gadolinium enhancement (LGE was performed. Images were evaluated by two blinded readers. Diagnostic accuracy was determined with coronary

  19. Effects of stress on the development and progression of cardiovascular disease.

    Science.gov (United States)

    Kivimäki, Mika; Steptoe, Andrew

    2017-12-07

    Cardiovascular disease remains the leading cause of disease burden globally, which underlies the continuing need to identify new complementary targets for prevention. Over the past 5-10 years, the pooling of multiple data sets into 'mega-studies' has accelerated progress in research on stress as a risk and prognostic factor for cardiovascular disease. Severe stressful experiences in childhood, such as physical abuse and household substance abuse, can damage health and increase the risk of multiple chronic conditions in adulthood. Compared with childhood stress and adulthood classic risk factors, such as smoking, high blood pressure, and high serum cholesterol levels, the harmful effects of stress in adulthood are generally less marked. However, adulthood stress has an important role as a disease trigger in individuals who already have a high atherosclerotic plaque burden, and as a determinant of prognosis and outcome in those with pre-existing cardiovascular or cerebrovascular disease. In real-life settings, mechanistic studies have corroborated earlier laboratory-based observations on stress-related pathophysiological changes that underlie triggering, such as lowered arrhythmic threshold and increased sympathetic activation with related increases in blood pressure, as well as pro-inflammatory and procoagulant responses. In some clinical guidelines, stress is already acknowledged as a target for prevention for people at high overall risk of cardiovascular disease or with established cardiovascular disease. However, few scalable, evidence-based interventions are currently available.

  20. Cardiovascular outcomes of a positive nuclear stress test but ...

    African Journals Online (AJOL)

    Background: Patients presenting with chest pain and evidence of functional ... In this study, we sought to evaluate the long-term outcomes of this ... The occurrence of adverse cardiovascular outcomes (chest pain, congestive heart failure, acute ...

  1. Neuroendocrine and cardiovascular reactions to acute psychological stress are attenuated in smokers

    NARCIS (Netherlands)

    Ginty, Annie T; Jones, Alexander; Carroll, Douglas; Roseboom, Tessa J; Phillips, Anna C; Painter, Rebecca; de Rooij, Susanne R

    2014-01-01

    A number of studies have now examined the association between smoking and the magnitude of physiological reactions to acute psychological stress. However, no large-scale study has demonstrated this association incorporating neuroendocrine in addition to cardiovascular reactions to stress. The

  2. The Role of Endoplasmic Reticulum Stress in Cardiovascular Disease and Exercise

    Directory of Open Access Journals (Sweden)

    Junyoung Hong

    2017-01-01

    Full Text Available Endoplasmic reticulum (ER stress, which is highly associated with cardiovascular disease, is triggered by a disturbance in ER function because of protein misfolding or an increase in protein secretion. Prolonged disruption of ER causes ER stress and activation of the unfolded protein response (UPR and leads to various diseases. Eukaryotic cells respond to ER stress via three major sensors that are bound to the ER membrane: activating transcription factor 6 (ATF6, inositol-requiring protein 1α (IRE1α, and protein kinase RNA-like ER kinase (PERK. Chronic activation of ER stress causes damage in endothelial cells (EC via apoptosis, inflammation, and oxidative stress signaling pathways. The alleviation of ER stress has recently been accepted as a potential therapeutic target to treat cardiovascular diseases such as heart failure, hypertension, and atherosclerosis. Exercise training is an effective nonpharmacological approach for preventing and alleviating cardiovascular disease. We here review the recent viewing of ER stress-mediated apoptosis and inflammation signaling pathways in cardiovascular disease and the role of exercise in ER stress-associated diseases.

  3. Adenosine triphosphate stress dual-source computed tomography to identify myocardial ischemia: comparison with invasive coronary angiography.

    Science.gov (United States)

    Kido, Teruhito; Watanabe, Kouki; Saeki, Hideyuki; Shigemi, Susumu; Matsuda, Takeshi; Yamamoto, Masaya; Kurata, Akira; Kanza, Rene Epunza; Itoh, Toshihide; Mochizuki, Teruhito

    2014-01-01

    The purpose of this study was to investigate the utility incremental diagnostic value of combined assessment with coronary CT angiography (CCTA) and myocardial CT perfusion imaging (CTP) using dual-energy technology with an Adenosine Triphosphate (ATP) load technique. Twenty-one patients underwent ATP-provocation dual-energy CT and CAG. We compared the diagnostic accuracy with CAG, for ischemic region due coronary stenosis by CCTA alone and CCTA combined with CTP (Combined CCTA/CTP). All of 21 patients CTP images could be evaluated, however 8 CCTA images could not be evaluated by calcification and motion artifact, so assessability was 61.9% (13/21) for CCTA alone, and 100% for Combined CCTA/CTP. With CAG results as a comparison, the sensitivity, specificity, positive predictive value, and negative predictive value were, respectively, 83.3% (20/24), 74.4% (29/39), 66.7% (20/30), and 87.8% (29/33) for CCTA alone, and 66.7% (16/24), 92.3% (36/39), 84.2% (16/19), and 81.8% (36/44) for combined CCTA/CTP. The diagnostic accuracy of the two methods were 77.8% (49/63) and 82.5% (52/63). Dual-energy CT may be a useful modality for perfusion assessment and correlated well with the severity of stenosis on CAG. This technique may even be of use in cases of severe calcification in the coronary artery wall.

  4. Adenosine-stress dynamic myocardial perfusion imaging using 128-slice dual-source CT: optimization of the CT protocol to reduce the radiation dose.

    Science.gov (United States)

    Kim, Sung Mok; Kim, Yoo Na; Choe, Yeon Hyeon

    2013-04-01

    The aim of this study was to compare the radiation dose and image quality of different adenosine-stress dynamic myocardial perfusion CT protocols using a 128-slice dual-source computed tomography (DSCT) scanner. We included 330 consecutive patients with suspected coronary artery disease. Protocols employed the following dynamic scan parameters: protocol I, a 30-s scan with a fixed tube current (FTC, n = 172); protocol II, a 30-s scan using an automatic tube current modulation (ATCM) technique (n = 108); protocol III, a 14-s scan using an ATCM (n = 50). To determine the scan interval for protocol III, we analyzed time-attenuation curves of 26 patients with myocardial perfusion who had been scanned using protocol I or II. The maximum attenuation difference between normal and abnormal myocardium occurred at 18.0 s to 30.3 s after initiation of contrast injection. Myocardial perfusion images of FTC and ATCM were of diagnostic image quality based on visual analysis. The mean radiation dose associated with protocols I, II, and III was 12.1 ± 1.6 mSv, 7.7 ± 2.5 mSv, and 3.8 ± 1.3 mSv, respectively (p stress CT enables significant dose reduction while maintaining diagnostic image quality.

  5. Dissecting the genetic architecture of the cardiovascular and renal stress response.

    Science.gov (United States)

    Snieder, Harold; Harshfield, Gregory A; Barbeau, Paule; Pollock, David M; Pollock, Jennifer S; Treiber, Frank A

    2002-10-01

    We review the evidence for a genetic basis of the cardiovascular and renal stress response. A bio-behavioral model of stress-induced hypertension is presented that explains how repeated exposure to stress in combination with genetic susceptibility might lead to the development of hypertension. In this model, we focus on three underlying physiological systems that mediate the stress response of the heart, vasculature and kidney: the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS) and the endothelial system (ES). We then review the evidence for a genetic influence on cardiovascular reactivity to psychological stress and stress-induced sodium retention using data from twin and family studies and a limited number of candidate gene studies. Finally, by describing the underlying physiological systems of our model and their genetic underpinning we emphasize the importance of inclusion of genetic measurements in any future studies testing the reactivity hypothesis.

  6. Relationship among stress, depression, cardiovascular and metabolic changes and physical exercise

    OpenAIRE

    Sanches,Andrea; Costa, Rafaela; Marcondes,Fernanda Klein; Cunha,Tatiana Sousa

    2016-01-01

    Abstract Introduction: Stress is considered one of the most significant health problems in modern society. It can be characterized as any changes in the homeostasis of an individual that require an adaptive response. An imbalance in the secretion of the primary stress mediators may be responsible for the onset and development of several diseases. Thus, chronic stress has been recognized as a risk factor for depression as well as cardiovascular and metabolic diseases. Given the pathophysiolog...

  7. Statins and oxidative stress in the cardiovascular system.

    Science.gov (United States)

    Margaritis, Marios; Sanna, Fabio; Antoniades, Charalambos

    2017-09-26

    Statins are widely established as an important class of medications for primary and secondary prevention of cardiovascular disease. In addition to their lipid-lowering effects, mounting evidence suggests that statins exhibit non-lipid-lowering mediated effects in the cardiovascular system. These so called "pleiotropic" effects are partly due to antioxidant properties of statins. These are mediated by inhibition of the mevalonate pathway, which interferes with small GTP-ase protein prenylation. This, in turn, leads to anti-oxidant effects of statins via a plethora of mechanisms. Statins prevent the activation of the pro-oxidant enzyme NADPH-oxidase by interfering with Rac1 activation and translocation to the membrane, as well as reducing expression of crucial subunits of NADPH-oxidase. Statins also enhance the expression, enzymatic activity and coupling of endothelial nitric oxide synthase (eNOS), through mevalonate-dependent effects. The net result is a restoration of the redox balance in the cardiovascular system, with subsequent anti-atherosclerotic and cardioprotective effects. While the evidence from basic science studies and animal models is strong, more clinical trials are required to establish the relevance of these pleiotropic effects to human cardiovascular disease and potentially lead to expanded indications for statin treatment or alternative therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Gender-Related Differences in Cardiovascular Responses to Orthostatic Stress

    Science.gov (United States)

    Fritsch-Yelle, Janice M.; DAunno, Dominick S.; Waters, Wendy W.; Freeman-Perez, Sondra

    1999-01-01

    There is evidence that men and women have different cardiovascular responses to standing, and that women are more susceptible to orthostatic hypotension than men. The present study seeks to determine if decreased orthostatic tolerance in women is caused by diminished vasoconstrictive responses.

  9. Quantitative circumferential strain analysis using adenosine triphosphate-stress/rest 3-T tagged magnetic resonance to evaluate regional contractile dysfunction in ischemic heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Masashi, E-mail: m.nakamura1230@gmail.com [Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295 (Japan); Kido, Tomoyuki [Department of Radiology, Saiseikai Matsuyama Hospital, Ehime 791-0295 (Japan); Kido, Teruhito; Tanabe, Yuki; Matsuda, Takuya; Nishiyama, Yoshiko; Miyagawa, Masao; Mochizuki, Teruhito [Department of Radiology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295 (Japan)

    2015-08-15

    Highlights: • Infarcted segments could be differentiated from non-ischemic and ischemic segments with high sensitivity and specificity under at rest conditions. • The time-to-peak circumferential strain values in infarcted segments were more significantly delayed than those in non-ischemic and ischemic segments. • Both circumferential strain and circumferential systolic strain rate values under ATP-stress conditions were significantly lower in ischemic segments than in non-ischemic segments. • Subtracting stress and rest circumferential strain had a higher diagnostic capability for ischemia relative to only utilizing rest or ATP-stress circumferential strain values. • A circumferential strain analysis using tagged MR can quantitatively assess contractile dysfunction in ischemic and infarcted myocardium. - Abstract: Purpose: We evaluated whether a quantitative circumferential strain (CS) analysis using adenosine triphosphate (ATP)-stress/rest 3-T tagged magnetic resonance (MR) imaging can depict myocardial ischemia as contractile dysfunction during stress in patients with suspected coronary artery disease (CAD). We evaluated whether it can differentiate between non-ischemia, myocardial ischemia, and infarction. We assessed its diagnostic performance in comparison with ATP-stress myocardial perfusion MR and late gadolinium enhancement (LGE)-MR imaging. Methods: In 38 patients suspected of having CAD, myocardial segments were categorized as non-ischemic (n = 485), ischemic (n = 74), or infarcted (n = 49) from the results of perfusion MR and LGE-MR. The peak negative CS value, peak circumferential systolic strain rate (CSR), and time-to-peak CS were measured in 16 segments. Results: A cutoff value of −12.0% for CS at rest allowed differentiation between infarcted and other segments with a sensitivity of 79%, specificity of 76%, accuracy of 76%, and an area under the curve (AUC) of 0.81. Additionally, a cutoff value of 477.3 ms for time-to-peak CS at rest

  10. Cardiovascular Mitochondrial Dysfunction Induced by Cocaine: Biomarkers and Possible Beneficial Effects of Modulators of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Manuela Graziani

    2017-01-01

    Full Text Available Cocaine abuse has long been known to cause morbidity and mortality due to its cardiovascular toxic effects. The pathogenesis of the cardiovascular toxicity of cocaine use has been largely reviewed, and the most recent data indicate a fundamental role of oxidative stress in cocaine-induced cardiovascular toxicity, indicating that mitochondrial dysfunction is involved in the mechanisms of oxidative stress. The comprehension of the mechanisms involving mitochondrial dysfunction could help in selecting the most appropriate mitochondria injury biological marker, such as superoxide dismutase-2 activity and glutathionylated hemoglobin. The potential use of modulators of oxidative stress (mitoubiquinone, the short-chain quinone idebenone, and allopurinol in the treatment of cocaine cardiotoxic effects is also suggested to promote further investigations on these potential mitochondria-targeted antioxidant strategies.

  11. Adenosine dysfunction in epilepsy

    Science.gov (United States)

    Boison, Detlev

    2011-01-01

    Extracellular levels of the brain’s endogenous anticonvulsant and neuroprotectant adenosine largely depend on an astrocyte-based adenosine cycle, comprised of ATP release, rapid degradation of ATP into adenosine, and metabolic reuptake of adenosine through equilibrative nucleoside transporters and phosphorylation by adenosine kinase (ADK). Changes in ADK expression and activity therefore rapidly translate into changes of extracellular adenosine, which exerts its potent anticonvulsive and neuroprotective effects by activation of pre- and postsynaptic adenosine A1 receptors. Increases in ADK increase neuronal excitability, whereas decreases in ADK render the brain resistant to seizures and injury. Importantly, ADK was found to be overexpressed and associated with astrogliosis and spontaneous seizures in rodent models of epilepsy, as well as in human specimen resected from patients with hippocampal sclerosis and temporal lobe epilepsy. Several lines of evidence indicate that overexpression of astroglial ADK and adenosine deficiency are pathological hallmarks of the epileptic brain. Consequently, adenosine augmentation therapies constitute a powerful approach for seizure prevention, which is effective in models of epilepsy that are resistant to conventional antiepileptic drugs. The adenosine kinase hypothesis of epileptogenesis suggests that adenosine dysfunction in epilepsy undergoes a biphasic response: An acute surge of adenosine that can be triggered by any type of injury might contribute to the development of astrogliosis via adenosine receptor –dependent and –independent mechanisms. Astrogliosis in turn is associated with overexpression of ADK, which was shown to be sufficient to trigger spontaneous recurrent electrographic seizures. Thus, ADK emerges as a promising target for the prediction and prevention of epilepsy. PMID:22700220

  12. Study of cardiovascular reactivity to mental stress in different phases of menstrual cycle.

    Science.gov (United States)

    Shenoy, Jnaneshwara P; Pa, Sahana; J, Shivakumar

    2014-06-01

    It is a well known fact that normally female sex hormone levels fluctuate during the menstrual cycle. The presence of receptors for these hormones on both heart and blood vessels may also hint at variations in physiological functions during menstrual cycle. So this study was an attempt to determine whether the follicular and luteal phases of menstrual cycle are characterized by variations in cardiovascular parameters in the resting state and also examine changes in cardiovascular reactivity to mental stress challenge during both the phases of menstrual cycle. Thirty healthy females in the age group of 18-25 years with regular menstrual cycles fulfilling the inclusion criteria were examined for cardiovascular parameters (heart rate and blood pressures) at rest and their reactivity to mental stress during the follicular and luteal phase and were compared by using paired t-test. A p-value of stress, in terms of blood pressure and heart rate increases, but the two phases of menstrual cycle were indistinguishable in so far as reactivity patterns were considered. The resting values of these cardiovascular parameters were also alike during the two phases. We were unable to unearth any differences in resting and reactivity values of cardiovascular parameters during the course of a normal menstrual cycle. This shows that stress reactivity variations during different phases of menstrual cycle may not be due to variations in hormonal levels per se, but due to collusion of hormonal variations and unknown genetic influences.

  13. Response of the Cardiovascular System to Vibration and Combined Stresses

    Science.gov (United States)

    1983-11-30

    such as endurance training or cardiovascular deconditioning or as a result of the onset of disease states like diabetes. IN 14 REFERENCES 1. Knapp, C. F...limit of 60 to 8) K mm. ag is usually imposed by physical discomfort. In addition, head-up tilt may provoke an involuntary increase in skeletal muscle...minute stage. Recovery measure- ments were made at one, three, and six minutes post- exercise. Training Program. The physical training program employed

  14. Behavioral cardiology: recognizing and addressing the profound impact of psychosocial stress on cardiovascular health.

    Science.gov (United States)

    Das, Sajal; O'Keefe, James H

    2008-10-01

    Psychosocial stress exerts independent adverse effects on cardiovascular health. The INTERHEART study reported that psychosocial stress accounted for approximately 30% of the attributable risk of acute myocardial infarction. Prospective studies consistently indicate that hostility, depression, and anxiety are related to increased risk of coronary heart disease and cardiovascular death. A sense of hopelessness, in particular, appears to be strongly correlated with adverse cardiovascular outcomes. Time urgency and impatience have not been consistently related to risk of coronary disease, but increase the likelihood of developing hypertension. Psychosocial stress appears to adversely affect autonomic and hormonal homeostasis, resulting in metabolic abnormalities, inflammation, insulin resistance, and endothelial dysfunction. Also, stress is often associated with self-destructive behavior and medication noncompliance. Psychosocial stress is a highly modifiable risk; many factors have been shown to be protective. These include psychosocial support, regular exercise, stress reduction training, sense of humor, optimism, altruism, faith, and pet ownership. Simple screening questions are available to reliably indicate a patient at risk for psychosocial stress-related health problems.

  15. Endoplasmic Reticulum Stress, NRF2 Signalling and Cardiovascular Diseases in a Nutshell.

    Science.gov (United States)

    Mozzini, Chiara; Cominacini, Luciano; Garbin, Ulisse; Fratta Pasini, Anna Maria

    2017-08-01

    This short review is intended primarily to summarize the understanding of the interrelated roles of endoplasmic reticulum (ER) stress, oxidative stress and inflammation in cardiovascular diseases. Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER. An excess of proteins folding in the ER is known as ER stress. This condition initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signalling is induced. Moreover, the role of the protective nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE) and the activation of the pro-inflammatory nuclear factor-kappa B (NF-kB) are analysed. Authors summarize evidence that oxidative stress, inflammation and ER stress are closely entwined phenomena. They are involved in the pathogenesis of different cardiovascular diseases. Current literature data are presented, focusing on three topics of related pathologies: atherosclerotic plaque, coronary artery disease and diabetes. This review will provide a basic platform for study and application to several other conditions in which oxidative stress, ER stress and inflammation are key features. Future studies in this area may identify the most promising molecules to be investigated as common targets for cardiovascular diseases.

  16. In adenosine A2B knockouts acute treatment with inorganic nitrate improves glucose disposal, oxidative stress and AMPK signaling in the liver

    Directory of Open Access Journals (Sweden)

    Maria ePeleli

    2015-08-01

    Full Text Available Rationale: Accumulating studies suggest that nitric oxide (NO deficiency and oxidative stress are central pathological mechanisms in type 2 diabetes. Recent findings demonstrate therapeutic effects by boosting a nitrate-nitrite-NO pathway, an alternative pathway for NO formation. This study aimed at investigating the acute effects of inorganic nitrate on glucose and insulin signaling in adenosine A2B receptor knockout mice (A2B-/-, a genetic model of impaired metabolic regulation.Methods: Acute effects of nitrate treatment were investigated in aged wild-type (WT and A2B-/- mice. One hour after injection with nitrate or placebo, metabolic regulation was evaluated by glucose and insulin tolerance tests. NADPH oxidase-mediated superoxide production and AMPK phosphorylation were measured in livers obtained from non-treated or glucose-treated mice, with or without prior nitrate injection. Plasma was used to determine insulin resistance (HOMA-IR and NO signaling.Results: A2B-/- displayed increased body weight, reduced glucose clearance and attenuated overall insulin responses compared with age-matched WT. Nitrate treatment increased circulating levels of nitrate, nitrite and cGMP in A2B-/-, and improved glucose clearance. In WT mice, however, nitrate treatment did not influence glucose clearance. HOMA-IR increased following glucose injection in A2B-/-, but remained at basal levels in mice pretreated with nitrate. NADPH oxidase activity in livers from A2B-/-, but not WT mice, was reduced by nitrate. Livers from A2B-/- displayed reduced AMPK phosphorylation compared with WT mice, and this was increased by nitrate treatment. Injection with the anti-diabetic agent metformin induced similar therapeutic effects in the A2B-/- as observed with nitrate. Conclusion: The A2B-/- mouse is a genetic model of metabolic syndrome. Acute treatment with nitrate improved the metabolic profile, at least partly via reduction in oxidative stress and improved AMPK signaling

  17. [CARDIOVASCULAR SYSTEM REACTIVITY IN PRENATALLY STRESSED RATS DURING THE LATE PERIOD OF ONTOGENESIS].

    Science.gov (United States)

    Khudaverdyan, A; Saroyan, M; Khudaverdyan, D

    2015-09-01

    Systolic, diastolic blood pressure and heart rate were determined in normal rats and those exposed to influence of chronic stress during gestation. Data were registered six months after the birth and in 5, 24 and 48 hours after their immobilization. Analysis of the data showed that in rats undergoing stress, recorded systolic, diastolic blood pressure and heart rate both before and during all periods of immobilization were significantly below than in control group. It is concluded that the maximum limit of motor activity in the prenatally stressed rats accompanied by a decrease in the values ​​recorded performance of the cardiovascular system, which is reflecting the decrease in these animals reactivity of the cardiovascular system, and thus the adaptive capacity for action of stress factors.

  18. Plasma Homocysteine and Oxidative Stress in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    S. S. Moselhy

    2003-01-01

    Full Text Available Hyperhomocysteinemia (Hhcy has been associated with pathological and stressfull conditions and is a risk factor for cardiovascular disease (CVD. The aim of this study was to evaluate the correlation between plasma homocysteine (hcy and lipid peroxidation in patient with CVD. This study was carried out on 40 patients with CVD as well as 15 healthy volunteers of comparable age and gender as control group. The patients were divided into 2 groups as follows: group I, included 20 patients with acute myocardial infarction and group II, included 20 patients with atherosclerotic coronary artery disease with no evidence of previous myocardial infarction . Plasma hcy, nitric oxide (NO and malondialdhyde (MDA [as index of lipid peroxidation] were measured in all groups. In addition serum total-cholesterol, HDL, LDL and triglycerides were evaluated. Results obtained showed that, there was a significant elevation in the levels of plasma hcy, NO and MDA in groups I and II as compared to control group. There was a strong positive correlation between plasma hcy and MDA (r = 0.59, p < 0.001. Also NO was positively correlated with both hcy (r = 0.49, p < 0.001 and MDA (r = 0.51, p < 0.001 . Serum total cholesterol, LDL, and triglycerids were also significantly elevated while serum HDL was significantly decreased in groups I and II as compared to control group. It can be concluded that, hyperhomocysteinemia is a possible factor in free radical generation and therefore cardiovascular diseases.

  19. Isometric stress in cardiovascular magnetic resonance - a simple and easily replicable method of assessing cardiovascular differences not apparent at rest

    Energy Technology Data Exchange (ETDEWEB)

    Mortensen, Kristian H.; Jones, Alexander; Steeden, Jennifer A.; Taylor, Andrew M.; Muthurangu, Vivek [UCL Centre for Cardiovascular MR, UCL Institute of Cardiovascular Science, Level 6 Old Nurses Home, Cardiorespiratory Unit, Great Ormond Street Hospital for Children, London (United Kingdom)

    2016-04-15

    Isometric exercise may unmask cardiovascular disease not evident at rest, and cardiovascular magnetic resonance (CMR) imaging is proven for comprehensive resting assessment. This study devised a simple isometric exercise CMR methodology and assessed the hemodynamic response evoked by isometric exercise. A biceps isometric exercise technique was devised for CMR, and 75 healthy volunteers were assessed at rest, after 3-minute biceps exercise, and 5-minute of recovery using: (1) blood pressure (BP) and (2) CMR measured aortic flow and left ventricular function. Total peripheral resistance (SVR) and arterial compliance (TAC), cardiac output (CO), left ventricular volumes and function (ejection fraction, stroke volume, power output), blood pressure (BP), heart rate (HR), and rate pressure product were assessed at all time points. Image quality was preserved during stress. During exercise there were increases in CO (+14.9 %), HR (+17.0 %), SVR (+9.8 %), systolic BP (+22.4 %), diastolic BP (+25.4 %) and mean BP (+23.2 %). In addition, there were decreases in TAC (-22.0 %) and left ventricular ejection fraction (-6.3 %). Age and body mass index modified the evoked response, even when resting measures were similar. Isometric exercise technique evokes a significant cardiovascular response in CMR, unmasking physiological differences that are not apparent at rest. (orig.)

  20. Cardiovascular reflexes during rest and exercise modified by gravitational stresses

    Science.gov (United States)

    Bonde-petersen, Flemming

    The hypotheses tested were whether variations in central venous pressure via the low pressure baroreceptors would take over or modify the arterial baroreceptor function, and further to which extent local and "whole body" hydrostatic stresses influence blood flow distribution. We investigated total forearm and skin blood flow (venous occlusion plethysmography and 133-Xe clearance) and cardiac output (rebreathing method) among other parameters. Hypo-and hypergravitational stresses were simulated by LBNP, LBPP, water immersion and lowering of the arm. The changes in flow distribution in the arm were ascribed to arterial baroreceptor function and not to low pressure baroreceptor activity. The enhancement of venous return during water immersion increased exercise tolerance during heat stress presumably due both to increased stroke volume and decreased venous pooling. The response to sustained handgrip exercise during LBNP and LBPP was not different from control measurements and the effects explained by arterial baroreceptor function. Application of exercise and local hydrostatic stresses in combination with gravitational stresses represent an interesting model for further study of the mechanisms behind the distribution of cardiac output to the peripheral organs.

  1. Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication.

    Directory of Open Access Journals (Sweden)

    Faith C H Li

    Full Text Available BACKGROUND: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH, the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM, which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. METHODOLOGY/PRINCIPAL FINDINGS: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemical events were reversed on microinjection into RVLM of a mobile electron carrier in the mitochondrial respiratory chain, coenzyme Q10; a mitochondria-targeted antioxidant and superoxide anion scavenger, Mito-TEMPO; or an oxidative stress-induced necrotic cell death inhibitor, IM-54. CONCLUSION: We conclude that sustained anoxia and cessation of local blood flow

  2. Sex Differences in Cardiovascular and Subjective Stress Reactions: Prospective Evidence in a Realistic Military Setting

    Science.gov (United States)

    2014-01-01

    this study require comment. Importantly, we did not control for menstrual phase or oral contraceptive use. Reproductive hormones may be implicated in...Cigarette smoking and oral contra- ceptive use influence women’s lipid, lipoprotein, and cardiovascular responses during stress. Health Psychol 9(6

  3. Cardiovascular Responsivity, Physical and Psychosocial Job Stress, and the Risk of Preterm Delivery

    National Research Council Canada - National Science Library

    Hatch, Maureen

    1999-01-01

    ... at Wilford Hall Medical Center. The role of cardiovascular reactivity in the stress response and how this affects risk of preterm delivery will also be examined. The study, now in its final year, will continue recruitment of subjects and will begin to conduct preliminary data analyses.

  4. Cardiovascular Responsivity, Physical and Psychosocial Job Stress, and the Risk of Preterm Delivery

    National Research Council Canada - National Science Library

    Hatch, Maureen

    2000-01-01

    .... The role of cardiovascular reactivity in the stress response and how this affects risk of pre term delivery will also be examined. Recruitment, now complete, took longer than anticipated due to a high rate of ineligibles. We propose to complete the analyses under a no-cost extension.

  5. Retinal vascular caliber is associated with cardiovascular biomarkers of oxidative stress and inflammation: the POLA study.

    Directory of Open Access Journals (Sweden)

    Vincent Daien

    Full Text Available PURPOSE: Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology. PATIENTS AND METHODS: Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3 activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP and orosomucoid. RESULTS: In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003 whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001 and orosomucoid (p = 0.01. CONCLUSION: In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.

  6. Cardiovascular response to mental stress in offspring of hypertensive parents: The Dutch Hypertension and Offspring Study

    NARCIS (Netherlands)

    D.C. de Visser (D.); I.M.S. van Hooft (I. M S); L.J.P. van Doornen (Lorenz); A. Hofman (Albert); J.F. Orlebeke (J.); D.E. Grobbee (Diederick)

    1995-01-01

    textabstractObjective: To compare blood pressure-regulating mechanisms during mental stress in two groups of offspring with contrasting risk for hypertension. Design: Cardiovascular reactivity to two different types of mental stressors was studied in adolescents and young adults with two

  7. Antioxidants, oxidative stress, and cardiovascular diseases : cross-cultural comparisons and prospective cohort studies

    NARCIS (Netherlands)

    Buijsse, B.

    2008-01-01

    Background: Antioxidants in plant foods have been proposed to reduce the risk of cardiovascular diseases (CVD) by reducing oxidative stress. The objective was to confirm prospective studies on CVD and traditional antioxidants (beta-carotene, alpha-tocopherol), and to investigate emerging

  8. Interactions between immune, stress-related hormonal and cardiovascular systems following strenuous physical exercise.

    Science.gov (United States)

    Menicucci, Danilo; Piarulli, Andrea; Mastorci, Francesca; Sebastiani, Laura; Laurino, Marco; Garbella, Erika; Castagnini, Cinzia; Pellegrini, Silvia; Lubrano, Valter; Bernardi, Giulio; Metelli, Maria; Bedini, Remo; L'abbate, Antonio; Pingitore, Alessandro; Gemignani, Angelo

    2013-09-01

    Physical exercise represents a eustress condition that promotes rapid coordinated adjustments in the immune, stress-related hormonal and cardiovascular systems, for maintaining homeostasis in response to increased metabolic demands. Compared to the tight multisystem coordination during exercise, evidence of between-systems cross talk in the early post exercise is still lacking. This study was aimed at identifying possible interactions between multiple systems following strenuous physical exercise (Ironman race) performed by twenty well-trained triathletes. Cardiac hemodynamics, left ventricle systolic and diastolic function and heart rate variability were measured along with plasma concentrations of immune messengers (cytokines and C-reactive protein) and stress-related hormones (catecholamines and cortisol) both 24h before and within 20 min after the race. Observed changes in antiinflammatory pathways, stress-related hormones and cardiovascular function were in line with previous findings; moreover, correlating parameters' changes (post versus pre-race) highlighted a dependence of cardiovascular function on the post-race biohumoral milieu: in particular, individual post-race variations of heart rate and diastolic function were strongly correlated with individual variations of anti-inflammatory cytokines, while individual baroreflex sensitivity changes were linked to IL-8 increase. Multiple correlations between anti-inflammatory cytokines and catecholamines were also found according with the autonomic regulation of immune function. Observed post-race cytokine and hormone levels were presumptively representative of the increases reached at the effort end while the cardiovascular parameters after the race were measured during the cardiovascular recovery; thus, results suggest that sustained strenuous exercise produced a stereotyped cardiovascular early recovery, whose speed could be conditioned by the immune and stress-related hormonal milieu.

  9. Biological markers of oxidative stress: Applications to cardiovascular research and practice

    Directory of Open Access Journals (Sweden)

    Edwin Ho

    2013-01-01

    Full Text Available Oxidative stress is a common mediator in pathogenicity of established cardiovascular risk factors. Furthermore, it likely mediates effects of emerging, less well-defined variables that contribute to residual risk not explained by traditional factors. Functional oxidative modifications of cellular proteins, both reversible and irreversible, are a causal step in cellular dysfunction. Identifying markers of oxidative stress has been the focus of many researchers as they have the potential to act as an “integrator” of a multitude of processes that drive cardiovascular pathobiology. One of the major challenges is the accurate quantification of reactive oxygen species with very short half-life. Redox-sensitive proteins with important cellular functions are confined to signalling microdomains in cardiovascular cells and are not readily available for quantification. A popular approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. However, these may not accurately reflect redox stress at the cell/tissue level. Many of these modifications are “functionally silent”. Functional significance of the oxidative modifications enhances their validity as a proposed biological marker of cardiovascular disease, and is the strength of the redox cysteine modifications such as glutathionylation. We review selected biomarkers of oxidative stress that show promise in cardiovascular medicine, as well as new methodologies for high-throughput measurement in research and clinical settings. Although associated with disease severity, further studies are required to examine the utility of the most promising oxidative biomarkers to predict prognosis or response to treatment.

  10. Effect of modified slow breathing exercise on perceived stress and basal cardiovascular parameters

    Directory of Open Access Journals (Sweden)

    G Sunil Naik

    2018-01-01

    Full Text Available Context: Different types of breathing exercises have varied effects on cardiovascular parameters and the stress levels in an individual. Aim: The aim of this study was to assess the effect of a modified form of isolated alternate nostril, slow breathing exercise on perceived stress, and cardiovascular parameters in young, male volunteers. Settings and Design: This was a randomized control study carried out at Advanced Centre for Yoga Therapy Education and Research, Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry in 2014. Subjects and Methods: Hundred healthy male volunteers were randomized into control group, n = 50 and slow breathing group (study, n = 50. Slow breathing exercise training was given to study group for 30 min a day, 5 times/week for 12 weeks, under the supervision of certified yoga trainers. Perceived Stress Scale (PSS using Cohen's questionnaire, anthropometric parameters such as body mass index (BMI, waist-hip ratio (WHR, and cardiovascular parameters such as heart rate (HR, systolic blood pressure (SBP, and diastolic blood pressure (DBP were recorded at baseline and after 12 weeks. The control group did not receive any intervention. Slow breathing exercise training was provided for the study group. During the study period, one volunteer opted out of the study group due to personal reasons. Results: HR, SBP, DBP, and PSS decreased significantly (P 0.05 was observed in BMI and WHR. There was no significant change in the control group. Conclusion: Twelve weeks of modified slow breathing exercise reduced perceived stress and improved the cardiovascular parameters. The above results indicate that our modified slow breathing exercise is effective in reducing stress and improving the cardiovascular parameters.

  11. Adenosine and dialysis hypotension

    NARCIS (Netherlands)

    Franssen, CMF

    In this issue, Imai et al. report the results of a double-blind placebo-controlled study on the effect of an adenosine A1 receptor antagonist, FK352, on the incidence of dialysis hypotension in hypotension-prone patients. This Commentary discusses the use of selective adenosine A1 receptor

  12. Social stress increases blood pressure and cardiovascular pathology in a normotensive rat model.

    Science.gov (United States)

    Andrews, Ellen; Jenkins, Cathleen; Seachrist, Darcie; Dunphy, Gail; Ely, Daniel

    2003-02-01

    Territorial stress (TS) elevates blood pressure (BP) in several mammalian species. However, cardiovascular pathology following chronic stress has not been consistently shown in a non-genetic hypertension model. Therefore, the hypothesis tested was that social stress would directly increase: BP, collagen deposition in coronary and mesenteric arteries, and myocardial fibrosis. Wistar-Kyoto (WKY) male rats, four weeks of age, were divided into one of three groups: controls (n = 9), territorial stress (TS, n = 12), and social isolation followed by territorial stress (SITS, n = 11). Blood pressure was measured biweekly, and blood samples biweekly for serum testosterone, corticosterone, epinephrine and norepinephrine. Blood pressure significantly increased in the TS (130 mmHg, p stress treatments increased BP and cardiac pathology in a normotensive rat strain.

  13. Cardiovascular profile of defensive hostile women in a real stressful situation

    Directory of Open Access Journals (Sweden)

    Francisco Palmero

    2015-05-01

    Full Text Available The main objective of this study was to analyze the impact of defensive hostility on cardiovascular response in a stressful situation. By measuring three of the most commonly used cardiovascular indexes (heart rate, systolic blood pressure and diastolic blood pressure over three experimental phases (adaptation, task and recovery, the evolution of cardiovascular response was analyzed minute by minute throughout the entire experimental session, to check if the defensive hostility influences the cardiovascular function. Two scales were used: the Cook-Medley Composite Hostility Scale and the Marlowe-Crowne Social Desirability Scale. Based on the scores on these scales, there were formed four groups (high hostility and high defensiveness, high hostility and low defensiveness, low hostility and high defensiveness, and low hostility and low defensiveness. The stressful situation which was used in the task phase was a real academic examination (exam of the Psychology degree. The hypothesis was that cardiovascular response, activation and recovery, minute by minute, will be greater in hostile defensive women, with an intraphase evolution profile characterized by maintenance or sensitization and slow recovery. Results show that defensive hostile individuals present the highest values in the physiological variables recorded, and less adaptive profiles.

  14. Psychosocial stress and cardiovascular disease risk: the role of physical activity.

    Science.gov (United States)

    Hamer, Mark

    2012-01-01

    Chronic stress and depression are associated with increased risk of cardiovascular disease and poorer prognosis, and physical (in)activity may be a key underlying biobehavioral mechanism. Physical activity has antidepressant effects, and physically fitter, more active individuals seem to be more biologically resilient to psychosocial stressors. This article will present data from a series of population cohort studies and laboratory-based psychophysiological studies to explore the role of physical activity as a protective factor against the effects of psychosocial stress on cardiovascular disease. These mechanisms may improve the treatment and prevention of stress-related illnesses and, thus, has important implications for public health and clinical care of high-risk patients.

  15. Fish consumption and cardiovascular response during mental stress

    Directory of Open Access Journals (Sweden)

    Yamakoshi Takehiro

    2012-06-01

    Full Text Available Abstract Background Frequent fish consumption is related to a lower risk of coronary heart disease. However, the physiological mechanisms underlying this cardioprotective effect are as yet unknown. We therefore examined certain cardiovascular physiological variables of fish eaters during rest, whilst conducting mental arithmetic, and during recovery. Findings The participants were 12 fish eaters (eating baked fish more than 3–4 times/week and 13 controls (eating fish less than 1–2 times/week. Analysis of the collected data revealed that heart rate, blood pressure, and pulse wave velocity were significantly lower and pre-ejection period and baroreflex sensitivity were significantly higher in the fish eaters than in the controls during both rest and mental arithmetic, and that systolic and mean blood pressure recovery from mental arithmetic were faster in the fish eaters than in the controls. Conclusions These findings suggest a possible physiological mechanism that may explain why frequent fish consumption reduces coronary heart disease risk.

  16. Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

    Science.gov (United States)

    Murphy, M O; Cohn, D M; Loria, A S

    2017-03-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Effect of fast and slow pranayama on perceived stress and cardiovascular parameters in young health-care students

    OpenAIRE

    Vivek Kumar Sharma; Madanmohan Trakroo; Velkumary Subramaniam; Rajajeyakumar, M.; Bhavanani, Anand B; Ajit Sahai

    2013-01-01

    Context: Perceived stress is higher for students in various healthcare courses. Previous studies have shown that pranayama practice is beneficial for combating stress and improve cardiovascular functions but both fast and slow pranayama practice produce different physiological responses. Aim: Present study was conducted to compare the effects of commonly practiced slow and fast pranayama on perceived stress and cardiovascular functions in young health-care students. Materials and Methods: Pre...

  18. Examination stress results in altered cardiovascular responses to acute challenge and lower cortisol.

    Science.gov (United States)

    Loft, Patricia; Thomas, Mark G; Petrie, Keith J; Booth, Roger J; Miles, Jeremy; Vedhara, Kavita

    2007-05-01

    The present study examined how cardiovascular and salivary cortisol responses varied in response to an acute challenge in medical students under exam stress versus those not under exam stress. One hundred and twenty-nine medical students were randomly assigned to undertake a CO2 inhalation test either prior to an examination period (exam group) or during a regular academic period (non-exam group). Heart rate (HR) and blood pressure (BP) were measured for 5 min before and 5 min after the task, and salivary cortisol samples were collected 1 min before and 10 and 30 min after the CO2 inhalation test. Participants also completed a questionnaire measuring self-reported perceived stress. The exam group exhibited significantly higher HR reactivity following the CO2 inhalation test and slower systolic blood pressure (SBP) recovery compared with the non-exam group. The exam group also reported higher perceived stress and higher stress scores were related to higher HR reactivity following CO2 inhalation. Female students across both groups exhibited significantly lower SBP reactivity compared with male students. Salivary cortisol levels were consistently lower in the exam group. These findings indicate that ongoing natural stress alters cortisol secretion and cardiovascular responses in the face of an acute stress challenge.

  19. Cardiovascular responses to heat stress in late gestation fetal sheep.

    Science.gov (United States)

    Walker, D W; Hale, J R; Fawcett, A A; Pratt, N M

    1995-09-01

    Heat stress during pregnancy in sheep is associated with respiratory alkalosis in both the mother and fetus, and, if prolonged, fetal growth is retarded. In seven pregnant sheep at 130-137 days gestation we used 15 microns diameter radioactive microspheres to determine the effect of raising the environmental temperature from 20 to 43 degrees C for 8 h on uteroplacental blood flows and the distribution of cardiac output in the ewe and fetus. Fetal cardiac output increased slightly from 47.0 +/- 3.2 (mean +/- S.E.M.) to 54.0 +/- 3.6 ml min-1 (100 g tissue)-1, fetal arterial pressure and heart rate were unchanged, and total vascular conductance in the fetus increased significantly from 12397 +/- 1111 to 14732 +/- 1569 ml min-1 kg-1 mmHg-1 (P release of vasodilator substances, or a decrease of sympathoadrenal effector responses. Blood flow to the fetal and maternal sides of the placenta did not change during the heat stress, suggesting that perfusion-dependent transfer of heat from fetus to mother across the placenta does not increase under hyperthermic conditions.

  20. Adiposity is associated with blunted cardiovascular, neuroendocrine and cognitive responses to acute mental stress.

    Directory of Open Access Journals (Sweden)

    Alexander Jones

    Full Text Available Obesity and mental stress are potent risk factors for cardiovascular disease but their relationship with each other is unclear. Resilience to stress may differ according to adiposity. Early studies that addressed this are difficult to interpret due to conflicting findings and limited methods. Recent advances in assessment of cardiovascular stress responses and of fat distribution allow accurate assessment of associations between adiposity and stress responsiveness. We measured responses to the Montreal Imaging Stress Task in healthy men (N = 43 and women (N = 45 with a wide range of BMIs. Heart rate (HR and blood pressure (BP measures were used with novel magnetic resonance measures of stroke volume (SV, cardiac output (CO, total peripheral resistance (TPR and arterial compliance to assess cardiovascular responses. Salivary cortisol and the number and speed of answers to mathematics problems in the task were used to assess neuroendocrine and cognitive responses, respectively. Visceral and subcutaneous fat was measured using T(2 (*-IDEAL. Greater BMI was associated with generalised blunting of cardiovascular (HR:β = -0.50 bpm x unit(-1, P = 0.009; SV:β = -0.33 mL x unit(-1, P = 0.01; CO:β = -61 mL x min(-1 x unit(-1, P = 0.002; systolic BP:β = -0.41 mmHg x unit(-1, P = 0.01; TPR:β = 0.11 WU x unit(-1, P = 0.02, cognitive (correct answers: r = -0.28, P = 0.01; time to answer: r = 0.26, P = 0.02 and endocrine responses (cortisol: r = -0.25, P = 0.04 to stress. These associations were largely determined by visceral adiposity except for those related to cognitive performance, which were determined by both visceral and subcutaneous adiposity. Our findings suggest that adiposity is associated with centrally reduced stress responsiveness. Although this may mitigate some long-term health risks of stress responsiveness, reduced performance under stress may be a more immediate

  1. Impact of acute psychological stress on cardiovascular risk factors in face of insulin resistance.

    Science.gov (United States)

    Jones, Kristian T; Shelton, Richard C; Wan, Jun; Li, Li

    2016-11-01

    Individuals with insulin resistance (IR) are at greater risk for cardiovascular disease (CVD). Psychological stress may contribute to develop CVD in IR, although mechanisms are poorly understood. Our aim was to test the hypothesis that individuals with IR have enhanced emotional and physiological responses to acute psychological stress, leading to increased CVD risk. Sixty participants were enrolled into the study, and classified into IR group (n = 31) and insulin sensitive group (n = 29) according to the Quantitative insulin sensitivity check index, which was calculated based on an oral glucose tolerance test. The Trier social stress test, a standardized experimental stress paradigm, was performed on each participant, and emotional and physiological responses were examined. Blood was collected from each subject for insulin, cytokines, and cortisol measurements. Compared with the insulin-sensitive group, individuals with IR had significantly lower ratings of energy and calm, but higher fatigue levels in response to acute stressors. Individuals with IR also showed blunted heart rate reactivity following stress. In addition, the IR status was worsened by acute psychological stress as demonstrated by further increased insulin secretion. Furthermore, individuals with IR showed significantly increased levels of leptin and interleukin-6, but decreased levels of adiponectin, at baseline, stress test, and post-stress period. Our findings in individuals with IR under acute stress would allow a better understanding of the risks for developing CVD and to tailor the interventions for better outcomes.

  2. Subliminal activation of social ties moderates cardiovascular reactivity during acute stress.

    Science.gov (United States)

    Carlisle, McKenzie; Uchino, Bert N; Sanbonmatsu, David M; Smith, Timothy W; Cribbet, Matthew R; Birmingham, Wendy; Light, Kathleen C; Vaughn, Allison A

    2012-03-01

    The quality of one's personal relationships has been reliably linked to important physical health outcomes, perhaps through the mechanism of physiological stress responses. Most studies of this mechanism have focused on whether more conscious interpersonal transactions influence cardiovascular reactivity. However, whether such relationships can be automatically activated in memory to influence physiological processes has not been determined. The primary aims of this study were to examine whether subliminal activation of relationships could influence health-relevant physiological processes and to examine this question in the context of a more general relationship model that incorporates both positive and negative dimensions. We randomly assigned participants to be subliminally primed with existing relationships that varied in their underlying positivity and negativity (i.e., indifferent, supportive, aversive, ambivalent). They then performed acute psychological stressors while cardiovascular and self-report measures were assessed. Priming negative relationships was associated with greater threat, lower feelings of control, and higher diastolic blood pressure reactivity during stress. Moreover, priming relationships high in positivity and negativity (ambivalent ties) was associated with the highest heart rate reactivity and greatest respiratory sinus arrhythmia decreases during stress. Exploratory analyses during the priming task itself suggested that the effects of negative primes on biological measures were prevalent across tasks, whereas the links to ambivalent ties was specific to the subsequent stressor task. These data highlight novel mechanisms by which social ties may impact cardiovascular health, and further suggest the importance of incorporating both positivity and negativity in the study of relationships and physical health.

  3. Oxidative stress biomarkers in type 2 diabetes mellitus for assessment of cardiovascular disease risk.

    Science.gov (United States)

    Robson, Roy; Kundur, Avinash R; Singh, Indu

    2017-12-30

    Type-2 Diabetes Mellitus (T2DM) is one of the most prevalent and progressive metabolic conditions affecting approximately 8.5% of the global population. Individuals with T2DM have a significantly increased risk of developing chronic conditions such as cardiovascular disease (CVD) and its associated complications, therefore, it is of great importance to establish strategies for combatting T2DM and its associated chronic conditions. Current literature has identified several biomarkers that are known to play a key role in the pathogenesis of CVD. Many of these biomarkers affecting CVD are influenced by an increase in oxidative stress as seen in T2DM. The purpose of this review is to analyse and correlate the oxidative stress-related biomarkers that have been identified in the literature to provide an updated summary of their significance in CVD risk factors. This review has analysed current research on T2DM, CVD, and oxidative stress. Four key cardiovascular risk factors: thrombosis, inflammation, vascular homeostasis and cellular proliferation were searched to identify potential biomarkers for this review. These biomarkers stem from seven major cellular pathways; NF-κB, Keap1-Nrf2, protein kinase-C, macrophage activation, arachidonic acid mobilisation, endothelial dysfunction and advanced glycation end products. The pathways and biomarkers were analysed to show their role as contributing factors to CVD development and a summary is made regarding the assessment of cardiovascular risk in T2DM individuals. Copyright © 2017. Published by Elsevier Ltd.

  4. Oxidative Stress in Cardiovascular Diseases and Obesity: Role of p66Shc and Protein Kinase C

    Science.gov (United States)

    Baldassari, Federica; Wieckowski, Mariusz R.

    2013-01-01

    Reactive oxygen species (ROS) are a byproduct of the normal metabolism of oxygen and have important roles in cell signalling and homeostasis. An imbalance between ROS production and the cellular antioxidant defence system leads to oxidative stress. Environmental factors and genetic interactions play key roles in oxidative stress mediated pathologies. In this paper, we focus on cardiovascular diseases and obesity, disorders strongly related to each other; in which oxidative stress plays a fundamental role. We provide evidence of the key role played by p66Shc protein and protein kinase C (PKC) in these pathologies by their intracellular regulation of redox balance and oxidative stress levels. Additionally, we discuss possible therapeutic strategies aimed at attenuating the oxidative damage in these diseases. PMID:23606925

  5. Cardiovagal modulation, oxidative stress, and cardiovascular risk factors in prehypertensive subjects: cross-sectional study.

    Science.gov (United States)

    Thiyagarajan, Ramkumar; Pal, Pravati; Pal, Gopal Krushna; Subramanian, Senthil Kumar; Bobby, Zachariah; Das, Ashok Kumar; Trakroo, Madanmohan

    2013-07-01

    Hypertension, one of the modifiable risk factors for cardiovascular disease (CVD), is known to be associated with increased oxidative stress and reduced cardiovagal modulation. Similar to hypertension, prehypertension is associated with increased risk of adverse cardiovascular (CV) events. We planned this study to find the association between prehypertension, cardiovagal modulation, oxidative stress, and associated CV risk factors. We recruited 178 subjects through hypertension screening camps conducted in Puducherry, India. Subjects were grouped into prehypertensive (n = 97) and normotensive (n = 81) groups. They were further subdivided, based on age, as young (20-39 years) and middle-aged (40-60 years) adults. We measured basal physiological parameters, heart rate variability, oxidative stress (thiobarbituric acid reactive substance and total antioxidant capacity (TAC)), and CV risk factors. We found significant increase in oxidative stress in prehypertensive subjects of both age groups but the cardiovagal modulation decreased significantly in young prehypertensive subjects when compared with normotensive subjects. Correlation of TAC with root mean square of the sum of successive R wave to R wave (RR) interval differences (RMSSD), a cardiovagal modulation parameter (r = 0. 437; P risk factors. The correlation between MAP and RMSSD (r = 0.199; P = 0.009) was reduced after adjusting for CV risk factors. Prehypertension in young adults is associated with increased oxidative stress and altered cardiovagal modulation. The risk factors for CVDs in prehypertensive young adults were found to be equivalent to that of middle-aged adults who are in the twilight zone for developing CV dysfunctions.

  6. Comparative assessment of rest and post-stress left ventricular volumes and left ventricular ejection fraction on gated myocardial perfusion imaging (MPI) and echocardiography in patients with transient ischaemic dilation on adenosine MPI: myocardial stunning or subendocardial hypoperfusion?

    Science.gov (United States)

    Emmett, Louise; Ng, Austin; Ha, Leo; Russo, Robert; Mansberg, Robert; Zhao, Wei; Chow, S Vincent; Kritharides, Leonard

    2012-08-01

    Transient ischaemic dilation (TID) on myocardial perfusion imaging (MPI) is an important finding, conveying a high risk of subsequent cardiac events. However, the mechanism leading to TID on MPI is not well elucidated. This study aimed to determine if TID is due to true LV cavity dilation and ventricular stunning, or is due to relative subendocardial hypoperfusion. 31 patients undergoing single-day Tc-99m adenosine sestamibi MPI were recruited. All had routine ECG-gated single-day rest-stress adenosine MPI, with transthoracic echocardiograms (echo) acquired concurrently at rest, and both immediately, and 2 hours, post-stress. Echocardiography was performed using a Vivid-7 (GE). LV volumes and LVEF were quantified blinded to MPI results, using biplane Simpson method on echo, and quantitatively (including TID) with QGS(®), on MPI. Patients were divided into quartiles for TID, with the top quartile considered TID positive [TID+ 9/31 (TID ratio 1.3 ± 0.09)], and TID negative [TID- 22/31 (TID ratio 1.01 ± 0.04)]. There was good correlation between resting echo and MPI physical measurements (LVEDV r(2) = 0.79, LVESV r(2) = 0.9, and LVEF r(2) = 0.75). On MPI, a significant drop in LVEF was observed between rest and early stress in the TID+ group (56.6% vs 46.5%, P subendocardial hypoperfusion and impaired coronary flow reserve.

  7. Anxious women do not show the expected decrease in cardiovascular stress responsiveness as pregnancy advances.

    Science.gov (United States)

    Braeken, M A K A; Jones, A; Otte, R A; Widjaja, D; Van Huffel, S; Monsieur, G J Y J; van Oirschot, C M; Van den Bergh, B R H

    2015-10-01

    Altered stress responsiveness is a risk factor for mental and physical illness. In non-pregnant populations, it is well-known that anxiety can alter the physiological regulation of stress reactivity. Characterization of corresponding risks for pregnant women and their offspring requires greater understanding of how stress reactivity and recovery are influenced by pregnancy and women's anxiety feelings. In the current study, women were presented repeatedly with mental arithmetic stress tasks in the first and third pregnancy trimester and reported their trait anxiety using the state trait anxiety inventory. Cardiovascular stress reactivity in late pregnancy was lower than reactivity in the first pregnancy trimester (heart rate (HR): t(197)=4.98, p<.001; high frequency heart rate variability (HF HRV): t(196)=-2.09, p=.04). Less attenuation of stress reactivity occurred in more anxious women (HR: b=0.15, SE=0.06, p=.008; HF HRV: b=-10.97, SE=4.79, p=.02). The study design did not allow the influence of habituation to repeated stress task exposure to be assessed separately from the influence of pregnancy progression. Although this is a limitation, the clear differences between anxious and non-anxious pregnant women are important, regardless of the extent to which differing habituation between the groups is responsible. Less dampened stress reactivity through pregnancy may pose long-term risks for anxious women and their offspring. Follow-up studies are required to determine these risks. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Beata Skibska

    2015-01-01

    Full Text Available Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system.

  9. The psychoemotional status and cardiovascular system functional state of the first-year students under the influence of examination stress

    National Research Council Canada - National Science Library

    Liliana K. Tokaeva; Svetlana S. Parshina; S.S. Pavlenkovich

    2012-01-01

    The aim of this research is to study of the influence of examination stress on psycho-emotional status and functional state of the cardiovascular system of the 1-st year students of pedagogical high school. Methods...

  10. WEB downloadable software for training in cardiovascular hemodynamics in the (3-D stress echo lab

    Directory of Open Access Journals (Sweden)

    Arpesella Giorgio

    2010-11-01

    Full Text Available Abstract When a physiological (exercise stress echo is scheduled, interest focuses on wall motion segmental contraction abnormalities to diagnose ischemic response to stress, and on left ventricular ejection fraction to assess contractile reserve. Echocardiographic evaluation of volumes (plus standard assessment of heart rate and blood pressure is ideally suited for the quantitative and accurate calculation of a set of parameters allowing a complete characterization of cardiovascular hemodynamics (including cardiac output and systemic vascular resistance, left ventricular elastance (mirroring left ventricular contractility, theoretically independent of preload and afterload changes heavily affecting the ejection fraction, arterial elastance, ventricular arterial coupling (a central determinant of net cardiovascular performance in normal and pathological conditions, and diastolic function (through the diastolic mean filling rate. All these parameters were previously inaccessible, inaccurate or labor-intensive and now become, at least in principle, available in the stress echocardiography laboratory since all of them need an accurate estimation of left ventricular volumes and stroke volume, easily derived from 3 D echo. Aims of this paper are: 1 to propose a simple method to assess a set of parameters allowing a complete characterization of cardiovascular hemodynamics in the stress echo lab, from basic measurements to calculations 2 to propose a simple, web-based software program, to learn and training calculations as a phantom of the everyday activity in the busy stress echo lab 3 to show examples of software testing in a way that proves its value. The informatics infrastructure is available on the web, linking to http://cctrainer.ifc.cnr.it

  11. Habitual alcohol consumption is associated with lower cardiovascular stress responses--a novel explanation for the known cardiovascular benefits of alcohol?

    Science.gov (United States)

    Jones, Alexander; McMillan, Merlin R; Jones, Russell W; Kowalik, Grzegorz T; Steeden, Jennifer A; Pruessner, Jens C; Taylor, Andrew M; Deanfield, John E; Muthurangu, Vivek

    2013-07-01

    In contrast to heavy alcohol consumption, which is harmful, light to moderate drinking has been linked to reduced cardiovascular morbidity and mortality. Effects on lipid status or clotting do not fully explain these benefits. Exaggerated cardiovascular responses to mental stress are detrimental to cardiovascular health. We hypothesized that habitual alcohol consumption might reduce these responses, with potential benefits. Advanced magnetic resonance techniques were used to accurately measure cardiovascular responses to an acute mental stressor (Montreal Imaging Stress Task) in 88 healthy adults (∼1:1 male:female). Salivary cortisol and task performance measures were used to assess endocrine and cognitive responses. Habitual alcohol consumption and confounding factors were assessed by questionnaire. Alcohol consumption was inversely related to responses of heart rate (HR) (r = -0.31, p = 0.01), cardiac output (CO) (r = -0.32, p = 0.01), vascular resistance (r = 0.25, p = 0.04) and mean blood pressure (r = -0.31, p = 0.01) provoked by stress, but not to stroke volume (SV), or arterial compliance changes. However, high alcohol consumers had greater cortisol stress responses, compared to moderate consumers (3.5 versus 0.7 nmol/L, p = 0.04). Cognitive measures did not differ. Findings were not explained by variations in age, sex, social class, ethnicity, physical activity, adrenocortical activity, adiposity, smoking, menstrual phase and chronic stress. Habitual alcohol consumption is associated with reduced cardiac responsiveness during mental stress, which has been linked to lower risk of hypertension and vascular disease. Consistent with established evidence, our findings suggest a mechanism by which moderate alcohol consumption might reduce cardiovascular disease, but not high consumption, where effects such as greater cortisol stress responses may negate any benefits.

  12. cardiovasculares

    Directory of Open Access Journals (Sweden)

    Cristina Guerrero

    2006-01-01

    Full Text Available Uno de los aspectos que más discusión ha suscitado en los últimos tiempos entre quienes nos dedicamos al estudio de la emoción tiene que ver con la eventual asociación entre percepción, valoración y respuesta fisiológica. Esto es, siguiendo la máxima aristotélica, cabría cuestionar si las cosas son como son o son como cada quien las percibe. El objetivo de este experimento ha sido establecer la existencia de una conexión entre percepción de control y responsividad cardiovascular. La muestra estudiada ha estado conformada por estudiantes de la Universidad de Castellón; todos ellos han participado de forma voluntaria. La prueba de estrés ha consistido en un examen real de una asignatura troncal de la titulación que cursaban los participantes. Así pues, utilizando una situación de estrés real, hipotetizamos que las respuestas cardiovasculares (medidas a través de la tasa cardiaca, la presión sanguínea sistólica y la presión sanguínea diastólica dependen de la percepción de control que el individuo tiene, o cree tener, sobre la situación.

  13. Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

    Science.gov (United States)

    Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

    2015-01-01

    This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic

  14. Associations between life stress and subclinical cardiovascular disease are partly mediated by depressive and anxiety symptoms.

    Science.gov (United States)

    Bomhof-Roordink, Hanna; Seldenrijk, Adrie; van Hout, Hein P J; van Marwijk, Harm W J; Diamant, Michaela; Penninx, Brenda W J H

    2015-04-01

    Stress experienced during childhood or adulthood has been associated with cardiovascular disease (CVD), but it is not clear whether associations are already prevalent on a subclinical cardiovascular level. This study investigates associations between indicators of life stress and subclinical CVD, and whether these are mediated by depression and anxiety. Subjects were 650 participants of the Netherlands Study of Depression and Anxiety, aged 20-66 years, with or without (27.5%) depressive and anxiety disorders. Life stress included childhood trauma, negative life events and recently experienced daily hassles or job strain. Subclinical CVD was measured as 1) carotid atherosclerosis (intima-media thickness and the presence of plaques) using B-mode ultrasonography, and 2) central arterial stiffness (heart rate normalized augmentation index) using calibrated radial applanation tonometry. Increased central arterial stiffness was shown in subjects who had experienced childhood trauma (per SD increase: β=.07; p=.01), or reported recently experienced daily hassles (per SD increase: β=.06; p=.02), negative life events (per SD increase: β=.05; p=.03), or job strain (high versus low: β=.09; p=.01). Associations between life stress and arterial stiffness appeared to be partly mediated by severity of depressive and anxiety symptoms. No significant associations were found for childhood life events, nor between indicators of life stress and carotid atherosclerosis. Childhood trauma and recent life stress were associated with increased central arterial stiffness. This suggests that life stress - partly via depression and anxiety - might enhance the development and progression of CVD. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Cardiovascular and psychiatric characteristics associated with oxidative stress markers among adolescents with bipolar disorder.

    Science.gov (United States)

    Hatch, Jessica; Andreazza, Ana; Olowoyeye, Omodele; Rezin, Gislane Tezza; Moody, Alan; Goldstein, Benjamin I

    2015-09-01

    In the field of bipolar disorder (BD) research there is an absence of validated biomarkers and limited understanding of the biology underlying excessive and premature cardiovascular disease (CVD). Oxidative stress is a potential biomarker in both BD and CVD. To examine psychiatric and cardiovascular characteristics associated with peripheral oxidative stress markers among adolescents with BD, who are at high risk for CVD. Participants were 30 adolescents, 13-19years old, with BD and without CVD. Ultrasonography was used to evaluate vascular function and structure. Traditional CVD risk factors were also measured. Psychiatric assessments were conducted via semi-structured interview. Serum levels of oxidative stress (lipid hydroperoxides (LPH) and protein carbonylation (PC)) were assayed. Compared to published data on adults with BD, adolescents had significantly lower levels of LPH and PC (t52(11.34), ptheories for BD. Oxidative stress is robustly associated with a proxy measure of atherosclerosis and may explain in part the increased risk of CVD in BD. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Unraveling mechanisms of toxicant-induced oxidative stress in cardiovascular disease.

    Science.gov (United States)

    Dugas, Tammy R

    2018-02-01

    To date, numerous clinical studies examining correlations between oxidative stress biomarkers and cardiovascular diseases (CVD) have repeatedly suggested a role for oxidant injury in the pathogenesis of diseases such as atherosclerosis. Despite this, antioxidant supplementation trials have not demonstrated a reduction in disease progression. Nevertheless, small animal and epidemiological studies have linked exposures to certain toxicants with increased CVD risk involving putative oxidative stress mechanisms. A few prototypical vascular toxicants will be discussed as examples of toxicants that likely act via oxidative stress mechanisms. For discussion, we will classify these toxicants as those that induce direct (e.g., arsenic, nucleoside reverse transcriptase inhibitors) versus indirect (particulate matter, ozone) oxidative stress mechanisms, and those that likely induce CVD through both direct and indirect mechanisms (cigarette smoke). Finally, new findings in oxidative stress research, including the emerging importance of reactive sulfur species, hydrogen peroxide as a presumed endothelium-derived hyperpolarizing factors, etc., will be discussed, as well as the need to determine the role of toxicants in modulating these newly identified pathways. Moreover, given the lack of success in conclusively demonstrating the roles of oxidative stress in CVD risk stratification, research probing the roles of toxicant exposures in propagating CVD pathogenesis may be a novel approach for more conclusively delineating the causal role of oxidative stress in CVD initiation and progression.

  17. Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

    Science.gov (United States)

    Liu, Mei-qing; Chen, Zhe; Chen, Lin-xi

    2016-01-01

    Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS. PMID:26838072

  18. The effects of task demand and decision latitude on cardiovascular reactivity to stress.

    Science.gov (United States)

    Hutt, J; Weidner, G

    1993-01-01

    This study investigated the effects of task demand (absence or presence of time pressure) and decision latitude (choice or no choice over a task) on cardiovascular and affective responses to stressful tasks among 70 college students. Subjects also rated whether they felt under pressure and the extent to which they felt in control. Time pressure was related to elevated systolic blood pressure (SBP) responses among men and increased negative affect for both sexes. Lack of choice over the task also resulted in increased negative affect in both sexes. The least stressful condition--having a choice in the absence of time pressure--resulted in reduced negative affect. In addition to the effects of manipulated decision latitude and demand, perceptions of being in control were associated with reduced SBP among women who had a choice. Perceived control also contributed to reduced negative affect among men. These results suggest that the postulated negative effects of high demand and low decision latitude (ie, job strain) on cardiovascular health may be mediated in part by increased cardiovascular reactivity and negative affect.

  19. The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

    Directory of Open Access Journals (Sweden)

    Rebecca Hutcheson

    2012-01-01

    Full Text Available The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs, and angiotensin II converting enzyme (ACE inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.

  20. The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

    Science.gov (United States)

    Hutcheson, Rebecca; Rocic, Petra

    2012-01-01

    The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD) in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs), and angiotensin II converting enzyme (ACE) inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome. PMID:22829804

  1. Predictive value of a positive exercise stress testing and correlations with cardiovascular risk factors.

    Science.gov (United States)

    Mitu, O; Roca, M; Leon, Maria Magdalena; Mitu, F

    2014-01-01

    Electrocardiogram exercise stress test (EST) is a widespread technique in assessment of coronary artery disease, stratifying cardiovascular risk and prognosis. Evaluation of the impact of cardiovascular risk factors upon the results of EST. The 2-year retrospective study included 294 patients referred to an EST. All patients were assessed according to: presence of typical angina chest pain at admission, medical history of angina or myocardial infarction, resting electrocardiogram, global ejection fraction at echocardiographic exam and traditional cardiovascular risk factors. We compared the results between two groups: positive and negative EST. The patients were age- and sex-matched. 160 patients (54.42%) had a positive EST. Positive EST was associated with typical angina chest pain at admission (88.12% vs. 76.11%, p = 0.008), coronary artery disease history (61.87% vs. 41.04%, p = 0.0003), resting ECG abnormalities (49.37% vs. 36.56%, p = 0.026), arterial hypertension (85.62% vs. 74.62%, p = 0.019). Ejection fraction was higher in the negative EST group (63.34 +/- 8.57% vs. 61.18 +/- 11.34%, p = 0.035). Type 2 diabetes mellitus, smoking, obesity, dyslipidemia and inflammatory syndrome did not significantly influence the results of the EST. Typical angina, medical history of coronary artery disease, arterial hypertension, and reduced ejection fraction are strong predictors for a positive exercise stress test.

  2. Adenosine receptor neurobiology: overview.

    Science.gov (United States)

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases. © 2014 Elsevier Inc. All rights reserved.

  3. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.

    Science.gov (United States)

    Fiorentino, Teresa Vanessa; Prioletta, Annamaria; Zuo, Pengou; Folli, Franco

    2013-01-01

    Diabetes mellitus is associated to an increased risk of cardiovascular diseases. Hyperglycemia is an important factor in cardiovascular damage, working through different mechanisms such as activation of protein kinase C, polyol and hexosamine pathways, advanced glycation end products production. All of these pathways, in association to hyperglycemia-induced mitochondrial dysfunction and endoplasmic reticulum stress, promote reactive oxygen species (ROS) accumulation that, in turn, promote cellular damage and contribute to the diabetic complications development and progression. ROS can directly damage lipids, proteins or DNA and modulate intracellular signaling pathways, such as mitogen activated protein kinases and redox sensitive transcription factors causing changes in protein expression and, therefore, irreversible oxidative modifications. Hyperglycemia-induced oxidative stress induces endothelial dysfunction that plays a central role in the pathogenesis of micro- and macro-vascular diseases. It may also increase pro-inflammatory and pro-coagulant factors expression, induce apoptosis and impair nitric oxide release. Oxidative stress induces several phenotypic alterations also in vascular smooth-muscle cell (VSMC). ROS is one of the factors that can promote both VSMC proliferation/migration in atherosclerotic lesions and VSMC apoptosis, which is potentially involved in atherosclerotic plaque instability and rupture. Currently, there are contrasting clinical evidences on the benefits of antioxidant therapies in the prevention/treatment of diabetic cardiovascular complications. Appropriate glycemic control, in which both hypoglycemic and hyperglycemic episodes are reduced, in association to the treatment of dyslipidemia, hypertension, kidney dysfunction and obesity, conditions which are also associated to ROS overproduction, can counteract oxidative stress and, therefore, both microvascular and macrovascular complications of diabetes mellitus.

  4. Cardiovascular and cerebrovascular effects in response to red bull consumption combined with mental stress.

    Science.gov (United States)

    Grasser, Erik Konrad; Dulloo, Abdul G; Montani, Jean-Pierre

    2015-01-15

    The sale of energy drinks is often accompanied by a comprehensive and intense marketing with claims of benefits during periods of mental stress. As it has been shown that Red Bull negatively impacts human hemodynamics at rest, we investigated the cardiovascular and cerebrovascular consequences when Red Bull is combined with mental stress. In a randomized cross-over study, 20 young healthy humans ingested either 355 ml of a can Red Bull or water and underwent 80 minutes after the respective drink a mental arithmetic test for 5 minutes. Continuous cardiovascular and cerebrovascular recordings were performed for 20 minutes before and up to 90 minutes after drink ingestion. Measurements included beat-to-beat blood pressure (BP), heart rate, stroke volume, and cerebral blood flow velocity. Red Bull increased systolic BP (+7 mm Hg), diastolic BP (+4 mm Hg), and heart rate (+7 beats/min), whereas water drinking had no significant effects. Cerebral blood flow velocity decreased more in response to Red Bull than to water (-9 vs -3 cm/s, p Red Bull; similar increases were also observed after water ingestion. In combination, Red Bull and mental stress increased systolic BP by about 10 mm Hg, diastolic BP by 7 mm Hg, and heart rate by 20 beats/min and decreased cerebral blood flow velocity by -7 cm/s. In conclusion, the combination of Red Bull and mental stress impose a cumulative cardiovascular load and reduces cerebral blood flow even under a mental challenge. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients

    DEFF Research Database (Denmark)

    Devereux, Richard B; Bang, Casper N; Roman, Mary J

    2015-01-01

    randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P≤0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product......In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference...... in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular mass×wall stress×heart rate (triple product) in 905 LIFE participants. The triple product was included as time...

  6. Stress-associated cardiovascular reaction masks heart rate dependence on physical load in mice.

    Science.gov (United States)

    Andreev-Andrievskiy, A A; Popova, A S; Borovik, A S; Dolgov, O N; Tsvirkun, D V; Custaud, M; Vinogradova, O L

    2014-06-10

    When tested on the treadmill mice do not display a graded increase of heart rate (HR), but rather a sharp shift of cardiovascular indices to high levels at the onset of locomotion. We hypothesized that under test conditions cardiovascular reaction to physical load in mice is masked with stress-associated HR increase. To test this hypothesis we monitored mean arterial pressure (MAP) and heart rate in C57BL/6 mice after exposure to stressful stimuli, during spontaneous locomotion in the open-field test, treadmill running or running in a wheel installed in the home cage. Mice were treated with β1-adrenoblocker atenolol (2mg/kg ip, A), cholinolytic ipratropium bromide (2mg/kg ip, I), combination of blockers (A+I), anxiolytic diazepam (5mg/kg ip, D) or saline (control trials, SAL). MAP and HR in mice increased sharply after handling, despite 3weeks of habituation to the procedure. Under stressful conditions of open field test cardiovascular parameters in mice were elevated and did not depend on movement speed. HR values did not differ in I and SAL groups and were reduced with A or A+I. HR was lower at rest in D pretreated mice. In the treadmill test HR increase over speeds of 6, 12 and 18m/min was roughly 1/7-1/10 of HR increase observed after placing the mice on the treadmill. HR could not be increased with cholinolytic (I), but was reduced after sympatholytic (A) or A+I treatment. Anxiolytic (D) reduced heart rate at lower speeds of movement and its overall effect was to unmask the dependency of HR on running speed. During voluntary running in non-stressful conditions of the home cage HR in mice linearly increased with increasing running speeds. We conclude that in test situations cardiovascular reactions in mice are governed predominantly by stress-associated sympathetic activation, rendering efforts to evaluate HR and MAP reactions to workload unreliable. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. A Unique "Angiotensin-Sensitive" Neuronal Population Coordinates Neuroendocrine, Cardiovascular, and Behavioral Responses to Stress.

    Science.gov (United States)

    de Kloet, Annette D; Wang, Lei; Pitra, Soledad; Hiller, Helmut; Smith, Justin A; Tan, Yalun; Nguyen, Dani; Cahill, Karlena M; Sumners, Colin; Stern, Javier E; Krause, Eric G

    2017-03-29

    Stress elicits neuroendocrine, autonomic, and behavioral responses that mitigate homeostatic imbalance and ensure survival. However, chronic engagement of such responses promotes psychological, cardiovascular, and metabolic impairments. In recent years, the renin-angiotensin system has emerged as a key mediator of stress responding and its related pathologies, but the neuronal circuits that orchestrate these interactions are not known. These studies combine the use of the Cre-recombinase/loxP system in mice with optogenetics to structurally and functionally characterize angiotensin type-1a receptor-containing neurons of the paraventricular nucleus of the hypothalamus, the goal being to determine the extent of their involvement in the regulation of stress responses. Initial studies use neuroanatomical techniques to reveal that angiotensin type-1a receptors are localized predominantly to the parvocellular neurosecretory neurons of the paraventricular nucleus of the hypothalamus. These neurons are almost exclusively glutamatergic and send dense projections to the exterior portion of the median eminence. Furthermore, these neurons largely express corticotrophin-releasing hormone or thyrotropin-releasing hormone and do not express arginine vasopressin or oxytocin. Functionally, optogenetic stimulation of these neurons promotes the activation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as well as a rise in systolic blood pressure. When these neurons are optogenetically inhibited, the activity of these neuroendocrine axes are suppressed and anxiety-like behavior in the elevated plus maze is dampened. Collectively, these studies implicate this neuronal population in the integration and coordination of the physiological responses to stress and may therefore serve as a potential target for therapeutic intervention for stress-related pathology.SIGNIFICANCE STATEMENT Chronic stress leads to an array of physiological responses that ultimately

  8. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    Science.gov (United States)

    Daffu, Gurdip; del Pozo, Carmen Hurtado; O’Shea, Karen M.; Ananthakrishnan, Radha; Ramasamy, Ravichandran; Schmidt, Ann Marie

    2013-01-01

    Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease. PMID:24084731

  9. Number of recent stressful life events and incident cardiovascular disease: Moderation by lifetime depressive disorder.

    Science.gov (United States)

    Berntson, Jessica; Patel, Jay S; Stewart, Jesse C

    2017-08-01

    We investigated whether number of recent stressful life events is associated with incident cardiovascular disease (CVD) and whether this relationship is stronger in adults with a history of clinical depression. Prospective data from 28,583 U.S. adults (mean age=45years) initially free of CVD who participated in Waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were examined. Number of past-year stressful life events (Wave 1), lifetime depressive disorder (Wave 1), and incident CVD (Wave 2) were determined by structured interviews. There were 1069 cases of incident CVD. Each additional stressful life event was associated with a 15% increased odds of incident CVD [Odds Ratio (OR)=1.15, 95% Confidence Interval (CI): 1.11, 1.19]. As hypothesized, a stressful life events by lifetime depressive disorder interaction was detected (P=0.003). Stratified analyses indicated that stressful life events had a stronger association with incident CVD among adults with (OR=1.18, 95% CI: 1.10, 1.27, n=4908) versus without (OR=1.10, 95% CI: 1.07, 1.14, n=23,675) a lifetime depressive disorder. Our findings suggest that a greater number of recent stressful life events elevate the risk of new-onset CVD and that this risk is potentiated in adults with a history of clinical depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    Directory of Open Access Journals (Sweden)

    Radha Ananthakrishnan

    2013-10-01

    Full Text Available Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.

  11. Long-term effects of prenatal stress : Changes in adult cardiovascular regulation and sensitivity to stress

    NARCIS (Netherlands)

    Mastorci, Francesca; Vicentini, Massimo; Viltart, Odile; Manghi, Massimo; Graiani, Gallia; Quaini, Federico; Meerlo, Peter; Nalivaiko, Eugene; Maccari, Stefania; Sgoifo, Andrea

    2009-01-01

    Prenatal environment exerts profound influences on the development of an organism and stressful events during pregnancy can bring about long-term physiological/behavioral alterations in the offspring. Epidemiological evidence points to a relationship between intrauterine growth restriction (IUGR),

  12. Effect of noise stress on cardiovascular system in adult male albino rat: implication of stress hormones, endothelial dysfunction and oxidative stress.

    Science.gov (United States)

    Said, Mona A; El-Gohary, Ola A

    2016-07-01

    Noise pollution has been realized as an environmental stressor associated with modern life style that affects our health without being consciously aware of it. The present study investigated the effect of acute, chronic intermittent and chronic continuous exposure to noise of intensity 80-100 dB on heart rate and mean systemic arterial blood pressure in rats and the possible underlying mechanisms. Noise stress causes significant increase in heart rate, mean systemic arterial blood pressure as well as significant increase in plasma levels of corticosterone, adrenaline, noradrenaline, endothelin-1, nitric oxide and malondialdehyde with significant decrease in superoxide dismutase and these values are significantly more worse in chronic continuous exposure to noise than acute or chronic intermittent exposure. These findings suggest that noise stress has many adverse effects on cardiovascular system via increasing plasma levels of stress hormones, oxidative stress and endothelial dysfunction. These findings have major implication in the management of adverse cardiovascular reactions of people subjected to daily noise stress.

  13. Emotion, stress, and cardiovascular response: an experimental test of models of positive and negative affect.

    Science.gov (United States)

    Dowd, Haulie; Zautra, Alex; Hogan, Michael

    2010-09-01

    The nature of the relationship between positive affect (PA) and negative affect (NA) has been a topic of debate for some time. In particular, there are gaps in our knowledge of the independent effects of PA and NA on health under stress. The study examined the effects of a laboratory-induced stressor on the experience of PA and NA, and the effects of affect on cardiovascular (CV) reactivity and recovery. A sample of 56 female college students was randomly assigned to a public speaking (stress) task or a silent reading (control) task. Pre- and posttask PA and NA were measured using the Positive and Negative Affect Schedule (PANAS Watson J Pers Soc Psychol 54:1,063-1,070, 1988). Baseline, task, and posttask cardiovascular measures were also recorded. The results indicated that PA and NA responded differently to the stressor and contributed independently to the prediction of both CV reactivity and recovery. Of particular interest was the finding that higher levels of both PA and NA predicted greater CV recovery. Results are discussed in light of the debate concerning the (in)dependence of positive and negative emotions and the importance of understanding the dynamics of emotions, stress, and health.

  14. Platelet oxidative stress and its relationship with cardiovascular diseases in type 2 diabetes mellitus patients.

    Science.gov (United States)

    El Haouari, Mohammed

    2017-10-05

    Enhanced platelet activation and thrombosis are linked to various cardiovascular diseases. Among other mechanisms, oxidative stress seems to play a pivotal role in platelet hyperactivity. Indeed, upon stimulation by physiological agonists, human platelets generate and release several types of reactive oxygen species (ROS) such as O2-, H2O2 or OH- , further amplifying the platelet activation response via various signalling pathways, including, formation of isoprostanes, Ca2+ mobilization and NO inactivation. Furthermore, excessive platelet ROS generation, incorporation of free radicals from environment and/or depletion of antioxidants induce pro-oxidant, pro-inflammatory and platelet hyperaggregability effects, leading to the incidence of cardiovascular events. Here, we review the current knowledge regarding the effect of oxidative stress on platelet signaling pathways and its implication in CVD such as type 2 diabetes mellitus. We also summarize the role of natural antioxidants included in vegetables, fruits and medicinal herbs in reducing platelet function via an oxidative stress-mediated mechanism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease.

    Science.gov (United States)

    Cohen, Beth E; Edmondson, Donald; Kronish, Ian M

    2015-11-01

    The notion that psychological states can influence physical health is hardly new, and perhaps nowhere has the mind-body connection been better studied than in cardiovascular disease (CVD). Recently, large prospective epidemiologic studies and smaller basic science studies have firmly established a connection between CVD and several psychological conditions, including depression, chronic psychological stress, posttraumatic stress disorder (PTSD), and anxiety. In addition, numerous clinical trials have been conducted to attempt to prevent or lessen the impact of these conditions on cardiovascular health. In this article, we review studies connecting depression, stress/PTSD, and anxiety to CVD, focusing on findings from the last 5 years. For each mental health condition, we first examine the epidemiologic evidence establishing a link with CVD. We then describe studies of potential underlying mechanisms and finally discuss treatment trials and directions for future research. © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2015. This work is written by (a) US Government employees(s) and is in the public domain in the US.

  16. Cardiovascular and Hepatic Toxicity of Cocaine: Potential Beneficial Effects of Modulators of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Manuela Graziani

    2016-01-01

    Full Text Available Oxidative stress (OS is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy.

  17. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    DEFF Research Database (Denmark)

    Assies, Johanna; Mocking, Roel J T; Lok, Christianne A

    2014-01-01

    Objective: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive resp......-occurrence of) psychiatric disorders and CVD. This might have implications for research into diagnosis and (preventive) treatment of (CVD in) psychiatric patients. © 2014 The Authors.......Objective: Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive...... responses, might underlie comorbidity between CVD and psychiatric disorders. Method: We conducted a literature search and integrated data in a narrative review. Results: Oxidative stress, mainly generated in mitochondria, is implicated in both psychiatric and cardiovascular pathophysiology. Oxidative stress...

  18. Coping with racism: the impact of prayer on cardiovascular reactivity and post-stress recovery in African American women.

    Science.gov (United States)

    Cooper, Denise C; Thayer, Julian F; Waldstein, Shari R

    2014-04-01

    Prayer is often used to cope with racism-related stress. Little is known about its impact on cardiovascular function. This study examined how prayer coping relates to cardiovascular reactivity (CVR), post-stress recovery, and affective reactivity in response to racism-related stress. African American women (n =81; mean age=20 years) reported their use of prayer coping on the Perceived Racism Scale and completed anger recall and racism recall tasks while undergoing monitoring of systolic and diastolic blood pressure (DBP), heart rate, heart rate variability (HRV), and hemodynamic measures. Prayer coping was examined for associations with CVR, recovery, and affective change scores using general linear models with repeated measures. Higher prayer coping was associated with decreased state stress and DBP reactivity during racism recall (p'sracism recall recovery(p'sracism by utilizing prayer may have cardiovascular benefits for African American women.

  19. Simultaneous measurement of left and right ventricular volumes and ejection fraction during dobutamine stress cardiovascular magnetic resonance.

    Science.gov (United States)

    Mandapaka, Sangeeta; Hamilton, Craig A; Morgan, Timothy M; Hundley, William Gregory

    2011-01-01

    During cardiovascular stress, if right ventricular (RV) stroke volume exceeds left ventricular (LV) stroke volume, then a large volume of blood is displaced into the pulmonary circulation that may precipitate pulmonary edema. We sought to determine the metrics by which cardiovascular magnetic resonance (CMR) could measure simultaneous displacement of RV and LV stroke volumes during dobutamine stress. Thirteen healthy subjects (5 women) aged 53 ± 10 years without medical conditions and taking no medications underwent 2 CMR examinations at 1.5 T separated by 4 to 8 weeks in which RV and LV stroke volumes were determined during intravenous dobutamine and atropine infused to achieve 80% of the maximum predicted heart rate response for age. The RV and LV stroke volumes were highly correlated at each level of stress (rest: r = 0.98, P = 0.007; low stress: r = 0.87, P = 0.001; and peak stress: r = 0.88, P = 0.001), and the mean difference in SV at each level of stress (rest, low stress, and peak stress was 0 to 2 mL on examinations 1 and 2. Simultaneous change in right and left ventricular stroke volumes can be assessed in a highly reproducible manner throughout the course of dobutamine CMR stress administered to achieve 80% of maximum predicted heart rate response for age. This technology may help identify discrepancies in RV and LV stroke volumes during cardiovascular stress that are associated with the development of pulmonary edema.

  20. Effect of Particulate Matter Air Pollution on Cardiovascular Oxidative Stress Pathways.

    Science.gov (United States)

    Rao, Xiaoquan; Zhong, Jixin; Brook, Robert D; Rajagopalan, Sanjay

    2017-12-12

    Particulate matter (PM) air pollution is a leading cause of global cardiovascular morbidity and mortality. Understanding the biological action of PM is of particular importance in improvement of public health. Recent Advances: Both fine (PM effects through redox regulated pathways. A rather simplistic graded ramp model of redox stress has been replaced by a more sophisticated understanding of the role of oxidative stress in signaling, and the realization that many of the observed effects may involve disruption and/or enhancement of normal endogenous redox signaling and induction of a potent immune-mediated response, through entrainment of multiple reactive oxygen species (ROS). The molecular events by which pulmonary oxidative stress in response to inhalational exposure to air pollution triggers inflammation, major ROS (e.g., superoxide, hydroxyl radical, nitric oxide, and peroxynitrite) generated in air pollution exposure, types of oxidative tissue damage in target organs, contributions of nonimmune and immune cells in inflammation, and the role of protective proteins (e.g., surfactant, proteins, and antioxidants) are highly complex and may differ depending on models and concomitant disease states. While the role of oxidative stress in the lung has been well demonstrated, the role of oxidative stress in mediating systemic effects especially in inflammation and injury processes needs further work. The role of antioxidant defenses with chronic exposure will also need further exploration. Antioxid. Redox Signal. 00, 000-000.

  1. Impact of oral contraception and neuroticism on cardiovascular stress reactivity across the menstrual cycle.

    Science.gov (United States)

    Schallmayer, Sabine; Hughes, Brian M

    2010-01-01

    In order to avoid interpretation problems relating to the impact of reproductive hormones on cardiovascular variables, research on the psychosomatic etiology of cardiovascular disease frequently excludes women who use oral contraceptives (OCs), and sometimes women as a whole, from study samples. However, such conventions are based on a body of research that suffers from methodological limitations and, in any event, has produced inconclusive findings. Further, the relevant research fails to control for personality differences between users and non-users of OC that may, in turn, lead to differences in stress reactivity. In the present study, using a counterbalanced mixed-factorial design, 24 women (12 OC users and 12 non-users), drawn from a screening sample of 110, were tested across a 4-month timeframe. Cardiovascular reactivity (CVR) was measured during both the follicular and luteal phases of each woman's menstrual cycle. Menstrual phase and OC use were found to exert synergistic effects on CVR. A significant relationship between neuroticism and systolic blood pressure reactivity was observed, which was found to be contingent on menstrual phase. It is concluded that while menstrual phase and OC use are relevant, their contaminating influence on CVR research can be circumvented.

  2. Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA.

    Science.gov (United States)

    Nair, Nandini; Gongora, Enrique

    2017-01-01

    The concept of antioxidant therapies assumes high importance as oxidative stress is associated with cardiovascular aging via endothelial dysfunction. This review focuses on exploring the interaction between nrf-2 and ADMA in influencing the nitric oxide pathway and cardiovascular function. A systematic review of literature from 1990 to 2016 was conducted using Pubmed and Google Scholar. The literature suggests a strong influence of nrf-2 activation on up regulation of DDAH I which degrades ADMA, the endogenous inhibitor of nitric oxide synthase. The resulting decrease of ADMA would in turn enhance nitric oxide (NO) production. This would support endothelial function by adequate NO production and homeostasis of endothelial function. As NO production has many positive pleiotropic effects in the cardiovascular system, such an interaction could be utilized for designing molecular therapeutics. The targets for therapy need not be limited to activation of nrf-2. Modulation of molecules downstream such as DDAH I can be used to regulate ADMA levels. Most current literature is supported by animal studies. The concept of antioxidant therapies needs to be tested in well-defined randomized control trials. The biochemical basis of nrf-2 activation needs to be substantiated in human studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

    Science.gov (United States)

    Sallam, Nada

    2016-01-01

    Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential. PMID:26823952

  4. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases.

    Science.gov (United States)

    Sallam, Nada; Laher, Ismail

    2016-01-01

    Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential.

  5. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Nada Sallam

    2016-01-01

    Full Text Available Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual’s characteristics; therefore, the development of personalized exercise programs is essential.

  6. Presence of a pet dog and human cardiovascular responses to mild mental stress.

    Science.gov (United States)

    Kingwell, B A; Lomdahl, A; Anderson, W P

    2001-10-01

    The mechanisms underlying the possible cardiovascular benefits of pet ownership have not been established. Using a randomized design, the effect of a friendly dog on cardiovascular and autonomic responses to acute, mild mental stress was investigated. Seventy-two subjects (aged 40 +/- 14 y; mean +/- SD) participated. Rest was alternated with mental stress during four 10-minute periods. An unknown dog was randomly selected to be present during the first or the second half of the study. Blood pressure (BP) and heart rate (HR) were monitored continuously and cardiac autonomic function assessed using spectral analysis of heart period. Heart period variability data were expressed as the ratio of 0.1 Hz to respiratory or high frequency variation (LF/HF). Whereas mental stress significantly increased BP and HR in the absence of the dog (from 125/71 +/- 3/2 to 133/75 +/- 3/2 mm Hg; p <0.001), the presence of the dog had no effect on these variables. Heart period LF/HF ratio was lowest in dog owners in the presence of the dog (dog present 2.8 +/- 0.3 versus dog absent 3.4 +/- 0.4; p <0.001) and in non-dog owners in the absence of the dog (dog present 3.4 +/- 0.4 versus dog absent 2.8 +/- 0.3; p <0.001). In conclusion, a friendly but unfamiliar dog does not influence BP or HR either at rest or during mild mental stress. Cardiac autonomic profile was most favorable in the presence of the dog for dog owners and in the absence of the dog for non-owners.

  7. Heat and Dehydration Additively Enhance Cardiovascular Outcomes following Orthostatically-Stressful Calisthenics Exercise.

    Science.gov (United States)

    Akerman, Ashley P; Lucas, Samuel J E; Katare, Rajesh; Cotter, James D

    2017-01-01

    Exercise and exogenous heat each stimulate multiple adaptations, but their roles are not well delineated, and that of the related stressor, dehydration, is largely unknown. While severe and prolonged hypohydration potentially "silences" the long-term heat acclimated phenotype, mild and transient dehydration may enhance cardiovascular and fluid-regulatory adaptations. We tested the hypothesis that exogenous heat stress and dehydration additively potentiate acute (24 h) cardiovascular and hematological outcomes following exercise. In a randomized crossover study, 10 physically-active volunteers (mean ± SD: 173 ± 11 cm; 72.1 ± 11.5 kg; 24 ± 3 year; 6 females) completed three trials of 90-min orthostatically-stressful calisthenics, in: (i) temperate conditions (22°C, 50% rh, no airflow; CON); (ii) heat (40°C, 60% rh) whilst euhydrated (HEAT), and (iii) heat with dehydration (no fluid ~16 h before and during exercise; HEAT+DEHY). Using linear mixed effects model analyses, core temperature (TCORE) rose 0.7°C more in HEAT than CON (95% CL: [0.5, 0.9]; p calisthenics.

  8. Heat and Dehydration Additively Enhance Cardiovascular Outcomes following Orthostatically-Stressful Calisthenics Exercise

    Science.gov (United States)

    Akerman, Ashley P.; Lucas, Samuel J. E.; Katare, Rajesh; Cotter, James D.

    2017-01-01

    Exercise and exogenous heat each stimulate multiple adaptations, but their roles are not well delineated, and that of the related stressor, dehydration, is largely unknown. While severe and prolonged hypohydration potentially “silences” the long-term heat acclimated phenotype, mild and transient dehydration may enhance cardiovascular and fluid-regulatory adaptations. We tested the hypothesis that exogenous heat stress and dehydration additively potentiate acute (24 h) cardiovascular and hematological outcomes following exercise. In a randomized crossover study, 10 physically-active volunteers (mean ± SD: 173 ± 11 cm; 72.1 ± 11.5 kg; 24 ± 3 year; 6 females) completed three trials of 90-min orthostatically-stressful calisthenics, in: (i) temperate conditions (22°C, 50% rh, no airflow; CON); (ii) heat (40°C, 60% rh) whilst euhydrated (HEAT), and (iii) heat with dehydration (no fluid ~16 h before and during exercise; HEAT+DEHY). Using linear mixed effects model analyses, core temperature (TCORE) rose 0.7°C more in HEAT than CON (95% CL: [0.5, 0.9]; p exercise increased in all trials; the 7% increase in HEAT was not reliably more than in CON (5%; p = 0.335), but was an additional 4% larger after HEAT+DEHY ([1, 8]; p = 0.005 vs. HEAT). Pooled-trial correlational analysis showed the rise in TCORE predicted the hypotension (r = −0.4) and plasma volume expansion (r = 0.6) at 24 h, with more hypotension reflecting more plasma expansion (r = −0.5). In conclusion, transient dehydration with heat potentiates short-term (24-h) hematological (hypervolemic) and cardiovascular (hypotensive) outcomes following calisthenics. PMID:29062280

  9. Gender-Specific Association of Oxidative Stress and Inflammation with Cardiovascular Risk Factors in Arab Population

    Directory of Open Access Journals (Sweden)

    Abdelkrim Khadir

    2015-01-01

    Full Text Available Background. The impact of gender difference on the association between metabolic stress and cardiovascular disease (CVD remains unclear. We have investigated, for the first time, the gender effect on the oxidative and inflammatory stress responses and assessed their correlation with classical cardiometabolites in Arab population. Methods. A total of 378 adult Arab participants (193 females were enrolled in this cross-sectional study. Plasma levels of CRP, IL-6, IL-8, TNF-α, ROS, TBARs, and PON1 were measured and correlated with anthropometric and cardiometabolite parameters of the study population. Results. Compared to females, males had significantly higher FBG, HbA1c, TG, and blood pressure but lower BMI, TC, and HDL (P < 0.05. After adjustment for BMI and WC, females had higher levels of ROS, TBARS, and CRP (P < 0.001 whereas males had increased levels of IL-8, IL-6, and TNF-α (P < 0.05. Moreover, after adjustment for age, BMI, and gender, the levels of TNF-α, IL-6, and ROS were associated with central obesity but not general obesity. Conclusion. Inflammation and oxidative stress contribution to CVD risk in Arab population linked to gender and this risk is better reflected by central obesity. Arab females might be at risk of CVD complications due to increased oxidative stress.

  10. Associations of chronic stress burden, perceived stress, and traumatic stress with cardiovascular disease prevalence and risk factors in the HCHS/SOL Sociocultural Ancillary Study

    Science.gov (United States)

    Gallo, Linda C.; Roesch, Scott C.; Fortmann, Addie L.; Carnethon, Mercedes R.; Penedo, Frank J.; Perreira, Krista; Birnbaum-Weitzman, Orit; Wassertheil-Smoller, Sylvia; Castañeda, Sheila F.; Talavera, Gregory A.; Sotres-Alvarez, Daniela; Daviglus, Martha L.; Schneiderman, Neil; Isasi, Carmen R.

    2015-01-01

    Objective The current study examined multiple stress indicators (chronic, perceived, traumatic) in relation to prevalent coronary heart disease (CHD), stroke, and major cardiovascular disease (CVD) risk factors (i.e., diabetes, dyslipidemia, hypertension, current smoking) in the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study (2010–2011). Methods Participants were 5313 men and women, 18–74 years old, representing diverse Hispanic/Latino ethnic backgrounds, who underwent a comprehensive baseline clinical exam and sociocultural exam with measures of stress. Results Chronic stress burden was related to a higher prevalence of CHD after adjusting for sociodemographic, behavioral and biological risk factors [OR (95% CI) = 1.22, (1.10–1.36)] and related to stroke prevalence in the model adjusted for demographic and behavioral factors [OR (95% CI) = 1.26, (1.03–1.55∂)]. Chronic stress was also related to a higher prevalence of diabetes [OR=1.20, (1.11–1.31)] and hypertension [OR=1.10 (1.02–1.19)] in individuals free from CVD (N=4926). Perceived stress [OR=1.03 (1.01–1.05)] and traumatic stress [OR=1.15 (1.05–1.26)] were associated with a higher prevalence of smoking. Participants who reported a greater number of lifetime traumatic events also unexpectedly showed a lower prevalence of diabetes [OR=.89 (.83–.97)] and hypertension [OR=.88 (.82–.93)]. Effects were largely consistent across age and sex groups. Conclusions The study underscores the utility of examining multiple indicators of stress in relation to health, since the direction and consistency of associations may vary across distinct stress conceptualizations. In addition, the study suggests that chronic stress is related to higher CVD risk and prevalence in Hispanics/Latinos, the largest U.S. ethnic minority group. PMID:24979579

  11. The Effect of Binaural Beat Technology on the Cardiovascular Stress Response in Military Service Members With Postdeployment Stress.

    Science.gov (United States)

    Gantt, MeLisa A; Dadds, Stephanie; Burns, Debra S; Glaser, Dale; Moore, Angelo D

    2017-07-01

    To assess the efficacy of embedded theta brainwave frequency in music using binaural beat technology (BBT) compared to music alone on the cardiovascular stress response in military service members with postdeployment stress. A double-blinded, randomized, pre- and postintervention trial. Seventy-four military services members with complaint of postdeployment stress were randomized to either music with BBT or music alone. Each group listened to their respective intervention for a minimum of 30 min at bedtime for three consecutive nights a week for a total of 4 weeks. A 20-min pre- and postintervention heart rate variability (HRV) stress test and daily perceived stress via diaries assessed intervention efficacy. There was a statistical difference (p = .01) in low-frequency HRV between the music with BBT group compared to the music only group. The average low-frequency HRV decreased in the music with BBT group 2.5 ms 2 /Hz, while in the music only group it increased 7.99 ms 2 /Hz. There was also a significant difference (p = .01) in the high-frequency HRV measures, with the music with BBT group showing an increase in HRV by 2.5 ms 2 /Hz compared to the music only group, which decreased by 7.64 ms 2 /Hz. There were significant (p = .01) differences found in total power measures, with the music only group decreasing by 1,113.64 ms 2 /Hz compared to 26.68 ms 2 /Hz for the music with BBT group. Finally, daily diaries consistently showed that participants who used BBT reported less stress over the course of the 4 weeks. When placed under an acute stressor, participants who used music with embedded BBT showed a decrease in sympathetic responses and an increase in parasympathetic responses, while participants who used music alone had the opposite effect. The use of BBT in the theta brainwave frequency embedded into music decreases physical and psychological indications of stress. BBT embedded with beta and delta frequencies may improve cognitive functioning and sleep quality

  12. Dislipidemia and oxidative stress in mild and in severe psoriasis as a risk for cardiovascular disease.

    Science.gov (United States)

    Rocha-Pereira, P; Santos-Silva, A; Rebelo, I; Figueiredo, A; Quintanilha, A; Teixeira, F

    2001-01-01

    Psoriasis is a common chronic and recurrent inflammatory skin disorder that has been associated with oxidative stress, abnormal plasma lipid metabolism and with high frequency of cardiovascular events. This prevalence seems to be related to the severity of psoriasis, as it occurs more frequently in patients presenting large areas of the body affected with psoriasis lesions. The aim of our work was to evaluate the development of oxidative stress and of dislipidemia in psoriasis, and to look for a correlation between their levels and worsening of psoriasis. We evaluated lipid profile, total antioxidant capacity, antioxidant vitamins A and E, and lipoperoxidation products. The study was performed in controls and in patients presenting mild and severe psoriasis. Patients presented risk changes in lipid profile (a rise in cholesterol (P<0.01), triglycerides (P<0.001), low density lipoprotein cholesterol (P<0.01), very low density lipoprotein cholesterol (P<0.01), apolipoprotein B (P<0.001) and lipoprotein(a) (P<0.001); and a reduction in high density lipoprotein cholesterol (P<0.001)), a rise in lipoperoxidation products (P<0.001) and a reduction in total antioxidant capacity (P<0.001) and in antioxidant vitamins A (P<0.001) and E (P<0.05). Moreover, we found that the worsening of psoriasis was associated with the enhancement of oxidative stress and of the lipid risk changes. Our data suggest that psoriasis patients must be considered as a group at risk for cardiovascular disease and that this risk seems to be higher in severe psoriasis. In addition, a possible benefit of an enriched diet or of a supplement of vitamins A and E in psoriasis patients should be further studied.

  13. Environmental stress and vestibular inputs modulate cardiovascular responses to orthostasis in hypertensive rats.

    Science.gov (United States)

    Raffai, Gábor; Csekő, Csongor; Nádasy, György; Kocsis, László; Dézsi, László; Hunyor, Stephen N; Monos, Emil

    2018-01-01

    The frequent accompaniment of hypertension by orthostatic circulatory disorders prompted us to investigate the effect of repeated and sustained head-up and head-down tilt positions on cardiovascular responses in spontaneously hypertensive rats vs. Wistar rats using radiotelemetric implants. Repeated orthostasis caused a transient elevation in blood pressure (7.3±1.7 mmHg) and heart rate (39.7±10.5 BPM), while repeated antiorthostasis led only to reversible tachycardia (85.6±11.7-54.3±16.8 BPM) in spontaneously hypertensive rats. In contrast to the Wistar rats, sustained tilt failed to affect the blood pressure or heart rate in spontaneously hypertensive rats because the environmental stress of being placed in horizontal tilt cages prior to the sustained tilt test induced marked changes in cardiovascular parameters. Non-specific stress responses were eliminated both by the anxiolytic diazepam and a sub-anesthetic dose of chloralose. Unlike diazepam, chloralose amplified the orthostatic pressor responses in the Wistar rats. In contrast to diazepam preventing the pressor response and associated tachycardia in spontaneously hypertensive rats, chloralose elicited this effect during both sustained orthostasis (36.0±7.3 mmHg, 63.7±21.8 BPM) and antiorthostasis (42.9±10.9 mmHg, 82.8±25.4 BPM), with a reduced baroreflex sensitivity. However, during sustained orthostasis, removal of the vestibular input led to a depressor response with bradycardia (12.5±3.2 mmHg, 59.3±17.3 BPM), whereas antiorthostasis only reduced blood pressure (20.5±7.1 mmHg) in the spontaneously hypertensive rats. We conclude that repeated tilts induce a transient pressor response and/or tachycardia in spontaneously hypertensive rats. Cardiovascular parameters are suppressed by diazepam, whereas chloralose evokes both blood pressure and heart rate responses during sustained tilts, which are primarily elicited by baroreflex suppression in hypertension. Vestibular inputs

  14. Detection of ischaemic myocardial lesions with coronary CT angiography and adenosine-stress dynamic perfusion imaging using a 128-slice dual-source CT: diagnostic performance in comparison with cardiac MRI.

    Science.gov (United States)

    Kim, S M; Choi, J-H; Chang, S-A; Choe, Y H

    2013-12-01

    We assessed the diagnostic performance of adenosine-stress dynamic CT perfusion (ASDCTP) imaging and coronary CT angiography (CCTA) for the detection of ischaemic myocardial lesions using 128-slice dual-source CT compared with that of 1.5 T cardiac MRI. This prospective study included 33 patients (61±8 years, 82% male) with suspected coronary artery diseases who underwent ASDCTP imaging and adenosine-stress cardiac MRI. Two investigators independently evaluated ASDCTP images in correlation with significant coronary stenosis on CCTA using two different thresholds of 50% and 70% diameter stenosis. Hypoattenuated myocardial lesions on ASDCTP associated with significant coronary stenoses on CCTA were regarded as true perfusion defects. All estimates of diagnostic performance were calculated and compared with those of cardiac MRI. With use of a threshold of 50% diameter stenosis on CCTA, the diagnostic estimates per-myocardial segment were as follows: sensitivity, 81% [95% confidence interval (CI): 70-92%]; specificity, 94% (95% CI: 92-96%); and accuracy 93% (95% CI: 91-95%). With use of a threshold of 70%, the diagnostic estimates were as follows: sensitivity, 48% (95% CI: 34-62%); specificity, 99% (95% CI: 98-100%); and accuracy, 94% (95% CI: 92-96%). Dynamic CTP using 128-slice dual-source CT enables the assessment of the physiological significance of coronary artery lesions with high diagnostic accuracy in patients with clinically suspected coronary artery disease. Combined CCTA and ASDCTP yielded high accuracy in the detection of perfusion defects regardless of the threshold of significant coronary stenosis.

  15. Immediate and long-term effects of psychological stress during adolescence in cardiovascular function: comparison of homotypic vs heterotypic stress regimens.

    Science.gov (United States)

    Duarte, Josiane O; Planeta, Cleopatra S; Crestani, Carlos C

    2015-02-01

    Adolescence has been proposed as an ontogenic period of vulnerability to stress. Nevertheless, the impact of stressful events during adolescence in cardiovascular activity is poorly understood. Therefore, the purpose of this study was to investigate the immediate and long-lasting effects of exposure to stressful events during adolescence in cardiovascular function of rats. To this end, we compared the impact of 10-days exposure to two chronic stress protocols: the repeated restraint stress (RRS, homotypic) and chronic variable stress (CVS, heterotypic). Independent groups of animals were tested 24h (immediate) or three weeks (long-lasting) following completion of stress period. Exposure to CVS, but not RRS, during adolescence increased basal HR values without affecting arterial pressure, which was followed by augmented power of oscillatory component at low frequency (sympathetic-related) of the pulse interval (PI). RRS enhanced variance of the PI with an increase in the power of both low and high (parasympathetic-related) frequency components. RRS also increased the baroreflex gain. Neither RRS nor CVS affected systolic arterial pressure variability. The RRS-evoked changes in PI variability were long-lasting and persisted into adulthood while all alterations evoked by the CVS were reversed in adulthood. These findings indicate a stress type-specific influence in immediate and long-term effects of stress during adolescence in cardiovascular function. While immediate changes in cardiovascular function were mainly observed following CVS, long-lasting autonomic consequences in adulthood were observed only in animals exposed to RRS during adolescence. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  16. Recreational scuba diving: negative or positive effects of oxidative and cardiovascular stress?

    Science.gov (United States)

    Perovic, Antonija; Unic, Adriana; Dumic, Jerka

    2014-01-01

    Environmental conditions and increased physical activity during scuba diving are followed by increased production of free radicals and disturbed redox balance. Redox balance disorder is associated with damage of cellular components, changes of cellular signaling pathways and alterations of gene expression. Oxidative stress leads to increased expression of sirtuins (SIRTs), molecules which play an important role in the antioxidant defense, due to their sensitivity to the changes in the redox status and their ability to regulate redox homeostasis. These facts make SIRTs interesting to be considered as molecules affected by scuba diving and in that sense, as potential biomarkers of oxidative status or possible drug targets in reduction of reactive oxygen species (ROS) accumulation. In addition, SIRTs effects through currently known targets make them intriguing molecules which can act positively on health in general and whose expression can be induced by scuba diving.A demanding physical activity, as well as other circumstances present in scuba diving, has the greatest load on the cardiovascular function (CV). The mechanisms of CV response during scuba diving are still unclear, but diving-induced oxidative stress and the increase in SIRTs expression could be an important factor in CV adaptation. This review summarizes current knowledge on scuba diving-induced oxidative and CV stress and describes the important roles of SIRTs in the (patho)physiological processes caused by the redox balance disorder.

  17. Oxidative Stress and Salvia miltiorrhiza in Aging-Associated Cardiovascular Diseases

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    Cheng-Chieh Chang

    2016-01-01

    Full Text Available Aging-associated cardiovascular diseases (CVDs have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging-associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti-inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low-density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood-brain barrier, and promotes self-renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well-designed and randomized control trials will be necessary to confirm the efficacy of SM in aging-associated CVDs.

  18. Obstructive Sleep Apnea, Oxidative Stress and Cardiovascular Disease: Lessons from Animal Studies

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    Rio Dumitrascu

    2013-01-01

    Full Text Available Obstructive sleep apnea (OSA is an independent risk factor for cardiovascular (CV diseases such as arterial hypertension, heart failure, and stroke. Based on human research, sympathetic activation, inflammation, and oxidative stress are thought to play major roles in the pathophysiology of OSA-related CV diseases. Animal models of OSA have shown that endothelial dysfunction, vascular remodelling, and systemic and pulmonary arterial hypertension as well as heart failure can develop in response to chronic intermittent hypoxia (CIH. The available animal data are clearly in favour of oxidative stress playing a key role in the development of all of these CV manifestations of OSA. Presumably, the oxidative stress is due to an activation of NADPH oxidase and other free oxygen radicals producing enzymes within the CV system as evidenced by data from knockout mice and pharmacological interventions. It is hoped that animal models of OSA-related CV disease will continue to contribute to a deeper understanding of their underlying pathophysiology and will foster the way for the development of cardioprotective treatment options other than conventional CPAP therapy.

  19. Oxidative Stress and Salvia miltiorrhiza in Aging-Associated Cardiovascular Diseases.

    Science.gov (United States)

    Chang, Cheng-Chieh; Chang, Yu-Chun; Hu, Wen-Long; Hung, Yu-Chiang

    2016-01-01

    Aging-associated cardiovascular diseases (CVDs) have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM) has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging-associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti-inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low-density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood-brain barrier, and promotes self-renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well-designed and randomized control trials will be necessary to confirm the efficacy of SM in aging-associated CVDs.

  20. Rat cardiac myocyte adenosine transport and metabolism

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    Ford, D.A.; Rovetto, M.J.

    1987-01-01

    Based on the importance of myocardial adenosine and adenine nucleotide metabolism, the adenosine salvage pathway in ventricular myocytes was studied. Accurate estimates of transport rates, separate from metabolic fllux, were determined. Adenosine influx was constant between 3 and 60 s. Adenosine metabolism maintained intracellular adenosine concentrations < 10% of the extracellular adenosine concentrations and thus unidirectional influx could be measured. Myocytes transported adenosine via saturable and nonsaturable processes. A minimum estimate of the V/sub max/ of myocytic adenosine kinase indicated the saturable component of adenosine influx was independent of adenosine kinase activity. Saturable transport was inhibited by nitrobenzylthioinosine and verapamil. Extracellular adenosine taken up myocytes was rapidly phosphorylated to adenine taken up by myocytes was rapidly phosphorylated to adenine nucleotides. Not all extracellular adenosine, though, was phosphorylated on entering myocytes, since free, as opposed to protein-bound, intracellular adenosine was detected after digitonin extraction of cells in the presence of 1 mM ethylene-diaminetetraacetic acid.

  1. Sustained Adenosine Exposure Causes Lung Endothelial Barrier Dysfunction via Nucleoside Transporter–Mediated Signaling

    Science.gov (United States)

    Newton, Julie; Hsiao, Vivian; Shamirian, Paul; Blackburn, Michael R.; Pedroza, Mesias

    2012-01-01

    Previous studies by our group as well as others have shown that acute adenosine exposure enhances lung vascular endothelial barrier integrity and protects against increased permeability lung edema. In contrast, there is growing evidence that sustained adenosine exposure has detrimental effects on the lungs, including lung edema. It is well established that adenosine modulates lung inflammation. However, little is known concerning the effect of sustained adenosine exposure on lung endothelial cells (ECs), which are critical to the maintenance of the alveolar–capillary barrier. We show that exogenous adenosine plus adenosine deaminase inhibitor caused sustained elevation of adenosine in lung ECs. This sustained adenosine exposure decreased EC barrier function, elevated cellular reactive oxygen species levels, and activated p38, JNK, and RhoA. Inhibition of equilibrative nucleoside transporters (ENTs) prevented sustained adenosine-induced p38 and JNK activation and EC barrier dysfunction. Inhibition of p38, JNK, or RhoA also partially attenuated sustained adenosine-induced EC barrier dysfunction. These data indicate that sustained adenosine exposure causes lung EC barrier dysfunction via ENT-dependent intracellular adenosine uptake and subsequent activation of p38, JNK, and RhoA. The antioxidant N-acetylcysteine and the NADPH inhibitor partially blunted sustained adenosine-induced JNK activation but were ineffective in attenuation of p38 activation or barrier dysfunction. p38 was activated exclusively in mitochondria, whereas JNK was activated in mitochondria and cytoplasm by sustained adenosine exposure. Our data further suggest that sustained adenosine exposure may cause mitochondrial oxidative stress, leading to activation of p38, JNK, and RhoA in mitochondria and resulting in EC barrier dysfunction. PMID:22744860

  2. Stress through the mind of the beholder: preliminary differences in child and maternal perceptions of child stress in relation to child cortisol and cardiovascular activity.

    Science.gov (United States)

    Allwood, Maureen A; Gaffey, Allison E; Vergara-Lopez, Chrystal; Stroud, Laura R

    2017-07-01

    The present study examined associations among parent and child reports of youth's stressful life events (SLEs), perceived stress, and biological measures of stress activity (i.e. cortisol and cardiovascular activity). Examining these aspects of youth stress presents several challenges. Unlike adult studies of individual differences in which information regarding SLEs, perceptions of events, and biological activity are gathered from one individual, assessment of individual differences among children usually involves other informants (e.g. parent). However, parent and child reports of SLEs and the child's psychological response to such events are often discordant. Moreover, examinations of youth perception of stress are hampered by limitations of child cognitive processes, as well as parents' limited knowledge of their child's perception of stress. In a preliminary effort to unscramble the complex effects of youth SLEs and perceived stress in relation to biological response to acute stressors, this study examined 51 boys and girls aged 7-16, with no history of psychopathology or medical concerns. Contrary to hypotheses, findings revealed that compared to actual experiences of stress, perceived stress has greater associations with both cortisol and cardiovascular activity. That is, perceived stress is more biologically salient relative to actual stress. Results also suggest that informant differences may explain some previous inconsistent findings in studies of youth's stress reactivity. The current findings mirror the adult studies that show appraisal and perception of traumatic and stressful events may be more predictive of negative health and mental health outcomes than the severity of the events. Further studies are needed to understand the impact of youth's perceptions of stress on their biological stress reactions and later health outcomes such as clinical disorders.

  3. Cardiovascular Reactivity in Patients With Major Depressive Disorder With High- or Low-Level Depressive Symptoms: A Cross-Sectional Comparison of Cardiovascular Reactivity to Laboratory-Induced Mental Stress.

    Science.gov (United States)

    Wang, Mei-Yeh; Chiu, Chen-Huan; Lee, Hsin-Chien; Su, Chien-Tien; Tsai, Pei-Shan

    2016-03-01

    Depression increases the risk of adverse cardiac events. Cardiovascular reactivity is defined as the pattern of cardiovascular responses to mental stress. An altered pattern of cardiovascular reactivity is an indicator of subsequent cardiovascular disease. Because depression and adverse cardiac events may have a dose-dependent association, this study examined the differences in cardiovascular reactivity to mental stress between patients with major depressive disorder (MDD) with high depression levels and those with low depression levels. Moreover, autonomic nervous system regulation is a highly plausible biological mechanism for the pattern of cardiovascular reactivity to mental stress. The association between cardiovascular reactivity and parameters of heart rate variability (HRV), an index for quantifying autonomic nervous system activity modulation, was thus examined. This study included 88 patients with MDD. HRV was measured before stress induction. The Stroop Color and Word Test and mirror star-tracing task were used to induce mental stress. We observed no significant association between depressive symptom level and any of the cardiovascular reactivity parameters. Cardiovascular reactivity to mental stress was comparable between patients with MDD with high-level depressive symptoms and those with low-level depressive symptoms. After adjusting for confounding variables, the high-frequency domain of HRV was found to be an independent predictor of the magnitude of heart rate reactivity (β = -.33, p = .002). In conclusion, the magnitude of cardiovascular reactivity may be independent of depression severity in patients with MDD. The autonomic regulation of cardiovascular responses to mental stress primarily influences heart rate reactivity in patients with MDD. © The Author(s) 2015.

  4. Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence.

    Science.gov (United States)

    Cruz, Fábio C; Duarte, Josiane O; Leão, Rodrigo M; Hummel, Luiz F V; Planeta, Cleopatra S; Crestani, Carlos C

    2016-01-01

    It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc.

  5. Effects of acupuncture on behavioral, cardiovascular and hormonal responses in restraint-stressed Wistar rats

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    Guimarães C.M.

    1997-01-01

    Full Text Available Stress is a well-known entity and may be defined as a threat to the homeostasis of a being. In the present study, we evaluated the effects of acupuncture on the physiological responses induced by restraint stress. Acupuncture is an ancient therapeutic technique which is used in the treatment and prevention of diseases. Its proposed mechanisms of action are based on the principle of homeostasis. Adult male Wistar EPM-1 rats were divided into four groups: group I (N = 12, unrestrained rats with cannulas previously implanted into their femoral arteries for blood pressure and heart rate measurements; group II (N = 12, rats that were also cannulated and were submitted to 60-min immobilization; group III (N = 12, same as group II but with acupuncture needles implanted at points SP6, S36, REN17, P6 and DU20 during the immobilization period; group IV (N = 14, same as group III but with needles implanted at points not related to acupuncture (non-acupoints. During the 60-min immobilization period animals were assessed for stress-related behaviors, heart rate, blood pressure and plasma corticosterone, noradrenaline and adrenaline levels. Group III animals showed a significant reduction (60% on average, P<0.02 in restraint-induced behaviors when compared to groups II and IV. Data from cardiovascular and hormonal assessments indicated no differences between group III and group II and IV animals, but tended to be lower (50% reduction on average in group I animals. We hypothesize that acupuncture at points SP6, S36, REN17, P6 and DU20 has an anxiolytic effect on restraint-induced stress that is not due to a sedative action

  6. Exercise training reduces sympathetic modulation on cardiovascular system and cardiac oxidative stress in spontaneously hypertensive rats.

    Science.gov (United States)

    Bertagnolli, Mariane; Schenkel, Paulo C; Campos, Cristina; Mostarda, Cristiano T; Casarini, Dulce E; Belló-Klein, Adriane; Irigoyen, Maria C; Rigatto, Katya

    2008-11-01

    Spontaneously hypertensive rats (SHRs) show increased cardiac sympathetic activity, which could stimulate cardiomyocyte hypertrophy, cardiac damage, and apoptosis. Norepinephrine (NE)-induced cardiac oxidative stress seems to be involved in SHR cardiac hypertrophy development. Because exercise training (ET) decreases sympathetic activation and oxidative stress, it may alter cardiac hypertrophy in SHR. The aim of this study was to determine, in vivo, whether ET alters cardiac sympathetic modulation on cardiovascular system and whether a correlation exists between cardiac oxidative stress and hypertrophy. Male SHRs (15-weeks old) were divided into sedentary hypertensive (SHR, n = 7) and exercise-trained hypertensive rats (SHR-T, n = 7). Moderate ET was performed on a treadmill (5 days/week, 60 min, 10 weeks). After ET, cardiopulmonary reflex responses were assessed by bolus injections of 5-HT. Autoregressive spectral estimation was performed for systolic arterial pressure (SAP) with oscillatory components quantified as low (LF: 0.2-0.75 Hz) and high (HF: 0.75-4.0 Hz) frequency ranges. Cardiac NE concentration, lipid peroxidation, antioxidant enzymes activities, and total nitrates/nitrites were determined. ET reduced mean arterial pressure, SAP variability (SAP var), LF of SAP, and cardiac hypertrophy and increased cardiopulmonary reflex responses. Cardiac lipid peroxidation was decreased in trained SHRs and positively correlated with NE concentrations (r = 0.89, P < 0.01) and heart weight/body weight ratio (r = 0.72, P < 0.01), and inversely correlated with total nitrates/nitrites (r = -0.79, P < 0.01). Moreover, in trained SHR, cardiac total nitrates/nitrites were inversely correlated with NE concentrations (r = -0.82, P < 0.01). ET attenuates cardiac sympathetic modulation and cardiac hypertrophy, which were associated with reduced oxidative stress and increased nitric oxide (NO) bioavailability.

  7. Heat and Dehydration Additively Enhance Cardiovascular Outcomes following Orthostatically-Stressful Calisthenics Exercise

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    Ashley P. Akerman

    2017-10-01

    Full Text Available Exercise and exogenous heat each stimulate multiple adaptations, but their roles are not well delineated, and that of the related stressor, dehydration, is largely unknown. While severe and prolonged hypohydration potentially “silences” the long-term heat acclimated phenotype, mild and transient dehydration may enhance cardiovascular and fluid-regulatory adaptations. We tested the hypothesis that exogenous heat stress and dehydration additively potentiate acute (24 h cardiovascular and hematological outcomes following exercise. In a randomized crossover study, 10 physically-active volunteers (mean ± SD: 173 ± 11 cm; 72.1 ± 11.5 kg; 24 ± 3 year; 6 females completed three trials of 90-min orthostatically-stressful calisthenics, in: (i temperate conditions (22°C, 50% rh, no airflow; CON; (ii heat (40°C, 60% rh whilst euhydrated (HEAT, and (iii heat with dehydration (no fluid ~16 h before and during exercise; HEAT+DEHY. Using linear mixed effects model analyses, core temperature (TCORE rose 0.7°C more in HEAT than CON (95% CL: [0.5, 0.9]; p < 0.001, and another 0.4°C in HEAT+DEHY ([0.2, 0.5]; p < 0.001, vs. HEAT. Skin temperature also rose 1.2°C more in HEAT than CON ([0.6, 1.8]; p < 0.001, and similarly to HEAT+DEHY (p = 0.922 vs. HEAT. Peak heart rate was 40 b·min−1 higher in HEAT than in CON ([28, 51]; p < 0.001, and another 15 b·min−1 higher in HEAT+DEHY ([3, 27]; p = 0.011, vs. HEAT. Mean arterial pressure at 24-h recovery was not consistently below baseline after CON or HEAT (p ≥ 0.452, but was reduced 4 ± 1 mm Hg after HEAT+DEHY ([0, 8]; p = 0.020 vs. baseline. Plasma volume at 24 h after exercise increased in all trials; the 7% increase in HEAT was not reliably more than in CON (5%; p = 0.335, but was an additional 4% larger after HEAT+DEHY ([1, 8]; p = 0.005 vs. HEAT. Pooled-trial correlational analysis showed the rise in TCORE predicted the hypotension (r = −0.4 and plasma volume expansion (r = 0.6 at 24 h, with

  8. Cardiovascular reactions to psychological stress and abuse history: the role of occurrence, frequency, and type of abuse.

    Science.gov (United States)

    Ginty, Annie T; Masters, Nicole A; Nelson, Eliza B; Kaye, Karen T; Conklin, Sarah M

    2017-03-01

    Extreme cardiovascular reactions to psychological stress have been associated with traumatic life experiences. Previous studies have focused on the occurrence or frequency of abuse rather than type of abuse. We examined how occurrence, frequency, and the type of abuse history are related to cardiovascular reactivity (CVR) to acute psychological stress. The study consisted of between group and continuous analyses to examine the association between occurrence, type, and frequency of abuse with cardiovascular reactions to acute psychological stress. Data from 64 participants were collected. Heart rate, systolic blood pressure, and diastolic blood pressure were measured at baseline and during a standard mental arithmetic stress task. Individuals who experienced abuse showed diminished CVR to acute psychological stress; this was driven specifically by the history of sexual abuse. Frequency of abuse did not relate to stress reactions. These findings accord with previous work suggesting a relationship between traumatic life experience and hypoarousal in physiological reactivity and extend previous findings by suggesting the relationship may be driven by sexual abuse.

  9. Mindfulness may both moderate and mediate the effect of physical fitness on cardiovascular responses to stress: a speculative hypothesis.

    Directory of Open Access Journals (Sweden)

    Marcelo Marcos Piva Demarzo

    2014-03-01

    Full Text Available The psychological construct of mindfulness refers to an awareness that emerges by intentionally paying attention to the present experience in a non-judgmental or evaluative way. This particular quality of awareness has been associated to several indicators of physical and psychological health, and can be developed using mindfulness-based interventions (MBIs, and therefore MBIs have been successfully applied as preventive and complementary interventions and therapies in medicine and psychology. Together with quiet sitting and lying meditation practices, mindful physical exercises such as mindful walking and mindful movement are key elements in MBIs and couple muscular activity with an internally directed focus, improving interoceptive attention to bodily sensations. In addition, MBIs seem to share similar mechanisms with physical fitness by which they may influence cardiovascular responses to stress. Based on these facts, it is feasible to raise the question of whether physical training itself may induce the development of that particular quality of awareness associated with mindfulness, or if one’s dispositional mindfulness (the tendency to be more mindful in daily life could moderate the effects of exercise on cardiovascular response to stress. The role of mindfulness as a mediator or moderator of the effect of exercise training on cardiovascular responses to stress has barely been studied. In this study, we have hypothesized pathways (moderation and mediation by which mindfulness could significantly influence the effects of physical fitness on cardiovascular responses to stress and have discuss potential practical ways to test these hypotheses.

  10. Mindfulness may both moderate and mediate the effect of physical fitness on cardiovascular responses to stress: a speculative hypothesis.

    Science.gov (United States)

    Demarzo, Marcelo M P; Montero-Marin, Jesús; Stein, Phyllis K; Cebolla, Ausiàs; Provinciale, Jaime G; García-Campayo, Javier

    2014-01-01

    The psychological construct of mindfulness refers to an awareness that emerges by intentionally paying attention to the present experience in a non-judgmental or evaluative way. This particular quality of awareness has been associated to several indicators of physical and psychological health, and can be developed using mindfulness-based interventions (MBIs), and therefore MBIs have been successfully applied as preventive and complementary interventions and therapies in medicine and psychology. Together with quiet sitting and lying meditation practices, mindful physical exercises such as "mindful walking" and "mindful movement" are key elements in MBIs and couple muscular activity with an internally directed focus, improving interoceptive attention to bodily sensations. In addition, MBIs seem to share similar mechanisms with physical fitness (PF) by which they may influence cardiovascular responses to stress. Based on these facts, it is feasible to raise the question of whether physical training itself may induce the development of that particular quality of awareness associated with mindfulness, or if one's dispositional mindfulness (DM) (the tendency to be more mindful in daily life) could moderate the effects of exercise on cardiovascular response to stress. The role of mindfulness as a mediator or moderator of the effect of exercise training on cardiovascular responses to stress has barely been studied. In this study, we have hypothesized pathways (moderation and mediation) by which mindfulness could significantly influence the effects of PF on cardiovascular responses to stress and discussed potential practical ways to test these hypotheses.

  11. Terrorism, acute stress, and cardiovascular health: a 3-year national study following the September 11th attacks.

    Science.gov (United States)

    Holman, E Alison; Silver, Roxane Cohen; Poulin, Michael; Andersen, Judith; Gil-Rivas, Virginia; McIntosh, Daniel N

    2008-01-01

    The terrorist attacks of 9/11 (September 11, 2001) present an unusual opportunity to examine prospectively the physical health impact of extreme stress in a national sample. To examine the degree to which acute stress reactions to the 9/11 terrorist attacks predict cardiovascular outcomes in a national probability sample over the subsequent 3 years. A national probability sample of 2729 adults (78.1% participation rate), 95.0% of whom had completed a health survey before 9/11 (final health sample, 2592), completed a Web-based assessment of acute stress responses approximately 9 to 14 days after the terrorist attacks. Follow-up health surveys reassessed physician-diagnosed cardiovascular ailments 1 (n = 1923, 84.3% participation rate), 2 (n = 1576, 74.2% participation rate), and 3 (n = 1950, 78.9% participation rate) years following the attacks. Reports of physician-diagnosed cardiovascular ailments over the 3 years following the attacks. Acute stress responses to the 9/11 attacks were associated with a 53% increased incidence of cardiovascular ailments over the 3 subsequent years, even after adjusting for pre-9/11 cardiovascular and mental health status, degree of exposure to the attacks, cardiovascular risk factors (ie, smoking, body mass index, and number of endocrine ailments), total number of physical health ailments, somatization, and demographics. Individuals reporting high levels of acute stress immediately following the attacks reported an increased incidence of physician-diagnosed hypertension (rate ratios, 2.15 at 1 year and 1.75 at 2 years) and heart problems (rate ratios, 2.98 at 1 year and 3.12 at 2 years) over 2 years. Among individuals reporting ongoing worry about terrorism post-9/11, high 9/11-related acute stress symptoms predicted increased risk of physician-diagnosed heart problems 2 to 3 years following the attacks (rate ratios, 4.67 at 2 years and 3.22 at 3 years). Using health data collected before 9/11 as a baseline, acute stress response to

  12. Respiratory gating in cardiac PET: Effects of adenosine and dipyridamole.

    Science.gov (United States)

    Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E; Kjær, Andreas; Hasbak, Philip

    2017-12-01

    Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim of our study was to compare the resulting imaging quality by the use of a time-based respiratory gating system in two groups administered either adenosine or dipyridamole as the pharmacological stress agent. Forty-eight patients were randomized to adenosine or dipyridamole cardiac stress 82RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4.7) min-1, P respiratory gating compared to dipyridamole (47% vs 71%, P = .12). As a result, imaging quality was superior in the dipyridamole group compared to adenosine. If respiratory gating is considered for use in cardiac PET, a dipyridamole stress protocol is recommended as it, compared to adenosine, causes a more uniform respiration and results in a higher frequency of successful respiratory gating and thereby superior imaging quality.

  13. Genetics Home Reference: adenosine deaminase 2 deficiency

    Science.gov (United States)

    ... Twitter Home Health Conditions Adenosine deaminase 2 deficiency Adenosine deaminase 2 deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized ...

  14. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial.

    Science.gov (United States)

    Iskandrian, Ami E; Bateman, Timothy M; Belardinelli, Luiz; Blackburn, Brent; Cerqueira, Manuel D; Hendel, Robert C; Lieu, Hsiao; Mahmarian, John J; Olmsted, Ann; Underwood, S Richard; Vitola, João; Wang, Whedy

    2007-01-01

    Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging. This multicenter, double-blinded phase 3 trial involved 784 patients at 54 sites. Each patient underwent 2 sets of gated single photon emission computed tomography myocardial perfusion imaging studies: an initial qualifying study with adenosine and a subsequent randomized study with either regadenoson (2/3 of patients) or adenosine. Regadenoson was administered as a rapid bolus (adenosine-regadenoson images and adenosine-adenosine images, lay above a prespecified noninferiority margin. Other prospectively defined safety and tolerability comparisons and supporting analyses were also performed. The average agreement rate based on the median of 3 independent blinded readers was 0.63 +/- 0.03 for regadenoson-adenosine and 0.64 +/- 0.04 for adenosine-adenosine-a 1% absolute difference with the lower limit of the 95% confidence interval lying above the prespecified noninferiority margin. Side-by-side interpretation of regadenoson and adenosine images provided comparable results for detecting reversible defects. The peak increase in heart rate was greater with regadenoson than adenosine, but the blood pressure nadir was similar. A summed symptom score of flushing, chest pain, and dyspnea was less with regadenoson than adenosine (P = .013). This phase 3 trial shows that regadenoson provides diagnostic information comparable to a standard adenosine infusion. There were no serious drug-related side effects, and regadenoson was better tolerated than adenosine.

  15. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    Science.gov (United States)

    Assies, J; Mocking, R J T; Lok, A; Ruhé, H G; Pouwer, F; Schene, A H

    2014-01-01

    Objective Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive responses, might underlie comorbidity between CVD and psychiatric disorders. Method We conducted a literature search and integrated data in a narrative review. Results Oxidative stress, mainly generated in mitochondria, is implicated in both psychiatric and cardiovascular pathophysiology. Oxidative stress affects the intrinsically linked FA and 1-C cycle metabolism: FAs decrease in chain length and unsaturation (particularly omega-3 polyunsaturated FAs), and lipid peroxidation products increase; the 1-C cycle shifts from the methylation to transsulfuration pathway (lower folate and higher homocysteine and antioxidant glutathione). Interestingly, corresponding alterations were reported in psychiatric disorders and CVD. Potential mechanisms through which FA and 1-C cycle metabolism may be involved in brain (neurocognition, mood regulation) and cardiovascular system functioning (inflammation, thrombosis) include membrane peroxidizability and fluidity, eicosanoid synthesis, neuroprotection and epigenetics. Conclusion While oxidative-stress-induced alterations in FA and 1-C metabolism may initially enhance oxidative stress resistance, persisting chronically, they may cause damage possibly underlying (co-occurrence of) psychiatric disorders and CVD. This might have implications for research into diagnosis and (preventive) treatment of (CVD in) psychiatric patients. PMID:24649967

  16. Gender differences and the relationships of perceived background stress and psychological distress with cardiovascular responses to laboratory stressors.

    Science.gov (United States)

    Allen, Michael T; Bocek, Christine M; Burch, Ashley E

    2011-09-01

    The primary aim of this study was to evaluate the relationships of perceived background stress and self-reported psychological distress on cardiovascular reactivity during acute laboratory stressors. The Perceived Stress Scale (PSS) was used as the measure of perceived background stress, and the General Health Questionnaire (GHQ) was used as the measure of psychological distress. A secondary aim was to examine whether background stress and psychological distress affected the susceptibility to induction of a negative mood using music. Heart rate (HR) and blood pressure (BP) were measured in 149 female and male college students at rest and during a stressful mental arithmetic (MA) task and a mood induction procedure. Higher scores on the GHQ were associated with lower systolic BP reactivity during the MA task by all participants. Higher scores on the PSS and GHQ were also associated with lower diastolic BP and HR reactivity, but only in females. Thus, higher self-reports of background stress and psychological distress tended to result in blunted reactivity to an acute laboratory challenge. Higher levels of background stress and psychological distress were not associated with greater susceptibility to a negative mood induction. This study adds to the growing literature indicating that potentially negative health outcomes may be associated with diminished cardiovascular reactivity under certain conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Regadenoson provides perfusion results comparable to adenosine in heterogeneous patient populations: a quantitative analysis from the ADVANCE MPI trials.

    Science.gov (United States)

    Mahmarian, John J; Peterson, Leif E; Xu, Jiaqiong; Cerqueira, Manuel D; Iskandrian, Ami E; Bateman, Timothy M; Thomas, Gregory S; Nabi, Faisal

    2015-04-01

    Total and reversible left ventricular (LV) perfusion defect size (PDS) predict patient outcome. Limited data exist as to whether regadenoson induces similar perfusion abnormalities as observed with adenosine. We sought to determine whether regadenoson induces a similar LV PDS as seen with adenosine across varying patient populations. ADVANCE MPI were prospective, double-blind randomized trials comparing regadenoson to standard adenosine myocardial perfusion tomography (SPECT). Following an initial adenosine SPECT, patients were randomized to either regadenoson (N = 1284) or a second adenosine study (N = 660). SPECT quantification was performed blinded to randomization and image sequence. Propensity analysis was used to define comparability of regadenoson and adenosine perfusion results. Baseline clinical and SPECT results were similar in the two randomized groups. There was a close correlation between adenosine and regadenoson-induced total (r (2) = 0.98, P regadenoson vs adenosine, respectively, and irrespective of age, gender, diabetic status, body mass index, or prior cardiovascular history. By propensity analysis, regadenoson-induced total PDS was significantly larger than observed with adenosine. This is the first study to show that regadenoson induces similar, if not larger, perfusion defects than those observed with adenosine across different patient populations and demonstrates the value of quantitative analysis for defining serial changes in SPECT perfusion results. Regadenoson should provide comparable diagnostic and prognostic SPECT information to that obtained with adenosine.

  18. The Implicit Positive And Negative Affect Test: validity and relationship with cardiovascular stress-responses

    Directory of Open Access Journals (Sweden)

    Melanie M. Van Der Ploeg

    2016-03-01

    Full Text Available Self-report, i.e. explicit, measures of affect cannot fully explain the cardiovascular (CV responses to stressors. Measuring affect beyond self-report, i.e. using implicit measures, could add to our understanding of stress-related CV activity. The Implicit Positive and Negative Affect Test (IPANAT was administered in two studies to test its ecological validity and relation with CV responses and self-report measures of affect. In study 1 students (N = 34 viewed four film clips inducing anger, happiness, fear, or no emotion, and completed the IPANAT and the Positive And Negative Affect Scale at baseline and after each clip. Implicit negative affect (INA was higher and implicit positive affect (IPA was lower after the anger inducing clip and vice versa after the happiness inducing clip. In study 2 students performed a stressful math task with (n = 14 or without anger harassment (n = 15 and completed the IPANAT and a Visual Analogue Scale as an explicit measure afterwards. Systolic (SBP, diastolic (DBP blood pressure, heart rate (HR, heart rate variability (HRV and total peripheral resistance (TPR were recorded throughout. SBP and DBP were higher and TPR was lower in the harassment condition during the task with a prolonged effect on SBP and DBP during recovery. As expected, explicit negative affect (ENA was higher and explicit positive affect (EPA lower after harassment, but ENA and EPA were not related to CV activity. Although neither INA nor IPA differed between the tasks, during both tasks higher INA was related to higher SBP, lower HRV and lower TPR and to slower recovery of DBP after both tasks. Low IPA was related to slower recovery of SBP and DBP after the tasks. Implicit affect was not related to recovery of HR, HRV and TPR. In conclusion, the IPANAT seems to respond to film clip-induced negative and positive affect and was related to CV activity during and after stressful tasks. These findings support the theory that implicitly measured

  19. The Implicit Positive and Negative Affect Test: Validity and Relationship with Cardiovascular Stress-Responses

    Science.gov (United States)

    van der Ploeg, Melanie M.; Brosschot, Jos F.; Thayer, Julian F.; Verkuil, Bart

    2016-01-01

    Self-report, i.e., explicit, measures of affect cannot fully explain the cardiovascular (CV) responses to stressors. Measuring affect beyond self-report, i.e., using implicit measures, could add to our understanding of stress-related CV activity. The Implicit Positive and Negative Affect Test (IPANAT) was administered in two studies to test its ecological validity and relation with CV responses and self-report measures of affect. In Study 1 students (N = 34) viewed four film clips inducing anger, happiness, fear, or no emotion, and completed the IPANAT and the Positive And Negative Affect Scale at baseline and after each clip. Implicit negative affect (INA) was higher and implicit positive affect (IPA) was lower after the anger inducing clip and vice versa after the happiness inducing clip. In Study 2 students performed a stressful math task with (n = 14) or without anger harassment (n = 15) and completed the IPANAT and a Visual Analog Scale as an explicit measure afterwards. Systolic (SBP), diastolic (DBP) blood pressure, heart rate (HR), heart rate variability (HRV), and total peripheral resistance (TPR) were recorded throughout. SBP and DBP were higher and TPR was lower in the harassment condition during the task with a prolonged effect on SBP and DBP during recovery. As expected, explicit negative affect (ENA) was higher and explicit positive affect (EPA) lower after harassment, but ENA and EPA were not related to CV activity. Although neither INA nor IPA differed between the tasks, during both tasks higher INA was related to higher SBP, lower HRV and lower TPR and to slower recovery of DBP after both tasks. Low IPA was related to slower recovery of SBP and DBP after the tasks. Implicit affect was not related to recovery of HR, HRV, and TPR. In conclusion, the IPANAT seems to respond to film clip-induced negative and positive affect and was related to CV activity during and after stressful tasks. These findings support the theory that implicitly measured affect

  20. Resveratrol Prevents Cardiovascular Complications in the SHR/STZ Rat by Reductions in Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Rebecca K. Vella

    2015-01-01

    Full Text Available The cardioprotective effects of resveratrol are well established in animal models of metabolic disease but are yet to be investigated in a combined model of hypertension and diabetes. This study investigated the ability of resveratrol’s antioxidant and anti-inflammatory effects to prevent cardiovascular complications in the spontaneously hypertensive streptozotocin-induced diabetic rat. Diabetes was induced in eight-week-old male spontaneously hypertensive rats via a single intravenous injection of streptozotocin. Following this, resveratrol was administered orally for an eight-week period until the animals were sixteen weeks of age. Upon completion of the treatment regime assessments of oxidative stress, lipid peroxidation, inflammation, and cardiovascular function were made. Resveratrol administration to hypertensive-diabetic animals did not impact upon blood glucose or haemodynamics but significantly reduced oxidative stress, lipid peroxidation, and inflammatory cytokines. Reductions in systemic levels of oxidative stress and inflammation conferred improvements in vascular reactivity and left ventricular pump function and electrophysiology. This study demonstrates that resveratrol administration to hypertensive diabetic animals can elicit cardioprotective properties via antioxidant and anti-inflammatory effects. The observed preservation of cardiovascular function was independent of changes in blood glucose concentration and haemodynamics, suggesting that oxidative stress and inflammation are key components within the pathological cascade associated with hypertension and diabetes.

  1. [Screening of silent myocardial ischaemia by dobutamine stress echocardiography among type 2 diabetics at high cardiovascular risk in Senegal].

    Science.gov (United States)

    Mbaye, A; Yaméogo, N V; Ndiaye, M B; Kane, A D; Diack, B; Dioum, M; Hakim, R; Diagne, D; Kane, M; Diao, M; Diallo, A; Diop, S N; Kane, A

    2011-04-01

    Diabetes is a major risk factor for coronary artery disease witch may develop insidiously. Several non-invasive methods are used to detect silent myocardial ischaemia, especially in diabetic patients at high cardiovascular risk. We project to screen, by dobutamine stress echocardiography, silent myocardial ischaemia in type 2 diabetics in Senegal. We randomly recruited in hospital in Senegal type 2 diabetics aged at least 40 years and a dobutamine stress echocardiography was performed in those selected according to the French Society of Cardiology and the French Language Association for the Study of Diabetes and Metabolic Diseases. Dobutamine stress echocardiography was performed in 79 diabetics at high cardiovascular risk, including 56 women. The average age was 58.8±11.8 years. The exam was positive in 67.1% of cases (53/79), with a predominance of motion abnormalities in anterior territory (83%). Cardiovascular risk factors associated with positivity of test were microalbuminuria (p=0.0001), inactivity (p=0.0001), dyslipidemia (p=0.0002), arterial hypertension (p=0.001), smoking (0.003) and male sex (p=0.004). In Africa, dobutamine stress echocardiography has the advantage of its accessibility and its feasibility. Early detection of silent myocardial ischaemia in diabetics at high risk could optimize their care. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  2. Increased Cardiac Sympathetic Activity and Oxidative Stress in Habitual Electronic Cigarette Users: Implications for Cardiovascular Risk.

    Science.gov (United States)

    Moheimani, Roya S; Bhetraratana, May; Yin, Fen; Peters, Kacey M; Gornbein, Jeffrey; Araujo, Jesus A; Middlekauff, Holly R

    2017-03-01

    Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non-tobacco cigarette, non-e-cigarette user control participants. Heart rate variability components were analyzed for the high-frequency component (0.15-0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04-0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low

  3. Does coronary vasodilation after adenosine override endothelin-1-induced coronary vasoconstriction?

    Science.gov (United States)

    Loghin, Catalin; Sdringola, Stefano; Gould, K Lance

    2007-01-01

    Endothelin-1 is a powerful coronary vasoconstrictor that is overexpressed in coronary artery disease. Adenosine is a powerful coronary vasodilator used for myocardial perfusion imaging to identify flow-limiting coronary artery stenosis. Therefore, in an animal model we tested the hypothesis that intracoronary endothelin-1 may cause myocardial perfusion abnormalities by positron emission tomography (PET) at resting conditions that may persist or only partially improve after intravenous adenosine stress in the absence of myocardial scar and flow-limiting stenosis. Fourteen dogs underwent serial PET perfusion imaging with rubidium-82 before and after subselective intracoronary infusion of endothelin-1, followed by intravenous and then intracoronary adenosine. Small physiological doses of endothelin-1 infused into the mid-left circumflex coronary artery caused quantitatively significant resting perfusion abnormalities that normalized after intracoronary adenosine but not consistently after intravenous adenosine used for diagnostic imaging. After effects of adenosine abated, resting perfusion defects returned, lasting up to 5 h in some animals. Cumulative doses of endothelin-1 caused perfusion defects that did not normalize after intravenous adenosine. In an animal model without myocardial scar or flow-limiting stenosis, intracoronary endothelin-1 causes visually apparent, quantitatively significant, long-lasting myocardial perfusion defects at resting conditions that may persist or only partially improve after intravenous adenosine used for diagnostic imaging. These results may potentially explain resting perfusion abnormalities or heterogeneity by clinical PET that may persist or only partially improve after adenosine stress perfusion imaging in the absence of myocardial scar and flow-limiting stenosis.

  4. NOX4 NADPH Oxidase-Dependent Mitochondrial Oxidative Stress in Aging-Associated Cardiovascular Disease.

    Science.gov (United States)

    Vendrov, Aleksandr E; Vendrov, Kimberly C; Smith, Alberto; Yuan, Jinling; Sumida, Arihiro; Robidoux, Jacques; Runge, Marschall S; Madamanchi, Nageswara R

    2015-12-20

    Increased oxidative stress and vascular inflammation are implicated in increased cardiovascular disease (CVD) incidence with age. We and others demonstrated that NOX1/2 NADPH oxidase inhibition, by genetic deletion of p47phox, in Apoe(-/-) mice decreases vascular reactive oxygen species (ROS) generation and atherosclerosis in young age. The present study examined whether NOX1/2 NADPH oxidases are also pivotal to aging-associated CVD. Both aged (16 months) Apoe(-/-) and Apoe(-/-)/p47phox(-/-) mice had increased atherosclerotic lesion area, aortic stiffness, and systolic dysfunction compared with young (4 months) cohorts. Cellular and mitochondrial ROS (mtROS) levels were significantly higher in aortic wall and vascular smooth muscle cells (VSMCs) from aged wild-type and p47phox(-/-) mice. VSMCs from aged mice had increased mitochondrial protein oxidation and dysfunction and increased vascular cell adhesion molecule 1 expression, which was abrogated with (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) treatment. NOX4 expression was increased in the vasculature and mitochondria of aged mice and its suppression with shRNA in VSMCs from aged mice decreased mtROS levels and improved function. Increased mtROS levels were associated with enhanced mitochondrial NOX4 expression in aortic VSMCs from aged subjects, and NOX4 expression levels in arterial wall correlated with age and atherosclerotic severity. Aged Apoe(-/-) mice treated with MitoTEMPO and 2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione had decreased vascular ROS levels and atherosclerosis and preserved vascular and cardiac function. These data suggest that NOX4, but not NOX1/2, and mitochondrial oxidative stress are mediators of CVD in aging under hyperlipidemic conditions. Regulating NOX4 activity/expression and using mitochondrial antioxidants are potential approaches to reducing aging-associated CVD.

  5. Ticagrelor Does Not Inhibit Adenosine Transport at Relevant Concentrations: A Randomized Cross-Over Study in Healthy Subjects In Vivo

    NARCIS (Netherlands)

    Berg, T.N.A. van den; Messaoudi, S. El; Rongen, G.A.P.J.M.; Broek, P.H.H. van den; Bilos, A.; Donders, A.R.T.; Gomes, M.E.; Riksen, N.P.

    2015-01-01

    BACKGROUND AND PURPOSE: In patients with myocardial infarction, ticagrelor reduces cardiovascular and sepsis-related mortality, and can cause dyspnea. It is suggested that this is caused by adenosine receptor stimulation, because in preclinical studies, ticagrelor blocks the nucleoside transporter

  6. Evaluation of oxidative stress markers and cardiovascular risk factors in Fabry Disease patients

    Directory of Open Access Journals (Sweden)

    Karen B. Müller

    2012-01-01

    Full Text Available Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease. The aim of this study was to evaluate plasma Hcy and other parameters involved in the methionine cycle, as well as oxidative stress markers. The sample consisted of a group of 10 male FD patients and a control group of 8 healthy individuals, paired by age. Venous blood was collected for Hcy determination, molecular analysis, identification of thiobarbituric acid reactive substances, total glutathione and antioxidant enzymes activity, as well as vitamins quantification. Comparative analysis of FD patients versus the control group indicated hyperhomocysteinemia in 8 of the 10 FD patients, as well as a significant increase in overall glutathione levels and catalase activity. It is inferred that FD patients, apart from activation of the antioxidant system, present increased levels of plasma Hcy, although this is probably unrelated to common alterations in the methionine cycle.

  7. Evaluation of oxidative stress markers and cardiovascular risk factors in Fabry Disease patients.

    Science.gov (United States)

    Müller, Karen B; Galdieri, Luciano C; Pereira, Vanessa G; Martins, Ana M; D'Almeida, Vânia

    2012-04-01

    Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy) is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease. The aim of this study was to evaluate plasma Hcy and other parameters involved in the methionine cycle, as well as oxidative stress markers. The sample consisted of a group of 10 male FD patients and a control group of 8 healthy individuals, paired by age. Venous blood was collected for Hcy determination, molecular analysis, identification of thiobarbituric acid reactive substances, total glutathione and antioxidant enzymes activity, as well as vitamins quantification. Comparative analysis of FD patients versus the control group indicated hyperhomocysteinemia in 8 of the 10 FD patients, as well as a significant increase in overall glutathione levels and catalase activity. It is inferred that FD patients, apart from activation of the antioxidant system, present increased levels of plasma Hcy, although this is probably unrelated to common alterations in the methionine cycle.

  8. Oxidative Stress in the Rostral Ventrolateral Medulla Contributes To Cardiovascular Regulation in Preeclampsia

    Science.gov (United States)

    Yan, Jiu-Qiong; Huang, Fang; Hao, Fan; Su, Xiao-Ling; Meng, Qi; Xu, Ming-Juan

    2017-01-01

    Background: It has been demonstrated that preeclampsia, a pregnancy-specific hypertension disorder, is characterized by high blood pressure (BP) and sympathetic overactivity. Increased reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM), a key region for controlling sympathetic tone, has been reported to contribute to high level of BP and sympathetic outflow. The aim of the present study was to determine the role of the RVLM ROS in mediating the preeclampsia-associated cardiovascular dysfunction. Methods: The animal model of preeclampsia was produced by administration of desoxycorticosterone acetate (DOCA) to pregnant rats. Results: Compared with normal pregnant rats without DOCA treatment (NP), the protein concentration and norepinephrine excretion in 24-h urine, as well as BP in pregnant rats with DOCA treatment (PDS) were significantly increased. The levels of superoxide anion and the protein expression of NADPH oxidase subtype (NOX4) in the RVLM were significantly increased in PDS than in NP groups. Furthermore, microinjection of the superoxide dismutase (SOD) mimic Tempol (5 nmol) into the RVLM significantly decreased BP, heart rate, and renal sympathetic never activity in PDS but not in NP group. Conclusion: The present data suggest that high BP and sympathetic overactivity in preeclampsia rats is associated with increased oxidative stress in the RVLM via upregulation of NOX4 expression. PMID:29085302

  9. Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk.

    Science.gov (United States)

    Matsuda, Morihiro; Shimomura, Iichiro

    2014-08-01

    Obesity leads to the development of type 2 diabetes mellitus, which is a strong risk factor for cardiovascular disease. A better understanding of the molecular basis of obesity will lead to the establishment of effective prevention strategies for cardiovascular diseases. Adipocytes have been shown to generate a variety of endocrine factors termed adipokines/adipocytokines. Obesity-associated changes to these adipocytokines contribute to the development of cardiovascular diseases. Adiponectin, which is one of the most well-characterized adipocytokines, is produced exclusively by adipocytes and exerts insulin-sensitizing and anti-atherogenic effects. Obese subjects have lower levels of circulating adiponectin, and this is recognized as one of the factors involved in obesity-induced insulin resistance and atherosclerosis. Another pathophysiological feature of obesity may involve the low-grade chronic inflammation in adipose tissue. This inflammatory process increases oxidative stress in adipose tissue, which may affect remote organs, leading to the development of diabetes, hypertension, and atherosclerosis. Nuclear hormone receptors (NRs) regulate the transcription of the target genes in response to binding with their ligands, which include metabolic and nutritional substrates. Among the various NRs, peroxisome proliferator-activated receptor γ promotes the transcription of adiponectin and antioxidative enzymes, whereas mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid to induce oxidative stress in adipocytes. It is hypothesized that both play crucial roles in the pathophysiology of obesity-associated insulin resistance and cardiovascular diseases. Thus, reduced adiponectin and increased oxidative stress play pathological roles in obesity-associated insulin resistance to increase the cardiovascular disease risk, and various NRs may be involved in this pathogenesis.

  10. Adenosine prevents isoprenaline-induced cardiac contractile and electrophysiological dysfunction.

    Science.gov (United States)

    Shao, Yangzhen; Redfors, Björn; Mattson-Hultén, Lillemor; Scharing Täng, Margareta; Daryoni, Elma; Said, Mohammed; Omerovic, Elmir

    2013-10-15

    Excessive levels of catecholamines are believed to contribute to cardiac dysfunction in a variety of disease states, including myocardial infarction and heart failure, and are particularly implicated in stress-induced cardiomyopathy, an increasingly recognized cardiomyopathy associated with significant morbidity and mortality. We have previously shown that a high dose of isoprenaline induces reversible regional dysfunction of the left ventricle in mice. We now hypothesize that adenosine can prevent cardiac dysfunction in this mouse model of stress-induced cardiomyopathy. Hundred male C57BL/6 mice were injected with 400mg/kg isoprenaline and then randomized to either 400mg/kg adenosine or saline. Cardiac function was evaluated by echocardiography at baseline and 2, 24, 48, 72, 96 and 120 min post isoprenaline. Myocardial fibrosis was quantified after 10 days. Intracellular lipid accumulation was quantified after 2 and 24h. Electrophysiological parameters and degree of lipid accumulation were evaluated in cultured HL1 cardiomyocytes. Two hours post isoprenaline treatment, echocardiographic parameters of global and posterior wall regional function were significantly better in adenosine-treated mice (P<0.05). This difference persisted at 24h, but saline-treated mice gradually recovered over the next 96 h. Intracellular lipid accumulation was also significantly lower in adenosine mice. We found no sign of fibrosis in the adenosine mice, whereas the extent of fibrosis in isoprenaline mice was 1.3% (P<0.05). Furthermore, adenosine-treated HL1 cells showed preserved electrophysiological function and displayed less severe intracellular lipid accumulation in response to isoprenaline. In conclusion, adenosine attenuates isoprenaline-induced cardiac dysfunction in mice and cells. © 2013 Elsevier B.V. All rights reserved.

  11. Effectiveness of myocardial contrast echocardiography quantitative analysis during adenosine stress versus visual analysis before percutaneous therapy in acute coronary pain: a coronary artery TIMI grading comparing study.

    Science.gov (United States)

    Yang, Lixia; Mu, Yuming; Quaglia, Luiz Augusto; Tang, Qi; Guan, Lina; Wang, Chunmei; Shih, Ming Chi

    2012-01-01

    The study aim was to compare two different stress echocardiography interpretation techniques based on the correlation with thrombosis in myocardial infarction (TIMI ) flow grading from acute coronary syndrome (ACS) patients. Forty-one patients with suspected ACS were studied before diagnostic coronary angiography with myocardial contrast echocardiography (MCE) at rest and at stress. The correlation of visual interpretation of MCE and TIMI flow grade was significant. The quantitative analysis (myocardial perfusion parameters: A, β, and A × β) and TIMI flow grade were significant. MCE visual interpretation and TIMI flow grade had a high degree of agreement, on diagnosing myocardial perfusion abnormality. If one considers TIMI flow grade TIMI flow grading. MCE quantitative analysis at stress has showed a direct correlation with TIMI flow grade, more significant than the visual interpretation technique. Further studies could measure the clinical relevance of this more objective approach to managing acute coronary syndrome patient before percutaneous coronary intervention (PCI).

  12. Stress, depression, and cardiovascular dysregulation: A review of neurobiological mechanisms and the integration of research from preclinical disease models

    Science.gov (United States)

    Grippo, Angela J.; Johnson, Alan Kim

    2008-01-01

    A bidirectional association between mood disorders such as depression, and cardiovascular diseases such as myocardial infarction and congestive heart failure, has been described; however, the precise neurobiological mechanisms that underlie these associations have not been fully elucidated. This review is focused on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders, with an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction including dopamine, norepinephrine and serotonin, and (e) behavioral changes including fatigue and physical inactivity. We also focus specifically on experimental investigations with preclinical disease models, conducted to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with the extensive literature describing findings from human research, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and can promote the development of better treatments and interventions for individuals with these co

  13. Hypoxia Stress Test Reveals Exaggerated Cardiovascular Effects in Hypertensive Rats After Exposure to the Air Pollutant Acrolein

    OpenAIRE

    Perez, Christina M.; Ledbetter, Allen D.; Hazari, Mehdi S.; Haykal-Coates, Najwa; Carll, Alex P.; Winsett, Darrell W.; Costa, Daniel L.; Farraj, Aimen K.

    2013-01-01

    Exposure to air pollution increases the risk of cardiovascular morbidity and mortality, especially in susceptible populations. Despite increased risk, adverse responses are often delayed and require additional stress tests to reveal latent effects of exposure. The goal of this study was to use an episode of “transient hypoxia” as an extrinsic stressor to uncover latent susceptibility to environmental pollutants in a rodent model of hypertension. We hypothesized that exposure to acrolein, an u...

  14. Heat- and cold-stress effects on cardiovascular mortality and morbidity among urban and rural populations in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Urban, Aleš; Davídkovová, Hana; Kyselý, Jan

    2014-01-01

    Roč. 58, č. 6 (2014), s. 1057-1068 ISSN 0020-7128 R&D Projects: GA ČR(CZ) GAP209/11/1985 Institutional support: RVO:68378289 Keywords : heat and cold stress * cardiovascular disease * mortality * morbidity * urban and rural differences * Central Europe Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 3.246, year: 2014 http://link.springer.com/article/10.1007%2Fs00484-013-0693-4#page-1

  15. New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus*

    Science.gov (United States)

    Bowman, Lisa; Zeden, Merve S.; Kaever, Volkhard

    2016-01-01

    Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5′-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism. PMID:27834680

  16. New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus.

    Science.gov (United States)

    Bowman, Lisa; Zeden, Merve S; Schuster, Christopher F; Kaever, Volkhard; Gründling, Angelika

    2016-12-30

    Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5'-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Heat- and cold-stress effects on cardiovascular mortality and morbidity among urban and rural populations in the Czech Republic

    Science.gov (United States)

    Urban, Aleš; Davídkovová, Hana; Kyselý, Jan

    2014-08-01

    Several studies have examined the relationship of high and low air temperatures to cardiovascular mortality in the Czech Republic. Much less is understood about heat-/cold-related cardiovascular morbidity and possible regional differences. This paper compares the effects of warm and cold days on excess mortality and morbidity for cardiovascular diseases (CVDs) in the city of Prague and a rural region of southern Bohemia during 1994-2009. Population size and age structure are similar in the two regions. The results are evaluated for selected population groups (men and women). Excess mortality (number of deaths) and morbidity (number of hospital admissions) were determined as differences between observed and expected daily values, the latter being adjusted for long-term changes, annual and weekly cycles, and epidemics of influenza/acute respiratory infections. Generally higher relative excess CVD mortality on warm days than on cold days was identified in both regions. In contrast to mortality, weak excess CVD morbidity was observed for both warm and cold days. Different responses of individual CVDs to heat versus cold stress may be caused by the different nature of each CVD and different physiological processes induced by heat or cold stress. The slight differences between Prague and southern Bohemia in response to heat versus cold stress suggest the possible influence of environmental and socioeconomic factors such as the effects of urban heat island and exposure to air pollution, lifestyle differences, and divergence in population structure, which may result in differing vulnerability of urban versus rural population to temperature extremes.

  18. The psychoemotional status and cardiovascular system functional state of the first-year students under the influence of examination stress

    Directory of Open Access Journals (Sweden)

    Liliana K. Tokaeva

    2012-12-01

    Full Text Available The aim of this research is to study of the influence of examination stress on psycho-emotional status and functional state of the cardiovascular system of the 1-st year students of pedagogical high school. Methods – The study involved 105 young men aged 17-18 enrolled in the specialty "Physical Education". The studies were conducted during the period in-between the exams and during the examination session. The psycho-emotional status was determined by the SAN test questionnaire and test and the CH.D. Spielberg test, adapted for Russia by Ju.L. Khanin. The state of CVS autonomic regulation was evaluated by heart rate, blood pressure, endurance ratio, Kerdo index and the adaptive capacities by P.M. Bayevsky. Results – In the absence of exposure to stress in the majority of young men the studied parameters are within normal limits, indicating sufficient adaptive capabilities. A clear correlation between the level of personal anxiety in students and the nature of their reactivity to examination stress was found: the higher the anxiety level in a student is, the more stress resistance decreases and more pronounced changes in the cardiovascular system autonomic regulation appear. The strain of adaptation mechanism was found in a stressful situation in the first-year students with a high level of personal anxiety and satisfactory adaptation – in young men with average and low personal anxiety.

  19. Adenosine-Associated Delivery Systems

    Science.gov (United States)

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2016-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  20. Cardiovascular responses of Type A and Type B behavior patterns to visual stimulation during rest, stress and recovery.

    Science.gov (United States)

    Lee, Jeong-Mi; Watanuki, Shigeki

    2007-01-01

    Differences in the cardiovascular responses of individuals with behavior patterns of Type A and Type B were investigated during rest, stress, and recovery by visual stimulation. Thirty healthy undergraduate and graduate students (mean age: 22.18+/-1.44 years) were categorized as Type A (N=14), or Type B (N=16) based on the Kwansei Gakuin's daily life questionnaire. The cardiovascular reactivity of all participants was repetitively monitored for 6 sessions, with each session comprising 3 conditional phases, viz., resting, stress, and post-stress recovery. A gray screen was displayed during resting, displeasure-evoking images were displayed under the stress condition, and video clips of a forest or a control image (a gray screen) were displayed during the recovery condition. When participants were subjected to different stimuli on a 42-inch plasma television screen in each session, electrocardiograms (ECG), impedance cardiograms and the blood pressure (BP) of the respective participants were continuously monitored. According to the results, Type A indicated higher sympathetic reactivity than Type B during resting and under stress. As such, Type A indicated a shorter pre-ejection period (PEP) level during resting and a greater cardiac output (CO) increase under stress than Type B. Furthermore, parasympathetic predominance and parasympathetic antagonism accompanying the enhanced sympathetic activity induced by the unpleasant stress images decreased heart rate (HR) in both Type A and Type B, although the decrease in Type A was relatively meager. Unlike previous studies, the present study demonstrated that Type A indicated more enhanced sympathetic reactivity than Type B in resting physiological arousal levels and visual stimulus-induced stress.

  1. Diagnostic performance of combined noninvasive anatomic and functional assessment with dual-source CT and adenosine-induced stress dual-energy CT for detection of significant coronary stenosis.

    Science.gov (United States)

    Ko, Sung Min; Choi, Jin Woo; Hwang, Hweung Kon; Song, Meong Gun; Shin, Je Kyoun; Chee, Hyun Keun

    2012-03-01

    The purpose of our study was to prospectively evaluate the incremental diagnostic value of combined dual-source coronary CT angiography (CTA) and CT myocardial perfusion imaging (MPI) for the detection of significant coronary stenoses. Forty-five patients with known coronary artery disease detected by dual-source coronary CTA were investigated by adenosine-induced stress dual-source CTA and conventional coronary angiography. Analysis was performed in three steps: classification of coronary stenosis severity using dual-source coronary CTA, identification of myocardial perfusion defects using rest and stress CT MPI, and reclassification of coronary stenosis severity according to combined dual-source coronary CTA and CT MPI. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of dual-source coronary CTA before and after CT MPI were calculated on a per-vessel basis compared with conventional coronary angiography as the standard of reference. Dual-source coronary CTA revealed 87 significantly stenotic vessels in 45 patients. Conventional coronary angiography revealed significant stenoses in 73 vessels in 42 patients. CT MPI showed myocardial perfusion defects in 81 vessel territories in 43 patients. After the CT MPI analysis, dual-source coronary CTA identified significant stenoses in 77 coronary vessels in 42 patients. Sensitivity, specificity, PPV, and NPV of the dual-source coronary CTA on a per-vessel basis before CT MPI were 91.8%, 67.7%, 73.6%, and 87.5%, respectively, and after CT MPI were 93.2%, 85.5%, 88.3%, and 91.4%, respectively. The area under the receiver operating characteristic curve increased significantly from 0.798 to 0.893 (p = 0.004). Combined dual-source coronary CTA and CT MPI provides incremental diagnostic value compared with dual-source coronary CTA alone for the detection of significant coronary stenoses.

  2. Enhanced cellular adenosine uptake limits adenosine receptor stimulation in patients with hyperhomocysteinemia.

    NARCIS (Netherlands)

    Riksen, N.P.; Rongen, G.A.; Boers, G.H.J.; Blom, H.J.; Broek, P.H.H. van den; Smits, P.

    2005-01-01

    OBJECTIVE: Endogenous adenosine has several cardioprotective effects. We postulate that in patients with hyperhomocysteinemia increased intracellular formation of S-adenosylhomocysteine decreases free intracellular adenosine. Subsequently, facilitated diffusion of extracellular adenosine into cells

  3. Effect of a 16-week Bikram yoga program on heart rate variability and associated cardiovascular disease risk factors in stressed and sedentary adults: A randomized controlled trial

    OpenAIRE

    Hewett, Zoe L.; Pumpa, Kate L.; Smith, Caroline A.; Fahey, Paul P.; Birinder S. Cheema

    2017-01-01

    Background Chronic activation of the stress-response can contribute to cardiovascular disease risk, particularly in sedentary individuals. This study investigated the effect of a Bikram yoga intervention on the high frequency power component of heart rate variability (HRV) and associated cardiovascular disease (CVD) risk factors (i.e. additional domains of HRV, hemodynamic, hematologic, anthropometric and body composition outcome measures) in stressed and sedentary adults. Methods Eligible ad...

  4. Differential protection against oxidative stress and nitric oxide overproduction in cardiovascular and pulmonary systems by propofol during endotoxemia

    Directory of Open Access Journals (Sweden)

    Liu Yen-Chin

    2009-01-01

    Full Text Available Abstract Background Both overproduction of nitric oxide (NO and oxidative injury of cardiovascular and pulmonary systems contribute to fatal cardiovascular depression during endotoxemia. We investigated in the present study the relative contribution of oxidative stress and NO to cardiovascular depression during different stages of endotoxemia, and delineated their roles in cardiovascular protective effects of a commonly used anesthetic propofol during endotoxemia. Methods Experimental endotoxemia was induced by systemic injection of E. coli lipopolysaccharide (LPS, 15 mg/kg to Sprague-Dawley rats that were maintained under propofol (15 or 30 mg/kg/h, i.v. anesthesia. Mean systemic arterial pressure (MSAP and heart rate (HR were monitored for 6 h after the endotoxin. Tissue level of NO was measured by chemical reduction-linked chemiluminescence and oxidative burst activity was determined using dihydroethidium method. Expression of NO synthase (NOS was determined by immunoblotting. The Scheffé multiple range test was used for post hoc statistical analysis. Results Systemic injection of LPS (15 mg/kg induced biphasic decreases in MSAP and HR. In the heart, lung and aorta, an abrupt increase in lipid peroxidation, our experimental index of oxidative tissue injury, was detected in early stage and sustained during late stage cardiovascular depression. LPS injection, on the other hand, induced a gradual increase in tissue nitrite and nitrate levels in the same organs that peaked during late stage endotoxemia. Propofol infusion (15 or 30 mg/kg/h, i.v. significantly attenuated lipid peroxidation in the heart, lung and aorta during early and late stage endotoxemia. High dose (30 mg/kg/h, i.v. propofol also reversed the LPS-induced inducible NO synthase (iNOS upregulation and NO production in the aorta, alongside a significant amelioration of late stage cardiovascular depression and increase in survival time during endotoxemia. Conclusion Together these

  5. Ticagrelor Does Not Inhibit Adenosine Transport at Relevant Concentrations: A Randomized Cross-Over Study in Healthy Subjects In Vivo.

    Directory of Open Access Journals (Sweden)

    T N A van den Berg

    Full Text Available In patients with myocardial infarction, ticagrelor reduces cardiovascular and sepsis-related mortality, and can cause dyspnea. It is suggested that this is caused by adenosine receptor stimulation, because in preclinical studies, ticagrelor blocks the nucleoside transporter and increases cellular ATP release. We now investigated the effects of ticagrelor on the adenosine system in humans in vivo.In a double-blinded, placebo-controlled cross-over trial in 14 healthy subjects, we have tested whether ticagrelor (180 mg affects adenosine- and dipyridamole-induced forearm vasodilation, as surrogates of nucleoside uptake inhibition and adenosine formation, respectively. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was measured. Primary endpoint was adenosine-induced vasodilation.Ticagrelor did not affect adenosine- or dipyridamole-induced forearm vasodilation. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was not affected by ticagrelor. In vitro, ticagrelor dose-dependently inhibited nucleoside uptake, but only at supra-physiological concentrations.In conclusion, at relevant plasma concentration, ticagrelor does not affect adenosine transport, nor adenosine formation in healthy subjects. Therefore, it is unlikely that this mechanism is a relevant pleiotropic effect of ticagrelor.ClinicalTrials.gov NCT01996735.

  6. Ticagrelor Does Not Inhibit Adenosine Transport at Relevant Concentrations: A Randomized Cross-Over Study in Healthy Subjects In Vivo

    Science.gov (United States)

    Rongen, G. A.; van den Broek, P. H. H.; Bilos, A.; Donders, A. R. T.; Gomes, M. E.; Riksen, N. P.

    2015-01-01

    Background and Purpose In patients with myocardial infarction, ticagrelor reduces cardiovascular and sepsis-related mortality, and can cause dyspnea. It is suggested that this is caused by adenosine receptor stimulation, because in preclinical studies, ticagrelor blocks the nucleoside transporter and increases cellular ATP release. We now investigated the effects of ticagrelor on the adenosine system in humans in vivo. Experimental Approach In a double-blinded, placebo-controlled cross-over trial in 14 healthy subjects, we have tested whether ticagrelor (180 mg) affects adenosine- and dipyridamole-induced forearm vasodilation, as surrogates of nucleoside uptake inhibition and adenosine formation, respectively. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was measured. Primary endpoint was adenosine-induced vasodilation. Key Results Ticagrelor did not affect adenosine- or dipyridamole-induced forearm vasodilation. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was not affected by ticagrelor. In vitro, ticagrelor dose-dependently inhibited nucleoside uptake, but only at supra-physiological concentrations. Conclusion and Implications In conclusion, at relevant plasma concentration, ticagrelor does not affect adenosine transport, nor adenosine formation in healthy subjects. Therefore, it is unlikely that this mechanism is a relevant pleiotropic effect of ticagrelor. Trial Registration ClinicalTrials.gov NCT01996735 PMID:26509673

  7. Prevention of angiotensin II-induced hypertension, cardiovascular hypertrophy and oxidative stress by acetylsalicylic acid in rats.

    Science.gov (United States)

    Wu, Rong; Laplante, Marc-André; De Champlain, Jacques

    2004-04-01

    Angiotensin II (Ang II)-induced oxidative stress has been suspected to play an important part in the pathogenesis of many cardiovascular diseases. Our previous study demonstrated that acetylsalicylic acid (ASA) possesses potent antioxidative properties. To evaluate the pathogenetic role of oxidative stress in Ang II-induced hypertension and cardiovascular hypertrophy. Chronic infusion of Ang II (200 ng/kg per min for 12 days) increased the aortic and cardiac tissue production of superoxide anion (O2) (lucigenin-enhanced chemiluminescence method) by 77 and 35%, respectively. These effects were associated with progressive increases in systolic blood pressure (from 135 to 194 mmHg) and heart/body weight ratio (from 2.25 to 2.69). Chronic treatment with oral ASA alone (100 mg/kg per day for 12 days) significantly reduced aortic and cardiac production of O2 (by 31 and 33%, respectively), without alteration in blood pressure and heart/body weight ratio in control normotensive animals. However, concurrent treatment with ASA in Ang II-infused rats completely prevented the Ang II-induced production of O2, in addition to hypertension and cardiac hypertrophy. Similar protective effects were observed in cultured aortic smooth muscle cells, in which increases in O2 production and [H]leucine incorporation (221 and 38%, respectively) induced by Ang II (10 mol/l) were totally prevented by concurrent incubation with ASA (10 mol/l). Losartan, but not PD 123319, also blocked the Ang II-induced oxidative and hypertrophic effects in those cells. Other anti-inflammatory drugs, such as salicylic acid, indomethacin and ibuprofen, did not show similar anti-Ang II and antioxidative effects in vivo. Oxidative stress plays a major part in chronic Ang II-induced hypertension and cardiovascular hypertrophy. Chronic concurrent treatment with ASA was found to prevent those Ang II-induced effects on the cardiovascular system, presumably through its antioxidative properties.

  8. Partial Adenosine A1 Agonist in Heart Failure.

    Science.gov (United States)

    Dinh, Wilfried; Albrecht-Küpper, Barbara; Gheorghiade, Mihai; Voors, Adriaan A; van der Laan, Michael; Sabbah, Hani N

    2017-01-01

    Adenosine exerts a variety of physiological effects by binding to cell surface G-protein-coupled receptor subtypes, namely, A1, A2a, A2b, and A3. The central physiological role of adenosine is to preclude tissue injury and promote repair in response to stress. In the heart, adenosine acts as a cytoprotective modulator, linking cardiac function to metabolic demand predominantly via activation of adenosine A1 receptors (A1Rs), which leads to inhibition of adenylate cyclase activity, modulation of protein kinase C, and opening of ATP-sensitive potassium channels. Activation of myocardial adenosine A1Rs has been shown to modulate a variety of pathologies associated with ischemic cardiac injury, including arrhythmogenesis, coronary and ventricular dysfunction, apoptosis, mitochondrial dysfunction, and ventricular remodeling. Partial A1R agonists are agents that are likely to elicit favorable pharmacological responses in heart failure (HF) without giving rise to the undesirable cardiac and extra-cardiac effects observed with full A1R agonism. Preclinical data have shown that partial adenosine A1R agonists protect and improve cardiac function at doses that do not result in undesirable effects on heart rate, atrioventricular conduction, and blood pressure, suggesting that these compounds may constitute a valuable new therapy for chronic HF. Neladenoson bialanate (BAY1067197) is the first oral partial and highly selective A1R agonist that has entered clinical development for the treatment of HF. This review provides an overview of adenosine A1R-mediated signaling in the heart, summarizes the results from preclinical and clinical studies of partial A1R agonists in HF, and discusses the potential benefits of these drugs in the clinical setting.

  9. Effect of fast and slow pranayama on perceived stress and cardiovascular parameters in young health-care students.

    Science.gov (United States)

    Sharma, Vivek Kumar; Trakroo, Madanmohan; Subramaniam, Velkumary; Rajajeyakumar, M; Bhavanani, Anand B; Sahai, Ajit

    2013-07-01

    Perceived stress is higher for students in various healthcare courses. Previous studies have shown that pranayama practice is beneficial for combating stress and improve cardiovascular functions but both fast and slow pranayama practice produce different physiological responses. Present study was conducted to compare the effects of commonly practiced slow and fast pranayama on perceived stress and cardiovascular functions in young health-care students. Present study was carried out in Departments of Physiology and Advanced Centre for Yoga Therapy Education and Research, JIPMER, Pondicherry. Ninety subjects (age 18-25 years) were randomized to fast pranayama (Group 1), slow pranayama (Group 2) and control group (Group 3). Group 1 subjects practiced Kapalabhati, Bhastrika and Kukkuriya Pranayama while Group 2 subjects practiced Nadishodhana, Savitri and Pranav Paranayama. Supervised pranayama training was given for 30 min, 3 times a week for the duration of 12 weeks to Groups 1 and 2 subjects by certified yoga trainer. Following parameters were recorded at the baseline and after 12 weeks of training; perceived stress scale (PSS), heart rate (HR), respiratory rate, systolic blood pressure and diastolic blood pressure (DBP), mean arterial pressure (MAP), rate pressure product (RPP), and double product (Do P). There was a significant decrease in PSS scores in both Group 1 and Group 2 subjects but percentage decrease was comparable in these groups. Significant decrease in HR, DBP, RPP, and Do P was seen in only Group 2 subjects. This study demonstrates that both types of pranayama practice are beneficial in reducing PSS in the healthy subjects but beneficial effect on cardiovascular parameters occurred only after practicing slow pranayama.

  10. Changes in relative fit of human heat stress indices to cardiovascular, respiratory, and renal hospitalizations across five Australian urban populations

    Science.gov (United States)

    Goldie, James; Alexander, Lisa; Lewis, Sophie C.; Sherwood, Steven C.; Bambrick, Hilary

    2017-09-01

    Various human heat stress indices have been developed to relate atmospheric measures of extreme heat to human health impacts, but the usefulness of different indices across various health impacts and in different populations is poorly understood. This paper determines which heat stress indices best fit hospital admissions for sets of cardiovascular, respiratory, and renal diseases across five Australian cities. We hypothesized that the best indices would be largely dependent on location. We fit parent models to these counts in the summers (November-March) between 2001 and 2013 using negative binomial regression. We then added 15 heat stress indices to these models, ranking their goodness of fit using the Akaike information criterion. Admissions for each health outcome were nearly always higher in hot or humid conditions. Contrary to our hypothesis that location would determine the best-fitting heat stress index, we found that the best indices were related largely by health outcome of interest, rather than location as hypothesized. In particular, heatwave and temperature indices had the best fit to cardiovascular admissions, humidity indices had the best fit to respiratory admissions, and combined heat-humidity indices had the best fit to renal admissions. With a few exceptions, the results were similar across all five cities. The best-fitting heat stress indices appear to be useful across several Australian cities with differing climates, but they may have varying usefulness depending on the outcome of interest. These findings suggest that future research on heat and health impacts, and in particular hospital demand modeling, could better reflect reality if it avoided "all-cause" health outcomes and used heat stress indices appropriate to specific diseases and disease groups.

  11. Enhanced involvement of brain vasopressin V1 receptors in cardiovascular responses to stress in rats with myocardial infarction.

    Science.gov (United States)

    Dobruch, Jakub; Cudnoch-Jedrzejewska, Agnieszka; Szczepanska-Sadowska, Ewa

    2005-12-01

    Stress is one of the factors provoking cardiovascular complications. The purpose of the study was to explore the role of vasopressin (VP) in central control of arterial blood pressure and heart rate under resting conditions and during stimulation by an alarming stress (air jet stress) in myocardial infarct-induced cardiac failure. Six groups of male Sprague Dawley (SD) rats were subjected either to sham surgery (sham rats) or to ligation of a left coronary artery (infarcted rats). After 5 weeks both infarcted and sham rats were subjected either to intracerebroventricular infusion of artificial cerebrospinal fluid (aCSF) (sham aCSF and infarcted aCSF), [Arg8]-VP (sham VP and infarcted VP) or VP V1a receptor antagonist (d(CH2)5[Tyr(Me)2Ala-]VP, sham V1ANT and infarcted V1ANT). Air jet stress elicited significantly greater increases in mean arterial blood pressure (MABP) and heart rate in the infarcted aCSF than in the sham aCSF rats. Intracerebroventricular infusion of V1ANT significantly reduced resting MABP and MABP and heart rate increases in response to stress in the infarcted but not in the sham rats. Intracerebroventricular infusion of VP elicited a significant increase in resting MABP in the infarcted VP but not in the sham VP rats. The results provide evidence for enhanced engagement of the brain V1 VP receptors in regulation of resting MABP and in generation of exaggerated cardiovascular responses to air jet stress during the post-infarct state.

  12. Involvement of endocannabinoid neurotransmission in the bed nucleus of stria terminalis in cardiovascular responses to acute restraint stress in rats

    Science.gov (United States)

    Gomes‐de‐Souza, Lucas; Oliveira, Leandro A; Benini, Ricardo; Rodella, Patrícia; Costa‐Ferreira, Willian

    2016-01-01

    Background and Purpose Endocannabinoid signalling has been reported as an important neurochemical mechanism involved in responses to stress. Previous studies provided evidence of endocannabinoid release in the bed nucleus of the stria terminalis (BNST) during aversive stimuli. Nevertheless, a possible involvement of this neurochemical mechanism in stress responses has never been evaluated. Therefore, in the present study we investigated the involvement of BNST endocannabinoid neurotransmission, acting via local CB1 receptors, in the cardiovascular responses to acute restraint stress in rats. Experimental Approach The selective CB1 receptor antagonist AM251 (1, 30 and 100 pmol 100 nL−1) and/or the fatty acid amide hydrolase (FAAH) enzyme inhibitor URB597 (30 pmol 100 nL−1) or the monoacylglycerol lipase (MAGL) enzyme inhibitor JZL184 (30 pmol 100 nL−1) was microinjected into the BNST before the acute restraint stress. Key Results Microinjection of AM251 into the BNST enhanced the tachycardia caused by restraint stress, without affecting the increase in arterial pressure and the sympathetic‐mediated cutaneous vasoconstrictor response. Conversely, the increased endogenous levels of AEA in the BNST evoked by local treatment with the FAAH enzyme inhibitor URB597 decreased restraint‐evoked tachycardia. Inhibition of the hydrolysis of 2‐arachidonoylglycerol (2‐AG) in the BNST by local microinjection of the MAGL enzyme inhibitor JZL184 also decreased the HR response. These effects of URB597 and JZL184 were abolished by BNST pretreatment with AM251. Conclusions and Implications These findings indicate an involvement of BNST endocannabinoid neurotransmission, acting via CB1 receptors, in cardiovascular adjustments during emotional stress, which may be mediated by the local release of either AEA or 2‐AG. PMID:27441413

  13. Adenosine-stress dynamic myocardial perfusion imaging using 128-slice dual-source CT in patients with normal body mass indices: effect of tube voltage, tube current, and iodine concentration on image quality and radiation dose.

    Science.gov (United States)

    Kim, Sung Mok; Cho, Young Kwon; Choe, Yeon Hyeon

    2014-12-01

    The aim of this study was to evaluate the image quality and radiation dose in adenosine-stress dynamic myocardial CT perfusion (CTP) imaging using different tube voltages, tube current settings, and contrast materials containing different iodine concentrations in subjects with normal body mass indices (BMI). We included 92 patients (BMI range, 18.5-24.8) who underwent dynamic CTP for the evaluation of coronary artery disease using a 128-slice dual-source computed tomography. The protocols employed the following dynamic scan parameters: protocol I with 100 kV, fixed tube current (FTC), and medium-concentration contrast material (MC, 350 mg iodine/mL); protocol II with 100 kV, automatic tube current modulation (ATCM), and MC; protocol III with 100 kV, ATCM, and high-concentration contrast material (HC, 400 mg iodine/mL); protocol IV with 80 kV, adopted FTC, and HC. Subjective image quality on a 1-3 point scale and objective image quality with respect to the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were assessed. Protocol IV showed higher CNR and SNR than the other protocols (P < 0.01), while the CNR and SNR values did not significantly differ among the other three protocols. There was no significant difference in subjective image quality among the protocols. The radiation dose in protocol IV was the lowest among the protocols (P < 0.01), while protocol IV resulted in a 54% overall reduction in mean effective radiation dose compared with protocol I. Dynamic myocardial CTP performed at 80 kV with adapted FTC provided high CNR and SNR while preserving subjective image quality and reducing radiation exposure.

  14. Study of Cardiovascular Reactivity to Mental Stress in Different Phases of Menstrual Cycle

    OpenAIRE

    Shenoy, Jnaneshwara P; PA, Sahana; J, Shivakumar

    2014-01-01

    Background: It is a well known fact that normally female sex hormone levels fluctuate during the menstrual cycle. The presence of receptors for these hormones on both heart and blood vessels may also hint at variations in physiological functions during menstrual cycle. So this study was an attempt to determine whether the follicular and luteal phases of menstrual cycle are characterized by variations in cardiovascular parameters in the resting state and also examine changes in cardiovascular ...

  15. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

    OpenAIRE

    Nada Sallam; Ismail Laher

    2015-01-01

    Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases a...

  16. Extracellular guanosine regulates extracellular adenosine levels

    Science.gov (United States)

    Cheng, Dongmei; Jackson, Travis C.; Verrier, Jonathan D.; Gillespie, Delbert G.

    2013-01-01

    The aim of this investigation was to test the hypothesis that extracellular guanosine regulates extracellular adenosine levels. Rat preglomerular vascular smooth muscle cells were incubated with adenosine, guanosine, or both. Guanosine (30 μmol/l) per se had little effect on extracellular adenosine levels. Extracellular adenosine levels 1 h after addition of adenosine (3 μmol/l) were 0.125 ± 0.020 μmol/l, indicating rapid disposition of extracellular adenosine. Extracellular adenosine levels 1 h after addition of adenosine (3 μmol/l) plus guanosine (30 μmol/l) were 1.173 ± 0.061 μmol/l, indicating slow disposition of extracellular adenosine. Cell injury increased extracellular levels of endogenous adenosine and guanosine, and the effects of cell injury on endogenous extracellular adenosine were modulated by altering the levels of endogenous extracellular guanosine with exogenous purine nucleoside phosphorylase (converts guanosine to guanine) or 8-aminoguanosine (inhibits purine nucleoside phosphorylase). Extracellular guanosine also slowed the disposition of extracellular adenosine in rat preglomerular vascular endothelial cells, mesangial cells, cardiac fibroblasts, and kidney epithelial cells and in human aortic and coronary artery vascular smooth muscle cells and coronary artery endothelial cells. The effects of guanosine on adenosine levels were not mimicked or attenuated by 5-iodotubericidin (adenosine kinase inhibitor), erythro-9-(2-hydroxy-3-nonyl)-adenine (adenosine deaminase inhibitor), 5-aminoimidazole-4-carboxamide (guanine deaminase inhibitor), aristeromycin (S-adenosylhomocysteine hydrolase inhibitor), low sodium (inhibits concentrative nucleoside transporters), S-(4-nitrobenzyl)−6-thioinosine [inhibits equilibrative nucleoside transporter (ENT) type 1], zidovudine (inhibits ENT type 2), or acadesine (known modulator of adenosine levels). Guanosine also increases extracellular inosine, uridine, thymidine, and cytidine, yet decreases

  17. Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space

    Science.gov (United States)

    Baisch, J. F.; Wolfram, G.; Beck, L.; Drummer, C.; Stormer, I.; Buckey, J.; Blomqvist, G.

    2000-01-01

    In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often.

  18. Beneficial and detrimental role of adenosine signaling in diseases and therapy

    Science.gov (United States)

    Liu, Hong

    2015-01-01

    Adenosine is a major signaling nucleoside that orchestrates cellular and tissue adaptation under energy depletion and ischemic/hypoxic conditions by activation of four G protein-coupled receptors (GPCR). The regulation and generation of extracellular adenosine in response to stress are critical in tissue protection. Both mouse and human studies reported that extracellular adenosine signaling plays a beneficial role during acute states. However, prolonged excess extracellular adenosine is detrimental and contributes to the development and progression of various chronic diseases. In recent years, substantial progress has been made to understand the role of adenosine signaling in different conditions and to clarify its significance during the course of disease progression in various organs. These efforts have and will identify potential therapeutic possibilities for protection of tissue injury at acute stage by upregulation of adenosine signaling or attenuation of chronic disease progression by downregulation of adenosine signaling. This review is to summarize current progress and the importance of adenosine signaling in different disease stages and its potential therapeutic effects. PMID:26316513

  19. Insulin/adenosine axis linked signalling

    NARCIS (Netherlands)

    Silva, Luis; Subiabre, Mario; Araos, Joaquín; Sáez, Tamara; Salsoso, Rocío; Pardo, Fabián; Leiva, Andrea; San Martín, Rody; Toledo, Fernando; Sobrevia, Luis

    Regulation of blood flow depends on systemic and local release of vasoactive molecules such as insulin and adenosine. These molecules cause vasodilation by activation of plasma membrane receptors at the vascular endothelium. Adenosine activates at least four subtypes of adenosine receptors (A(1)AR,

  20. The Relationship Between Autonomy and Relatedness and Adolescents' Adrenocortical and Cardiovascular Stress Response.

    Science.gov (United States)

    Cook, Emily C; Chaplin, Tara M; Stroud, Laura R

    2015-11-01

    Developing autonomy and maintaining relatedness within the parent-adolescent relationship marks a realignment process that shifts adolescents' decision making and regulation from parents to youth. This process may be stressful for some adolescents, particularly those who perceive their daily lives as stressful. This study examined the associations of autonomy, relatedness and perceived stress with adolescents' cortisol and blood pressure response to conflict in a mother-adolescent interaction task among 100 adolescents (M age = 15.09; 68 % girls, 78 % Caucasian). Few direct associations were found, but results indicated that perceived stress moderated the effect of autonomy and relatedness such that youth who reported more perceived stress and whose mothers' restricted their autonomy and undermined their relatedness evidenced increased cortisol and systolic blood pressure when compared to youth lower in perceived stress. The results highlight the importance of examining individual differences in the association between normative developmental transitions and adolescents' neurobiological response to stress.

  1. On the track of syncope induced by orthostatic stress - feedback mechanisms regulating the cardiovascular system

    DEFF Research Database (Denmark)

    Ottesen, Johnny T.

    2009-01-01

    A physiological realistic model of the controlled cardiovascular system is constructed and validated against clinical data. Special attention is paid to the heart rate control. Both sit-to-stand and head-up-tilt experiments are encapsulated by the model. The model may be used in studies of syncop...

  2. Effects of Neonatal Dexamethasone Treatment on the Cardiovascular Stress Response of Children at School Age

    NARCIS (Netherlands)

    Karemaker, Rosa; Karemaker, John M.; Kavelaars, Annemieke; Tersteeg-Kamperman, Marijke; Baerts, Wim; Veen, Sylvia; Samsom, Jannie F.; van Bel, Frank; Heijnen, Cobi J.

    2008-01-01

    OBJECTIVE. The goal was to investigate cardiovascular responses to a psychosocial stressor in school-aged, formerly premature boys and girls who had been treated neonatally with dexamethasone or hydrocortisone because of chronic lung disease. METHODS. We compared corticosteroid-treated, formerly

  3. Development of patient specific cardiovascular models predicting dynamics in response to orthostatic stress challenges

    DEFF Research Database (Denmark)

    Ottesen, Johnny T.

    2013-01-01

    Physiological realistic models of the controlled cardiovascular system are constructed and validated against clinical data. Special attention is paid to the control of blood pressure, cerebral blood flow velocity, and heart rate during postural challenges, including sit-to-stand and head-up tilt....

  4. A definition of normovolaemia and consequences for cardiovascular control during orthostatic and environmental stress

    NARCIS (Netherlands)

    Truijen, J.; Bundgaard-Nielsen, M.; van Lieshout, J.J.

    2010-01-01

    The Frank-Starling mechanism describes the relationship between stroke volume and preload to the heart, or the volume of blood that is available to the heart-the central blood volume. Understanding the role of the central blood volume for cardiovascular control has been complicated by the fact that

  5. Contrasting effects of verapamil and amlodipine on cardiovascular stress responses in hypertension

    NARCIS (Netherlands)

    Lefrandt, JD; Heitmann, J; Sevre, K; Castellano, M; Hausberg, M; Fallon, M; Urbigkeit, A; Rostrup, M; Agabiti-Rosei, E; Rahn, KH; Murphy, M; Zannad, F; de Kam, PJ; Smit, AJ

    2001-01-01

    Aims To compare the effects of two long-acting calcium antagonists of different types on cardiovascular,tress responses in hypertension. Methods One-hundred and forty-five patients with mild to moderate hypertension and a mean (+/- s.e.mean) age of 51 +/- 0.9 years received for 8 weeks the

  6. “Soldier’s Heart”: A Genetic Basis for Elevated Cardiovascular Disease Risk Associated with Post-traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Harvey B. Pollard

    2016-09-01

    Full Text Available Soldier’s Heart, is an American Civil War term linking post-traumatic stress disorder (PTSD with increased propensity for cardiovascular disease (CVD. We have hypothesized that there might be a quantifiable genetic basis for this linkage. To test this hypothesis we identified a comprehensive set of candidate risk genes for PTSD, and tested whether any were also independent risk genes for CVD. A functional analysis algorithm was used to identify associated signaling networks.We identified 106 PTSD studies that report one or more polymorphic variants in 87 candidate genes in 83,463 subjects and controls. The top upstream drivers for these PTSD risk genes are predicted to be the glucocorticoid receptor (NR3C1 and Tumor Necrosis Factor alpha (TNFA. We find that 37 of the PTSD candidate risk genes are also candidate independent risk genes for CVD. The association between PTSD and CVD is significant by Fisher’s Exact Test (P= 3*10-54. We also find 15 PTSD risk genes that are independently associated with Type 2 Diabetes Mellitus (T2DM; also significant by Fisher’s Exact Test (P= 1.8*10-16. Our findings offer quantitative evidence for a genetic link between post-traumatic stress and cardiovascular disease, Computationally, the common mechanism for this linkage between PTSD and CVD is innate immunity and NFκB-mediated inflammation.

  7. Air pollution, cardiovascular endpoints and susceptibility by stress and material resources: a systematic review of the evidence.

    Science.gov (United States)

    Fuller, Christina H; Feeser, Karla R; Sarnat, Jeremy A; O'Neill, Marie S

    2017-06-14

    Evidence shows that both the physical and social environments play a role in the development of cardiovascular disease. The purpose of this systematic review is two-fold: First, we summarize research from the past 12 years from the growing number of studies focused on effect modification of the relationships between air pollution and cardiovascular disease (CVD) outcomes by socioeconomic position (SEP) and; second, we identify research gaps throughout the published literature on this topic and opportunities for addressing these gaps in future study designs. We identified 30 articles that examined the modifying effects of either material resources or psychosocial stress (both related to SEP) on associations between short and long-term air pollution exposure and CVD endpoints. Although 18 articles identified at least one interaction between an air pollutant and material resource indicator, 11 others did not. Support for susceptibility to air pollution by psychosocial stress was weaker; however, only three articles tested this hypothesis. Further studies are warranted to investigate how air pollution and SEP together may influence CVD. We recommend that such research include thorough assessment of air pollution and SEP correlations, including spatial correlation; investigate air pollution indices or multi-pollutant models; use standardized metrics of SEP to enhance comparability across studies; and evaluate potentially susceptible populations.

  8. "Soldier's Heart": A Genetic Basis for Elevated Cardiovascular Disease Risk Associated with Post-traumatic Stress Disorder.

    Science.gov (United States)

    Pollard, Harvey B; Shivakumar, Chittari; Starr, Joshua; Eidelman, Ofer; Jacobowitz, David M; Dalgard, Clifton L; Srivastava, Meera; Wilkerson, Matthew D; Stein, Murray B; Ursano, Robert J

    2016-01-01

    "Soldier's Heart," is an American Civil War term linking post-traumatic stress disorder (PTSD) with increased propensity for cardiovascular disease (CVD). We have hypothesized that there might be a quantifiable genetic basis for this linkage. To test this hypothesis we identified a comprehensive set of candidate risk genes for PTSD, and tested whether any were also independent risk genes for CVD. A functional analysis algorithm was used to identify associated signaling networks. We identified 106 PTSD studies that report one or more polymorphic variants in 87 candidate genes in 83,463 subjects and controls. The top upstream drivers for these PTSD risk genes are predicted to be the glucocorticoid receptor (NR3C1) and Tumor Necrosis Factor alpha (TNFA). We find that 37 of the PTSD candidate risk genes are also candidate independent risk genes for CVD. The association between PTSD and CVD is significant by Fisher's Exact Test (P = 3 × 10-54). We also find 15 PTSD risk genes that are independently associated with Type 2 Diabetes Mellitus (T2DM; also significant by Fisher's Exact Test (P = 1.8 × 10-16). Our findings offer quantitative evidence for a genetic link between post-traumatic stress and cardiovascular disease, Computationally, the common mechanism for this linkage between PTSD and CVD is innate immunity and NFκB-mediated inflammation.

  9. “Soldier's Heart”: A Genetic Basis for Elevated Cardiovascular Disease Risk Associated with Post-traumatic Stress Disorder

    Science.gov (United States)

    Pollard, Harvey B.; Shivakumar, Chittari; Starr, Joshua; Eidelman, Ofer; Jacobowitz, David M.; Dalgard, Clifton L.; Srivastava, Meera; Wilkerson, Matthew D.; Stein, Murray B.; Ursano, Robert J.

    2016-01-01

    “Soldier's Heart,” is an American Civil War term linking post-traumatic stress disorder (PTSD) with increased propensity for cardiovascular disease (CVD). We have hypothesized that there might be a quantifiable genetic basis for this linkage. To test this hypothesis we identified a comprehensive set of candidate risk genes for PTSD, and tested whether any were also independent risk genes for CVD. A functional analysis algorithm was used to identify associated signaling networks. We identified 106 PTSD studies that report one or more polymorphic variants in 87 candidate genes in 83,463 subjects and controls. The top upstream drivers for these PTSD risk genes are predicted to be the glucocorticoid receptor (NR3C1) and Tumor Necrosis Factor alpha (TNFA). We find that 37 of the PTSD candidate risk genes are also candidate independent risk genes for CVD. The association between PTSD and CVD is significant by Fisher's Exact Test (P = 3 × 10−54). We also find 15 PTSD risk genes that are independently associated with Type 2 Diabetes Mellitus (T2DM; also significant by Fisher's Exact Test (P = 1.8 × 10−16). Our findings offer quantitative evidence for a genetic link between post-traumatic stress and cardiovascular disease, Computationally, the common mechanism for this linkage between PTSD and CVD is innate immunity and NFκB-mediated inflammation. PMID:27721742

  10. Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution: Part 3 of a 3-Part Series.

    Science.gov (United States)

    Niemann, Bernd; Rohrbach, Susanne; Miller, Mark R; Newby, David E; Fuster, Valentin; Kovacic, Jason C

    2017-07-11

    Oxidative stress occurs whenever the release of reactive oxygen species (ROS) exceeds endogenous antioxidant capacity. In this paper, we review the specific role of several cardiovascular risk factors in promoting oxidative stress: diabetes, obesity, smoking, and excessive pollution. Specifically, the risk of developing heart failure is higher in patients with diabetes or obesity, even with optimal medical treatment, and the increased release of ROS from cardiac mitochondria and other sources likely contributes to the development of cardiac dysfunction in this setting. Here, we explore the role of different ROS sources arising in obesity and diabetes, and the effect of excessive ROS production on the development of cardiac lipotoxicity. In parallel, contaminants in the air that we breathe pose a significant threat to human health. This paper provides an overview of cigarette smoke and urban air pollution, considering how their composition and biological effects have detrimental effects on cardiovascular health. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. The Impact of Escitalopram on Vagally Mediated Cardiovascular Function to Stress and the Moderating Effects of Vigorous Physical Activity: A Randomised Controlled Treatment Study in Healthy Participants

    Directory of Open Access Journals (Sweden)

    Camilla S Hanson

    2013-09-01

    Full Text Available Recent concerns over the impact of antidepressant medications, including the selective serotonin reuptake inhibitors (SSRIs, on cardiovascular function highlight the importance of research on the moderating effects of specific lifestyle factors such as physical activity. Studies in affective neuroscience have demonstrated robust acute effects of SSRIs, yet the impact of SSRIs on cardiovascular stress responses and the moderating effects of physical activity remain to be determined. This was the goal of the present study, which involved a double-blind, randomised, placebo-controlled, cross-over trial of a single-dose of escitalopram (20mg in 44 healthy females; outcomes were heart rate and its variability. Participants engaging in at least 30 minutes of vigorous physical activity at least 3 times per week (regular exercisers showed a more resilient cardiovascular stress response than irregular vigorous exercisers, a finding associated with a moderate effect size (Cohen’s d=0.48. Escitalopram attenuated the cardiovascular stress response in irregular exercisers only (heart rate decreased: Cohen’s d=0.80; heart rate variability increased: Cohen’s d=0.33. Heart rate during stress under escitalopram in the irregular exercisers was similar to that during stress under placebo in regular exercisers.. These findings highlight that the effects of regular vigorous exercise during stress are comparable to the effects of an acute dose of escitalopram, highlighting the beneficial effects of this particular antidepressant in irregular exercisers. Given that antidepressant drugs alone do not seem to protect patients from cardiovascular disease, longitudinal studies are needed to evaluate the impact of exercise on cardiovascular stress responses in patients receiving long-term antidepressant treatment.

  12. The impact of escitalopram on vagally mediated cardiovascular function to stress and the moderating effects of vigorous physical activity: a randomized controlled treatment study in healthy participants.

    Science.gov (United States)

    Hanson, Camilla S; Outhred, Tim; Brunoni, Andre R; Malhi, Gin S; Kemp, Andrew H

    2013-01-01

    Recent concerns over the impact of antidepressant medications, including the selective serotonin reuptake inhibitors (SSRIs), on cardiovascular function highlight the importance of research on the moderating effects of specific lifestyle factors such as physical activity. Studies in affective neuroscience have demonstrated robust acute effects of SSRIs, yet the impact of SSRIs on cardiovascular stress responses and the moderating effects of physical activity remain to be determined. This was the goal of the present study, which involved a double-blind, randomized, placebo-controlled, cross-over trial of a single-dose of escitalopram (20 mg) in 44 healthy females; outcomes were heart rate (HR) and its variability. Participants engaging in at least 30 min of vigorous physical activity at least 3 times per week (regular exercisers) showed a more resilient cardiovascular stress response than irregular vigorous exercisers, a finding associated with a moderate effect size (Cohen's d = 0.48). Escitalopram attenuated the cardiovascular stress response in irregular exercisers only (HR decreased: Cohen's d = 0.80; HR variability increased: Cohen's d = 0.33). HR during stress under escitalopram in the irregular exercisers was similar to that during stress under placebo in regular exercisers. These findings highlight that the effects of regular vigorous exercise during stress are comparable to the effects of an acute dose of escitalopram, highlighting the beneficial effects of this particular antidepressant in irregular exercisers. Given that antidepressant drugs alone do not seem to protect patients from cardiovascular disease (CVD), longitudinal studies are needed to evaluate the impact of exercise on cardiovascular stress responses in patients receiving long-term antidepressant treatment.

  13. The perfusion pattern in coronary artery occlusion: comparison of exercise and adenosine.p6.

    Science.gov (United States)

    Iskandrian, A S; Kegel, J; Heo, J; Ogilby, J D; Untereker, W J; Cave, V

    1992-12-01

    This study compared exercise to adenosine thallium-201 single photon emission computed tomography in detecting occlusion of left anterior descending or right coronary arteries in patients with no previous myocardial infarction. There were 41 patients who underwent adenosine thallium imaging (adenosine infusion at a rate of 140 micrograms/kg/min for 6 min), and 143 patients who underwent exercise thallium imaging. There were more patients with right coronary than left anterior descending coronary artery occlusion. Thus, in the adenosine group, there were 15 patients with left anterior descending artery occlusion, and 26 with right coronary artery occlusion, and in the exercise group, there were 46 patients with left anterior descending artery occlusion, and 97 patients with right coronary artery occlusion. In the adenosine group, the thallium images were abnormal in 41 patients (100%), while in the exercise group, the thallium images were abnormal in 125 patients (87%, P exercise group (P:NS). In patients with isolated single vessel occlusion, the size of the perfusion abnormality was 28 +/- 9% with adenosine, and 21 +/- 12% with exercise (P:NS). Thus, most patients with occlusion of the left anterior descending or right coronary artery have regional perfusion abnormality during stress; the different role of collaterals with each type of stress may explain the higher percentage of abnormal results with adenosine than exercise.

  14. The Effects of Cognitive Hardiness on Stress, Health, Performance, and Cardiovascular/Neuroendocrine Function

    National Research Council Canada - National Science Library

    Drummond, Johathan

    1997-01-01

    .... Hardiness has also been thought to exert main effects on health and performance outcomes. In Study 1, relationships between hardiness, perceived stress, depression, and academic performance were investigated...

  15. Benefit of social support for resilience-building is contingent on social context: examining cardiovascular adaptation to recurrent stress in women.

    Science.gov (United States)

    Howard, Siobhán; Hughes, Brian M

    2012-07-01

    Previous work on social support and stress tolerance using laboratory-based cardiovascular stress response paradigms has suggested that perceived social support may be effective in building resilience in recipients. However, such paradigms are often socially de-contextualized insofar as they fail to take account of the social aspects of stress itself. Using 90 healthy college women, the present study sought to examine the association between self-reported perceived social support and cardiovascular stress tolerance. Participants underwent two consecutive exposures to a mental arithmetic task. On second exposure to the stressor, participants completed the task under either social threat or control conditions. Social threat was manipulated using socially salient instructions, to create a high social context. Adaptation to stress was established in terms of comparisons between cardiovascular responses to successive exposures. Results showed that cardiovascular responses tended to habituate across time, with perceived social support associated with the degree of habituation, but only under certain contextual conditions; high perceived support was associated with effective habituation under control conditions only. This response pattern is consistent with the view that high perceived social support buffers against stress in healthful ways, but only in asocial contexts.

  16. Anxious women do not show the expected decrease in cardiovascular stress responsiveness as pregnancy advances

    NARCIS (Netherlands)

    Braeken, M A K A; Jones, A; Otte, R A; Widjaja, D; Van Huffel, S; Monsieur, G J Y J; van Oirschot, C M; Van den Bergh, B R H

    2015-01-01

    Altered stress responsiveness is a risk factor for mental and physical illness. In non-pregnant populations, it is well-known that anxiety can alter the physiological regulation of stress reactivity. Characterization of corresponding risks for pregnant women and their offspring requires greater

  17. Endogenous Production of Extracellular Adenosine by Trabecular Meshwork Cells: Potential Role in Outflow Regulation

    Science.gov (United States)

    Wu, Jing; Li, Guorong; Luna, Coralia; Spasojevic, Ivan; Epstein, David L.; Gonzalez, Pedro

    2012-01-01

    Purpose. To investigate the mechanisms for endogenous production of extracellular adenosine in trabecular meshwork (TM) cells and evaluate its physiological relevance to the regulation of aqueous humor outflow facility. Methods. Extra-cellular levels of adenosine monophosphate (AMP) and adenosine in porcine trabecular meshwork (PTM) cells treated with adenosine triphosphate (ATP), AMP, cAMP or forskolin with or without specific inhibitors of phosphodiesterases (IBMX) and CD73 (AMPCP) were determined by high-pressure liquid chromatography fluorometry. Extracellular adenosine was also evaluated in cell cultures subjected to cyclic mechanical stress (CMS) (20% stretching; 1 Hz) and after disruption of lipid rafts with methyl-β-cyclodextrin. Expression of CD39 and CD73 in porcine TM cells and tissue were examined by Q-PCR and Western blot. The effect of inhibition of CD73 on outflow facility was evaluated in perfused living mouse eyes. Results. PTM cells generated extracellular adenosine from extracellular ATP and AMP but not from extracellular cAMP. Increased intracellular cAMP mediated by forskolin led to a significant increase in extracellular adenosine production that was not prevented by IBMX. Inhibition of CD73 resulted, in all cases, in a significant decrease in extracellular adenosine. CMS induced a significant activation of extracellular adenosine production. Inhibition of CD73 activity with AMPCP in living mouse eyes resulted in a significant decrease in outflow facility. Conclusions. These results support the concept that the extracellular adenosine pathway might play an important role in the homeostatic regulation of outflow resistance in the TM, and suggest a novel mechanism by which pathologic alteration of the TM, such as increased tissue rigidity, could lead to abnormal elevation of IOP in glaucoma. PMID:22997289

  18. The cardiovascular effects of methylxanthines

    NARCIS (Netherlands)

    Riksen, N.P.; Smits, P.; Rongen, G.A.P.J.M.

    2011-01-01

    In the concentration range that is normally achieved in humans, e.g., after the drinking of coffee or in patients treated with theophylline, the cardiovascular effects of methylxanthines are primarily due to antagonism of adenosine A(1) and A(2) receptors. Inhibition of phosphodiesterases or

  19. Novel aspects of extracellular adenosine dynamics revealed by adenosine sensor cells

    Directory of Open Access Journals (Sweden)

    Kunihiko Yamashiro

    2017-01-01

    Full Text Available Adenosine modulates diverse physiological and pathological processes in the brain, including neuronal activities, blood flow, and inflammation. However, the mechanisms underlying the dynamics of extracellular adenosine are not fully understood. We have recently developed a novel biosensor, called an adenosine sensor cell, and we have characterized the neuronal and astrocytic pathways for elevating extracellular adenosine. In this review, the physiological implications and therapeutic potential of the pathways revealed by the adenosine sensor cells are discussed. We propose that the multiple pathways regulating extracellular adenosine allow for the diverse functions of this neuromodulator, and their malfunctions cause various neurological and psychiatric disorders.

  20. Of larks and hearts--morningness/eveningness, heart rate variability and cardiovascular stress response at different times of day.

    Science.gov (United States)

    Roeser, Karolin; Obergfell, Friederike; Meule, Adrian; Vögele, Claus; Schlarb, Angelika A; Kübler, Andrea

    2012-05-15

    Inter-individual differences in the circadian period of physical and mental functions can be described on the dimension of morningness/eveningness. Previous findings support the assumption that eveningness is related to greater impulsivity and susceptibility to stress than morningness. Heart rate variability (HRV) serves as a physiological correlate of self- and emotional regulation and has not yet been investigated in relation to chronotypes. The study explores differences in HRV and other cardiovascular measures in morning- and evening-types at rest and under stress at different times of day (8-11 a.m. or 4-7 p.m.). Students (N=471) were screened for chronotype and n=55 females (27 morning- and 28 evening-types) were recruited for testing. These participants performed a mental arithmetic task while heart rate (HR) and blood pressure (BP) were recorded. Spectral components and a time-domain measure of HRV were calculated on HR data from resting and mental stress periods. Evening-types had significantly higher HR and systolic BP, but lower HRV than morning-types both at baseline and during stress. Stress induced in the evening had a significantly stronger impact on absolute and baseline corrected physiological measures in both chronotypes. The interaction of chronotype and testing time did not reach the level of significance for any of the dependent variables. The enhanced physiological arousal in evening-types might contribute to increased vulnerability to psychological distress. Hence, previous behavioral findings are supported by the physiological data of this study. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Coenzyme Q10 and oxidative stress, the association with peripheral sensory neuropathy and cardiovascular disease in type 2 diabetes mellitus.

    Science.gov (United States)

    Forsberg, Elisabete; Xu, Cheng; Grünler, Jacob; Frostegård, Johan; Tekle, Michael; Brismar, Kerstin; Kärvestedt, Lars

    2015-01-01

    Our study aimed to explore associations between metabolic control, oxidative stress and coenzyme Q10 (CoQ10) in relation to diabetes complications in a representative population of type 2 diabetes. A geographic cohort of 156 subjects was recruited. Serum concentrations of CoQ10 and vitamin E were measured by HPLC. ROS was determined by free oxygen radicals testing (FORT). Glutaredoxin (Grx) activity, oxidized LDL cholesterol (oxLDLc), high sensitive CRP (hsCRP), HbA1c, urine albumin, serum creatinine, serum cystatin C, and plasma lipids were assayed with routine laboratory protocols. Serum CoQ10 was higher than in nondiabetics. HbA1c, fP-glucose, hyperlipidemia, inflammation (hsCRP), and increased BMI were associated with signs of oxidative stress as increased levels of FORT, Grx activity and/or increased levels of oxLDLc Oxidative stress was found to be strongly correlated with prevalence of cardiovascular disease (CVD) and peripheral sensory neuropathy (PSN). In both gender groups there were positive correlations between CoQ10 and oxLDLc, and between BMI and the ratio CoQ10/chol. Grx activity was inversely correlated to oxLDLc and CoQ10. Women with CVD and PSN had higher waist index, oxLDLc, and FORT levels compared to men but lower CoQ10 levels. Men had worse kidney function and lower vitamin E. Multiple regression analysis showed increased levels of CoQ10 to be significantly correlated with increased levels of cholesterol, triglycerides, vitamin E, fB-glucose and BMI. Hyperlipidemia, hyperglycemia and inflammation were associated with oxidative stress, which was correlated to the prevalence of diabetes complications. CoQ10 was increased in response to oxidative stress. There were gender differences in the risk factors associated with diabetes complications. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

    Science.gov (United States)

    Buchhorn, Reiner; Meint, Sebastian; Willaschek, Christian

    2016-01-01

    Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children-allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)-have the highest risk for 'stress diseases' such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children.

  3. The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

    Directory of Open Access Journals (Sweden)

    Reiner Buchhorn

    Full Text Available Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life.Compared to the healthy control group heart rate variability (HRV is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA, children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD, who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF-Power is indicating reduced vagal activity as a sign of autonomic imbalance.It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children-allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes-have the highest risk for 'stress diseases' such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children.

  4. Hypoxia stress test reveals exaggerated cardiovascular effects in hypertensive rats after exposure to the air pollutant acrolein.

    Science.gov (United States)

    Perez, Christina M; Ledbetter, Allen D; Hazari, Mehdi S; Haykal-Coates, Najwa; Carll, Alex P; Winsett, Darrell W; Costa, Daniel L; Farraj, Aimen K

    2013-04-01

    Exposure to air pollution increases the risk of cardiovascular morbidity and mortality, especially in susceptible populations. Despite increased risk, adverse responses are often delayed and require additional stress tests to reveal latent effects of exposure. The goal of this study was to use an episode of "transient hypoxia" as an extrinsic stressor to uncover latent susceptibility to environmental pollutants in a rodent model of hypertension. We hypothesized that exposure to acrolein, an unsaturated aldehyde and mucosal irritant found in cigarette smoke, diesel exhaust, and power plant emissions, would increase cardiopulmonary sensitivity to hypoxia, particularly in hypertensive rats. Spontaneously hypertensive and Wistar Kyoto (normotensive) rats, implanted with radiotelemeters, were exposed once for 3h to 3 ppm acrolein gas or filtered air in whole-body plethysmograph chambers and challenged with a 10% oxygen atmosphere (10min) 24h later. Acrolein exposure increased heart rate, blood pressure, breathing frequency, and minute volume in hypertensive rats and also increased the heart rate variability parameter LF, suggesting a potential role for increased sympathetic tone. Normotensive rats only had increased blood pressure during acrolein exposure. The hypoxia stress test after acrolein exposure revealed increased diastolic blood pressure only in hypertensive rats and increased minute volume and expiratory time only in normotensive rats. These results suggest that hypertension confers exaggerated sensitivity to air pollution and that the hypoxia stress test is a novel tool to reveal the potential latent effects of air pollution exposure.

  5. Cardiovascular Responsivity, Physical and Psychosocial Job Stress, and the Risk of Preterm Delivery

    National Research Council Canada - National Science Library

    Hatch, MauMaureen

    1998-01-01

    The overall goal of this grant is to examine the effects of physical and psychological stress as risk factors for preterm delivery among an ethnically diverse population of 1 000 active duty military...

  6. Mental stress and nursing intervention in critically ill patients after cardiovascular surgery

    Directory of Open Access Journals (Sweden)

    Vivian Rodríguez Marrero

    2016-03-01

    Conclusiones: The main mental stress triggers were the bad impression caused by medical devices, inability to sleep and physical isolation. Nurses generally had a good level of knowledge, and acceptable procedures.

  7. Heat and Dehydration Additively Enhance Cardiovascular Outcomes following Orthostatically-Stressful Calisthenics Exercise

    National Research Council Canada - National Science Library

    Ashley P. Akerman; Samuel J. E. Lucas; Rajesh Katare; James D. Cotter

    2017-01-01

    ...) completed three trials of 90-min orthostatically-stressful calisthenics, in: (i) temperate conditions (22°C, 50% rh, no airflow; CON); (ii) heat (40°C, 60% rh) whilst euhydrated (HEAT), and (iii...

  8. Design of an ex vivo culture system to investigate the effects of shear stress on cardiovascular tissue.

    Science.gov (United States)

    Sucosky, Philippe; Padala, Muralidhar; Elhammali, Adnan; Balachandran, Kartik; Jo, Hanjoong; Yoganathan, Ajit P

    2008-06-01

    Mechanical forces are known to affect the biomechanical properties of native and engineered cardiovascular tissue. In particular, shear stress that results from the relative motion of heart valve leaflets with respect to the blood flow is one important component of their mechanical environment in vivo. Although different types of bioreactors have been designed to subject cells to shear stress, devices to expose biological tissue are few. In an effort to address this issue, the aim of this study was to design an ex vivo tissue culture system to characterize the biological response of heart valve leaflets subjected to a well-defined steady or time-varying shear stress environment. The novel apparatus was designed based on a cone-and-plate viscometer. The device characteristics were defined to limit the secondary flow effects inherent to this particular geometry. The determination of the operating conditions producing the desired shear stress profile was streamlined using a computational fluid dynamic (CFD) model validated with laser Doppler velocimetry. The novel ex vivo tissue culture system was validated in terms of its capability to reproduce a desired cone rotation and to maintain sterile conditions. The CFD results demonstrated that a cone angle of 0.5 deg, a cone radius of 40 mm, and a gap of 0.2 mm between the cone apex and the plate could limit radial secondary flow effects. The novel cone-and-plate permits to expose nine tissue specimens to an identical shear stress waveform. The whole setup is capable of accommodating four cone-and-plate systems, thus concomitantly subjecting 36 tissue samples to desired shear stress condition. The innovative design enables the tissue specimens to be flush mounted in the plate in order to limit flow perturbations caused by the tissue thickness. The device is capable of producing shear stress rates of up to 650 dyn cm(-2) s(-1) (i.e., maximum shear stress rate experienced by the ventricular surface of an aortic valve leaflet

  9. Aerobic Fitness Level Affects Cardiovascular and Salivary Alpha Amylase Responses to Acute Psychosocial Stress.

    Science.gov (United States)

    Wyss, Thomas; Boesch, Maria; Roos, Lilian; Tschopp, Céline; Frei, Klaus M; Annen, Hubert; La Marca, Roberto

    2016-12-01

    Good physical fitness seems to help the individual to buffer the potential harmful impact of psychosocial stress on somatic and mental health. The aim of the present study is to investigate the role of physical fitness levels on the autonomic nervous system (ANS; i.e. heart rate and salivary alpha amylase) responses to acute psychosocial stress, while controlling for established factors influencing individual stress reactions. The Trier Social Stress Test for Groups (TSST-G) was executed with 302 male recruits during their first week of Swiss Army basic training. Heart rate was measured continuously, and salivary alpha amylase was measured twice, before and after the stress intervention. In the same week, all volunteers participated in a physical fitness test and they responded to questionnaires on lifestyle factors and personal traits. A multiple linear regression analysis was conducted to determine ANS responses to acute psychosocial stress from physical fitness test performances, controlling for personal traits, behavioural factors, and socioeconomic data. Multiple linear regression revealed three variables predicting 15 % of the variance in heart rate response (area under the individual heart rate response curve during TSST-G) and four variables predicting 12 % of the variance in salivary alpha amylase response (salivary alpha amylase level immediately after the TSST-G) to acute psychosocial stress. A strong performance at the progressive endurance run (high maximal oxygen consumption) was a significant predictor of ANS response in both models: low area under the heart rate response curve during TSST-G as well as low salivary alpha amylase level after TSST-G. Further, high muscle power, non-smoking, high extraversion, and low agreeableness were predictors of a favourable ANS response in either one of the two dependent variables. Good physical fitness, especially good aerobic endurance capacity, is an important protective factor against health

  10. On the continuity of mean total normal stress in geometrical multiscale cardiovascular problems

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, Pablo J., E-mail: pjblanco@lncc.br [LNCC, Laboratório Nacional de Computação Científica, Av. Getúlio Vargas 333, Quitandinha, 25651-075 Petrópolis (Brazil); INCT-MACC, Instituto Nacional de Ciência e Tecnologia em Medicina Assistida por Computação Científica, Petrópolis (Brazil); Deparis, Simone, E-mail: simone.deparis@epfl.ch [CMCS, Chair of Modeling and Scientific Computing, MATHICSE, Mathematics Institute of Computational Science and Engineering, EPFL, École Polytechnique Fédérale de Lausanne, Station 8, CH-1015 Lausanne (Switzerland); Malossi, A. Cristiano I., E-mail: cristiano.malossi@epfl.ch [CMCS, Chair of Modeling and Scientific Computing, MATHICSE, Mathematics Institute of Computational Science and Engineering, EPFL, École Polytechnique Fédérale de Lausanne, Station 8, CH-1015 Lausanne (Switzerland)

    2013-10-15

    In this work an iterative strategy to implicitly couple dimensionally-heterogeneous blood flow models accounting for the continuity of mean total normal stress at interface boundaries is developed. Conservation of mean total normal stress in the coupling of heterogeneous models is mandatory to satisfy energetic consistency between them. Nevertheless, existing methodologies are based on modifications of the Navier–Stokes variational formulation, which are undesired when dealing with fluid–structure interaction or black box codes. The proposed methodology makes possible to couple one-dimensional and three-dimensional fluid–structure interaction models, enforcing the continuity of mean total normal stress while just imposing flow rate data or even the classical Neumann boundary data to the models. This is accomplished by modifying an existing iterative algorithm, which is also able to account for the continuity of the vessel area, when required. Comparisons are performed to assess differences in the convergence properties of the algorithms when considering the continuity of mean normal stress and the continuity of mean total normal stress for a wide range of flow regimes. Finally, examples in the physiological regime are shown to evaluate the importance, or not, of considering the continuity of mean total normal stress in hemodynamics simulations.

  11. A definition of normovolaemia and consequences for cardiovascular control during orthostatic and environmental stress

    DEFF Research Database (Denmark)

    Truijen, Jasper; Bundgaard-Nielsen, Morten; van Lieshout, Johannes J

    2010-01-01

    not increase further indicating that in the supine resting position the heart operates on the plateau of the Frank-Starling curve which, therefore, may be taken as a functional definition of normovolaemia. Since the capacity of the vascular system surpasses the blood volume, orthostatic and environmental...... redistribution becomes dependent on sympathetic activation affecting not only skin and splanchnic blood flow, but also flow to skeletal muscles and the brain. This review addresses the hypothesis that deviations from normovolaemia significantly influence these cardiovascular responses....

  12. Effects of surgical stress and insulin on cardiovascular function and norepinephrine kinetics

    DEFF Research Database (Denmark)

    Christensen, N J; Hilsted, J; Hegedüs, Laszlo

    1984-01-01

    In resting supine subjects the whole-body clearance of norepinephrine (NE) based on arterial and venous sampling averaged 1.4 and 2.5 liters/min, respectively (P less than 0.02). The difference in clearance values was due to a peripheral uptake of NE averaging 45%. The calculation of plasma NE cl...... insulin-dependent diabetics show abnormalities in the regulation of cardiovascular function and sympathetic nervous activity that may be related to the lack of rise in endogenous insulin in these patients. These results suggest that insulin may be of importance for the normal function...

  13. Comparison of intravenous adenosine and intravenous regadenoson for the measurement of pressure-derived coronary fractional flow reserve.

    Science.gov (United States)

    Arumugham, Pradeep; Figueredo, Vincent M; Patel, Parul B; Morris, D Lynn

    2013-02-22

    Defining the clinical and physiologic significance of an intermediate coronary artery stenosis is aided by measurement of fractional flow reserve (FFR). Adenosine is the most common agent used in the cardiac catheterisation laboratory for the measurement of FFR. Regadenoson, a selective adenosine receptor agonist, with fewer side effects than adenosine has been used extensively in stress testing to induce hyperaemia. We postulated that FFR measurements would be equivalent following administration of regadenoson and adenosine. Twenty patients with an angiographic intermediate coronary artery stenosis (50% to 80%) were included in the study. FFR was measured during three minutes of intravenous (IV) adenosine infusion and for five minutes after an injection of regadenoson. The mean difference between the FFR measured by IV adenosine and IV regadenoson was 0.0040 (min -0.04, max +0.04, standard deviation [SD] 0.025). There was a strong linear correlation between the FFR measured by IV adenosine and IV regadenoson (R2 linear=0.933). The FFR at maximum hyperaemia was achieved earlier using regadenoson than adenosine (59±24.5 sec vs. 93±44.5 sec, p=0.01). Regadenoson produces similar pressure-derived FFR compared to IV adenosine infusion.

  14. Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

    Science.gov (United States)

    Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

    2017-02-01

    Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

  15. Adenosine-to-Inosine RNA Editing in Health and Disease.

    Science.gov (United States)

    Gatsiou, Aikaterini; Vlachogiannis, Nikolaos; Lunella, Federica Francesca; Sachse, Marco; Stellos, Konstantinos

    2017-09-26

    Adenosine deamination in transcriptome results in the formation of inosine, a process that is called A-to-I RNA editing. Adenosine deamination is one of the more than 140 described RNA modifications. A-to-I RNA editing is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes and is essential for life. Recent Advances: Accumulating evidence supports a critical role of RNA editing in all aspects of RNA metabolism, including mRNA stability, splicing, nuclear export, and localization, as well as in recoding of proteins. These advances have significantly enhanced the understanding of mechanisms involved in development and in homeostasis. Furthermore, recent studies have indicated that RNA editing may be critically involved in cancer, aging, neurological, autoimmune, or cardiovascular diseases. This review summarizes recent and significant achievements in the field of A-to-I RNA editing and discusses the importance and translational value of this RNA modification for gene expression, cellular, and organ function, as well as for disease development. Elucidation of the exact RNA editing-dependent mechanisms in a single-nucleotide level may pave the path toward the development of novel therapeutic strategies focusing on modulation of ADAR function in the disease context. Antioxid. Redox Signal. 00, 000-000.

  16. Cardiovascular and cortisol reactions to acute psychological stress under conditions of high versus low social evaluative threat: associations with the type D personality construct.

    Science.gov (United States)

    Bibbey, Adam; Carroll, Douglas; Ginty, Annie T; Phillips, Anna C

    2015-06-01

    Social evaluative threat is an important factor in the cardiovascular response to mental stress. This study examined whether Type D personality, characterized by social inhibition and negative affectivity, is associated with an adverse cardiovascular response to a non-social and social evaluative threat. A total of 2300 students were screened for Type D personality, and 130 were selected for a nonsocial stress exposure condition (31 Type D, 30 non-Type D: 52% female) or a condition high in social evaluative threat (35 Type D, 34 non-Type D: 55% female). Systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and salivary cortisol were measured. Social evaluative threat resulted in higher cardiovascular responses than the nonsocial challenge (SBP, p = .001, η = 0.092;DBP, p = .006, η = 0.058;HR, p = .006, η = 0.059). The greatest cardiovascular stress reactions were exhibited by Type D participants in the high social evaluation condition; reflected in significant group by condition interactions for SBP (F(1,126) = 7.29, p = .008, η = 0.055), DBP (F(1,126) = 5.23, p = .024, η = 0.040), and HR (F(1,126) = 5.04, p = .027, η = 0.038) reactivity. Only Type Ds in the social condition mounted a positive cortisol response (F(1,33) = 5.07, p = .031, η = 0.133). Type D individuals show different stress reactions depending on the social evaluative nature of the stress exposure. These findings suggest that dysregulation of the stress response in social situations potentially increases cardiovascular disease risk.

  17. Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats.

    Science.gov (United States)

    Almeida, Jeferson; Duarte, Josiane O; Oliveira, Leandro A; Crestani, Carlos C

    2015-01-01

    Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.

  18. Problematic Internet use, excessive alcohol consumption, their comorbidity and cardiovascular and cortisol reactions to acute psychological stress in a student population.

    Science.gov (United States)

    Bibbey, Adam; Phillips, Anna C; Ginty, Annie T; Carroll, Douglas

    2015-06-01

    Problematic Internet use and excessive alcohol consumption have been associated with a host of maladaptive outcomes. Further, low (blunted) cardiovascular and stress hormone (e.g. cortisol) reactions to acute psychological stress are a feature of individuals with a range of adverse health and behavioural characteristics, including dependencies such as tobacco and alcohol addiction. The present study extended this research by examining whether behavioural dependencies, namely problematic Internet use, excessive alcohol consumption, and their comorbidity would also be associated with blunted stress reactivity. A large sample of university students (N = 2313) were screened using Internet and alcohol dependency questionnaires to select four groups for laboratory testing: comorbid Internet and alcohol dependence (N = 17), Internet dependence (N = 17), alcohol dependence (N = 28), and non-dependent controls (N = 26). Cardiovascular activity and salivary cortisol were measured at rest and in response to a psychological stress protocol comprising of mental arithmetic and public speaking tasks. Neither problematic Internet behaviour nor excessive alcohol consumption, either individually or in combination, were associated with blunted cardiovascular or cortisol stress reactions. Discussion It is possible that problematic Internet behaviour and excessive alcohol consumption in a student population were not related to physiological reactivity as they may not reflect ingrained addictions but rather an impulse control disorder and binging tendency. The present results serve to indicate some of the limits of the developing hypothesis that blunted stress reactivity is a peripheral marker of the central motivational dysregulation in the brain underpinning a wide range of health and behavioural problems.

  19. GRACE and TIMI risk scores but not stress imaging predict long-term cardiovascular follow-up in patients with chest pain after a rule-out protocol

    NARCIS (Netherlands)

    van der Zee, P. M.; Verberne, H. J.; Cornel, J. H.; Kamp, O.; van der Zant, F. M.; Bholasingh, R.; de Winter, R. J.

    2011-01-01

    Objective To determine the long-term prognostic value of stress imaging and clinical risk scoring for cardiovascular mortality in chest pain patients after ruling out acute coronary syndrome (ACS). Methods A standard rule-out protocol was performed in emergency room patients with a normal or

  20. Air particulate matter induced oxidative stress and inflammation in cardiovascular disease and atherosclerosis: The role of Nrf2 and AhR-mediated pathways.

    Science.gov (United States)

    Lawal, Akeem O

    2017-03-15

    Air particulate matter (PM) is an important component of air pollution, which has been reported to play important role in the adverse health effects of the latter. Extensive experimental data and epidemiological studies have shown that the increased cardiovascular morbidity and mortality and atherosclerosis caused by air pollution are mainly due to the PM component. Implicated in these adverse health effects of PM, is their ability to induce oxidative stress and pro-inflammatory events in the vascular system. The association between the cardiovascular ischemic events and atherosclerosis induced by PM has been linked to the ultrafine and fine components. These particles have a high content of redox cyclic chemicals. This, together with their ability to combine with proatherogenic molecules enhanced tissue oxidative stress. Studies have shown that the oxidative stress induced by PM could up-regulates the expression of phase I and phase II metabolize enzymes. This up-regulation occurs by the activation of transcription factors (such as nuclear factor (erythroid-derived 2) -like 2-related factor (Nrf2) and aryl hydrocarbon receptor (AhR)). This review will focus on data supporting the role of oxidative stress and inflammation in PM-induced cardiovascular diseases and atherosclerosis and the importance of Nrf2-and AhR- dependent regulatory pathways in the PM-induced cardiovascular events and atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Both α1- and α2-adrenoceptors in the Insular Cortex Are Involved in the Cardiovascular Responses to Acute Restraint Stress in Rats

    Science.gov (United States)

    Alves, Fernando H. F.; Crestani, Carlos C.; Resstel, Leonardo B. M.; Corrêa, Fernando M. A.

    2014-01-01

    The insular cortex (IC) is a limbic structure involved in cardiovascular responses observed during aversive threats. However, the specific neurotransmitter mediating IC control of cardiovascular adjustments to stress is yet unknown. Therefore, in the present study we investigated the role of local IC adrenoceptors in the cardiovascular responses elicited by acute restraint stress in rats. Bilateral microinjection of different doses (0.3, 5, 10 and 15 nmol/100 nl) of the selective α1-adrenoceptor antagonist WB4101 into the IC reduced both the arterial pressure and heart rate increases elicited by restraint stress. However, local IC treatment with different doses (0.3, 5, 10 and 15 nmol/100 nl) of the selective α2-adrenoceptor antagonist RX821002 reduced restraint-evoked tachycardia without affecting the pressor response. The present findings are the first direct evidence showing the involvement of IC adrenoceptors in cardiovascular adjustments observed during aversive threats. Our findings indicate that IC noradrenergic neurotransmission acting through activation of both α1- and α2-adrenoceptors has a facilitatory influence on pressor response to acute restraint stress. Moreover, IC α1-adrenoceptors also play a facilitatory role on restraint-evoked tachycardiac response. PMID:24404141

  2. Shift work and cardiovascular disease - pathways from circadian stress to morbidity.

    Science.gov (United States)

    Puttonen, Sampsa; Härmä, Mikko; Hublin, Christer

    2010-03-01

    In order to establish a causal relation between shift work and cardiovascular disease (CVD), we need to verify the pathways from the former to the latter. This paper aims to review the current knowledge of the mechanisms between shift work and CVD. Shift work can increase the risk of CVD by several interrelated psychosocial, behavioral, and physiological mechanisms. The psychosocial mechanisms relate to difficulties in controlling working hours, decreased work-life balance, and poor recovery following work. The most probable behavioral changes are weight gain and smoking. The plausible physiological and biological mechanisms are related to the activation of the autonomic nervous system, inflammation, changed lipid and glucose metabolism, and related changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The data provide evidence for possible disease mechanisms between shift work and CVD, but compelling evidence on any specific mechanism is missing.

  3. Effect of noise stress on some cardiovascular parameters and audiovisual reaction time.

    Science.gov (United States)

    Saha, S; Gandhi, A; Das, S; Kaur, P; Singh, S H

    1996-01-01

    A study of the effect of noise stress on some of the physiological parameters was carried out on healthy male workers of thermal power station (exposed to sound level 90-113 dBA) and compared with age and sex matched healthy controls (exposed to sound level 48-66 dBA). The parameters recorded were heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), galvanic skin resistance (GSR), auditory and visual reaction time (ART and VRT) and audiogram. Significant impairment in audiogram at 3000 Hz and 4000 Hz, increase in HR, SBP, DBP and decrease in GSR, ART and VRT were recorded in workers who were exposed to noise stress. Also a higher prevalence of hypertension was observed in them and that they were at a higher risk of developing hypertension than the control group. It was also observed that these modifications are related to duration of exposure to noise stress. It is presumed that all the above extra auditory effects are due to activation of autonomic nervous system and hypothalamo-hypophyseal adrenal axis, and the resultant release of catecholamines from adrenal medulla due to noise stress.

  4. The cardiovascular perfusionist as a model for the successful technologist in high stress situations.

    Science.gov (United States)

    Friday, P J; Mook, W J

    1991-01-01

    This study investigates the psychological profiles of highly stressed medical technologists. One hundred and four individuals representing a cross-section of the United States who function as operators of heart-lung machines during open heart surgery (perfusionists) were studied using both internal and external models based on the works of Eric Berne and Karen Horney. Daily exposure to life and death responsibilities combined with the constant pressures of maintaining current technical skills can make the profession selected for this study representative of high technology professions that require a great deal of coping. Results of this study indicate that there is a balanced psychological profile in successful technologists functioning in long-term, high-stressed occupations. Female perfusionists appear to be more aggressive and critical than their male counterparts. This is seen as an attempt by female perfusionists to compensate for what has historically been a male dominanted, highly technical and high-stressed occupation. Generalizations for candidate selections to high stressed occupations could be made as well as projections of foundations for possible progressive disillusionment (burn out).

  5. Regulation of neutrophil function by adenosine

    Science.gov (United States)

    Barletta, Kathryn E.; Ley, Klaus; Mehrad, Borna

    2012-01-01

    Adenosine is an endogenously released purine nucleoside that signals via four widely expressed G-protein coupled receptors: A1, A2A, A2B, and A3. In the setting of inflammation, the generation and release of adenosine is greatly enhanced. Neutrophils play an important role in host defense against invading pathogens and are the cellular hallmark of acute inflammation. Neutrophils both release adenosine and can respond to it via expression of all four adenosine receptor subtypes. At low concentrations, adenosine can act via the A1 and A3 adenosine receptor subtypes to promote neutrophil chemotaxis and phagocytosis. At higher concentrations, adenosine acts at the lower-affinity A2A and A2B receptors to inhibit neutrophil trafficking and effector functions such as oxidative burst, inflammatory mediator production, and granule release. Modulation of neutrophil function by adenosine is relevant in a broad array of disease models, including ischemia reperfusion injury, sepsis, and non-infectious acute lung injury. This review will summarize relevant research in order to provide a framework for understanding how adenosine directly regulates various elements of neutrophil function. PMID:22423037

  6. Cine and tagged cardiovascular magnetic resonance imaging in normal rat at 1.5 T: a rest and stress study

    Directory of Open Access Journals (Sweden)

    Lepetit-Coiffé Matthieu

    2008-11-01

    Full Text Available Abstract Background The purpose of this study was to measure regional contractile function in the normal rat using cardiac cine and tagged cardiovascular magnetic resonance (CMR during incremental low doses of dobutamine and at rest. Methods Five rats were investigated for invasive left ventricle pressure measurements and five additional rats were imaged on a clinical 1.5 T MR system using a cine sequence (11–20 phases per cycle, 0.28/0.28/2 mm and a C-SPAMM tag sequence (18–25 phases per cycle, 0.63/1.79/3 mm, tag spacing 1.25 mm. For each slice, wall thickening (WT and circumferential strains (CS were calculated at rest and at stress (2.5, 5 and 10 μg/min/kg of dobutamine. Results Good cine and tagged images were obtained in all the rats even at higher heart rate (300–440 bpm. Ejection fraction and left ventricular (LV end-systolic volume showed significant changes after each dobutamine perfusion dose (p Conclusion Robust cardiac cine and tagging CMR measurements can be obtained in the rat under incremental dobutamine stress using a clinical 1.5 T MR scanner.

  7. Therapeutic Strategies for Oxidative Stress-Related Cardiovascular Diseases: Removal of Excess Reactive Oxygen Species in Adult Stem Cells

    Directory of Open Access Journals (Sweden)

    Hyunyun Kim

    2016-01-01

    Full Text Available Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS causes cardiovascular diseases (CVDs, atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs, for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence of ex vivo expanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS-scavenging compounds are crucial and promising therapeutic strategies for vascular repair.

  8. Adenosine-induced neuroprotection : involvement of glia cells and cytokines

    NARCIS (Netherlands)

    Wittendorp, Maria Catharina

    2004-01-01

    Adenosine is released during pathological conditions and has significant neuroprotective effects mainly by stimulating adenosine A1 receptors in neurons. These neuroprotective effects are increased following upregulation of adenosine A1 receptors. Much research has been performed to enhance the

  9. Effects of bench step exercise intervention on work ability in terms of cardiovascular risk factors and oxidative stress: a randomized controlled study.

    Science.gov (United States)

    Ohta, Masanori; Eguchi, Yasumasa; Inoue, Tomohiro; Honda, Toru; Morita, Yusaku; Konno, Yoshimasa; Yamato, Hiroshi; Kumashiro, Masaharu

    2015-01-01

    Work ability is partly determined by physical and mental fitness. Bench step exercise can be practiced anywhere at any time. The aim of this study was to determine the effects of a bench step exercise on work ability by examining cardiovascular risk factors and oxidative stress. Thirteen volunteers working in a warehousing industry comprised the bench step exercise group (n=7) and the control group (n=6). The participants in the step exercise group were encouraged to practice the step exercise at home for 16 weeks. The step exercise improved glucose metabolism and antioxidative capacity and increased work ability by reducing absences from work and improving the prognosis of work ability. The improvement in work ability was related to a reduction in oxidative stress. These results suggest that a bench step exercise may improve work ability by reducing cardiovascular risk factors and oxidative stress.

  10. El impacto de la reducción del estrés en la hipertensión esencial y las enfermedades cardiovasculares. (Impact of stress reduction on essential hypertension and cardiovascular disease.

    Directory of Open Access Journals (Sweden)

    David W. Orme-Johnson

    2008-07-01

    Full Text Available ResumenSe ha considerado que el estrés contribuye a la patogénesis y la progresión de las enfermedades cardiovasculares (ECV. Se ha demostrado que la reducción del estrés mediante la Meditación Trascendental [Transcendental Meditation (TM®] ha bajado los niveles de presión arterial (PA y reducido el riesgo de ECV en adultos y adolescentes. Este artículo repasa los resultados que sugieren el impacto beneficioso de la TM en reducir la PA en adultos hipertensos en reposo y en adolescentes pre-hipertensos en reposo, durante un estrés agudo creado en el laboratorio y durante la actividad diaria normal. Dichos resultados tienen implicaciones importantes para la inclusión de la TM en los esfuerzos que se realizan para prevenir y tratar las ECV y sus consecuencias clínicas.AbstractStress has been thought to contribute to the pathogenesis and progression of cardiovascular diseases (CVD. Stress reduction via Trasncendental Meditation (TM® has been shown to lower blood pressure (BP levels and reduce CVD risk in adults and adolescents. This article reviews findings suggesting a beneficial BP-lowering impact of TM in hypertensive adults at rest and in pre-hypertensive adolescents at rest, during acute laboratory stress and during normal daily activity. These findings have important implications for inclusion of TM efforts to prevent and treat cardiovascular diseases and their clinical consequences.

  11. Targeting Oxidative Stress Using Nanoparticles as a Theranostic Strategy for Cardiovascular Diseases.

    Science.gov (United States)

    Kim, Kye S; Song, Chul Gyu; Kang, Peter M

    2017-12-11

    Nanomedicine is an application of nanotechnology that provides solutions to unmet medical challenges. The unique features of nanoparticles, such as their small size, modifiable components and diverse functionality, make them attractive and suitable materials for novel diagnostic, therapeutic or theranostic applications. Cardiovascular diseases (CVDs) are the major cause of non-communicable illness in both developing and developed countries. Nanomedicine offers novel theranostic options for the treatment of CVDs. Recent Advances. Many innovative nanoparticles to target reactive oxygen species (ROS) have been developed. In this article, we review the characteristics of nanoparticles that are responsive to ROS, their limitations, and their potential clinical uses. Significant advances made in diagnosis of atherosclerosis and treatment of acute coronary syndrome using nanoparticles are discussed. Although there is a tremendous potential for the nanoparticle applications in medicine, their safety should be considered while using in humans. We discuss the challenges that may be encountered with some of the innovative nanoparticles used in CVDs. The unique properties of nanoparticles offer novel diagnostic tool and potential therapeutic strategies. However, nanomedicine is still in its infancy, and further in-depth studies are needed before wide clinical application is achieved.

  12. Effect of fluid countermeasures of varying osmolarity on cardiovascular responses to orthostatic stress

    Science.gov (United States)

    Davis, John E.

    1989-01-01

    Current operational procedures for shuttle crewmembers include the ingestion of a fluid countermeasure approximately 2 hours before reentry into the earth's gravitational field. The ingestion of the fluid countermeasure is thought to restore plasma volume and improve orthostatic responses upon reentry. The present countermeasure consists of ingesting salt tablets and water to achieve an isotonic solution. It has yet to be determined whether this is the optimal drink to restore orthostatic tolerance. It is also not known whether the drink solution is effective in increasing plasma volume. The purpose here is to evaluate the effectiveness of drink solutions of different osmolarity on restoring plasma volume and orthostatic responses. A hypertonic drink solution was more effective in restoring plasma volume after dehydration than an isotonic solution. However, there were no differences in their effects on an orthostatic challenge. These data suggest that the plasma volume differences produced in this study were not sufficient to produce differences in the cardiovascular responses to an orthostatic challenge, or there are other changes that occur during space flight that are more important in determining orthostatic intolerance.

  13. Role of Creatine Supplementation on Exercise-Induced Cardiovascular Function and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Michael I. C. Kingsley

    2009-01-01

    Full Text Available Many degenerative diseases are associated with increased oxidative stress. Creatine has the potential to act as an indirect and direct antioxidant; however, limited data exist to evaluate the antioxidant capabilities of creatine supplementation within in vivo human systems. This study aimed to investigate the effects of oral creatine supplementation on markers of oxidative stress and antioxidant defenses following exhaustive cycling exercise. Following preliminary testing and two additional familiarization sessions, 18 active males repeated two exhaustive incremental cycling trials (T1 and T2 separated by exactly 7 days. The subjects were assigned, in a double-blind manner, to receive either 20 g of creatine (Cr or a placebo (P for the 5 days preceding T2. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol and blood samples were obtained at rest (preexercise, at the end of exercise (postexercise, and the day following exercise (post24 h. Serum hypdroperoxide concentrations were elevated at postexercise by 17 ± 5% above preexercise values (p = 0.030. However, supplementation did not influence lipid peroxidation (serum hypdroperoxide concentrations, resistance of low density lipoprotein to oxidative stress (t1/2max LDL oxidation and plasma concentrations of non-enzymatic antioxidants (retinol, α-carotene, β-carotene, α-tocopherol, γ-tocopherol, lycopene and vitamin C. Heart rate and oxygen uptake responses to exercise were not affected by supplementation. These findings suggest that short-term creatine supplementation does not enhance non-enzymatic antioxidant defence or protect against lipid peroxidation induced by exhaustive cycling in healthy males.

  14. Exhaustion-related changes in cardiovascular and cortisol reactivity to acute psychosocial stress

    DEFF Research Database (Denmark)

    Jönsson, Peter; Österberg, Kai; Wallergård, Mattias

    2015-01-01

    in exhaustion disorder (ED). We examined whether a DSR is present during the early stages of ED, and still is present after recovery. Three groups were studied: 1. Former ED patients (n=14); 2. persons who during the past 6month had experienced stress at work and had a Shirom-Melamed Burnout Questionnaire (SMBQ...... of exhaustion (SMBQ). This led us to assign former ED patients with lower ratings into the low SMBQ group (LOWS) and those with higher ratings to the high SMBQ group (HIGHS). When repeating the analyses a different picture emerged; the HIGHS showed a lower cortisol response to the V-TSST than did the LOWS. Both...

  15. Cardiovascular disease.

    Science.gov (United States)

    Gavagan, Thomas

    2002-06-01

    The primary care physician is in a position to advise patients on the efficacy of alternative and complementary therapies as they relate to cardiovascular diseases. Anti-oxidant vitamin supplementation has not been shown to be efficacious in decreasing cardiovascular events. N-3 fatty acids appear to be beneficial in secondary prevention of cardiovascular events but their use in primary prevention is not clear. Adoption of vegetable-based diets, including whole grains, can be recommended to decrease cardiovascular events, lower cholesterol and help lower blood pressure. For patients with hypercholesterolemia, cholestin, a red-yeast rice supplement, has been shown to be effective. Garlic supplements may have some mild cholesterol-lowering effect, but this effect is not significant enough to recommend clinically. Herbal therapies with hawthorn and ubiquinone (Q10) are of possible benefit in congestive heart failure. An integrated program of rigorous diet, exercise and stress reduction in motivated patients with cardiovascular disease may have value as an alternative to cardiovascular medications and surgical interventions.

  16. Halobacterial adenosine triphosphatases and the adenosine triphosphatase from Halobacterium saccharovorum

    Science.gov (United States)

    Kristjansson, Hordur; Sadler, Martha H.; Hochstein, Lawrence I.

    1986-01-01

    Membranes prepared from various members of the genus Halobacterium contained a Triton X-l00 activated adenosine triphosphatase. The enzyme from Halobacterium saccharovorum was unstable in solutions of low ionic strength and maximally active in the presence of 3.5 M NaCl. A variety of nucleotide triphosphates was hydrolyzed. MgADP, the product of ATP hydrolysis, was not hydrolyzed and was a competitive inhibitor with respect to MgATP. The enzyme from H. saccharovorum was composed of at least 2 and possibly 4 subunits. The 83-kDa and 60-kDa subunits represented about 90 percent of total protein. The 60-kDa subunit reacted with dicyclohexyl-carbodiimide when inhibition was carried out in an acidic medium. The enzyme from H. saccharovorum, possesses properties of an F(1)F(0) as well as an E(1)E(2) ATPase.

  17. Effect of Stress-free Therapy on Cerebral Blood Flow: Comparisons among patients with metabolic cardiovascular disease, healthy subjects and placebo-treated subjects

    Science.gov (United States)

    Ryotokuji, Kenji; Ishimaru, Keisou; Kihara, Kazuhiko; Namiki, Yoshihisa; Nakashima, Takuma; Otani, Satoru

    2014-01-01

    Background and aims: We have developed a Stress-free Therapy® device wherein “Pinpoint Plantar Long-wavelength Infrared Light Irradiation (PP-LILI)” increases peripheral-deep body temperature and blood flow volume and stabilizes blood pressure as well as significantly reduces stress hormones such as adrenocorticotrophic hormone and cortisol without using drugs. Moreover, we have found this therapy to significantly improve blood glucose and insulin resistance in patients with type 2 diabetes. Based on this background of clinical efficacy, we validated changes in cerebral blood flow in patients with metabolic cardiovascular disease and examined the efficacy of Stress-free Therapy® on cerebral blood flow as compared to that in healthy control subjects and placebo-treated patients. Results: The change in cerebral blood flow volume during 15-minute PP-LILI was 5.1 ± 1.8 mL/min in patients with metabolic cardiovascular disease, showing a significant increase (P<0.05) of 3.1 mL/min as compared with the mean blood flow value after resting for 15 minutes. Conclusions: Our results suggested Stress-free Therapy® to significantly increase cerebral blood flow, possibly leading to the prevention of metabolic cardiovascular disease. PMID:24771966

  18. Elevated stress-hemoconcentration in major depression is normalized by antidepressant treatment: secondary analysis from a randomized, double-blind clinical trial and relevance to cardiovascular disease risk.

    Directory of Open Access Journals (Sweden)

    Ma-Li Wong

    Full Text Available BACKGROUND: Major depressive disorder (MDD is an independent risk factor for cardiovascular disease (CVD; the presence of MDD symptoms in patients with CVD is associated with a higher incidence of cardiac complications following acute myocardial infarction (MI. Stress-hemoconcentration, a result of psychological stress that might be a risk factor for the pathogenesis of CVD, has been studied in stress-challenge paradigms but has not been systematically studied in MDD. METHODS: Secondary analysis of stress hemoconcentration was performed on data from controls and subjects with mild to moderate MDD participating in an ongoing pharmacogenetic study of antidepressant treatment response to desipramine or fluoxetine. Hematologic and hemorheologic measures of stress-hemoconcentration included blood cell counts, hematocrit, hemoglobin, total serum protein, and albumin, and whole blood viscosity. FINDINGS: Subjects with mild to moderate MDD had significantly increased hemorheologic measures of stress-hemoconcentration and blood viscosity when compared to controls; these measures were correlated with depression severity. Measures of stress-hemoconcentration improved significantly after 8 weeks of antidepressant treatment. Improvements in white blood cell count, red blood cell measures and plasma volume were correlated with decreased severity of depression. CONCLUSIONS: Our secondary data analyses support that stress-hemoconcentration, possibly caused by decrements in plasma volume during psychological stress, is present in Mexican-American subjects with mild to moderate MDD at non-challenged baseline conditions. We also found that after antidepressant treatment hemorheologic measures of stress-hemoconcentration are improved and are correlated with improvement of depressive symptoms. These findings suggest that antidepressant treatment may have a positive impact in CVD by ameliorating increased blood viscosity. Physicians should be aware of the potential

  19. Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Holley, J.L.; Fenton, R.A.; Arthur, R.S. (Univ. of Pittsburgh, PA (USA))

    1991-05-01

    This study assessed the usefulness of thallium stress testing as a predictor of perioperative cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Demographic factors influencing the exercise performance in these patients were also examined. The medical records of 189 consecutive patients with diabetic nephropathy who were evaluated for cadaveric renal transplantation were reviewed. Thallium stress testing was the initial examination of cardiovascular status in 141 patients. An adequate examination was one in which at least 70% of maximum heart rate was achieved. A thallium stress test was normal if there were no ST segment depressions on the electrocardiogram and no perfusion abnormalities on the thallium scan. Forty-four patients underwent cardiac catheterization as the initial evaluation (Group C) and four patients underwent transplantation without a formal cardiovascular evaluation (Group D). Sixty-four of the 141 patients undergoing thallium stress testing had an adequate and normal examination (Group A). The incidence of perioperative cardiac events in this group was 2%. Seventy-seven patients (Group B) had an abnormal (n = 41) or an inadequate (n = 36) thallium stress test and most (n = 61) then underwent coronary angiography. The use of beta-blockers was the only predictor of an abnormal or inadequate thallium stress test. Forty-three percent of patients with inadequate or abnormal thallium stress tests had significant coronary artery disease on cardiac catheterization. The perioperative risk of cardiac events was not different in Group A versus Groups B, C, and D combined. Survival of Group A and B patients was not different but was significantly longer than that of Group C patients.

  20. Intravenous adenosine (adenoscan) versus exercise in the noninvasive assessment of coronary artery disease by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    LaManna, M.M.; Mohama, R.; Slavich, I.L. 3d.; Lumia, F.J.; Cha, S.D.; Rambaran, N.; Maranhao, V. (Deborah Heart and Lung Center, Browns Mills, NJ (USA))

    1990-11-01

    Fifteen patients at a mean age of 58 underwent adenosine and maximal exercise thallium SPECT imaging. All scans were performed 1 week apart and within 4 weeks of cardiac catheterization. SPECT imaging was performed after the infusion of 140 micrograms/kg/min of adenosine for 6 minutes. Mean heart rate increment during adenosine administration was 67 +/- 3.7 to 77 +/- 4.1. Mean blood pressure was 136 +/- 7.2 to 135 +/- 6.2 systolic and 78 +/- 1.8 to 68 +/- 2.6 diastolic. No adverse hemodynamic effects were observed. There were no changes in PR or QRS in intervals. Five stress ECGs were ischemic. No ST changes were observed with adenosine. Although 68% of the patients had symptoms of flushing, light-headedness, and dizziness during adenosine infusion, symptoms resolved within 1 minute of dosage adjustment or termination of the infusion in all but one patient, who required theophylline. Sensitivity for coronary artery detection was 77% and specificity 100%. Concordance between adenoscans and exercise thallium scintigraphy was high (13/15 = 87%). In two patients, there were minor scintigraphic differences. The authors conclude that adenosine is a sensitive, specific, and safe alternative to exercise testing in patients referred for thallium imaging and may be preferable to dipyridamole.

  1. Structured lifestyle intervention in patients with the metabolic syndrome mitigates oxidative stress but fails to improve measures of cardiovascular autonomic neuropathy.

    Science.gov (United States)

    Pennathur, Subramaniam; Jaiswal, Mamta; Vivekanandan-Giri, Anuradha; White, Elizabeth A; Ang, Lynn; Raffel, David M; Rubenfire, Melvyn; Pop-Busui, Rodica

    2017-09-01

    To assess the role of oxidative stress in mediating adverse outcomes in metabolic syndrome (MetS) and resultant cardiovascular autonomic neuropathy (CAN), and to evaluate the effects of lifestyle interventions on measures of oxidative stress and CAN in subjects with MetS. Pilot study in 25 non-diabetic subjects with MetS (age 49±10years, 76% females) participating in a 24-week lifestyle intervention (supervised aerobic exercise/Mediterranean diet), and 25 age-matched healthy controls. CAN was assessed by cardiovascular reflex tests, heart rate variability (HRV) and PET imaging with sympathetic analog [ 11 C] meta-hydroxyephedrine ([ 11 C]HED). Specific oxidative fingerprints were measured by liquid-chromatography/mass-spectrometry (LC/MS). At baseline, MetS subjects had significantly higher oxidative stress markers [3-nitrotyrosine (234±158 vs. 54±47μmol/mol tyrosine), ortho-tyrosine (59±38 vs. 18±10μmol/molphenylalanine, all Poxidative stress markers (all Poxidative stress in the absence of diabetes. The 24-week lifestyle intervention was effective in ameliorating oxidative stress, but did not improve measures of CAN. Larger clinical trials with longer duration are required to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Dobutamine stress MRI. Part I. Safety and feasibility of dobutamine cardiovascular magnetic resonance in patients suspected of myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kuijpers, Dirkjan [State University and Academic Hospital Groningen, Department of Radiology, Groningen (Netherlands); Bronovo Hospital, Department of Radiology and Cardiology, Bronovolaan 1, P.O. Box 96900, The Hague (Netherlands); Janssen, Caroline H.C.; Oudkerk, Matthijs [State University and Academic Hospital Groningen, Department of Radiology, Groningen (Netherlands); Dijkman, Paul R.M. van [Bronovo Hospital, Department of Radiology and Cardiology, Bronovolaan 1, P.O. Box 96900, The Hague (Netherlands)

    2004-10-01

    The aim of the study was to evaluate safety and feasibility of dobutamine cardiovascular magnetic resonance (CMR) in patients with proven or suspected coronary artery disease. Dobutamine CMR was evaluated retrospectively in 400 consecutive patients with suspicion of myocardial ischemia. Dobutamine was infused using an incremental protocol up to 40 {mu}g/kg body weight per minute. All anti-anginal medication was stopped 4 days before the CMR study and infusion time of dobutamine was 6 min per stage. Hemodynamic data, CMR findings and side effects were reported. Patients with contraindications to CMR (metallic implants and claustrophobia) were excluded from analysis. Dobutamine CMR was successfully performed in 355 (89%) patients. Forty-five (11%) patients could not be investigated adequately because of non-cardiac side effects in 29 (7%) and cardiac side effects in 16 (4%) patients. Hypotension (1.5%) and arrhythmias (1%) were the most frequent cardiac side effects. One patient developed a severe complication (ventricular fibrillation) at the end of the study. There were no myocardial infarctions or fatal complications of the stress test. The most frequent non-cardiac side effects were nausea, vomiting and claustrophobia. Age >70 years, prior myocardial infarction and rest wall motion abnormalities showed no significant differences with side effects (P>0.05). Dobutamine CMR is safe and feasible in patients with suspicion of myocardial ischemia. (orig.)

  3. Disruption of fetal hormonal programming (prenatal stress) implicates shared risk for sex differences in depression and cardiovascular disease.

    Science.gov (United States)

    Goldstein, J M; Handa, R J; Tobet, S A

    2014-01-01

    Comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) represents the fourth leading cause of morbidity and mortality worldwide, and women have a two times greater risk than men. Thus understanding the pathophysiology has widespread implications for attenuation and prevention of disease burden. We suggest that sex-dependent MDD-CVD comorbidity may result from alterations in fetal programming consequent to the prenatal maternal environments that produce excess glucocorticoids, which then drive sex-dependent developmental alterations of the fetal hypothalamic-pituitary-adrenal (HPA) axis circuitry impacting mood, stress regulation, autonomic nervous system (ANS), and the vasculature in adulthood. Evidence is consistent with the hypothesis that disruptions of pathways associated with gamma aminobutyric acid (GABA) in neuronal and vascular development and growth factors have critical roles in key developmental periods and adult responses to injury in heart and brain. Understanding the potential fetal origins of these sex differences will contribute to development of novel sex-dependent therapeutics. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Cardiovascular disease-related parameters and oxidative stress in SHROB rats, a model for metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Eunice Molinar-Toribio

    Full Text Available SHROB rats have been suggested as a model for metabolic syndrome (MetS as a situation prior to the onset of CVD or type-2 diabetes, but information on descriptive biochemical parameters for this model is limited. Here, we extensively evaluate parameters related to CVD and oxidative stress (OS in SHROB rats. SHROB rats were monitored for 15 weeks and compared to a control group of Wistar rats. Body weight was recorded weekly. At the end of the study, parameters related to CVD and OS were evaluated in plasma, urine and different organs. SHROB rats presented statistically significant differences from Wistar rats in CVD risk factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100, abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In adipose tissue, liver and brain, the endogenous antioxidant systems were activated, yet there was no significant oxidative damage to lipids (MDA or proteins (carbonylation. We conclude that SHROB rats present significant alterations in parameters related to inflammation, endothelial dysfunction, thrombotic activity, insulin resistance and OS measured in plasma as well as enhanced redox defence systems in vital organs that will be useful as markers of MetS and CVD for nutrition interventions.

  5. Cardiovascular response of individuals with spinal cord injury to dynamic functional electrical stimulation under orthostatic stress.

    Science.gov (United States)

    Yoshida, Takashi; Masani, Kei; Sayenko, Dimitry G; Miyatani, Masae; Fisher, Joseph A; Popovic, Milos R

    2013-01-01

    In this pilot study, we examined how effectively functional electrical stimulation (FES) and passive stepping mitigated orthostatic hypotension in participants with chronic spinal cord injury (SCI). While being tilted head-up to 70 (°) from the supine position, the participants underwent four 10-min conditions in a random sequence: 1) no intervention, 2) passive stepping, 3) isometric FES of leg muscles, and 4) FES of leg muscles combined with passive stepping. We found that FES and passive stepping independently mitigated a decrease in stroke volume and helped to maintain the mean blood pressure. The effects of FES on stroke volume and mean blood pressure were greater than those of passive stepping. When combined, FES and passive stepping did not interfere with each other, but they also did not synergistically increase stroke volume or mean blood pressure. Thus, the present study suggests that FES delivered to lower limbs can be used in individuals with SCI to help them withstand orthostatic stress. Additional studies are needed to confirm whether this use of FES is applicable to a larger population of individuals with SCI.

  6. Homeostatic Control of Synaptic Activity by Endogenous Adenosine is Mediated by Adenosine Kinase

    Science.gov (United States)

    Diógenes, Maria José; Neves-Tomé, Raquel; Fucile, Sergio; Martinello, Katiuscia; Scianni, Maria; Theofilas, Panos; Lopatář, Jan; Ribeiro, Joaquim A.; Maggi, Laura; Frenguelli, Bruno G.; Limatola, Cristina; Boison, Detlev; Sebastião, Ana M.

    2014-01-01

    Extracellular adenosine, a key regulator of neuronal excitability, is metabolized by astrocyte-based enzyme adenosine kinase (ADK). We hypothesized that ADK might be an upstream regulator of adenosine-based homeostatic brain functions by simultaneously affecting several downstream pathways. We therefore studied the relationship between ADK expression, levels of extracellular adenosine, synaptic transmission, intrinsic excitability, and brain-derived neurotrophic factor (BDNF)-dependent synaptic actions in transgenic mice underexpressing or overexpressing ADK. We demonstrate that ADK: 1) Critically influences the basal tone of adenosine, evaluated by microelectrode adenosine biosensors, and its release following stimulation; 2) determines the degree of tonic adenosine-dependent synaptic inhibition, which correlates with differential plasticity at hippocampal synapses with low release probability; 3) modulates the age-dependent effects of BDNF on hippocampal synaptic transmission, an action dependent upon co-activation of adenosine A2A receptors; and 4) influences GABAA receptor-mediated currents in CA3 pyramidal neurons. We conclude that ADK provides important upstream regulation of adenosine-based homeostatic function of the brain and that this mechanism is necessary and permissive to synaptic actions of adenosine acting on multiple pathways. These mechanistic studies support previous therapeutic studies and implicate ADK as a promising therapeutic target for upstream control of multiple neuronal signaling pathways crucial for a variety of neurological disorders. PMID:22997174

  7. Myocardial feature tracking reduces observer-dependence in low-dose dobutamine stress cardiovascular magnetic resonance.

    Directory of Open Access Journals (Sweden)

    Andreas Schuster

    Full Text Available To determine whether quantitative wall motion assessment by CMR myocardial feature tracking (CMR-FT would reduce the impact of observer experience as compared to visual analysis in patients with ischemic cardiomyopathy (ICM.15 consecutive patients with ICM referred for assessment of hibernating myocardium were studied at 3 Tesla using SSFP cine images at rest and during low dose dobutamine stress (5 and 10 μg/kg/min of dobutamine. Conventional visual, qualitative analysis was performed independently and blinded by an experienced and an inexperienced reader, followed by post-processing of the same images by CMR-FT to quantify subendocardial and subepicardial circumferential (Eccendo and Eccepi and radial (Err strain. Receiver operator characteristics (ROC were assessed for each strain parameter and operator to detect the presence of inotropic reserve as visually defined by the experienced observer.141 segments with wall motion abnormalities at rest were eligible for the analysis. Visual scoring of wall motion at rest and during dobutamine was significantly different between the experienced and the inexperienced observer (p0.05. Eccendo was the most accurate (AUC of 0.76, 10 μg/kg/min of dobutamine parameter. Diagnostic accuracy was worse for resting strain with differences between operators for Eccendo and Eccepi (p0.05.Whilst visual analysis remains highly dependent on operator experience, quantitative CMR-FT analysis of myocardial wall mechanics during DS-CMR provides diagnostic accuracy for the detection of inotropic reserve regardless of operator experience and hence may improve diagnostic robustness of low-dose DS-CMR in clinical practice.

  8. Identify potential drugs for cardiovascular diseases caused by stress-induced genes in vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Chien-Hung Huang

    2016-09-01

    Full Text Available Background Abnormal proliferation of vascular smooth muscle cells (VSMC is a major cause of cardiovascular diseases (CVDs. Many studies suggest that vascular injury triggers VSMC dedifferentiation, which results in VSMC changes from a contractile to a synthetic phenotype; however, the underlying molecular mechanisms are still unclear. Methods In this study, we examined how VSMC responds under mechanical stress by using time-course microarray data. A three-phase study was proposed to investigate the stress-induced differentially expressed genes (DEGs in VSMC. First, DEGs were identified by using the moderated t-statistics test. Second, more DEGs were inferred by using the Gaussian Graphical Model (GGM. Finally, the topological parameters-based method and cluster analysis approach were employed to predict the last batch of DEGs. To identify the potential drugs for vascular diseases involve VSMC proliferation, the drug-gene interaction database, Connectivity Map (cMap was employed. Success of the predictions were determined using in-vitro data, i.e. MTT and clonogenic assay. Results Based on the differential expression calculation, at least 23 DEGs were found, and the findings were qualified by previous studies on VSMC. The results of gene set enrichment analysis indicated that the most often found enriched biological processes are cell-cycle-related processes. Furthermore, more stress-induced genes, well supported by literature, were found by applying graph theory to the gene association network (GAN. Finally, we showed that by processing the cMap input queries with a cluster algorithm, we achieved a substantial increase in the number of potential drugs with experimental IC50 measurements. With this novel approach, we have not only successfully identified the DEGs, but also improved the DEGs prediction by performing the topological and cluster analysis. Moreover, the findings are remarkably validated and in line with the literature. Furthermore

  9. Measurement of coronary flow response to cold pressor stress in asymptomatic women with cardiovascular risk factors using spiral velocity-encoded cine MRI at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Maroules, Christopher D.; Peshock, Ronald M. (Dept. of Radiology, Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)), e-mail: Ron.Peshock@UTSouthwestern.edu; Chang, Alice Y.; Kontak, Andrew (Dept. of Internal Medicine, Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)); Dimitrov, Ivan; Kotys, Melanie (Dept. of Philips Medical Systems, Cleveland, OH (United States))

    2010-05-15

    Background: Coronary sinus (CS) flow in response to a provocative stress has been used as a surrogate measure of coronary flow reserve, and velocity-encoded cine (VEC) magnetic resonance imaging (MRI) is an established technique for measuring CS flow. In this study, the cold pressor test (CPT) was used to measure CS flow response because it elicits an endothelium-dependent coronary vasodilation that may afford greater sensitivity for detecting early changes in coronary endothelial function. Purpose: To investigate the feasibility and reproducibility of CS flow reactivity (CSFR) to CPT using spiral VEC MRI at 3 Tesla in a sample of asymptomatic women with cardiovascular risk factors. Material and Methods: Fourteen asymptomatic women (age 38 years +- 10) with cardiovascular risk factors were studied using 3D spiral VEC MRI of the CS at 3 T. The CPT was utilized as a provocative stress to measure changes in CS flow. CSFR to CPT was calculated from the ratio of CS flow during peak stress to baseline CS flow. Results: CPT induced a significant hemodynamic response as measured by a 45% increase in rate-pressure product (P<0.01). A significant increase in CS volume flow was also observed (baseline, 116 +- 26 ml/min; peak stress, 152 +- 34 ml/min, P=0.01). CSFR to CPT was 1.31 +- 0.20. Test-retest variability of CS volume flow was 5% at baseline and 6% during peak stress. Conclusion: Spiral CS VEC MRI at 3 T is a feasible and reproducible technique for measuring CS flow in asymptomatic women at risk for cardiovascular disease. Significant changes in CSFR to CPT are detectable, without demanding pharmacologic stress

  10. AT1 and AT2 Receptors in the Prelimbic Cortex Modulate the Cardiovascular Response Evoked by Acute Exposure to Restraint Stress in Rats.

    Science.gov (United States)

    Brasil, Taíz F S; Fassini, Aline; Corrêa, Fernando M

    2017-07-10

    The prelimbic cortex (PL) is an important structure in the neural pathway integrating stress responses. Brain angiotensin is involved in cardiovascular control and modulation of stress responses. Blockade of angiotensin receptors has been reported to reduce stress responses. Acute restraint stress (ARS) is a stress model, which evokes sustained blood pressure increase, tachycardia, and reduction in tail temperature. We therefore hypothesized that PL locally generated angiotensin and angiotensin receptors modulate stress autonomic responses. To test this hypothesis, we microinjected an angiotensin-converting enzyme (ACE) inhibitor or angiotensin antagonists into the PL, prior to ARS. Male Wistar rats were used; guide cannulas were bilaterally implanted in the PL for microinjection of vehicle or drugs. A polyethylene catheter was introduced into the femoral artery to record cardiovascular parameters. Tail temperature was measured using a thermal camera. ARS was started 10 min after PL treatment with drugs. Pretreatment with ACE inhibitor lisinopril (0.5 nmol/100 nL) reduced the pressor response, but did not affect ARS-evoked tachycardia. At a dose of 1 nmol/100 nL, it reduced both ARS pressor and tachycardic responses. Pretreatment with candesartan, AT1 receptor antagonist reduced ARS-evoked pressor response, but not tachycardia. Pretreatment with PD123177, AT2 receptor antagonist, reduced tachycardia, but did not affect ARS pressor response. No treatment affected ARS fall in tail temperature. Results suggest involvement of PL angiotensin in the mediation of ARS cardiovascular responses, with participation of both AT1 and AT2 receptors. In conclusion, results indicate that PL AT1-receptors modulate the ARS-evoked pressor response, while AT2-receptors modulate the tachycardic component of the autonomic response.

  11. A Multimode Responsive Aptasensor for Adenosine Detection

    Directory of Open Access Journals (Sweden)

    Na Zhao

    2014-01-01

    Full Text Available We report a novel multimode detection aptasensor with three signal responses (i.e., fluorescence recovery, enhanced Raman signal, and color change. The presence of adenosine induces the conformational switch of the adenosine aptamer (Apt, forming adenosine-aptamer complex and releasing quantum dots (QDs from AuNPs, resulting in the recovered fluorescence, the enhanced Raman signal, and color change of the solution. The multimode signal recognition is potentially advantageous in improving the precision and reliability of the detection in complex environments compared to the conventional single-mode sensing system. The multimode detection strategy opens up a new possibility in sensing and quantifying more other target molecules.

  12. Effects of adenosine and a selective A2A adenosine receptor agonist on hemodynamic and thallium-201 and technetium-99m-sestaMIBI biodistribution and kinetics.

    Science.gov (United States)

    Mekkaoui, Choukri; Jadbabaie, Farid; Dione, Donald P; Meoli, David F; Purushothaman, Kailasnath; Belardinelli, Luiz; Sinusas, Albert J

    2009-10-01

    The purpose of this study was to compare a selective A(2A) adenosine receptor agonist (regadenoson) with adenosine in clinically relevant canine models with regard to effects on hemodynamics and thallium-201 ((201)Tl) and technetium-99m ((99m)Tc)-sestaMIBI biodistribution and kinetics. The clinical application of vasodilator stress for perfusion imaging requires consideration of the effects of these vasodilating agents on systemic hemodynamics, coronary flow, and radiotracer uptake and clearance kinetics. Sequential imaging and arterial blood sampling was performed on control, anesthetized closed-chest canines (n = 7) to evaluate radiotracer biodistribution and kinetics after either a bolus administration of regadenoson (2.5 microg/kg) or 4.5-min infusion of adenosine (280 microg/kg). The effects of regadenoson on coronary flow and myocardial radiotracer uptake were then evaluated in an open-chest canine model of a critical stenosis (n = 7). Results from ex vivo single-photon emission computed tomography were compared with tissue well-counting. The use of regadenoson compared favorably with adenosine in regard to the duration and magnitude of the hemodynamic effects and the effect on (201)Tl and (99m)Tc-sestaMIBI biodistribution and kinetics. The arterial blood clearance half-time was significantly faster for (99m)Tc-sestaMIBI (regadenoson: 1.4 +/- 0.03 min; adenosine: 1.5 +/- 0.08 min) than for (201)Tl (regadenoson: 2.5 +/- 0.16 min, p adenosine: 2.7 +/- 0.04 min, p regadenoson stress was significantly greater than the relative perfusion defect with (99m)Tc-sestaMIBI (0.69 +/- 0.03%, p regadenoson produced a hyperemic response comparable to a standard infusion of adenosine. The biodistribution and clearance of both (201)Tl and (99m)Tc-sestaMIBI during regadenoson were similar to adenosine vasodilation. Ex vivo perfusion images under the most ideal conditions permitted detection of a critical stenosis, although (201)Tl offered significant advantages over (99m

  13. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adenosine triphosphate release assay. 864.7040... Adenosine triphosphate release assay. (a) Identification. An adenosine triphosphate release assay is a device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation...

  14. Fasting Serum Glucose and Cholesterol as Predictors of Cardiovascular Reactivity to Acute Stress in a Sample of African American College Students.

    Science.gov (United States)

    Clark, Vernessa R; Perkins, Patrice; Carson, Bernice L; Boyd, Kimberly; Jefferson, Trayce M

    2015-01-01

    African Americans are at a greater risk of cardiovascular hyperactivity to stress than Caucasians; however the risk factors for this activity are not clearly delineated for African Americans. The purpose of this study was to determine the ability of fasting serum cholesterol concentration and fasting serum glucose (FSG) to predict cardiovascular reactivity to stress in African Americans. Serum cholesterol concentration and FSG levels were measured in 48 (40 women, 8 men) African American college students aged 18-30 years. Heart rate, cardiac output, stroke volume, mean arterial pressure and systolic and diastolic blood pressure were measured as the participants viewed a racially noxious scene on a digital video disc. Measurements were taken prior to the scene (pre stressor period), during the scene (stressor period), and while the participant recovered from the scene (recovery period). A multiple regression analysis revealed that total serum cholesterol and LDL significantly predicted diastolic blood pressure during the pre-stressor period. FSG significantly predicted mean arterial pressure during the recovery period, and predicted stroke volume during the pre-stressor period, stressor period, and the recovery period. FSG was a better predictor of cardiovascular reactivity to stress than serum cholesterol concentration, predicting mean arterial pressure and stroke volume. This finding may be due to the association of glucose with diabetes, which is more prevalent in African Americans.

  15. Regadenoson induces comparable left ventricular perfusion defects as adenosine: a quantitative analysis from the ADVANCE MPI 2 trial.

    Science.gov (United States)

    Mahmarian, John J; Cerqueira, Manuel D; Iskandrian, Ami E; Bateman, Timothy M; Thomas, Gregory S; Hendel, Robert C; Moye, Lemuel A; Olmsted, Ann W

    2009-08-01

    This study sought to determine whether regadenoson induces left ventricular perfusion defects of similar size and severity as seen with adenosine stress. Total and ischemic left ventricular perfusion defect size predict patient outcome. Therefore, it is important to show that newer stressor agents induce similar perfusion abnormalities as observed with currently available ones. The ADVANCE MPI 2 (Adenosine versus Regadenoson Comparative Evaluation for Myocardial Perfusion Imaging) study was a prospective, double-blind, randomized trial comparing image results in patients undergoing standard gated adenosine single-photon emission computed tomography (SPECT) myocardial perfusion imaging who were then randomized in a 2:1 ratio to either regadenoson (N = 495) or a second adenosine SPECT (N = 260). Quantitative SPECT analysis was used to determine total left ventricular perfusion defect size and the extent of ischemia. Quantification was performed by a single observer who was blinded to randomization and image sequence. Baseline gated perfusion results were similar in patients randomized to adenosine or regadenoson. No significant differences in total (11.5 +/- 15.7 vs. 11.4 +/- 15.8, p = 0.88) or ischemic (4.8 +/- 9.2 vs. 4.6 +/- 8.9, p = 0.43) perfusion defect sizes were observed between the regadenoson and adenosine groups, respectively. Linear regression showed a close correlation between adenosine and regadenoson for total (r = 0.97, p regadenoson versus adenosine, respectively. The good correlation between serial adenosine and regadenoson studies regarding total (0.41 +/- 5.43 vs. 0.21 +/- 5.23, p = 0.76) and ischemic (0.17 +/- 5.31 vs. 0.23 +/- 6.08, p = 0.94) perfusion defects persisted in the subgroup of 308 patients with an abnormal baseline SPECT. Applying quantitative analysis, regadenoson induces virtually identical scintigraphic results as adenosine regarding the size and severity of left ventricular perfusion defects and the extent of scintigraphic

  16. Placental Growth Factor Levels in Populations with High Versus Low Risk for Cardiovascular Disease and Stressful Physiological Environments such as Microgravity: A Pilot Study

    Science.gov (United States)

    Sundaresan, Alamelu; Mehta, Satish K.; Schlegel, Todd. T.; Russomano, Thais; Pierson, Duane L.; Mann, Vivek; Mansoor, Elvedina; Olamigoke, Loretta; Okoro, Elvis

    2017-02-01

    This pilot study compared placental growth factor (PIGF) levels in populations with high versus low risk for cardiovascular disease. Previous experiments from our laboratory (Sundaresan et al. 2005, 2009) revealed that the angiogenic factor PIGF was up regulated in modeled microgravity conditions in human lymphocytes leading to possible atherogenesis and pathogenesis in microgravity. Since the findings came from microgravity analog experiments, there is a strong link to its usefulness in the microgravity field as a biomarker. It is important to understand, that these findings came from both studies on expression levels of this cardiovascular marker in human lymphocytes in microgravity ( in vitro microgravity analog), and a follow up gene expression study in hind limb suspended mice ( in vivo microgravity analog). The relevance is enhanced because in life on earth, PIGF is an inflammatory biomarker for cardiovascular disease. Studies on the levels of PIGF would help to reduce the risk and prevention of heart failures in astronauts. If we can use this marker to predict and reduce the risk of cardiac events in astronauts and pilots, it would significantly help aerospace medicine operations. The investigations here confirmed that in a cardiovascular stressed population such as coronary artery disease (CAD) and acute coronary syndrome (ACS) patients, PIGF could be overexpressed. We desired to re-evaluate this marker in patients with cardiovascular disease in our own study. PIGF is a marker of inflammation and a predictor of short-term and long-term adverse outcome in ACS. In addition, elevated PIGF levels may be associated with increased risk for CAD.PIGF levels were determined in thirty-one patients undergoing cardiovascular catheterization for reasons other than ACS and in thirty-three low-risk asymptomatic subjects. Additional data on traditional cardiovascular risk factors for both populations were also compiled and compared. We found that PIGF levels were

  17. Adenosine receptors as drug targets — what are the challenges?

    Science.gov (United States)

    Chen, Jiang-Fan; Eltzschig, Holger K.; Fredholm, Bertil B.

    2014-01-01

    Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors — either directly or indirectly — have now entered the clinic. However, only one adenosine receptor-specific agent — the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma) — has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges. PMID:23535933

  18. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation

    Directory of Open Access Journals (Sweden)

    Noam eRudich

    2012-06-01

    Full Text Available Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease (COPD patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells, as an attractive drug candidate. Four subtypes (A1, A2a, A2b and A3 of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R in mediating hyper responsiveness to adenosine in mast cells, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human mast cells. The relevance of mouse studies to the human is discussed.

  19. Cognitive-behavioural stress management does not improve biological cardiovascular risk indicators in women with ischaemic heart disease: a randomized-controlled trial.

    Science.gov (United States)

    Claesson, M; Birgander, L S; Jansson, J-H; Lindahl, B; Burell, G; Asplund, K; Mattsson, C

    2006-10-01

    Psychosocial factors, such as stress and vital exhaustion, are associated with an increased risk of cardiovascular events, and women report more psychosocial ill-being after an acute myocardial infarction than men. We have earlier shown that a cognitive-behavioural intervention in women with ischaemic heart disease (IHD) improved psychosocial well-being. In the present study, we tested the hypothesis that the improvement in psychosocial well-being is associated with an improvement in biochemical indicators of cardiovascular risk. Randomized-controlled trial in northern Sweden. Outpatient care. Women with IHD were randomized to either a 1-year cognitive-behavioural stress management programme or usual care. Of the 159 women who completed the study, 77 were in the intervention group, and 82 in the control group. A 1-year cognitive-behavioural stress management programme versus conventional care. Group assignment was not found to be a determinant of waist circumference, high sensitive C-reactive protein (hs-CRP), fibrinogen, von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator (tPA) activity, tPA antigen, tPA-PAI-1 complex, leptin, or HOMA2 insulin resistance index (HOMA2-IR) at follow up. Changes in psychosocial variables were not associated with changes in any of the biological risk indicators. Even if our cognitive-behavioural stress management programme had effects on proximal targets, such as stress behaviour and vital exhaustion, we found no improvement in intermediate biochemical targets related to the metabolic syndrome and IHD. Our results challenge the proposition that the relationship between psychological well-being and biological cardiovascular risk indicators is a direct cause-effect phenomenon.

  20. Structure-Based Rational Design of Adenosine Receptor Ligands.

    Science.gov (United States)

    Gutiérrez-de-Terán, Hugo; Sallander, Jessica; Sotelo, Eddy

    2017-01-01

    The family of adenosine receptors (ARs) is focus of several medicinal chemistry programs aimed to find new potent and selective drugs. Each receptor subtype has been proposed as a relevant drug target in the treatment of, e.g., cardiovascular or inflammatory diseases, asthma or Parkinson's disease. Until recently, most of these efforts have been dominated by ligand-based or empirical approaches. However, the latest advances in G protein-coupled receptor (GPCR) crystallography allowed for a thorough structural characterization of the A2AAR subtype, which has been crystalized with a number of agonists and antagonists. Consequently, the ligand discovery of AR ligands has been enriched with a number of structure-based approaches. These include the generation of higher-confident homology models for the remaining AR subtypes, virtual screening identification of novel chemotypes, structure-based lead-optimization programs, rationalization of selectivity profiles, or the structural characterization of novel binding sites that enable the design of novel allosteric modulators. Computational methodologies have importantly contributed to the success of these structure-based approaches, and the recent advances in the field are also analyzed in this review. We conclude that the design of adenosine receptor ligands has improved dramatically with the consideration of structure- based approaches, which is paving the way to a better understanding of the biology and pharmacological modulation of this relevant family of receptors.

  1. Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons

    Science.gov (United States)

    Hawryluk, J. M.; Ferrari, L. L.; Keating, S. A.

    2012-01-01

    Adenosine has been proposed as an endogenous homeostatic sleep factor that accumulates during waking and inhibits wake-active neurons to promote sleep. It has been specifically hypothesized that adenosine decreases wakefulness and promotes sleep recovery by directly inhibiting wake-active neurons of the basal forebrain (BF), particularly BF cholinergic neurons. We previously showed that adenosine directly inhibits BF cholinergic neurons. Here, we investigated 1) how adenosine modulates glutamatergic input to BF cholinergic neurons and 2) how adenosine uptake and adenosine metabolism are involved in regulating extracellular levels of adenosine. Our experiments were conducted using whole cell patch-clamp recordings in mouse brain slices. We found that in BF cholinergic neurons, adenosine reduced the amplitude of AMPA-mediated evoked glutamatergic excitatory postsynaptic currents (EPSCs) and decreased the frequency of spontaneous and miniature EPSCs through presynaptic A1 receptors. Thus we have demonstrated that in addition to directly inhibiting BF cholinergic neurons, adenosine depresses excitatory inputs to these neurons. It is therefore possible that both direct and indirect inhibition may synergistically contribute to the sleep-promoting effects of adenosine in the BF. We also found that blocking the influx of adenosine through the equilibrative nucleoside transporters or inhibiting adenosine kinase and adenosine deaminase increased endogenous adenosine inhibitory tone, suggesting a possible mechanism through which adenosine extracellular levels in the basal forebrain are regulated. PMID:22357797

  2. Prognostic Value of Stress Echocardiography in Patients With Low-Intermediate or High Short-Term (10 Years) Versus Low (Risk of Cardiovascular Disease According to the American College of Cardiology/American Heart Association 2013 Cardiovascular Risk Calculator.

    Science.gov (United States)

    Yao, Siu-Sun; Supariwala, Azhar; Yao, Amanda; Dukkipati, Sai Sreenija; Wyne, Jamshad; Chaudhry, Farooq A

    2015-09-01

    This study evaluates the prognostic value of stress echocardiography (Secho) in short-term (10 years) and lifetime atherosclerotic cardiovascular disease risk-defined groups according to the American College of Cardiology/American Heart Association 2013 cardiovascular risk calculator. The ideal risk assessment and management of patients with low-to-intermediate or high short-term versus low (risk is unclear. The purpose of this study was to evaluate the prognostic value of Secho in short-term and lifetime CV risk-defined groups. We evaluated 4,566 patients (60 ± 13 years; 46% men) who underwent Secho (41% treadmill and 59% dobutamine) with low-intermediate short-term (risk divided into low (risk and third group with high short-term risk (≥20%, n = 3,537). Follow-up (3.2 ± 1.5 years) for nonfatal myocardial infarction (n = 102) and cardiac death (n = 140) were obtained. By univariate analysis, age (p risk and also in those with high short-term CV risk group (3.5% vs 1.0% per year, p risk assessment in patients with low-intermediate or high short-term versus low or high lifetime cardiovascular risk. Event rate with normal Secho is low (≤1% per year) but higher in patients with high short-term CV risk by the American College of Cardiology/American Heart Association 2013 cardiovascular risk calculator. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Cardiovascular Adaptation to Stress

    Science.gov (United States)

    1979-05-01

    diiaaaniic pre’ssure and leart rrate. A new pa’a’.’.arc required fair cclasiai noted. Dillaaing~ pausa aiaal 465 I’,Iii £ittothe dev ice w as aga in c...aortic afferents lus intensities (rapidly conducting A fiber activa - Circulation Research. Vol. 37. July 1975 .-- J A AORTIC AFFERENT HEART RATE

  4. Effect of fast and slow pranayama on perceived stress and cardiovascular parameters in young health-care students

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Sharma

    2013-01-01

    Conclusion: This study demonstrates that both types of pranayama practice are beneficial in reducing PSS in the healthy subjects but beneficial effect on cardiovascular parameters occurred only after practicing slow pranayama.

  5. Capadenoson, a clinically trialed partial adenosine A1receptor agonist, can stimulate adenosine A2Breceptor biased agonism.

    Science.gov (United States)

    Baltos, Jo-Anne; Vecchio, Elizabeth A; Harris, Matthew A; Qin, Cheng Xue; Ritchie, Rebecca H; Christopoulos, Arthur; White, Paul J; May, Lauren T

    2017-07-01

    The adenosine A 2B receptor (A 2B AR) has been identified as an important therapeutic target in cardiovascular disease, however in vitro and in vivo targeting has been limited by the paucity of pharmacological tools, particularly potent agonists. Interestingly, 2-((6-amino-3,5-dicyano-4-(4-(cyclopropylmethoxy)phenyl)-2-pyridinyl)thio)acetamide (BAY60-6583), a potent and subtype-selective A 2B AR agonist, has the same core structure as 2-amino-6-[[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methylsulfanyl]-4-[4-(2-hydroxyethoxy)phenyl]pyridine-3,5-dicarbonitril (capadenoson). Capadenoson, currently classified as an adenosine A 1 receptor (A 1 AR) partial agonist, has undergone two Phase IIa clinical trials, initially in patients with atrial fibrillation and subsequently in patients with stable angina. Capadenoson has also been shown to decrease cardiac remodeling in an animal model of advanced heart failure and a capadenoson derivative, neladenoson bialanate, recently entered clinical development for the treatment of chronic heart failure. The therapeutic effects of capadenoson are currently thought to be mediated through the A 1 AR. However, the ability of capadenoson to stimulate additional adenosine receptor subtypes, in particular the A 2B AR, has not been rigorously assessed. In this study, we demonstrate that capadenoson does indeed have significant A 2B AR activity in physiologically relevant cells, cardiac fibroblasts and cardiomyocytes, which endogenously express the A 2B AR. Relative to the non-selective adenosine receptor agonist NECA, capadenoson was a biased A 2B AR agonist with a preference for cAMP signal transduction over other downstream mediators in cells with recombinant and endogenous A 2B AR expression. These findings suggest the reclassification of capadenoson as a dual A 1 AR/A 2B AR agonist. Furthermore, a potential A 2B AR contribution should be an important consideration for the future clinical development of capadenoson-like therapeutics, as the A

  6. Effects of exercise and stress management training on markers of cardiovascular risk in patients with ischemic heart disease: a randomized controlled trial.

    Science.gov (United States)

    Blumenthal, James A; Sherwood, Andrew; Babyak, Michael A; Watkins, Lana L; Waugh, Robert; Georgiades, Anastasia; Bacon, Simon L; Hayano, Junichiro; Coleman, R Edward; Hinderliter, Alan

    2005-04-06

    Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality, but the effects of behavioral interventions on psychosocial and medical end points remain uncertain. To determine the effect of 2 behavioral programs, aerobic exercise training and stress management training, with routine medical care on psychosocial functioning and markers of cardiovascular risk. Randomized controlled trial of 134 patients (92 male and 42 female; aged 40-84 years) with stable ischemic heart disease (IHD) and exercise-induced myocardial ischemia. Conducted from January 1999 to February 2003. Routine medical care (usual care); usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks; usual care plus weekly 1.5-hour stress management training for 16 weeks. Self-reported measures of general distress (General Health Questionnaire [GHQ]) and depression (Beck Depression Inventory [BDI]); left ventricular ejection fraction (LVEF) and wall motion abnormalities (WMA); flow-mediated dilation; and cardiac autonomic control (heart rate variability during deep breathing and baroreflex sensitivity). Patients in the exercise and stress management groups had lower mean (SE) BDI scores (exercise: 8.2 [0.6]; stress management: 8.2 [0.6]) vs usual care (10.1 [0.6]; P = .02); reduced distress by GHQ scores (exercise: 56.3 [0.9]; stress management: 56.8 [0.9]) vs usual care (53.6 [0.9]; P = .02); and smaller reductions in LVEF during mental stress testing (exercise: -0.54% [0.44%]; stress management: -0.34% [0.45%]) vs usual care (-1.69% [0.46%]; P = .03). Exercise and stress management were associated with lower mean (SE) WMA rating scores (exercise: 0.20 [0.07]; stress management: 0.10 [0.07]) in a subset of patients with significant stress-induced WMA at baseline vs usual care (0.36 [0.07]; P = .02). Patients in the exercise and stress management groups had greater mean (SE) improvements in

  7. Air pollution, cardiovascular endpoints and susceptibility by stress and material resources: a systematic review of the evidence

    OpenAIRE

    Fuller, Christina H.; Feeser, Karla R; Sarnat, Jeremy A.; O'Neill, Marie S.

    2017-01-01

    Background and Methods Evidence shows that both the physical and social environments play a role in the development of cardiovascular disease. The purpose of this systematic review is two-fold: First, we summarize research from the past 12?years from the growing number of studies focused on effect modification of the relationships between air pollution and cardiovascular disease (CVD) outcomes by socioeconomic position (SEP) and; second, we identify research gaps throughout the published lite...

  8. Effects of Music Therapy on the Cardiovascular and Autonomic Nervous System in Stress-Induced University Students: A Randomized Controlled Trial.

    Science.gov (United States)

    Lee, Kyoung Soon; Jeong, Hyeon Cheol; Yim, Jong Eun; Jeon, Mi Yang

    2016-01-01

    Stress is caused when a particular relationship between the individual and the environment emerges. Specifically, stress occurs when an individual's abilities are challenged or when one's well-being is threatened by excessive environmental demands. The aim of this study was to measure the effects of music therapy on stress in university students. Randomized controlled trial. Sixty-four students were randomly assigned to the experimental group (n = 33) or the control group (n = 31). Music therapy. Initial measurement included cardiovascular indicators (blood pressure and pulse), autonomic nervous activity (standard deviation of the normal-to-normal intervals [SDNN], normalized low frequency, normalized high frequency, low/high frequency), and subjective stress. After the first measurement, participants in both groups were exposed to a series of stressful tasks, and then a second measurement was conducted. The experimental group then listened to music for 20 minutes and the control group rested for 20 minutes. A third and final measurement was then taken. There were no significant differences between the two groups in the first or second measurement. However, after music therapy, the experimental group and the control group showed significant differences in all variables, including systolic blood pressure (p = .026), diastolic blood pressure (p = .037), pulse (p music therapy as an intervention for stress reduction.

  9. Role of Adenosine Signaling in Penile Erection and Erectile Disorders

    Science.gov (United States)

    Phatarpekar, Prasad V.; Wen, Jiaming; Xia, Yang

    2010-01-01

    Introduction Penile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection. Aim To summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders. Main Outcome Measures Evidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism. Methods The article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism. Results Adenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A2B receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism. Conclusion Overall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism. PMID:19889148

  10. Role of adenosine signaling in penile erection and erectile disorders.

    Science.gov (United States)

    Phatarpekar, Prasad V; Wen, Jiaming; Xia, Yang

    2010-11-01

    Penile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection. To summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders. Evidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism. The article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism. Adenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A(2B) receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism. Overall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism. © 2009 International Society for Sexual Medicine.

  11. The reaction of the cardio-vascular and sympathico-adrenal systems to intellectual activity with emotional stress. [human operator performance

    Science.gov (United States)

    Tomashevskaya, L. I.

    1975-01-01

    The effect of emotiogenic factors on an operator's intellectual activity were studied for differing working regimes on an experimental control panel that provided for light, sonic, and electrocutaneous stimuli. The latter stimulus was activated automatically if the subject gave an incorrect response. It was shown that the working capacity of the operator under stress depends to a great extent on the effect of the emotiogenic factors on the individual functioning characteristics of the cardiovascular and sympathetic-adrenal systems. Moral, intellectual, willpower, emotional, and other personality traits are decisive factors of operator function.

  12. Anesthetic Cardioprotection: The Role of Adenosine

    Science.gov (United States)

    Bonney, Stephanie; Hughes, Kelly; Eckle, Tobias

    2014-01-01

    Brief periods of cardiac ischemia and reperfusion exert a protective effect against subsequent longer ischemic periods, a phenomenon coined ischemic preconditioning. Similar, repeated brief episodes of coronary occlusion and reperfusion at the onset of reperfusion, called post-conditioning, dramatically reduce infarct sizes. Interestingly, both effects can be achieved by the administration of any volatile anesthetic. In fact, cardio-protection by volatile anesthetics is an older phenomenon than ischemic pre- or post-conditioning. Although the mechanism through which anesthetics can mimic ischemic pre- or post-conditioning is still unknown, adenosine generation and signaling are the most redundant triggers in ischemic pre- or postconditioning. In fact, adenosine signaling has been implicated in isoflurane-mediated cardioprotection. Adenosine acts via four receptors designated as A1, A2a, A2b, and A3. Cardioprotection has been associated with all subtypes, although the role of each remains controversial. Much of the controversy stems from the abundance of receptor agonists and antagonists that are, in fact, capable of interacting with multiple receptor subtypes. Recently, more specific receptor agonists and new genetic animal models have become available paving way towards new discoveries. As such, the adenosine A2b receptor was shown to be the only 1 of the adenosine receptors whose cardiac expression is induced by ischemia in both mice and humans and whose function is implicated in ischemic pre- or post-conditioning. In the current review, we will focus on adenosine signaling in the context of anesthetic cardioprotection and will highlight new discoveries, which could lead to new therapeutic concepts to treat myocardial ischemia using anesthetic preconditioning. PMID:24502579

  13. Mechanisms of adenosine-induced renal vasodilatation in hypertensive patients.

    NARCIS (Netherlands)

    Wierema, T.K.; Houben, A.J.H.M.; Kroon, A.A.; Postma, C.T.; Koster, D.; Engelshoven, J.M. van; Smits, P.; Leeuw, P.W. de

    2005-01-01

    BACKGROUND: Adenosine is an endogenous nucleoside with potent vasodilatory capacities, released under ischaemic conditions in particular. Its mechanisms of action, however, remain elusive. OBJECTIVE: To evaluate the role of adenosine, using a non-selective purinergic receptor antagonist, and the

  14. Adenosine induced ventricular arrhythmias in the emergency room

    NARCIS (Netherlands)

    Tan, H. L.; Spekhorst, H. H.; Peters, R. J.; Wilde, A. A.

    2001-01-01

    While adenosine effectively terminates most supraventricular tachycardias (SVT), rare case reports have demonstrated its proarrhythmic potential, including induction of ventricular tachycardia (VT). The aim of this study was to define the proarrhythmic effects of adenosine in a large, unselected

  15. Impaired adenosine-mediated angiogenesis in preeclampsia: potential implications for fetal programming

    Directory of Open Access Journals (Sweden)

    Carlos Alonso Escudero

    2014-06-01

    Full Text Available Preeclampsia is a pregnancy-specific syndrome, defined by such clinical hallmarks as the onset of maternal hypertension and proteinuria after 20 weeks of gestation. The syndrome is also characterized by impaired blood flow through the utero-placental circulation and relative placental ischemia, which in turn, may generate feto-placental endothelial dysfunction. Endothelial dysfunction in offspring born from preeclamptic pregnancies has been associated with an increased risk of cardiovascular disease, including hypertension, later in life. Interestingly, diminished endothelial function, manifested by low angiogenic capacity, leads to hypertension in animal studies. Recently, we have shown that the adenosine receptor A2A/nitric oxide/vascular endothelial growth factor axis is reduced in human umbilical vein endothelial cells derived from preeclamptic pregnancies, an effect correlated with gestational age at onset of preeclampsia. We and others suggested that impaired vascular function might be associated with high cardiovascular risk in offspring exposed to pregnancy diseases. However, we are not aware of any studies that examine impaired adenosine-mediated angiogenesis as a possible link to hypertension in offspring born from preeclamptic pregnancies. In this review, we present evidence supporting the hypothesis that reduced adenosine-mediated angiogenesis during preeclamptic pregnancies might be associated with development of hypertension in the offspring.

  16. Mechanism of protection of adenosine from sulphate radical anion ...

    Indian Academy of Sciences (India)

    The photooxidation of adenosine in presence of peroxydisulphate (PDS) has been studied by spectrophotometrically measuring the absorbance of adenosine at 260 nm. The rates of oxidation of adenosine by sulphate radical anion have been determined in the presence of different concentrations of caffeic acid. Increase in ...

  17. Addition of adenosine to hyperbaric bupivacaine in spinal ...

    African Journals Online (AJOL)

    Background: Systemic administration of adenosine produces anti-nociception. Although literature supports intrathecal adenosine for neuropathic pain, its efficacy in postoperative pain remains unproven. There has been no study on the efficacy of adenosine on postoperative pain when administered with hyperbaric ...

  18. Adenosine and its Related Nucleotides may Modulate Gastric Acid ...

    African Journals Online (AJOL)

    Studies on lumen-perfused rat isolated stomachs showed that adenosine, adenosine monophosphate (AMP) and reduced nicotinamide adenine dinucleotide (NADH) inhibited histamine-induced gastric acid secretion. The inhibitions and the calcium levels of the serosal solution exhibited inverse relationship. Adenosine ...

  19. Cardiovascular consequences of hypophosphatemia.

    Science.gov (United States)

    Ariyoshi, Nobuhiro; Nogi, Masayuki; Ando, Akika; Watanabe, Hideaki; Umekawa, Sari

    2017-09-01

    Few studies have been conducted to evaluate the effect of hypophosphatemia on cardiovascular consequences. The goal of this review was to determine whether hypophosphatemia is associated with cardiovascular consequences and to increase its awareness as a new clinical entity and a reversible cause of cardiovascular consequences. We searched MEDLINE and PubMed through September 2016 for primary studies that reported the relationship between hypophosphatemia and cardiovascular consequences including cardiomyopathy and arrhythmia. A total of 937 articles were initially obtained. Of these articles, 921 publications were excluded according to the inclusion and exclusion criteria. Sixteen articles were included in this review. These articles included 3 prospective cohort studies, 1 retrospective cohort study, 7 case series or case reports, 2 case-control studies, 1 pre- vs. post-test in a single group, and 2 animal studies. The mechanisms of hypophosphatemia in cardiomyopathy and arrhythmia have been reported to be a depletion of adenosine triphosphate in myocardial cells and decreased 2,3-diphosphoglycerate in erythrocytes. Left ventricular performance seems to improve when severe hypophosphatemia is corrected, but not in those with mild to moderate hypophosphatemia. However, analyses of the relationship between cardiac function and hypophosphatemia using clinical end points have not been conducted. The association between hypophosphatemia and arrhythmia remains unclear, but anecdotal reports exist in the literature.

  20. Comparison of the prognostic value of normal regadenoson with normal adenosine myocardial perfusion imaging with propensity score matching.

    Science.gov (United States)

    Iqbal, Fahad M; Hage, Fadi G; Ahmed, Ali; Dean, Phillip J; Raslan, Saleem; Heo, Jaekyeong; Iskandrian, Ami E

    2012-10-01

    The aim of this study was to test the hypothesis that patients with normal regadenoson myocardial perfusion imaging (MPI) have a low rate of cardiac events, similar to patients with normal adenosine MPI. Regadenoson, a new selective adenosine A(2A) receptor agonist, is now a widely used stress agent for MPI. The low rate of cardiac events in patients with normal adenosine MPI is well-documented, but the prognostic implications of a normal regadenoson MPI have not been examined and compared with those with adenosine. Data on primary composite endpoint (cardiac death, myocardial infarction, and coronary revascularization) were collected for 2,000 patients (1,000 regadenoson, and 1,000 adenosine stress) with normal myocardial perfusion and left ventricular ejection fraction referred for vasodilator MPI. In addition, propensity scores were used to assemble a balanced cohort of 505 pairs of patients who were balanced on 36 baseline characteristics. The primary endpoint occurred in 21 (2.1%; 1.1%/year) patients in the regadenoson group and 33 (3.3%; 1.7%/year) patients in the adenosine group (hazard ratio [HR] for regadenoson vs. adenosine: 0.62; 95% confidence interval [CI]: 0.36 to 1.08; p = 0.090). In the propensity-matched pairs, the primary endpoint occurred in 7 (1.4%; 0.7%/year) patients in the regadenoson group and 13 (2.6%; 1.3%/year) patients in the adenosine group (matched HR: 0.58; 95% CI: 0.23 to 1.48; p = 0.257). Cardiac deaths were infrequent in the entire sample and in the propensity-matched groups; the cardiac death rate was 0.9%/year and 1.15%/year in the regadenoson and adenosine groups (HR: 0.77; 95% CI: 0.42 to 1.43; p = 0.404) in the pre-match sample and 0.5%/year and 0.7%/year in the matched groups, respectively (HR: 0.83; 95% CI: 0.25 to 2.73; p = 0.763). Major cardiac events are infrequent in patients with normal regadenoson MPI. These findings provide assurance that normal MPI using a simpler stress protocol with regadenoson provides prognostic

  1. Social support and cardiovascular responding to laboratory stress: Moderating effects of gender role identification, sex and type of support

    NARCIS (Netherlands)

    van Well, S.; Kolk, A.M.

    2008-01-01

    The objective of the present study was to examine moderating effects of gender role identification, sex, and type of support on the buffering role of social support on cardiovascular responses. We hypothesized that (a) gender role identification, more than sex, would moderate the effect of social

  2. The Effect of Intermittent Noise Stress on Ozone-Induced Cardiovascular Dysfunction in Wistar-Kyoto Rats

    Science.gov (United States)

    Previous studies have established that acute exposure to air pollution increases the risk of cardiovascular dysfunction. Intrinsic factors are likely the most important determinants of how the body responds to an exposure. But data also suggests that non-environmental stressors l...

  3. Structural Mapping of Adenosine Receptor Mutations

    DEFF Research Database (Denmark)

    Jespers, Willem; Schiedel, Anke C; Heitman, Laura H

    2018-01-01

    The four adenosine receptors (ARs), A1, A2A, A2B, and A3, constitute a subfamily of G protein-coupled receptors (GPCRs) with exceptional foundations for structure-based ligand design. The vast amount of mutagenesis data, accumulated in the literature since the 1990s, has been recently supplemente...

  4. Participation in a US community-based cardiovascular health study: investigating nonrandom selection effects related to employment, perceived stress, work-related stress, and family caregiving.

    Science.gov (United States)

    MacDonald, Leslie A; Fujishiro, Kaori; Howard, Virginia J; Landsbergis, Paul; Hein, Misty J

    2017-09-01

    Participation in health studies may be inversely associated with employment and stress. We investigated whether employment, perceived stress, work-related stress, and family caregiving were related to participation in a longitudinal US community-based health study of black and white men and women aged ≥45 years. Prevalence ratios and confidence intervals were estimated for completion of the second stage (S2) of a two-stage enrollment process by employment (status, type), and stress (perceived stress, work-related stress, caregiving), adjusting for age, sex, race, region, income, and education. Eligibility and consent for a follow-up occupational survey were similarly evaluated. Wage- but not self-employed participants were less likely than the unemployed to complete S2. Among the employed, S2 completion did not vary by stress; however, family caregivers with a short time burden of care (stress levels. Limited evidence of selection bias was seen by employment and stress within a large US community-based cohort, but findings suggest the need for enrollment procedures to consider possible barriers to participation among wage-employed individuals. Published by Elsevier Inc.

  5. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation

    Science.gov (United States)

    Wen, Jiaming; Grenz, Almut; Zhang, Yujin; Dai, Yingbo; Kellems, Rodney E.; Blackburn, Michael R.; Eltzschig, Holger K.; Xia, Yang

    2011-01-01

    Normal penile erection is under the control of multiple factors and signaling pathways. Although adenosine signaling is implicated in normal and abnormal penile erection, the exact role and the underlying mechanism for adenosine signaling in penile physiology remain elusive. Here we report that shear stress leads to increased adenosine release from endothelial cells. Subsequently, we determined that ecto-5′-nucleotidase (CD73) is a key enzyme required for the production of elevated adenosine from ATP released by shear-stressed endothelial cells. Mechanistically, we demonstrate that shear stress-mediated elevated adenosine functions through the adenosine A2B receptor (A2BR) to activate the PI3K/AKT signaling cascade and subsequent increased endothelial nitric oxide synthase (eNOS) phosphorylation. These in vitro studies led us to discover further that adenosine was induced during sustained penile erection and contributes to PI3K/AKT activation and subsequent eNOS phosphorylation via A2BR signaling in intact animal. Finally, we demonstrate that lowering adenosine in wild-type mice or genetic deletion of A2BR in mutant mice significantly attenuated PI3K/AKT activation, eNOS phosphorylation, and subsequent impaired penile erection featured with the reduction of ratio of maximal intracavernosal pressure to systemic arterial pressure from 0.49 ± 0.03 to 0.41 ± 0.05 and 0.38 ± 0.04, respectively (both Ppenile erection via PI3K/AKT-dependent eNOS activation. These studies suggest that this signaling pathway may be a novel therapeutic target for erectile disorders.—Wen, J., Grenz, A., Zhang, Y., Dai, Y., Kellems, R. E., Blackburn, M. R., Eltzschig, H. K., Xia, Y. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation. PMID:21566208

  6. Opinion - Are we over oxidized? Oxidative stress, cardiovascular disease, and the future of intervention studies with antioxidants

    Directory of Open Access Journals (Sweden)

    Greg J Dusting

    2005-07-01

    Full Text Available Greg J Dusting1, Chris Triggle21Howard Florey Institute, University of Melbourne, VIC, Australia; 2School of Medical Sciences, RMIT University, VIC, AustraliaAre we over oxidized? A number of recent clinical trials with antioxidants, notably vitamin C and E, have provided no support for the commonly held view that increasing our intake of antioxidants will offset the ravages of cardiovascular disease as well as other diseases (for extensive critical reviews see: Kritharides and Stocker 2002; Antoniades et al 2003; Touyz 2004. Is this conclusion justified? The role of antioxidant dietary adjuncts and therapy in prevention and treatment remains a highly important clinical question. In this opinion article we address the question: Is there a future for antioxidant therapy in the treatment and prevention of cardiovascular disease? We conclude that there is a need for better-designed studies as well as a re-thinking of the choice of antioxidants.

  7. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats

    Science.gov (United States)

    Resstel, Leonardo BM; Tavares, Rodrigo F; Lisboa, Sabrina FS; Joca, Sâmia RL; Corrêa, Fernando MA; Guimarães, Francisco S

    2009-01-01

    Background and purpose Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT1A receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT1A receptors. Experimental approach Male Wistar rats received i.p. injections of vehicle or CBD (1, 10 or 20 mg kg−1) and 30 min later were submitted to 60 min of restraint where their cardiovascular responses were recorded. The protocol of the second experiment was similar to the first one except that animals received i.p. injections of the 5-HT1A receptor antagonist WAY100635 (0.1 mg kg−1) before CBD treatment and exposure to restraint. 24 h later they were also tested in the elevated plus-maze (EPM), an animal model of anxiety. Key results Exposure to RS increased blood pressure and heart rate and induced an anxiogenic response in the EPM 24 h later. These effects were attenuated by CBD. WAY100635 by itself did not change the cardiovascular and anxiogenic response to RS, but blocked the effects of CBD. Conclusion and implications The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT1A receptor-mediated neurotransmission. PMID:19133999

  8. The association between changes in pressure pain sensitivity and changes in cardiovascular physiological factors associated with persistent stress

    DEFF Research Database (Denmark)

    Ballegaard, Søren; Petersen, Pernille B.; Harboe, Gitte S.

    2014-01-01

    -two office workers with an elevated PPS (≥ 60 arbitrary units) as a sign of increased level of persistent stress, completed a single-blinded cluster randomized controlled trial. The active treatment was a PPS (self-measurement)-guided stress management programme. Primary endpoints: Blood pressure (BP), heart...

  9. Molecular Mechanisms of Cardiovascular Aging

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-12-01

    Full Text Available BACKGROUND: The average lifespan of humans is increasing, and with it the percentage of people entering the 65 and older age group is growing rapidly and will continue to do so in the next 20 years. Within this age group, cardiovascular disease will remain the leading cause of death, and the cost associated with treatment will continue to increase. Aging is an inevitable part of life and unfortunately poses the largest risk factor for cardiovascular disease. CONTENT: We provide an overview of some of the molecular mechanisms involved in regulating lifespan and health, including mitochondria, telomeres, stem cells, sirtuins, Adenosine Monophosphate-activated Protein Kinase, Mammalian Target of Rapamycin and Insulin-like Growth Factor 1. We also provide future perspectives of lifespan and health, which are intimately linked fields. SUMMARY: Aging remains the biggest non-modifiable risk factor for cardiovascular disease. The biological, structural and mechanical changes in senescent cardiovascular system are thought to contribute in increasing incidence of cardiovascular disease in aging. Understanding the mechanisms contributing to such changes is therefore crucial for both prevention and development of treatment for cardiovascular diseases. KEYWORDS: cardiovascular aging, mitochondria, telomeres, sirtuin, stem cells.

  10. The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging.

    Science.gov (United States)

    Hoffmeister, C; Preuss, R; Weise, R; Burchert, W; Lindner, O

    2014-12-01

    The effect of beta blockers on myocardial blood flow (MBF) under vasodilators has been studied in several SPECT and PET myocardial perfusion imaging (MPI) studies with divergent results. The present study evaluated the effect of a beta blocker withdrawal on quantitative adenosine MBF and on MPI results. Twenty patients with beta blockers and CAD history were studied with quantitative adenosine N-13 ammonia PET. The first study was performed under complete medication and the second after beta blocker withdrawal. The PET studies were independently read with respect to MPI result and clinical decision making. Global MBF showed an increase from 180.2 ± 59.9 to 193.6 ± 60.8 mL·minute(-1)/100 g (P = .02) after beta blocker withdrawal. The segmental perfusion values were closely correlated (R(2) = 0.82) over the entire range of perfusion values. An essentially different interpretation after beta blocker discontinuation was found in two cases (10%). A beta blocker withdrawal induces an increase in adenosine MBF. In the majority of cases, MPI interpretation and decision making are independent of beta blocker intake. If a temporary beta blocker withdrawal before MPI is not possible or was not realized by the patient, it is appropriate to perform adenosine stress testing without loss of the essential MPI result.

  11. Cardiovascular and sympathetic responses to a mental stress task in young patients with hypertension and/or obesity.

    Science.gov (United States)

    Garafova, A; Penesova, A; Cizmarova, E; Marko, A; Vlcek, M; Jezova, D

    2014-01-01

    Present study was aimed to investigate sympathetic responses to mental stress with hypothesis that the presence of obesity in patients with hypertension has a modifying effect. Young male subjects, 8 with hypertension grade I, with BMI 25 kg/m(2) (HT), 10 with hypertension grade I, and BMI 30 kg/m(2) (HT OB), 14 healthy controls with BMI 30 kg/m(2) (OB), and 13 healthy controls with BMI 25 kg/m(2) (C) underwent the Stroop test. ECG was recorded continuously to evaluate heart rate variability (HRV). Blood pressure (BP) and catecholamine concentrations were measured at baseline, at the end of mental stress test and 15 min thereafter. Patients with HT demonstrated increased adrenaline concentrations and enhanced stress-induced noradrenaline release compared to that in healthy controls. In obese subjects, stress-induced increase of systolicBP was lower compared to lean individuals. Stress exposure induced a significant rise in the low frequency power component of HRV, however the increase was lower in the HT OB group compared to C. Obesity in patients with hypertension did not lead to a different reaction in comparison with lean hypertensive subjects. The present data demonstrate higher sympathoadrenal activity in early-stage of hypertension. Obesity is connected with higher resting systolicBP and modifies the HRV response to mental stress.

  12. Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.

    Directory of Open Access Journals (Sweden)

    Olena Rudyk

    Full Text Available Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11 or lard-enriched (23.6% fat, n = 16 chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old offspring cardiovascular parameters were measured (radiotelemetry. The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF and controls (OC. However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP and Δheart rate (HR with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week male OF demonstrated higher SBP (p<0.05 in the awake phase (night-time and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.

  13. Relationship between selected oxidative stress markers and lipid risk factors for cardiovascular disease in middle-aged adults and its possible clinical relevance.

    Science.gov (United States)

    Viktorinova, Alena; Svitekova, Klara; Stecova, Anna; Krizko, Marian

    2016-08-01

    Decreased activity of HDL-associated paraoxonase 1 (PON1) and elevated levels of lipid peroxides together with abnormal lipid profile may prognosticate the progression of atherosclerosis. The aim of this study was to assess associations between selected oxidative stress markers (PON1, lipid peroxides) and lipid risk factors for cardiovascular disease in middle-aged subjects. Arylesterase activity of PON1; lipid peroxides; total-, HDL-, LDL-, non-HDL-cholesterol; triglycerides; apolipoproteins A-I (ApoA-I) and B (ApoB), and lipid risk indexes were determined in serum of 75 volunteers (mean age 41.7±8.2years). Forty six volunteers were divided into normolipidemic (NL) and hyperlipidemic (HL) group. Elevated levels of atherogenic cholesterol (LDL, non-HDL), lipid risk indexes (pdiseases. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  14. Adenosine Signaling During Acute and Chronic Disease States

    Science.gov (United States)

    Karmouty-Quintana, Harry; Xia, Yang; Blackburn, Michael R.

    2013-01-01

    Adenosine is a signaling nucleoside that is produced following tissue injury, particularly injury involving ischemia and hypoxia. The production of extracellular adenosine and its subsequent signaling through adenosine receptors plays an important role in orchestrating injury responses in multiple organs. There are four adenosine receptors that are widely distributed on immune, epithelial, endothelial, neuronal and stromal cells throughout the body. Interestingly, these receptors are subject to altered regulation following injury. Studies in mouse models and human cells and tissues have identified that the production of adenosine and its subsequent signaling through its receptors plays largely beneficial roles in acute disease states, with the exception of brain injury. In contrast, if elevated adenosine levels are sustained beyond the acute injury phase, adenosine responses can become detrimental by activating pathways that promote tissue injury and fibrosis. Understanding when during the course of disease adenosine signaling is beneficial as opposed to detrimental and defining the mechanisms involved will be critical for the advancement of adenosine based therapies for acute and chronic diseases. The purpose of this review is to discuss key observations that define the beneficial and detrimental aspects of adenosine signaling during acute and chronic disease states with an emphasis on cellular processes such as inflammatory cell regulation, vascular barrier function and tissue fibrosis. PMID:23340998

  15. Protocol for an experimental investigation of the roles of oxytocin and social support in neuroendocrine, cardiovascular, and subjective responses to stress across age and gender

    Directory of Open Access Journals (Sweden)

    Block Jason

    2009-12-01

    Full Text Available Abstract Background Substantial empirical evidence has demonstrated that individuals who are socially isolated or have few positive social connections seem to age at a faster rate and have more chronic diseases. Oxytocin is a neurohypophyseal hormone hypothesized to coordinate both the causes and effects of positive social interactions, and may be involved in positive physiological adaptations such as buffering the deleterious effects of stress and promoting resilience. The proposed research will examine whether and how oxytocin influences responses to stress in humans and will consider effects in relation to those of social support. Methods/Design Experimental research will be used to determine whether exogenously administered oxytocin (intranasal influences psychological and physiological outcomes under conditions of stress across gender and age in adulthood. Hypotheses to be tested are: 1 Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress; 2 Oxytocin and social support have similar and additive stress-buffering effects; 3 Oxytocin effects are stronger in women versus men; and 4 Oxytocin effects are similar across a range of adult ages. Hypotheses will be tested with a placebo-controlled, double-blind study using a sample of healthy men and women recruited from the community. Participants are randomly assigned to receive either oxytocin or placebo. They undergo a social stress manipulation with and without social support (randomly assigned, and outcome measures are obtained at multiple times during the procedure. Discussion Understanding the determinants of healthy aging is a major public health priority and identifying effective measures to prevent or delay the onset of chronic diseases is an important goal. Experimental research on oxytocin, social relationships, and health in adulthood will contribute to the scientific knowledge base for maximizing active life and health expectancy. At

  16. Cardiovascular and cortisol reactivity and habituation to a virtual reality version of the Trier Social Stress Test: a pilot study

    DEFF Research Database (Denmark)

    Jönsson, Peter; Wallergård, Mattias; Osterberg, Kai

    2010-01-01

    reactivity and habituation to repeated stress provocations using a virtual reality (VR) version of TSST. The VR system was a CAVE™ system with three rear projected walls (4 m×3 m), and one floor projection. The system also included a head tracking system and passive stereoscopy. The virtual audience......, suggested to be related to sympathetic influence on myocardial performance) were assessed. Cortisol secretion showed a marked increase (88% vs. baseline) during the first stress provocation, but habituated in the second session. The magnitude of HR and TWA reactivity during stress provocation...... was approximately the same at both sessions, implying a stable increase in sympathetic activity. Heart rate showed a maximum increase of 40% at the first session, and 32% at the second. TWA showed a maximum decrease of 42% at the first session, and 39% at the second. The results resemble those obtained in prior...

  17. Interaction of sleep quality and psychosocial stress on obesity in African Americans: the Cardiovascular Health Epidemiology Study (CHES

    Directory of Open Access Journals (Sweden)

    Meng Yuan-Xiang

    2010-09-01

    Full Text Available Abstract Background Compared with whites, sleep disturbance and sleep deprivation appear more prevalent in African Americans (AA. Long-term sleep deprivation may increase the risk of obesity through multiple metabolic and endocrine alterations. Previous studies have reported contradictory results on the association between habitual sleep duration and obesity. Accordingly, we aimed to assess whether sleep quality and duration are inversely associated with body mass index (BMI and obesity and test whether these associations are modified by psychosocial stress, known to influence sleep quality. Methods A sample of 1,515 AA residents of metropolitan Atlanta, aged 30-65 years, was recruited by a random-digit-dialing method in 2007-08. The outcome obesity was defined by BMI (kg/m2 continuously and categorically (BMI ≥ 30 versus BMI Results The mean (standard deviation age was 47.5 (17.0 years, and 1,096 (72% were women. GSQ score categorized into tertiles was associated with BMI. Among women, after multivariable adjustment that included age, gender, physical activity, smoking status, education, total family income, financial stress and history of hypertension, hypercholesterolemia, diabetes and myocardial infarction, obesity was associated with sleep quality as assessed by GSQ continuous score, [odds ratio, OR (95% C.I.: 1.08 (1.03 - 1.12], and with a worse sleep disturbance subcomponent score [OR (95% C.I.: 1.48 (1.16 - 1.89]. Among all participants, stress modified the association between obesity and sleep quality; there was an increased likelihood of obesity in the medium stress category, OR (95% C.I.: 1.09 (1.02 - 1.17. Conclusion Sleep quality was associated with obesity in women. The association of sleep quality with obesity was modified by perceived stress. Our results indicate the need for simultaneous assessment of sleep and stress.

  18. Stress

    Science.gov (United States)

    ... natural disaster. This type of stress can cause post-traumatic stress disorder (PTSD). Different people may feel stress in different ways. Some people experience digestive symptoms. Others may have headaches, sleeplessness, depressed mood, anger, ...

  19. [The involvement of adenosine and adenosine deaminase in experimental myocardial infarct].

    Science.gov (United States)

    Stratone, A; Busuioc, A; Roşca, V; Bazgan, L; Popa, M; Hăulică, I

    1989-01-01

    By the ligature of the left coronary artery in the rat anesthetized with nembutal (10 mg/100 i.p.) a significant increase of the 5'-nucleotidase activity (Wooton method) was noticed 10 minutes after the left ventricle infarction (from an average value of 1038.5 +/- 187 mU/g tissue to 1537 +/- 225 mU/g fresh tissue). The adenosine desaminase levels spectrophotometrically determined by Denstedt technique, do not appear significantly modified 10 or 30 minutes after the left ventricle infarction. The chromatographically determined adenosine levels, by HPLC technique, decrease from the average value of 11.63 +/- 1.4 micrograms/mg PT to 8.60 +/- 1.0 micrograms/mg PT 30 minutes after infarction. The observed changes are explained by the conditions of hypoxia in the infarcted ventricle which lead to the raise in adenosine levels by activating the 5'-nucleotidase and their depression by a very fast metabolism of the same substance.

  20. Effect of adenosine and adenosine analogs on ( sup 14 C)aminopyrine accumulation by rabbit parietal cells

    Energy Technology Data Exchange (ETDEWEB)

    Ota, S.; Hiraishi, H.; Terano, A.; Mutoh, H.; Kurachi, Y.; Shimada, T.; Ivey, K.J.; Sugimoto, T. (Univ. of Tokyo (Japan))

    1989-12-01

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on (14C)aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. (14C)Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated (14C)aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on (14C)aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased (14C)aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.

  1. Pooled comparison of regadenoson versus adenosine for measuring fractional flow reserve and coronary flow in the catheterization laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Stolker, Joshua M., E-mail: jstolker@yahoo.com [Mercy Heart and Vascular, 901 Patients First Drive, Washington, MO 63090 (United States); Saint Louis University, 3635 Vista Ave, St. Louis, MO 63110 (United States); Lim, Michael J., E-mail: limmj@slu.edu [Saint Louis University, 3635 Vista Ave, St. Louis, MO 63110 (United States); Shavelle, David M., E-mail: david.shavelle@med.usc.edu [University of Southern California, 1510 San Pablo St, Suite 322, Los Angeles, CA 90033 (United States); Morris, D. Lynn, E-mail: morrisdl@einstein.edu [Albert Einstein Medical Center, 5501 Old York Rd, Philadelphia, PA 19141 (United States); Angiolillo, Dominick J., E-mail: dominick.angiolillo@jax.ufl.edu [University of Florida Health-Jacksonville, 655 West 8th St, Jacksonville, FL 32209 (United States); Guzman, Luis A., E-mail: luis.guzman@jax.ufl.edu [University of Florida Health-Jacksonville, 655 West 8th St, Jacksonville, FL 32209 (United States); Kennedy, Kevin F., E-mail: kfkennedy@saint-lukes.org [Saint Luke' s Mid America Heart Institute, 4401 Wornall Road, Kansas City, MO 64111 (United States); Weber, Elizabeth, E-mail: eweber1@slu.edu [Saint Louis University, 3635 Vista Ave, St. Louis, MO 63110 (United States); Zareh, Meena, E-mail: meena.zareh@med.usc.edu [University of Southern California, 1510 San Pablo St, Suite 322, Los Angeles, CA 90033 (United States); Neumayr, Robert H., E-mail: robneumayr@gmail.com [Mercy Heart and Vascular, 901 Patients First Drive, Washington, MO 63090 (United States); Saint Louis University, 3635 Vista Ave, St. Louis, MO 63110 (United States); Zenni, Martin M., E-mail: martin.zenni@jax.ufl.edu [University of Florida Health-Jacksonville, 655 West 8th St, Jacksonville, FL 32209 (United States)

    2015-07-15

    Background: Adenosine is the gold standard for augmenting coronary flow during fractional flow reserve (FFR) testing of intermediate coronary stenoses. However, intravenous infusion is time-consuming and intracoronary injection is subject to variability. Regadenoson is a newer adenosine alternative administered as a single intravenous bolus during nuclear stress testing, but its efficacy and safety during FFR testing have been evaluated only in small, single-center studies. Methods: We pooled data from 5 academic hospitals, in which patients undergoing clinically-indicated FFR prospectively underwent comparison of intravenous adenosine infusion (140–175 mcg/kg/min) versus regadenoson bolus (400 mcg). Hemodynamics and symptoms with adenosine were recorded until maximal hyperemia occurred, and after returning to baseline hemodynamics, regadenoson was administered and monitoring was repeated. In a subset of patients with coronary flow data, average peak velocity (APV) at the distal flow sensor was recorded. Results: Of 149 patients enrolled, mean age was 59 ± 9 years, 76% were male, and 54% underwent testing of the left anterior descending artery. Mean adenosine-FFR and regadenoson-FFR were identical (0.82 ± 0.10) with excellent correlation of individual values (r = 0.96, p < 0.001) and no difference in patient-reported symptoms. Four patients (2.6%) had discrepancies between the 2 drugs for the clinical decision-making cutoff of FFR ≤ 0.80. Coronary flow responses to adenosine and regadenoson were similar (APV at maximal hyperemia 36 cm/s for both, p = 0.81). Conclusions: Regadenoson single-bolus administration has comparable FFR, symptoms, and coronary flow augmentation when compared with standard intravenous adenosine infusion. With its greater ease of administration, regadenoson may be a more “user-friendly” option for invasive ischemic testing.

  2. Pooled comparison of regadenoson versus adenosine for measuring fractional flow reserve and coronary flow in the catheterization laboratory.

    Science.gov (United States)

    Stolker, Joshua M; Lim, Michael J; Shavelle, David M; Morris, D Lynn; Angiolillo, Dominick J; Guzman, Luis A; Kennedy, Kevin F; Weber, Elizabeth; Zareh, Meena; Neumayr, Robert H; Zenni, Martin M

    2015-01-01

    Adenosine is the gold standard for augmenting coronary flow during fractional flow reserve (FFR) testing of intermediate coronary stenoses. However, intravenous infusion is time-consuming and intracoronary injection is subject to variability. Regadenoson is a newer adenosine alternative administered as a single intravenous bolus during nuclear stress testing, but its efficacy and safety during FFR testing have been evaluated only in small, single-center studies. We pooled data from 5 academic hospitals, in which patients undergoing clinically-indicated FFR prospectively underwent comparison of intravenous adenosine infusion (140-175mcg/kg/min) versus regadenoson bolus (400mcg). Hemodynamics and symptoms with adenosine were recorded until maximal hyperemia occurred, and after returning to baseline hemodynamics, regadenoson was administered and monitoring was repeated. In a subset of patients with coronary flow data, average peak velocity (APV) at the distal flow sensor was recorded. Of 149 patients enrolled, mean age was 59±9years, 76% were male, and 54% underwent testing of the left anterior descending artery. Mean adenosine-FFR and regadenoson-FFR were identical (0.82±0.10) with excellent correlation of individual values (r=0.96, p<0.001) and no difference in patient-reported symptoms. Four patients (2.6%) had discrepancies between the 2 drugs for the clinical decision-making cutoff of FFR≤0.80. Coronary flow responses to adenosine and regadenoson were similar (APV at maximal hyperemia 36cm/s for both, p=0.81). Regadenoson single-bolus administration has comparable FFR, symptoms, and coronary flow augmentation when compared with standard intravenous adenosine infusion. With its greater ease of administration, regadenoson may be a more "user-friendly" option for invasive ischemic testing. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress

    NARCIS (Netherlands)

    J.H.M. Tulen (Joke); P. Moleman (Peter); F. Boomsma (Frans); H.G. van Steenis (H.); V.J.H.M. van den Heuij (Venantius)

    1991-01-01

    textabstractDose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male

  4. Conditioned Neuroendocrine and Cardiovascular Stress Responsiveness Accompanying Behavioral Passivity and Activity in Aged and in Young Rats

    NARCIS (Netherlands)

    Korte, S.M.; Buwalda, B.; Bouws, G.A.H.; Koolhaas, J.M.; Maes, F.W.; Bohus, B.

    1992-01-01

    Mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E), plasma norepinephrine (NE), and plasma corticosterone (CORT) were measured in 3-month- and 24-month-old male Wistar rats exposed to a conditioned emotional stress response (CER) paradigm and a conditioned defensive burying (CDB)

  5. Endothelial function and cardiovascular stress markers after a single dive in aging rats (ApoE knockout rats)

    DEFF Research Database (Denmark)

    Berenji Ardestani, Simin; Pedersen, Michael

    Diving exposes body to a variety of stressors during the dive itself, and gas bubbles that develop during the decompression (ascent) phase. The compressed gas breath augments partial pressure of oxygen (PO2) causing the oxygen concentration of the blood to increase above normal (hyperoxia) likely...... causing excessive oxidative stress, including transient endothelial dysfunction in venous and arterial vessels....

  6. Adenosine Kinase Deficiency in the Brain Results in Maladaptive Synaptic Plasticity.

    Science.gov (United States)

    Sandau, Ursula S; Colino-Oliveira, Mariana; Jones, Abbie; Saleumvong, Bounmy; Coffman, Shayla Q; Liu, Long; Miranda-Lourenço, Catarina; Palminha, Cátia; Batalha, Vânia L; Xu, Yiming; Huo, Yuqing; Diógenes, Maria J; Sebastião, Ana M; Boison, Detlev

    2016-11-30

    Adenosine kinase (ADK) deficiency in human patients (OMIM:614300) disrupts the methionine cycle and triggers hypermethioninemia, hepatic encephalopathy, cognitive impairment, and seizures. To identify whether this neurological phenotype is intrinsically based on ADK deficiency in the brain or if it is secondary to liver dysfunction, we generated a mouse model with a brain-wide deletion of ADK by introducing a Nestin-Cre transgene into a line of conditional ADK deficient Adk(fl/fl) mice. These Adk(Δbrain) mice developed a progressive stress-induced seizure phenotype associated with spontaneous convulsive seizures and profound deficits in hippocampus-dependent learning and memory. Pharmacological, biochemical, and electrophysiological studies suggest enhanced adenosine levels around synapses resulting in an enhanced adenosine A1 receptor (A1R)-dependent protective tone despite lower expression levels of the receptor. Theta-burst-induced LTP was enhanced in the mutants and this was dependent on adenosine A2A receptor (A2AR) and tropomyosin-related kinase B signaling, suggesting increased activation of these receptors in synaptic plasticity phenomena. Accordingly, reducing adenosine A2A receptor activity in Adk(Δbrain) mice restored normal associative learning and contextual memory and attenuated seizure risk. We conclude that ADK deficiency in the brain triggers neuronal adaptation processes that lead to dysregulated synaptic plasticity, cognitive deficits, and increased seizure risk. Therefore, ADK mutations have an intrinsic effect on brain physiology and may present a genetic risk factor for the development of seizures and learning impairments. Furthermore, our data show that blocking A2AR activity therapeutically can attenuate neurological symptoms in ADK deficiency. A novel human genetic condition (OMIM #614300) that is based on mutations in the adenosine kinase (Adk) gene has been discovered recently. Affected patients develop hepatic encephalopathy, seizures

  7. [Influence of microinflammation and oxidative stress on atherosclerosis progression and calcifications in cardiovascular system of hemodialyzed patients during two years follow-up].

    Science.gov (United States)

    Kraśniak, Andrzej; Drozdz, Maciej; Pasowicz, Mieczysław; Chmiel, Grzegorz; Kowalczyk-Michałek, Martyna; Szumilak, Dorota; Podolec, Piotr; Klimeczek, Piotr; Konieczyńska, Małgorzata; Wicher-Muniak, Ewa; Tracz, Wiesława; Sułowicz, Władysław; Drueke, Tilman

    2007-01-01

    Atherosclerosis and calcifications in the cardio-vascular system are the most frequent causes of increased morbidity and mortality in patients with end-stage renal disease treated with hemodialyses. The aim of this study was to estimate the atherosclerosis progression and presence of calcifications in the circulatory system in patients treated with hemodialyses using, non-invasive imaging diagnostic techniques and to search for the relationships between these changes and microinflammation and oxidative stress during two years. The study was performed in 73 patients (36 female and 37 male), aged 25 to 75 years (mean -49.5), treated with hemodialyses, 3 times/week for 12 to 275 months (mean -73.8). In each patient before starting hemodialysis levels of: ox-LDL, Lp (a), procalcitonin, IL-1beta, IL-6, CRP, TGFbeta, TNFalpha, PDGF, AOPP and MPO were determined. Presence of artery calcifications was detected by Multi-Row Spiral Computed Tomography (MSCT) and expressed as coronary artery calcification score (CACS). Ultrasonography was used to evaluate CCA-IMT. During the study CACS increased significantly after 12 and 24 months (p atherosclerosis and calcification in the circulatory system of patients treated with maintenance hemodialyses depends on microinflammation and oxidative stress. Reasonable tools for diagnostic algorithm estimation of atherosclerosis advancement in this group of patients are non-invasive, visual diagnostic techniques such as MSCT and ultrasonography.

  8. Effects of time-of-day on oxidative stress, cardiovascular parameters, biochemical markers, and hormonal response following level-1 Yo-Yo intermittent recovery test.

    Science.gov (United States)

    Aloui, K; Abedelmalek, S; Chtourou, H; Wong, D P; Boussetta, N; Souissi, N

    2017-03-01

    The aim of this study was to investigate the effect of time-of-day on oxidative stress, cardiovascular parameters, muscle damage parameters, and hormonal responses following the level-1 Yo-Yo intermittent recovery test (YYIRT). A total of 11 healthy subjects performed an intermittent test (YYIRT) at two times-of-day (i.e., 07:00 h and 17:00 h), with a recovery period of ≥36 h in-between, in a randomized order. Blood samples were taken at the rest (baseline) and immediately (post-YYIRT) after the YYIRT for measuring oxidative stress, biochemical markers, and hormonal response. Data were statistically analyzed using one-way and two-way repeated measures ANOVA and Bonferroni test at p evening (17:00 h). There was also a main effect of time-of-day for cortisol and testosterone concentration, which were higher after the YYIRT in the morning (p evening. Low-density lipoprotein, systolic blood pressure, diastolic blood pressure, and lactate levels (p > 0.05) were similar for the morning and evening test. In conclusion, our findings suggest that aerobic performance presents diurnal variation with great result observed in the evening accompanied by an improvement of hormonal, metabolic, and oxidative responses. These data may help to guide athletes and coaches and contribute to public health recommendations on exercise and muscle damage particularly in the competitive periods.

  9. Effect of a 16-week Bikram yoga program on heart rate variability and associated cardiovascular disease risk factors in stressed and sedentary adults: A randomized controlled trial.

    Science.gov (United States)

    Hewett, Zoe L; Pumpa, Kate L; Smith, Caroline A; Fahey, Paul P; Cheema, Birinder S

    2017-04-21

    Chronic activation of the stress-response can contribute to cardiovascular disease risk, particularly in sedentary individuals. This study investigated the effect of a Bikram yoga intervention on the high frequency power component of heart rate variability (HRV) and associated cardiovascular disease (CVD) risk factors (i.e. additional domains of HRV, hemodynamic, hematologic, anthropometric and body composition outcome measures) in stressed and sedentary adults. Eligible adults were randomized to an experimental group (n = 29) or a no treatment control group (n = 34). Experimental group participants were instructed to attend three to five supervised Bikram yoga classes per week for 16 weeks at local studios. Outcome measures were assessed at baseline (week 0) and completion (week 17). Sixty-three adults (37.2 ± 10.8 years, 79% women) were included in the intention-to-treat analysis. The experimental group attended 27 ± 18 classes. Analyses of covariance revealed no significant change in the high-frequency component of HRV (p = 0.912, partial η 2 = 0.000) or in any secondary outcome measure between groups over time. However, regression analyses revealed that higher attendance in the experimental group was associated with significant reductions in diastolic blood pressure (p = 0.039; partial η 2 = 0.154), body fat percentage (p = 0.001, partial η 2 = 0.379), fat mass (p = 0.003, partial η 2 = 0.294) and body mass index (p = 0.05, partial η 2 = 0.139). A 16-week Bikram yoga program did not increase the high frequency power component of HRV or any other CVD risk factors investigated. As revealed by post hoc analyses, low adherence likely contributed to the null effects. Future studies are required to address barriers to adherence to better elucidate the dose-response effects of Bikram yoga practice as a medium to lower stress-related CVD risk. Retrospectively registered with Australia New Zealand Clinical Trials Registry ACTRN

  10. Adenosine signalling in diabetes mellitus--pathophysiology and therapeutic considerations.

    Science.gov (United States)

    Antonioli, Luca; Blandizzi, Corrado; Csóka, Balázs; Pacher, Pál; Haskó, György

    2015-04-01

    Adenosine is a key extracellular signalling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors, A1, A2A, A2B and A1 adenosine receptors. Accumulating evidence highlights a critical role for the adenosine system in the regulation of glucose homeostasis and the pathophysiology of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Although adenosine signalling is known to affect insulin secretion, new data indicate that adenosine signalling also contributes to the regulation of β-cell homeostasis and activity by controlling the proliferation and regeneration of these cells as well as the survival of β cells in inflammatory microenvironments. Furthermore, adenosine is emerging as a major regulator of insulin responsiveness by controlling insulin signalling in adipose tissue, muscle and liver; adenosine also indirectly mediates effects on inflammatory and/or immune cells in these tissues. This Review critically discusses the role of the adenosine-adenosine receptor system in regulating both the onset and progression of T1DM and T2DM, and the potential of pharmacological manipulation of the adenosinergic system as an approach to manage T1DM, T2DM and their associated complications.

  11. The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Krithika Srikanthan

    2016-09-01

    Full Text Available Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS, which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.

  12. Social support and cardiovascular responding to laboratory stress: moderating effects of gender role identification, sex, and type of support.

    Science.gov (United States)

    van Well, Sonja; Kolk, Annemarie M

    2008-01-01

    The objective of the present study was to examine moderating effects of gender role identification, sex, and type of support on the buffering role of social support on cardiovascular responses. We hypothesized that (a) gender role identification, more than sex, would moderate the effect of social support and (b) to obtain optimal attenuating effects of social support, type of support provided should match type of support preferred in terms of one's gender role identification. That is, feminine participants would benefit more from relatively direct support, whereas masculine participants would benefit more from indirect support. Healthy participants (N = 100) performed a psychological stressor in the presence of a friend, after mental activation of a friend, or alone. Results revealed no moderating effects of gender role identification whether or not in combination with type of support. Nevertheless, results demonstrated an attenuating effect of mental support on heart rate and cardiac output in men. It is concluded that pathways linking social relationships and health may differ between women and men.

  13. Heat exposure, cardiovascular stress and work productivity in rice harvesters in India: implications for a climate change future.

    Science.gov (United States)

    Sahu, Subhashis; Sett, Moumita; Kjellstrom, Tord

    2013-01-01

    Excessive workplace heat exposures create well-known risks of heat stroke, and it limits the workers' capacity to sustain physical activity. There is very limited evidence available on how these effects reduce work productivity, while the quantitative relationship between heat and work productivity is an essential basis for climate change impact assessments. We measured hourly heat exposure in rice fields in West Bengal and recorded perceived health problems via interviews of 124 rice harvesters. In a sub-group (n = 48) heart rate was recorded every minute in a standard work situation. Work productivity was recorded as hourly rice bundle collection output. The hourly heat levels (WBGT = Wet Bulb Globe Temperature) were 26-32°C (at air temperatures of 30-38°C), exceeding international standards. Most workers reported exhaustion and pain during work on hot days. Heart rate recovered quickly at low heat, but more slowly at high heat, indicating cardiovascular strain. The hourly number of rice bundles collected was significantly reduced at WBGT>26°C (approximately 5% per°C of increased WBGT). We conclude that high heat exposure in agriculture caused heat strain and reduced work productivity. This reduction will be exacerbated by climate change and may undermine the local economy.

  14. Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle erythrocyte sphingosine kinase 1 activity

    Science.gov (United States)

    Sun, Kaiqi; Zhang, Yujin; Bogdanov, Mikhail V.; Wu, Hongyu; Song, Anren; Li, Jessica; Dowhan, William; Idowu, Modupe; Juneja, Harinder S.; Molina, Jose G.; Blackburn, Michael R.; Kellems, Rodney E.

    2015-01-01

    Erythrocyte possesses high sphingosine kinase 1 (SphK1) activity and is the major cell type supplying plasma sphingosine-1-phosphate, a signaling lipid regulating multiple physiological and pathological functions. Recent studies revealed that erythrocyte SphK1 activity is upregulated in sickle cell disease (SCD) and contributes to sickling and disease progression. However, how erythrocyte SphK1 activity is regulated remains unknown. Here we report that adenosine induces SphK1 activity in human and mouse sickle and normal erythrocytes in vitro. Next, using 4 adenosine receptor-deficient mice and pharmacological approaches, we determined that the A2B adenosine receptor (ADORA2B) is essential for adenosine-induced SphK1 activity in human and mouse normal and sickle erythrocytes in vitro. Subsequently, we provide in vivo genetic evidence that adenosine deaminase (ADA) deficiency leads to excess plasma adenosine and elevated erythrocyte SphK1 activity. Lowering adenosine by ADA enzyme therapy or genetic deletion of ADORA2B significantly reduced excess adenosine-induced erythrocyte SphK1 activity in ADA-deficient mice. Finally, we revealed that protein kinase A-mediated extracellular signal-regulated kinase 1/2 activation functioning downstream of ADORA2B underlies adenosine-induced erythrocyte SphK1 activity. Overall, our findings reveal a novel signaling network regulating erythrocyte SphK1 and highlight innovative mechanisms regulating SphK1 activity in normal and SCD. PMID:25587035

  15. Moderate exercise training promotes adaptations in coronary blood flow and adenosine production in normotensive rats

    Directory of Open Access Journals (Sweden)

    Fernanda R. Roque

    2011-01-01

    Full Text Available OBJECTIVES: Aerobic exercise training prevents cardiovascular risks. Regular exercise promotes functional and structural adaptations that are associated with several cardiovascular benefits. The aim of this study is to investigate the effects of swimming training on coronary blood flow, adenosine production and cardiac capillaries in normotensive rats. METHODS: Wistar rats were randomly divided into two groups: control (C and trained (T. An exercise protocol was performed for 10 weeks and 60 min/day with a tail overload of 5% bodyweight. Coronary blood flow was quantified with a color microsphere technique, and cardiac capillaries were quantified using light microscopy. Adenine nucleotide hydrolysis was evaluated by enzymatic activity, and protein expression was evaluated by western blot. The results are presented as the means ± SEMs (p<0.05. RESULTS: Exercise training increased the coronary blood flow and the myocardial capillary-to-fiber ratio. Moreover, the circulating and cardiac extracellular adenine nucleotide hydrolysis was higher in the trained rats than in the sedentary rats due to the increased activity and protein expression of enzymes, such as E-NTPDase and 59- nucleotidase. CONCLUSIONS: Swimming training increases coronary blood flow, number of cardiac capillaries, and adenine nucleotide hydrolysis. Increased adenosine production may be an important contributor to the enhanced coronary blood flow and angiogenesis that were observed in the exercise-trained rats; collectively, these results suggest improved myocardial perfusion.

  16. Application of spatial synoptic classification in evaluating links between heat stress and cardiovascular mortality and morbidity in Prague, Czech Republic

    Science.gov (United States)

    Urban, Aleš; Kyselý, Jan

    2015-09-01

    Spatial synoptic classification (SSC) is here first employed in assessing heat-related mortality and morbidity in Central Europe. It is applied for examining links between weather patterns and cardiovascular (CVD) mortality and morbidity in an extended summer season (16 May-15 September) during 1994-2009. As in previous studies, two SSC air masses (AMs)—dry tropical (DT) and moist tropical (MT)—are associated with significant excess CVD mortality in Prague, while effects on CVD hospital admissions are small and insignificant. Excess mortality for ischaemic heart diseases is more strongly associated with DT, while MT has adverse effect especially on cerebrovascular mortality. Links between the oppressive AMs and excess mortality relate also to conditions on previous days, as DT and MT occur in typical sequences. The highest CVD mortality deviations are found 1 day after a hot spell's onset, when temperature as well as frequency of the oppressive AMs are highest. Following this peak is typically DT- to MT-like weather transition, characterized by decrease in temperature and increase in humidity. The transition between upward (DT) and downward (MT) phases is associated with the largest excess CVD mortality, and the change contributes to the increased and more lagged effects on cerebrovascular mortality. The study highlights the importance of critically evaluating SSC's applicability and benefits within warning systems relative to other synoptic and epidemiological approaches. Only a subset of days with the oppressive AMs is associated with excess mortality, and regression models accounting for possible meteorological and other factors explain little of the mortality variance.

  17. Application of spatial synoptic classification in evaluating links between heat stress and cardiovascular mortality and morbidity in Prague, Czech Republic

    Science.gov (United States)

    Urban, Aleš; Kyselý, Jan

    2018-01-01

    Spatial synoptic classification (SSC) is here first employed in assessing heat-related mortality and morbidity in Central Europe. It is applied for examining links between weather patterns and cardiovascular (CVD) mortality and morbidity in an extended summer season (16 May-15 September) during 1994-2009. As in previous studies, two SSC air masses (AMs)—dry tropical (DT) and moist tropical (MT)—are associated with significant excess CVD mortality in Prague, while effects on CVD hospital admissions are small and insignificant. Excess mortality for ischaemic heart diseases is more strongly associated with DT, while MT has adverse effect especially on cerebrovascular mortality. Links between the oppressive AMs and excess mortality relate also to conditions on previous days, as DT and MT occur in typical sequences. The highest CVD mortality deviations are found 1 day after a hot spell's onset, when temperature as well as frequency of the oppressive AMs are highest. Following this peak is typically DT- to MT-like weather transition, characterized by decrease in temperature and increase in humidity. The transition between upward (DT) and downward (MT) phases is associated with the largest excess CVD mortality, and the change contributes to the increased and more lagged effects on cerebrovascular mortality. The study highlights the importance of critically evaluating SSC's applicability and benefits within warning systems relative to other synoptic and epidemiological approaches. Only a subset of days with the oppressive AMs is associated with excess mortality, and regression models accounting for possible meteorological and other factors explain little of the mortality variance.

  18. Slow breathing and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ashish Chaddha

    2015-01-01

    Full Text Available Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.

  19. Partial agonism of theophylline-7-riboside on adenosine receptors

    NARCIS (Netherlands)

    IJzerman, A. P.; van der Wenden, E. M.; von Frijtag Drabbe Künzel, J. K.; Mathôt, R. A.; Danhof, M.; Borea, P. A.; Varani, K.

    1994-01-01

    Theophylline-7-riboside was evaluated as a partial agonist for rat adenosine receptors. Radioligand binding experiments were performed on both A1 and A2a adenosine receptors, using several methodologies to discriminate between agonists and antagonists. Mainly from thermodynamic data it was concluded

  20. Elevated Placental Adenosine Signaling Contributes to the Pathogenesis of Preeclampsia

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F.; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A.; Blackwell, Sean C.; Sibai, Baha M.; Chan, Lee-Nien L.; Chan, Teh-Sheng; Hicks, M. John; Blackburn, Michael R.; Kellems, Rodney E.; Xia, Yang

    2016-01-01

    Background Preeclampsia (PE) is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be due to placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways leading to impaired placentas and maternal disease development remain elusive. Methods and Results By using two independent animal models of PE—1) genetically-engineered pregnant mice with elevated adenosine exclusively in placentas, and 2) a pathogenic autoantibody-induced PE mouse model—we demonstrated here that chronically elevated placental adenosine was sufficient to induce hallmark features of PE including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacologic approaches revealed that elevated placental adenosine coupled with excessive A2B adenosine receptor (ADORA2B) signaling contributed to the development of these features of PE. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to PE. Conclusions We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for PE. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of PE, and, thereby highlight novel therapeutic targets. PMID:25538227

  1. Comorbidities in Neurology: Is Adenosine the Common Link?

    Science.gov (United States)

    Boison, Detlev; Aronica, Eleonora

    2015-01-01

    Comorbidities in Neurology represent a major conceptual and therapeutic challenge. For example, temporal lobe epilepsy (TLE) is a syndrome comprised of epileptic seizures and comorbid symptoms including memory and psychiatric impairment, depression, and sleep dysfunction. Similarly, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are accompanied by various degrees of memory dysfunction. Patients with AD have an increased likelihood for seizures, whereas all four conditions share certain aspects of psychosis, depression, and sleep dysfunction. This remarkable overlap suggests common pathophysiological mechanisms, which include synaptic dysfunction and synaptotoxicity, as well as glial activation and astrogliosis. Astrogliosis is linked to synapse function via the tripartite synapse, but astrocytes also control the availability of gliotransmitters and adenosine. Here we will specifically focus on the ‘adenosine hypothesis of comorbidities’ implying that astrocyte activation, via overexpression of adenosine kinase (ADK), induces a deficiency in the homeostatic tone of adenosine. We present evidence from patient-derived samples showing astrogliosis and overexpression of ADK as common pathological hallmark of epilepsy, AD, PD, and ALS. We discuss a transgenic ‘comorbidity model’, in which brain-wide overexpression of ADK and resulting adenosine deficiency produces a comorbid spectrum of seizures, altered dopaminergic function, attentional impairment, and deficits in cognitive domains and sleep regulation. We conclude that dysfunction of adenosine signaling is common in neurological conditions, that adenosine dysfunction can explain comorbid phenotypes, and that therapeutic adenosine augmentation might be effective for the treatment of comorbid symptoms in multiple neurological conditions. PMID:25979489

  2. Adenosine deaminase activities and fasting blood glucose in obesity ...

    African Journals Online (AJOL)

    Background: A complex relationship seems to exist between adenosine deaminase (ADA) and insulin in obesity. Through its effect on adenosine, the enzyme can modulate the action of insulin and affect blood glucose while the administration of insulin is said to decrease the activities of the enzyme. Aim: To investigate the ...

  3. Endogenous adenosine curtails lipopolysaccharide-stimulated tumour necrosis factor synthesis

    NARCIS (Netherlands)

    Eigler, A; Greten, T F; Sinha, B; Haslberger, C; Sullivan, G W; Endres, S

    Recent studies have demonstrated the inhibitory effect of exogenous adenosine on TNF production. During inflammation endogenous adenosine levels are elevated and may be one of several anti-inflammatory mediators that reduce TNF synthesis. In the present study the authors investigated this role of

  4. Adenosine Deaminase, (ADA) level in leprosy | Ogbu | International ...

    African Journals Online (AJOL)

    Background: Adenosine deaminase (ADA) is involved in and the catabolism of toxic de-oxynucleotides (5) and modulation of insulin action. Although its activities in leprosy have been measured, its characteristics have not been reported. Objective: To determine adenosine deaminase activities in leprosy and possible ...

  5. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  6. Exercise-induced hypertension, cardiovascular events, and mortality in patients undergoing exercise stress testing: a systematic review and meta-analysis.

    Science.gov (United States)

    Schultz, Martin G; Otahal, Petr; Cleland, Verity J; Blizzard, Leigh; Marwick, Thomas H; Sharman, James E

    2013-03-01

    The prognostic relevance of a hypertensive response to exercise (HRE) is ill-defined in individuals undergoing exercise stress testing. The study described here was intended to provide a systematic review and meta-analysis of published literature to determine the value of exercise-related blood pressure (BP) (independent of office BP) for predicting cardiovascular (CV) events and mortality. Online databases were searched for published longitudinal studies reporting exercise-related BP and CV events and mortality rates. We identified for review 12 longitudinal studies with a total of 46,314 individuals without significant coronary artery disease, with total CV event and mortality rates recorded over a mean follow-up of 15.2±4.0 years. After adjustment for age, office BP, and CV risk factors, an HRE at moderate exercise intensity carried a 36% greater rate of CV events and mortality (95% CI, 1.02-1.83, P = 0.039) than that of subjects without an HRE. Additionally, each 10mm Hg increase in systolic BP during exercise at moderate intensity was accompanied by a 4% increase in CV events and mortality, independent of office BP, age, or CV risk factors (95% CI, 1.01-1.07, P = 0.02). Systolic BP at maximal workload was not significantly associated with the outcome of an increased rate of CV, whether analyzed as a categorical (HR=1.49, 95% CI, 0.90-2.46, P = 0.12) or a continuous (HR=1.01, 95% CI, 0.98-1.04, P = 0.53) variable. An HRE at moderate exercise intensity during exercise stress testing is an independent risk factor for CV events and mortality. This highlights the need to determine underlying pathophysiological mechanisms of exercise-induced hypertension.

  7. Sympathovagal imbalance contributes to prehypertension status and cardiovascular risks attributed by insulin resistance, inflammation, dyslipidemia and oxidative stress in first degree relatives of type 2 diabetics.

    Directory of Open Access Journals (Sweden)

    Gopal Krushna Pal

    Full Text Available BACKGROUND: Though cardiovascular (CV risks are reported in first-degree relatives (FDR of type 2 diabetics, the pathophysiological mechanisms contributing to these risks are not known. We investigated the association of sympathovagal imbalance (SVI with CV risks in these subjects. SUBJECTS AND METHODS: Body mass index (BMI, basal heart rate (BHR, blood pressure (BP, rate-pressure product (RPP, spectral indices of heart rate variability (HRV, autonomic function tests, insulin resistance (HOMA-IR, lipid profile, inflammatory markers, oxidative stress (OS marker, rennin, thyroid profile and serum electrolytes were measured and analyzed in subjects of study group (FDR of type 2 diabetics, n = 72 and control group (subjects with no family history of diabetes, n = 104. RESULTS: BMI, BP, BHR, HOMA-IR, lipid profile, inflammatory and OS markers, renin, LF-HF (ratio of low-frequency to high-frequency power of HRV, a sensitive marker of SVI were significantly increased (p<0.0001 in study group compared to the control group. SVI in study group was due to concomitant sympathetic activation and vagal inhibition. There was significant correlation and independent contribution of markers of insulin resistance, dyslipidemia, inflammation and OS to LF-HF ratio. Multiple-regression analysis demonstrated an independent contribution of LF-HF ratio to prehypertension status (standardized beta 0.415, p<0.001 and bivariate logistic-regression showed significant prediction (OR 2.40, CI 1.128-5.326, p = 0.002 of LF-HF ratio of HRV to increased RPP, the marker of CV risk, in study group. CONCLUSION: SVI in FDR of type 2 diabetics occurs due to sympathetic activation and vagal withdrawal. The SVI contributes to prehypertension status and CV risks caused by insulin resistance, dyslipidemia, inflammation and oxidative stress in FDR of type 2 diabetics.

  8. A High-Affinity Adenosine Kinase from Anopheles Gambiae

    Energy Technology Data Exchange (ETDEWEB)

    M Cassera; M Ho; E Merino; E Burgos; A Rinaldo-Matthis; S Almo; V Schramm

    2011-12-31

    Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (K{sub m} = 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site, but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap{sub 4}A (2.0 {angstrom} resolution) reveals interactions for adenosine and ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg{sup 2+} ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layer {alpha}/{beta}/{alpha} sandwich, and a small cap domain in contact with adenosine. The specificity and tight binding for adenosine arise from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168, and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64, and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. The structure is more similar to that of human adenosine kinase (48% identical) than to that of AK from Toxoplasma gondii (31% identical). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role for this enzyme in the maintenance of the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects.

  9. The Personality and Psychological Stress Predict Major Adverse Cardiovascular Events in Patients With Coronary Heart Disease After Percutaneous Coronary Intervention for Five Years

    Science.gov (United States)

    Du, Jinling; Zhang, Danyang; Yin, Yue; Zhang, Xiaofei; Li, Jifu; Liu, Dexiang; Pan, Fang; Chen, Wenqiang

    2016-01-01

    Abstract To investigate the effects of personality type and psychological stress on the occurrence of major adverse cardiovascular events (MACEs) at 5 years in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Two hundred twenty patients with stable angina (SA) or non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with PCI completed type A behavioral questionnaire, type D personality questionnaire, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Trait Coping Style Questionnaire (TCSQ), and Symptom Checklist 90 (SCL-90) at 3 days after PCI operation. Meanwhile, biomedical markers (cTnI, CK-MB, LDH, LDH1) were assayed. MACEs were monitored over a 5-year follow-up. NSTE-ACS group had higher ratio of type A behavior, type A/D behavior, and higher single factor scores of type A personality and type D personality than control group and SAP group. NSTE-ACS patients had more anxiety, depression, lower level of mental health (P personality and this tendency was associated with myocardial injury. They also had obvious anxiety, depression emotion, and lower level of mental health, which were related to personality and coping style. Type D personality was an independent predictor of adverse events. PMID:27082597

  10. Role of oxidative stress in cardiovascular effects of anemia treatment with erythropoietin in predialysis patients with chronic kidney disease.

    Science.gov (United States)

    Martinez-Vea, Alberto; Marcas, Luis; Bardají, Alfredo; Romeu, Marta; Gutierrez, Cristina; García, Carmen; Compte, Teresa; Nogues, Rosa; Peralta, Carmen; Giralt, Montserrat

    2012-03-01

    Oxidative stress (OS) is involved in left ventricular hypertrophy (LVH). Short-term treatment with erythropoietin (EPO) in chronic kidney disease (CKD) complicated by anemia and LVH is associated with a reduction in left ventricular mass (LVM). We proposed to assess whether the pro-oxidant status of CKD influences these outcomes. Predialysis patients (n = 76) with CKD and hemoglobin (Hb) levels 10% were considered "responders" (n = 25) to treatment and those with LVM change < 10% were considered "non-responders" (n = 24). Measurement of OS included plasma and erythrocyte oxidized (GSSG) and reduced (GSH) glutathione, GSH redox ratio (GSSG/GSH), erythrocyte glutathione peroxidase (GPx) and oxidized LDL (Ox- LDL). 49 patients completed the study. With EPO therapy, mean Hb levels increased from 9.9 ± 0.6 to 12.8 ± 1.5 g/ dl (p < 0.0001) and LVM index decreased from 69.2 ± 17.7 to 64.1 ± 19.6 g/m2.7 (p = 0.01). At 6 months, "non-responders" had higher systolic blood pressure, pulse pressure, GSSG and GSH redox ratio and lower GSH than "responders". In multivariate analysis, and following adjustment for confounding variables, systolic blood pressure and GSH redox ratio independently predicted LVH regression. Blood pressure and plasma GSH redox ratio (a marker of OS) are important predictors of LVH regression in anemic predialysis patients treated with EPO.

  11. Echogenecity of the carotid intima-media complex is related to cardiovascular risk factors, dyslipidemia, oxidative stress and inflammation: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    Science.gov (United States)

    Andersson, Jessika; Sundström, Johan; Gustavsson, Thomas; Hulthe, Johannes; Elmgren, Anders; Zilmer, Kersti; Zilmer, Mihkel; Lind, Lars

    2009-06-01

    Increased carotid artery intima-media thickness (IMT), measured by ultrasound, is related to an increased risk of cardiovascular disease. Since presence of echolucent plaques increases the risk further, we investigated if echogenecity of the carotid intima-media complex is related to markers of cardiovascular risk. Our aim was therefore to investigate if intima-media echogenecity is related to cardiovascular risk factors, or to markers of inflammation and oxidation in an exploratory investigation. The PIVUS cohort study is an observational study of 1016 (509 women and 507 men) randomly chosen individuals aged 70 living in Uppsala, Sweden. Carotid artery ultrasound measurements were performed. IMT and the grey scale median (GSM) value were calculated in the intima-media complex (IM-GSM) in the far wall of the common carotid artery. Traditional risk factors were evaluated together with indices of oxidative stress and inflammation. In the multiple regression analysis, HDL-cholesterol, body mass index, conjugated diens, glutathione, e-selectin and TNF alfa were significantly related to IM-GSM. IMT was independently related to blood pressure, smoking and body mass index. The echolucency of the carotid intima-media was related to several cardiovascular risk factors not related to IMT, such as dyslipidemia, oxidative stress and inflammation. Since the echogenecity of the carotid intima-media complex was related to different risk factors compared to carotid IMT, it is worthwhile to further explore the usefulness of this new marker of the vascular wall.

  12. Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus.

    Science.gov (United States)

    Hage, Fadi G; Heo, Jaekyeong; Franks, Billy; Belardinelli, Luiz; Blackburn, Brent; Wang, Whedy; Iskandrian, Ami E

    2009-04-01

    Adenosine and regadenoson increase heart rate (HR) when used as stress agents to produce coronary hyperemia due to direct sympathetic stimulation. We hypothesized that the HR response will be lower in patients with than in those without diabetes mellitus (DM). We studied the HR response (percentage maximal increase) in 2,000 patients in The ADenoscan Versus regAdenosoN Comparative Evaluation for Myocardial Perfusion Imaging (ADVANCE MPI 1 and 2) Trials with known DM status. There were 643 patients with a history of DM (65.4 +/- 0.4 years, 32% women) and 1,357 patients with no DM (65.5 +/- 0.3 years, 29% women). Compared with non-DM, the DM group had higher HR at baseline (68.4 +/- 0.48 vs 65.2 +/- 0.31 beat/min, P adenosine or regadenoson administration (29.4% +/- 0.64% vs 36.1% +/- 0.54%, P adenosine and regadenoson in patients with DM is blunted. If additional studies confer an agreement between traditional tests for determination of autonomic neuropathy and this measure, then examination of HR response to these agents during myocardial perfusion imaging might add prognostic power.

  13. Carbohydrate management, anaerobic metabolism, and adenosine levels in the armoured catfish, Liposarcus pardalis (castelnau), during hypoxia.

    Science.gov (United States)

    Maccormack, Tyson James; Lewis, Johanne Mari; Almeida-Val, Vera Maria Fonseca; Val, Adalberto Luis; Driedzic, William Robert

    2006-04-01

    The armoured catfish, Liposarcus pardalis, tolerates severe hypoxia at high temperatures. Although this species can breathe air, it also has a strong anaerobic metabolism. We assessed tissue to plasma glucose ratios and glycogen and lactate in a number of tissues under "natural" pond hypoxia, and severe aquarium hypoxia without aerial respiration. Armour lactate content and adenosine in brain and heart were also investigated. During normoxia, tissue to plasma glucose ratios in gill, brain, and heart were close to one. Hypoxia increased plasma glucose and decreased tissue to plasma ratios to less than one, suggesting glucose phosphorylation is activated more than uptake. High normoxic white muscle glucose relative to plasma suggests gluconeogenesis or active glucose uptake. Excess muscle glucose may serve as a metabolic reserve since hypoxia decreased muscle to plasma glucose ratios. Mild pond hypoxia changed glucose management in the absence of lactate accumulation. Lactate was elevated in all tissues except armour following aquarium hypoxia; however, confinement in aquaria increased armour lactate, even under normoxia. A stress-associated acidosis may contribute to armour lactate sequestration. High plasma lactate levels were associated with brain adenosine accumulation. An increase in heart adenosine was triggered by confinement in aquaria, although not by hypoxia alone.

  14. Adenosine monophosphate–activated protein kinase in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Yaeni Kim

    2016-06-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 5′ adenosine monophosphate–activated protein kinase (AMPK, an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

  15. Increased plasma S-adenosylhomocysteine-accelerated atherosclerosis is associated with epigenetic regulation of endoplasmic reticulum stress in apoE-/- mice.

    Science.gov (United States)

    Xiao, Yunjun; Huang, Wei; Zhang, Jinzhou; Peng, Chaoqiong; Xia, Min; Ling, Wenhua

    2015-01-01

    S-Adenosylhomocysteine (SAH) is a better predictor of cardiovascular disease than homocysteine is, and it has been implicated in mediating the pathogenicity of hyperhomocysteinemia in atherosclerosis via an epigenetic mechanism. However, the underlying mechanism remains unclear. Here, we tested the hypothesis whether the effect of SAH on atherosclerosis is involved in epigenetic regulation of endoplasmic reticulum stress. A total of 48 apolipoprotein E-deficient mice at 8 weeks were randomly divided into 4 groups (n=12 for each group). The control group was fed a conventional diet, the adenosine dialdehyde group was fed a diet that was supplemented with the SAH hydrolase inhibitor adenosine dialdehyde, and the other 2 groups were intravenously injected with a retrovirus that expressed either SAH hydrolase short hairpin RNA or scrambled short hairpin RNA semiweekly for 16 weeks. Plasma SAH levels and atherosclerotic lesion size were significantly increased in adenosine dialdehyde and SAH hydrolase short hairpin RNA groups when compared with control group. Expression of endoplasmic reticulum stress markers glucose-regulated protein-78 and CEBP-homologous protein was significantly increased in the mice with elevated plasma SAH levels. Moreover, plasma SAH was negatively associated with a decrease in the expression of trimethylated histone H3 lysine 9 and histone methyltransferases. Chromatin immunoprecipitation assays showed a significant decrease in trimethylated histone H3 lysine 9 occupancy at the glucose-regulated protein-78 and CEBP-homologous protein promoters in mice treated with adenosine dialdehyde and SAH hydrolase short hairpin RNA when compared with control mice. Our results suggest that elevated plasma SAH levels-accelerated atherosclerosis was associated with the activation of endoplasmic reticulum stress via modulation of histone methylation. © 2014 American Heart Association, Inc.

  16. Ticagrelor and Rosuvastatin Have Additive Cardioprotective Effects via Adenosine.

    Science.gov (United States)

    Birnbaum, Yochai; Birnbaum, Gilad D; Birnbaum, Itamar; Nylander, Sven; Ye, Yumei

    2016-12-01

    Ticagrelor inhibits the equilibrative-nucleoside-transporter-1 and thereby, adenosine cell re-uptake. Ticagrelor limits infarct size (IS) in non-diabetic rats and the effect is adenosine-dependent. Statins, via ecto-5'-nucleotidase activation, also increase adenosine levels and limit IS. Ticagrelor and rosuvastatin have additive effects on myocardial adenosine levels, and therefore, on IS and post-reperfusion activation of the NLRP3-inflammasome. Diabetic ZDF rats received via oral gavage; water (control), ticagrelor (150 mg/kg/d), prasugrel (7.5 mg/kg/d), rosuvastatin (5 mg/kg/d), ticagrelor + rosuvastatin and prasugrel + rosuvastatin for 3d. On day 4, rats underwent 30 min coronary artery occlusion and 24 h of reperfusion. Two additional groups received, ticagrelor + rosuvastatin or water in combination with CGS15943 (CGS, an adenosine receptor antagonist, 10 mg/kg i.p. 1 h before ischemia). Both ticagrelor and rosuvastatin increased myocardial adenosine levels with an additive effect of the combination whereas prasugrel had no effect. Similarly, both ticagrelor and rosuvastatin significantly reduced IS with an additive effect of the combination whereas prasugrel had no effect. The effect on IS was adenosine dependent as CGS15943 reversed the effect of ticagrelor + rosuvastatin. The ischemia-reperfusion injury increased myocardial mRNA levels of NLRP3, ASC, IL-1β and IL-6. Ticagrelor and rosuvastatin, but not prasugrel, significantly decreased these pro-inflammatory mediators with a trend to an additive effect of the combination. The combination also increased the levels of anti-inflammatory 15-epilipoxin A4. Ticagrelor and rosuvastatin when given in combination have an additive effect on local myocardial adenosine levels in the setting of ischemia reperfusion. This translates into an additive cardioprotective effect mediated by adenosine-induced effects including downregulation of pro- but upregulation of anti-inflammatory mediators.

  17. Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

    Science.gov (United States)

    Mikhed, Yuliya; Daiber, Andreas; Steven, Sebastian

    2015-01-01

    The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan. PMID:26184181

  18. Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

    Directory of Open Access Journals (Sweden)

    Yuliya Mikhed

    2015-07-01

    Full Text Available The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS leads to oxidative stress, loss of nitric oxide (•NO signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging than for the maximal lifespan.

  19. Adenosine through the A2A adenosine receptor increases IL-1β in the brain contributing to anxiety

    Science.gov (United States)

    Chiu, Gabriel S.; Darmody, Patrick T.; Walsh, John P.; Moon, Morgan L.; Kwakwa, Kristin A.; Bray, Julie K.; McCusker, Robert H.; Freund, Gregory G.

    2014-01-01

    Anxiety is one of the most commonly reported psychiatric conditions, but its pathogenesis is poorly understood. Ailments associated with activation of the innate immune system, however, are increasingly linked to anxiety disorders. In adult male mice, we found that adenosine doubled caspase-1 activity in brain by a pathway reliant on ATP-sensitive potassium (KATP) channels, protein kinase A (PKA) and the A2A adenosine receptor (AR). In addition, adenosine-dependent activation of caspase-1 increased interleukin (IL)-1β in the brain by two-fold. Peripheral administration of adenosine in wild-type (WT) mice led to a 2.3-fold increase in caspase-1 activity in the amygdala and to a 33% and 42% reduction in spontaneous locomotor activity and food intake, respectively, that were not observed in caspase-1 knockout (KO), IL-1 receptor type 1 (IL-1R1) KO and A2A AR KO mice or in mice administered a caspase-1 inhibitor centrally. Finally, adenosine administration increased anxiety-like behaviors in WT mice by 28% in the open field test and by 55% in the elevated zero-maze. Caspase-1 KO mice, IL-1R1 KO mice, A2A AR KO mice and WT mice treated with the KATP channel blocker, glyburide, were resistant to adenosine-induced anxiety-like behaviors. Thus, our results indicate that adenosine can act as an anxiogenic by activating caspase-1 and increasing IL-1β in the brain. PMID:24907587

  20. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

    Science.gov (United States)

    Mi, Tiejuan; Abbasi, Shahrzad; Zhang, Hong; Uray, Karen; Chunn, Janci L.; Xia, Ling Wei; Molina, Jose G.; Weisbrodt, Norman W.; Kellems, Rodney E.; Blackburn, Michael R.; Xia, Yang

    2008-01-01

    Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A2B adenosine receptor–mediated (A2BR-mediated) cAMP and cGMP induction was required for elevated adenosine–induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A2BR activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada–/– and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A2BR activation may prove beneficial in the treatment of this disorder. PMID:18340377

  1. Cardiovascular Deconditioning

    Science.gov (United States)

    Charles, John B.; Fritsch-Yelle, Janice M.; Whitson, Peggy A.; Wood, Margie L.; Brown, Troy E.; Fortner, G. William

    1999-01-01

    Spaceflight causes adaptive changes in cardiovascular function that may deleteriously affect crew health and safety. Over the last three decades, symptoms of cardiovascular changes have ranged from postflight orthostatic tachycardia and decreased exercise capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented symptom of cardiovascular dysfunction, postflight orthostatic intolerance, has affected a significant percentage of U.S. Space Shuttle astronauts. Problems of cardiovascular dysfunction associated with spaceflight are a concern to NASA. This has been particularly true during Shuttle flights where the primary concern is the crew's physical health, including the pilot's ability to land the Orbiter, and the crew's ability to quickly egress and move to safety should a dangerous condition arise. The study of astronauts during Shuttle activities is inherently more difficult than most human research. Consequently, sample sizes have been small and results have lacked consistency. Before the Extended Duration Orbiter Medical Project (EDOMP), there was a lack of normative data on changes in cardiovascular parameters during and after spaceflight. The EDOMP for the first time allowed studies on a large enough number of subjects to overcome some of these problems. There were three primary goals of the Cardiovascular EDOMP studies. The first was to establish, through descriptive studies, a normative data base of cardiovascular changes attributable to spaceflight. The second goal was to determine mechanisms of cardiovascular changes resulting from spaceflight (particularly orthostatic hypotension and cardiac rhythm disturbances). The third was to evaluate possible countermeasures. The Cardiovascular EDOMP studies involved parallel descriptive, mechanistic, and countermeasure evaluations.

  2. Interrelationships Among Flow-Mediated Vasodilation, Nitroglycerine-Induced Vasodilation, Baseline Brachial Artery Diameter, Hyperemic Shear Stress, and Cardiovascular Risk Factors.

    Science.gov (United States)

    Maruhashi, Tatsuya; Iwamoto, Yumiko; Kajikawa, Masato; Oda, Nozomu; Kishimoto, Shinji; Matsui, Shogo; Hashimoto, Haruki; Aibara, Yoshiki; Yusoff, Farina Mohamad; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Noma, Kensuke; Nakashima, Ayumu; Goto, Chikara; Hida, Eisuke; Higashi, Yukihito

    2017-12-29

    Flow-mediated vasodilation (FMD) of the brachial artery has been used for the assessment of endothelial function. Considering the mechanism underlying the vasodilatory response of the brachial artery to reactive hyperemia, hyperemic shear stress (HSS), a stimulus for FMD; nitroglycerine-induced vasodilation (NID), an index of endothelium-independent vasodilation; and baseline brachial artery diameter (BAD) are also involved in vasodilatory response. The purpose of this study was to investigate the interrelationships among FMD, HSS, NID, baseline BAD, and cardiovascular risk factors. We measured FMD, HSS, NID, and baseline BAD simultaneously in 1033 participants (633 men and 400 women; mean age: 58.6±17.0 years). Framingham risk score was negatively correlated with FMD, HSS, and NID and was positively correlated with baseline BAD. HSS and NID were positively correlated with FMD, and baseline BAD was negatively correlated with FMD. In participants with normal NID, FMD was correlated with HSS, NID, and baseline BAD, all of which were independent variables of FMD in multivariate analysis. In participants with impaired NID, FMD was correlated with NID and baseline BAD, both of which were independent variables of FMD in multivariate analysis, but there was no association between FMD and HSS. NID and baseline BAD were independent variables of FMD regardless of the status of endothelium-independent vasodilation, whereas there was a significant association between FMD and HSS in participants with normal NID but not in those with impaired NID. The influence of HSS on FMD seems to be dependent on the status of endothelium-independent vasodilation. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  3. Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity.

    Directory of Open Access Journals (Sweden)

    Gustavo S Masson

    Full Text Available Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR. Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training and sedentary (S SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC, NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR, p38 MAPK and ERK1/2 expression (Western blotting, NF-κB content (electrophoretic mobility shift assay and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control showed increased mean arterial pressure (172±3 mmHg, pressure variability and heart rate (358±7 b/min, decreased baroreflex sensitivity and heart rate variability, increased p47phox and reactive oxygen species production, elevated NF-κB activity and increased TNF-α and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04±0.31 vs. 2.31±0.19 b/min/mmHg in SHR-S. These responses were followed by increased vagal component of heart rate variability (1.9-fold and resting bradycardia (-13% at the 4th week, and, by reduced vasomotor component of pressure variability (-28% and decreased mean arterial pressure (-7% only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro

  4. Theacrine: A purine alkaloid from Camellia assamica var. kucha with a hypnotic property via the adenosine system.

    Science.gov (United States)

    Qiao, Haoyi; Ye, Xiansheng; Bai, Xiaoyu; He, Jun; Li, Tingli; Zhang, Jia; Zhang, Weiku; Xu, Jiekun

    2017-10-17

    Theacrine (l,3,7,9-tetramethyluric acid), a purine alkaloid from Camellia assamica var. kucha, has diverse pharmacological properties, including sedative and hypnotic activities, anti-inflammatory and analgesic activities, antidepressant effects, and a protective effect against stress-provoked liver damage. The present study aims to investigate the possible mechanism of the hypnotic activity of theacrine. The results revealed that theacrine significantly enhanced pentobarbital-induced sleep at a dose of 3.0mg/kg (i.g.) in mice. Sleep parameter analysis by EEG and EMG showed that theacrine obviously shortened wake time and increased NREM sleep time and that theacrine almost had no effect on REM sleep. Meanwhile, theacrine markedly attenuated caffeine (a nonselective antagonist of adenosine receptor)-induced insomnia. In pretreatment with the adenosine A 1 receptor antagonist DPCPX and the A 2A receptor antagonist SCH 58261, theacrine significantly reversed the decrease in sleeping time in pentobarbital-treated mice. In addition, theacrine also markedly increased the adenosine content in the hippocampus of rats. These results suggested that theacrine might mediate the adenosine system to augment pentobarbital-induced sleep. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Inhibition of uptake of adenosine into human blood platelets

    NARCIS (Netherlands)

    Lips, J.P.M.; Sixma, J.J.; Trieschnigg, A.C.

    1980-01-01

    Adenosine transport into human blood platelets is mediated by two independent systems with different affinities. Both systems transport only purine nucleosides and no pyrimidine nucleosides. In experiments with differently substituted purine nucleosides, purines and analogues, differences in carrier

  6. Adenosin deaminasa como molecula coestimuladora y marcador de inmunidad celular

    National Research Council Canada - National Science Library

    Perez-Aguilar, Mary Carmen; Goncalves, Loredana; Ibarra, Alba; Bonfante-Cabarcas, Rafael

    2010-01-01

    La adenosin deaminasa (ADA), es una enzima del metabolismo de las purinas que ha sido objeto de mucho interes debido a que el defecto congenito de esta enzima causa el sindrome de inmunodeficiencia combinada severa...

  7. Addition of adenosine to hyperbaric bupivacaine in spinal ...

    African Journals Online (AJOL)

    2011-04-17

    effects, ... efficacy of adenosine on postoperative pain when administered with hyperbaric bupivacaine. The aim of our present study ... lower back, or ingestion of methylxanthine-containing food or beverages within 12 hours of ...

  8. Adenosine-deaminase (ADA activity in Psoriasis (A Preliminary Study

    Directory of Open Access Journals (Sweden)

    S D Chaudhry

    1988-01-01

    Full Text Available Study of adenosine-deaminase activity ′in 23 patients hav-mg psoriasis compared with an equal number of healthy controls revealed significantly high ADA-activity in the psotiatic patients.

  9. Vasoconstrictor and vasodilator effects of adenosine in the kidney

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Schnermann, Jurgen

    2003-01-01

    Adenosine is an ATP breakdown product that in most vessels causes vasodilatation and that contributes to the metabolic control of organ perfusion, i.e., to the match between oxygen demand and oxygen delivery. In the renal vasculature, in contrast, adenosine can produce vasoconstriction, a response...... that has been suggested to be an organ-specific version of metabolic control designed to restrict organ perfusion when transport work increases. However, the vasoconstriction elicited by an intravenous infusion of adenosine is only short lasting, being replaced within 1-2 min by vasodilatation. It appears...... that the steady-state response to the increase of plasma adenosine levels above normal resulting from the infusion is global renal vasorelaxation that is the result of A2AR activation in most parts of the renal vasculature, including larger renal arteries, juxtamedullary afferent arterioles, efferent arterioles...

  10. Stress

    DEFF Research Database (Denmark)

    Keller, Hanne Dauer

    2015-01-01

    Kapitlet handler om stress som følelse, og det trækker primært på de få kvalitative undersøgelser, der er lavet af stressforløb.......Kapitlet handler om stress som følelse, og det trækker primært på de få kvalitative undersøgelser, der er lavet af stressforløb....

  11. Effects of Concurrent Depressive Symptoms and Perceived Stress on Cardiovascular Risk in Low- and High-Income Participants: Findings From the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study.

    Science.gov (United States)

    Sumner, Jennifer A; Khodneva, Yulia; Muntner, Paul; Redmond, Nicole; Lewis, Marquita W; Davidson, Karina W; Edmondson, Donald; Richman, Joshua; Safford, Monika M

    2016-10-10

    Psychosocial risk for cardiovascular disease (CVD) may be especially deleterious in persons with low socioeconomic status. Most work has focused on psychosocial factors individually, but emerging research suggests that the confluence of psychosocial risk may be particularly harmful. Using data from the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study, we examined associations among depressive symptoms and stress, alone and in combination, and incident CVD and all-cause mortality as a function of socioeconomic status. At baseline, 22 658 participants without a history of CVD (58.8% female, 41.7% black, mean age 63.9±9.3 years) reported on depressive symptoms, stress, annual household income, and education. Participants were classified into 1 of 3 psychosocial risk groups at baseline: (1) neither depressive symptoms nor stress, (2) either depressive symptoms or stress, or (3) both depressive symptoms and stress. Cox proportional hazards models were used to predict physician-adjudicated incident total CVD events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and all-cause mortality over a median of 7.0 years (interquartile range 5.4-8.3 years) of follow-up. In fully adjusted models, participants with both depressive symptoms and stress had the greatest elevation in risk of developing total CVD (hazard ratio 1.48, 95% CI 1.21-1.81) and all-cause mortality (hazard ratio 1.33, 95% CI 1.13-1.56) but only for those with low income (symptoms and stress in low-income persons may help identify those at increased risk of incident CVD and mortality. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  12. Feasibility of perfusion cardiovascular magnetic resonance in paediatric patients

    Directory of Open Access Journals (Sweden)

    Kellenberger Christian

    2009-01-01

    Full Text Available Abstract Aims As coronary artery disease may also occur during childhood in some specific conditions, we sought to assess the feasibility and accuracy of perfusion cardiovascular magnetic resonance (CMR in paediatric patients. Methods and results First-pass perfusion CMR studies were performed under pharmacological stress with adenosine and by using a hybrid echo-planar pulse sequence with slice-selective saturation recovery preparation. Fifty-six perfusion CMR examinations were performed in 47 patients. The median age was 12 years (1 month-18 years, and weight 42.8 kg (2.6-82 kg. General anaesthesia was required in 18 patients. Mean examination time was 67 ± 19 min. Diagnostic image quality was obtained in 54/56 examinations. In 23 cases the acquisition parameters were adapted to patient's size. Perfusion CMR was abnormal in 16 examinations. The perfusion defects affected the territory of the left anterior descending coronary artery in 11, of the right coronary artery in 3, and of the circumflex coronary artery in 2 cases. Compared to coronary angiography, perfusion CMR showed a sensitivity of 87% (CI 52-97% and a specificity of 95% (CI 79-99%. Conclusion In children, perfusion CMR is feasible and accurate. In very young children (less than 1 year old, diagnostic image quality may be limited.

  13. Mitochondria and Cardiovascular Aging

    Science.gov (United States)

    Dai, Dao-Fu; Ungvari, Zoltan

    2013-01-01

    Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

  14. Cell Type-Specific Effects of Adenosine on Cortical Neurons

    Science.gov (United States)

    van Aerde, Karlijn I.; Qi, Guanxiao; Feldmeyer, Dirk

    2015-01-01

    The neuromodulator adenosine is widely considered to be a key regulator of sleep homeostasis and an indicator of sleep need. Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date. To that purpose, we performed in vitro whole-cell patch-clamp recordings and biocytin staining of pyramidal neurons and interneurons throughout all layers of rat prefrontal and somatosensory cortex, followed by morphological analysis. We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location. Interneurons and pyramidal neurons in layer 2 and a subpopulation of layer 3 pyramidal neurons that displayed regular spiking were insensitive to adenosine application, whereas other pyramidal cells in layers 3–6 were hyperpolarized (range 1.2–10.8 mV). Broad tufted pyramidal neurons with little spike adaptation showed a small adenosine response, whereas slender tufted pyramidal neurons with substantial adaptation showed a bigger response. These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening. PMID:24108800

  15. Isolation and characterization of coronary endothelial and smooth muscle cells from A1 adenosine receptor-knockout mice

    OpenAIRE

    Teng, Bunyen; Ansari, Habib R.; Oldenburg, Peter J.; Schnermann, J.; Mustafa, S. Jamal

    2005-01-01

    Mice have been used widely in in vivo and in vitro cardiovascular research. The availability of knockout mice provides further clues to the physiological significance of specific receptor subtypes. Adenosine A1 receptor (A1AR)-knockout (A1KO) mice and their wild-type (A1WT) controls were employed in this investigation. The heart and aortic arch were carefully removed and retroinfused with enzyme solution (1 mg/ml collagenase type I, 0.5 mg/ml soybean trypsin inhibitor, 3% BSA, and 2% antibiot...

  16. Adenosine myocardial perfusion single-photon emission computed tomography in women compared with men. Impact of diabetes mellitus on incremental prognostic value and effect on patient management.

    Science.gov (United States)

    Berman, Daniel S; Kang, Xingping; Hayes, Sean W; Friedman, John D; Cohen, Ishac; Abidov, Aiden; Shaw, Leslee J; Amanullah, Aman M; Germano, Guido; Hachamovitch, Rory

    2003-04-02

    This study was designed to assess the incremental prognostic value of adenosine stress myocardial perfusion single-photon emission computed tomography (MPS) in women versus men, and to explore the prognostic impact of diabetes mellitus. Limited data are available regarding the incremental value of adenosine stress MPS for the prediction of cardiac death in women versus men and the impact of diabetes mellitus on post-adenosine MPS outcomes. Of 6,173 consecutive patients who underwent rest thallium-201/adenosine technetium-99m sestamibi MPS, 254 (4.1%) were lost to follow-up, and 586 with early revascularization women and 2,677 men. Women had significantly smaller adenosine stress, rest, and reversible defects than men. During 27.0 +/- 8.8 month follow-up, cardiac death rates were lower in women than men (2.0%/year vs. 2.7%/year, respectively, p men and women as a function of MPS results. Multivariable models revealed that MPS results provided incremental prognostic value over pre-scan data for the prediction of cardiac death in both genders. Also, while comparative unadjusted rates of early (women (p men and women. Importantly, diabetic women had a significantly greater risk of cardiac death compared with other patients. Also, after risk adjustment, patients with insulin-dependent diabetes mellitus (IDDM) had higher risk of cardiac death for any MPS result than patients with non-insulin-dependent diabetes mellitus. The findings suggest that adenosine MPS has comparable incremental value for prediction of cardiac death in women and men and that MPS is appropriately influencing subsequent invasive management decisions in both genders. Diabetic women and patients with IDDM appear to have greater risk of cardiac death than other patients for any MPS result.

  17. Adenosine A2B receptor-mediated leukemia inhibitory factor release from astrocytes protects cortical neurons against excitotoxicity

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    Moidunny Shamsudheen

    2012-08-01

    Full Text Available Abstract Background Neuroprotective and neurotrophic properties of leukemia inhibitory factor (LIF have been widely reported. In the central nervous system (CNS, astrocytes are the major source for LIF, expression of which is enhanced following disturbances leading to neuronal damage. How astrocytic LIF expression is regulated, however, has remained an unanswered question. Since neuronal stress is associated with production of extracellular adenosine, we investigated whether LIF expression in astrocytes was mediated through adenosine receptor signaling. Methods Mouse cortical neuronal and astrocyte cultures from wild-type and adenosine A2B receptor knock-out animals, as well as adenosine receptor agonists/antagonists and various enzymatic inhibitors, were used to study LIF expression and release in astrocytes. When needed, a one-way analysis of variance (ANOVA followed by Bonferroni post-hoc test was used for statistical analysis. Results We show here that glutamate-stressed cortical neurons induce LIF expression through activation of adenosine A2B receptor subtype in cultured astrocytes and require signaling of protein kinase C (PKC, mitogen-activated protein kinases (MAPKs: p38 and ERK1/2, and the nuclear transcription factor (NF-κB. Moreover, LIF concentration in the supernatant in response to 5′-N-ethylcarboxamide (NECA stimulation was directly correlated to de novo protein synthesis, suggesting that LIF release did not occur through a regulated release pathway. Immunocytochemistry experiments show that LIF-containing vesicles co-localize with clathrin and Rab11, but not with pHogrin, Chromogranin (CgA and CgB, suggesting that LIF might be secreted through recycling endosomes. We further show that pre-treatment with supernatants from NECA-treated astrocytes increased survival of cultured cortical neurons against glutamate, which was absent when the supernatants were pre-treated with an anti-LIF neutralizing antibody. Conclusions

  18. The 1976C>T polymorphism in the adenosine A2A receptor gene does not affect the vasodilator response to adenosine in humans in vivo

    NARCIS (Netherlands)

    Riksen, N.P.; Franke, B.; Broek, P. van den; Smits, P.; Rongen, G.A.

    2007-01-01

    The 1976C>T polymorphism in the adenosine A2A receptor gene (ADORA2A) modulates the psychological response to administration of the adenosine receptor antagonist caffeine. We quantified the vascular response to adenosine and caffeine to determine the relevance of this variant allele in the

  19. Stress

    OpenAIRE

    Jensen, Line Skov; Lova, Lotte; Hansen, Zandra Kulikovsky; Schønemann, Emilie; Larsen, Line Lyngby; Colberg Olsen, Maria Sophia; Juhl, Nadja; Magnussen, Bogi Roin

    2012-01-01

    Stress er en tilstand som er meget omdiskuteret i samfundet, og dette besværliggør i en vis grad konkretiseringen af mulige løsningsforslag i bestræbelsen på at forebygge den såkaldte folkesygdom. Hovedkonklusionen er, at selv om der bliver gjort meget for at forebygge, er der ikke meget der aktivt kan sættes i værk for at reducere antallet af stressramte, før en fælles forståelse af stressårsager og effektiv stresshåndtering er fremlagt. Problemformuleringen er besvaret gennem en undersø...

  20. Adenosine deaminase, xanthine oxidase, uric acid, and nitric oxide metabolism in the pathogenesis of disease in patients with colon polyps

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    Rafet Mete

    2014-03-01

    Full Text Available Objective: Protrusion of colonic mucosa to the lumen is called polyp. Since adenomatous polyps are neoplastic polyps, determining the factors contributing to the pathogenesis of the disease would be helpful in terms of reducing mortality and morbidity. Variety studies have showed that increased oxidative stress might play an important role in carcinogenesis. The aim of this study was to investigate the relationship between adenosine deaminase, xanthine oxidase nitric oxide, uric acid levels and oxidative stress in patients with colonic polyps to help the elucidation of pathophysiology of the disease. Methods: The study was conducted at Gastroenterology Clinics of Namik Kemal University Training and Research Hospital. Thirty-five subjects who underwent colonoscopy because of any gastrointestinal symptom and whose pathologic evaluation of colonoscopic biopsy revealed adenomatous polyps were enrolled as patient group. Control group was consisted of 36 healthy subjects. Uric acid was measured by an autoanalyzer using photometric method. Adenosine deaminase, xanthine oxidase, and nitric oxide were measured manually using a spectrophotometric method. Results: Xanthine oxidase, uric acid, and nitric oxide levels were found to be significantly higher in patients with colonic polyp compared that of the healthy controls. (p = 0.007; p = 0.02; p<0.001, respectively.Although adenosine deaminase levels were significantly higher in patient group, the difference was not statistically significant (p = 0.07 Conclusion: Increased serum levels of adenosine deaminase, xanthine oxidase, nitric oxide, and uric acid levels in patients with colonic adenomatous polyp may indicate the increased oxidative stress and the oxidative impairment of the colonic mucosa which may play an important role in the pathophysiology of the disease. Further studies would be useful to assess antioxidant treatment options in these patients.

  1. Adenosine Receptors As Drug Targets for Treatment of Pulmonary Arterial Hypertension

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    Allan K. N. Alencar

    2017-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a clinical condition characterized by pulmonary arterial remodeling and vasoconstriction, which promote chronic vessel obstruction and elevation of pulmonary vascular resistance. Long-term right ventricular (RV overload leads to RV dysfunction and failure, which are the main determinants of life expectancy in PAH subjects. Therapeutic options for PAH remain limited, despite the introduction of prostacyclin analogs, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and soluble guanylyl cyclase stimulators within the last 15 years. Through addressing the pulmonary endothelial and smooth muscle cell dysfunctions associated with PAH, these interventions delay disease progression but do not offer a cure. Emerging approaches to improve treatment efficacy have focused on beneficial actions to both the pulmonary vasculature and myocardium, and several new targets have been investigated and validated in experimental PAH models. Herein, we review the effects of adenosine and adenosine receptors (A1, A2A, A2B, and A3 on the cardiovascular system, focusing on the A2A receptor as a pharmacological target. This receptor induces pulmonary vascular and heart protection in experimental models, specifically models of PAH. Targeting the A2A receptor could potentially serve as a novel and efficient approach for treating PAH and concomitant RV failure. A2A receptor activation induces pulmonary endothelial nitric oxide synthesis, smooth muscle cell hyperpolarization, and vasodilation, with important antiproliferative activities through the inhibition of collagen deposition and vessel wall remodeling in the pulmonary arterioles. The pleiotropic potential of A2A receptor activation is highlighted by its additional expression in the heart tissue, where it participates in the regulation of intracellular calcium handling and maintenance of heart chamber structure and function. In this way, the activation of A2A

  2. Intracellular ATP concentration contributes to the cytotoxic and cytoprotective effects of adenosine.

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    Shujue Li

    Full Text Available Extracellular adenosine (ADE interacts with cells by two pathways: by activating cell surface receptors at nanomolar/micromolar concentrations; and by interfering with the homeostasis of the intracellular nucleotide pool at millimolar concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the underlying mechanisms remain unclear. In the present study, the effects of adenosine-mediated ATP on cell viability were investigated. Adenosine treatment was found to be cytoprotective in the low intracellular ATP state, but cytotoxic under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection rely on adenosine-derived ATP formation, but not via the adenosine receptor pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP generation. These data provide a new pathway by which adenosine exerts dual biological effects on cell viability, suggesting an important role for adenosine as an ATP precursor besides the adenosine receptor pathway.

  3. Role of A3 adenosine receptor in diabetic neuropathy.

    Science.gov (United States)

    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Skeletal muscle expresses the extracellular cyclic AMP–adenosine pathway

    Science.gov (United States)

    Chiavegatti, T; Costa, V L; Araújo, M S; Godinho, R O

    2007-01-01

    Background and purpose: cAMP is a key intracellular signalling molecule that regulates multiple processes of the vertebrate skeletal muscle. We have shown that cAMP can be actively pumped out from the skeletal muscle cell. Since in other tissues, cAMP efflux had been associated with extracellular generation of adenosine, in the present study we have assessed the fate of interstitial cAMP and the existence of an extracellular cAMP-adenosine signalling pathway in skeletal muscle. Experimental approach: cAMP efflux and/or its extracellular degradation were analysed by incubating rat cultured skeletal muscle with exogenous cAMP, forskolin or isoprenaline. cAMP and its metabolites were quantified by radioassay or HPLC, respectively. Key results: Incubation of cells with exogenous cAMP was followed by interstitial accumulation of 5′-AMP and adenosine, a phenomenon inhibited by selective inhibitors of ecto-phosphodiesterase (DPSPX) and ecto-nucleotidase (AMPCP). Activation of adenylyl cyclase (AC) in cultured cells with forskolin or isoprenaline increased cAMP efflux and extracellular generation of 5′-AMP and adenosine. Extracellular cAMP-adenosine pathway was also observed after direct and receptor-dependent stimulation of AC in rat extensor muscle ex vivo. These events were attenuated by probenecid, an inhibitor of ATP binding cassette family transporters. Conclusions and implications: Our results show the existence of an extracellular biochemical cascade that converts cAMP into adenosine. The functional relevance of this extracellular signalling system may involve a feedback modulation of cellular response initiated by several G protein-coupled receptor ligands, amplifying cAMP influence to a paracrine mode, through its metabolite, adenosine. PMID:18157164

  5. Adenosinergic regulation of the cardiovascular system in the red-eared slider Trachemys scripta.

    Science.gov (United States)

    Joyce, William; Wang, Tobias

    2014-08-01

    Few studies have investigated adenosinergic regulation of the cardiovascular system in reptiles. The haemodynamic effect of a bolus intra-arterial adenosine injection (2.5 μM kg⁻¹) was investigated in nine anaesthetised red-eared sliders (Trachemys scripta). Adenosine caused a transient bradycardia, which was accompanied by systemic vasodilatation as evidenced by an increase in systemic flow and a decrease in systemic pressure. Meanwhile, pulmonary flow fell significantly. Both the bradycardia and increase in systemic conductance were significantly attenuated by theophylline (4 mg kg⁻¹), demonstrating an involvement of P₁ receptors. These results suggest that adenosine is likely to play a significant role in reptile cardiovascular physiology. In turtles specifically, adenosinergic regulation may be particularly relevant during periods of apnoea. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Increased Levels of Oxidative Stress Markers, Soluble CD40 Ligand, and Carotid Intima-Media Thickness Reflect Acceleration of Atherosclerosis in Male Patients with Ankylosing Spondylitis in Active Phase and without the Classical Cardiovascular Risk Factors

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    Agata Stanek

    2017-01-01

    Full Text Available Objective. The primary aim of the study was to assess levels of oxidative stress markers, soluble CD40 ligand (sCD40L, serum pregnancy-associated plasma protein-A (PAPP-A, and placental growth factor (PlGF as well as carotid intima-media thickness (IMT in patients with ankylosing spondylitis (AS with active phase without concomitant classical cardiovascular risk factors. Material and methods. The observational study involved 96 male subjects: 48 AS patients and 48 healthy ones, who did not differ significantly regarding age, BMI, comorbid disorders, and distribution of classical cardiovascular risk factors. In both groups, we estimated levels of oxidative stress markers, lipid profile, and inflammation parameters as well as sCD40L, serum PAPP-A, and PlGF. In addition, we estimated carotid IMT in each subject. Results. The study showed that markers of oxidative stress, lipid profile, and inflammation, as well as sCD40L, PlGF, and IMT, were significantly higher in the AS group compared to the healthy group. Conclusion. Our results demonstrate that ankylosing spondylitis may be associated with increased risk for atherosclerosis.

  7. Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging integrated ADVANCE-MPI trial results.

    Science.gov (United States)

    Cerqueira, Manuel D; Nguyen, Patricia; Staehr, Peter; Underwood, S Richard; Iskandrian, Ami E

    2008-05-01

    To compare the effects of age, gender, body mass index, and diabetes on the safety and efficacy of regadenoson stress myocardial perfusion imaging, and to assess the noninferiority of regadenoson to adenosine for the detection of reversible myocardial perfusion defects. Previous reports have shown that a fixed unit bolus of regadenoson is safe and noninferior to adenosine for the detection of reversible perfusion defects by radionuclide imaging. Using a database of 2,015 patients, we evaluated the effects of age, gender, body mass index, and diabetes on the safety and efficacy of regadenoson compared to adenosine. For detection of ischemia relative to adenosine, noninferiority was demonstrated for all patients (agreement rate difference 0%, 95% CI -6.2% to +6.8%). The average agreement rate between adenosine-adenosine and adenosine-regadenoson were 0.62 +/- 0.03 and 0.63 +/- 0.02. Detection of ischemia was also comparable in specific subgroups. Agreement was less for both agents in women versus men with moderate and large areas of ischemia. Compared to adenosine, regadenoson had a lower combined symptom score and less chest pain, flushing, and throat, neck, or jaw pain, but more headache and gastrointestinal discomfort. This was true in nearly all subgroups. Regadenoson patients reported feeling more comfortable (1.7 +/- .02 vs. 1.9 +/- 0.03, p Regadenoson can be safely administered as a fixed unit bolus and is as efficacious as adenosine in detecting ischemia regardless of age, gender, body mass index, and diabetes. Regadenoson is better tolerated overall and across various subgroups.

  8. Nrf2 and Cardiovascular Defense

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    Reuben Howden

    2013-01-01

    Full Text Available The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E 2-related factor 2 (Nrf2, regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis. The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  9. Nrf2 and cardiovascular defense.

    Science.gov (United States)

    Howden, Reuben

    2013-01-01

    The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  10. Adenosine hypothesis of schizophrenia –opportunities for pharmacotherapy

    Science.gov (United States)

    Boison, Detlev; Singer, Philipp; Shen, Hai-Ying; Feldon, Joram; Yee, Benjamin K.

    2011-01-01

    Pharmacotherapy of schizophrenia based on the dopamine hypothesis remains unsatisfactory for the negative and cognitive symptoms of the disease. Enhancing N-methyl-d-aspartate receptors (NMDAR) function is expected to alleviate such persistent symptoms, but successful development of novel clinically effective compounds remains challenging. Adenosine is a homeostatic bioenergetic network modulator that is able to affect complex networks synergistically at different levels (receptor dependent pathways, biochemistry, bioenergetics, and epigenetics). By affecting brain dopamine and glutamate activities it represents a promising candidate for restoring the functional imbalance in these neurotransmitter systems believed to underlie the genesis of schizophrenia symptoms, as well as restoring homeostasis of bioenergetics. Suggestion of an adenosine hypothesis of schizophrenia further posits that adenosinergic dysfunction might contribute to the emergence of multiple neurotransmitter dysfunctionscharacteristic of schizophrenia via diverse mechanisms. Given the importance of adenosine in early brain development and regulation of brain immune response, it also bears direct relevance to the aetiology of schizophrenia. Here, we provide an overview of the rationale and evidence in support of the therapeutic potential of multiple adenosinergic targets, including the high-affinity adenosine receptors (A1R and A2AR), and the regulatory enzyme adenosine kinase (ADK). Key preliminary clinical data and preclinical findings are reviewed. PMID:21315743

  11. [Hypocretins and adenosine in the regulation of sleep].

    Science.gov (United States)

    Salín-Pascual, R J

    To review the recent discovery of hypocretins (orexins) and their link to the pathophysiology of narcolepsy and the role of adenosine in the integration of brain metabolism and sleep. The importance of the functions carried out by the hypothalamus in the regulation of sleep and the waking state has been consolidated by the discovery of hypocretins and the role played by cerebral adenosine. Hypocretins are two peptides made up of 33 and 28 amino acids whose neurons are located predominantly in the lateral hypothalamus and surrounding regions. In the Doberman canine narcolepsy model, in which this disease is presented with an autosomal recessive pattern, a mutation was detected in one of the receptors involved in the hypocretin system, namely the hypocretin-2 receptor. Failures in the hypocretin system have been confirmed as a key factor in narcolepsy by other findings in laboratory animals and humans. Adenosine, on the other hand, is accumulated during the waking state as a result of neuronal metabolism and this in turn is related to drowsiness. Sleep episodes lower the levels of this substance in the brain. Adenosine receptor antagonists increase wakefulness (e.g. caffeine), while the agonists promote slow-wave sleep. Hypocretins and adenosine from the hypothalamus perform functions involving the regulation of sleep and wakefulness. Understanding these two systems can have repercussions on clinical problems such as insomnia, hypersomnia and other neuropsychiatric disorders.

  12. Regioselective 1-N-Alkylation and Rearrangement of Adenosine Derivatives.

    Science.gov (United States)

    Oslovsky, Vladimir E; Drenichev, Mikhail S; Mikhailov, Sergey N

    2015-01-01

    Several methods for the preparation of some N(6)-substituted adenosines based on selective 1-N-alkylation with subsequent Dimroth rearrangement were developed. The proposed methods seem to be effective for the preparation of natural N(6)-isopentenyl- and N(6)-benzyladenosines, which are known to possess pronounced biological activities. Direct 1-N-alkylation of 2',3',5'-tri-O-acetyladenosine and 3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides in N,N-dimethylformamide (DMF) in the presence of BaCO3 and KI gave 1-N-substituted derivatives with quantitative yields, whereas 1-N-alkylation of adenosine was accompanied by significant O-alkylation. Moreover, the reaction of trimethylsilyl derivatives of N(6)-acetyl-2',3',5'-tri-O-acetyladenosine and N(6)-acetyl-3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides leads to the formation of the stable 1-N-substituted adenosines. Dimroth rearrangement of 1-N-substituted adenosines in aqueous ammonia yields pure N(6)-substituted adenosines.

  13. Common genetic polymorphisms of adenosine A2A receptor do not influence response to regadenoson.

    Science.gov (United States)

    Berlacher, Mark; Mastouri, Ronald; Philips, Santosh; Skaar, Todd C; Kreutz, Rolf P

    2017-04-01

    Hemodynamic response to regadenoson varies greatly, and underlying mechanisms for variability are poorly understood. We hypothesized that five common variants of adenosine A2A receptor (ADORA2A) are associated with altered response to regadenoson. Consecutive subjects (n = 357) undergoing resting regadenoson nuclear stress imaging were enrolled. Genotyping was performed using Taqman-based assays for rs5751862, rs2298383, rs3761422, rs2267076 and rs5751876. There was no significant difference in heart rate or blood pressure between different genotypes following regadenoson administration. There was also no significant difference in myocardial ischemia detected by nuclear perfusion imaging as defined by summed difference score, or in self-reported side effects among the genotypes tested. The common A2A variants studied are not associated with variability in hemodynamic response to regadenoson or variability in detection of ischemia with nuclear perfusion stress imaging.

  14. Reduction in hypercholesterolemia and risk of cardiovascular diseases by mixtures of plant food extract: a study on plasma lipid profile, oxidative stress and testosterone in rats

    Directory of Open Access Journals (Sweden)

    Mohamed, Doha A.

    2010-12-01

    reduction in plasm