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Sample records for cardiac sympathetic activity

  1. Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension

    NARCIS (Netherlands)

    van Brussel, Peter M.; Eeftinck Schattenkerk, Daan W.; Dobrowolski, Linn C.; de Winter, Robbert J.; Reekers, Jim A.; Verberne, Hein J.; Vogt, Liffert; van den Born, Bert-Jan H.

    2016-01-01

    Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity

  2. Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity.

    Science.gov (United States)

    Holbein, Walter W; Toney, Glenn M

    2013-06-15

    Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller (P analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.

  3. Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

    Science.gov (United States)

    Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

    2014-01-01

    Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic

  4. A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia.

    Science.gov (United States)

    Fu, Liang-Wu; Longhurst, John C

    2010-12-01

    Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and α,β-methylene ATP (α,β-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T(2)-T(5)) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25-4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 Aδ, 37 C fibers). Epicardial application of ATP (1-4 μmol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 μmol), ADP (2 μmol), a P2Y agonist, and α,β-meATP (0.5 μmol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 μmol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2-4 μmol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory

  5. Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy

    International Nuclear Information System (INIS)

    Momose, Mitsuru; Inaba, Shigeki; Emori, Toshiaki; Imamura, Kimiharu; Kawano, Katsunori; Ueda, Tetsuro; Kobayashi, Hideki; Hosoda, Saichi

    1997-01-01

    Clinical manifestations of hypothyroidism, such as bradycardia, suggest decreased sympathetic tone. However, previous studies in patients with hypothyroidism have suggested that increased plasma noradrenaline (NA) levels represent enhanced general sympathetic activity. As yet, cardiac sympathetic activity (CSA) in hypothyroidism has not been clarified. To evaluate CSA in patients with hypothyroidism, iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed in eight patients with hypothyroidism before therapy and in ten normal control patients. Planar images were obtained at 15 min and 4 h after injection of MIBG. The ratio of early myocardial uptake to the total injected dose (MU) and myocardial clearance of MIBG within 4 h p.i. (MC) were calculated. Plasma NA was also measured, and echocardiography was performed in all patients. Those patients with hypothyroidism in the euthyroid state after medical therapy were also evaluated in a similar manner. Left ventricular ejection fraction, measured by echocardiography, did not differ significantly between the groups. NA, MU and MC were significantly higher in patients with hypothyroidism than in controls, and all parameters were decreased after therapy. MC was well correlated with NA in hypothyroidism (r=0.86) before therapy. We conclude that CSA is increased in patients with hypothyroidism, in parallel with the enhanced general sympathetic activity. (orig.). With 4 figs., 2 tabs

  6. Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

    Science.gov (United States)

    Donazzan, Luca; Mahfoud, Felix; Ewen, Sebastian; Ukena, Christian; Cremers, Bodo; Kirsch, Carl-Martin; Hellwig, Dirk; Eweiwi, Tareq; Ezziddin, Samer; Esler, Murray; Böhm, Michael

    2016-04-01

    To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

  7. Effect of Atorvastatin vs. Rosuvastatin on cardiac sympathetic nerve activity in non-diabetic patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsutamoto, Takayoshi; Ibe, Kunihiro [Toyosato Hospital, Toyosato, Shiga (Japan); Sakai, Hiroshi; Yamaji, Masayuki; Kawahara, Chiho; Nakae, Ichiro; Fujii, Masanori; Yamamoto, Takashi; Horie, Minoru [Shiga Univ. of Medical Science, Faculty of Medicine, Otsu, Shiga (Japan)

    2011-08-15

    Effects of statin therapy on cardiac sympathetic nerve activity in patients with chronic heart failure (CHF) have not previously been evaluated. To compare the effects of lipophilic atorvastatin and hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were already receiving standard therapy for CHF, were randomized to atorvastatin (n=32) or rosuvastatin (n=31). We evaluated cardiac sympathetic nerve activity by cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and after 6 months of treatment. There were no differences in the baseline characteristics of the 2 groups. In the rosuvastatin group, there were no changes in MIBG parameters, left ventricular ejection fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a significant increase in the delayed heart/mediastinum count ratio (2.18{+-}0.4 vs. 2.36{+-}0.4, P<0.0001), and the washout rate was significantly decreased (34.8{+-}5.7 vs. 32.6{+-}6.3%, P=0.0001) after 6 months of treatment compared with the baseline values. The plasma NT-proBNP level was also significantly decreased (729{+-}858 vs. 558{+-}747 pg/ml, P=0.0139). Lipophilic atorvastatin but not hydrophilic rosuvastatin improves cardiac sympathetic nerve activity in CHF patients with DCM. (author)

  8. Higher exercise intensity delays postexercise recovery of impedance-derived cardiac sympathetic activity.

    Science.gov (United States)

    Michael, Scott; Jay, Ollie; Graham, Kenneth S; Davis, Glen M

    2017-08-01

    Systolic time intervals (STIs) provide noninvasive insights into cardiac sympathetic neural activity (cSNA). As the effect of exercise intensity on postexercise STI recovery is unclear, this study investigated the STI recovery profile after different exercise intensities. Eleven healthy males cycled for 8 min at 3 separate intensities: LOW (40%-45%), MOD (75%-80%), and HIGH (90%-95%) of heart-rate (HR) reserve. Bio-impedance cardiography was used to assess STIs - primarily pre-ejection period (PEP; inversely correlated with cSNA), as well as left ventricular ejection time (LVET) and PEP:LVET - during 10 min seated recovery immediately postexercise. Heart-rate variability (HRV), i.e., natural-logarithm of root mean square of successive differences (Ln-RMSSD), was calculated as an index of cardiac parasympathetic neural activity (cPNA). Higher preceding exercise intensity elicited a slower recovery of HR and Ln-RMSSD (p return to baseline by 10 min following any intensity (p ≤ 0.009). Recovery of STIs was also slower following higher intensity exercise (p ≤ 0.002). By 30 s postexercise, higher preceding intensity resulted in a lower PEP (98 ± 14 ms, 75 ± 6 ms, 66 ± 5 ms for LOW, MOD, and HIGH, respectively, p fashion. While exercise intensity must be considered, acute recovery may be a valuable period during which to concurrently monitor these noninvasive indices, to identify potentially abnormal cardiac autonomic responses.

  9. Diabetic cardiac autonomic dysfunction. Parasympathetic versus sympathetic

    International Nuclear Information System (INIS)

    Uehara, Akihiko; Kurata, Chinori; Sugi, Toshihiko; Mikami, Tadashi; Shouda, Sakae

    1999-01-01

    Diabetic cardiac autonomic dysfunction often causes lethal arrhythmia and sudden cardiac death. 123 I-Metaiodobenzylguanidine (MIBG) can evaluate cardiac sympathetic dysfunction, and analysis of heart rate variability (HRV) can reflect cardiac parasympathetic activity. We examined whether cardiac parasympathetic dysfunction assessed by HRV may correlate with sympathetic dysfunction assessed by MIBG in diabetic patients. In 24-hour electrocardiography, we analyzed 4 HRV parameters: high-frequency power (HF), HF in the early morning (EMHF), rMSSD and pNN50. MIBG planar images and SPECT were obtained 15 minutes (early) and 150 minutes (late) after injection and the heart washout rate was calculated. The defect score in 9 left ventricular regions was scored on a 4 point scale (0=normal - 3=severe defect). In 20 selected diabetic patients without congestive heart failure, coronary artery disease and renal failure, parasympathetic HRV parameters had a negative correlation with the sum of defect scores (DS) in the late images (R=-0.47 to -0.59, p<0.05) and some parameters had a negative correlation with the washout rate (R=-0.50 to -0.55, p<0.05). In a total of 64 diabetic patients also, these parameters had a negative correlation with late DS (R=-0.28 to -0.35, p<0.05) and early DS (R=-0.27 to -0.32, p<0.05). The progress of diabetic cardiac parasympathetic dysfunction may parallel the sympathetic one. (author)

  10. Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Iwasaki, Tsutomu; Suzuki, Tadashi [Gunma Univ., Maebashi (Japan). School of Medicine; Hoshizaki, Hiroshi; Oshima, Shigeru; Taniguchi, Koichi; Nagai, Ryozo

    2000-07-01

    This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59{+-}13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 {mu}g/kg/min before treatment. Patients were divided into good responders (LVEF increase {>=}15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with {beta}-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28{+-}6 to 17{+-}12 (p<0.05), H/M ratio increased from 1.79{+-}0.26 to 2.07{+-}0.32 (p<0.05), LVEF increased from 29{+-}8% to 48{+-}10% (p<0.01), and LVDd decreased from 65{+-}4 mm to 58{+-}5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

  11. Effects of short-term carvedilol on the cardiac sympathetic activity assessed by {sup 123}I-MIBG scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, Sandra Marina Ribeiro de; Mesquita, Evandro Tinoco; Freire, Fabiano de Lima; Ribeiro, Mario Luiz; Nobrega, Antonio Claudio Lucas da; Mesquita, Claudio Tinoco, E-mail: sandramarina@cardiol.b [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil); Azevedo, Jader Cunha; Barbirato, Gustavo Borges; Coimbra, Alexandro [Hospital Pro-Cardiaco, Rio de Janeiro, RJ (Brazil); Dohmann, Hans Fernando da Rocha [Centro de Ensino e Pesquisa do Pro-Cardiaco (PROCEP), Rio de Janeiro, RJ (Brazil)

    2010-03-15

    Background: autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine ({sup 123}I-MIBG) scintigraphy imaging of the heart. Objective: to evaluate the cardiac sympathetic activity through {sup 123}I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45%. Patients and methods: sixteen patients, aged 56.3 +- 12.6 years (11 males), with a mean LVEF of 28% +- 8% and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with {sup 123}I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. Results: patients' functional class showed improvement: before the treatment, 50% of the patients were FC II and 50% were FC III. After 3 months, 7 patients were FC I (43.8%) and 9 were FC II (56.2%), (rho = 0.0001). The mean LVEF assessed by RIV increased from 29% to 33% (rho = 0.017). There was no significant variation in cardiac adrenergic activity assessed by {sup 123}I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. Conclusion: the short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by {sup 123}I-MIBG scintigraphy, as well as the measurement of circulating catecholamines. (author)

  12. Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

    International Nuclear Information System (INIS)

    Karasawa, Kensuke; Ayusawa, Mamoru; Noto, Nobutaka; Sumitomo, Naokata; Okada, Tomoo; Harada, Kensuke

    2000-01-01

    Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5±6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33±0.22 in chronic heart failure class I, 2.50±0.34 in class II, 1.95±0.61 in class III, and 1.39±0.29 in class IV (p<0.05). %WR was 24.8±12.8% in chronic heart failure class I, 23.3±10.2% in class II, 49.2±24.5% in class III, and 66.3±26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure. (author)

  13. Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karasawa, Kensuke; Ayusawa, Mamoru; Noto, Nobutaka; Sumitomo, Naokata; Okada, Tomoo; Harada, Kensuke [Nihon Univ., Tokyo (Japan). School of Medicine

    2000-12-01

    Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5{+-}6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33{+-}0.22 in chronic heart failure class I, 2.50{+-}0.34 in class II, 1.95{+-}0.61 in class III, and 1.39{+-}0.29 in class IV (p<0.05). %WR was 24.8{+-}12.8% in chronic heart failure class I, 23.3{+-}10.2% in class II, 49.2{+-}24.5% in class III, and 66.3{+-}26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure. (author)

  14. Assessment of central chemosensitivity and cardiac sympathetic nerve activity using I-123 MIBG imaging in central sleep apnea syndrome in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Meguro, Kentaro; Nagai, Ryozo; Toyama, Takuji; Adachi, Hitoshi; Ohshima, Shigeru; Taniguchi, Koichi

    2007-01-01

    Iodine-123 m-iodobenzylguanidine (MIBG) imaging has been used to study cardiac sympathetic function in various cardiac diseases. Central sleep apnea syndrome (CSAS) occurs frequently in patients with chronic heart failure (CHF) and is reported to be associated with a poor prognosis. One of the mechanisms of its poor prognosis may be related to impaired cardiac sympathetic activity. However, the relationship between chemosensitivity to carbon dioxide, which is reported to correlate with the severity of CSAS, and cardiac sympathetic activity has not been investigated. Therefore, this study was undertaken to assess cardiac sympathetic function and chemosensitivity to carbon dioxide in CHF patients. The oxygen desaturation index (ODI) was evaluated in 21 patients with dilated cardiomyopathy (male/female: 19/2, left ventricular ejection fraction (LVEF) 5 times/h underwent polysomnography. Patients with an apnea hypopnea index >15/h but without evidence of obstructive apnea were defined as having CSAS. Early (15 min) and delayed (4 hr) planar MIBG images were obtained from these patients. The mean counts in the whole heart and the mediastinum were obtained. The heart-to-mediastinum count ratio of the delayed image (H/M) and the corrected myocardial washout rate (WR) were also calculated. The central chemoreflex was assessed with the rebreathing method using a hypercapnic gas mixture (7% CO 2 and 93% O 2 ). Ten of the 21 patients had CSAS. The H/M ratio was similar in patients both with and without CSAS (1.57±0.18 vs. 1.59±0.14, p=0.82). However, the WR was higher in patients with CSAS than in patients without CSAS (40±8% vs. 30±12%, p<0.05). ODI significantly correlated with central chemosensitivity to carbon dioxide. Moreover, there was a highly significant correlation between WR and central chemosensitivity (r=0.65, p<0.05). However, there was no correlation between ODI and the WR (r=0.36, p=0.11). Cardiac sympathetic nerve activity in patients with CHF and CSAS is

  15. The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

    Science.gov (United States)

    Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

    2006-04-01

    Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

  16. Cardiac sympathetic neuronal imaging using PET

    International Nuclear Information System (INIS)

    Lautamaeki, Riikka; Tipre, Dnyanesh; Bengel, Frank M.

    2007-01-01

    Balance of the autonomic nervous system is essential for adequate cardiac performance, and alterations seem to play a key role in the development and progression of various cardiac diseases. PET imaging of the cardiac autonomic nervous system has advanced extensively in recent years, and multiple pre- and postsynaptic tracers have been introduced. The high spatial and temporal resolution of PET enables noninvasive quantification of neurophysiologic processes at the tissue level. Ligands for catecholamine receptors, along with radiolabeled catecholamines and catecholamine analogs, have been applied to determine involvement of sympathetic dysinnervation at different stages of heart diseases such as ischemia, heart failure, and arrhythmia. This review summarizes the recent findings in neurocardiological PET imaging. Experimental studies with several radioligands and clinical findings in cardiac dysautonomias are discussed. (orig.)

  17. Assessment of cardiac sympathetic nerve integrity with positron emission tomography

    International Nuclear Information System (INIS)

    Raffel, David M.; Wieland, Donald M.

    2001-01-01

    The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation

  18. Abnormal sympathetic nerve activity in women exposed to cigarette smoke: a potential mechanism to explain increased cardiac risk.

    Science.gov (United States)

    Middlekauff, Holly R; Park, Jeanie; Agrawal, Harsh; Gornbein, Jeffrey A

    2013-11-15

    In women, cardiac deaths attributable to tobacco exposure have reached the same high levels as men. Normally, sympathetic nerve activity (SNA) fluctuates according to the menstrual phase, but in habitual smokers, SNA levels remain constant. Our purpose is to extend these observations to other groups of women exposed to tobacco smoke and to explore potential mechanisms. We hypothesize that women exposed to secondhand smoke, but not former smokers, have nonfluctuating SNA compared with never smokers, and that impaired baroreflex suppression of SNA, and/or heightened central SNA responses, underlie this nonfluctuating SNA. We also hypothesize that female smokers have impaired nocturnal blood pressure dipping, normally mediated by modulation of SNA. In 49 females (19 never, 12 current, 9 former, 9 passive smokers), SNA was recorded (microneurography) during high- and low-hormone ovarian phases at rest, during pharmacological baroreflex testing, and during the cold pressor test (CPT). Twenty-four hour blood pressure (BP) monitoring was performed. Current and passive smokers, but not former smokers, had a nonfluctuating pattern of SNA, unlike never smokers in whom SNA varied with the menstrual phase. Baroreflex control of SNA was significantly blunted in current smokers, independent of menstrual phase. In passive smokers, SNA response to CPT was markedly increased. Nondipping was unexpectedly high in all groups. SNA does not vary during the menstrual cycle in active and passive smokers, unlike never and former smokers. Baroreflex control of SNA is blunted in current smokers, whereas SNA response to CPT is heightened in passive smokers. Smoking cessation is associated with return of the altered SNA pattern to normal.

  19. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves

    Science.gov (United States)

    Longhurst, John C.; Tjen-A-Looi, Stephanie C.; Fu, Liang-Wu

    2016-01-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

  20. Physiological changes in human cardiac sympathetic innervation and activity assessed by 123I-metaiodobenzylguanidine (MIBG) imaging

    International Nuclear Information System (INIS)

    Sakata, Kazuyuki; Iida, Kei; Mochizuki, Nao; Ito, Michitoshi; Nakaya, Yoshihiro

    2009-01-01

    Physiologic changes in the human sympathetic nervous system (SNS) may be associated with cardiovascular diseases, so the present study assessed the age and gender differences in global cardiac SNS in normal subjects. The 163 subjects (74 men, 89 women; age range 40-89 years) whose coronary arteriogram was normal, and who had no other cardiac or neurohormonal diseases, and no medication affecting the autonomic nervous system were included. All study subjects underwent metaiodobenzylguanidine imaging. Both initial and delayed heart-to-mediastinum (H/M) ratios had a significant gender difference and showed a progressive decrease with aging. In addition, the initial H/M ratio had a significant positive correlation with the delayed H/M ratio (r=0.89, P<0.0001). Females (50-59 years) demonstrated significantly higher delayed H/M ratio than males of the same age. After the age of 60, the delayed H/M ratio in females progressively decreased with aging, similar to males. As for the washout rate, both genders had a significantly progressive increase with aging. In addition, there was a significant decrease in the delayed H/M ratio in 10 females with surgical menopause compared with 15 age-matched females without surgical menopause. Cardiac SNS appears to be regulated by various physiological factors. (author)

  1. Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure. Comparison with enalapril

    International Nuclear Information System (INIS)

    Tsutamoto, Takayoshi; Tanaka, Toshinari; Sakai, Hiroshi

    2008-01-01

    In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II delayed heart/mediastinum count ratio was significantly increased (2.0±0.07 vs 2.15±0.07, p=0.013) and the washout rate was significantly decreased (33.0±1.4 vs 30.5±1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP. (author)

  2. Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Suzuki, Tadashi; Kurabayashi, Masahiko [Gunma University School of Medicine, Department of Cardiovascular Medicine, Maebashi, Gunma (Japan); Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan, Department of Internal Medicine, Gunma (Japan)

    2005-08-01

    The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33{+-}7%] were randomly assigned to perindopril (2 mg/day; n=20) or enalapril (5 mg/day; n=20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. After treatment, in patients receiving perindopril, TDS decreased from 39{+-}10 to 34{+-}9 (P<0.01), H/M ratios increased from 1.62{+-}0.27 to 1.76{+-}0.29 (P<0.01), WR decreased from 50{+-}14% to 42{+-}14% (P<0.05) and plasma BNP concentrations decreased from 226{+-}155 to 141{+-}90 pg/ml (P<0.0005). In addition, the LVEDV decreased from 180{+-}30 to 161{+-}30 ml (P<0.05) and the LVESV decreased from 122{+-}35 to 105{+-}36 ml (P<0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33{+-}8% to 36{+-}12%; P=NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. Plasma BNP concentrations, {sup 123}I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF. (orig.)

  3. Myocardial Infarction Causes Transient Cholinergic Transdifferentiation of Cardiac Sympathetic Nerves via gp130.

    Science.gov (United States)

    Olivas, Antoinette; Gardner, Ryan T; Wang, Lianguo; Ripplinger, Crystal M; Woodward, William R; Habecker, Beth A

    2016-01-13

    Sympathetic and parasympathetic control of the heart is a classic example of norepinephrine (NE) and acetylcholine (ACh) triggering opposing actions. Sympathetic NE increases heart rate and contractility through activation of β receptors, whereas parasympathetic ACh slows the heart through muscarinic receptors. Sympathetic neurons can undergo a developmental transition from production of NE to ACh and we provide evidence that mouse cardiac sympathetic nerves transiently produce ACh after myocardial infarction (MI). ACh levels increased in viable heart tissue 10-14 d after MI, returning to control levels at 21 d, whereas NE levels were stable. At the same time, the genes required for ACh synthesis increased in stellate ganglia, which contain most of the sympathetic neurons projecting to the heart. Immunohistochemistry 14 d after MI revealed choline acetyltransferase (ChAT) in stellate sympathetic neurons and vesicular ACh transporter immunoreactivity in tyrosine hydroxylase-positive cardiac sympathetic fibers. Finally, selective deletion of the ChAT gene from adult sympathetic neurons prevented the infarction-induced increase in cardiac ACh. Deletion of the gp130 cytokine receptor from sympathetic neurons prevented the induction of cholinergic genes after MI, suggesting that inflammatory cytokines induce the transient acquisition of a cholinergic phenotype in cardiac sympathetic neurons. Ex vivo experiments examining the effect of NE and ACh on rabbit cardiac action potential duration revealed that ACh blunted both the NE-stimulated decrease in cardiac action potential duration and increase in myocyte calcium transients. This raises the possibility that sympathetic co-release of ACh and NE may impair adaptation to high heart rates and increase arrhythmia susceptibility. Sympathetic neurons normally make norepinephrine (NE), which increases heart rate and the contractility of cardiac myocytes. We found that, after myocardial infarction, the sympathetic neurons

  4. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves.

    Science.gov (United States)

    Guo, Zhi-Ling; Longhurst, John C; Tjen-A-Looi, Stephanie C; Fu, Liang-Wu

    2016-08-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. Copyright © 2016 the American Physiological Society.

  5. Cardiac Sympathetic Hyperactivity after Chemotherapy: Early Sign of Cardiotoxicity?

    Energy Technology Data Exchange (ETDEWEB)

    Guimarães, Sarita Lígia Pessoa de Melo Machado [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Hospital Agamenon Magalhães (HAM), Recife, PE (Brazil); Brandão, Simone Cristina Soares, E-mail: simonecordis@yahoo.com.br [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Andrade, Luciana Raposo [Hospital Santa Joana, Recife, PE (Brazil); Maia, Rafael José Coelho [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil); Hospital Agamenon Magalhães (HAM), Recife, PE (Brazil); Markman Filho, Brivaldo [Pós-Graduação em Ciências da Saúde da Universidade Federal de Pernambuco (PGCS-UFPE), Recife, PE (Brazil)

    2015-09-15

    Chemotherapy with anthracyclines and trastuzumab can cause cardiotoxicity. Alteration of cardiac adrenergic function assessed by metaiodobenzylguanidine labeled with iodine-123 ({sup 123}I-mIBG) seems to precede the drop in left ventricular ejection fraction. To evaluate and to compare the presence of cardiovascular abnormalities among patients with breast cancer undergoing chemotherapy with anthracyclines and trastuzumab, and only with anthracycline. Patients with breast cancer were analyzed clinical, laboratory, electrocardiographic and echocardiographic and cardiac sympathetic activity. In scintigraphic images, the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum, and the washout rate were calculated. The variables were compared between patients who received anthracyclines and trastuzumab (Group 1) and only anthracyclines (Group 2). Twenty patients, with mean age 57 ± 14 years, were studied. The mean left ventricular ejection fraction by echocardiography was 67.8 ± 4.0%. Mean washout rate was 28.39 ± 9.23% and the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum was 2.07 ± 0.28. Of the patients, 82% showed an increased in washout rate, and the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum decreased in 25%. Concerning the groups, the mean washout rate of Group 1 was 32.68 ± 9.30% and of Group 2 was 24.56 ± 7.72% (p = 0,06). The ratio of {sup 123}I-mIBG uptake between the heart and mediastinum was normal in all patients in Group 2, however, the Group 1, showed 50% the ratio of {sup 123}I-mIBG uptake between the heart and mediastinum ≤ 1.8 (p = 0.02). In women with breast cancer undergoing chemotherapy, assessment of cardiac sympathetic activity with {sup 123}I-mIBG appears to be an early marker of cardiotoxicity. The combination of chemotherapy showed higher risk of cardiac adrenergic hyperactivity.

  6. Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function.

    Science.gov (United States)

    Wengrowski, Anastasia M; Wang, Xin; Tapa, Srinivas; Posnack, Nikki Gillum; Mendelowitz, David; Kay, Matthew W

    2015-02-01

    Release of norepinephrine (NE) from sympathetic neurons enhances heart rate (HR) and developed force through activation of β-adrenergic receptors, and this sympathoexcitation is a key risk for the generation of cardiac arrhythmias. Studies of β-adrenergic modulation of cardiac function typically involve the administration of exogenous β-adrenergic receptor agonists to directly elicit global β-adrenergic receptor activation by bypassing the involvement of sympathetic nerve terminals. In this work, we use a novel method to activate sympathetic fibres within the myocardium of Langendorff-perfused hearts while measuring changes in electrical and mechanical function. The light-activated optogenetic protein channelrhodopsin-2 (ChR2) was expressed in murine catecholaminergic sympathetic neurons. Sympathetic fibres were then photoactivated to examine changes in contractile force, HR, and cardiac electrical activity. Incidence of arrhythmia was measured with and without exposure to photoactivation of sympathetic fibres, and hearts were optically mapped to detect changes in action potential durations and conduction velocities. Results demonstrate facilitation of both developed force and HR after photostimulated release of NE, with increases in contractile force and HR of 34.5 ± 5.5 and 25.0 ± 9.3%, respectively. Photostimulation of sympathetic fibres also made hearts more susceptible to arrhythmia, with greater incidence and severity. In addition, optically mapped action potentials displayed a small but significant shortening of the plateau phase (-5.5 ± 1.0 ms) after photostimulation. This study characterizes a powerful and clinically relevant new model for studies of cardiac arrhythmias generated by increasing the activity of sympathetic nerve terminals and the resulting activation of myocyte β-adrenergic receptors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  7. Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

    Science.gov (United States)

    Feng, Qiaoli; Lu, Chengzhi; Wang, Li; Song, Lijun; Li, Chao; Uppada, Ravi Chandra

    2017-02-17

    This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47 phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47 phox ,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0

  8. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    International Nuclear Information System (INIS)

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J.

    1990-01-01

    Sites of uptake, storage, and metabolism of [ 18 F]fluorodopamine and excretion of [ 18 F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [ 18 F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [ 18 F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function

  9. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    International Nuclear Information System (INIS)

    Kasama, Shu; Toyama, Takuji; Kurabayashi, Masahiko; Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi; Matsumoto, Naoya; Nakata, Tomoaki

    2014-01-01

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. 123 I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  10. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Nakata, Tomoaki [Sapporo Medical University School of Medicine, Second (Cardiology) Department of Internal Medicine, Sapporo, Hokkaido (Japan)

    2014-09-15

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. {sup 123}I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  11. Cardiac sympathetic nervous system imaging with (123)I-meta-iodobenzylguanidine: Perspectives from Japan and Europe

    NARCIS (Netherlands)

    Nakajima, K.; Scholte, A.; Nakata, T.; Dimitriu-Leen, A.C.; Chikamori, T.; Vitola, J.V.; Yoshinaga, K.

    2017-01-01

    Cardiac sympathetic nervous system dysfunction is closely associated with risk of serious cardiac events in patients with heart failure (HF), including HF progression, pump-failure death, and sudden cardiac death by lethal ventricular arrhythmia. For cardiac sympathetic nervous system imaging,

  12. Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Suzuki, Yasuyuki; Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Takasaki, Gunma (Japan)

    2015-04-01

    Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct. (orig.)

  13. The clinical value of cardiac sympathetic imaging in heart failure

    DEFF Research Database (Denmark)

    Christensen, Thomas Emil; Kjaer, Andreas; Hasbak, Philip

    2014-01-01

    The autonomic nervous system plays an important role in the pathology of heart failure. The single-photon emission computed tomography tracer iodine-123-metaiodobenzylguanidine ((123) I-MIBG) can be used to investigate the activity of the predominant neurotransmitter of the sympathetic nervous...

  14. Sympathetic- and Parasympathetic-Linked Cardiac Function and Prediction of Externalizing Behavior, Emotion Regulation, and Prosocial Behavior among Preschoolers Treated for ADHD

    Science.gov (United States)

    Beauchaine, Theodore P.; Gatzke-Kopp, Lisa; Neuhaus, Emily; Chipman, Jane; Reid, M. Jamila; Webster-Stratton, Carolyn

    2013-01-01

    Objective: To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Method: Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia…

  15. Sympathetic activation during early pregnancy in humans

    Science.gov (United States)

    Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2012-01-01

    Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

  16. Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure

    International Nuclear Information System (INIS)

    Arimoto, Takanori; Takeishi, Yasuchika; Niizeki, Takeshi

    2005-01-01

    Iodine-123-metaiodobenzylguanidine ( 123 I-MIBG) has been used to assess the integrity and function of the cardiac sympathetic nervous system in patients with heart failure. Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured, and H-FABP has been recently used as a novel marker for the diagnosis of ongoing myocardial damage. The aim of the present study was to compare cardiac sympathetic nervous activity assessed by 123 I-MIBG imaging with serum levels of H-FABP in patients with heart failure. Fifty patients with chronic heart failure were studied. 123 I-MIBG imaging was carried out at 30 min (early) and 240 min (delayed) after the tracer injection. We measured serum levels of H-FABP using a sandwich enzyme linked immunosorbent assay. Heart to mediastinum (H/M) ratios of 123 I-MIBG decreased and washout rate increased with higher New York Heart Association (NYHA) functional class. H-FABP, norepinephrine and brain natriuretic peptide (BNP) levels increased as the severity of NYHA class advanced. Delayed H/M ratio was significantly correlated with H-FABP (r=-0.296, p=0.029) and BNP (r=-0.335, p=0.0213). Myocardial washout rate of 123 I-MIBG was also correlated with H-FABP (r=0.469, p 123 I-MIBG imaging is an appropriate approach to evaluate non-invasively not only cardiac sympathetic nervous activity, but also latent ongoing myocardial damage in the failing heart. (author)

  17. Influence of the polyol pathway on norepinephrine transporter reduction in diabetic cardiac sympathetic nerves: implications for heterogeneous accumulation of MIBG

    International Nuclear Information System (INIS)

    Kiyono, Yasushi; Kajiyama, Satomi; Fujiwara, Hiromi; Kanegawa, Naoki; Saji, Hideo

    2005-01-01

    Cardiac scintigraphic studies using 123 I-labeled metaiodobenzylguanidine ([ 123 I]MIBG) have demonstrated heterogeneous myocardial accumulation of MIBG in diabetes. The accumulation has been found to correlate with a heterogeneous decrease in the expression of norepinephrine transporter (NET). In diabetic peripheral nerve tissue, polyol pathways are activated and cause nerve dysfunction and degeneration. However, there has been little research on the polyol pathway and cardiac sympathetic nerves. Therefore, to assess the influence of the polyol pathway on cardiac sympathetic nervous function, we investigated the regional accumulation of MIBG and NET protein expression in diabetic model rats treated with aldose reductase inhibitor (ARI) for the blockade of polyol pathways. Rats were given a single intravenous injection of streptozotocin (n=76, STZ-D rats). Starting the day after STZ injection, ARI was administered daily to 42 of the rats for 4 weeks (ARI-D rats). To assess the cardiac sympathetic nervous function, [ 125 I]MIBG autoradiographic experiments were carried out. Finally, NET protein expression was assessed with a saturation binding assay. The myocardial sorbitol concentration was significantly higher in STZ-D rats than in ARI-D rats. There was no heterogeneous accumulation of MIBG in ARI-D rats. There was a heterogeneous decrease of NET expression in STZ-D rats, but not in ARI-D or control rats. The gathered data indicate that the enhanced polyol pathway correlates with the decrease in regional cardiac sympathetic nervous function, and this impairment may lead to the reduction of NET protein in cardiac sympathetic nerves of the diabetic inferior wall. (orig.)

  18. Quantitation of cardiac sympathetic innervation in rabbits using 11C-hydroxyephedrine PET: relation to 123I-MIBG uptake

    International Nuclear Information System (INIS)

    Nomura, Yusuke; Kajinami, Kouji; Matsunari, Ichiro; Takamatsu, Hiroyuki; Murakami, Yoshihiro; Matsuya, Takahiro; Chen, Wei-Ping; Taki, Junichi; Nakajima, Kenichi; Nekolla, Stephan G.

    2006-01-01

    Although 11 C-hydroxyephedrine ( 11 C-HED) PET is used to map cardiac sympathetic innervation, no studies have shown the feasibility of quantitation of 11 C-HED PET in small- to medium-sized animals. Furthermore, its relation to 123 I-MIBG uptake, the most widely used sympathetic nervous tracer, is unknown. The aims of this study were to establish in vivo sympathetic nerve imaging in rabbits using 11 C-HED PET, and to compare the retention of 11 C-HED with that of 123 I-MIBG. Twelve rabbits were assigned to three groups; control (n=4), chemical denervation by 6-hydroxydopamine (6-OHDA) (n=4) and reserpine treated to inhibit vesicular uptake (n=4). After simultaneous injection of 11 C-HED and 123 I-MIBG, all animals underwent dynamic 11 C-HED PET for 40 min with arterial blood sampling. The 11 C-HED retention fraction and normalised 11 C-HED activity measured by tissue sampling were compared with those measured by PET. Both the 11 C-HED retention fraction and the normalised 11 C-HED activity measured by PET correlated closely with those measured by tissue sampling (R=0.96027, p 11 C-HED and 123 I-MIBG. Reserpine pretreatment reduced 11 C-HED retention by 50%, but did not reduce 123 I-MIBG retention at 40 min after injection. Non-invasive quantitation of cardiac sympathetic innervation using 11 C-HED PET is feasible and gives reliable estimates of cardiac sympathetic innervation in rabbits. Additionally, although both 11 C-HED and 123 I-MIBG are specific for sympathetic neurons, 11 C-HED may be more specific for intravesicular uptake than 123 I-MIBG in some situations, such as that seen in reserpine pretreatment. (orig.)

  19. Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats

    DEFF Research Database (Denmark)

    Neves, S R S; Machado, C R S; Pinto, A M T

    2006-01-01

    The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions a...

  20. Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones

    Science.gov (United States)

    Bhagat, B.

    1969-01-01

    1. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H-noradrenaline 1 hr after its intravenous administration. 2. Twenty-four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction. 3. Rate calculations from the decline of catecholamine levels after blockade of synthesis with α-methyl-tyrosine showed that cardiac synthesis of noradrenaline increased about four-fold after demedullation and about three-fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines. 4. There was no change in catechol-o-methyl-transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats. 5. It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones. PMID:5360339

  1. Effects of Antidepressants, but not Psychopathology, on Cardiac Sympathetic Control : A Longitudinal Study

    NARCIS (Netherlands)

    Licht, Carmilla M. M.; Penninx, Brenda W. J. H.; de Geus, Eco J. C.

    2012-01-01

    Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of

  2. Resting sympathetic activity is associated with the sympathetically mediated component of energy expenditure following a meal.

    Science.gov (United States)

    Limberg, Jacqueline K; Malterer, Katherine R; Matzek, Luke J; Levine, James A; Charkoudian, Nisha; Miles, John M; Joyner, Michael J; Curry, Timothy B

    2017-08-01

    Individuals with high plasma norepinephrine (NE) levels at rest have a smaller reduction in resting energy expenditure (REE) following β -adrenergic blockade. If this finding extends to the response to a meal, it could have important implications for the role of the sympathetic nervous system in energy balance and weight gain. We hypothesized high muscle sympathetic nerve activity (MSNA) would be associated with a low sympathetically mediated component of energy expenditure following a meal. Fourteen young, healthy adults completed two visits randomized to continuous saline (control) or intravenous propranolol to achieve systemic β -adrenergic blockade. Muscle sympathetic nerve activity and REE were measured (indirect calorimetry) followed by a liquid mixed meal (Ensure). Measures of energy expenditure continued every 30 min for 5 h after the meal and are reported as an area under the curve (AUC). Sympathetic support of energy expenditure was calculated as the difference between the AUC during saline and β -blockade (AUC P ropranolol -AUC S aline , β -REE) and as a percent (%) of control (AUC P ropranolol ÷AUC S aline  × 100). β -REE was associated with baseline sympathetic activity, such that individuals with high resting MSNA (bursts/100 heart beats) and plasma NE had the greatest sympathetically mediated component of energy expenditure following a meal (MSNA: β -REE R  =   -0.58, P =  0.03; %REE R  = -0.56, P =  0.04; NE: β -REE R  = -0.55, P  = 0.0535; %REE R  = -0.54, P  = 0.0552). Contrary to our hypothesis, high resting sympathetic activity is associated with a greater sympathetically mediated component of energy expenditure following a liquid meal. These findings may have implications for weight maintenance in individuals with varying resting sympathetic activity. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Assessing the strength of cardiac and sympathetic baroreflex controls via transfer entropy during orthostatic challenge

    Science.gov (United States)

    Porta, Alberto; Marchi, Andrea; Bari, Vlasta; De Maria, Beatrice; Esler, Murray; Lambert, Elisabeth; Baumert, Mathias

    2017-05-01

    The study assesses the strength of the causal relation along baroreflex (BR) in humans during an incremental postural challenge soliciting the BR. Both cardiac BR (cBR) and sympathetic BR (sBR) were characterized via BR sequence approaches from spontaneous fluctuations of heart period (HP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA). A model-based transfer entropy method was applied to quantify the strength of the coupling from SAP to HP and from DAP to MSNA. The confounding influences of respiration were accounted for. Twelve young healthy subjects (20-36 years, nine females) were sequentially tilted at 0°, 20°, 30° and 40°. We found that (i) the strength of the causal relation along the cBR increases with tilt table inclination, while that along the sBR is unrelated to it; (ii) the strength of the causal coupling is unrelated to the gain of the relation; (iii) transfer entropy indexes are significantly and positively associated with simplified causality indexes derived from BR sequence analysis. The study proves that causality indexes are complementary to traditional characterization of the BR and suggests that simple markers derived from BR sequence analysis might be fruitfully exploited to estimate causality along the BR. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

  4. Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

    Science.gov (United States)

    Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

    2018-01-27

    Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123 I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

  5. Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

    Science.gov (United States)

    Paolillo, S; Rengo, G; Pellegrino, T; Formisano, R; Pagano, G; Gargiulo, P; Savarese, G; Carotenuto, R; Petraglia, L; Rapacciuolo, A; Perrino, C; Piscitelli, S; Attena, E; Del Guercio, L; Leosco, D; Trimarco, B; Cuocolo, A; Perrone-Filardi, P

    2015-10-01

    Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  6. Scintigraphic assessment of cardiac sympathetic innervation with I-123-metaiodobenzylguanidine in cardiomyopathy. Special reference to cardiac arrhythmia

    Energy Technology Data Exchange (ETDEWEB)

    Asano, Takahisa; Otsuka, Nobuaki; Sone, Teruki; Mimura, Hiroaki; Yanagimoto, Shinichi; Tomomitsu, Tatsushi; Fukunaga, Masao [Kawasaki Medical School, Kurashiki, Okayama (Japan); Morita, Koichi

    1999-07-01

    Cardiac sympathetic imagings with I-123-metaiodobenzylguanidine (MIBG) were carried out in 5 cases with dilated cardiomyopathy (DCM), 26 cases with hypertrophic cardiomyopathy (HCM), and 4 cases without cardiac disease as a control to assess cardiac sympathetic innervation qualitatively and quantitatively, and to clarify the relation of MIBG accumulation to arrhythmia. MIBG scintigraphy was performed at 15 min. (early image) and 4 hr. (delayed image) after intravenous injection of MIBG 111 MBq. The MIBG uptake ratio of mediastinum (H/M) and the cardiac washout rate (WR) from early to delayed images were calculated. On both early and delayed SPECTs, MIBG uptake was assessed by defect scores (DSs). Regarding the cases with HCM, the MIBG uptake ratio, WR, and DS were also compared in cases with and without arrhythmia. In DCM, the MIBG uptake on delayed SPECT was markedly low, the H/M ratio was significantly lower, and the DS was significantly higher than in the control (all p<0.05). As for the WR, there was no significant difference between HCM, DCM and the control. In HCM, significantly reduced MIBG uptake was observed in cases with ventricular techycardia (VT) and in cases with atrial fibrillation (Af), as compared with cases without arrhythmia (all p<0.05). There results suggest that MIBG scintigraphy might be a useful tool in the assessment of cardiac sympathetic abnormalities in cardiomyopathy, especially in cases with arrhythmia. (author)

  7. Intracranial Pressure Is a Determinant of Sympathetic Activity

    Directory of Open Access Journals (Sweden)

    Eric A. Schmidt

    2018-02-01

    Full Text Available Intracranial pressure (ICP is the pressure within the cranium. ICP rise compresses brain vessels and reduces cerebral blood delivery. Massive ICP rise leads to cerebral ischemia, but it is also known to produce hypertension, bradycardia and respiratory irregularities due to a sympatho-adrenal mechanism termed Cushing response. One still unresolved question is whether the Cushing response is a non-synaptic acute brainstem ischemic mechanism or part of a larger physiological reflex for arterial blood pressure control and homeostasis regulation. We hypothesize that changes in ICP modulates sympathetic activity. Thus, modest ICP increase and decrease were achieved in mice and patients with respectively intra-ventricular and lumbar fluid infusion. Sympathetic activity was gauged directly by microneurography, recording renal sympathetic nerve activity in mice and muscle sympathetic nerve activity in patients, and gauged indirectly in both species by heart-rate variability analysis. In mice (n = 15, renal sympathetic activity increased from 29.9 ± 4.0 bursts.s−1 (baseline ICP 6.6 ± 0.7 mmHg to 45.7 ± 6.4 bursts.s−1 (plateau ICP 38.6 ± 1.0 mmHg and decreased to 34.8 ± 5.6 bursts.s−1 (post-infusion ICP 9.1 ± 0.8 mmHg. In patients (n = 10, muscle sympathetic activity increased from 51.2 ± 2.5 bursts.min−1 (baseline ICP 8.3 ± 1.0 mmHg to 66.7 ± 2.9 bursts.min−1 (plateau ICP 25 ± 0.3 mmHg and decreased to 58.8 ± 2.6 bursts.min−1 (post-infusion ICP 14.8 ± 0.9 mmHg. In patients 7 mmHg ICP rise significantly increases sympathetic activity by 17%. Heart-rate variability analysis demonstrated a significant vagal withdrawal during the ICP rise, in accordance with the microneurography findings. Mice and human results are alike. We demonstrate in animal and human that ICP is a reversible determinant of efferent sympathetic outflow, even at relatively low ICP levels. ICP is a biophysical stress related to the forces within the brain. But ICP

  8. Usefulness of cardiac 125I-metaiodobenzylguanidine uptake for evaluation of cardiac sympathetic nerve abnormalities in diabetic rats

    International Nuclear Information System (INIS)

    Abe, Nanami; Kashiwagi, Atsunori; Shigeta, Yukio

    1992-01-01

    We investigated cardiac sympathetic nerve abnormalities in streptozocin-induced diabetic rats using 125 I-metaiodobenzylguanidine (MIBG). The radioactivity ratio of cardiac tissue to 1 ml blood (H/B) was used as an index of cardiac MIBG uptake. Cardiac 125 I-MIBG uptake (H/B) in 4-, 8- and 20-wk diabetic rats was 48% lower than that in control rats. Similar results were obtained even when the data were corrected for g wet tissue weight. Although there was no improvement in H/B following 2-wk insulin treatment, the H/B ratio increased significantly, to 85% of control levels, following 4 wk insulin treatment indicating the reversibility of impaired MIBG uptake in diabetic rats. In vivo reserpine treatment resulted in a 50% reduction in the H/B value in control rats. However, the treatment did not significantly suppress uptake in diabetic rats. Cardiac norepinephrine content in both * 4- and ** 8-wk diabetic rats was significantly ( * p ** p 125 I-MIBG in diabetic rats is significantly impaired due to cardiac sympathetic nerve abnormalities. These abnormalities are reversible, however, dependent on the diabetic state. (author)

  9. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    International Nuclear Information System (INIS)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell'Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto; Pellegrino, Teresa; Petretta, Mario; Riccio, Eleonora; Pisani, Antonio

    2017-01-01

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by 123 I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by 123 I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r 2 = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, 123 I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  10. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell' Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Riccio, Eleonora; Pisani, Antonio [University of Naples Federico II, Department of Public Health, Naples (Italy)

    2017-12-15

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by {sup 123}I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by {sup 123}I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r{sup 2} = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, {sup 123}I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  11. Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.

    Science.gov (United States)

    Camargo-Silva, Gabriel; Turones, Larissa Córdova; da Cruz, Kellen Rosa; Gomes, Karina Pereira; Mendonça, Michelle Mendanha; Nunes, Allancer; de Jesus, Itamar Guedes; Colugnati, Diego Basile; Pansani, Aline Priscila; Pobbe, Roger Luis Henschel; Santos, Robson; Fontes, Marco Antônio Peliky; Guatimosim, Silvia; de Castro, Carlos Henrique; Ianzer, Danielle; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique

    2018-03-01

    Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Efficacy of B-Type Natriuretic Peptide Is Coupled to Phosphodiesterase 2A in Cardiac Sympathetic Neurons.

    Science.gov (United States)

    Li, Dan; Lu, Chieh-Ju; Hao, Guoliang; Wright, Hannah; Woodward, Lavinia; Liu, Kun; Vergari, Elisa; Surdo, Nicoletta C; Herring, Neil; Zaccolo, Manuela; Paterson, David J

    2015-07-01

    Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP. Because phosphodiesterase activity is altered in cardiovascular disease, we tested the hypothesis that BNP might lose its efficacy by minimizing the action of cGMP on downstream pathways coupled to neurotransmission. BNP decreased norepinephrine release from atrial preparations in response to field stimulation and also significantly reduced the heart rate responses to sympathetic nerve stimulation in vitro. Using electrophysiological recording and fluorescence imaging, BNP also reduced the depolarization evoked calcium current and intracellular calcium transient in isolated cardiac sympathetic neurons. Pharmacological manipulations suggested that the reduction in the calcium transient was regulated by a cGMP/protein kinase G pathway. Fluorescence resonance energy transfer measurements for cAMP, and an immunoassay for cGMP, showed that BNP increased cGMP, but not cAMP. In addition, overexpression of phosphodiesterase 2A after adenoviral gene transfer markedly decreased BNP stimulation of cGMP and abrogated the BNP responses to the calcium current, intracellular calcium transient, and neurotransmitter release. These effects were reversed on inhibition of phosphodiesterase 2A. Moreover, phosphodiesterase 2A activity was significantly elevated in stellate neurons from the prohypertensive rat compared with the normotensive control. Our data suggest that abnormally high levels of phosphodiesterase 2A may provide a brake against the inhibitory action of BNP on sympathetic transmission. © 2015 American Heart Association, Inc.

  13. The synthesis of a new cardiac sympathetic nerve imaging agent N-[11C]CH3-dopamine and biodistribution study

    International Nuclear Information System (INIS)

    Yulin He; Weina Zhou; Xiangcheng Wang; Baoliang Bao; Guojian Zhang; Cheng Wang; Chunmei Wang; Xuemei Wang; Wei Fang

    2014-01-01

    In this study, we synthesized and characterized N-[ 11 C]methyl-dopamine ([ 11 C]MDA) for cardiac sympathetic nerve imaging. [ 11 C]MDA was synthesized by direct N-methylation of dopamine with [ 11 C]methyl iodide and purified by semi-preparation reverse high pressure liquid chromatography (HPLC). The total synthesis time was 45 min including HPLC purification. The radiochemical yields of [ 11 C]MDA was 20 ± 3 %, without decay correction. The radiochemical purity was >98 % and the specific activity was about 50 GBq/mmol. The biological properties of [ 11 C]MDA were evaluated by biodistribution study in normal mice. PET imaging was performed in healthy Chinese mini-swines. Biodistribution study showed that [ 11 C]MDA had high myocardium uptake. PET/CT imaging showed [ 11 C]MDA had clear and symmetrical myocardium uptake, which was blocked obviously by injecting imipramine hydrochloride. [ 11 C]MDA would be a promising candidate of radiotracer for cardiac sympathetic nervous system imaging. (author)

  14. Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

    Science.gov (United States)

    Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

    2016-08-19

    Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

  15. Role of autoinhibitory feedback in cardiac sympathetic transmission

    International Nuclear Information System (INIS)

    Angus, J.A.; Korner, P.I.; Jackman, G.P.; Bobik, A.; Kopin, I.J.

    1984-01-01

    The relationship between two indices of transmitter release measured simultaneously and the frequency of 4 field pulses (0.125-2 Hz) were obtained from superfused guinea pig right atria after labelling with 3 H-noradrenaline. The relationships between 3 H-efflux or rate responses and frequency were hyperbolic. Autoinhibitory feedback did not play a role since phentolamine (1 microM) did not alter the 3 H-efflux or rate responses to 4 field pulses that gave 50-60% of the maximum rate response. In the presence of neuronal uptake block (desipramine (0.1 microM) phentolamine enhanced 3 H-efflux and rate responses to 4 field pulses at all frequencies. In the absence of desipramine prolonged trains of field pulses (8-12 pulses) at low frequency (0.25 Hz) were not sufficient to activate autoinhibitory feedback. At 2 Hz phentolamine enhanced both responses at 12 field pulses. We conclude that in the right atrium autoinhibitory feedback plays little role in the modulation of transmitter release at levels of stimulation that cause 50-60% of maximum tissue response. The presence of neuronal uptake inhibition or high stimulus strengths are necessary to evoke autoinhibitory feedback

  16. Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans.

    Science.gov (United States)

    Kaufmann, H; Biaggioni, I; Voustianiouk, A; Diedrich, A; Costa, F; Clarke, R; Gizzi, M; Raphan, T; Cohen, B

    2002-04-01

    It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.

  17. Baroreflex control of sympathetic activity in experimental hypertension

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    M.C.C. Irigoyen

    1998-09-01

    Full Text Available The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100% was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

  18. TNF-α receptor 1 knockdown in the subfornical organ ameliorates sympathetic excitation and cardiac hemodynamics in heart failure rats.

    Science.gov (United States)

    Yu, Yang; Wei, Shun-Guang; Weiss, Robert M; Felder, Robert B

    2017-10-01

    In systolic heart failure (HF), circulating proinflammatory cytokines upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain, contributing to sympathetic excitation and cardiac dysfunction. Important among these is the subfornical organ (SFO), a forebrain circumventricular organ that lacks an effective blood-brain barrier and senses circulating humors. We hypothesized that the tumor necrosis factor-α (TNF-α) receptor 1 (TNFR1) in the SFO contributes to sympathetic excitation and cardiac dysfunction in HF rats. Rats received SFO microinjections of a TNFR1 shRNA or a scrambled shRNA lentiviral vector carrying green fluorescent protein, or vehicle. One week later, some rats were euthanized to confirm the accuracy of the SFO microinjections and the transfection potential of the lentiviral vector. Other rats underwent coronary artery ligation (CL) to induce HF or a sham operation. Four weeks after CL, vehicle- and scrambled shRNA-treated HF rats had significant increases in TNFR1 mRNA and protein, NF-κB activity, and mRNA for inflammatory mediators, RAS components and c-Fos protein in the SFO and downstream in the hypothalamic paraventricular nucleus, along with increased plasma norepinephrine levels and impaired cardiac function, compared with vehicle-treated sham-operated rats. In HF rats treated with TNFR1 shRNA, TNFR1 was reduced in the SFO but not paraventricular nucleus, and the central and peripheral manifestations of HF were ameliorated. In sham-operated rats treated with TNFR1 shRNA, TNFR1 expression was also reduced in the SFO but there were no other effects. These results suggest a key role for TNFR1 in the SFO in the pathophysiology of systolic HF. NEW & NOTEWORTHY Activation of TNF-α receptor 1 in the subfornical organ (SFO) contributes to sympathetic excitation in heart failure rats by increasing inflammation and renin-angiotensin system activity in the SFO and downstream in the hypothalamic

  19. Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons.

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    Raffel, D M; Corbett, J R; del Rosario, R B; Gildersleeve, D L; Chiao, P C; Schwaiger, M; Wieland, D M

    1996-12-01

    The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.

  20. Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study

    International Nuclear Information System (INIS)

    Gimelli, Alessia; Genovesi, Dario; Giorgetti, Assuero; Kusch, Annette; Liga, Riccardo; Marzullo, Paolo

    2014-01-01

    To evaluate the relationships among myocardial sympathetic innervation, perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc-telluride (CZT) scintigraphy. A group of 29 patients underwent an evaluation of myocardial perfusion with 99m Tc-tetrofosmin CZT scintigraphy and adrenergic innervation with 123 I-metaiodobenzylguanidine (MIBG) CZT scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening score (STS), as well as the summed 123 I-MIBG defect score (SS-MIBG), were determined. Regional tracer uptake for both 99m Tc-tetrofosmin and 123 I-MIBG was also calculated. Finally, the presence of significant myocardial mechanical dyssynchrony was evaluated in phase analysis on gated CZT images and the region of latest mechanical activation identified. Significant mechanical dyssynchrony was present in 17 patients (59 %) and associated with higher SRS (P = 0.030), SMS (P 123 I-MIBG uptake (P = 0.012) that overwhelmed the effect of depressed regional perfusion. Left ventricular mechanical dyssynchrony is associated with greater depression in contractile function and greater impairments in regional myocardial perfusion and sympathetic activity. In patients with dyssynchrony, the region of latest mechanical activation is characterized by a significantly altered adrenergic tone. (orig.)

  1. Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Manrique, Alain; Hitzel, Anne; Vera, Pierre; Bernard, Mathieu; Bauer, Fabrice; Menard, Jean-Francois; Sabatier, Remi; Jacobson, Arnold; Agostini, Denis

    2008-01-01

    The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV-LV) and intraventricular (SD-RV and SD-LV) asynchrony were computed. Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 ± 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified. (orig.)

  2. Alterations of left ventricular deformation and cardiac sympathetic derangement in patients with systolic heart failure: a 3D speckle tracking echocardiography and cardiac {sup 123}I-MIBG study

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    Leosco, Dario; Parisi, Valentina; Pagano, Gennaro; Femminella, Grazia Daniela; Bevilacqua, Agnese; Formisano, Roberto; Ferro, Gaetana; De Lucia, Claudio; Ferrara, Nicola [University Federico II, Department of Translational Medical Science, Naples (Italy); Pellegrino, Teresa [Italian National Research Council (CNR), Institute of Biostructure and Bioimaging, Naples (Italy); University Federico II, Department of Advanced Biomedical Science, Naples (Italy); Paolillo, Stefania [University Federico II, Department of Advanced Biomedical Science, Naples (Italy); SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples (Italy); Prastaro, Maria; Filardi, Pasquale Perrone; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Science, Naples (Italy); Rengo, Giuseppe [University Federico II, Department of Translational Medical Science, Naples (Italy); Salvatore Maugeri Foundation, IRCCS, Istituto di Telese, Benevento, BN (Italy)

    2015-09-15

    Myocardial contractile function is under the control of cardiac sympathetic activity. Three-dimensional speckle tracking echocardiography (3D-STE) and cardiac imaging with {sup 123}I-metaiodobenzylguanidine ({sup 123}I-MIBG) are two sophisticated techniques for the assessment of left ventricular (LV) deformation and sympathetic innervation, respectively, which offer important prognostic information in patients with heart failure (HF). The purpose of this investigation was to explore, in patients with systolic HF, the relationship between LV deformation assessed by 3D-STE and cardiac sympathetic derangement evaluated by {sup 123}I-MIBG imaging. We prospectively studied 75 patients with systolic HF. All patients underwent a 3D-STE study (longitudinal, circumferential, area and radial) and {sup 123}I-MIBG planar and SPECT cardiac imaging. 3D-STE longitudinal, circumferential and area strain values were correlated with {sup 123}I-MIBG late heart to mediastinum (H/M) ratio and late SPECT total defect score. After stratification of the patients according to ischaemic or nonischaemic HF aetiology, we observed a good correlation of all 3D-STE measurements with late H/M ratio and SPECT data in the ischaemic group, but in patients with HF of nonischaemic aetiology, no correlation was found between LV deformation and cardiac sympathetic activity. At the regional level, the strongest correlation between LV deformation and adrenergic innervation was found for the left anterior descending coronary artery distribution territory for all four 3D-STE values. In multivariate linear regression analyses, including age, gender, LV ejection fraction, NYHA class, body mass index, heart rate and HF aetiology, only 3D-STE area and radial strain values significantly predicted cardiac sympathetic derangement on {sup 123}I-MIBG late SPECT. This study indicated that 3D-STE measurements are correlated with {sup 123}I-MIBG planar and SPECT data. Furthermore, 3D-STE area and radial strain values

  3. Autonomic nervous system dysfunction in children with severe tetanus: dissociation of cardiac and vascular sympathetic control

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    Mazzei de Davila C.A.

    2003-01-01

    Full Text Available The medical records of ten pediatric patients with a clinical diagnosis of tetanus were reviewed retrospectively. The heart rate and blood pressure of all tetanus patients were measured noninvasively every hour during the first two weeks of hospitalization. Six of ten tetanus patients presented clinical evidence of sympathetic hyperactivity (group A and were compared with a control group consisting of four children who required mechanical ventilation for diseases other than tetanus (group B. Heart rate and blood pressure simultaneously and progressively increased to a maximum by day 7. The increase over baseline was 43.70 ± 11.77 bpm (mean ± SD for heart rate (P<0.01 and 38.60 ± 26.40 mmHg for blood pressure (P<0.01. These values were higher and significantly different from those of the control group (group B at day 6, which had an average heart rate increase over baseline of 19.35 ± 12.26 bpm (P<0.05 and blood pressure of 10.24 ± 13.30 mmHg (P<0.05. By the end of the second week of hospitalization, in group A the increase of systolic blood pressure over baseline had diminished to 9.60 ± 15.37 mmHg (P<0.05, but the heart rate continued to be elevated (27.80 ± 33.92 bpm, P = NS, when compared to day 7 maximal values. The dissociation of these two cardiovascular variables at the end of the second week of hospitalization suggests the presence of asymmetric cardiac and vascular sympathetic control. One possible explanation for these observations is a selective and delayed action of tetanus toxin on the inhibitory neurons which control sympathetic outflow to the heart.

  4. Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT

    International Nuclear Information System (INIS)

    Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia

    2015-01-01

    Introduction: Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III–IV) after CRT using 11 C-hydroxyephedrine (HED) PET/CT. Methods: Ten IHF patients (mean age = 68; range = 55–81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. Results: At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with “impaired innervation” (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). Conclusion: As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. Advances in Knowledge: These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation

  5. Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.

    Science.gov (United States)

    DiBona, G F; Sawin, L L

    1999-02-01

    To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.

  6. Pneumatic antishock garment inflation activates the human sympathetic nervous system by abdominal compression.

    Science.gov (United States)

    Garvin, Nathan M; Levine, Benjamin D; Raven, Peter B; Pawelczyk, James A

    2014-01-01

    Pneumatic antishock garments (PASG) have been proposed to exert their blood pressure-raising effect mechanically, i.e. by increasing venous return and vascular resistance of the lower body. We tested whether, alternatively, PASG inflation activates the sympathetic nervous system. Five men and four women wore PASG while mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), heart rate and stroke volume were measured. One leg bladder (LEG) and the abdominal bladder (ABD) of the trousers were inflated individually and in combination (ABD+LEG), at 60 or 90 mmHg for 3 min. By the end of 3 min of inflation, conditions that included the ABD region caused significant increases in MAP in a dose-dependent fashion (7 ± 2, 8 ± 3, 14 ± 4 and 13 ± 5 mmHg for ABD60, ABD+LEG60, ABD90 and ABD+LEG90, respectively, P < 0.05). Likewise, inflation that included ABD caused significant increases in total MSNA compared with control values [306 ± 70, 426 ± 98 and 247 ± 79 units for ABD60, ABD90 and ABD+LEG90, respectively, P < 0.05 (units = burst frequency × burst amplitude]. There were no changes in MAP or MSNA in the LEG-alone conditions. The ABD inflation also caused a significant decrease in stroke volume (-11 ± 3 and -10 ± 3 ml per beat in ABD90 and ABD+LEG90, respectively, P < 0.05) with no change in cardiac output. Neither cardiopulmonary receptor deactivation nor mechanical effects can account for a slowly developing rise in both sympathetic activity and blood pressure during ABD inflation. Rather, these data provide direct evidence that PASG inflation activates the sympathetic nervous system secondarily to abdominal, but not leg, compression.

  7. Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study

    Energy Technology Data Exchange (ETDEWEB)

    Gimelli, Alessia; Genovesi, Dario; Giorgetti, Assuero; Kusch, Annette [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Liga, Riccardo [Scuola Superiore Sant' Anna, Pisa (Italy); Marzullo, Paolo [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); CNR, Institute of Clinical Physiology, Pisa (Italy)

    2014-05-15

    To evaluate the relationships among myocardial sympathetic innervation, perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc-telluride (CZT) scintigraphy. A group of 29 patients underwent an evaluation of myocardial perfusion with {sup 99m}Tc-tetrofosmin CZT scintigraphy and adrenergic innervation with {sup 123}I-metaiodobenzylguanidine (MIBG) CZT scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening score (STS), as well as the summed {sup 123}I-MIBG defect score (SS-MIBG), were determined. Regional tracer uptake for both {sup 99m}Tc-tetrofosmin and {sup 123}I-MIBG was also calculated. Finally, the presence of significant myocardial mechanical dyssynchrony was evaluated in phase analysis on gated CZT images and the region of latest mechanical activation identified. Significant mechanical dyssynchrony was present in 17 patients (59 %) and associated with higher SRS (P = 0.030), SMS (P < 0.001), STS (P = 0.003) and early SS-MIBG (P = 0.037) as well as greater impairments in left ventricular ejection fraction (P < 0.001) and end-diastolic volume (P < 0.001). In multivariate analysis a higher end-diastolic volume remained the only predictor of mechanical dyssynchrony (P = 0.047). Interestingly, while in the whole population regional myocardial perfusion and adrenergic activity were strongly correlated (R = 0.68), in patients with mechanical dyssynchrony the region of latest mechanical activation was predicted only by greater impairment in regional {sup 123}I-MIBG uptake (P = 0.012) that overwhelmed the effect of depressed regional perfusion. Left ventricular mechanical dyssynchrony is associated with greater depression in contractile function and greater impairments in regional myocardial perfusion and sympathetic activity. In patients with dyssynchrony, the region of latest mechanical activation is characterized by a significantly altered adrenergic tone. (orig.)

  8. Efeito do carvedilol a curto prazo na atividade simpática cardíaca pela cintilografia com 123I-MIBG Effects of short-term carvedilol on the cardiac sympathetic activity assessed by 123I-MIBG scintigraphy

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    Sandra Marina Ribeiro de Miranda

    2010-03-01

    Full Text Available FUNDAMENTO: Alterações autonômicas na insuficiência cardíaca estão associadas a um aumento da morbimortalidade. Vários métodos não invasivos têm sido empregados para avaliar a função simpática, incluindo a imagem cardíaca com 123I-MIBG. OBJETIVO: Avaliar a atividade simpática cardíaca, por meio da cintilografia com 123I-MIBG, antes e após três meses de terapia com carvedilol em pacientes com insuficiência cardíaca com fração de ejeção do VE BACKGROUND: Autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine (123I-MIBG scintigraphy imaging of the heart. OBJECTIVE: to evaluate the cardiac sympathetic activity through 123I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF < 45%. PATIENTS AND METHODS: Sixteen patients, aged 56.3 ± 12.6 years (11 males, with a mean LVEF of 28% ± 8% and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with 123I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine were measured; the radioisotope ventriculography (RIV was performed before and after a three-month therapy with carvedilol. RESULTS: Patients' functional class showed improvement: before the treatment, 50% of the patients were FC II and 50% were FC III. After 3 months, 7 patients were FC I (43.8% and 9 were FC II (56.2%, (p = 0.0001. The mean LVEF assessed by RIV increased from 29% to 33% (p = 0.017. There was no significant variation in cardiac adrenergic activity assessed by 123I-MIBG (early and late resting images and washout rate. No significant variation was observed regarding the measurement of catecholamines. CONCLUSION: The short-term treatment with carvedilol promoted the clinical

  9. Study of sympathetic nerve activity in young Indian obese individuals

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    B Kalpana

    2013-01-01

    Full Text Available Background: Obesity is the culmination of a chronic imbalance between energy intake and energy expenditure. This energy balance can be potentially affected by the activity of autonomic nervous system (ANS. Altered sympathetic nerve function may be of importance in obesity. Objective: The present study is an attempt to pinpoint the defect (if any in the activity of sympathetic limb of the ANS in obesity, by subjecting to isometric exercise stress. Materials and Methods: A total of 81 females belonging to the age group of 18-22 years were recruited for the study. The participants were divided into two groups as normal weight and obese based on WHO guidelines for Asia Pacific region. After recording the resting blood pressure, they were subjected to isometric exercise by Handgrip dynamometer. Blood pressure was recorded again, and the difference was noted down. All recorded parameters were compared between two groups using unpaired t test. The relationship between body mass index (BMI and rise in diastolic pressure was quantified by Pearson′s correlation test. A P value less than 0.05 was considered as significant. Results: In obese, the diastolic pressure was significantly higher at rest, but showed reduced rise during handgrip test in comparison with normal weight individuals. Also, the rise in diastolic pressure exhibited a negative relation with BMI. Conclusion: The result is suggestive of impaired autonomic function at rest and reduced sympathetic activity in the group of obese when subjected to stress. This could make them more prone for future development of hypertension or other cardiovascular disorders.

  10. Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol on parasympathetic and sympathetic activity: a comparison of clinical results

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    Heather L. Bloom

    2014-08-01

    Full Text Available Background Cardiovascular autonomic neuropathy (CAN is recognized as a significant health risk, correlating with risk of heart disease, silent myocardial ischemia or sudden cardiac death. Beta-blockers are often prescribed to minimize risk. Objectives In this second of two articles, the effects on parasympathetic and sympathetic activity of the alpha/beta-adrenergic blocker, Carvedilol, are compared with those of the selective beta-adrenergic blocker, Metoprolol. Methods Retrospective, serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1 introduced, (2 discontinued or (3 continued without adjustment. Group 3 served as the control. Results Introducing Carvedilol or Metoprolol decreased heart rate and blood pressure, and discontinuing them had the opposite effect. Parasympathetic activity increased with introducing Carvedilol. Sympathetic activity increased more after discontinuing Carvedilol, suggesting better sympathetic suppression. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol. Conclusion Carvedilol has a more profound effect on sympathovagal balance than Metoprolol. While both suppress sympathetic activity, only Carvedilol increases parasympathetic activity. Increased parasympathetic activity may underlie the lower mortality risk with Carvedilol.

  11. Impact of aging on cardiac sympathetic innervation measured by {sup 123}I-mIBG imaging in patients with systolic heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Rengo, Giuseppe; Ferrara, Nicola [Scientific Institute of Telese Terme, Salvatore Maugeri Foundation, IRCCS, Telese Terme (Italy); University of Naples Federico II, Division of Geriatrics, Department of Translational Medical Sciences, Naples (Italy); Pagano, Gennaro; Formisano, Roberto; Komici, Klara; Petraglia, Laura; Parisi, Valentina; Femminella, Grazia Daniela; De Lucia, Claudio; Cannavo, Alessandro; Memmi, Alessia; Leosco, Dario [University of Naples Federico II, Division of Geriatrics, Department of Translational Medical Sciences, Naples (Italy); Vitale, Dino Franco [Scientific Institute of Telese Terme, Salvatore Maugeri Foundation, IRCCS, Telese Terme (Italy); Paolillo, Stefania [Institute of Diagnostic and Nuclear Development, SDN Foundation, Naples (Italy); Attena, Emilio [Fatebenefratelli Hospital, Department of Cardiology, Naples (Italy); Pellegrino, Teresa [Institute of Biostructures and Bioimages of the National Council of Research, Naples (Italy); Federico II University of Naples, Division of Imaging, Radiotherapy, Neuroradiology, and Medical Physics, Department of Advanced Biomedical Sciences, Naples (Italy); Dellegrottaglie, Santo [Ospedale Medico-Chirurgico Accreditato Villa dei Fiori, Division of Cardiology, Acerra, Naples (Italy); Trimarco, Bruno; Filardi, Pasquale Perrone [Federico II University of Naples, Division of Cardiology, Department of Advanced Biomedical Sciences, Naples (Italy); Cuocolo, Alberto [Institute of Diagnostic and Nuclear Development, SDN Foundation, Naples (Italy); Federico II University of Naples, Division of Imaging, Radiotherapy, Neuroradiology, and Medical Physics, Department of Advanced Biomedical Sciences, Naples (Italy)

    2016-12-15

    Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine ({sup 123}I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac {sup 123}I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by {sup 123}I-mIBG scintigraphy, in patients with HF. We studied 180 HF patients (age = 66.1 ± 10.5 years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3 %) undergoing cardiac {sup 123}I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age = 77.7 ± 4.0 year), 67 patients aged 62-72 years (age = 67.9 ± 3.2 years) and 60 patients aged ≤61 year (age = 53.9 ± 5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by {sup 123}I-mIBG imaging. This finding suggests that cardiac {sup 123}I-mIBG uptake in patients with HF might be affected by patient age. (orig.)

  12. Superoxide Anions and NO in the Paraventricular Nucleus Modulate the Cardiac Sympathetic Afferent Reflex in Obese Rats

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    Qing-Bo Lu

    2017-12-01

    Full Text Available This study was conducted to explore the hypothesis that the endogenous superoxide anions (O2− and nitric oxide (NO system of the paraventricular nucleus (PVN regulates the cardiac sympathetic afferent reflex (CSAR contributing to sympathoexcitation in obese rats induced by a high-fat diet (42% kcal as fat for 12 weeks. CSAR was evaluated by monitoring the changes of renal sympathetic nerve activity (RSNA and the mean arterial pressure (MAP responses to the epicardial application of capsaicin (CAP in anaesthetized rats. In obese rats with hypertension (OH group or without hypertension (OB group, the levels of PVN O2−, angiotensinII (Ang II, Ang II type 1 receptor (AT1R, and nicotinamide adenine dinucleotide phosphate (NADPH oxidase were elevated, whereas neural NO synthase (nNOS and NO were significantly reduced. Moreover, CSAR was markedly enhanced, which promoted the elevation of plasma norepinephrine levels. The enhanced CSAR was attenuated by PVN application of the superoxide scavenger polyethylene glycol-superoxide dismutase (PEG-SOD and the NO donor sodium nitroprusside (SNP, and was strengthened by the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC and the nNOS inhibitor N(ω-propyl-l-arginine hydrochloride (PLA; conversely, there was a smaller CSAR response to PLA or SNP in rats that received a low-fat (12% kcal diet. Furthermore, PVN pretreatment with the AT1R antagonist losartan or with PEG-SOD, but not SNP, abolished Ang II-induced CSAR enhancement. These findings suggest that obesity alters the PVN O2− and NO system that modulates CSAR and promotes sympathoexcitation.

  13. Sympathetic- and parasympathetic-linked cardiac function and prediction of externalizing behavior, emotion regulation, and prosocial behavior among preschoolers treated for ADHD.

    Science.gov (United States)

    Beauchaine, Theodore P; Gatzke-Kopp, Lisa; Neuhaus, Emily; Chipman, Jane; Reid, M Jamila; Webster-Stratton, Carolyn

    2013-06-01

    To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia (RSA), an index of parasympathetic-linked cardiac activity, were assessed among 99 preschool children (ages 4-6 years) with ADHD both at rest and in response to behavioral challenge, before participants and their parents completed 1 of 2 versions of the Incredible Years parent and child interventions. Main effects of PEP activity and reactivity and of RSA activity and reactivity were found. Although samplewide improvements in behavior were observed at posttreatment, those who exhibited lengthened cardiac PEP at rest and reduced PEP reactivity to incentives scored higher on measures of conduct problems and aggression both before and after treatment. In contrast, children who exhibited lower baseline RSA and greater RSA withdrawal scored lower on prosocial behavior before and after treatment. Finally, children who exhibited greater RSA withdrawal scored lower on emotion regulation before and after treatment. We discuss these findings in terms of (a) individual differences in underlying neurobiological systems subserving appetitive (i.e., approach) motivation, emotion regulation, and social affiliation and (b) the need to develop more intensive interventions targeting neurobiologically vulnerable children.

  14. Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity.

    Science.gov (United States)

    Day, Danielle S; Gozansky, Wendolyn S; Bell, Christopher; Kohrt, Wendy M

    2011-10-01

    Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA. MSNA was measured in 9 women (30±2 years; mean±SE) on three separate occasions: during the mid-luteal menstrual cycle phase, on the fifth day of gonadotropin-releasing hormone antagonist (GnRHant) administration, and after 5 days add-back of either estradiol (n=4) or progesterone (n=3) during continued GnRHant administration. In response to GnRHant, there were significant reductions in serum estradiol and progesterone (both psuppression attenuates MSNA and that this may be related to the suppression of progesterone rather than estradiol.

  15. Usefulness of severe cardiac sympathetic dysfunction to predict the occurrence of rapid atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

    Science.gov (United States)

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Asano, Taku; Suyama, Jumpei; Tanno, Kaoru; Namiki, Atsuo; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

    2013-09-01

    Atrial fibrillation (AF) can be a potentially life-threatening arrhythmia when it conducts rapidly through the accessory pathway, which was not predicted by the noninvasive method. We evaluated the cardiac sympathetic activity for predicting the occurrence of AF in patients with Wolff-Parkinson-White (WPW) syndrome. Iodine-123 metaiodobenzylguanidine scintigraphy was performed under stable sinus rhythm conditions at rest syndrome than in the normal control group, and in the 15 patients with AF induced during EPS than in the 30 patients without AF (p syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.

    Science.gov (United States)

    Cardinal, R; Nadeau, R; Laurent, C; Boudreau, G; Armour, J A

    1996-09-01

    To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.

  17. Synergistic application of cardiac sympathetic decentralization and comprehensive psychiatric treatment in the management of anxiety and electrical storm

    Directory of Open Access Journals (Sweden)

    Sahib S Khalsa

    2014-01-01

    Full Text Available We report here, for the first time, two cases demonstrating a synergistic application of bilateral cardiac sympathetic decentralization and multimodal psychiatric treatment for the assessment and management of anxiety following recurrent Implantable Cardioverter Defibrillator (ICD shocks. In a first case the combination of bilateral cardiac sympathetic decentralization (BCSD, cognitive behavioral psychotherapy and anxiolytic medication was sufficient to attenuate the patient’s symptoms and maladaptive behaviors, with a maintained benefit at 1 year. Among the more prominent subjective changes, we observed a decrease in aversive interoceptive sensations, particularly of the heartbeat following BCSD. The patient continued to experience cognitive threat appraisals on a frequent basis, although these were no longer incapacitating. In a second case, we report the effect of BCSD on autonomic tone and subjective state. In the post-lesion state we observed attenuated sympathetic responses to the valsalva maneuver, isometric handgrip and mental arithmetic stressor, including decreased systolic and diastolic blood pressure and decreased skin conductance. Collectively, these preliminary findings suggest that an integrative, multidisciplinary approach to treating anxiety disorders in the setting of ventricular arrhythmias and recurrent ICD shocks can result in sustained improvements in physical, psychological and functional status. These findings raise the possibility of a potential role for the stellate ganglion in the modulation of emotional experience and afferent transmission of interoceptive information to the central nervous system.

  18. Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans

    DEFF Research Database (Denmark)

    Eldrup, E; Christensen, N J; Andreasen, J

    1989-01-01

    in diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6.55 (5.03-7.26, median [interquartile range], n = 8) nmol l-1 in diabetics with neuropathy, 7.41 (5.79-7.97, n = 8) nmol l-1...... in diabetics without neuropathy, and 6.85 (5.58-7.36, n = 8) nmol l-1 in controls. No relationship was obtained between baseline values of plasma NE and plasma DOPA. Plasma DOPA did not change in the upright position, whereas plasma NE increased significantly. Our results indicate that plasma DOPA...... is not related to sympathetic activity and may be of non-neuronal origin....

  19. Role of adenosine A2A receptor signaling in the nicotine-evoked attenuation of reflex cardiac sympathetic control

    International Nuclear Information System (INIS)

    El-Mas, Mahmoud M.; El-gowilly, Sahar M.; Fouda, Mohamed A.; Saad, Evan I.

    2011-01-01

    Baroreflex dysfunction contributes to increased cardiovascular risk in cigarette smokers. Given the importance of adenosinergic pathways in baroreflex control, the hypothesis was tested that defective central adenosinergic modulation of cardiac autonomic activity mediates the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate (HR) to increases or decreases in blood pressure (BP) evoked by i.v. doses (1-16 μg/kg) of phenylephrine (PE) and sodium nitroprusside (SNP), respectively, were constructed in conscious rats; slopes of the curves were taken as measures of baroreflex sensitivity (BRS). Nicotine (25 and 100 μg/kg i.v.) dose-dependently reduced BRS SNP in contrast to no effect on BRS PE . BRS SNP was also attenuated after intracisternal (i.c.) administration of nicotine. Similar reductions in BRS SNP were observed in rats pretreated with atropine or propranolol. The combined treatment with nicotine and atropine produced additive inhibitory effects on BRS, an effect that was not demonstrated upon concurrent exposure to nicotine and propranolol. BRS SNP was reduced in preparations treated with i.c. 8-phenyltheophylline (8-PT, nonselective adenosine receptor antagonist), 8-(3-Chlorostyryl) caffeine (CSC, A 2A antagonist), or VUF5574 (A 3 antagonist). In contrast, BRS SNP was preserved after blockade of A 1 (DPCPX) or A 2B (alloxazine) receptors or inhibition of adenosine uptake by dipyridamole. CSC or 8-PT abrogated the BRS SNP depressant effect of nicotine whereas other adenosinergic antagonists were without effect. Together, nicotine preferentially impairs reflex tachycardia via disruption of adenosine A 2A receptor-mediated facilitation of reflex cardiac sympathoexcitation. Clinically, the attenuation by nicotine of compensatory sympathoexcitation may be detrimental in conditions such as hypothalamic defense response, posture changes, and ventricular rhythms. - Research highlights: → The role of central adenosinergic sites in

  20. Thoracoscopic Left Cardiac Sympathetic Denervation for a Patient with Catecholaminergic Polymorphic Ventricular Tachycardia and Recurrent Implantable Cardioverter-Defibrillator Shocks

    Directory of Open Access Journals (Sweden)

    Woo-Sik Yu

    2015-06-01

    Full Text Available A patient presented with loss of consciousness and conversion. During an exercise test, catecholaminergic polymorphic ventricular tachycardia (CPVT resulted in cardiac arrest. He started taking medication (a beta-blocker and flecainide and an implantable cardioverter defibrillator (ICD was inserted, but the ventricular tachycardia did not resolve. Left cardiac sympathetic denervation (LCSD was then performed under general anesthesia, and the patient was discharged on the second postoperative day without complications. One month after the operation, no shock had been administered by the ICD, and an exercise stress test did not induce ventricular tachycardia. Although beta- blockers are the gold standard of therapy in patients with CPVT, thoracoscopic LCSD is safe and can be an effective alternative treatment option for patients with intractable CPVT.

  1. Significance of cardiac sympathetic nervous system abnormality for predicting vascular events in patients with idiopathic paroxysmal atrial fibrillation

    International Nuclear Information System (INIS)

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Kawamura, Mitsuharu; Asano, Taku; Hamazaki, Yuji; Tanno, Kaoru; Kobayashi, Youichi; Suyama, Jumpei; Shinozuka, Akira; Gokan, Takehiko

    2010-01-01

    Neuronal system activity plays an important role for the prognosis of patients with atrial fibrillation (AF). Using 123 I metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy, we investigated whether a cardiac sympathetic nervous system (SNS) abnormality would be associated with an increased risk of vascular events in patients with paroxysmal AF. 123 I-MIBG scintigraphy was performed in 69 consecutive patients (67 ± 13 years, 62% men) with paroxysmal AF who did not have structural heart disease. SNS integrity was assessed from the heart to mediastinum (H/M) ratio on delayed imaging. Serum concentration of C-reactive protein (CRP) was measured before 123 I-MIBG study. During a mean of 4.5 ± 3.6 years follow-up, 19 patients had myocardial infarction, stroke or heart failure (range: 0.2-11.5 years). SNS abnormality (H/M ratio <2.7) and high CRP (≥0.3 mg/dl) were associated with the vascular events (58.3% in 14 of 24 patients with SNS abnormality vs 11.1% in 5 of 45 patients without SNS abnormality, p < 0.0001, 52.4% in 11 of 21 patients with high CRP vs 16.7% in 8 of 48 patients without high CRP, p < 0.0001). After adjustment for potential confounding variables such as age, left atrial dimension and left ventricular function, SNS abnormality was an independent predictor of vascular events with a hazard ratio of 4.1 [95% confidence interval (CI): 1.3-12.6, p = 0.014]. Further, SNS abnormality had an incremental and additive prognostic power in combination with high CRP with an adjusted hazard ratio of 4.1 (95% CI: 1.5-10.9, p = 0.006). SNS abnormality is predictive of vascular events in patients with idiopathic paroxysmal AF. (orig.)

  2. Significance of cardiac sympathetic nervous system abnormality for predicting vascular events in patients with idiopathic paroxysmal atrial fibrillation

    Energy Technology Data Exchange (ETDEWEB)

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Kawamura, Mitsuharu; Asano, Taku; Hamazaki, Yuji; Tanno, Kaoru; Kobayashi, Youichi [Showa University School of Medicine, Division of Cardiology, Department of Medicine, Tokyo (Japan); Suyama, Jumpei; Shinozuka, Akira; Gokan, Takehiko [Showa University School of Medicine, Department of Radiology, Tokyo (Japan)

    2010-04-15

    Neuronal system activity plays an important role for the prognosis of patients with atrial fibrillation (AF). Using {sup 123}I metaiodobenzylguanidine ({sup 123}I-MIBG) scintigraphy, we investigated whether a cardiac sympathetic nervous system (SNS) abnormality would be associated with an increased risk of vascular events in patients with paroxysmal AF. {sup 123}I-MIBG scintigraphy was performed in 69 consecutive patients (67 {+-} 13 years, 62% men) with paroxysmal AF who did not have structural heart disease. SNS integrity was assessed from the heart to mediastinum (H/M) ratio on delayed imaging. Serum concentration of C-reactive protein (CRP) was measured before {sup 123}I-MIBG study. During a mean of 4.5 {+-} 3.6 years follow-up, 19 patients had myocardial infarction, stroke or heart failure (range: 0.2-11.5 years). SNS abnormality (H/M ratio <2.7) and high CRP ({>=}0.3 mg/dl) were associated with the vascular events (58.3% in 14 of 24 patients with SNS abnormality vs 11.1% in 5 of 45 patients without SNS abnormality, p < 0.0001, 52.4% in 11 of 21 patients with high CRP vs 16.7% in 8 of 48 patients without high CRP, p < 0.0001). After adjustment for potential confounding variables such as age, left atrial dimension and left ventricular function, SNS abnormality was an independent predictor of vascular events with a hazard ratio of 4.1 [95% confidence interval (CI): 1.3-12.6, p = 0.014]. Further, SNS abnormality had an incremental and additive prognostic power in combination with high CRP with an adjusted hazard ratio of 4.1 (95% CI: 1.5-10.9, p = 0.006). SNS abnormality is predictive of vascular events in patients with idiopathic paroxysmal AF. (orig.)

  3. Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

    Science.gov (United States)

    Baron, R; Wasner, G; Borgstedt, R; Hastedt, E; Schulte, H; Binder, A; Kopper, F; Rowbotham, M; Levine, J D; Fields, H L

    1999-03-23

    Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

  4. Clinical usefulness of 123I-metaiodobenzylguanidine myocardial scintigraphy in diabetic patients with cardiac sympathetic nerve dysfunction

    International Nuclear Information System (INIS)

    Miyanaga, Hajime; Yoneyama, Satoshi; Kamitani, Tadaaki; Kawasaki, Shingo; Takahashi, Toru; Kunishige, Hiroshi

    1995-01-01

    To assess the clinical utility of 123 I-metaiodobenzylguanidine (MIBG) scintigraphy in evaluating cardiac sympathetic nerve disturbance in diabetic patients, we performed MIBG scintigraphy in 18 diabetic patients and 11 normal controls. Diabetic patients with symptomatic neuropathy (DM2) had a significantly lower heart to mediastinum uptake ratio than did those without neuropathy or normal controls in initial and delayed images (initial image, 1.90±0.27 vs 2.32±0.38, 2.41±0.40, p<0.01; delayed image, 1.80±0.31 vs 2.48±0.35, 2.56±0.28, p<001, respectively). Defect score, assessed visually, were higher in DM2 patients than in patients in the other two groups (initial image, 7±2.6 vs 1.5±1.9, 0.7±0.9; delayed image 10.6±3.3 vs 4.0±2.5, 1.7±1.6 p<0.01, respectively). The maximum washout rate in DM2 patients was also higher than those in patients in the other two groups. The findings of these indices obtained from MIBG scintigraphy coincided with the % low-frequency power extracted from heart rate fluctuations using a power spectral analysis and the results of the Schellong test, which were used to evaluate sympathetic function. These results suggest that MIBG scintigraphy may be useful for evaluating cardiac sympathetic nerve disturbance in patients with diabetes. (author)

  5. Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans

    NARCIS (Netherlands)

    Kienbaum, P.; Heuter, T.; Michel, M. C.; Peters, J.

    2000-01-01

    BACKGROUND: Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent

  6. Further analysis of the inhibition by agmatine on the cardiac sympathetic outflow: Role of the α2-adrenoceptor subtypes.

    Science.gov (United States)

    Cobos-Puc, Luis; Aguayo-Morales, Hilda; Ventura-Sobrevilla, Janeth; Luque-Contreras, Diana; Chin-Chan, Miguel

    2017-06-15

    This study has investigated the role of the α 2 -adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300μg/kg; α 2A ), imiloxan (3000μg/kg; α 2B ), and JP-1302 (300μg/kg; α 2C ) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine. Also, the effect of the combination BRL 44408 plus JP-1302 plus AGN 192403 (3000μg/kg; I 1 antagonist) was evaluated. In this way, i.v. infusions of 1000μg/kg min of agmatine, but not 300, inhibited the tachycardic response induced by electrical stimulation. Furthermore, the antagonists used or their combinations had no effect on the electrically-induced tachycardic response. On the other hand, the inhibitory response of agmatine was: (1) partially antagonized by BRL 44408 or JP-1302 given separately, a similar response was observed when we administered their combination with imiloxan, but not by imiloxan alone, (2) antagonized in greater magnitude by the combination BRL 44408 plus JP-1302 or the combination BRL 44408 plus imiloxan plus JP-1302, and (3) abolished by the combination BRL 44408 plus JP-1302 plus AGN 192403. Taken together, these results demonstrate that the α 2A - and α 2C -adrenoceptor subtypes and I 1 -imidazoline receptors are involved in the inhibition of the cardiac sympathetic outflow induced by agmatine. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and γ-amino butyric acid in hypertensive rats.

    Science.gov (United States)

    Zhou, Hong; Sun, Hai-jian; Chang, Jin-rui; Ding, Lei; Gao, Qing; Tang, Chao-shu; Zhu, Guo-qing; Zhou, Ye-bo

    2014-10-01

    Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) and involves in the regulation of cardiovascular function in both peripheral tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of hypothalamus is an important site in the control of cardiac sympathetic afferent reflex (CSAR) which participates in sympathetic over-excitation of hypertension. The aim of this study is to investigate whether IMD in the PVN is involved in the inhibition of CSAR and its related mechanism in hypertension. Rats were subjected to two-kidney one-clip (2K1C) surgery to induce renovascular hypertension or sham-operation (Sham). Acute experiments were carried out four weeks later under anesthesia. The CSAR was evaluated with the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin. The RSNA and MAP were recorded in sinoaortic-denervated, cervical-vagotomized and anesthetized rats. Bilateral PVN microinjection of IMD (25 pmol) caused greater decrease in the CSAR in 2K1C rats than in Sham rats, which was prevented by pretreatment with adrenomedullin (AM) receptor antagonist AM22-52, non-selective nitric oxide (NO) synthase (NOS) inhibitor L-NAME or γ-amino butyric acid (GABA)B receptor blocker CGP-35348. PVN pretreatment with CGRP receptor antagonist CGRP8-37 or GABA(A) receptor blocker gabazine had no significant effect on the CSAR response to IMD. AM22-52, L-NAME and CGP-35348 in the PVN could increase CSAR in Sham and 2K1C rats. These data indicate that IMD in the PVN inhibits CSAR via AM receptor, and both NO and GABA in the PVN involve in the effect of IMD on CSAR in Sham and renovascular hypertensive rats. © 2014 by the Society for Experimental Biology and Medicine.

  8. {sup 123}I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Noordzij, Walter; Glaudemans, Andor W.J.M.; Rheenen, Ronald W.J. van; Dierckx, Rudi A.J.O.; Slart, Riemer H.J.A. [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, PO Box 30.001, Groningen (Netherlands); Hazenberg, Bouke P.C. [University of Groningen, Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen (Netherlands); Tio, Rene A. [University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen (Netherlands)

    2012-10-15

    Cardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. {sup 123}I-MIBG can detect these innervation changes. Patients with biopsy-proven amyloidosis underwent general work-up, echocardiography and {sup 123}I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG. Included in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 {+-} 0.75, and the mean wash-out rate was 8.6 {+-} 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 {+-} 0.70 versus 2.8 {+-} 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (-3.3 {+-} 9.9 % vs. 17 {+-} 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 {+-} 0.59 vs. 2.9 {+-} 0.50, p = 0.007). MIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, {sup 123}I-MIBG scintigraphy can detect cardiac denervation in

  9. Contemporary review on the pathogenesis of takotsubo syndrome: The heart shedding tears: Norepinephrine churn and foam at the cardiac sympathetic nerve terminals.

    Science.gov (United States)

    Y-Hassan, Shams; De Palma, Rodney

    2017-02-01

    Takotsubo syndrome (TS), an increasingly recognized acute cardiac disease entity, is characterized by a unique pattern of circumferential and typically regional left ventricular wall motion abnormality resulting in a conspicuous transient ballooning of the left ventricle during systole. The mechanism of the disease remains elusive. However, the sudden onset of acute myocardial stunning in a systematic pattern extending beyond a coronary artery territory; the history of a preceding emotional or physical stress factor in two thirds of cases; the signs of sympathetic denervation at the regions of left ventricular dysfunction on sympathetic scintigraphy; the finding of myocardial edema and other signs consistent with (catecholamine-induced) myocarditis shown by cardiac magnetic resonance imaging; and the contraction band necrosis on histopathological examination all argue strongly for the involvement of the cardiac sympathetic nervous system in the pathogenesis of TS. In this narrative review, extensive evidence in support of local cardiac sympathetic nerve hyperactivation, disruption and norepinephrine spillover causing TS in predisposed patients is provided. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Influence of exercise modality on cardiac parasympathetic and sympathetic indices during post-exercise recovery.

    Science.gov (United States)

    Michael, Scott; Jay, Ollie; Graham, Kenneth S; Davis, Glen M

    2018-02-12

    This study investigated indirect measures of post-exercise parasympathetic reactivation (using heart-rate-variability, HRV) and sympathetic withdrawal (using systolic-time-intervals, STI) following upper- and lower-body exercise. Randomized, counter-balanced, crossover. 13 males (age 26.4±4.7years) performed maximal arm-cranking (MAX-ARM) and leg-cycling (MAX-LEG). Subsequently, participants undertook separate 8-min bouts of submaximal HR-matched exercise of each mode (ARM and LEG). HRV (including natural-logarithm of root-mean-square-of-successive-differences, Ln-RMSSD) and STI (including pre-ejection-period, PEP) were assessed throughout 10-min seated recovery. Peak-HR was higher (p=0.001) during MAX-LEG (182±7beatsmin -1 ) compared with MAX-ARM (171±12beatsmin -1 ), while HR (preflecting sympathetic withdrawal). Exercise modality appears to influence post-exercise parasympathetic reactivation and sympathetic withdrawal in an intensity-dependent manner. These results highlight the need for test standardization and may be relevant to multi-discipline athletes and in clinical applications with varying modes of exercise testing. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  11. Effect of experimental hyperinsulinemia on sympathetic nervous system activity in the rat

    International Nuclear Information System (INIS)

    Young, J.B.

    1988-01-01

    Since insulin acutely stimulates the sympathetic nervous system, a role for sympathetic overactivity has been hypothesized to underlie the association between chronic hyperinsulinemia and hypertension. To assess the effect of sustained hyperinsulinemia on sympathetic function, [ 3 H]norepinephrine (NE) turnover was measured in rats injected with insulin for 14d. NE turnover in insulin-treated animals given free access to lab chow and a 10% sucrose solution was compared with that obtained in rats fed chow alone or chow plus sucrose. Sucrose ingestion increased NE turnover in heart, brown adipose tissue, and liver, but exogenous insulin did not augment turnover beyond that seen in animals given sucrose alone. This study, therefore, provides no evidence that chronic hyperinsulinemia, sufficient to induce peripheral insulin resistance, stimulates sympathetic activity more than that produced by chronic sucrose ingestion

  12. Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids.

    Science.gov (United States)

    Seidler, Frederic J; Slotkin, Theodore A

    2011-05-30

    Early-life exposure to organophosphate pesticides leads to subsequent hyperresponsiveness of β-adrenergic receptor-mediated cell signaling that regulates hepatic gluconeogenesis, culminating in metabolic abnormalities resembling prediabetes. In the current study, we evaluated the effects of chlorpyrifos or parathion on presynaptic sympathetic innervation to determine whether the postsynaptic signaling effects are accompanied by defects in neuronal input. We administered either chlorpyrifos or parathion to newborn rats using exposure paradigms known to elicit the later metabolic changes but found no alterations in either hepatic or cardiac norepinephrine levels in adolescence or adulthood. However, shifting chlorpyrifos exposure to the prenatal period did evoke changes: exposure early in gestation produced subsequent elevations in norepinephrine, whereas later gestational exposure produced significant deficits. We also distinguished the organophosphate effects from those of the glucocorticoid, dexamethasone, a known endocrine disruptor that leads to later-life metabolic and cardiovascular disruption. Postnatal exposure to dexamethasone elicited deficits in peripheral norepinephrine levels but prenatal exposure did not. Our results indicate that early-life exposure to organophosphates leads to subsequent abnormalities of peripheral sympathetic innervation through mechanisms entirely distinct from those of glucocorticoids, ruling out the possibility that the organophosphate effects are secondary to stress or disruption of the HPA axis. Further, the effects on innervation were separable from those on postsynaptic signaling, differing in critical period as well as tissue- and sex-selectivity. Organophosphate targeting of both presynaptic and postsynaptic β-adrenergic sites, each with different critical periods of vulnerability, thus sets the stage for compounding of hepatic and cardiac functional abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.

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    Yrsa Bergmann Sverrisdóttir

    Full Text Available BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m, (age 37+/-11 yrs, (BMI 24+/-3 kg/m(2 direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index, was within the normal range (1.9-3.3 and MSNA was as expected for age and gender (13-44 burst/minute. RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005. RH-PAT index and MSNA were reciprocally related to time (h/week spent on physical activity (p = 0.005 and p = 0.006 respectively and platelet concentration (PLT (p = 0.02 and p = 0.004 respectively. CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular

  14. Contributions of central command and muscle feedback to sympathetic nerve activity in contracting human skeletal muscle

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    Daniel eBoulton

    2016-05-01

    Full Text Available During voluntary contractions, muscle sympathetic nerve activity (MSNA to contracting muscles increases in proportion to force but the underlying mechanisms are not clear. To shed light on these mechanisms, particularly the influences of central command and muscle afferent feedback, the present study tested the hypothesis that MSNA is greater during voluntary compared with electrically-evoked contractions. Seven male subjects performed a series of 1-minute isometric dorsiflexion contractions (left leg separated by 2-minute rest periods, alternating between voluntary and electrically-evoked contractions at similar forces (5-10 % of maximum. MSNA was recorded continuously (microneurography from the left peroneal nerve and quantified from cardiac-synchronised, negative-going spikes in the neurogram. Compared with pre-contraction values, MSNA increased by 51 ± 34 % (P 0.05. MSNA analysed at 15-s intervals revealed that this effect of voluntary contraction appeared 15-30 s after contraction onset (P < 0.01, remained elevated until the end of contraction, and disappeared within 15 s after contraction. These findings suggest that central command, and not feedback from contracting muscle, is the primary mechanism responsible for the increase in MSNA to contracting muscle. The time-course of MSNA suggests that there is a longer delay in the onset of this effect compared with its cessation after contraction.

  15. RESISTIN, AN ADIPOKINE WITH NON-GENERALISED ACTIONS ON SYMPATHETIC NERVE ACTIVITY

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    Emilio eBadoer

    2015-11-01

    Full Text Available The World Health Organisation has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the skeletal muscle vasculature and to the kidneys. Obesity is now recognised as a chronic, low level inflammatory condition and pro-inflammatory cytokines are elevated including those produced by adipose tissue. The most well known adipokine released from fat tissue is leptin. The adipokine, resistin,, is also released from adipose tissue. Resistin can act in the central nervous system to influence the sympathetic nerve activity. Here, we review the effects of resistin on sympathetic nerve activity and compare them with leptin. We build an argument that resistin and leptin may have complex interactions. Firstly, they may augment each other as both are excitatory on sympathetic nerves innervating cardiovascular organs; In contrast, they could antagonize each other’s actions on brown adipose tissue, a key metabolic organ. These interactions may be important in conditions in which leptin and resistin are elevated, such as in obesity.

  16. Carotid body (Thermoreceptors, sympathetic neural activation, and cardiometabolic disease

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    Rodrigo Iturriaga

    Full Text Available The carotid body (CB is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome.

  17. Impact of malnutrition on cardiac autonomic modulation in children

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    Gláucia Siqueira Carvalho Barreto

    2016-11-01

    Conclusion: Malnourished children present changes in cardiac autonomic modulation, characterized by reductions in both sympathetic and parasympathetic activity, as well as increased heart rate and decreased blood pressure.

  18. Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

    Science.gov (United States)

    Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

    2017-01-01

    Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Marital Conflict and Children's Externalizing Behavior: Interactions between Parasympathetic and Sympathetic Nervous System Activity

    Science.gov (United States)

    El-Sheikh, Mona; Kouros, Chrystyna D.; Erath, Stephen; Cummings, E. Mark; Keller, Peggy; Staton, Lori

    2009-01-01

    Toward greater specificity in the prediction of externalizing problems in the context of interparental conflict, interactions between children's parasympathetic and sympathetic nervous system (PNS and SNS) activity were examined as moderators. PNS activity was indexed by respiratory sinus arrhythmia (RSA) and RSA reactivity (RSA-R) to lab…

  20. Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

    Science.gov (United States)

    Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Bivens, Tiffany B; Adams-Huet, Beverley; Levine, Benjamin D; Fu, Qi

    2013-01-01

    Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)−1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)−1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)−1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)−1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin–angiotensin–aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive

  1. Adolescent sympathetic activity and salivary C-reactive protein: The effects of parental behavior.

    Science.gov (United States)

    Nelson, Benjamin W; Byrne, Michelle L; Simmons, Julian G; Whittle, Sarah; Schwartz, Orli S; Reynolds, Eric C; O'Brien-Simpson, Neil M; Sheeber, Lisa; Allen, Nicholas B

    2017-10-01

    This study utilized a novel multisystem approach to investigate the effect of observed parental behavior on the relationship between biological mechanisms associated with disease processes (i.e., autonomic physiology and immune response) among their adolescent children. Thirty-three adolescents (23 males), aged 11-13, and their parents participated in a laboratory session in which adolescents provided baseline measures of autonomic (sympathetic) activity, and adolescents and 1 parent participated in a laboratory based dyadic conflict resolution interaction task. This included 3 male parent/male adolescent dyads, 20 female parent/male adolescent dyads, 3 male parent/female adolescent dyads, and 7 female parent/female adolescent dyads. Approximately 3 years later, adolescents provided a salivary measure of C-Reactive Protein (sCRP) to index inflammation. Analyses revealed a positive association between sympathetic activity and sCRP, as well as a moderating role of positive parental behavior in this relationship, such that the association between sympathetic activity and sCRP was greater among adolescents whose parents displayed shorter duration of positive affect. Overall findings indicate parental behavior may influence the association between adolescent sympathetic activity and inflammatory processes. These findings have important implications for understanding the impact of psychosocial factors on biological mechanisms of disease. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Mechanisms of sympathetic activation and blood pressure elevation by intermittent hypoxia.

    Science.gov (United States)

    Prabhakar, Nanduri R; Kumar, Ganesh K

    2010-11-30

    Sleep disordered breathing with recurrent apneas is one of the most frequently encountered breathing disorder in adult humans and preterm infants. Recurrent apnea patients exhibit several co-morbidities including hypertension and persistent sympathetic activation. Intermittent hypoxia (IH) resulting from apneas appears to be the primary stimulus for evoking autonomic changes. The purpose of this article is to briefly review the effects of IH on chemo- and baro-reflexes and circulating vasoactive hormones and their contribution to sympathetic activation and blood pressures. Sleep apnea patients and IH-treated rodents exhibit exaggerated arterial chemo-reflex. Studies on rodent models demonstrated that IH leads to hyperactive carotid body response to hypoxia. On the other hand, baro-reflex function is attenuated in patients with sleep apnea and in IH-treated rodents. Circulating vasoactive hormone levels are elevated in sleep apnea patients and in rodent models of IH. Thus, persistent sympathetic activation and hypertension associated with sleep apneas seems to be due to a combination of altered chemo- and baro-reflexes resulting in sympathetic activation and action of elevated circulating levels of vasoactive hormones on vasculature. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Exercise training attenuates sympathetic activation and oxidative stress in diet-induced obesity.

    Science.gov (United States)

    Li, G; Liu, J-Y; Zhang, H-X; Li, Q; Zhang, S-W

    2015-01-01

    It is known that excessive sympathetic activity and oxidative stress are enhanced in obesity. This study aimed to clarify whether exercise training (ET) attenuates sympathetic activation and oxidative stress in obesity. The obesity was induced by high-fat diet (HFD) for 12 weeks. Male Sprague-Dawley rats were assigned to four groups: regular diet (RD) plus sedentary (RD-S), RD plus ET (RD-ET), HFD plus sedentary (HFD-S), and HFD plus ET (HFD-ET). The rats in RD-ET and HFD-ET groups were trained on a motorized treadmill for 60 min/day, five days/week for 8 weeks. The sympathetic activity was evaluated by the plasma norepinephrine (NE) level. The superoxide anion, malondialdehyde and F2-isoprostanes levels in serum and muscles were measured to evaluate oxidative stress. The ET prevented the increases in the body weight, arterial pressure and white adipose tissue mass in HFD rats. The NE level in plasma and oxidative stress related parameters got lower in HFD-ET group compared with HFD-S group. We have found decreased mRNA and protein levels of toll-like receptor (TLR)-2 and TLR-4 by ET in HFD rats. These findings suggest that ET may be effective for attenuating sympathetic activation and oxidative stress in diet-induced obesity.

  4. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans

    NARCIS (Netherlands)

    Kox, M.; Eijk, L.T.G.J. van; Zwaag, J.; Wildenberg, J. van den; Sweep, F.C.; Hoeven, J.G. van der; Pickkers, P.

    2014-01-01

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot

  5. Enhanced sympathetic arousal in response to FMRI scanning correlates with task induced activations and deactivations.

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    Markus Muehlhan

    Full Text Available It has been repeatedly shown that functional magnetic resonance imaging (fMRI triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA, as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults.

  6. Functional role of diverse changes in sympathetic nerve activity in regulating arterial pressure during REM sleep.

    Science.gov (United States)

    Yoshimoto, Misa; Yoshida, Ikue; Miki, Kenju

    2011-08-01

    This study aimed to investigate whether REM sleep evoked diverse changes in sympathetic outflows and, if so, to elucidate why REM sleep evokes diverse changes in sympathetic outflows. Male Wistar rats were chronically implanted with electrodes to measure renal (RSNA) and lumbar sympathetic nerve activity (LSNA), electroencephalogram, electromyogram, and electrocardiogram, and catheters to measure systemic arterial and central venous pressure; these parameters were measured simultaneously and continuously during the sleep-awake cycle in the same rat. REM sleep resulted in a step reduction in RNSA by 36.1% ± 2.7% (P sleep. In contrast to REM sleep, RSNA, LSNA, systemic arterial pressure, and heart rate increased in a unidirectional manner associated with increases in physical activity levels in the order from NREM sleep, quiet awake, moving, and grooming state. Thus, the relationship between RSNA vs. LSNA and systemic arterial pressure vs. heart rate observed during REM sleep was dissociated compared with that obtained during the other behavioral states. It is suggested that the diverse changes in sympathetic outflows during REM sleep may be needed to increase systemic arterial pressure by balancing vascular resistance between muscles and vegetative organs without depending on the heart.

  7. Targeted NGF siRNA delivery attenuates sympathetic nerve sprouting and deteriorates cardiac dysfunction in rats with myocardial infarction.

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    Hesheng Hu

    Full Text Available Nerve growth factor (NGF is involved in nerve sprouting, hyper-innervation, angiogenesis, anti-apoptosis, and preservation of cardiac function after myocardial infarction (MI. Positively modulating NGF expression may represent a novel pharmacological strategy to improve post-infarction prognosis. In this study, lentivirus encoding NGF short interfering RNA (siRNA was prepared, and MI was modeled in the rat using left anterior descending coronary artery ligation. Rats were randomly grouped to receive intramyocardial injection of lentiviral solution containing NGF-siRNA (n = 19, MI-SiNGF group, lentiviral solution containing empty vector (n = 18, MI-GFP group or 0.9% NaCl solution (n = 18, MI-control group, or to receive thoracotomy and pericardiotomy (n = 17, sham-operated group. At 1, 2, 4, and 8 wk after transduction, rats in the MI-control group had higher levels of NGF mRNA and protein than those in the sham-operated group, rats in the MI-GFP group showed similar levels as the MI-control group, and rats in the MI-SiNGF group had lower levels compared to the MI-GFP group, indicating that MI model was successfully established and NGF siRNA effectively inhibited the expression of NGF. At 8 wk, echocardiographic and hemodynamic studies revealed a more severe cardiac dysfunction in the MI-siRNA group compared to the MI-GFP group. Moreover, rats in the MI-siRNA group had lower mRNA and protein expression levels of tyrosine hydroxylase (TH and growth-associated protein 43-positive nerve fibers (GAP-43 at both the infarcted border and within the non-infarcted left ventricles (LV. NGF silencing also reduced the vascular endothelial growth factor (VEGF expression and decreased the arteriolar and capillary densities at the infarcted border compared to the MI-GFP group. Histological analysis indicated a large infarcted size in the MI-SiNGF group. These findings suggested that endogenous NGF silencing attenuated sympathetic nerve sprouting

  8. Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Oey, P.L.; Vos, P.E.; Wieneke, G.H.; Wokke, J.H.J.; Blankestijn, P.J.; Karemaker, J.M.

    2002-01-01

    The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

  9. Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Oey, P. Liam; Vos, Pieter E.; Wieneke, George H.; Wokke, John H. J.; Blankestijn, Peter J.; Karemaker, John M.

    2002-01-01

    The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

  10. Clonidine, an α2 receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

    OpenAIRE

    Philbin, Kerry E.; Bateman, Ryan J.; Mendelowitz, David

    2010-01-01

    In hypertension there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Pre-sympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these pre-sympathetic neurons are catecholaminergic. In addition to their projection to the spina...

  11. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

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    Marcus May

    Full Text Available Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.ClinicalTrials.gov NCT01237431.

  12. Increase in Operator's Sympathetic Nerve Activity during Complicated Hepatobiliary Surgery: Evidence for Surgeons' Mental Stress.

    Science.gov (United States)

    Yamanouchi, Kosho; Hayashida, Naomi; Kuba, Sayaka; Sakimura, Chika; Kuroki, Tamotsu; Togo, Michita; Katayama, Noritada; Takamura, Noboru; Eguchi, Susumu

    2015-11-01

    Surgeons often experience stress during operations. The heart rate variability (HRV) is the variability in the beat-to-beat interval, which has been used as parameters of stress. The purpose of this study was to evaluate mental stress of surgeons before, during and after operations, especially during pancreaticoduodenectomy (PD) and living donor liver transplantation (LDLT). Additionally, the parameters were compared in various procedures during the operations. By frequency domain method using electrocardiograph, we measured the high frequency (HF) component, representing the parasympathetic activity, and the low frequency (LF)/HF ratio, representing the sympathetic activity. In all 5 cases of PD, the surgeon showed significantly lower HF component and higher LF/HF during operation, indicating predominance of sympathetic nervous system and increased stress, than those before the operation (p operation. Out of the 4 LDLT cases, the value of HF was decreased in two and the LF/HF increased in three cases (p operation compared to those before the operation. In all cases, the value of HF was decreased and/or the LF/HF increased significantly during the reconstruction of the vessels or bile ducts than during the removal of the liver. Thus, sympathetic nerve activity increased during hepatobiliary surgery compared with the level before the operation, and various procedures during the operations induced diverse changes in the autonomic nervous activities. The HRV analysis could assess the chronological changes of mental stress by measuring the autonomic nervous balances.

  13. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    Science.gov (United States)

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens

    2011-01-01

    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration ClinicalTrials.gov NCT01237431 PMID:22016786

  14. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    International Nuclear Information System (INIS)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-01-01

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  15. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria; Laorden, María-Luisa

    2015-02-15

    There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated by naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone

  16. Mechanisms of Sympathetic Activation and Blood Pressure Elevation by Intermittent Hypoxia

    OpenAIRE

    Prabhakar, Nanduri R.; Kumar, Ganesh K.

    2010-01-01

    Sleep disordered breathing with recurrent apneas is one of the most frequently encountered breathing disorder in adult humans and preterm infants. Recurrent apnea patients exhibit several co-morbidities including hypertension and persistent sympathetic activation. Intermittent hypoxia (IH) resulting from apneas appears to be the primary stimulus for evoking autonomic changes. The purpose of this article is to briefly review the effects of IH on chemo-and baro-reflexes and circulating vasoacti...

  17. The pattern of activation of the sympathetic nervous system during tilt-induced syncope.

    Science.gov (United States)

    Zyśko, Dorota; Gajek, Jacek; Sciborski, Ryszard; Smereka, Jacek; Checiński, Igor; Mazurek, Walentyna

    2007-04-01

    A 49-year-old patient with a history of situational syncope and minimal electrocardiographic signs of accessory pathway is described. The evidence for pre-excitation was present only during the sympathetic activation caused by exercise testing and isoprenaline infusion. This phenomenon served as an indicator of significant adrenergic drive to the heart after the tilt-induced syncope. The meaning of the observed electrocardiographic changes in the course of neurocardiogenic reaction and its contribution to the understanding of the sympatho-vagal balance during vasovagal syncope is discussed. The lack of preexcitation signs during syncope and its appearance several seconds after the syncope-related sinus pause indicates sympathetic withdrawal before and shortly after the asystole. The possible pathophysiological mechanisms are discussed.

  18. Pituitary adenylate cyclase-activating polypeptide stimulates glucose production via the hepatic sympathetic innervation in rats.

    Science.gov (United States)

    Yi, Chun-Xia; Sun, Ning; Ackermans, Mariette T; Alkemade, Anneke; Foppen, Ewout; Shi, Jing; Serlie, Mireille J; Buijs, Ruud M; Fliers, Eric; Kalsbeek, Andries

    2010-07-01

    The unraveling of the elaborate brain networks that control glucose metabolism presents one of the current challenges in diabetes research. Within the central nervous system, the hypothalamus is regarded as the key brain area to regulate energy homeostasis. The aim of the present study was to investigate the hypothalamic mechanism involved in the hyperglycemic effects of the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). Endogenous glucose production (EGP) was determined during intracerebroventricular infusions of PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. The specificity of their receptors was examined by coinfusions of receptor antagonists. The possible neuronal pathway involved was investigated by 1) local injections in hypothalamic nuclei, 2) retrograde neuronal tracing from the thoracic spinal cord to hypothalamic preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic or parasympathetic denervation to block the autonomic neuronal input to liver. Intracerebroventricular infusion of PACAP-38 increased EGP to a similar extent as a VIP/PACAP-2 (VPAC2) receptor agonist, and intracerebroventricular administration of VIP had significantly less influence on EGP. The PACAP-38 induced increase of EGP was significantly suppressed by preinfusion of a VPAC2 but not a PAC1 receptor antagonist, as well as by hepatic sympathetic but not parasympathetic denervation. In the hypothalamus, Fos immunoreactivity induced by PACAP-38 was colocalized within autonomic neurons in paraventricular nuclei projecting to preganglionic sympathetic neurons in the spinal cord. Local infusion of PACAP-38 directly into the PVN induced a significant increase of EGP. This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production.

  19. The pedunculopontine tegmentum controls renal sympathetic nerve activity and cardiorespiratory activities in nembutal-anesthetized rats.

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    Anne M Fink

    Full Text Available Elevated renal sympathetic nerve activity (RSNA accompanies a variety of complex disorders, including obstructive sleep apnea, heart failure, and chronic kidney disease. Understanding pathophysiologic renal mechanisms is important for determining why hypertension is both a common sequelae and a predisposing factor of these disorders. The role of the brainstem in regulating RSNA remains incompletely understood. The pedunculopontine tegmentum (PPT is known for regulating behaviors including alertness, locomotion, and rapid eye movement sleep. Activation of PPT neurons in anesthetized rats was previously found to increase splanchnic sympathetic nerve activity and blood pressure, in addition to altering breathing. The present study is the first investigation of the PPT and its potential role in regulating RSNA. Microinjections of DL-homocysteic acid (DLH were used to probe the PPT in 100-μm increments in Nembutal-anesthetized rats to identify effective sites, defined as locations where changes in RSNA could be evoked. A total of 239 DLH microinjections were made in 18 rats, which identified 20 effective sites (each confirmed by the ability to evoke a repeatable sympathoexcitatory response. Peak increases in RSNA occurred within 10-20 seconds of PPT activation, with RSNA increasing by 104.5 ± 68.4% (mean ± standard deviation from baseline. Mean arterial pressure remained significantly elevated for 30 seconds, increasing from 101.6 ± 18.6 mmHg to 135.9 ± 36.4 mmHg. DLH microinjections also increased respiratory rate and minute ventilation. The effective sites were found throughout the rostal-caudal extent of the PPT with most located in the dorsal regions of the nucleus. The majority of PPT locations tested with DLH microinjections did not alter RSNA (179 sites, suggesting that the neurons that confer renal sympathoexcitatory functions comprise a small component of the PPT. The study also underscores the importance of further investigation to

  20. Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity in the Context of Collagen-Induced Arthritis

    Science.gov (United States)

    Muschter, Dominique; Schäfer, Nicole; Stangl, Hubert; Straub, Rainer H.; Grässel, Susanne

    2015-01-01

    Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA). Concomitantly, local synovial changes comprise neuronal components of the peripheral sympathetic nervous system. Here, we wanted to analyze if collagen-induced arthritis (CIA) alters bone marrow-derived macrophage (BMM) osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters participate in this process. Therefore, BMMs from Dark Agouti rats at different CIA stages were differentiated into osteoclasts in vitro and osteoclast number, cathepsin K activity, matrix resorption and apoptosis were analyzed in the presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide (VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts without affecting protein level. CIA stage-dependently altered marker gene expression associated with osteoclast differentiation and activity without affecting osteoclast number or activity. Neurotransmitter stimulation modulated osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477, 10-6M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA alone does not affect metabolism of in vitro generated osteoclasts whereas stimulation with NA, VIP plus specific activation of adenylyl cyclase induced anti-resorptive effects probably mediated via cAMP signaling. Contrary, we suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via muscarinic receptors. PMID:26431344

  1. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

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    Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

    2015-04-16

    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.

    Science.gov (United States)

    Liao, Song-Yan; Liu, Yuan; Zuo, Mingliang; Zhang, Yuelin; Yue, Wensheng; Au, Ka-Wing; Lai, Wing-Hon; Wu, Yangsong; Shuto, Chika; Chen, Peter; Siu, Chung-Wah; Schwartz, Peter J; Tse, Hung-Fat

    2015-12-01

    Thoracic spinal cord stimulation (SCS) has been shown to improve left ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the optimal duration (intermittent vs. continuous) of stimulation and the mechanisms of action remain unclear. We performed chronic thoracic SCS at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All the animals were treated with daily oral metoprolol succinate (25 mg) plus ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS (4 h ×3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type natriuretic peptide (BNP) were measured. After sacrifice, immunohistological studies of myocardial sympathetic and parasympathetic nerve sprouting and innervation were performed. Echocardiogram revealed a significant increase in LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group compared with controls (P < 0.05). In both SCS groups, there was diffuse sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions compared with only the peri-infarct and infarct regions in the control group. In addition, sympathetic innervation at the peri-infarct and infarct regions was increased following SCS, but decreased in the control group. Myocardium norepinephrine spillover and serum BNP at 10 weeks was significantly decreased only in the continuous SCS group (P < 0.05). In a porcine model of HF, SCS induces significant remodelling of cardiac sympathetic innervation over the peri-infarct and infarct regions and is associated with improved LV function and reduced myocardial norepinephrine spillover. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  3. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ibrahim M Salman

    2015-08-01

    Full Text Available Chronic kidney disease (CKD is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n=16 were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2 and central chemoreflex (hypercapnia: 7% CO2 activation and acute stress (open-field exposure, were measured. As indicators of renal function, urinary protein (UPro and creatinine (Ucr levels were assessed. LPK rats had higher resting RSNA (1.2±0.1 vs. 0.6±0.1 µV, p<0.05 and MAP (151±8 vs. 97±2 mmHg, p<0.05 compared to Lewis. MAP was negatively correlated with Ucr (r=-0.80, p=0.002 and positively correlated with RSNA (r=0.66, p=0.014, with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p<0.05. This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

  4. Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

    Science.gov (United States)

    Longhurst, John C.

    2013-01-01

    Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

  5. [Relationship between sympathetic activity and response to treatment with atenolol in hypertensive patients. Investigation group of the study of efficiency and tolerance of atenolol in hypertensive patients with increase in the sympathetic activity].

    Science.gov (United States)

    de la Sierra, A

    1999-06-19

    Therapeutical response to antihypertensive treatment is poorly predicted by individual clinical or biochemical characteristics. Some preliminary data indicate that therapeutical response to atenolol might depend on physical and/or sympathetic activity. The aim of the present study was to evaluate the blood pressure response to atenolol depending on physical and sympathetic activity. One thousand one hundred forty hypertensive patients were treated with the beta adrenorecepetor blocker atenolol in an open fashion during 3 months. Before the beginning of the treatment, we evaluated current weekly physical activity (direct interview), as well as sympathetic activity (direct interview and baseline heart rate). Age or physical activity did not correlate with blood pressure response to atenolol. Conversely, hypertensive patients with symptoms suggesting sympathetic overactivity (three or more of the following symptoms: palpitations, anxiety, diaphoresis, headache, tremor or weakness; n = 456), showed a more pronounced decrease in systolic (27.7 [13.4] vs 25.8 [14.3] mmHg; p = 0.0226) and diastolic (17.6 [8.3] vs 15.5 [8.6] mmHg; p = 0.0001) blood pressures (SBP and DBP), with respect to the remaining hypertensive patients (n = 719). Moreover, we found a statistically significant correlation between blood pressure fall with atenolol and baseline heart rate (r = 0.107, P anxiety, emotional tension or sympathetic overactivity are associated with a more pronounced blood pressure fall to antihypertensive treatment with atenolol. These circumstances may play a role when choosing a new antihypertensive therapy.

  6. The sympathetic innervation of the heart: Important new insights.

    Science.gov (United States)

    Coote, J H; Chauhan, R A

    2016-08-01

    Autonomic control of the heart has a significant influence over development of life threatening arrhythmias that can lead to sudden cardiac death. Sympathetic activity is known to be upregulated during these conditions and hence the sympathetic nerves present a target for treatment. However, a better understanding of the anatomy and physiology of cardiac sympathetic nerves is required for the progression of clinical interventions. This review explores the organization of the cardiac sympathetic nerves, from the preganglionic origin to the postganglionic innervations, and provides an overview of literature surrounding anti-arrhythmic therapies including thoracic sympathectomy and dorsal spinal cord stimulation. Several features of the innervation are clear. The cardiac nerves differentially supply the nodal and myocardial tissue of the heart and are dependent on activity generated in spinal neurones in the upper thoracic cord which project to synapse with ganglion cells in the stellate complex on each side. Networks of spinal interneurones determine the pattern of activity. Groups of spinal neurones selectively target specific regions of the heart but whether they exhibit a functional selectivity has still to be elucidated. Electrical or ischemic signals can lead to remodeling of nerves in the heart or ganglia. Surgical and electrical methods are proving to be clinically beneficial in reducing atrial and ventricular arrhythmias, heart failure and severe cardiac pain. This is a rapidly developing area and we need more basic understanding of how these methods work to ensure safety and reduction of side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Reactive oxygen species in the paraventricular nucleus of the hypothalamus alter sympathetic activity during metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    JOSIANE CAMPOS CRUZ

    2015-12-01

    Full Text Available The paraventricular nucleus of the hypothalamus (PVN contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II, which activates AT1 receptors in the circumventricular organs (OCVs, mainly in the subfornical organ (SFO. Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS, leading to increases in sympathetic nerve activity (SNA. Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS: dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS.

  8. Coping with dehydration: sympathetic activation and regulation of glutamatergic transmission in the hypothalamic PVN

    Science.gov (United States)

    Bardgett, Megan E.; Chen, Qing-Hui; Guo, Qing; Calderon, Alfredo S.; Andrade, Mary Ann

    2014-01-01

    Autonomic and endocrine profiles of chronic hypertension and heart failure resemble those of acute dehydration. Importantly, all of these conditions are associated with exaggerated sympathetic nerve activity (SNA) driven by glutamatergic activation of the hypothalamic paraventricular nucleus (PVN). Here, studies sought to gain insight into mechanisms of disease by determining the role of PVN ionotropic glutamate receptors in supporting SNA and mean arterial pressure (MAP) during dehydration and by elucidating mechanisms regulating receptor activity. Blockade of PVN N-methyl-d-aspartate (NMDA) receptors reduced (P dehydrated (DH) (48 h water deprivation) rats, but had no effect in euhydrated (EH) controls. Blockade of PVN α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors had no effect in either group. NMDA in PVN caused dose-dependent increases of renal SNA and MAP in both groups, but the maximum agonist evoked response (Emax) of the renal SNA response was greater (P dehydration increases excitatory NMDA receptor tone in PVN. Reduced glial-mediated glutamate uptake was identified as a key contributing factor. Defective glutamate uptake in PVN could therefore be an important, but as yet unexplored, mechanism driving sympathetic hyperactivity in chronic cardiovascular diseases. PMID:24671240

  9. Evaluation of sympathetic activity by 123I-metaiodobenzylguanidine myocardial scintigraphy in dilated cardiomyopathy patients with sleep breathing disorder

    International Nuclear Information System (INIS)

    Nanjo, Shuji; Fujimoto, Shinichiro; Yamashiro, Yoshihiro

    2009-01-01

    Because increased sympathetic nervous activity (SNA) in patients with dilated cardiomyopathy (DCM) associated with sleep breathing disorder (SBD) is known to deteriorate the prognosis of cardiac failure, 123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was used as the investigative tool in the present study. The study group comprised 53 patients (47 men, 6 women; mean age 56±3 years) with chronic stable DCM. Patients were divided into SBD(+) or SBD(-) group according to 24-h pulse oximetry results. SBD(+) was defined when the 3% oxygen desaturation index was more than 15/h during sleep. In total, 32 patients were SBD(-) and 21 were SBD(+). In both groups, pulse oximetry were performed during sleep and awakening pulse rate, and measurement of the blood levels of catecholamines and B-type natriuretic peptide was performed. MIBG myocardial scintigraphy and echocardiography were performed at the same time. No significant difference was found between the 2 groups in catecholamine levels or left ventricular ejection fraction. However, MIBG had a significantly increased washout rate and a significantly decreased delayed heart to mediastinum ratio in the SBD(+) group compared with the SBD(-) group. SNA is increased in DCM patients when associated with SBD. MIBG myocardial scintigraphy may be a sensitive method of detecting increased SNA. (author)

  10. Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity

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    Ploj Karolina

    2005-09-01

    Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance. Methods Our objectives in this study were (1 to estimate sympathetic-adrenal medullary (SAM activity by measuring mean systolic blood pressure (MSAP in rats with estradiol valerate (EV-induced PCO; (2 to estimate alpha1a and alpha2a adrenoceptor expression in a brain area thought to mediate central effects on MSAP regulation and in the adrenal medulla; (3 to assess hypothalamic-pituitary-adrenal (HPA axis regulation by measuring adrenocorticotropic hormone (ACTH and corticosterone (CORT levels in response to novel-environment stress; and (4 to measure abdominal obesity, sex steroids, and insulin sensitivity. Results The PCO rats had significantly higher MSAP than controls, higher levels of alpha1a adrenoceptor mRNA in the hypothalamic paraventricular nucleus (PVN, and lower levels of alpha2a adrenoceptor mRNA in the PVN and adrenal medulla. After exposure to stress, PCO rats had higher ACTH and CORT levels. Plasma testosterone concentrations were lower in PCO rats, and no differences in insulin sensitivity or in the weight of intraabdominal fat depots were found. Conclusion Thus, rats with EV-induced PCO develop hypertension and increased sympathetic and HPA-axis activity without reduced insulin sensitivity, obesity, or hyperandrogenism. These findings may have implications for mechanisms underlying hypertension in PCOS.

  11. Mood states, sympathetic activity, and in vivo beta-adrenergic receptor function in a normal population.

    Science.gov (United States)

    Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G; Mills, Paul J; Dimsdale, Joel E

    2008-01-01

    The purpose of this study was to examine the relationship between mood states and beta-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or beta-adrenergic receptor function. Sixty-two participants aged 25-50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). Beta-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased beta-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of beta-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or beta-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) beta-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index.

  12. Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Koji; Nakatani, Yuko; Onishi, Satoshi [Dept. of Internal Medicine, Keihanna Hospital, Hirakata City, Osaka (Japan); Utsunomiya, Keita; Saika, Yoshinori [Dept. of Radiology, Keihanna Hospital, Hirakata City (Japan); Iwasaka, Toshiji [Cardiovascular Center, Kansai Medical University, Osaka (Japan)

    1999-10-01

    The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure {>=}140 and/or diastolic blood pressure {>=}90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55{+-}11 vs 63{+-}12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120{+-}12 vs 145{+-}16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1.81{+-}0.29 vs 2.27{+-}0.20, respectively, P<0.01). During the follow-up period (18{+-} 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%{+-}16.87% vs 12.89%{+-}11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant

  13. Skin conductance at baseline and postheel lance reflects sympathetic activation in neonatal opiate withdrawal.

    Science.gov (United States)

    Oji-Mmuo, Christiana N; Michael, Eric J; McLatchy, Jacqueline; Lewis, Mary M; Becker, Julie E; Doheny, Kim Kopenhaver

    2016-03-01

    Skin conductance (SC) provides an objective measure of autonomic system regulation through sympathetic-mediated filling of sweat glands. This study aimed to test the utility of SC to detect sympathetic activation in neonatal abstinence syndrome (NAS). Fourteen term (mean, SE: 38.8 ± 0.35 weeks gestational age) neonates with chronic prenatal opiate exposure were enrolled. SC (peaks/seconds and mean of peaks) was measured at baseline, during heel lance/squeeze (HLS) and recovery from HLS at 24-48 (mean 38) hours of life prior to treatment for NAS. Blinded coders with established reliability assessed neonates using the Modified Finnegan Neonatal Scoring System (MFNSS). Nonparametric tests were used to determine group differences, phase differences from baseline to HLS and HLS to recovery, and associations between MFNSS and SC measures. Neonates that would later require morphine treatment for NAS (n = 6) had higher baseline SC mean of peaks than those that did not require treatment (n = 8) (p < 0.05). Moreover, there were unique phase differences between groups and SC positively correlated with MFNSS (p < 0.05). SC provides early identification of NAS severity. However, a larger sample is needed to determine sensitivity and specificity of SC for early identification of NAS and treatment effectiveness. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  14. Effect of autogenic training on cardiac autonomic nervous activity in high-risk fire service workers for posttraumatic stress disorder.

    Science.gov (United States)

    Mitani, Satoko; Fujita, Masatoshi; Sakamoto, Satoko; Shirakawa, Taro

    2006-05-01

    We investigated the effect of autogenic training (AT) on cardiac autonomic nervous activity in fire services workers with the use of the questionnaire of the Japanese-language version of Impact of Event Scale-Revised (IES-R-J) and indexes of heart rate variability. We studied 22 male fire services workers who were divided into posttraumatic stress disorder (PTSD)-related stress group (n=10) and control group (n=12). They underwent AT twice or three times a week for 2 months. Posttraumatic stress disorder-related stress group showed a significantly higher cardiac sympathetic nervous activity and a significantly lower cardiac parasympathetic nervous activity than control group at baseline. Autogenic training significantly decreased cardiac sympathetic nervous activity and significantly increased cardiac parasympathetic nervous activity in both groups. These changes were accompanied by a significant decrease in the total points of IES-R-J. Autogenic training is effective for ameliorating the disturbance of cardiac autonomic nervous activity and psychological issues secondary to PTSD.

  15. Usefulness of {sup 123}I-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy for evaluation of cardiac sympathetic nervous system function in diabetic patients.

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Koji; Nakatani, Yuko; Doi, Kenji; Adachi, Gakuji; Takada, Kou

    2001-11-01

    The cardiac sympathetic nervous system function of diabetic patients with no definite cardiovascular complications other than hypertension was evaluated by {sup 123}I -MIBG myocardial scintigraphy. The subjects consisted of 82 diabetic patients, 59 men, 23 women, mean age 57 years, 17 with hypertension and 65 with normal blood pressure, and they were compared with normal controls (8 men and 3 women, mean age 54 years). Myocardial scintigraphy was performed 10 minutes and 4 hours after administration of MIBG. The superior mediastinum and whole myocardium were set as regions of interest, and the heart-to-mediastinum ratio (H/M ratio) and the washout rate (%WR) were calculated. The mean observation period was 18{+-}12 months, and 17 of the 65 diabetic patients with normal blood pressure before the study developed hypertension during the observation period. There were significant differences in H/M ratio and %WR between the diabetic patients and normal controls (H/M ratio; 1.96{+-}0.34 vs 2.27{+-}0.20, %WR; 24.71{+-}16.99% vs 12.89{+-}11.94). The diabetic patients with hypertension had higher morbidity with diabetic retinopathy and a lower H/M ratio. The 17 patients who developed hypertension during the observation period showed an increase in %WR and a reduction in the H/M ratio. Five patients who died during the observation period had a reduced H/M ratio and increased of %WR. {sup 123}I-MIBG myocardial scintigraphy in diabetic patients was shown to be useful for detecting cardiac sympathetic nervous system dysfunction, predicting the development of hypertension, and identifying patients who had a poor outcome. Diabetic patients with abnormal signals on MIBG myocardial scintigraphy need to be monitored much more carefully. (K.H.)

  16. Usefulness of 123I-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy for evaluation of cardiac sympathetic nervous system function in diabetic patients

    International Nuclear Information System (INIS)

    Tamura, Koji; Nakatani, Yuko; Doi, Kenji; Adachi, Gakuji; Takada, Kou; Onishi, Satoshi

    2001-01-01

    The cardiac sympathetic nervous system function of diabetic patients with no definite cardiovascular complications other than hypertension was evaluated by 123 I -MIBG myocardial scintigraphy. The subjects consisted of 82 diabetic patients, 59 men, 23 women, mean age 57 years, 17 with hypertension and 65 with normal blood pressure, and they were compared with normal controls (8 men and 3 women, mean age 54 years). Myocardial scintigraphy was performed 10 minutes and 4 hours after administration of MIBG. The superior mediastinum and whole myocardium were set as regions of interest, and the heart-to-mediastinum ratio (H/M ratio) and the washout rate (%WR) were calculated. The mean observation period was 18±12 months, and 17 of the 65 diabetic patients with normal blood pressure before the study developed hypertension during the observation period. There were significant differences in H/M ratio and %WR between the diabetic patients and normal controls (H/M ratio; 1.96±0.34 vs 2.27±0.20, %WR; 24.71±16.99% vs 12.89±11.94). The diabetic patients with hypertension had higher morbidity with diabetic retinopathy and a lower H/M ratio. The 17 patients who developed hypertension during the observation period showed an increase in %WR and a reduction in the H/M ratio. Five patients who died during the observation period had a reduced H/M ratio and increased of %WR. 123 I-MIBG myocardial scintigraphy in diabetic patients was shown to be useful for detecting cardiac sympathetic nervous system dysfunction, predicting the development of hypertension, and identifying patients who had a poor outcome. Diabetic patients with abnormal signals on MIBG myocardial scintigraphy need to be monitored much more carefully. (K.H.)

  17. Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Hansen, H P; Jacobsen, P

    1999-01-01

    AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity...... (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly...... constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably...

  18. Marital conflict and children's externalizing behavior: interactions between parasympathetic and sympathetic nervous system activity

    National Research Council Canada - National Science Library

    El-Sheikh, Mona; Beauchaine, Theodore P; Moore, Ginger A

    2009-01-01

    "Toward greater specificity in the prediction of externalizing problems in the context of interparental conflict, interactions between children's parasympathetic and sympathetic nervous system (PNS and SNS...

  19. Burst Activity and Heart Rhythm Modulation in the Sympathetic Outflow to the Heart

    National Research Council Canada - National Science Library

    Baselli, G

    2001-01-01

    In 13 decerebrate, artificially ventilated cats preganglionic sympathetic outflow to the heart was recorded with ECG and ventilation signal, A novel algorithm was implemented that extracts weighted...

  20. Polyphenols, Antioxidants and the Sympathetic Nervous System.

    Science.gov (United States)

    Bruno, Rosa Maria; Ghiadoni, Lorenzo

    2018-01-01

    A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic

  1. Cardiac sympathetic innervation assessed with (123)I-MIBG retains prognostic utility in diabetic patients with severe left ventricular dysfunction evaluated for primary prevention implantable cardioverter-defibrillator.

    Science.gov (United States)

    García-González, P; Fabregat-Andrés, Ó; Cozar-Santiago, P; Sánchez-Jurado, R; Estornell-Erill, J; Valle-Muñoz, A; Quesada-Dorador, A; Payá-Serrano, R; Ferrer-Rebolleda, J; Ridocci-Soriano, F

    2016-01-01

    Scintigraphy with iodine-123-metaiodobenzylguanidine ((123)I-MIBG) is a non-invasive tool for the assessment of cardiac sympathetic innervation (CSI) that has proven to be an independent predictor of survival. Recent studies have shown that diabetic patients with heart failure (HF) have a higher deterioration in CSI. It is unknown if (123)I-MIBG has the same predictive value for diabetic and non-diabetic patients with advanced HF. An analysis is performed to determine whether CSI with (123)I-MIBG retains prognostic utility in diabetic patients with HF, evaluated for a primary prevention implantable cardioverter-defibrillator (ICD). Seventy-eight consecutive HF patients (48 diabetic) evaluated for primary prevention ICD implantation were prospectively enrolled and underwent (123)I-MIBG to assess CSI (heart-to-mediastinum ratio - HMR). A Cox proportional hazards multivariate analysis was used to determine the influence of (123)I-MIBG images for prediction of cardiac events in both diabetic and non-diabetic patients. The primary end-point was a composite of arrhythmic event, cardiac death, or admission due to HF. During a mean follow-up of 19.5 [9.3-29.3] months, the primary end-point occurred in 24 (31%) patients. Late HMR was significantly lower in diabetic patients (1.30 vs. 1.41, p=0.014). Late HMR≤1.30 was an independent predictor of cardiac events in diabetic (hazard ratio 4.53; p=0.012) and non-diabetic patients (hazard ratio 12.31; p=0.023). Diabetic patients with HF evaluated for primary prevention ICD show a higher deterioration in CSI than non-diabetics; nevertheless (123)I-MIBG imaging retained prognostic utility for both diabetic and non-diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  2. Role of renal sympathetic nerve activity in prenatal programming of hypertension.

    Science.gov (United States)

    Baum, Michel

    2018-03-01

    Prenatal insults, such as maternal dietary protein deprivation and uteroplacental insufficiency, lead to small for gestational age (SGA) neonates. Epidemiological studies from many different parts of the world have shown that SGA neonates are at increased risk for hypertension and early death from cardiovascular disease as adults. Animal models, including prenatal administration of dexamethasone, uterine artery ligation and maternal dietary protein restriction, result in SGA neonates with fewer nephrons than controls. These models are discussed in this educational review, which provides evidence that prenatal insults lead to altered sodium transport in multiple nephron segments. The factors that could result in increased sodium transport are discussed, focusing on new information that there is increased renal sympathetic nerve activity that may be responsible for augmented renal tubular sodium transport. Renal denervation abrogates the hypertension in programmed rats but has no effect on control rats. Other potential factors that could cause hypertension in programmed rats, such as the renin-angiotensin system, are also discussed.

  3. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

    International Nuclear Information System (INIS)

    Tiradentes, R.V.; Pires, J.G.P.; Silva, N.F.; Ramage, A.G.; Santuzzi, C.H.; Futuro, H.A. Neto

    2014-01-01

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central

  4. [Increased sympathetic activity assessed by spectral analysis of heart rate variability in patients with CRPS I].

    Science.gov (United States)

    Schulze, J; Troeger, C

    2010-02-01

    The complex regional pain syndrome type I (CRPS I) is a painful neuropathic disorder with an antecedent disproportionate trauma leading to spontaneous pain, hyperalgesia, impaired motor function, swelling, changes in sweating and vascular abnormalities without nerve injury. Whether this syndrome is the result of central or peripheral autonomic dysfunction is still a matter of debate. The purpose of this study was to determine the activity of the sympathetic nervous system in patients with CRPS I by power spectral analysis of heart rate variability. This is a pilot study on 6 patients (mean age 50 years; 4 female, 2 male) diagnosed as suffering from CRPS I and 6 age-matched healthy controls. In the pain-free interval and after taking rest for 5 min, 512 subsequent heart beats were obtained with an ECG standard lead II in the supine and then sitting position. Using an autoregressive model, power spectral densities were calculated for the following frequency bands: CRPS I compared to the healthy controls in the supine position (LF/HF=4.01 vs. LF/HF=1.27; p=0.041). The application of stress by changing to the sitting position even increased that difference (6.72 vs. 1.93). Our results support the hypothesis that the pathogenesis of the early stage CRPS I might be related to an increased sympathetic activity. By assessing the autonomic influence on the heart rate variability in CRPS I patients we could also conclude that this disturbance occurs rather at a central level. Georg Thieme Verlag KG Stuttgart, New York.

  5. Losartan reduces the immediate and sustained increases in muscle sympathetic nerve activity after hyperacute intermittent hypoxia.

    Science.gov (United States)

    Jouett, Noah P; Moralez, Gilbert; Raven, Peter B; Smith, Michael L

    2017-04-01

    Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using losartan attenuates the immediate and immediately persistent increases in 1 ) SNA discharge and 2 ) mean arterial pressure (MAP) after hyperacute intermittent hypoxia training (IHT) using a randomized, placebo-controlled, repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in nine healthy human subjects, while muscle SNA (MSNA) was recorded in seven subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled two to three breaths of nitrogen, followed by a 20-s apnea and 40 s of room air breathing every minute for 20 min. Hyperacute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P 0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT. NEW & NOTEWORTHY This study demonstrates for the first time in humans that losartan, an angiotensin receptor blocker (ARB), abrogates the acute and immediately persistent increases in muscle sympathetic nerve activity and arterial pressure in response to acute intermittent hypoxia. This investigation, along with others, provides important beginning translational evidence for using ARBs in treatment of the intermittent hypoxia observed in obstructive sleep apnea patients. Copyright © 2017 the American Physiological Society.

  6. Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

    Science.gov (United States)

    Grassi, G; Seravalle, G; Dell'Oro, R; Turri, C; Pasqualinotto, L; Colombo, M; Mancia, G

    2001-12-01

    Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

  7. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans.

    Science.gov (United States)

    Kox, Matthijs; van Eijk, Lucas T; Zwaag, Jelle; van den Wildenberg, Joanne; Sweep, Fred C G J; van der Hoeven, Johannes G; Pickkers, Peter

    2014-05-20

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases.

  8. Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

    Energy Technology Data Exchange (ETDEWEB)

    Tiradentes, R.V. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Pires, J.G.P. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Silva, N.F. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Ramage, A.G. [Department of Neuroscience, Physiology and Pharmacology, University College London, London (United Kingdom); Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Futuro, H.A. Neto [Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES (Brazil); Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil)

    2014-05-30

    Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

  9. Mean 24-hours sympathetic nervous system activity decreases during head-down tilted bed rest but not during microgravity

    Science.gov (United States)

    Christensen, Nj; Heer, M.; Ivanova, K.; Norsk, P.

    Sympathetic nervous system activity is closely related to gravitational stress in ground based experiments. Thus a high activity is present in the standing-up position and a very low activity is observed during acute head-out water immersion. Adjustments in sympathetic activity are necessary to maintain a constant blood pressure during variations in venous return. Head-down tilted bed rest is applied as a model to simulate changes observed during microgravity. The aim of the present study was to test the hypothesis that mean 24-hours sympathetic activity was low and similar during space flight and in ground based observation obtained during long-term head-down tilted bed rest. Forearm venous plasma noradrenaline was measured by a radioenzymatic technique as an index of muscle sympathetic activity and thrombocyte noradrenaline and adrenaline were measured as indices of mean 24-hours sympathoadrenal activity. Previous results have indicated that thrombocyte noradrenaline level has a half-time of 2 days. Thus to reflect sympathetic activity during a specific experiment the study period must last for at least 6 days and a sample must be obtained within 12 hours after the experiment has ended. Ten normal healthy subjects were studied before and during a 14 days head-down tilted bed rest as well as during an ambulatory study period of a similar length. The whole experiment was repeated while the subjects were on a low calorie diet. Thrombocyte noradrenaline levels were studied in 4 cosmonauts before and within 12 hours after landing after more than 7 days in flight. Thrombocyte noradrenaline decreased markedly during the head-down tilted bed rest (pdifferent in cosmonauts and in subjects participating in the head down tilted bed rest study (170± 29% (Mean± SEM) vs. 57± 7%, respectively; presponse to combined effects of a reduced plasma volume and an increased vascular capacity in flight.

  10. Sympathetic activity of S-(+-ketamine low doses in the epidural space

    Directory of Open Access Journals (Sweden)

    Slobodan Mihaljevic

    2014-07-01

    ística. Conclusões: dose baixa de cetamina S-(+ administrada por via epidural não teve efeitos simpaticomiméticos; não alterou a pressão arterial, o pulso, os hormônios séricos ou o tempo de transição de pulso. Dose baixa de cetamina S-(+ administrada por via epidural não aprofundou o bloqueio simpático. A adição de 25 mg de cetamina S-(+ à bupivacaína a 0,5% não deprimiu o tônus simpático abaixo do nível do bloqueio peridural no momento máximo de bloqueio simpático e não tem efeito sobre o tônus simpático acima do nível do bloqueio. Keywords: S-(+-ketamine, Epidural space, Low doses, Sympathetic activity, Palavras-chave: Cetamina S-(+, Espaço epidural, Doses baixas, Atividade simpática

  11. alfa-Amylase as a reliable and convenient measure of sympathetic activity: don’t start salivating just yet!

    NARCIS (Netherlands)

    Bosch, JA; Veerman, J.W.; de Geus, E.J.C.; Proctor, J.

    2011-01-01

    Recent years have seen a growing interest in salivary α-amylase (sAA) as a non-invasive marker for sympathetic nervous system (SNS) activity. Saliva offers many advantages as a biomarker fluid and sAA is one of its most plentiful components. sAA is a digestive enzyme that breaks down starch, which

  12. α-Amylase as a reliable and convenient measure of sympathetic activity: don't start salivating just yet!

    NARCIS (Netherlands)

    Bosch, J.A.; Veerman, E.C.I.; de Geus, E.J.; Proctor, G.B.

    2011-01-01

    Recent years have seen a growing interest in salivary α-amylase (sAA) as a non-invasive marker for sympathetic nervous system (SNS) activity. Saliva offers many advantages as a biomarker fluid and sAA is one of its most plentiful components. sAA is a digestive enzyme that breaks down starch, which

  13. Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation

    NARCIS (Netherlands)

    Benthem, L; Keizer, Klaas-Jan; Wiegman, CH; De Boer, SF; Strubbe, JH; Steffens, AB; Kuipers, F; Scheurink, AJW

    2000-01-01

    We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the

  14. Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects

    Science.gov (United States)

    Carter, Jason R.; Ray, Chester A.; Downs, Emily M.; Cooke, William H.

    2003-01-01

    The effects of resistance training on arterial blood pressure and muscle sympathetic nerve activity (MSNA) at rest have not been established. Although endurance training is commonly recommended to lower arterial blood pressure, it is not known whether similar adaptations occur with resistance training. Therefore, we tested the hypothesis that whole body resistance training reduces arterial blood pressure at rest, with concomitant reductions in MSNA. Twelve young [21 +/- 0.3 (SE) yr] subjects underwent a program of whole body resistance training 3 days/wk for 8 wk. Resting arterial blood pressure (n = 12; automated sphygmomanometer) and MSNA (n = 8; peroneal nerve microneurography) were measured during a 5-min period of supine rest before and after exercise training. Thirteen additional young (21 +/- 0.8 yr) subjects served as controls. Resistance training significantly increased one-repetition maximum values in all trained muscle groups (P < 0.001), and it significantly decreased systolic (130 +/- 3 to 121 +/- 2 mmHg; P = 0.01), diastolic (69 +/- 3 to 61 +/- 2 mmHg; P = 0.04), and mean (89 +/- 2 to 81 +/- 2 mmHg; P = 0.01) arterial blood pressures at rest. Resistance training did not affect MSNA or heart rate. Arterial blood pressures and MSNA were unchanged, but heart rate increased after 8 wk of relative inactivity for subjects in the control group (61 +/- 2 to 67 +/- 3 beats/min; P = 0.01). These results indicate that whole body resistance exercise training might decrease the risk for development of cardiovascular disease by lowering arterial blood pressure but that reductions of pressure are not coupled to resistance exercise-induced decreases of sympathetic tone.

  15. Clinical relationship of myocardial sympathetic nervous activity to cardiovascular functions in chronic heart failure. Assessment by myocardial scintigraphy with 123I-metaiodobenzylguanidine

    International Nuclear Information System (INIS)

    Wada, Yukoh; Miura, Masaetsu; Fujiwara, Satomi; Mori, Shunpei; Seiji, Kazumasa; Kimura, Tokihisa

    2003-01-01

    The aim of this study was to clarify the relationship between cardiac sympathetic nervous activity (SNA) assessed by radioiodinated metaiodobenzylguanidine ( 123 I-MIBG), an analogue of norepinephrine and cardiovascular functions in patients with chronic heart failure (CHF). Subjects were 17 patients with CHF. A dose of 111 MBq of 123 I-MIBG was administered intravenously, and 5-minute anterior planar images were obtained 15 minutes (early image) and 3 hours (delayed image) after the injection. The heart/mediastinum (H/M) count ratio was defined to quantify cardiac 123 I-MIBG uptake. The washout ratio (WR) of 123 I-MIBG from the heart was calculated as follows: (early counts-delayed counts)/early counts x 100 (%). Echocardiography was performed on all patients within 1 week of 123 I-MIBG scintigraphy to measure stroke volume index (SVI). Blood pressure and heart rate (HR) in the resting state were also recorded to calculate cardiovascular functions including cardiac output, pulse pressure (PP), and mean blood pressure. Significant linear correlations were found between the early H/M ratio of 123 I-MIBG and SVI, and between the delayed H/M ratio of 123 I-MIBG and SVI, respectively. WR of 123 I-MIBG was correlated with HR, and was inversely correlated with SVI and with PP, respectively. It is likely that a decrease in SVI is associated with enhanced cardiac SNA in severe CHF. 123 I-MIBG scintigraphy is effective in assessing the cardiac functional status and SNA in patients with CHF in vivo. Moreover, changes in PP and HR indicate well alteration in SNA. (author)

  16. Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system.

    Science.gov (United States)

    Wang, Baile; Li, Ang; Li, Xiaomu; Ho, Philip Wl; Wu, Donghai; Wang, Xiaoqi; Liu, Zhuohao; Wu, Kelvin Kl; Yau, Sonata Sy; Xu, Aimin; Cheng, Kenneth Ky

    2018-04-01

    Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity. © 2018 The Authors.

  17. External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

    Science.gov (United States)

    Fan, Sabrina Mai-Yi; Chang, Yi-Ting; Chen, Chih-Lung; Wang, Wei-Hung; Pan, Ming-Kai; Chen, Wen-Pin; Huang, Wen-Yen; Xu, Zijian; Huang, Hai-En; Chen, Ting; Plikus, Maksim V; Chen, Shih-Kuo; Lin, Sung-Jan

    2018-06-29

    Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

  18. Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Tamura, Koji; Nakatani, Yuko; Onishi, Satoshi; Utsunomiya, Keita; Saika, Yoshinori; Iwasaka, Toshiji

    1999-01-01

    The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55±11 vs 63±12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120±12 vs 145±16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1.81±0.29 vs 2.27±0.20, respectively, P<0.01). During the follow-up period (18± 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%±16.87% vs 12.89%±11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant statistical differences

  19. CaMKII Regulates Synaptic NMDA Receptor Activity of Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension.

    Science.gov (United States)

    Li, De-Pei; Zhou, Jing-Jing; Zhang, Jixiang; Pan, Hui-Lin

    2017-11-01

    NMDAR activity in the hypothalamic paraventricular nucleus (PVN) is increased and critically involved in heightened sympathetic vasomotor tone in hypertension. Calcium/calmodulin-dependent protein kinase II (CaMKII) binds to and modulates NMDAR activity. In this study, we determined the role of CaMKII in regulating NMDAR activity of PVN presympathetic neurons in male spontaneously hypertensive rats (SHRs). NMDAR-mediated EPSCs and puff NMDA-elicited currents were recorded in spinally projecting PVN neurons in SHRs and male Wistar-Kyoto (WKY) rats. The basal amplitude of evoked NMDAR-EPSCs and puff NMDA currents in retrogradely labeled PVN neurons were significantly higher in SHRs than in WKY rats. The CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP) normalized the increased amplitude of NMDAR-EPSCs and puff NMDA currents in labeled PVN neurons in SHRs but had no effect in WKY rats. Treatment with AIP also normalized the higher frequency of NMDAR-mediated miniature EPSCs of PVN neurons in SHRs. CaMKII-mediated phosphorylation level of GluN2B serine 1303 (S1303) in the PVN, but not in the hippocampus and frontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased level of phosphorylated GluN2B S1303 in the PVN. In addition, microinjection of AIP into the PVN significantly reduced arterial blood pressure and lumbar sympathetic nerve discharges in SHRs. Our findings suggest that CaMKII activity is increased in the PVN and contributes to potentiated presynaptic and postsynaptic NMDAR activity to elevate sympathetic vasomotor tone in hypertension. SIGNIFICANCE STATEMENT Heightened sympathetic vasomotor tone is a major contributor to the development of hypertension. Although glutamate NMDA receptor (NMDAR)-mediated excitatory drive in the hypothalamus plays a critical role in increased sympathetic output in hypertension, the molecular mechanism involved in

  20. Neural and sympathetic activity associated with exploration in decision-making: Further evidence for involvement of insula

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    Hideki eOhira

    2014-11-01

    Full Text Available We previously reported that sympathetic activity was associated with exploration in decision-making indexed by entropy, which is a concept in information theory and indexes randomness of choices or the degree of deviation from sticking to recent experiences of gains and losses, and that activation of the anterior insula mediated this association. The current study aims to replicate and to expand these findings in a situation where contingency between options and outcomes is manipulated. Sixteen participants performed a stochastic decision-making task in which we manipulated a condition with low uncertainty of gain/loss (contingent-reward condition and a condition with high uncertainty of gain/loss (random-reward condition. Regional cerebral blood flow was measured by 15O-water positron emission tomography (PET, and cardiovascular parameters and catecholamine in the peripheral blood were measured, during the task. In the contingent-reward condition, norepinephrine as an index of sympathetic activity was positively correlated with entropy indicating exploration in decision-making. Norepinephrine was negatively correlated with neural activity in the right posterior insula, rostral anterior cingulate cortex, and dorsal pons, suggesting neural bases for detecting changes of bodily states. Furthermore, right anterior insular activity was negatively correlated with entropy, suggesting influences on exploration in decision-making. By contrast, in the random-reward condition, entropy correlated with activity in the dorsolateral prefrontal and parietal cortices but not with sympathetic activity. These findings suggest that influences of sympathetic activity on exploration in decision-making and its underlying neural mechanisms might be dependent on the degree of uncertainty of situations.

  1. Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

    Science.gov (United States)

    Cui, Jian; McQuillan, Patrick M.; Blaha, Cheryl; Kunselman, Allen R.

    2012-01-01

    We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects. PMID:22707559

  2. Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System

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    Kamran Rakhshan

    2015-10-01

    Full Text Available Exposure to stress leads to physiological changes called “stress response” which are the result ofthe changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA and sympatheticnervous system (SNS activity. In the present study, the effects of chronic physical and psychological stressand also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R injuries have beenstudied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 minreperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was donechemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes inheart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP and rate productpressure (RPP in both physical and psychological stress groups decreased significantly compared to those incontrol group (Pgroups. Infarct size significantly increased in both physical and psychological stress groups and control group(Pas compared with stress groups (Ppsychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seemsthat increased sympathetic activity in response to stress is responsible for these adverse effects of stress onischemic/reperfused heart.

  3. A shift in myocardial substrate, improved endothelial function, and diminished sympathetic activity may contribute to the anti-anginal impact of very-low-fat diets.

    Science.gov (United States)

    McCarty, M F

    2004-01-01

    A new category of anti-anginal drug - exemplified by ranolazine - is believed to work by partially inhibiting cardiac oxidation of fatty acids; oxidation of glucose requires less oxygen per mol of ATP generated, and thus is preferable to fat oxidation when oxygen availability is limiting in underperfused cardiac tissue. Unfortunately, there is no reason to believe that these drugs inhibit fat oxidation selectively in the heart; thus, chronic use of these drugs can be expected to increase body fat stores until the original rate of fat oxidation is restored by mass action - presumably negating the therapeutic benefit in angina, while exacerbating the manifold adverse effects of insulin resistance syndrome. The rational way to decrease cardiac metabolic reliance on fatty acids is to consume a very-low-fat quasi-vegan diet (i.e., 10% fat calories). Indeed, such diets are known to have a rapid and substantial therapeutic impact on anginal symptoms, while concurrently benefiting insulin sensitivity, markedly improving serum lipid profile, promoting leanness, and lessening coronary risk. A reduction in diurnal insulin secretion might also be achieved, which would be expected to decrease sympathetic activity. While reduced myocardial demand for oxygen doubtless contributes to the beneficial impact of such diets on angina, it is likely that improved cardiac perfusion consequent to improved endothelium-dependent vasodilation also plays a role in this regard. Supplemental carnitine, also beneficial in angina, appears to improve utilization of glucose in the ischemic myocardium by lowering elevated acetyl-coA levels and thereby disinhibiting pyruvate dehydrogenase. Certain other nutraceuticals may aid control of angina by improving endothelial function. In the longer term, these measures have the potential to slow or reverse the progression of stenotic lesions that underlie most cases of angina. These safe and relatively inexpensive nutritional strategies for coping with

  4. Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application.

    Science.gov (United States)

    Harada, Daisuke; Asanoi, Hidetsugu; Takagawa, Junya; Ishise, Hisanari; Ueno, Hiroshi; Oda, Yoshitaka; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

    2014-10-15

    Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P state MSNA was decreased by 31% (P state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure. Copyright © 2014 the American Physiological Society.

  5. [The influence of single moderate exercise on the sympathetic nervous system activity in patients with essential hypertension].

    Science.gov (United States)

    Gajek, Jacek; Zyśko, Dorota

    2002-12-01

    Sympathetic nervous system may play an important role in development and maintenance of hypertension. Its activity can be assessed by plasma levels of catecholamines, neuropeptide Y (NPY) and adrenergic receptor density. Hypertensive subjects may be more prone to reveal overactivity of sympathetic nervous system, for instance as a result of physical stress. The aim of the study was to determine the activity of sympathetic nervous system in young patients with newly recognized, untreated mild hypertension. The study was carried out in 22 patients (age 38.5 +/- 10.3 years) and 20 normotensive volunteers (age 38.5 +/- 8.6 years) as a control group, matched for sex. Density of alpha 2- and beta-adrenergic receptors using 3H-yohimbine and 125I-cyanopindolol respectively, total catecholamines and plasma renin activity using radioenzymatic assay, neuropeptide Y and aldosterone using radioimmunoassay were assessed in the blood taken in the supine position and after moderate bicycle ergometer exercise. Plasma concentration of NPY at rest did not differ between the groups, but increased significantly after exercise and was greater in hypertensive patients (p < 0.05). The density of alpha 2- and beta-adrenergic receptors at rest and after exercise in hypertensive subjects was unchanged when comparing to healthy individuals. The plasma concentrations of endogenous catecholamines, plasma renin activity and aldosterone level increase during exercise in both studied groups (p < 0.05). Aldosterone level was higher in hypertensive patients at rest (p < 0.05). There was a negative correlation between baseline aldosterone and NPY levels in hypertensive patients (r = -0.44, p < 0.05). Moderate exercise in hypertensive subjects causes the hyperactivity of sympathetic nervous system expressed as increase of NPY plasma level.

  6. Expression of adenosine triphosphate-sensitive potassium channels in rats with cirrhosis: correlationship with sympathetic activity and renal function

    Directory of Open Access Journals (Sweden)

    Julio Cesar Martins Monte

    2006-12-01

    Full Text Available Objective: The aim of this study was to perform a direct analysis ofKATP mRNA expression by RT-PCR in kidney and isolated aorta fromrats with cirrhosis (induced by carbon tetrachloride and controls.The present study also analyses the relation between induced cirrhosisand urinary excretion of sodium and sympathetic activity in cirrhoticrats. Methods: Rats were placed in metabolic cages and allowedfree access to food and water. Cirrhosis was induced by repeateddoses of carbon tetrachloride by gastric gavage. After some weeks,the kidney and aorta were dissected and utilized for RNA extraction.Blood and urine were analyzed for electrolytes. Renal function wasestimated by creatinine clearance and sodium urinary excretion.Serum catecholamines were measured by HPLC analysis. Results:First, RT-PCR analysis showed that KATP mRNA is expressed in liverwith cirrhosis and intense fibrosis, but not with moderate fibrosis.Second, RT-PCR analysis revealed that KATP mRNA was detectedonly in aorta dissected from rats with cirrhosis. Finally, an enhancedreabsorption of sodium without renal failure suggests a potentialmediator would increase the activity of the sympathetic system.Conclusion: These results suggest that KATP mRNA is expressed incirrhotic rats with sympathetic activation and renal dysfunction. Thischannel might be involved in another route where the vascular tonecan be modulated in cirrhosis.

  7. Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.

    Science.gov (United States)

    Nammas, Wail; Koistinen, Juhani; Paana, Tuomas; Karjalainen, Pasi P

    2017-08-01

    Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.

  8. Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

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    Yumie Morimoto-Kobayashi

    Full Text Available Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1 expression in brown adipose tissue (BAT was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA. Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional

  9. Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images.

    Science.gov (United States)

    Brown, Rachael; James, Cheree; Henderson, Luke A; Macefield, Vaughan G

    2012-01-01

    The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.

  10. Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

    Science.gov (United States)

    Briant, Linford J B; Stalbovskiy, Alexey O; Nolan, Matthew F; Champneys, Alan R; Pickering, Anthony E

    2014-12-01

    Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. Copyright © 2014 the American Physiological Society.

  11. Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine

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    Stanton, M.S.; Tuli, M.M.; Radtke, N.L.; Heger, J.J.; Miles, W.M.; Mock, B.H.; Burt, R.W.; Wellman, H.N.; Zipes, D.P. (Indiana Univ. School of Medicine, IN (USA))

    1989-11-15

    Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

  12. Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

    Science.gov (United States)

    Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

    2016-08-26

    Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Vagal and sympathetic activity in burnouts during a mentally demanding workday

    NARCIS (Netherlands)

    Zanstra, Ydwine J.; Schellekens, Jan M. H.; Schaap, Cas; Kooistra, Libbe

    2006-01-01

    Objective: We study differences in task performance and related sympathetic-vagal reaction patterns between burnouts and controls during a mentally demanding workday. Method: Thirty-nine adults with burnout and 40 healthy controls performed mental tasks during a simulated workday. At pretest, just

  14. Vibration sense and sympathetic vasoconstrictor activity in patients with occlusive arterial disease

    DEFF Research Database (Denmark)

    Bjerre-Jepsen, K; Henriksen, O; Parm, Martin Lehnsbo

    1983-01-01

    function was studied by the capability of the local sympathetic venoarteriolar reflex (Henriksen 1977) elicited by lowering the leg to induce an arteriolar constriction in subcutaneous tissue at the ankle level. Blood flow was measured by the local isotope washout technique. In only five patients with loss...

  15. Overexpression of Sarcoendoplasmic Reticulum Calcium ATPase 2a Promotes Cardiac Sympathetic Neurotransmission via Abnormal Endoplasmic Reticulum and Mitochondria Ca2+ Regulation

    Science.gov (United States)

    Shanks, Julia; Herring, Neil; Johnson, Errin; Liu, Kun; Li, Dan

    2017-01-01

    Reduced cardiomyocyte excitation–contraction coupling and downregulation of the SERCA2a (sarcoendoplasmic reticulum calcium ATPase 2a) is associated with heart failure. This has led to viral transgene upregulation of SERCA2a in cardiomyocytes as a treatment. We hypothesized that SERCA2a gene therapy expressed under a similar promiscuous cytomegalovirus promoter could also affect the cardiac sympathetic neural axis and promote sympathoexcitation. Stellate neurons were isolated from 90 to 120 g male, Sprague–Dawley, Wistar Kyoto, and spontaneously hypertensive rats. Neurons were infected with Ad-mCherry or Ad-mCherry-hATP2Aa (SERCA2a). Intracellular Ca2+ changes were measured using fura-2AM in response to KCl, caffeine, thapsigargin, and carbonylcyanide-p-trifluoromethoxyphenylhydrazine to mobilize intracellular Ca2+ stores. The effect of SERCA2a on neurotransmitter release was measured using [3H]-norepinephrine overflow from 340 to 360 g Sprague–Dawley rat atria in response to right stellate ganglia stimulation. Upregulation of SERCA2a resulted in greater neurotransmitter release in response to stellate stimulation compared with control (empty: 98.7±20.5 cpm, n=7; SERCA: 186.5±28.41 cpm, n=8; Pneurons, SERCA2a overexpression facilitated greater depolarization-induced Ca2+ transients (empty: 0.64±0.03 au, n=57; SERCA: 0.75±0.03 au, n=68; Pneurons resulted in increased neurotransmission and increased Ca2+ loading into intracellular stores. Whether the increased Ca2+ transient and neurotransmission after SERCA2A overexpression contributes to enhanced sympathoexcitation in heart failure patients remains to be determined. PMID:28223472

  16. Evaluation of sympathetic nerve system activity with MIBG. Comparison with heart rate variability

    International Nuclear Information System (INIS)

    Kurata, Chinori; Wakabayashi, Yasushi; Shouda, Sakae; Mikami, Tadashi; Tawarahara, Kei; Sugiyama, Tsuyoshi; Nakano, Tomoyasu; Suzuki, Toshihiko.

    1997-01-01

    Authors attempted to elucidate the relations of plasma concentration of norepinephrine (pNE) and findings of heart rate variability and MIBG myocardial scintigraphy and evaluated cardiac autonomic nervous activity in chronic renal failure. Subjects were 211 patients with various heart diseases (coronary artery lesion, cardiomyopathy, hypertension, diabetes mellitus, renal failure and so on), 60 patients with artificial kidney due to chronic renal failure, 13 of whom were found to have coronary arterial disease by Tl myocardial scintigraphy, and 14 normal volunteers. ECG was recorded with the portable recorder for heart rate variability. Together with collection of blood for pNE measurement, myocardial scintigraphy was done at 15 and 150 min after intravenous administration of 111 MBq of MIBG for acquisition of early and delayed, respectively, images of the frontal breast. Accumulation at and elimination during the time points of MIBG were computed in cps unit. Variability of heart rate was found to have the correlation positive with MIBG delayed accumulation and negative with the elimination, and pNE, negative with heart rate variability and the delayed accumulation and positive with the elimination. Thus cardiac autonomic nervous abnormality was suggested to occur before uremic cardiomyopathy. (K.H.)

  17. Sympathetic activity of S-(+-ketamine low doses in the epidural space

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    Slobodan Mihaljevic

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVES: S-(+-ketamine is an intravenous anaesthetic and sympathomimetic with properties of local anaesthetic. It has an effect of an analgetic and local anaesthetic when administered epidurally, but there are no data whether low doses of S-(+-ketamine have sympathomimetic effects. The aim of this study was to determine whether low doses of S-(+-ketamine, given epidurally together with local anaesthetic, have any effect on sympathetic nervous system, both systemic and below the level of anaesthetic block. METHODS: The study was conducted on two groups of patients to whom epidural anaesthesia was administered to. Local anaesthesia (0.5% bupivacaine was given to one group (control group while local anaesthesia and S-(+-ketamine were given to other group. Age, height, weight, systolic, diastolic and mean arterial blood pressure were measured. Non-competitive enzyme immunochemistry method (Cat Combi ELISA was used to determine the concentrations of catecholamines (adrenaline and noradrenaline. Immunoenzymometric determination with luminescent substrate on a machine called Vitros Eci was used to determine the concentration of cortisol. Pulse transit time was measured using photoplethysmography. Mann-Whitney U-test, Wilcoxon test and Friedman ANOVA were the statistical tests. Blood pressure, pulse, adrenaline, noradrenaline and cortisol concentrations were measured in order to estimate systemic sympathetic effects. RESULTS: 40 patients in the control group were given 0.5% bupivacaine and 40 patients in the test group were given 0.5% bupivacaine with S-(+-ketamine. Value p < 0.05 has been taken as a limit of statistical significance. CONCLUSIONS: Low dose of S-(+-ketamine administered epidurally had no sympathomimetic effects; it did not change blood pressure, pulse, serum hormones or pulse transit time. Low dose of S-(+-ketamine administered epidurally did not deepen sympathetic block. Adding 25 mg of S-(+-ketamine to 0

  18. Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.

    Science.gov (United States)

    Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

    2013-03-19

    Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

  19. Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

    Science.gov (United States)

    Jedel, Elizabeth; Gustafson, Deborah; Waern, Margda; Sverrisdottir, Yrsa Bergmann; Landén, Mikael; Janson, Per Olof; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2011-11-01

    Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

    Science.gov (United States)

    Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

    2013-01-01

    Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

  1. Cardiac Events During Competitive, Recreational, and Daily Activities in Children and Adolescents With Long QT Syndrome.

    Science.gov (United States)

    Chambers, Kristina D; Beausejour Ladouceur, Virginie; Alexander, Mark E; Hylind, Robyn J; Bevilacqua, Laura; Mah, Douglas Y; Bezzerides, Vassilios; Triedman, John K; Walsh, Edward P; Abrams, Dominic J

    2017-09-21

    The 2005 Bethesda Conference Guidelines advise patients with long QT syndrome against competitive sports. We assessed cardiac event rates during competitive and recreational sports, and daily activities among treated long QT syndrome patients. Long QT syndrome patients aged ≥4 years treated with anti-adrenergic therapy were included. Demographics included mechanism of presentation, corrected QT interval pretreatment, symptom history, medication compliance, and administration of QT-prolonging medications. Corrected QT interval ≥550 ms or prior cardiac arrest defined high risk. Sports were categorized by cardiovascular demand per the 2005 Bethesda Conference Guidelines. Each was classified as recreational or competitive. One hundred seventy-two patients (90; 52% female) with median age 15.2 years (interquartile range 11.4, 19.4) were included. Evaluation was performed for family history (102; 59%), incidental finding (34; 20%), and symptoms (36; 21%). Median corrected QT interval was 474 ms (interquartile range 446, 496) and 14 patients (8%) were deemed high risk. Treatment included β-blockers (171; 99%), implantable cardioverter-defibrillator (27; 16%), left cardiac sympathetic denervation (7; 4%), and pacemaker (3; 2%). Sports participation was recreational (66; 38%) or competitive (106; 62%), with 92 (53%) exercising against the Bethesda Conference Guidelines. There were no cardiac events in competitive athletes and no deaths. There were 13 cardiac events in 9 previously symptomatic patients during either recreational exercise or activities of daily life. In this cohort of appropriately managed children with long QT syndrome, cardiac event rates were low and occurred during recreational but not competitive activities. This study further supports the need for increased assessment of arrhythmia risk during exercise in this patient population. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  2. Sympathetic nervous activity and renal and systemic hemodynamics in cirrhosis: plasma norepinephrine concentration, hepatic extraction, and renal release

    DEFF Research Database (Denmark)

    Ring-Larsen, H; Hesse, B; Henriksen, Jens Henrik Sahl

    1982-01-01

    as previously reported in healthy controls. The right kidney released NE into the systemic circulation. Renal venous plasma NE exceeded arterial concentration by 34% (p less than 0.01). It is concluded that sympathetic nervous activity is enhanced in patients with cirrhosis, and that this hyperactivity may...... in patients than controls (82 vs. 95 mm Hg, p less than 0.05) but did not change during the tilt. Plasma norepinephrine (NE) concentration was significantly higher in another eight patients with cirrhosis than in eight healthy controls (mean: 0.45 vs. 0.21 ng per ml in recumbency, p less than 0.02). Following...

  3. Innervating sympathetic neurons regulate heart size and the timing of cardiomyocyte cell cycle withdrawal.

    Science.gov (United States)

    Kreipke, R E; Birren, S J

    2015-12-01

    Sympathetic drive to the heart is a key modulator of cardiac function and interactions between heart tissue and innervating sympathetic fibres are established early in development. Significant innervation takes place during postnatal heart development, a period when cardiomyocytes undergo a rapid transition from proliferative to hypertrophic growth. The question of whether these innervating sympathetic fibres play a role in regulating the modes of cardiomyocyte growth was investigated using 6-hydroxydopamine (6-OHDA) to abolish early sympathetic innervation of the heart. Postnatal chemical sympathectomy resulted in rats with smaller hearts, indicating that heart growth is regulated by innervating sympathetic fibres during the postnatal period. In vitro experiments showed that sympathetic interactions resulted in delays in markers of cardiomyocyte maturation, suggesting that changes in the timing of the transition from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes in heart size in the sympathectomized animals. There was also an increase in the expression of Meis1, which has been linked to cardiomyocyte cell cycle withdrawal, suggesting that sympathetic signalling suppresses cell cycle withdrawal. This signalling involves β-adrenergic activation, which was necessary for sympathetic regulation of cardiomyocyte proliferation and hypertrophy. The effect of β-adrenergic signalling on cardiomyocyte hypertrophy underwent a developmental transition. While young postnatal cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell size, mature cardiomyocytes showed an increase in cell size in response to the drug. Together, these results suggest that early sympathetic effects on proliferation modulate a key transition between proliferative and hypertrophic growth of the heart and contribute to the sympathetic regulation of adult heart size. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  4. Sympathetic rhythms and nervous integration.

    Science.gov (United States)

    Gilbey, Michael P

    2007-04-01

    1. The present review focuses on some of the processes producing rhythms in sympathetic nerves influencing cardiovascular functions and considers their potential relevance to nervous integration. 2. Two mechanisms are considered that may account for rhythmic sympathetic discharges. First, neuronal elements of peripheral or central origin produce rhythmic activity by phasically exciting and/or inhibiting neurons within central sympathetic networks. Second, rhythms arise within central sympathetic networks. Evidence is considered that indicates the operation of both mechanisms; the first in muscle and the second in skin sympathetic vasoconstrictor networks. 3. Sympathetic activity to the rat tail, a model for the nervous control of skin circulation, is regulated by central networks involved in thermoregulation and those associated with fear and arousal. In an anaesthetized preparation, activity displays an apparently autonomous rhythm (T-rhythm; 0.4-1.2 Hz) and the level of activity can be manipulated by regulating core body temperature. This model has been used to study rhythm generation in central sympathetic networks and possible functional relevance. 4. A unique insight provided by the T rhythm, into possible physiological function(s) underlying rhythmic sympathetic discharges is that the activity of single sympathetic post-ganglionic neurons within a population innervating the same target can have different rhythm frequencies. Therefore, the graded and dynamic entrainment of the rhythms by inputs, such as central respiratory drive and/or lung inflation-related afferent activity, can produce graded and dynamic synchronization of sympathetic discharges. The degree of synchronization may influence the efficacy of transmission in a target chain of excitable cells. 5. The T-rhythm may be generated within the spinal cord because the intrathecal application of 5-hydroxytryptamine at the L1 level of the spinal cord of a rat spinalized at T10-T11 produces a T-like rhythm

  5. Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

    Science.gov (United States)

    Prior, Larissa J; Davern, Pamela J; Burke, Sandra L; Lim, Kyungjoon; Armitage, James A; Head, Geoffrey A

    2014-02-01

    Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (Pfat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (Pfat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; Pfat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

  6. α-Amylase as a reliable and convenient measure of sympathetic activity: don't start salivating just yet!

    Science.gov (United States)

    Bosch, Jos A; Veerman, Enno C I; de Geus, Eco J; Proctor, Gordon B

    2011-05-01

    Recent years have seen a growing interest in salivary α-amylase (sAA) as a non-invasive marker for sympathetic nervous system (SNS) activity. Saliva offers many advantages as a biomarker fluid and sAA is one of its most plentiful components. sAA is a digestive enzyme that breaks down starch, which provides a simple means of quantification by measuring its enzymatic activity. This commentary will address a number of common misconceptions and methodological issues that surround the use of sAA as a marker of SNS activity and limit its utility in biobehavioral research. The usefulness of sAA as an SNS marker is undermined by the fact that the parasympathetic nerves also play a significant role in sAA release. Local parasympathetic nerves regulate sAA activity via: (1) α-amylase release from glands that are solely or mainly parasympathetically innervated; (2) via synergistic sympathetic-parasympathetic effects on protein secretion (known as 'augmented secretion'); and (3) via effects on salivary flow rate. Regarding methodology, we discuss why it is problematic: (1) to ignore the contribution of salivary flow rate; (2) to use absorbent materials for saliva collection, and; (3) to stimulate saliva secretion by chewing. While these methodological problems can be addressed by using standardized and timed collection of unstimulated saliva, the physiological regulation of sAA secretion presents less resolvable issues. We conclude that at present there is insufficient support for the use and interpretation of sAA activity as a valid and reliable measure of SNS activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Alterations in cardiac autonomic control in spinal cord injury

    DEFF Research Database (Denmark)

    Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan

    2018-01-01

    parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update...

  8. REFRACTORY HYPERTENSION: EVIDENCE OF HEIGHTENED SYMPATHETIC ACTIVITY AS A CAUSE OF ANTIHYPERTENSIVE TREATMENT FAILURE

    Science.gov (United States)

    Dudenbostel, Tanja; Acelajado, Maria C.; Pisoni, Roberto; Li, Peng; Oparil, Suzanne; Calhoun, David A.

    2015-01-01

    Refractory hypertension is an extreme phenotype of treatment failure defined as uncontrolled blood pressure (BP) in spite of ≥5 classes of antihypertensive agents, including chlorthalidone and a mineralocorticoid receptor antagonist. A prospective evaluation of possible mechanisms of refractory hypertension has not been done. The goal of this study was to test for evidence of heightened sympathetic tone as indicated by 24-hr urinary (U-) normetanephrine levels, clinic and ambulatory heart rate (HR), HR variability (HRV), arterial stiffness as indexed by pulse wave velocity (PWV), and systemic vascular resistance (SVR) compared to patients with controlled resistant hypertension. Forty-four consecutive patients, 15 with refractory and 29 with controlled resistant hypertension, were evaluated prospectively. Refractory hypertensive patients were younger (48±13.3 vs. 56.5±14.1 years, p=0.038) and more likely female (80.0 vs 51.9 %, p=0.047) compared to patients with controlled resistant hypertension. They also had higher U-normetanephrine levels (464.4±250.2 vs. 309.8±147.6 μg/24h, p=0.03), higher clinic HR (77.8±7.7 vs. 68.8±7.6 bpm, p=0.001) and 24-hr ambulatory HR (77.8±7.7 vs 68.8±7.6, p=0.0018), higher PWV (11.8±2.2 vs. 9.4±1.5 m/s, p=0.009), reduced HRV (4.48 vs. 6.11, p=0.03), and higher SVR (3795±1753 vs. 2382±349 dyne·sec·cm5·m2, p=0.008). These findings are consistent with heightened sympathetic tone being a major contributor to antihypertensive treatment failure and highlight the need for effective sympatholytic therapies in patients with refractory hypertension. PMID:25987662

  9. The sympathetic nervous system in polycystic ovary syndrome: a novel therapeutic target?

    Science.gov (United States)

    Lansdown, Andrew; Rees, D Aled

    2012-12-01

    Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term health risks, including type 2 diabetes and vascular dysfunction in addition to reproductive sequelae. Many of the common features of PCOS, such as central obesity, hyperinsulinaemia and obstructive sleep apnoea (OSA), are associated with chronic sympathetic overactivity, suggesting that sympathoexcitation may be involved in the pathogenesis of this condition. Rodent models of polycystic ovaries have shown that ovarian sympathetic outflow may be increased, accompanied by elevated intra-ovarian synthesis of nerve growth factor (NGF) which may be involved in initiation of ovarian pathology. Patients with PCOS have evidence of increased muscle sympathetic nerve activity (MSNA), altered heart rate variability and attenuated heart rate recovery postexercise, compared with age- and BMI-matched controls, suggesting a generalized increase in sympathetic nerve activity. Active weight loss can reduce MSNA and whole body noradrenaline spillover, whereas low-frequency electroacupuncture decreased MSNA in overweight women with PCOS. Treatment of OSA with continuous positive airways pressure may reduce plasma noradrenaline levels and diastolic blood pressure and improve cardiac sympathovagal balance. Renal sympathetic denervation also reduced MSNA, noradrenaline spillover and blood pressure in two PCOS subjects with hypertension, accompanied by improved insulin sensitivity. The sympathetic nervous system may thus offer a new therapeutic target in PCOS but larger and longer-term studies are needed before these treatments can be considered in clinical practice. © 2012 Blackwell Publishing Ltd.

  10. Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

    Directory of Open Access Journals (Sweden)

    Jihong Xing

    2016-11-01

    Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

  11. True or false? Memory is differentially affected by stress-induced cortisol elevations and sympathetic activity at consolidation and retrieval.

    Science.gov (United States)

    Smeets, Tom; Otgaar, Henry; Candel, Ingrid; Wolf, Oliver T

    2008-11-01

    Adrenal stress hormones released in response to acute stress may yield memory-enhancing effects when released post-learning and impairing effects at memory retrieval, especially for emotional memory material. However, so far these differential effects of stress hormones on the various memory phases for neutral and emotional memory material have not been demonstrated within one experiment. This study investigated whether, in line with their effects on true memory, stress and stress-induced adrenal stress hormones affect the encoding, consolidation, and retrieval of emotional and neutral false memories. Participants (N=90) were exposed to a stressor before encoding, during consolidation, before retrieval, or were not stressed and then were subjected to neutral and emotional versions of the Deese-Roediger-McDermott word list learning paradigm. Twenty-four hours later, recall of presented words (true recall) and non-presented critical lure words (false recall) was assessed. Results show that stress exposure resulted in superior true memory performance in the consolidation stress group and reduced true memory performance in the retrieval stress group compared to the other groups, predominantly for emotional words. These memory-enhancing and memory-impairing effects were strongly related to stress-induced cortisol and sympathetic activity measured via salivary alpha-amylase levels. Neutral and emotional false recall, on the other hand, was neither affected by stress exposure, nor related to cortisol and sympathetic activity following stress. These results demonstrate the importance of stress-induced hormone-related activity in enhancing memory consolidation and in impairing memory retrieval, in particular for emotional memory material.

  12. Concurrent sympathetic activation and vagal withdrawal in hyperthyroidism: Evidence from detrended fluctuation analysis of heart rate variability

    Science.gov (United States)

    Chen, Jin-Long; Shiau, Yuo-Hsien; Tseng, Yin-Jiun; Chiu, Hung-Wen; Hsiao, Tzu-Chien; Wessel, Niels; Kurths, Jürgen; Chu, Woei-Chyn

    2010-05-01

    Despite many previous studies on the association between hyperthyroidism and the hyperadrenergic state, controversies still exist. Detrended fluctuation analysis (DFA) is a well recognized method in the nonlinear analysis of heart rate variability (HRV), and it has physiological significance related to the autonomic nervous system. In particular, an increased short-term scaling exponent α1 calculated from DFA is associated with both increased sympathetic activity and decreased vagal activity. No study has investigated the DFA of HRV in hyperthyroidism. This study was designed to assess the sympathovagal balance in hyperthyroidism. We performed the DFA along with the linear analysis of HRV in 36 hyperthyroid Graves’ disease patients (32 females and 4 males; age 30 ± 1 years, means ± SE) and 36 normal controls matched by sex, age and body mass index. Compared with the normal controls, the hyperthyroid patients revealed a significant increase ( Phyperthyroid 1.28±0.04 versus control 0.91±0.02), long-term scaling exponent α2 (1.05±0.02 versus 0.90±0.01), overall scaling exponent α (1.11±0.02 versus 0.89±0.01), low frequency power in normalized units (LF%) and the ratio of low frequency power to high frequency power (LF/HF); and a significant decrease ( Phyperthyroidism is characterized by concurrent sympathetic activation and vagal withdrawal. This sympathovagal imbalance state in hyperthyroidism helps to explain the higher prevalence of atrial fibrillation and exercise intolerance among hyperthyroid patients.

  13. Eyeball pressure stimulation induces subtle sympathetic activation in patients with a history of moderate or severe traumatic brain injury.

    Science.gov (United States)

    Wang, Ruihao; Hösl, Katharina M; Ammon, Fabian; Markus, Jörg; Koehn, Julia; Roy, Sankanika; Liu, Mao; de Rojas Leal, Carmen; Muresanu, Dafin; Flanagan, Steven R; Hilz, Max J

    2018-06-01

    After traumatic brain injury (TBI), there may be persistent central-autonomic-network (CAN) dysfunction causing cardiovascular-autonomic dysregulation. Eyeball-pressure-stimulation (EPS) normally induces cardiovagal activation. In patients with a history of moderate or severe TBI (post-moderate-severe-TBI), we determined whether EPS unveils cardiovascular-autonomic dysregulation. In 51 post-moderate-severe-TBI patients (32.7 ± 10.5 years old, 43.1 ± 33.4 months post-injury), and 30 controls (29.1 ± 9.8 years), we recorded respiration, RR-intervals (RRI), systolic and diastolic blood-pressure (BPsys, BPdia), before and during EPS (120 sec; 30 mmHg), using an ocular-pressure-device (Okulopressor®). We calculated spectral-powers of mainly sympathetic low (LF: 0.04-0.15 Hz) and parasympathetic high (HF: 0.15-0.5 Hz) frequency RRI-fluctuations, sympathetically mediated LF-powers of BPsys, and calculated normalized (nu) LF- and HF-powers of RRI. We compared parameters between groups before and during EPS by repeated-measurement-analysis-of-variance with post-hoc analysis (significance: p < 0.05). At rest, sympathetically mediated LF-BPsys-powers were significantly lower in the patients than the controls. During EPS, only controls significantly increased RRIs and parasympathetically mediated HFnu-RRI-powers, but decreased LF-RRI-powers, LFnu-RRI-powers, and LF-BPsys-powers; in contrast, the patients slightly though significantly increased BPsys upon EPS, without changing any other parameter. In post-moderate-severe-TBI patients, autonomic BP-modulation was already compromised at rest. During EPS, our patients failed to activate cardiovagal modulation but slightly increased BPsys, indicating persistent CAN dysregulation. Our findings unveil persistence of subtle cardiovascular-autonomic dysregulation even years after TBI. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  14. Cardiac allograft immune activation: current perspectives

    Directory of Open Access Journals (Sweden)

    Chang D

    2014-12-01

    Full Text Available David Chang, Jon Kobashigawa Cedars-Sinai Heart Institute, Los Angeles, CA, USA Abstract: Heart transplant remains the most durable option for end-stage heart disease. Cardiac allograft immune activation and heart transplant rejection remain among the main complications limiting graft and recipient survival. Mediators of the immune system can cause different forms of rejection post-heart transplant. Types of heart transplant rejection include hyperacute rejection, cellular rejection, antibody-mediated rejection, and chronic rejection. In this review, we will summarize the innate and adaptive immune responses which influence the post-heart transplant recipient. Different forms of rejection and their clinical presentation, detection, and immune monitoring will be discussed. Treatment of heart transplant rejection will be examined. We will discuss potential treatment strategies for preventing rejection post-transplant in immunologically high-risk patients with antibody sensitization. Keywords: heart transplant, innate immunity, adaptive immunity, rejection, immunosuppression

  15. Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

    Science.gov (United States)

    Prior, Larissa J; Eikelis, Nina; Armitage, James A; Davern, Pamela J; Burke, Sandra L; Montani, Jean-Pierre; Barzel, Benjamin; Head, Geoffrey A

    2010-04-01

    The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (Pdiet rabbits and was correlated to plasma leptin (r=0.87; Pfat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.

  16. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

    Directory of Open Access Journals (Sweden)

    Joana Beatriz Sousa

    Full Text Available Nitric oxide (NO seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells and Confocal Microscopy. Results indicated that: 1 in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2 in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3 confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

  17. 6-sulfatoxymelatonin levels in pregnant women during workplace and nonworkplace stresses: a potential biologic marker of sympathetic activity.

    Science.gov (United States)

    Katz, V L; Ekstrom, R D; Mason, G A; Golden, R N

    1995-07-01

    Melatonin production is regulated by both catecholamines and sympathetic activity. Urine levels of the major metabolite of melatonin, 6-sulfatoxymelatonin, correlate well with serum melatonin levels and have been used to evaluate sympathetic output. We tested the hypothesis that urinary levels of 6-sulfatoxymelatonin would reflect the change in adrenergic activity on working days compared with nonworking days during pregnancy. Twenty-three healthy pregnant women, employed in a variety of occupations, including physicians, nurses, secretaries, salespeople, and laboratory workers were recruited from the clinics of the University of North Carolina School of Medicine. We measured 6-sulfatoxymelatonin levels in first morning voids and for the subsequent 10 hours at 24, 28, 32, and 36 weeks' gestation. Urine was collected in sets during working days and during nonworking days. 6-Sulfatoxymelatonin was measured by radioimmunoassay. In 11 women we also measured urine catecholamines by high-performance liquid chromatography. Levels of 6-sulfatoxymelatonin output did not change across gestation, although they tended to drift down as pregnancy progressed. Median levels at first morning void were 6.3 micrograms on workdays and 4.6 micrograms on nonworkdays. Although all values were skewed toward work being greater than nonwork, there were large interindividual variations. We therefore compared subjects against themselves and compared work levels for each subject to the corresponding gestational age-matched nonwork value. Among the 23 women, median 6-sulfatoxymelatonin levels were 81% greater during work than nonwork (p < 0.0002) when first morning collections were compared. Daytime urinary excretion of 6-sulfatoxymelatonin on workdays was 38% (p < 0.005) greater than during nonworkdays.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Asian women have attenuated sympathetic activation but enhanced renal–adrenal responses during pregnancy compared to Caucasian women

    Science.gov (United States)

    Okada, Yoshiyuki; Best, Stuart A; Jarvis, Sara S; Shibata, Shigeki; Parker, Rosemary S; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2015-01-01

    Abstract Asians have a lower prevalence of hypertensive disorders of pregnancy than Caucasians. Since sympathetic overactivity and dysregulation of the renal–adrenal system (e.g. low aldosterone levels) have been found in preeclamptic women, we hypothesized that Asians have lower muscle sympathetic nerve activity (MSNA) and greater aldosterone concentrations during normal pregnancy than Caucasians. In a prospective study, blood pressure (BP), heart rate (HR), and MSNA were measured during supine and upright tilt (30 deg and 60 deg for 5 min each) in 9 Asians (32 ± 1 years (mean ± SEM)) and 12 Caucasians (29 ± 1 years) during pre-, early (≤8 weeks of gestation) and late (32–36 weeks) pregnancy, and post-partum (6–10 weeks after delivery). Supine MSNA increased with pregnancy in both groups (P < 0.001); it was significantly lower in Asians than Caucasians (14 ± 3 vs. 23 ± 3 bursts min−1 and 16 ± 5 vs. 30 ± 3 bursts min−1 in early and late pregnancy, respectively; P = 0.023). BP decreased during early pregnancy (P < 0.001), but was restored during late pregnancy. HR increased during pregnancy (P < 0.001) with no racial difference (P = 0.758). MSNA increased during tilting and it was markedly lower in Asians than Caucasians in late pregnancy (31 ± 6 vs. 49 ± 3 bursts min−1 at 60 deg tilt; P = 0.003). Upright BP was lower in Asians, even in pre-pregnancy (P = 0.006), and this racial difference persisted during pregnancy. Direct renin and aldosterone increased during pregnancy (both P < 0.001); these hormones were greater in Asians (P = 0.086 and P = 0.014). Thus, Asians have less sympathetic activation but more upregulated renal–adrenal responses than Caucasians during pregnancy. These results may explain, at least in part, why Asian women are at low risk of hypertensive disorders in pregnancy. Key points Asian women have a lower prevalence of hypertensive disorders of pregnancy than Caucasian

  19. Deleterious effect of salusin-β in paraventricular nucleus on sympathetic activity and blood pressure via NF-κB signaling in a rat model of obesity hypertension.

    Science.gov (United States)

    Huang, Xiaodong; Wang, Yanchun; Ren, Kuang

    2015-08-01

    The paraventricular nucleus (PVN) has been shown to play a critical role in regulating blood pressure and sympathetic activity in obesity hypertension (OH). Salusin-β is a bioactive peptide with potential roles in mediating cardiovascular activity. The study was designed to test the hypothesis that salusin-β in the PVN can modulate sympathetic activity and blood pressure in OH. Male Sprague-Dawley rats were used to induce OH by a 12-week feeding of a high-fat diet (42% kcal as fat). Microinjection of salusin-β into the PVN increased the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner, whereas salusin-β antibody elicited significant decreases in RSNA, MAP and HR, and abolished the effects of salusin-β only in the OH rats. As expected, the OH rats had a higher norepinephrine level, which was further increased by salusin-β. Furthermore, salusin-β in the PVN accelerated the nuclear translocation of the p65 subunit of nuclear factor kappa B (NF-KB) and the degradation of IKB-α (an endogenous inhibitor of NF-KB). Pretreatment with pyrrolidine dithiocarbamate (an exogenous inhibitor of NF-KB) decreased RSNA, MAP and HR, and abolished the effects of salusin-β in the PVN in the OH rats. We concluded that salusin-β in the PVN markedly increased sympathetic outflow and blood pressure in diet-induced OH rats via NF-κB signaling.

  20. Sympathetic Activity, Assessed by Power Spectral Analysis of Heart Rate Variability, in White-Coat, Masked and Sustained Hypertension Versus True Normotension

    Czech Academy of Sciences Publication Activity Database

    Fagard, R.H.; Stolarz, K.; Kuznetsova, T.; Seidlerová, J.; Tikhonoff, V.; Grodzicki, T.; Nikitin, Y.; Filipovský, J.; Peleška, Jan; Casiglia, E.; Thijs, L.; Staessen, J.A.; Kawecka-Jaszcz, K.

    2007-01-01

    Roč. 25, č. 11 (2007), s. 2280-2285 ISSN 0263-6352 Institutional research plan: CEZ:AV0Z10300504 Keywords : heart rate variability * masked hypertension * power spectral analysis * sympathetic activity * white-coat hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.364, year: 2007

  1. Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

    Science.gov (United States)

    Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

    2014-10-01

    Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  2. Alterations in electrodermal activity and cardiac parasympathetic tone during hypnosis.

    Science.gov (United States)

    Kekecs, Zoltán; Szekely, Anna; Varga, Katalin

    2016-02-01

    Exploring autonomic nervous system (ANS) changes during hypnosis is critical for understanding the nature and extent of the hypnotic phenomenon and for identifying the mechanisms underlying the effects of hypnosis in different medical conditions. To assess ANS changes during hypnosis, electrodermal activity and pulse rate variability (PRV) were measured in 121 young adults. Participants either received hypnotic induction (hypnosis condition) or listened to music (control condition), and both groups were exposed to test suggestions. Blocks of silence and experimental sound stimuli were presented at baseline, after induction, and after de-induction. Skin conductance level (SCL) and high frequency (HF) power of PRV measured at each phase were compared between groups. Hypnosis decreased SCL compared to the control condition; however, there were no group differences in HF power. Furthermore, hypnotic suggestibility did not moderate ANS changes in the hypnosis group. These findings indicate that hypnosis reduces tonic sympathetic nervous system activity, which might explain why hypnosis is effective in the treatment of disorders with strong sympathetic nervous system involvement, such as rheumatoid arthritis, hot flashes, hypertension, and chronic pain. Further studies with different control conditions are required to examine the specificity of the sympathetic effects of hypnosis. © 2015 Society for Psychophysiological Research.

  3. Alpha-Blocker Treatment Response in Men With Lower Urinary Tract Symptoms Based on Sympathetic Activity: Prospective, Multicenter, Open-Labeled, Observational Study

    Directory of Open Access Journals (Sweden)

    Sung Gon Park

    2015-06-01

    Full Text Available Purpose: In this study, we compared the treatment outcomes for an α-blocker between 2 groups of men, one with high sympathetic activity (HSA and another with low sympathetic activity (LSA or normal sympathetic activity. Methods: A total of 159 men (≥50 years of age with lower urinary tract symptoms resulting from benign prostatic hyperplasia were analyzed. We assigned patients to groups according to their sympathetic activity, which was evaluated by heart ratevariability measurements. HSA was defined as a low frequency/high frequency ratio greater than 1.6. All patients received 10mg of alfuzosin once a day for 12 weeks. The primary end point was a change in the total International Prostate SymptomScore (IPSS at 12 weeks from baseline. Results: Sixty-seven men were assigned to the HSA group and 92 men were assigned to the LSA group. The baseline characteristics were not significantly different between the 2 groups, and the response to alfuzosin was good in both groups. Themean total IPSS change was not different between the groups. Both groups were not significantly different with respect to the changes in maximal flow rate, IPSS voiding or storage symptom subscores, quality of life, and rates of adverse drug events. TheHSA group showed a similar willingness to continue treatment compared to the LSA group, although their treatment satisfaction rating was lower. Conclusions: The therapeutic effects of alfuzosin did not differ in regards to the differences in sympathetic activity, but treatment satisfaction ratings were lower in the HSA group.

  4. Burnout versus work engagement in their effects on 24-hour ambulatory monitored cardiac autonomic function

    NARCIS (Netherlands)

    L.J.P. van Doornen (Lorenz); J.H. Houtveen (Jan); S. Langelaan (Saar); A.B. Bakker (Arnold); W. van Rhenen (Willem); W.B. Schaufeli (Wilmar)

    2009-01-01

    textabstractBurnout has been associated with increased risk of cardiovascular disease. This relationship may be mediated by a stress-related disruption in cardiac autonomic activity. The aim of the present study was to assess cardiac autonomic activity (sympathetic and parasympathetic) during a

  5. SYMPATHETIC NEURAL AND HEMODYNAMIC RESPONSES DURING COLD PRESSOR TEST IN ELDERLY BLACKS AND WHITES

    Science.gov (United States)

    Okada, Yoshiyuki; Jarvis, Sara S.; Best, Stuart A.; Edwards, Jeffrey G.; Hendrix, Joseph M.; Adams-Huet, Beverley; Vongpatanasin, Wanpen; Levine, Benjamin D.; Fu, Qi

    2016-01-01

    The sympathetic response during the cold pressor test (CPT) has been reported to be greater in young blacks than whites, especially in those with a family history of hypertension. Since blood pressure (BP) increases with age, we evaluated whether elderly blacks have greater sympathetic activation during CPT than age-matched whites. BP, heart rate (HR), cardiac output (Qc), and muscle sympathetic nerve activity (MSNA) were measured during supine baseline, 2-min CPT, and 3-min recovery in 47 elderly [68±7 (SD) yrs] volunteers (12 blacks, 35 whites). Baseline BP, HR, Qc, or MSNA did not differ between races. Systolic and diastolic BP (DBP) and HR increased during CPT (all P0.05). Qc increased during CPT and up to 30 sec of recovery in both groups, but was lower in blacks than whites. MSNA increased during CPT in both groups (both P<0.001); the increase in burst frequency was similar between groups, while the increase in total activity was smaller in blacks (P=0.030 for interaction). Peak change (Δ) in DBP was correlated with Δ total activity at 1 min into CPT in both blacks (r=0.78, P=0.003) and whites (r=0.43, P=0.009), while the slope was significantly greater in blacks (P=0.007). Thus, elderly blacks have smaller sympathetic and central hemodynamic (e.g., Qc) responses, but a greater pressor response for a given sympathetic activation during CPT than elderly whites. This response may stem from augmented sympathetic vascular transduction, greater sympathetic activation to other vascular bed(s), and/or enhanced non-adrenergically mediated vasoconstriction in elderly blacks. PMID:27021009

  6. A model-based approach for the evaluation of vagal and sympathetic activities in a newborn lamb.

    Science.gov (United States)

    Le Rolle, Virginie; Ojeda, David; Beuchée, Alain; Praud, Jean-Paul; Pladys, Patrick; Hernández, Alfredo I

    2013-01-01

    This paper proposes a baroreflex model and a recursive identification method to estimate the time-varying vagal and sympathetic contributions to heart rate variability during autonomic maneuvers. The baroreflex model includes baroreceptors, cardiovascular control center, parasympathetic and sympathetic pathways. The gains of the global afferent sympathetic and vagal pathways are identified recursively. The method has been validated on data from newborn lambs, which have been acquired during the application of an autonomic maneuver, without medication and under beta-blockers. Results show a close match between experimental and simulated signals under both conditions. The vagal and sympathetic contributions have been simulated and, as expected, it is possible to observe different baroreflex responses under beta-blockers compared to baseline conditions.

  7. Activation in the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system in women with carpal tunnel syndrome.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Díaz-Rodríguez, Lourdes; Salom-Moreno, Jaime; Galiano-Castillo, Noelia; Valverde-Herreros, Lis; Martínez-Martín, Javier; Pareja, Juan A

    2014-08-01

    The aim of this study is to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), α-amylase activity (sympathetic nervous system [SNS]), and immunoglobulin A (IgA; immune system) concentrations between women with carpal tunnel syndrome (CTS) and healthy women. A cross-sectional study. Activation of HPA, SNS, and immune system in CTS has not been clearly determined. One hundred two women (age: 45 ± 7 years) with electrodiagnostic and clinical diagnosis of CTS and 102 matched healthy women. The intensity of the pain was assessed with a Numerical Pain Rating Scale (0-10), and disability was determined with Boston Carpal Tunnel Questionnaire. Salivary cortisol concentration, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. Women with CTS exhibited lower salivary flow rate (P  0.2) were found between groups as a total. Women with severe CTS exhibited lower salivary flow rate (P < 0.001), higher α-amylase activity (P = 0.002), and higher cortisol concentration (P = 0.03) than healthy women and than those with minimal/moderate CTS (P < 0.05). Within women with CTS, significant positive associations between α-amylase activity and the intensity of pain were found: the highest the level of pain, the higher the α-amylase activity, i.e., higher SNS activation. These results suggest that women with severe CTS exhibit changes in activation in the HPA axis and SNS but not in the humoral immune system. Activation of the SNS was associated with the intensity of pain. Future studies are needed to elucidate the direction of this relationship. Wiley Periodicals, Inc.

  8. Effects of 12 months continuous positive airway pressure on sympathetic activity related brainstem function and structure in obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Luke Anthony Henderson

    2016-03-01

    Full Text Available Muscle sympathetic nerve activity (MSNA is greatly elevated in patients with obstructive sleep apnoea (OSA during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 subjects with OSA prior to and following 6 and 12 months of continuous positive airway pressure (CPAP treatment. We found that 6 and 12 months of CPAP treatment significantly reduced the elevated resting MSNA in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MNSA likely due to its effects on restoring brainstem structure and function.

  9. Leucine deprivation stimulates fat loss via increasing CRH expression in the hypothalamus and activating the sympathetic nervous system.

    Science.gov (United States)

    Cheng, Ying; Zhang, Qian; Meng, Qingshu; Xia, Tingting; Huang, Zhiying; Wang, Chunxia; Liu, Bin; Chen, Shanghai; Xiao, Fei; Du, Ying; Guo, Feifan

    2011-09-01

    We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three β-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis.

  10. In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

    Science.gov (United States)

    Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

    2013-04-01

    Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

  11. Evaluation of cardiac function in active and hibernating grizzly bears.

    Science.gov (United States)

    Nelson, O Lynne; McEwen, Margaret-Mary; Robbins, Charles T; Felicetti, Laura; Christensen, William F

    2003-10-15

    To evaluate cardiac function parameters in a group of active and hibernating grizzly bears. Prospective study. 6 subadult grizzly bears. Indirect blood pressure, a 12-lead ECG, and a routine echocardiogram were obtained in each bear during the summer active phase and during hibernation. All measurements of myocardial contractility were significantly lower in all bears during hibernation, compared with the active period. Mean rate of circumferential left ventricular shortening, percentage fractional shortening, and percentage left ventricular ejection fraction were significantly lower in bears during hibernation, compared with the active period. Certain indices of diastolic function appeared to indicate enhanced ventricular compliance during the hibernation period. Mean mitral inflow ratio and isovolumic relaxation time were greater during hibernation. Heart rate was significantly lower for hibernating bears, and mean cardiac index was lower but not significantly different from cardiac index during the active phase. Contrary to results obtained in hibernating rodent species, cardiac index was not significantly correlated with heart rate. Cardiac function parameters in hibernating bears are opposite to the chronic bradycardic effects detected in nonhibernating species, likely because of intrinsic cardiac muscle adaptations during hibernation. Understanding mechanisms and responses of the myocardium during hibernation could yield insight into mechanisms of cardiac function regulation in various disease states in nonhibernating species.

  12. Change in sympathetic nerve firing pattern associated with dietary weight loss in the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Elisabeth Annie Lambert

    2011-08-01

    Full Text Available Sympathetic activation in subjects with the metabolic syndrome (MS plays a role in the pathogenesis of cardiovascular disease development. Diet-induced weight loss decreases sympathetic outflow. However the mechanisms that account for sympathetic inhibition are not known. We sought to provide a detailed description of the sympathetic response to diet by analyzing the firing behavior of single-unit sympathetic nerve fibres. Fourteen subjects (57±2 years, 9 men, 5 females fulfilling ATP III criteria for the MS underwent a 3-month low calorie diet. Metabolic profile, hemodynamic parameters and multi-unit and single unit muscle sympathetic nerve activity (MSNA, microneurography were assessed prior to and at the end of the diet. Patients’ weight dropped from 96±4 to 88±3 kg (P<0.001. This was associated with a decrease in systolic and diastolic blood pressure (-12 ±3 and -5±2 mmHg, P<0.05, and in heart rate (-7±2 bpm, P<0.01 and an improvement in all metabolic parameters (fasting glucose: -0.302.1±0.118 mmol/l, total cholesterol: -0.564±0.164 mmol/l, triglycerides: -0.414±0.137 mmol/l, P<0.05. Multi-unit MSNA decreased from 68±4 to 59±5 bursts per 100 heartbeats (P<0.05. Single-unit MSNA indicated that the firing rate of individual vasoconstrictor fibres decreased from 59±10 to 32±4 spikes per 100 heart beats (P<0.05. The probability of firing decreased from 34±5 to 23±3 % of heartbeats (P<0.05, and the incidence of multiple firing decreased from 14±4 to 6±1 % of heartbeats (P<0.05. Cardiac and sympathetic baroreflex function were significantly improved (cardiac slope: 6.57±0.69 to 9.57±1.20 msec.mmHg-1; sympathetic slope: -3.86±0.34 to -5.05±0.47 bursts per 100 heartbeats.mmHg-1 P<0.05 for both. Hypocaloric diet decreased sympathetic activity and improved hemodynamic and metabolic parameters. The sympathoinhibition associated with weight loss involves marked changes, not only in the rate but also in the firing pattern of

  13. P2-28: An Amplification of Feedback from Facial Muscles Strengthened Sympathetic Activations to Emotional Facial Cues

    Directory of Open Access Journals (Sweden)

    Younbyoung Chae

    2012-10-01

    Full Text Available The facial feedback hypothesis suggests that feedback from cutaneous and muscular afferents influences our emotions during the control of facial expressions. Enhanced facial expressiveness is correlated with an increase in autonomic arousal, and self-reported emotional experience, while limited facial expression attenuates these responses. The present study was aimed at investigating the difference in emotional response in imitated versus observed facial expressions. For this, we measured the facial electromyogram of the corrugator muscle as well as the skin conductance response (SCR while participants were either imitating or simply observing emotional facial expressions. We found that participants produced significantly greater facial electromyogram activation during imitations compared to observations of angry faces. Similarly, they exhibited significantly greater SCR during imitations to angry faces compared to observations. An amplification of feedback from face muscles during imitation strengthened sympathetic activation to negative emotional cues. These findings suggest that manipulations of muscular feedback could modulate the bodily expression of emotion and perhaps also the emotional response itself.

  14. Urotensin II promotes vagal-mediated bradycardia by activating cardiac-projecting parasympathetic neurons of nucleus ambiguus.

    Science.gov (United States)

    Brailoiu, Gabriela Cristina; Deliu, Elena; Rabinowitz, Joseph E; Tilley, Douglas G; Koch, Walter J; Brailoiu, Eugen

    2014-05-01

    Urotensin II (U-II) is a cyclic undecapeptide that regulates cardiovascular function at central and peripheral sites. The functional role of U-II nucleus ambiguus, a key site controlling cardiac tone, has not been established, despite the identification of U-II and its receptor at this level. We report here that U-II produces an increase in cytosolic Ca(2+) concentration in retrogradely labeled cardiac vagal neurons of nucleus ambiguus via two pathways: (i) Ca(2+) release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptor; and (ii) Ca(2+) influx through P/Q-type Ca(2+) channels. In addition, U-II depolarizes cultured cardiac parasympathetic neurons. Microinjection of increasing concentrations of U-II into nucleus ambiguus elicits dose-dependent bradycardia in conscious rats, indicating the in vivo activation of the cholinergic pathway controlling the heart rate. Both the in vitro and in vivo effects were abolished by the urotensin receptor antagonist, urantide. Our findings suggest that, in addition, to the previously reported increase in sympathetic outflow, U-II activates cardiac vagal neurons of nucleus ambiguus, which may contribute to cardioprotection. © 2014 International Society for Neurochemistry.

  15. Sympathetic nervous system activity measured by skin conductance quantifies the challenge of walking adaptability tasks after stroke.

    Science.gov (United States)

    Clark, David J; Chatterjee, Sudeshna A; McGuirk, Theresa E; Porges, Eric C; Fox, Emily J; Balasubramanian, Chitralakshmi K

    2018-02-01

    Walking adaptability tasks are challenging for people with motor impairments. The construct of perceived challenge is typically measured by self-report assessments, which are susceptible to subjective measurement error. The development of an objective physiologically-based measure of challenge may help to improve the ability to assess this important aspect of mobility function. The objective of this study to investigate the use of sympathetic nervous system (SNS) activity measured by skin conductance to gauge the physiological stress response to challenging walking adaptability tasks in people post-stroke. Thirty adults with chronic post-stroke hemiparesis performed a battery of seventeen walking adaptability tasks. SNS activity was measured by skin conductance from the palmar surface of each hand. The primary outcome variable was the percent change in skin conductance level (ΔSCL) between the baseline resting and walking phases of each task. Task difficulty was measured by performance speed and by physical therapist scoring of performance. Walking function and balance confidence were measured by preferred walking speed and the Activities-specific Balance Confidence Scale, respectively. There was a statistically significant negative association between ΔSCL and task performance speed and between ΔSCL and clinical score, indicating that tasks with greater SNS activity had slower performance speed and poorer clinical scores. ΔSCL was significantly greater for low functioning participants versus high functioning participants, particularly during the most challenging walking adaptability tasks. This study supports the use of SNS activity measured by skin conductance as a valuable approach for objectively quantifying the perceived challenge of walking adaptability tasks in people post-stroke. Published by Elsevier B.V.

  16. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children : The ABCD Study

    NARCIS (Netherlands)

    Vrijkotte, Tanja G M; van den Born, Bert-Jan H; Hoekstra, Christine M C A; Gademan, Maaike G J; van Eijsden, Manon; de Rooij, Susanne R; Twickler, Marcel T B

    2015-01-01

    BACKGROUND: In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system

  17. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia

    Directory of Open Access Journals (Sweden)

    Suuronen Erik J

    2011-08-01

    Full Text Available Abstract Background Diabetes mellitus is strongly associated with cardiovascular dysfunction, derived in part from impairment of sympathetic nervous system signaling. Glucose, insulin, and non-esterified fatty acids are potent stimulants of sympathetic activity and norepinephrine (NE release. We hypothesized that sustained hyperglycemia in the high fat diet-fed streptozotocin (STZ rat model of sustained hyperglycemia with insulin resistance would exhibit progressive sympathetic nervous dysfunction in parallel with deteriorating myocardial systolic and/or diastolic function. Methods Cardiac sympathetic nervous integrity was investigated in vivo via biodistribution of the positron emission tomography radiotracer and NE analogue [11C]meta-hydroxyephedrine ([11C]HED. Cardiac systolic and diastolic function was evaluated by echocardiography. Plasma and cardiac NE levels and NE reuptake transporter (NET expression were evaluated as correlative measurements. Results The animal model displays insulin resistance, sustained hyperglycemia, and progressive hypoinsulinemia. After 8 weeks of persistent hyperglycemia, there was a significant 13-25% reduction in [11C]HED retention in myocardium of STZ-treated hyperglycemic but not euglycemic rats as compared to controls. There was a parallel 17% reduction in immunoblot density for NE reuptake transporter, a 1.2 fold and 2.5 fold elevation of cardiac and plasma NE respectively, and no change in sympathetic nerve density. No change in ejection fraction or fractional area change was detected by echocardiography. Reduced heart rate, prolonged mitral valve deceleration time, and elevated transmitral early to atrial flow velocity ratio measured by pulse-wave Doppler in hyperglycemic rats suggest diastolic impairment of the left ventricle. Conclusions Taken together, these data suggest that sustained hyperglycemia is associated with elevated myocardial NE content and dysregulation of sympathetic nervous system

  18. Dysregulation of Neuronal Ca2+ Channel Linked to Heightened Sympathetic Phenotype in Prohypertensive States

    OpenAIRE

    Larsen, Hege E.; Bardsley, Emma N.; Lefkimmiatis, Konstantinos; Paterson, David J.

    2016-01-01

    Hypertension is associated with impaired nitric oxide (NO)–cyclic nucleotide (CN)-coupled intracellular calcium (Ca2+) homeostasis that enhances cardiac sympathetic neurotransmission. Because neuronal membrane Ca2+ currents are reduced by NO-activated S-nitrosylation, we tested whether CNs affect membrane channel conductance directly in neurons isolated from the stellate ganglia of spontaneously hypertensive rats (SHRs) and their normotensive controls. Using voltage-clamp and cAMP–protein kin...

  19. Sympathetic nervous activity decreases during head-down bed rest but not during microgravity

    DEFF Research Database (Denmark)

    Christensen, Niels J; Heer, Martina; Ivanova, Krassimira

    2005-01-01

    We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy......, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P

  20. Neurotrophin responsiveness of sympathetic neurons is regulated by rapid mobilization of the p75 receptor to the cell surface through TrkA activation of Arf6.

    Science.gov (United States)

    Edward Hickman, F; Stanley, Emily M; Carter, Bruce D

    2018-05-22

    The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is up regulated resulting in formation of TrkA-p75 complexes, which are high affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 GEFs. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth while the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface

  1. Evidence that central dopamine receptors modulate sympathetic neuronal activity to the adrenal medulla to alter glucoregulatory mechanisms.

    Science.gov (United States)

    Arnerić, S P; Chow, S A; Bhatnagar, R K; Webb, R L; Fischer, L J; Long, J P

    1984-02-01

    Previous reports suggest that analogs of dopamine (DA) can produce hyperglycemia in rats by interacting with DA receptors. Experiments reported here indicate the site of action and describe the metabolic sequalae associated with the hyperglycemic effect of apomorphine (APO), produced in conscious unrestrained rats. Apomorphine was more potent when administered by intracerebroventricular (i.c.v.) injection than when given subcutaneously (s.c.). Very small doses of the DA receptor antagonist pimozide, given intraventricularly, blocked the hyperglycemic effect of apomorphine administered subcutaneously. Sectioning of the spinal cord at thoracic vertebra T1-2 or sectioning the greater splanchnic nerve blocked apomorphine-induced hyperglycemia; whereas section of the superior colliculus or section at T5-6 had no effect. A dose of apomorphine or epinephrine (EPI) producing a similar degree of hyperglycemia elevated the concentration of EPI in serum to a similar degree, and the increase in EPI in serum preceded the increase in glucose in serum. Fasting animals for 2 or 18 hr had no significant effect on EPI- or apomorphine-induced hyperglycemia despite a reduction (91-93%) of the glycogen content of liver and skeletal muscle during the 18 hr fast. 5-Methoxyindole-2-carboxylic acid (MICA), an inhibitor of gluconeogenesis, blocked EPI- and apomorphine-induced hyperglycemia in rats fasted for 18 hr. However, 5-methoxyindole-2-carboxylic acid was ineffective in blocking hyperglycemia in animals fasted for 2 hr. Changes in insulin or glucagon in serum alone cannot account for the hyperglycemic action of apomorphine. These data demonstrate that apomorphine interacts with central DA receptors located in the hindbrain to activate sympathetic neuronal activity to the adrenal gland which subsequently releases epinephrine to alter homeostasis of glucose. Epinephrine may then, depending on the nutritional status, facilitate glycogenolytic or gluconeogenic processes to produce

  2. Axon Guidance of Sympathetic Neurons to Cardiomyocytes by Glial Cell Line-Derived Neurotrophic Factor (GDNF)

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Hirabayashi, Masumi; Watabe, Kazuhiko; Jimbo, Yasuhiko; Kodama, Itsuo; Komuro, Issei

    2013-01-01

    Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal

  3. Hypothalamic-Pituitary-Adrenal and Sympathetic Nervous System Activity and Children's Behavioral Regulation

    Science.gov (United States)

    Lisonbee, Jared A.; Pendry, Patricia; Mize, Jacquelyn; Gwynn, Eugenia Parrett

    2010-01-01

    Self-regulation ability is an important component of children's academic success. Physiological reactivity may relate to brain activity governing attention and behavioral regulation. Saliva samples collected from 186 preschool children (101 boys, mean age = 53 months, 34% minority) before and after a series of mildly challenging games and again 30…

  4. External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

    Science.gov (United States)

    Hogan, T S

    2012-10-01

    Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient's cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

  5. External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

    LENUS (Irish Health Repository)

    Hogan, T S

    2012-10-01

    Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient\\'s cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

  6. Cardiac imaging in RASopathies/mitogen activated protein kinase syndromes

    Directory of Open Access Journals (Sweden)

    Rita Gravino

    2014-07-01

    Full Text Available RASopathies include a spectrum of disorders due to dysregulation of RAS/mitogen activated protein kinase pathway that plays an essential role in the control of the cell cycle and differentiation. As a consequence, its dysregulation has profound developmental consequences, in particular cardiac malformations. RASopathies with cardiac features are: Noonan syndrome, multiple lentigines syndrome, cardio-faciocutaneous syndrome, Costello syndrome, neurofibromatosis- 1, Legius syndrome, neurofibromatosis- Noonan syndrome. The former syndromes are associated with a high rate of cardiac involvement (60-85% and 12 genes: PTPN11, SOS1, RAF1, KRAS, HRAS, BRAF, MEK1/MAP2K1, MEK2/MAP2K2, NRAS, SHOC2, CBL and SPRED1. Although the majority of these diseases are readily distinguishable in clinical terms, an integrated imaging study of the cardiac condition associated to RASopathies helps to better define risk assessment, surveillance, and management of these patients.

  7. Snoring, sympathetic activity and cardiovascular risk factors in a 70 year old population

    DEFF Research Database (Denmark)

    Jennum, P; Schultz-Larsen, K; Christensen, Niels Juel

    1993-01-01

    ), plasma lipids (triglycerides, cholesterol, high density lipoprotein), plasma catecholamines (epinephrine, norepinephrine), fasting blood glucose and glucose tolerance test (1 gram glucose per kg body weight given and blood glucose was measured 1 and 2 hours thereafter) were evaluated in all participants......In order to describe the relation between snoring, cardiovascular risk factors, metabolic factors and sympathetitic activity, 804 70-year-old males and females were classified according to snoring habits and life-style factors (alcohol and tobacco consumption), blood pressure, body mass index (BMI....... Self-reported snoring was associated with gender (males showed higher prevalence than females, p glucose tolerance test (p

  8. Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo

    Directory of Open Access Journals (Sweden)

    Daisuke Kajimura

    2014-10-01

    Full Text Available The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1Dbh−/− display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1Dbh−/− mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual.

  9. Bradykinin receptor blockade restores the baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal failure rats.

    Science.gov (United States)

    Abdulla, M H; Duff, M; Swanton, H; Johns, E J

    2016-11-01

    This study investigated the effect of renal bradykinin B1 and B2 receptor blockade on the high- and low-pressure baroreceptor reflex regulation of renal sympathetic nerve activity (RSNA) in rats with cisplatin-induced renal failure. Cisplatin (5 mg/kg) or saline was given intraperitoneally 4 days prior to study. Following chloralose/urethane anaesthesia, rats were prepared for measurement of mean arterial pressure (MAP), heart rate and RSNA and received intrarenal infusions of either Lys-[des-Arg 9 , Leu 8 ]-bradykinin (LBK), a bradykinin B1 receptor blocker, or bradyzide (BZ), a bradykinin B2 receptor blocker. RSNA baroreflex gain curves and renal sympatho-inhibitory responses to volume expansion (VE) were obtained. In the control and renal failure groups, basal MAP (89 ± 3 vs. 80 ± 8 mmHg) and RSNA (2.0 ± 0.3 vs. 1.7 ± 0.6 μV.s) were similar but HR was lower in the latter group (331 ± 8 vs. 396 ± 9 beats/min). The baroreflex gain for RSNA in the renal failure rats was 39% (P renal failure rats. Intrarenal LBK infusion in the renal failure rats normalized the VE induced renal sympatho-inhibition whereas BZ only partially restored the response. These findings suggest that pro-inflammatory bradykinin acting at different receptors within the kidney generates afferent neural signals which impact differentially within the central nervous system on high- and low-pressure regulation of RSNA. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  10. Effect of cortisol on muscle sympathetic nerve activity in Pima Indians and Caucasians

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Weyer, Christian; Snitker, Soren

    2003-01-01

    . Although glucocorticoids inhibit SNS activity, Pima Indians are not hypercortisolemic compared with Caucasians. This does not exclude the possibility that the SNS is more responsive to an inhibitory effect of cortisol in the former than in the latter group. We measured fasting plasma ACTH and cortisol...... (metyrapone) followed by cortisol replacement (hydrocortisone) on plasma ACTH, cortisol, and MSNA. There were no ethnic differences in fasting plasma ACTH or cortisol, but MSNA adjusted for percent body fat was lower in Pimas than in Caucasians (P cortisol...... to a tonic inhibitory effect of cortisol. However, an acute release of cortisol is likely to more effectively contain sympathoexcitation during stress in Pima Indians than in Caucasians, which may be an important mechanism of cardioprotection in this Native American population....

  11. Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

    Science.gov (United States)

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2016-10-01

    We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

  12. The effects of carbonated water upon gastric and cardiac activities and fullness in healthy young women.

    Science.gov (United States)

    Wakisaka, Shiori; Nagai, Hajime; Mura, Emi; Matsumoto, Takehiro; Moritani, Toshio; Nagai, Narumi

    2012-01-01

    Although previous reports suggested that carbonated water drinking was effective against gastrointestinal symptoms, there is little information about the effects of carbonated water on gastric and appetite sensation. We therefore investigated the effect of carbonated water on short-term fullness with respect to gastric and cardiac responses in 19 healthy young women. Each subject was tested on three separate days at approximately 9 a.m. after an overnight fast. Gastric motility, evaluated by electrogastrography (EGG) and heart rate (HR), was measured for 20 min in the fasting state and 40 min after ingestion of water. Preloads consisted of an equivalent amount (250 mL) of water (W) or carbonated water (CW) and no drinking (blank). Fullness scores were measured using visual analog scales. To determine gastric motility, we assessed the component of bradygastria (1-2 cycles/min [cpm]), normogastria (2-4 cpm), tachygastria (4-9 cpm), and dominant frequency of the EGG power spectrum. After ingestion of CW, significant increases in fullness scores were observed compared with W. All postprandial EGG powers were significantly greater than preprandial, but no group difference was found. However, a dominant frequency tended to shift toward a lower band after ingestion of W. A significantly higher HR was found following consumption of CW as opposed to W. Multiple regression analysis revealed that increased HR was a significant variable contributing to the variances in fullness after ingestion of CW at 40 min. Our data suggest that CW may induce a short-term, but significant, satiating effect through enhanced postprandial gastric and cardiac activities due possibly to the increased sympathetic activity and/or withdrawal of parasympathetic activity.

  13. Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation.

    Science.gov (United States)

    Belza, A; Jessen, A B

    2005-06-01

    Bioactive food ingredients influence energy balance by exerting weak thermogenic effects. We studied whether the thermogenic effect of a combination of capsaicin, green tea extract (catechins and caffeine), tyrosine, and calcium was maintained after 7-day treatment and whether local effects in the gastric mucosa were involved in the efficacy. The present study was designed as a 3-way crossover, randomised, placebo-controlled, double-blinded intervention. Department of Human Nutrition, RVAU, Denmark. A total of 19 overweight to obese men (BMI: 28.0+/-2.7 kg/m2) were recruited by advertising locally. The subjects took the supplements for a period of 7 days. The supplements were administrated as a simple supplement with the bioactive ingredients, a similar enterocoated version, or placebo. In all, 24-h energy expenditure (EE), substrate oxidations, spontaneous physical activity (SPA), and heart rate were measured in respiration chambers on the seventh day of each test period. After adjustment for changes in body weight and SPA, 24-h EE was increased by 160 kJ/day (95% CI: 15-305) by the simple preparation as compared to placebo, whereas the enterocoated preparation had no such effect (53 kJ/day, -92 to 198); simple vs enterocoated versions (P=0.09). The simple preparation produced a deficit in 24-h energy balance of 193 kJ/day (49-338, P=0.03). Fat and carbohydrate oxidation were equally increased by the supplements. A supplement containing bioactive food ingredients increased daily EE by approximately 200 kJ or 2%, without raising the heart rate or any observed adverse effects. The lack of effect of the enterocoated preparation suggests that a local action of capsaicin in the gastric mucosa is a prerequisite for exerting the thermogenic effect.

  14. CAPSAICIN SUPPLEMENTATION FAILS TO MODULATE AUTONOMIC AND CARDIAC ELECTROPHYSIOLOGIC ACTIVITY DURING EXERCISE IN THE OBESE: WITH VARIANTS OF UCP2 AND UCP3 POLYMORPHISM

    Directory of Open Access Journals (Sweden)

    Ki Ok Shin

    2008-09-01

    Full Text Available We investigated the effects of capsaicin supplementation (150mg on alterations of autonomic nervous system (ANS activity associated with adverse effects of cardiac depolarization-repolarization intervals during aerobic exercise in obese humans. Nine obese males (26.1 ± 1.5 yrs volunteered between study designed. The cardiac ANS activities evaluated by means of heart rate variability of power spectral analysis and cardiac QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilation threshold (50%VTmax on stationary ergometer with placebo (CON or capsaicin (CAP oral administration chosen at random. The uncoupling protein (UCP 2 and UCP 3 genetic variants of the subjects were analyzed by noninvasive genotyping method from collecting buccal mucosa cells. The results indicated that there were no significant differences in cardiac ANS activities during rest and exercise between CON and CAP trials. Although no significant difference, A/A allele of UCP2 polymorphism showed a reduced sympathetic nervous system (SNS index activity compared to G/G + G/A allele during exercise intervention in our subjects. On the other hand, the data on cardiac QT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, our results suggest that capsaicin supplementation 1 h before exercise intervention has no effect on cardiac ANS activities and cardiac electrical stability during exercise in obese individuals. Further studies should also consider genetic variants for exercise efficacy against obesity

  15. Evaluation of cardiac blood blow, metabolism and sympathetic nerve function in patients with cardiac failure using PET and SPECT. Prognostic diagnosis based on the analysis of aggravating factors of the disease

    International Nuclear Information System (INIS)

    Ishida, Yoshio; Shimozu, Junko; Yasumura, Yoshio; Nagatani, Kenzo; Miyatake, Kunio

    1998-01-01

    Focusing on the failure of energy metabolism, which is assumed to be attributed to the cardiac muscle disorder of a patient with cardiac failure, the characteristics and diagnostic significance of the metabolic disorders of cadiac muscles were investigated in those patients. The diagnostic efficacy of β-methyl iodophenyl pentadecanoic acid (BMIPP) which is a imaging agent for lipid metabolism in the cardiac muscle was assessed in the clinical states of cardiac failure due to pulmonary hypertension. Even if there was a considerable increase in the mean pulmonary arterial pressure (mPAP), the initial accumulation of BMIPP linearly increased, similarly to the increase in the accumulation of MIBI, a blood flow agent. The initial accumulation of BMIPP was thought to reflect a thicken cardiac muscle and/or increased blood flow. Also, its washing-out rate was suggested to be usable as an clinical indicator to estimate the loading of ventricular pressure. (M.N.)

  16. Evaluation of cardiac blood blow, metabolism and sympathetic nerve function in patients with cardiac failure using PET and SPECT. Prognostic diagnosis based on the analysis of aggravating factors of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Yoshio; Shimozu, Junko; Yasumura, Yoshio; Nagatani, Kenzo; Miyatake, Kunio [National Cardiovascular Center, Suita, Osaka (Japan)

    1998-02-01

    Focusing on the failure of energy metabolism, which is assumed to be attributed to the cardiac muscle disorder of a patient with cardiac failure, the characteristics and diagnostic significance of the metabolic disorders of cadiac muscles were investigated in those patients. The diagnostic efficacy of {beta}-methyl iodophenyl pentadecanoic acid (BMIPP) which is a imaging agent for lipid metabolism in the cardiac muscle was assessed in the clinical states of cardiac failure due to pulmonary hypertension. Even if there was a considerable increase in the mean pulmonary arterial pressure (mPAP), the initial accumulation of BMIPP linearly increased, similarly to the increase in the accumulation of MIBI, a blood flow agent. The initial accumulation of BMIPP was thought to reflect a thicken cardiac muscle and/or increased blood flow. Also, its washing-out rate was suggested to be usable as an clinical indicator to estimate the loading of ventricular pressure. (M.N.)

  17. Time delay between cardiac and brain activity during sleep transitions

    NARCIS (Netherlands)

    Long, X.; Arends, J.B.A.M.; Aarts, R.M.; Haakma, R.; Fonseca, P.; Rolink, J.

    2015-01-01

    Human sleep consists of wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep that includes light and deep sleep stages. This work investigated the time delay between changes of cardiac and brain activity for sleep transitions. Here, the brain activity was quantified by

  18. Measure of synchrony in the activity of intrinsic cardiac neurons

    International Nuclear Information System (INIS)

    Longpré, Jean-Philippe; Salavatian, Siamak; Jacquemet, Vincent; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

    2014-01-01

    Recent multielectrode array recordings in ganglionated plexi of canine atria have opened the way to the study of population dynamics of intrinsic cardiac neurons. These data provide critical insights into the role of local processing that these ganglia play in the regulation of cardiac function. Low firing rates, marked non-stationarity, interplay with the cardiovascular and pulmonary systems and artifacts generated by myocardial activity create new constraints not present in brain recordings for which almost all neuronal analysis techniques have been developed. We adapted and extended the jitter-based synchrony index (SI) to (1) provide a robust and computationally efficient tool for assessing the level and statistical significance of SI between cardiac neurons, (2) estimate the bias on SI resulting from neuronal activity possibly hidden in myocardial artifacts, (3) quantify the synchrony or anti-synchrony between neuronal activity and the phase in the cardiac and respiratory cycles. The method was validated on firing time series from a total of 98 individual neurons identified in 8 dog experiments. SI ranged from −0.14 to 0.66, with 23 pairs of neurons with SI > 0.1. The estimated bias due to artifacts was typically <1%. Strongly cardiovascular- and pulmonary-related neurons (SI > 0.5) were found. Results support the use of jitter-based SI in the context of intrinsic cardiac neurons. (paper)

  19. Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

    Science.gov (United States)

    Yamakawa, Kentaro; Howard-Quijano, Kimberly; Zhou, Wei; Rajendran, Pradeep; Yagishita, Daigo; Vaseghi, Marmar; Ajijola, Olujimi A.; Armour, J. Andrew; Shivkumar, Kalyanam; Ardell, Jeffrey L.

    2015-01-01

    Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks. PMID:26661096

  20. Sarcopenia and physical activity in older male cardiac patients.

    Science.gov (United States)

    Izawa, Kazuhiro P; Watanabe, Satoshi; Oka, Koichiro; Kasahara, Yusuke; Morio, Yuji; Hiraki, Koji; Hirano, Yasuyuki; Omori, Yutaka; Suzuki, Norio; Kida, Keisuke; Suzuki, Kengo; Akashi, Yoshihiro J

    2016-11-01

    There is little information on the association of sarcopenia with physical activity in elderly cardiac patients. This study determined differences in physical activity and cutoff values for physical activity according to the presence or absence of sarcopenia in elderly male cardiac patients. Sixty-seven consecutive men aged ≥65 years with cardiac disease were enrolled. We defined sarcopenia using the European Working Group on Sarcopenia in Older People algorithm. Patients were divided into the sarcopenia group (n=25) and the non-sarcopenia group (n=42). In the patients with and without sarcopenia of physical activities were evaluated to determine cutoff values of physical activity. After adjusting for patient characteristics, both the average daily number of steps (3361.43±793.23 vs. 5991.55±583.57 steps, P=0.021) and the average daily energy expenditure of physical activity (71.84±22.19 vs. 154.57±16.18kcal, P=0.009) were significantly lower in the sarcopenia versus non-sarcopenia group. Receiver-operating characteristic analysis identified a cutoff value for steps of physical activity of 3551.80steps/day for 1 week, with a sensitivity of 0.73 and 1-specificity of 0.44 and a cutoff value for energy expenditure of physical activity of 85.17kcal/day for 1 week, with a sensitivity of 0.73 and 1-specificity of 0.27. Physical activity in the male cardiac patients with sarcopenia was significantly lower than that in those without sarcopenia. The cutoff values reported here may be useful values to aid in the identification of elderly male cardiac patients with sarcopenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Time delay between cardiac and brain activity during sleep transitions

    Science.gov (United States)

    Long, Xi; Arends, Johan B.; Aarts, Ronald M.; Haakma, Reinder; Fonseca, Pedro; Rolink, Jérôme

    2015-04-01

    Human sleep consists of wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep that includes light and deep sleep stages. This work investigated the time delay between changes of cardiac and brain activity for sleep transitions. Here, the brain activity was quantified by electroencephalographic (EEG) mean frequency and the cardiac parameters included heart rate, standard deviation of heartbeat intervals, and their low- and high-frequency spectral powers. Using a cross-correlation analysis, we found that the cardiac variations during wake-sleep and NREM sleep transitions preceded the EEG changes by 1-3 min but this was not the case for REM sleep transitions. These important findings can be further used to predict the onset and ending of some sleep stages in an early manner.

  2. The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension

    DEFF Research Database (Denmark)

    Gordin, Daniel; Fadl Elmula, Fadl Elmula M; Andersson, Bert

    2017-01-01

    ). Results: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow......Objective: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. Methods: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory...... hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization...

  3. Myocardial structural, contractile and electrophysiological changes in the guinea-pig heart failure model induced by chronic sympathetic activation

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Osadchiy, Oleg; Olesen, Søren-Peter

    2011-01-01

    Widely used murine models of adrenergic-induced cardiomyopathy offer little insight into electrical derangements seen in human heart failure owing to profound differences in the characteristics of ventricular repolarization in mice and rats compared with humans. We therefore sought to determine...... whether sustained adrenergic activation may produce a clinically relevant heart failure phenotype in the guinea-pig, an animal species whose ventricular action potential shape and restitution properties resemble those determined in humans. Isoprenaline (ISO), a ß-adrenoceptor agonist, was infused...... at variable dosage and duration using either subcutaneously implanted osmotic minipumps or daily injections, in an attempt to establish the relevant treatment protocol. We found that 3 months of daily ISO injections (final dose of 1 mg kg(-1), i.p.) promote heart failure evidenced by cardiac hypertrophy...

  4. Sympathetic reflex control of blood flow in human peripheral tissues

    DEFF Research Database (Denmark)

    Henriksen, O

    1991-01-01

    Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...... sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno...... skeletal muscle, cutaneous and subcutaneous tissues of the limbs indicate that the situation is more complex. Measurements have been carried out during acute as well as chronic sympathetic denervation. Spinal sympathetic reflex mechanisms have been evaluated in tetraplegic patients, where supraspinal...

  5. Sympathetic Nervous System Modulation of Inflammation and Remodeling in the Hypertensive Heart

    Science.gov (United States)

    Levick, Scott P.; Murray, David B.; Janicki, Joseph S.; Brower, Gregory L.

    2010-01-01

    Chronic activation of the sympathetic nervous system (SNS) is a key component of cardiac hypertrophy and fibrosis. However, previous studies have provided evidence to also implicate inflammatory cells, including mast cells, in the development of cardiac fibrosis. The current study investigated the potential interaction of cardiac mast cells with the SNS. Eight week old male SHR were sympathectomized to establish the effect of the SNS on cardiac mast cell density, myocardial remodeling and cytokine production in the hypertensive heart. Age-matched WKY served as controls. Cardiac fibrosis and hypertension were significantly attenuated and left ventricular mass normalized while cardiac mast cell density was markedly increased in sympathectomized SHR. Sympathectomy normalized myocardial levels of IFN-γ, IL-6 and IL-10, but had no effect on IL-4. The effect of norepinephrine and substance P on isolated cardiac mast cell activation was investigated as potential mechanisms of interaction between the two. Only substance P elicited mast cell degranulation. Substance P was also shown to induce the production of angiotensin II by a mixed population of isolated cardiac inflammatory cells, including mast cells, lymphocytes and macrophages. These results demonstrate the ability of neuropeptides to regulate inflammatory cell function, providing a potential mechanism by which the SNS and afferent nerves may interact with inflammatory cells in the hypertensive heart. PMID:20048196

  6. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

    Science.gov (United States)

    Li, Peng; Huang, Pei-Pei; Yang, Yun; Liu, Chi; Lu, Yan; Wang, Fang; Sun, Wei; Kong, Xiang-Qing

    2017-01-01

    results suggest a possible clinical efficacy of RSD for renovascular hypertension. The effects of renal sympathetic denervation (RSD) on hypertension, cardiac function, vascular fibrosis, and renal apoptosis were studied in the 2K1C rat model. Results showed that RSD attenuated hypertension, improved vascular remodeling, and reduced vascular fibrosis through decreased sympathetic activity in the 2K1C rat model, but it did not change the kidney size, renal apoptosis, or renal caspase-3 expression. These results could suggest possible clinical efficacy of RSD for renovascular hypertension. Copyright © 2017 the American Physiological Society.

  7. Short-Term Red Wine Consumption Promotes Differential Effects on Plasma Levels of High-Density Lipoprotein Cholesterol, Sympathetic Activity, and Endothelial Function in Hypercholesterolemic, Hypertensive, and Healthy Subjects

    Science.gov (United States)

    Andrade, Ana CM; Cesena, Fernando HY; Consolim-Colombo, Fernanda M; Coimbra, Silmara R; Benjó, Alexandre M; Krieger, Eduardo M; da Luz, Protasio Lemos

    2009-01-01

    OBJECTIVES: To compare the metabolic, hemodynamic, autonomic, and endothelial responses to short-term red wine consumption in subjects with hypercholesterolemia or arterial hypertension, and healthy controls. METHODS: Subjects with hypercholesterolemia (n=10) or arterial hypertension (n=9), or healthy controls (n=7) were given red wine (250 mL/night) for 15 days. Analyses were performed before and after red wine intake. RESULTS: Red wine significantly increased the plasma levels of HDL-cholesterol in the controls, but not in the other groups. The effects on hemodynamic measurements were mild, non-significantly more prominent in healthy subjects, and exhibited high interindividual variability. Across all participants, mean blood pressure decreased 7 mmHg (p <0.01) and systemic vascular resistance decreased 7% (p = 0.05). Heart rate and cardiac output did not significantly change in any group. Red wine enhanced muscle sympathetic fibular nerve activity in hypercholesterolemic and hypertensive patients, but not in controls. At baseline, brachial artery flow-mediated dilation was impaired in patients with hypercholesterolemia and arterial hypertension; red wine restored the dilation in the hypercholesterolemic group but not in the hypertensive group. CONCLUSIONS: Red wine elicits different metabolic, autonomic, and endothelial responses among individuals with hypercholesterolemia or arterial hypertension and healthy controls. Our findings highlight the need to consider patient characteristics when evaluating the response to red wine. PMID:19488610

  8. Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy. A comparison of 123I-MIBG scintigraphic and echocardiographic data

    International Nuclear Information System (INIS)

    Naruse, Hitoshi; Arii, Tohru; Kondo, Tomohiro

    2000-01-01

    It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123 I-MIBG scintigraphy. Both of these methods are associated with β-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patents with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography; and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123[ 123 I]meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123 I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r=0.682, p=0.0146), wall motion after dobutamine stress (r=0.758, p=0.0043), the change in wall motion (r=0.667, p=0.0178), and with left ventricular diastolic diameter (r=0.837, p=0.0007). In addition, the 123 I-MIBG washout rate correlated with baseline wall motion (r=0.608, p=0.0360), wall motion after dobutamine stress (r=0.703, p=0.0107), and with the change in wall motion (r=0.664, p=0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure. (author)

  9. Focal Reduction in Cardiac 123I-Metaiodobenzylguanidine Uptake in Patients With Anderson-Fabry Disease.

    Science.gov (United States)

    Yamamoto, Saori; Suzuki, Hideaki; Sugimura, Koichiro; Tatebe, Shunsuke; Aoki, Tatsuo; Miura, Masanobu; Yaoita, Nobuhiro; Sato, Haruka; Kozu, Katuya; Ota, Hideki; Takanami, Kentaro; Takase, Kei; Shimokawa, Hiroaki

    2016-11-25

    It remains to be elucidated whether cardiac sympathetic nervous activity is impaired in patients with Anderson-Fabry disease (AFD).Methods and Results:We performed 123 I-meta-iodobenzylguanidine (MIBG) scintigraphy and gadolinium-enhanced cardiovascular magnetic resonance (CMR) in 5 AFD patients. MIBG uptake in the inferolateral wall, where wall thinning and delayed enhancement were noted on CMR, was significantly lower compared with the anteroseptal wall. The localized reduction in MIBG uptake was also noted in 2 patients with no obvious abnormal findings on CMR. Cardiac sympathetic nervous activity is impaired in AFD before development of structural myocardial abnormalities. (Circ J 2016; 80: 2550-2551).

  10. The effect of a high-carbohydrate meal on postprandial thermogenesis and sympathetic nervous system activity in boys with a recent onset of obesity.

    Science.gov (United States)

    Nagai, Narumi; Sakane, Naoki; Hamada, Taku; Kimura, Tetsuya; Moritani, Toshio

    2005-04-01

    The purpose of the present study was to investigate the thermic effect of food (TEF) and sympathetic nervous system (SNS) activity in obese boys. Ten obese (9.2+/-0.4 years) and 13 lean boys (8.8+/-0.4 years) were examined for energy expenditure and fat oxidation measured via indirect calorimetry for 3 hours after a high-carbohydrate (HC; 70% carbohydrate, 20% fat, and 10% protein) or a high-fat (HF; 20% carbohydrate, 70% fat, and 10% protein) meal served on 2 different days at random. The activity of the SNS was assessed by means of a power spectral analysis of the heart rate variability. The TEF, expressed as a percentage of the consumed energy, was significantly lower in obese boys than in lean boys after the HC meal; however, such a difference was not observed after the HF meal. Multiple regression analysis revealed that obesity was a significant variable contributing to the variances in the TEF induced by the HC meal. Moreover, after the HC meal, the boys with a recent onset of obesity (duration, frequency component of the heart rate variability, an index of thermoregulatory SNS functions, compared with the remaining obese and lean boys. In conclusion, obese boys possessed normal metabolic and sympathetic responses to the HF meal but showed a diminished thermogenic response to the HC meal, especially during the early phase of obesity.

  11. Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease.

    Science.gov (United States)

    Larsen, Hege E; Lefkimmiatis, Konstantinos; Paterson, David J

    2016-12-14

    Many therapeutic interventions in disease states of heightened cardiac sympathetic activity are targeted to the myocytes. However, emerging clinical data highlights a dominant role in disease progression by the neurons themselves. Here we describe a novel experimental model of the peripheral neuro-cardiac axis to study the neuron's ability to drive a myocyte cAMP phenotype. We employed a co-culture of neonatal ventricular myocytes and sympathetic stellate neurons from normal (WKY) and pro-hypertensive (SHR) rats that are sympathetically hyper-responsive and measured nicotine evoked cAMP responses in the myocytes using a fourth generation FRET cAMP sensor. We demonstrated the dominant role of neurons in driving the myocyte ß-adrenergic phenotype, where SHR cultures elicited heightened myocyte cAMP responses during neural activation. Moreover, cross-culturing healthy neurons onto diseased myocytes rescued the diseased cAMP response of the myocyte. Conversely, healthy myocytes developed a diseased cAMP response if diseased neurons were introduced. Our results provide evidence for a dominant role played by the neuron in driving the adrenergic phenotype seen in cardiovascular disease. We also highlight the potential of using healthy neurons to turn down the gain of neurotransmission, akin to a smart pre-synaptic ß-blocker.

  12. Comparable attenuation of sympathetic nervous system activity in obese subjects with normal glucose tolerance, impaired glucose tolerance and treatment naïve type 2 diabetes following equivalent weight loss

    Directory of Open Access Journals (Sweden)

    Nora E. Straznicky

    2016-11-01

    Full Text Available Background and Purpose: Elevated sympathetic nervous system (SNS activity is a characteristic of obesity and type 2 diabetes (T2D that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n=15, impaired glucose tolerant (IGT, n=24 and newly-diagnosed T2D (n=15 consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate for 4-months. The three groups were matched for baseline age (56 + 1 years, body mass index (BMI, 32.9 + 0.7 kg/m2 and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography, spontaneous cardiac baroreflex sensitivity (BRS and oral glucose tolerance test. Results: Weight loss averaged -7.5 + 0.8, -8.1 + 0.5 and -8.0 + 0.9 % of body weight in NGT, IGT and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0-120 compared to NGT and IGT (group effect, P<0.001. Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group x time, P=0.04. The magnitude of reduction in MSNA (-7 + 3, -8 + 4, -15 + 4 burst/100hb, respectively and whole-body norepinephrine spillover rate (-28 + 8, -18 + 6 and -25 + 7 %, respectively, time effect both P<0.001, did not differ between groups. After adjustment for age and change in body weight, ∆ insulin AUC0-120 was independently associated with reduction in arterial norepinephrine concentration, whilst ∆ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different baseline glucose tolerance

  13. Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

    1997-08-01

    This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

  14. Clinical efficacy of efonidipine hydrochloride, a T-type calcium channel inhibitor, on sympathetic activities. Examination using spectral analysis of heart rate/blood pressure variabilities and 123I-Metaiodobenzylguanidine myocardial scintigraphy

    International Nuclear Information System (INIS)

    Harada, Kenji; Nomura, Masahiro; Nishikado, Akiyoshi; Uehara, Kouzoh; Nakaya, Yutaka; Ito, Susumu

    2003-01-01

    Dihydropyridine Ca antagonists cause reflex tachycardia related to their hypotensive effects. Efonidipine hydrochloride has inhibitory effects on T-type Ca channels, even as it inhibits reflex tachycardia. In the present study, the influence of efonidipine hydrochloride on heart rate and autonomic nervous function was investigated. Using an electrocardiogram and a tonometric blood pressure measurement, autonomic nervous activity was evaluated using spectral analysis of heart rate/systolic blood pressure variability. Three protocols were used: a single dose of efonidipine hydrochloride was administered orally to healthy subjects with resting heart rate values of 75 beats/min or more (high-heart rate (HR) group) and to healthy subjects with resting heart rate values less than 75 beats/min (low-HR group); efonidipine hydrochloride was newly administered to untreated patients with essential hypertension, and autonomic nervous activity was investigated after a 4-week treatment period; and patients with high heart rate values (≥75 beats/min) who had been treated with a dihydropyridine L-type Ca channel inhibitor for 1 month or more were switched to efonidipine hydrochloride and any changes in autonomic nervous activity were investigated. In all protocols, administration of efonidipine hydrochloride decreased the heart rate in patients with a high heart rate, reduced sympathetic nervous activity, and enhanced parasympathetic nervous activity. In addition, myocardial scintigraphy with 123 I-metaiodobenzylguanidine showed significant improvement in the washout rate and heart to mediastinum (H/M) ratio of patients who were switched from other dihydropyridine Ca antagonists to efonidipine hydrochloride. Efonidipine hydrochloride inhibits increases in heart rate and has effects on the autonomic nervous system. It may be useful for treating hypertension and angina pectoris, and may also have a cardiac protective function. (author)

  15. Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

    Science.gov (United States)

    Nohara, Kazunari; Waraich, Rizwana S; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S; Karsenty, Gérard; Burcelin, Rémy; Mauvais-Jarvis, Franck

    2013-06-15

    Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

  16. Clinical application of l-123 MlBG cardiac imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young [College of Medicine, Donga Univ., Busan (Korea, Republic of)

    2004-10-01

    Cardiac neurotransmission imaging allows in vivo assessment of presynaptic reuptake, neurotransmitter storage and postsynaptic receptors. Among the various neurotransmitter, I-123 MlBG is most available and relatively well-established. Metaiodobenzylguanidine (MIBG) is an analogue of the false neurotransmitter guanethidine. It is taken up to adrenergic neurons by uptake-1 mechanism as same as norepinephrine. As tagged with I-123, it can be used to image sympathetic function in various organs including heart with planar or SPECT techniques. I-123 MIBG imaging has a unique advantage to evaluate myocardial neuronal activity in which the heart has no significant structural abnormality or even no functional derangement measured with other conventional examination. In patients with cardiomyopathy and heart failure, this imaging has most sensitive technique to predict prognosis and treatment response of betablocker or ACE inhibitor. In diabetic patients, it allow very early detection of autonomic neuropathy. In patients with dangerous arrhythmia such as ventricular tachycardia or fibrillation, MIBG imaging may be only an abnormal result among various exams. In patients with ischemic heart disease, sympathetic derangement may be used as the method of risk stratification. In heart transplanted patients, sympathetic reinnervation is well evaluated. Adriamycin-induced cardiotoxicity is detected earlier than ventricular dysfunction with sympathetic dysfunction. Neurodegenerative disorder such as Parkinson's disease or dementia with Lewy bodies has also cardiac sympathetic dysfunction. Noninvasive assessment of cardiac sympathetic nerve activity with l-123 MlBG imaging may be improve understanding of the pathophysiology of cardiac disease and make a contribution to predict survival and therapy efficacy.

  17. Clinical application of l-123 MlBG cardiac imaging

    International Nuclear Information System (INIS)

    Kang, Do Young

    2004-01-01

    Cardiac neurotransmission imaging allows in vivo assessment of presynaptic reuptake, neurotransmitter storage and postsynaptic receptors. Among the various neurotransmitter, I-123 MlBG is most available and relatively well-established. Metaiodobenzylguanidine (MIBG) is an analogue of the false neurotransmitter guanethidine. It is taken up to adrenergic neurons by uptake-1 mechanism as same as norepinephrine. As tagged with I-123, it can be used to image sympathetic function in various organs including heart with planar or SPECT techniques. I-123 MIBG imaging has a unique advantage to evaluate myocardial neuronal activity in which the heart has no significant structural abnormality or even no functional derangement measured with other conventional examination. In patients with cardiomyopathy and heart failure, this imaging has most sensitive technique to predict prognosis and treatment response of betablocker or ACE inhibitor. In diabetic patients, it allow very early detection of autonomic neuropathy. In patients with dangerous arrhythmia such as ventricular tachycardia or fibrillation, MIBG imaging may be only an abnormal result among various exams. In patients with ischemic heart disease, sympathetic derangement may be used as the method of risk stratification. In heart transplanted patients, sympathetic reinnervation is well evaluated. Adriamycin-induced cardiotoxicity is detected earlier than ventricular dysfunction with sympathetic dysfunction. Neurodegenerative disorder such as Parkinson's disease or dementia with Lewy bodies has also cardiac sympathetic dysfunction. Noninvasive assessment of cardiac sympathetic nerve activity with l-123 MlBG imaging may be improve understanding of the pathophysiology of cardiac disease and make a contribution to predict survival and therapy efficacy

  18. Effects of cilnidipine on sympathetic nerve activity and cardiorenal function in hypertensive patients with type 2 diabetes mellitus: association with BNP and aldosterone levels.

    Science.gov (United States)

    Tanaka, Masami; Sekioka, Risa; Nishimura, Takeshi; Ichihara, Atsuhiro; Itoh, Hiroshi

    2014-12-01

    Hypertension stimulates the sympathetic nervous system and this phenomenon is exacerbated by diabetes mellitus. We investigated the effects of cilnidipine, an N/L-type calcium channel blocker, on aspects of this system in patients with type 2 diabetes mellitus. In 33 hypertensive patients with type 2 diabetes mellitus treated with a calcium channel blocker other than cilnidipine, we evaluated the influence of switching to cilnidipine on blood pressure, heart rate, catecholamine, plasma renin and aldosterone concentration, brain natriuretic peptide, urine liver-type fatty acid binding protein, and urinary albumin excretion ratio in the same patients by a cross-over design. Other biochemical parameters were also evaluated. Switching to cilnidipine did not change blood pressure but caused reduction in catecholamine concentrations in blood and urine and plasma aldosterone concentration, accompanied by significant reduction in brain natriuretic peptide, urine liver-type fatty acid binding protein, and albumin excretion ratio. These parameters other than brain natriuretic peptide were significantly increased after cilnidipine was changed to the original calcium channel blocker. In 33 hypertensive patients with type 2 diabetes mellitus, compared to other calcium channel blockers, cilnidipine suppressed sympathetic nerve activity and aldosterone, and significantly improved markers of cardiorenal disorders. Therefore, cilnidipine may be an important calcium channel blocker for use in combination with renin-angiotensin-aldosterone system inhibitors when dealing with hypertension complicated with diabetes mellitus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Christian Stevns; Hasbak, Philip

    2016-01-01

    Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM......). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

  20. Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity.

    Science.gov (United States)

    O'Malley, K; Velasco, M; Wells, J; McNay, J L

    1975-01-01

    A study was made of the possible mechanism(s) underlying minoxidil-induced increase in plasma renin activity (PRA). 10 patients with essential hypertension were treated with minoxidil and subsequently with a combination of minoxidil plus propranolol. Minoxidil lowered mean arterial pressure 31.6 plus or minus 3.3 mm Hg, mean plus or minus SEM. There was an associated increase in both PRA, 6.26 plus or minus 2.43 NG/ML/H, and heart rate, 21.4 plus or minus 2.7 beats/min. The changes in PRA and heart rate were positively correlated, r, 0.79. Addition of propranolol reduced mean arterial pressure by a further 10.1 plus or minus 1.5 mm Hg and returned heart rate to control levels. Propranolol reduced PRA significantly but not to control levels. Control PRA positively correlated with PRA on minoxidil, r, 0.97, and with PRA on minoxidil plus propranolol, r, 0.98. We conclude that control PRA is a major determinant of change in PRA with minoxidil. Minoxidil increased PRA by at least two mechanisms: (a) an adrenergic mechanism closely related to change in heart rate and blocked by propranolol, and (b) a mechanism(s) not sensitive to propranolol and possibly related to decrease in renal perfusion pressure. PMID:1127099

  1. BLOCKADE OF ROSTRAL VENTROLATERAL MEDULLA (RVLM BOMBESIN RECEPTOR TYPE 1 DECREASES BLOOD PRESSURE AND SYMPATHETIC ACTIVITY IN ANESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Izabella Silva De Jesus Pinto

    2016-06-01

    Full Text Available IIntrathecal injection of bombesin (BBS promoted hypertensive and sympathoexcitatory effects in normotensive (NT rats. However, the involvement of rostral ventrolateral medulla (RVLM in these responses is still unclear. In the present study, we investigated: (1 the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR; (2 the contribution of RVLM bombesin type 1 receptors (BB1 to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v. were instrumented to record mean arterial pressure (MAP, diaphragm (DIA motor and renal sympathetic nerve activity (RSNA. In NT rats and SHR, BBS (0.3 mM nanoinjected into RVLM increased MAP (33.9 ± 6.6 mmHg and 37.1 ± 4.5 mmHg, respectively; p < 0.05 and RSNA (97.8 ± 12.9 % and 84.5 ± 18.1 %, respectively; p < 0.05. In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7 %; p < 0.05. BB1 receptors antagonist (BIM-23127; 3 mM reduced MAP (-19.9 ± 4.4 mmHg; p < 0.05 and RSNA (-17.7 ± 3.8 %; p < 0.05 in SHR, but not in NT rats (-2.5 ± 2.8 mmHg; -2.7 ± 5.6 %, respectively. These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.

  2. Auditory driving of the autonomic nervous system: Listening to theta-frequency binaural beats post-exercise increases parasympathetic activation and sympathetic withdrawal.

    Science.gov (United States)

    McConnell, Patrick A; Froeliger, Brett; Garland, Eric L; Ives, Jeffrey C; Sforzo, Gary A

    2014-01-01

    Binaural beats are an auditory illusion perceived when two or more pure tones of similar frequencies are presented dichotically through stereo headphones. Although this phenomenon is thought to facilitate state changes (e.g., relaxation), few empirical studies have reported on whether binaural beats produce changes in autonomic arousal. Therefore, the present study investigated the effects of binaural beating on autonomic dynamics [heart rate variability (HRV)] during post-exercise relaxation. Subjects (n = 21; 18-29 years old) participated in a double-blind, placebo-controlled study during which binaural beats and placebo were administered over two randomized and counterbalanced sessions (within-subjects repeated-measures design). At the onset of each visit, subjects exercised for 20-min; post-exercise, subjects listened to either binaural beats ('wide-band' theta-frequency binaural beats) or placebo (carrier tones) for 20-min while relaxing alone in a quiet, low-light environment. Dependent variables consisted of high-frequency (HF, reflecting parasympathetic activity), low-frequency (LF, reflecting sympathetic and parasympathetic activity), and LF/HF normalized powers, as well as self-reported relaxation. As compared to the placebo visit, the binaural-beat visit resulted in greater self-reported relaxation, increased parasympathetic activation and increased sympathetic withdrawal. By the end of the 20-min relaxation period there were no observable differences in HRV between binaural-beat and placebo visits, although binaural-beat associated HRV significantly predicted subsequent reported relaxation. Findings suggest that listening to binaural beats may exert an acute influence on both LF and HF components of HRV and may increase subjective feelings of relaxation.

  3. Auditory driving of the autonomic nervous system: Listening to theta-frequency binaural beats post-exercise increases parasympathetic activation and sympathetic withdrawal

    Directory of Open Access Journals (Sweden)

    Patrick eMcConnell

    2014-11-01

    Full Text Available Binaural beats are an auditory illusion perceived when two or more pure tones of similar frequencies are presented dichotically through stereo headphones. Although this phenomenon is thought to facilitate state changes (e.g., relaxation, few empirical studies have reported on whether binaural beats produce changes in autonomic arousal. Therefore, the present study investigated the effects of binaural beating on autonomic dynamics (heart-rate variability (HRV during post-exercise relaxation. Subjects (n = 21; 18-29 years old participated in a double-blind, placebo-controlled study during which binaural beats and placebo were administered over two randomized and counterbalanced sessions (within-subjects repeated-measures design. At the onset of each visit, subjects exercised for 20-min; post-exercise, subjects listened to either binaural beats (‘wide-band’ theta-frequency binaural beats or placebo (carrier tone for 20-min while relaxing alone in a quiet, low-light environment. Dependent variables consisted of high frequency (HF, reflecting parasympathetic activity, low frequency (LF, reflecting sympathetic and parasympathetic activity and LF/HF normalized powers, as well as self-reported relaxation. As compared to the placebo visit, the binaural beat visit resulted in greater self-reported relaxation, as well as increased parasympathetic activation and sympathetic withdrawal. By the end of the 20-min relaxation period there were no observable differences in HRV between binaural beat and placebo visits, although binaural-beat associated HRV significantly predicted subsequent reported relaxation. Findings suggest that listening to binaural beats may exert an acute influence on both LF and HF components of HRV and may increase subjective feelings of relaxation.

  4. Effect of 4G-alpha-glucopyranosyl hesperidin on brown fat adipose tissue- and cutaneous-sympathetic nerve activity and peripheral body temperature.

    Science.gov (United States)

    Shen, Jiao; Nakamura, Hiroyasu; Fujisaki, Yoshiyuki; Tanida, Mamoru; Horii, Yuko; Fuyuki, Risa; Takumi, Hiroko; Shiraishi, Koso; Kometani, Takashi; Nagai, Katsuya

    2009-09-11

    Changes in the activity of the autonomic nervous system are good indicators of alterations in physiological phenomena such as the body temperature, blood glucose, blood pressure. Hesperidin, a flavanone known as vitamin P, has been shown to reduce the levels of serum lipids, cholesterol, and blood pressure. However, hesperidin is not water-soluble and is not well absorbed from the intestine. G-hesperidin (4G-alpha-glucopyranosyl hesperidin) is more water-soluble and more rapidly absorbed than hesperidin. In order to clarify the functions of G-hesperidin, we examined the effects of oral administration of G-hesperidin on interscapular brown adipose tissue-sympathetic nerve activity (BAT-SNA) and cutaneous sympathetic nerve activity (CASNA) in rats weighing about 300 g. In this study, we found that oral administration of 60 mg of G-hesperidin increased the BAT-SNA but decreased the CASNA in urethane-anesthetized rats. Since an elevation in BAT-SNA increases heat production (i.e. body temperature (BT)) and a decrease in CASNA increases cutaneous perfusion, we examined whether oral administration of G-hesperidin had an effect on the peripheral BT in rats. Consequently, we observed that the subcutaneous BT at the caudal end of the back after oral administration of 60 mg of G-hesperidin was significantly higher than the subcutaneous BT after oral administration of water in conscious rats. These findings suggest that G-hesperidin enhances the BAT-SNA and suppresses the CASNA resulting in an increase in the peripheral BT, probably by an increase in the thermogenesis in the BAT and an elevation in the cutaneous blood flow.

  5. Direct radiofluorination of dopamine: 18F-labeled 6-fluorodopamine for imaging cardiac sympathetic innervation in humans using positron emission tomography

    International Nuclear Information System (INIS)

    Chirakal, Raman; Coates, Geoff; Firnau, Guenter; Schrobilgen, Gary J.; Nahmias, Claude

    1996-01-01

    Fluorine-18 labeled fluorodopamine (FDA) was synthesized by the direct fluorination with [ 18 F]F 2 [produced by the nuclear reaction 18 O(p,n) 18 F] of dopamine in anhydrous hydrogen fluoride containing b boron trifluoride at -65 deg. C. Reverse-phase high-performance liquid chromatography (HPLC) was used to separate [ 18 F]6-FDA from the reaction mixture containing 18 F-labeled 2- and 5-FDA. The radio-chemical yield of [ 18 F]6-FDA, with respect to [ 18 F]F 2 , was 10 ± 2% at the end of the 120-min synthesis from EOB1. The specific activity of [ 18 F]6-FDA at the end of synthesis, 10 ± 1.5 Ci/mmol, is sufficiently high that the amount of 6-FDA associated with the infusion of a dose of 5 mCi of [ 18 F]6-FDA over 3 min into a 50-kg human (0.5-0.7 μg/kg/min) is considerably lower than therapeutic doses (2-10 μg/kg/min) of dopamine

  6. Macaque cardiac physiology is sensitive to the valence of passively viewed sensory stimuli.

    Directory of Open Access Journals (Sweden)

    Eliza Bliss-Moreau

    Full Text Available Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period increased and parasympathetic activity (as measured by respiratory sinus arrhythmia decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals.

  7. Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

    Science.gov (United States)

    Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

    2018-01-01

    Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

  8. Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Fangyun Tian

    2018-02-01

    Full Text Available Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG and electroencephalogram (EEG signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

  9. Sympathetic vasoconstriction takes an unexpected pannexin detour

    DEFF Research Database (Denmark)

    Schak Nielsen, Morten

    2015-01-01

    Sympathetic vasoconstriction plays an important role in the control of blood pressure and the distribution of blood flow. In this issue of Science Signaling, Billaud et al. show that sympathetic vasoconstriction occurs through a complex scheme involving the activation of large-pore pannexin 1...... channels and the subsequent release of adenosine triphosphate that promotes contraction in an autocrine and paracrine manner. This elaborate mechanism may function as a point of intercept for other signaling pathways-for example, in relation to the phenomenon "functional sympatholysis," in which exercise...... abrogates sympathetic vasoconstriction in skeletal muscle. Because pannexin 1 channels are inhibited by nitric oxide, they may function as a switch to turn off adrenergic signaling in skeletal muscle during exercise....

  10. Sympathetic chain Schwannoma

    International Nuclear Information System (INIS)

    Al-Mashat, Faisal M.

    2009-01-01

    Schwannomas are rare, benign, slowly growing tumors arising from Schwann cells that line nerve sheaths. Schwannomas arising from the cervical sympathetic chain are extremely rare. Here, we report a case of a 70-year-old man who presented with only an asymptomatic neck mass. Physical examination revealed a left sided Horner syndrome and a neck mass with transmitted pulsation and anterior displacement of the carotid artery. Computed tomography (CT) showed a well-defined non-enhancing mass with vascular displacement. The nerve of origin of this encapsulated tumor was the sympathetic chain. The tumor was excised completely intact. The pathologic diagnosis was Schwannoma (Antoni type A and Antoni type B). The patient has been well and free of tumor recurrence for 14 months with persistence of asymptomatic left sided Horner syndrome. The clinical, radiological and pathological evaluations, therapy and postoperative complications of this tumor are discussed. (author)

  11. Cardiac retention of PET neuronal imaging agent LMI1195 in different species: Impact of norepinephrine uptake-1 and -2 transporters

    International Nuclear Information System (INIS)

    Yu, Ming; Bozek, Jody; Kagan, Mikhail; Guaraldi, Mary; Silva, Paula; Azure, Michael; Onthank, David; Robinson, Simon P.

    2013-01-01

    Introduction: Released sympathetic neurotransmitter norepinephrine (NE) in the heart is cleared by neuronal uptake-1 and extraneuronal uptake-2 transporters. Cardiac uptake-1 and -2 expression varies among species, but the uptake-1 is the primary transporter in humans. LMI1195 is an NE analog labeled with 18 F for PET evaluation of cardiac neuronal function. This study investigated the impact of cardiac neuronal uptake-1 associated with different species on LMI1195 heart uptake. Methods: Cardiac uptake-1 was blocked by desipramine, a selective uptake-1 inhibitor, and sympathetic neuronal denervation was induced by 6-hydroxydopamine, a neurotoxin, in rats, rabbits and nonhuman primates (NHP). Tissue biodistribution and cardiac imaging of LMI1195 and 123 I-metaiodobenzylguanidine (MIBG) were performed. Results: In rats, uptake-1 blockade did not alter LMI1195 heart uptake compared to the control at 60-min post injection [1.41 ± 0.07 vs. 1.47 ± 0.23 % injected dose per gram tissue (%ID/g)]. In contrast, LMI1195 heart uptake was reduced by 80% in uptake-1 blocked rabbits. In sympathetically denervated rats, LMI1195 heart uptake was similar to the control (2.18 ± 0.40 vs. 2.58 ± 0.76 %ID/g). However, the uptake decreased by 79% in denervated rabbits. Similar results were found in MIBG heart uptake in rats and rabbits with uptake-1 blockade. Consistently, LMI1195 cardiac imaging showed comparable myocardial activity in uptake-1 blocked or sympathetically denervated rats to the control, but marked activity reduction in uptake-1 blocked or denervated rabbits and NHPs. Conclusions: LMI1195 is retained in the heart of rabbits and NHPs primarily via the neuronal uptake-1 with high selectivity and can be used for evaluation of cardiac sympathetic denervation. Similar to the human, the neuronal uptake-1 is the dominant transporter for cardiac retention of NE analogs in rabbits and NHPs, but not in rats

  12. Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

    OpenAIRE

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    1999-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, ...

  13. Active Bleeding after Cardiac Surgery: A Prospective Observational Multicenter Study.

    Directory of Open Access Journals (Sweden)

    Pascal H Colson

    Full Text Available To estimate the incidence of active bleeding after cardiac surgery (AB based on a definition directly related on blood flow from chest drainage; to describe the AB characteristics and its management; to identify factors of postoperative complications.AB was defined as a blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation for hemostasis during the first 12 postoperative hours. The definition was applied in a prospective longitudinal observational study involving 29 French centers; all adult patients undergoing cardiac surgery with cardiopulmonary bypass were included over a 3-month period. Perioperative data (including blood product administration were collected. To study possible variation in clinical practice among centers, patients were classified into two groups according to the AB incidence of the center compared to the overall incidence: "Low incidence" if incidence is lower and "High incidence" if incidence is equal or greater than overall incidence. Logistic regression analysis was used to identify risk factors of postoperative complications.Among 4,904 patients, 129 experienced AB (2.6%, among them 52 reoperation. Postoperative bleeding loss was 1,000 [820;1,375] ml and 1,680 [1,280;2,300] ml at 6 and 24 hours respectively. Incidence of AB varied between centers (0 to 16% but was independent of in-centre cardiac surgical experience. Comparisons between groups according to AB incidence showed differences in postoperative management. Body surface area, preoperative creatinine, emergency surgery, postoperative acidosis and red blood cell transfusion were risk factors of postoperative complication.A blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or early reoperation for hemostasis seems a relevant definition of AB. This definition, independent of transfusion, adjusted to body weight, may assess real time bleeding occurring early after surgery.

  14. Active Bleeding after Cardiac Surgery: A Prospective Observational Multicenter Study.

    Science.gov (United States)

    Colson, Pascal H; Gaudard, Philippe; Fellahi, Jean-Luc; Bertet, Héléna; Faucanie, Marie; Amour, Julien; Blanloeil, Yvonnick; Lanquetot, Hervé; Ouattara, Alexandre; Picot, Marie Christine

    2016-01-01

    To estimate the incidence of active bleeding after cardiac surgery (AB) based on a definition directly related on blood flow from chest drainage; to describe the AB characteristics and its management; to identify factors of postoperative complications. AB was defined as a blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation for hemostasis during the first 12 postoperative hours. The definition was applied in a prospective longitudinal observational study involving 29 French centers; all adult patients undergoing cardiac surgery with cardiopulmonary bypass were included over a 3-month period. Perioperative data (including blood product administration) were collected. To study possible variation in clinical practice among centers, patients were classified into two groups according to the AB incidence of the center compared to the overall incidence: "Low incidence" if incidence is lower and "High incidence" if incidence is equal or greater than overall incidence. Logistic regression analysis was used to identify risk factors of postoperative complications. Among 4,904 patients, 129 experienced AB (2.6%), among them 52 reoperation. Postoperative bleeding loss was 1,000 [820;1,375] ml and 1,680 [1,280;2,300] ml at 6 and 24 hours respectively. Incidence of AB varied between centers (0 to 16%) but was independent of in-centre cardiac surgical experience. Comparisons between groups according to AB incidence showed differences in postoperative management. Body surface area, preoperative creatinine, emergency surgery, postoperative acidosis and red blood cell transfusion were risk factors of postoperative complication. A blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or early reoperation for hemostasis seems a relevant definition of AB. This definition, independent of transfusion, adjusted to body weight, may assess real time bleeding occurring early after surgery.

  15. Pulse-driven magnetoimpedance sensor detection of cardiac magnetic activity.

    Directory of Open Access Journals (Sweden)

    Shinsuke Nakayama

    Full Text Available This study sought to establish a convenient method for detecting biomagnetic activity in the heart. Electrical activity of the heart simultaneously induces a magnetic field. Detection of this magnetic activity will enable non-contact, noninvasive evaluation to be made. We improved the sensitivity of a pulse-driven magnetoimpedance (PMI sensor, which is used as an electric compass in mobile phones and as a motion sensor of the operation handle in computer games, toward a pico-Tesla (pT level, and measured magnetic fields on the surface of the thoracic wall in humans. The changes in magnetic field detected by this sensor synchronized with the electric activity of the electrocardiogram (ECG. The shape of the magnetic wave was largely altered by shifting the sensor position within 20 mm in parallel and/or perpendicular to the thoracic wall. The magnetic activity was maximal in the 4th intercostals near the center of the sterna. Furthermore, averaging the magnetic activity at 15 mm in the distance between the thoracic wall and the sensor demonstrated magnetic waves mimicking the P wave and QRS complex. The present study shows the application of PMI sensor in detecting cardiac magnetic activity in several healthy subjects, and suggests future applications of this technology in medicine and biology.

  16. NaCl and osmolarity produce different responses in organum vasculosum of the lamina terminalis neurons, sympathetic nerve activity and blood pressure.

    Science.gov (United States)

    Kinsman, Brian J; Browning, Kirsteen N; Stocker, Sean D

    2017-09-15

    Changes in extracellular osmolarity stimulate thirst and vasopressin secretion through a central osmoreceptor; however, central infusion of hypertonic NaCl produces a greater sympathoexcitatory and pressor response than infusion of hypertonic mannitol/sorbitol. Neurons in the organum vasculosum of the lamina terminalis (OVLT) sense changes in extracellular osmolarity and NaCl. In this study, we discovered that intracerebroventricular infusion or local OVLT injection of hypertonic NaCl increases lumbar sympathetic nerve activity, adrenal sympathetic nerve activity and arterial blood pressure whereas equi-osmotic mannitol/sorbitol did not alter any variable. In vitro whole-cell recordings demonstrate the majority of OVLT neurons are responsive to hypertonic NaCl or mannitol. However, hypertonic NaCl stimulates a greater increase in discharge frequency than equi-osmotic mannitol. Intracarotid or intracerebroventricular infusion of hypertonic NaCl evokes a greater increase in OVLT neuronal discharge frequency than equi-osmotic sorbitol. Collectively, these novel data suggest that subsets of OVLT neurons respond differently to hypertonic NaCl versus osmolarity and subsequently regulate body fluid homeostasis. These responses probably reflect distinct cellular mechanisms underlying NaCl- versus osmo-sensing. Systemic or central infusion of hypertonic NaCl and other osmolytes readily stimulate thirst and vasopressin secretion. In contrast, central infusion of hypertonic NaCl produces a greater increase in arterial blood pressure (ABP) than equi-osmotic mannitol/sorbitol. Although these responses depend on neurons in the organum vasculosum of the lamina terminalis (OVLT), these observations suggest OVLT neurons may sense or respond differently to hypertonic NaCl versus osmolarity. The purpose of this study was to test this hypothesis in Sprague-Dawley rats. First, intracerebroventricular (icv) infusion (5 μl/10 min) of 1.0 m NaCl produced a significantly greater

  17. Detection of cardiac activity changes from human speech

    Science.gov (United States)

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

    2015-05-01

    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  18. Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

    International Nuclear Information System (INIS)

    Kirby, M.; Stewart, D.

    1984-01-01

    Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [ 3 H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [ 3 H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [ 3 H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine

  19. Enhanced pyruvate dehydrogenase activity improves cardiac outcomes in a murine model of cardiac arrest.

    Directory of Open Access Journals (Sweden)

    Lin Piao

    Full Text Available Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH, the limiting step in mitochondrial glucose oxidation, is inhibited by increased expression of PDH kinase (PDK during ischemia/reperfusion injury. This results in decreased utilization of glucose to generate cellular ATP. Post-cardiac arrest (CA hypothermia improves outcomes and alters metabolism, but its influence on PDH and PDK activity following CA are unknown. We hypothesized that therapeutic hypothermia (TH following CA is associated with the inhibition of PDK activity and increased PDH activity. We further hypothesized that an inhibitor of PDK activity, dichloroacetate (DCA, would improve PDH activity and post-CA outcomes.Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent a 12-minute KCl-induced CA followed by cardiopulmonary resuscitation. Compared to normothermic (37°C CA controls, administering TH (30°C improved overall survival (72-hour survival rate: 62.5% vs. 28.6%, P<0.001, post-resuscitation myocardial function (ejection fraction: 50.9±3.1% vs. 27.2±2.0%, P<0.001; aorta systolic pressure: 132.7±7.3 vs. 72.3±3.0 mmHg, P<0.001, and neurological scores at 72-hour post CA (9.5±1.3 vs. 5.4±1.3, P<0.05. In both heart and brain, CA increased lactate concentrations (1.9-fold and 3.1-fold increase, respectively, P<0.01, decreased PDH enzyme activity (24% and 50% reduction, respectively, P<0.01, and increased PDK protein expressions (1.2-fold and 1.9-fold, respectively, P<0.01. In contrast, post-CA treatment with TH normalized lactate concentrations (P<0.01 and P<0.05 and PDK expressions (P<0.001 and P<0.05, while increasing PDH activity (P<0.01 and P<0.01 in both the heart and brain. Additionally, treatment with DCA (0.2 mg/g body weight 30 min prior to CA improved both myocardial hemodynamics 2 hours post-CA (aortic systolic pressure: 123±3 vs. 96±4 mmHg, P<0.001 and 72-hour survival rates

  20. Role of Nuclear Medicine in the cardiac resinchronization therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Simone Cristina Soares, E-mail: simonecordis@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Giorgi, Maria Clementina Pinto; D' Orio, Silvana Angelina; Meneghetti, Jose Claudio [Instituto do Coracao (InCor/FM/USP), Sao Paulo, SP (Brazil)

    2011-10-15

    Cardiac resynchronization therapy (CRT) emerged as one of the most promising approaches in the treatment of cardiac dyssynchrony in heart failure patients' refractory to medical treatment. However, despite very promising clinical and functional results, individual response analyses show that a significant number of patients do not respond to treatment. The role of nuclear medicine and molecular imaging in the selection of CRT candidates by the assessment of cardiac dyssynchrony, myocardial viability, myocardial perfusion and blood flow and sympathetic cardiac activity has been discussed in this review. The potential utilization of this tool to improve the comprehension of detrimental effects of dyssynchrony on cardiac function and the evaluation and monitoring of the response to CRT were also considered. Other molecular targets that characterize glucose and fatty acid metabolism, apoptosis, angiotensin converting enzyme activity and angiogenesis that can be evaluated with this technique were described. (author)

  1. Role of Nuclear Medicine in the cardiac resinchronization therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Simone Cristina Soares, E-mail: simonecordis@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Giorgi, Maria Clementina Pinto; D' Orio, Silvana Angelina; Meneghetti, Jose Claudio [Instituto do Coracao (InCor/FM/USP), Sao Paulo, SP (Brazil)

    2011-10-15

    Cardiac resynchronization therapy (CRT) emerged as one of the most promising approaches in the treatment of cardiac dyssynchrony in heart failure patients' refractory to medical treatment. However, despite very promising clinical and functional results, individual response analyses show that a significant number of patients do not respond to treatment. The role of nuclear medicine and molecular imaging in the selection of CRT candidates by the assessment of cardiac dyssynchrony, myocardial viability, myocardial perfusion and blood flow and sympathetic cardiac activity has been discussed in this review. The potential utilization of this tool to improve the comprehension of detrimental effects of dyssynchrony on cardiac function and the evaluation and monitoring of the response to CRT were also considered. Other molecular targets that characterize glucose and fatty acid metabolism, apoptosis, angiotensin converting enzyme activity and angiogenesis that can be evaluated with this technique were described. (author)

  2. The Potential of the Bi-Directional Gaze: A Call for Neuroscientific Research on the Simultaneous Activation of the Sympathetic and Parasympathetic Nervous Systems through Tantric Practice

    Directory of Open Access Journals (Sweden)

    Jeffrey S. Lidke

    2016-11-01

    Full Text Available This paper is a call for the development of a neuroscientific research protocol for the study of the impact of Tantric practice on the autonomic nervous system. Tantric texts like Abhinavagupta’s Tantrāloka map out a complex meditative ritual system in which inward-gazing, apophatic, sense-denying contemplative practices are combined with outward-gazing, kataphatic sense-activating ritual practices. Abhinavagupta announces a culminating “bi-directional” state (pratimīlana-samādhi as the highest natural state (sahaja-samādhi in which the practitioner becomes a perfected yogi (siddhayogi. This state of maximized cognitive capacities, in which one’s inward gaze and outward world-engagement are held in balance, appears to be one in which the anabolic metabolic processes of the parasympathetic nervous system and the catabolic metabolic processes of the sympathetic nervous systems are simultaneously activated and integrated. Akin to secularized mindfulness and compassion training protocols like Emory’s CBCT, I propose the development of secularized “Tantric protocols” for the development of secular and tradition-specific methods for further exploring the potential of the human neurological system.

  3. Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis

    Directory of Open Access Journals (Sweden)

    Pengjiao Xi

    2018-05-01

    Full Text Available Background/Aims: Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. Methods: Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 108 or 2.0 × 1010 vector genomes or Control-AAV-EGFP (2.0 × 108 vector genomes was injected into the third ventricle. After administration, the rats were fed a high-fat diet (HFD for 9 weeks to induce obesity. Rats fed a chow fat diet were used as normal controls. Results: LKB1 delivery decreased body weight, energy intake, fat mass, and serum lipid levels. LKB1 also improved HFD-induced hepatic fatty degeneration. Interestingly, LKB1 over-expression in the hypothalamus activated the AMPK-POMC neurons-sympathetic nervous system (SNS axis, which can release epinephrine to promote white fat browning. Conversely, the elevated expression of MC3R/MC4R inhibited food intake. These two factors worked together to inhibit the development of obesity. Conclusions: LKB1 in the hypothalamus may have therapeutic potential for DIO through the activation of the AMPK-POMC neurons-SNS axis.

  4. Intraventricular Injection of LKB1 Inhibits the Formation of Diet-Induced Obesity in Rats by Activating the AMPK-POMC Neurons-Sympathetic Nervous System Axis.

    Science.gov (United States)

    Xi, Pengjiao; Du, Jianying; Liang, Huimin; Han, Jie; Wu, Zhaoxia; Wang, Haomin; He, Lu; Wang, Qiming; Ge, Haize; Li, Yongmei; Xue, Jie; Tian, Derun

    2018-01-01

    Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO) is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 108 or 2.0 × 1010 vector genomes) or Control-AAV-EGFP (2.0 × 108 vector genomes) was injected into the third ventricle. After administration, the rats were fed a high-fat diet (HFD) for 9 weeks to induce obesity. Rats fed a chow fat diet were used as normal controls. LKB1 delivery decreased body weight, energy intake, fat mass, and serum lipid levels. LKB1 also improved HFD-induced hepatic fatty degeneration. Interestingly, LKB1 over-expression in the hypothalamus activated the AMPK-POMC neurons-sympathetic nervous system (SNS) axis, which can release epinephrine to promote white fat browning. Conversely, the elevated expression of MC3R/MC4R inhibited food intake. These two factors worked together to inhibit the development of obesity. LKB1 in the hypothalamus may have therapeutic potential for DIO through the activation of the AMPK-POMC neurons-SNS axis. © 2018 The Author(s). Published by S. Karger AG, Basel.

  5. Sudden Cardiac Death During Sports Activities in the General Population.

    Science.gov (United States)

    Narayanan, Kumar; Bougouin, Wulfran; Sharifzadehgan, Ardalan; Waldmann, Victor; Karam, Nicole; Marijon, Eloi; Jouven, Xavier

    2017-12-01

    Regular exercise reduces cardiovascular and overall mortality. Participation in sports is an important determinant of cardiovascular health and fitness. Regular sports activity is associated with a smaller risk of sudden cardiac death (SCD). However, there is a small risk of sports-related SCD. Sports-related SCD accounts for approximately 5% of total SCD. SCD among athletes comprises only a fraction of all sports-related SCD. Sport-related SCD has a male predominance and an average age of affliction of 45 to 50 years. Survival is better than for other SCD. This review summarizes links between sports and SCD and discusses current knowledge and controversies. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Does Cardiac Rehabilitation After an Acute Cardiac Syndrome Lead to Changes in Physical Activity Habits? Systematic Review

    NARCIS (Netherlands)

    ter Hoeve, Nienke; Huisstede, Bionka M. A.; Stam, Henk J.; van Domburg, Ron T.; Sunamura, Madoka; van den Berg-Emons, Rita J. G.

    Background. Optimal physical activity levels have health benefits for patients with acute coronary syndrome (ACS) and are an important goal of cardiac rehabilitation (CR). Purpose. The purpose of this study was to systematically review literature regarding short-term effects (= 6 months after

  7. Sympathetic arousal as a marker of chronicity in childhood stuttering.

    Science.gov (United States)

    Zengin-Bolatkale, Hatun; Conture, Edward G; Walden, Tedra A; Jones, Robin M

    2018-01-01

    This study investigated whether sympathetic activity during a stressful speaking task was an early marker for stuttering chronicity. Participants were 9 children with persisting stuttering, 23 children who recovered, and 17 children who do not stutter. Participants performed a stress-inducing picture-naming task and skin conductance was measured across three time points. Findings indicated that at the initial time point, children with persisting stuttering exhibited higher sympathetic arousal during the stressful speaking task than children whose stuttering recovered. Findings are taken to suggest that sympathetic activity may be an early marker of heightened risk for chronic stuttering.

  8. A new method based on fractal variance function for analysis and quantification of sympathetic and vagal activity in variability of R-R time series in ECG signals

    Energy Technology Data Exchange (ETDEWEB)

    Conte, Elio [Department of Pharmacology and Human Physiology and Tires, Center for Innovative Technologies for Signal Detection and Processing, University of Bari, Bari (Italy); School of Advanced International Studies on Nuclear, Theoretical and Nonlinear Methodologies-Bari (Italy)], E-mail: fisio2@fisiol.uniba.it; Federici, Antonio [Department of Pharmacology and Human Physiology and Tires, Center for Innovative Technologies for Signal Detection and Processing, University of Bari, Bari (Italy); Zbilut, Joseph P. [Department of Molecular Biophysics and Physiology, Rush University Medical Center, 1653W Congress, Chicago, IL 60612 (United States)

    2009-08-15

    It is known that R-R time series calculated from a recorded ECG, are strongly correlated to sympathetic and vagal regulation of the sinus pacemaker activity. In human physiology it is a crucial question to estimate such components with accuracy. Fourier analysis dominates still to day the data analysis efforts of such data ignoring that FFT is valid under some crucial restrictions that results largely violated in R-R time series data as linearity and stationarity. In order to go over such approach, we introduce a new method, called CZF. It is based on variogram analysis. It is aimed from a profound link with Recurrence Quantification Analysis that is a basic tool for investigation of non linear and non stationary time series. Therefore, a relevant feature of the method is that it finally may be applied also in cases of non linear and non stationary time series analysis. In addition, the method enables also to analyze the fractal variance function, the Generalized Fractal Dimension and, finally, the relative probability density function of the data. The CZF gives very satisfactory results. In the present paper it has been applied to direct experimental cases of normal subjects, patients with hypertension before and after therapy and in children under some different conditions of experimentation.

  9. Altered activity of the sympathetic nervous system and changes in the balance of hypophyseal, pituitary and adrenal hormones in patients with cluster headache.

    Science.gov (United States)

    Strittmatter, M; Hamann, G F; Grauer, M; Fischer, C; Blaes, F; Hoffmann, K H; Schimrigk, K

    1996-05-17

    Twelve patients (age 43.4 +/- 6.3 years) with episodic cluster headache (CH) were examined during the cluster period. Plasma norepinephrine levels in patients suffering from CH were significantly decreased compared with the control group (p < 0.01). There were also statistically significant correlations between norepinephrine levels and clinical features of the pain attacks including duration (r = 0.75, p < 0.05), intensity (r = 0.64, p < 0.05) and frequency (r = 0.68, p < 0.06), thereby suggesting a pathophysiological involvement of the sympathetic nervous system in CH. Increased plasma levels of plasmacortisol and ACTH in patients with CH, especially in the morning and in the evening, suggest an alteration of the feedback circuit involving the hypothalamus, the pituitary and the adrenal gland, an imbalance in the hormones related to these structures, as well as an alteration of the circadian rhythm. In addition, CH patients demonstrated significantly decreased levels of norepinephrine (p < 0.05), HVA (p < 0.01) and 5-HIAA (p < 0.01) in the cerebrospinal fluid (CSF) consistent with a central genesis of CH. These significant relationships between neurochemical parameters and the clinical patterns suggest a complex interplay between the hypothalamus, neuroendocrinological parameters, activity of the autonomic nervous system and the pain of CH.

  10. A new method based on fractal variance function for analysis and quantification of sympathetic and vagal activity in variability of R-R time series in ECG signals

    International Nuclear Information System (INIS)

    Conte, Elio; Federici, Antonio; Zbilut, Joseph P.

    2009-01-01

    It is known that R-R time series calculated from a recorded ECG, are strongly correlated to sympathetic and vagal regulation of the sinus pacemaker activity. In human physiology it is a crucial question to estimate such components with accuracy. Fourier analysis dominates still to day the data analysis efforts of such data ignoring that FFT is valid under some crucial restrictions that results largely violated in R-R time series data as linearity and stationarity. In order to go over such approach, we introduce a new method, called CZF. It is based on variogram analysis. It is aimed from a profound link with Recurrence Quantification Analysis that is a basic tool for investigation of non linear and non stationary time series. Therefore, a relevant feature of the method is that it finally may be applied also in cases of non linear and non stationary time series analysis. In addition, the method enables also to analyze the fractal variance function, the Generalized Fractal Dimension and, finally, the relative probability density function of the data. The CZF gives very satisfactory results. In the present paper it has been applied to direct experimental cases of normal subjects, patients with hypertension before and after therapy and in children under some different conditions of experimentation.

  11. Parental overcontrol x OPRM1 genotype interaction predicts school-aged children's sympathetic nervous system activation in response to performance challenge.

    Science.gov (United States)

    Partington, Lindsey C; Borelli, Jessica L; Smiley, Patricia; Jarvik, Ella; Rasmussen, Hannah F; Seaman, Lauren C; Nurmi, Erika L

    2018-04-26

    Parental overcontrol (OC), the excessive regulation of a child's behavior, cognition, and emotion, is associated with the development of child anxiety. While studies have shown that genetic factors may increase sensitivity to stress, genetic vulnerability to parental OC has not been examined in anxiety etiology. A functional polymorphism in the mu opioid receptor OPRM1 (A118G, rs1799971) has been shown to impact stress reactivity. Using a community sample of children (N = 85, 9-12 years old), we examined the main and interactive effects of maternal OC and child OPRM1 genotype in predicting children's sympathetic nervous system reactivity during a performance stressor. Neither OC nor genotype predicted children's electrodermal activity (EDA); however, the interaction between OC and child genotype significantly predicted stress reactivity, as indexed by EDA, during the challenging task. Among children with the minor G-allele, higher maternal OC was associated with higher reactivity. In A homozygotes, maternal OC was not associated with EDA, suggesting a diathesis-stress pattern of gene x environment interaction. We discuss implications for anxiety etiology and intervention. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Effect of heat-killed Lactobacillus brevis SBC8803 on cutaneous arterial sympathetic nerve activity, cutaneous blood flow and transepidermal water loss in rats.

    Science.gov (United States)

    Horii, Y; Kaneda, H; Fujisaki, Y; Fuyuki, R; Nakakita, Y; Shigyo, T; Nagai, K

    2014-05-01

    To evaluate the efficacy of the effects of heat-killed Lactobacillus brevis SBC8803 (HK-SBC8803) on the standard physiological markers of skin health of cutaneous arterial sympathetic nerve activity (CASNA), cutaneous blood flow and transepidermal water loss (TEWL) and to determine whether SBC8803 targets serotonin 5-HT3 receptors in rats. A set of three experiments were conducted to examine the effects of SBC8803 on CASNA, cutaneous blood flow and TEWL using Wistar and hairless rats. Two additional experiments further attempted to determine whether HK-SBC8803 was targeting the serotonin 5-HT3 receptors by pretreatment with the 5-HT3 antagonist granisetron. Administration of HK-SBC8803 in the first three experiments caused marked inhibition of CASNA and significant elevation of cutaneous blood flow under urethane anaesthesia as well as significant decrease in TEWL on the dorsal skin of conscious hairless rats. Pretreatment with granisetron decreased the effects of HK-SBC8803 on CASNA and cutaneous blood flow. These findings suggest that HK-SBC8803 reduces CASNA, increases cutaneous blood flow and decreases TEWL and that 5-HT3 receptors may be involved in CASNA and cutaneous blood flow responses. HK-SBC8803 could be a useful substance in the treatment/prevention of skin problems, specifically chapped or dry skin. © 2014 The Society for Applied Microbiology.

  13. Renal sympathetic nerve ablation for treatment-resistant hypertension

    Science.gov (United States)

    Krum, Henry; Schlaich, Markus; Sobotka, Paul

    2013-01-01

    Hypertension is a major risk factor for increased cardiovascular events with accelerated sympathetic nerve activity implicated in the pathogenesis and progression of disease. Blood pressure is not adequately controlled in many patients, despite the availability of effective pharmacotherapy. Novel procedure- as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation, have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate. This approach may also have potential in other disorders associated with enhanced sympathetic nerve activity such as congestive heart failure, chronic kidney disease and metabolic syndrome. This review will focus on the current status of percutaneous renal sympathetic nerve denervation, clinical efficacy and safety outcomes and prospects beyond refractory hypertension. PMID:23819768

  14. AMPUTATION AND REFLEX SYMPATHETIC DYSTROPHY

    NARCIS (Netherlands)

    GEERTZEN, JHB; EISMA, WH

    Reflex sympathetic dystrophy is a chronic pain syndrome characterized by chronic burning pain, restricted range of motion, oedema and vasolability. Patients are difficult to treat and the prognosis is very often poor. This report emphasizes that an amputation in case of a reflex sympathetic

  15. Glutamate and GABA in vestibulo-sympathetic pathway neurons

    Directory of Open Access Journals (Sweden)

    Gay R Holstein

    2016-02-01

    Full Text Available The vestibulo-sympathetic reflex actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The vestibulo-sympathetic reflex pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively. The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the vestibulo-sympathetic reflex pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation was employed to activate these pathways. Central vestibular neurons of the vestibulo-sympathetic reflex were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified vestibulo-sympathetic reflex pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. Vestibulo-sympathetic reflex pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the

  16. A case of delayed cardiac perforation of active ventricular lead

    Directory of Open Access Journals (Sweden)

    Hangyuan Guo

    2011-12-01

    Full Text Available A 65-year-old man was admitted as for one month of repetitive dizziness and one episode of syncope. Electrocardiogram showed sinus bradycardia and his Holter monitoring also showed sinus bradycardia with sinus arrest, sino-atrial block and a longest pause of 4.3 s. Then sick sinus syndrome and Adam-Stokes syndrome were diagnosed. Then a dual chamber pacemaker (Medtronic SDR303 was implanted and the parameters were normal by detection. The patient was discharged 1 week later with suture removed. Then 1.5 month late the patient was presented to hospital once again for sudden onset of chest pain with exacerbation after taking deep breath. Pacemaker programming showed both pacing and sensing abnormality with threshold of?5.0V and resistance of 1200?. Lead perforation was revealed by chest X-ray and confirmed by echocardiogram. Considering the fact that there was high risk to remove ventricular lead, spiral tip of previous ventricular lead was withdrew followed by implantation of a new ventricular active lead to the septum. Previous ventricular lead was maintained. As we know that the complications of lead perforation in the clinic was rare. Here we discuss the clinical management and the possible reasons for cardiac perforation of active ventricular lead.

  17. Sympathetic β-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.

    Science.gov (United States)

    Kadow, Brian T; Lyon, Timothy D; Zhang, Zhaocun; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-07-01

    This study investigated the role of the hypogastric nerve and β-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition. Copyright © 2016 the American Physiological Society.

  18. The influence of motor activity on the development of cardiac arrhythmias during experimental emotional stress

    Science.gov (United States)

    Ulyaninskiy, L. S.; Urmancheyeva, T. G.; Stepanyan, Y. P.; Fufacheva, A. A.; Gritsak, A. V.; Kuznetsova, B. A.; Kvitka, A. A.

    1982-01-01

    Experimental emotional stress which can produce various disorders of cardiac rhythm: sinus tachycardia, atrial fibrillation, ventricular, extrasystoles and paroxysmal ventricular tachysystoles was studied. In these conditions the adrenalin content in the blood and myocardium is increased 3 to 4 times. It is found that moderate motor activity leads to a relative decrease of adrenalin in the myocardium and arrest of cardiac arrhythmias.

  19. A 3D active shape model driven by fuzzy inference : application to cardiac CT and MR

    NARCIS (Netherlands)

    Assen, van H.C.; Danilouchkine, M.G.; Dirksen, M.S.; Reiber, J.H.C.; Lelieveldt, B.P.F.

    2008-01-01

    Abstract—Manual quantitative analysis of cardiac left ventricular function using Multislice CT and MR is arduous because of the large data volume. In this paper, we present a 3-D active shape model (ASM) for semiautomatic segmentation of cardiac CT and MRvolumes, without the requirement of

  20. Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Garrott, Kara; Dyavanapalli, Jhansi; Cauley, Edmund; Dwyer, Mary Kate; Kuzmiak-Glancy, Sarah; Wang, Xin; Mendelowitz, David; Kay, Matthew W

    2017-09-01

    A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were

  1. Contribution of α-adrenoceptors to depolarization and contraction evoked by continuous asynchronous sympathetic nerve activity in rat tail artery

    Science.gov (United States)

    Brock, J A; McLachlan, E M; Rayner, S E

    1997-01-01

    The effects of continuous but asynchronous nerve activity induced by ciguatoxin (CTX-1) on the membrane potential and contraction of smooth muscle cells have been investigated in rat proximal tail arteries isolated in vitro. These effects have been compared with those produced by the continuous application of phenylephrine (PE).CTX-1 (0.4 nM) and PE (10 μM) produced a maintained depolarization of the arterial smooth muscle that was almost completely blocked by α-adrenoceptor blockade. In both cases, the depolarization was more sensitive to the selective α2-adrenoceptor antagonist, idazoxan (0.1 μM), than to the selective α1-adrenoceptor antagonist, prazosin (0.01 μM).In contrast, the maintained contraction of the tail artery induced by CTX-1 (0.2 nM) and PE (2 and 10 μM) was more sensitive to prazosin (0.01) μM, than to idazoxan (0.01 μM). In combination, these antagonists almost completely inhibited contraction to both agents.Application of the calcium channel antagonist, nifedipine (1 μM), had no effect on the depolarization induced by either CTX-1 or PE but maximally reduced the force of the maintained contraction to both agents by about 50%.We conclude that the constriction of the tail artery induced by CTX-1, which mimics the natural discharge of postganglionic perivascular axons, is due almost entirely to α-adrenoceptor activation. The results indicate that neuronally released noradrenaline activates more than one α-adrenoceptor subtype. The depolarization is dependent primarily on α2-adrenoceptor activation whereas the contraction is dependent primarily on α1-adrenoceptor activation. The links between α-adrenoceptor activation and the voltage-dependent and voltage-independent mechanisms that deliver Ca2+ to the contractile apparatus appear to be complex. PMID:9113373

  2. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    International Nuclear Information System (INIS)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C.; Irigoyen, M.C.; De Angelis, K.

    2015-01-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation

  3. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Shimojo, G.L.; Palma, R.K.; Brito, J.O.; Sanches, I.C. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil); Irigoyen, M.C. [Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); De Angelis, K. [Laboratório de Fisiologia Translacional, Programa de Ciências da Reabilitação, Universidade Nove de Julho, São Paulo, SP (Brazil)

    2015-03-27

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation.

  4. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

    International Nuclear Information System (INIS)

    Schwaiger, M.; Kalff, V.; Rosenspire, K.; Haka, M.S.; Molina, E.; Hutchins, G.D.; Deeb, M.; Wolfe, E. Jr.; Wieland, D.M.

    1990-01-01

    The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart

  5. Bidirectional Prospective Associations between Cardiac Autonomic Activity and Inflammatory Markers

    NARCIS (Netherlands)

    Hu, Mandy X; Lamers, Femke; Neijts, Melanie; Willemsen, Gonneke; de Geus, Eco J C; Penninx, Brenda W J H

    2018-01-01

    OBJECTIVE: Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic

  6. Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Ring-Larsen, H; Christensen, N J

    1987-01-01

    clearance of 3H-NA equal in the two groups (1.6 v 1.7 l/min, ns), while as the overall appearance rate of NA was significantly higher in alcoholic cirrhosis (4.2 v 2.6 nmol/min, p less than 0.02) indicating an enhanced sympathoadrenal activity in this group. The hepatic intestinal clearances of A, NA, and 3...

  7. SYMPATHETIC ACTIVATION CAUSES FOCAL ADHESION SIGNALING ALTERATION IN EARLY COMPENSATED VOLUME OVERLOAD DUE TO ISOLATED MITRAL REGURGITATION IN THE DOG

    OpenAIRE

    Sabri, Abdelkarim; Rafiq, Khadija; Seqqat, Rachid; Kolpakov, Mikhail A; Dillon, Ray; Dell’italia, Louis J

    2008-01-01

    We reported that left ventricular (LV) dilatation after four weeks of isolated mitral regurgitation (MR) in the dogs is marked by extracellular matrix (ECM) loss and an increase in adrenergic drive. Given that ECM proteins and their receptors integrins influence β-adrenergic receptor (β-AR) responses in-vitro, we tested whether β1-AR activation modulates focal adhesion (FA) signaling and LV remodeling in these same dogs with isolated MR. Normal dogs (NL) were compared with dogs with MR of 4-w...

  8. Effect of nerve activity on transport of nerve growth factor and dopamine β-hydroxylase antibodies in sympathetic neurones

    International Nuclear Information System (INIS)

    Lees, G.; Chubb, I.; Freeman, C.; Geffen, L.; Rush, R.

    1981-01-01

    The effect of nerve activity on the uptake and retrograde transport of nerve growth factor (NGF) and dopamine β-hydroxylase (DBH) antibodies was studied by injecting 125 I-labelled NGF and anti-DBH into the anterior eye chamber of guinea-pigs. Decentralization of the ipsilateral superior cervical ganglion (SCG) had no significant effect on the retrograde transport of either NGF or anti-DBH. Phenoxybenzamine produced a 50% increase in anti-DBH but not NGF accumulation and this effect was prevented by prior decentralization. This demonstrates that NGF is taken up independently of the retrieval of synaptic vesicle components. (Auth.)

  9. Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

    Science.gov (United States)

    Liang, Chang-seng; Huckabee, William E.

    1973-01-01

    When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. These results suggest that the cardiac output response to cyanide infusion consists of three components: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors

  10. New horizons in cardiac innervation imaging. Introduction of novel {sup 18}F-labeled PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Ryohei [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nihon Medi-Physics Co., Ltd., Research Centre, Chiba (Japan); Chen, Xinyu [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Hospital of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); Werner, Rudolf A. [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Hospital of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Sciences, Baltimore, MD (United States); Lapa, Constantin [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Javadi, Mehrbod S. [Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Sciences, Baltimore, MD (United States); Higuchi, Takahiro [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Hospital of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); National Cerebral and Cardiovascular Center, Department of Biomedical Imaging, Research Institute, Suita (Japan)

    2017-12-15

    Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue {sup 123}I-meta-iodobenzylguanidine ({sup 123}I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional {sup 11}C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising {sup 18}F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using {sup 18}F-labeled radiotracers along with their possible applications are reviewed. (orig.)

  11. New horizons in cardiac innervation imaging. Introduction of novel 18F-labeled PET tracers

    International Nuclear Information System (INIS)

    Kobayashi, Ryohei; Chen, Xinyu; Werner, Rudolf A.; Lapa, Constantin; Javadi, Mehrbod S.; Higuchi, Takahiro

    2017-01-01

    Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11 C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18 F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18 F-labeled radiotracers along with their possible applications are reviewed. (orig.)

  12. Sympathetic Responses to Central Hypovolemia: New Insights from Microneurographic Recordings

    Science.gov (United States)

    2012-04-26

    Surgical Research, Fort Sam Houston, TX, USA 2 Department of Health and Kinesiology , The University of Texas at San Antonio, San Antonio, TX, USA Edited...suggested that this phenomenon may represent sympathetic baroreflex deafferentation (Cooke et al., 2009), as the fused bursts observed during intense ...Convertino, V. A. (2009). Muscle sympathetic nerve activity during intense lower body negative pressure to presyn- cope in humans. J. Physiol. (Lond

  13. Separate neurochemical classes of sympathetic postganglionic neurons project to the left ventricle of the rat heart.

    Science.gov (United States)

    Richardson, R J; Grkovic, I; Allen, A M; Anderson, C R

    2006-04-01

    The sympathetic innervation of the rat heart was investigated by retrograde neuronal tracing and multiple label immunohistochemistry. Injections of Fast Blue made into the left ventricular wall labelled sympathetic neurons that were located along the medial border of both the left and right stellate ganglia. Cardiac projecting sympathetic postganglionic neurons could be grouped into one of four neurochemical populations, characterised by their content of calbindin and/or neuropeptide Y (NPY). The subpopulations of neurons contained immunoreactivity to both calbindin and NPY, immunoreactivity to calbindin only, immunoreactivity to NPY only and no immunoreactivity to calbindin or NPY. Sympathetic postganglionic neurons were also labelled in vitro with rhodamine dextran applied to the cut end of a cardiac nerve. The same neurochemical subpopulations of sympathetic neurons were identified by using this technique but in different proportions to those labelled from the left ventricle. Preganglionic terminals that were immunoreactive for another calcium-binding protein, calretinin, preferentially surrounded retrogradely labelled neurons that were immunoreactive for both calbindin and NPY. The separate sympathetic pathways projecting to the rat heart may control different cardiac functions.

  14. Bidirectional Prospective Associations Between Cardiac Autonomic Activity and Inflammatory Markers.

    Science.gov (United States)

    Hu, Mandy Xian; Lamers, Femke; Neijts, Melanie; Willemsen, Gonneke; de Geus, Eco J C; Penninx, Brenda W J H

    2018-06-01

    Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers. Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6. The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = -.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up. Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.

  15. Sweat pore reactivity as a surrogate measure of sympathetic nervous system activity in trauma-exposed individuals with and without posttraumatic stress disorder.

    Science.gov (United States)

    Familoni, Babajide O; Gregor, Kristin L; Dodson, Thomas S; Krzywicki, Alan T; Lowery, Bobby N; Orr, Scott P; Suvak, Michael K; Rasmusson, Ann M

    2016-09-01

    Stress analysis by FLIR (forward-looking infrared) evaluation (SAFE) has been demonstrated to monitor sweat pore activation (SPA) as a novel surrogate measure of sympathetic nervous system (SNS) activity in a normal population. SNS responses to a series of 15 1-s, 82 dB, white noise bursts were measured by skin conductance (SC) and SAFE monitoring of SPA on the fingers (FiP) and face (FaP) in 10 participants with posttraumatic stress disorder (PTSD) and 16 trauma-exposed participants without PTSD (Mage  = 48.92 ± 12.00 years; 26.9% female). Within participants, SC and FiP responses across trials were strongly correlated (r = .92, p < .001). Correlations between SC and FaP (r = .76, p = .001) and between FiP and FaP (r = .47, p = .005) were smaller. The habituation of SNS responses across the 15 trials was substantial (SC: d = -2.97; FiP: d = -2.34; FaP: d = -1.02). There was a strong correlation between habituation effects for SC and FiP (r = .76, p < .001), but not for SC and FaP (r = .15, p = .45) or FiP and FaP (r = .29, p = .16). Participants with PTSD showed larger SNS responses to the first loud noise than those without PTSD. PTSD reexperiencing symptoms assessed by the PTSD Checklist on the day of testing were associated with the SNS responses to the first loud noise measured by SC (d = 1.19) and FiP (d = .99), but not FaP (d = .10). This study confirms convergence of SAFE and SC as valid measures of SNS activity. SAFE FiP and SC responses were highly predictive of self-rated PTSD reexperiencing symptoms. SAFE may offer an attractive alternative for applications in PTSD and similar populations. © 2016 Society for Psychophysiological Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  16. Regular physical exercise improves cardiac autonomic and muscle vasodilatory responses to isometric exercise in healthy elderly

    Science.gov (United States)

    Sarmento, Adriana de Oliveira; Santos, Amilton da Cruz; Trombetta, Ivani Credidio; Dantas, Marciano Moacir; Oliveira Marques, Ana Cristina; do Nascimento, Leone Severino; Barbosa, Bruno Teixeira; Dos Santos, Marcelo Rodrigues; Andrade, Maria do Amparo; Jaguaribe-Lima, Anna Myrna; Brasileiro-Santos, Maria do Socorro

    2017-01-01

    The objective of this study was to evaluate cardiac autonomic control and muscle vasodilation response during isometric exercise in sedentary and physically active older adults. Twenty healthy participants, 10 sedentary and 10 physically active older adults, were evaluated and paired by gender, age, and body mass index. Sympathetic and parasympathetic cardiac activity (spectral and symbolic heart rate analysis) and muscle blood flow (venous occlusion plethysmography) were measured for 10 minutes at rest (baseline) and during 3 minutes of isometric handgrip exercise at 30% of the maximum voluntary contraction (sympathetic excitatory maneuver). Variables were analyzed at baseline and during 3 minutes of isometric exercise. Cardiac autonomic parameters were analyzed by Wilcoxon and Mann–Whitney tests. Muscle vasodilatory response was analyzed by repeated-measures analysis of variance followed by Tukey’s post hoc test. Sedentary older adults had higher cardiac sympathetic activity compared to physically active older adult subjects at baseline (63.13±3.31 vs 50.45±3.55 nu, P=0.02). The variance (heart rate variability index) was increased in active older adults (1,438.64±448.90 vs 1,402.92±385.14 ms, P=0.02), and cardiac sympathetic activity (symbolic analysis) was increased in sedentary older adults (5,660.91±1,626.72 vs 4,381.35±1,852.87, P=0.03) during isometric handgrip exercise. Sedentary older adults showed higher cardiac sympathetic activity (spectral analysis) (71.29±4.40 vs 58.30±3.50 nu, P=0.03) and lower parasympathetic modulation (28.79±4.37 vs 41.77±3.47 nu, P=0.03) compared to physically active older adult subjects during isometric handgrip exercise. Regarding muscle vasodilation response, there was an increase in the skeletal muscle blood flow in the second (4.1±0.5 vs 3.7±0.4 mL/min per 100 mL, P=0.01) and third minute (4.4±0.4 vs 3.9±0.3 mL/min per 100 mL, P=0.03) of handgrip exercise in active older adults. The results indicate that

  17. SYMPATHETIC SOLAR FILAMENT ERUPTIONS

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rui; Liu, Ying D.; Zimovets, Ivan; Hu, Huidong; Yang, Zhongwei [State Key Laboratory of Space Weather, National Space Science Center, Chinese Academy of Sciences, Beijing 100190 (China); Dai, Xinghua, E-mail: liuxying@spaceweather.ac.cn [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

    2016-08-10

    The 2015 March 15 coronal mass ejection as one of the two that together drove the largest geomagnetic storm of solar cycle 24 so far was associated with sympathetic filament eruptions. We investigate the relations between the different filaments involved in the eruption. A surge-like small-scale filament motion is confirmed as the trigger that initiated the erupting filament with multi-wavelength observations and using a forced magnetic field extrapolation method. When the erupting filament moved to an open magnetic field region, it experienced an obvious acceleration process and was accompanied by a C-class flare and the rise of another larger filament that eventually failed to erupt. We measure the decay index of the background magnetic field, which presents a critical height of 118 Mm. Combining with a potential field source surface extrapolation method, we analyze the distributions of the large-scale magnetic field, which indicates that the open magnetic field region may provide a favorable condition for F2 rapid acceleration and have some relation with the largest solar storm. The comparison between the successful and failed filament eruptions suggests that the confining magnetic field plays an important role in the preconditions for an eruption.

  18. VEGETATIVE SUPPORT OF CARDIAC ACTIVITY IN ATHLETES WITH DIFFERENT ANTHROPOMETRIC PROFILE

    Directory of Open Access Journals (Sweden)

    O. N. Kudrya

    2016-01-01

    Full Text Available The purpose of research – to study the features of the functioning of the cardiovascular system and regulatory mechanisms of the young athletes of different heights.Materials and methods. The study included athletes aged 15-16 (32 girls and 36 boys engaged in competitive sports. To study the autonomic regulation of the cardiovascular system using mathematical methods and spectral analysis of heart rate variability. To characterize the vegetative support the circulatory apparatus, all subjects performed an active orthostatic test.Results. The features of vegetative maintenance of heart activity in tall athletes: stress regulatory mechanisms observed resting in tall men and decrease the functionality of the sympathetic division of the autonomic nervous system during active orthostatic test in athletes of different sex. Athletes tall urgent adaptation of the cardiovascular system to changing external conditions associated with activation of suprasegmental divisions of the autonomic nervous system and the excessive activation of the sympathetic division, which is an inefficient way of adaptation.Conclusion. Thus, high growth is evident not only in the increase of total size of the body of athletes, but also in the peculiarities of morphofunctional state involved, indicating the need of individual rationing of loads for tall players. The revealed morphofunctional characteristics of the organism tall athletes allow us to recommend an increase in the proportion of aerobic exercise to enhance the adaptive capacities of the organism. 

  19. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

    International Nuclear Information System (INIS)

    Glowniak, J.V.; Turner, F.E.; Gray, L.L.; Palac, R.T.; Lagunas-Solar, M.C.; Woodward, W.R.

    1989-01-01

    Iodine-123 metaiodobenzylguanidine ([ 123 I]MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with [ 123 I]MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiac transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy

  20. Aircraft noise effects on sleep: a systematic comparison of EEG awakenings and automatically detected cardiac activations

    International Nuclear Information System (INIS)

    Basner, Mathias; Müller, Uwe; Elmenhorst, Eva-Maria; Kluge, Götz; Griefahn, Barbara

    2008-01-01

    Polysomnography is the gold standard for investigating noise effects on sleep, but data collection and analysis are sumptuous and expensive. We recently developed an algorithm for the automatic identification of cardiac activations associated with cortical arousals, which uses heart rate information derived from a single electrocardiogram (ECG) channel. We hypothesized that cardiac activations can be used as estimates for EEG awakenings. Polysomnographic EEG awakenings and automatically detected cardiac activations were systematically compared using laboratory data of 112 subjects (47 male, mean ± SD age 37.9 ± 13 years), 985 nights and 23 855 aircraft noise events (ANEs). The probability of automatically detected cardiac activations increased monotonically with increasing maximum sound pressure levels of ANEs, exceeding the probability of EEG awakenings by up to 18.1%. If spontaneous reactions were taken into account, exposure–response curves were practically identical for EEG awakenings and cardiac activations. Automatically detected cardiac activations may be used as estimates for EEG awakenings. More investigations are needed to further validate the ECG algorithm in the field and to investigate inter-individual differences in its ability to predict EEG awakenings. This inexpensive, objective and non-invasive method facilitates large-scale field studies on the effects of traffic noise on sleep

  1. [Leisure-time sport activities and cardiac outpatient therapy in coronary patients].

    Science.gov (United States)

    Heitkamp, Hans-Christian; Schimpf, Thomas M; Hipp, Arno; Niess, Andreas

    2005-03-01

    Exercise intensity in coronary patients is controlled by heart rate measurements. Very few investigations have compared the maximum heart rate in cardiac outpatient groups, in leisure-time sport activities, and especially in swimming. Within different exercise conditions 21 coronary patients, nine in well-compensated cardiac condition joining a training group and twelve joining the exercise group with lower intensity, without signs of heart failure, engaged in an incremental bicycle ergometry. A six-lead ECG was derived at the same time with a 24-h ECG. The performance tolerance was measured by the pulse limit derived in 20 patients; one patient failed to show signs of subjective or objective ischemia. During a 24-h ECG monitoring, the patients took part in a 1-h standardized cardiac outpatient program, a standardized swimming program 4 x 25 m, and a typical self-selected leisure-time activity. The patients showed a peak work capacity of 2.2 W/kg and a symptom-free work capacity of 1.3 W/kg. The derived upper heart rate limit was passed during swimming by 19, during leisure-time activity by 16, and during cardiac outpatient program by two patients. The maximum of the mean overriding the limit occurred in leisure-time activity. Signs of ischemia occurred during ergometry in 15, during swimming training in ten patients, during leisure-time activity in eight, and during cardiac outpatient therapy in one. Arrhythmia leisure-time sport activity in 15, during cardiac outpatient therapy in 17, and during swimming in eight patients. Arrhythmia Lown IVa occurred in one patient each during ergometry, leisure sports, and during the night. Coronary patients are in danger to exercise beyond the pulse limit during swimming and other leisure-time sports and not during cardiac outpatient therapy. The upper heart rate limit should be observed during swimming and other endurance leisure-time activities, and is of little importance during cardiac outpatient therapy.

  2. Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K+ current by different G-protein coupled receptors.

    Science.gov (United States)

    Liu, Xueli; Wang, Yuhong; Zhang, Hua; Shen, Li; Xu, Yanfang

    2017-12-01

    Elevated angiotensin II (Ang II) and sympathetic activity contributes to a high risk of ventricular arrhythmias in heart disease. The rapidly activating delayed rectifier K + current (I Kr ) carried by the hERG channels plays a critical role in cardiac repolarization, and decreased I Kr is involved in increased cardiac arrhythmogenicity. Stimulation of α 1A -adrenoreceptors or angiotensin II AT 1 receptors is known to inhibit I Kr via PKC. Here, we have identified the PKC isoenzymes mediating the inhibition of I Kr by activation of these two different GPCRs. The whole-cell patch-clamp technique was used to record I Kr in guinea pig cardiomyocytes and HEK293 cells co-transfected with hERG and α 1A -adrenoreceptor or AT 1 receptor genes. A broad spectrum PKC inhibitor Gö6983 (not inhibiting PKCε), a selective cPKC inhibitor Gö6976 and a PKCα-specific inhibitor peptide, blocked the inhibition of I Kr by the α 1A -adrenoreceptor agonist A61603. However, these inhibitors did not affect the reduction of I Kr by activation of AT 1 receptors, whereas the PKCε-selective inhibitor peptide did block the effect. The effects of angiotensin II and the PKCε activator peptide were inhibited in mutant hERG channels in which 17 of the 18 PKC phosphorylation sites were deleted, whereas a deletion of the N-terminus of the hERG channels selectively prevented the inhibition elicited by A61603 and the cPKC activator peptide. Our results indicated that inhibition of I Kr by activation of α 1A -adrenoreceptors or AT 1 receptors were mediated by PKCα and PKCε isoforms respectively, through different molecular mechanisms. © 2017 The British Pharmacological Society.

  3. Gritty people try harder: grit and effort-related cardiac autonomic activity during an active coping challenge.

    Science.gov (United States)

    Silvia, Paul J; Eddington, Kari M; Beaty, Roger E; Nusbaum, Emily C; Kwapil, Thomas R

    2013-05-01

    Grit, a recently proposed personality trait associated with persistence for long-range goals, predicts achievement in a wide range of important life outcomes. Using motivational intensity theory, the present research examined the physiological underpinnings of grit during an active coping task. Forty young adults completed the Short Grit Scale and worked on a self-paced mental effort task. Effort-related autonomic nervous system (ANS) activity was assessed using impedance cardiography, which yielded measures of sympathetic activity (pre-ejection period; PEP) and parasympathetic activity (respiratory sinus arrhythmia; RSA). Multilevel models revealed that people high on the Perseverance of Effort subscale showed autonomic coactivation: both PEP and RSA became stronger during the task, reflecting higher activity of both ANS divisions. The Consistency of Interest subscale, in contrast, predicted only weaker sympathetic activity (slower PEP). Taken together, the findings illuminate autonomic processes associated with how "gritty" people pursue goals, and they suggest that more attention should be paid to the facets' distinct effects. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. ATPase activity and contraction in porcine and human cardiac muscle

    Czech Academy of Sciences Publication Activity Database

    Griffiths, P. J.; Isackson, H.; Redwood, C.; Marston, S.; Pelc, Radek; Funari, S.; Watkins, H.; Ashley, C. C.

    2008-01-01

    Roč. 29, 6-8 (2008), s. 277-277 ISSN 0142-4319. [European Muscle Conference of the European Society for Muscle Research /37./. 13.09.2008-16.09.2008, Oxford] R&D Projects: GA MŠk(CZ) LC06063 Grant - others:EC(XE) RII3-CT-2004-506008 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * ATP-asa * cardiac muscle * molecular motor Subject RIV: ED - Physiology

  5. Pet measurements of presynaptic sympathetic nerve terminals in the heart

    International Nuclear Information System (INIS)

    Schwaiger, M.; Hutchins, G.D.; Wieland, D.M.

    1991-01-01

    [ 18 F]Metaraminol (FMR) and [ 11 C]hydroxyephedrine (HED) are catecholamine analogues that have been developed at the University of Michigan for the noninvasive characterization of the sympathetic nervous system of the heart using positron emission tomography (PET). Pharmacological studies employing neurotoxins and uptake inhibitors have demonstrated that both FMR and HED specifically trace the uptake and storage of catecholamines in sympathetic nerve terminals with little nonspecific tracer accumulation. These compounds exhibit excellent qualitative imaging characteristics with heart-to-blood ratios exceeding 6:1 as early as 15 min after intravenous injection in both animals (HED and FMR) and humans (HED). Tracer kinetic modeling techniques have been employed for the quantitative assessment of neuronal catecholamine uptake and storage. Indices of neuronal function, such as the volume of tracer distribution derived from the kinetic models, have been employed in preliminary human studies. Comparison of the tissue distribution volume of HED between normal (control subjects) and denervated (recent transplant patients) cardiac tissue demonstrates a dynamic range of approximately 5:1. This distribution volume is reduced by 60% from normal in patients with dilated cardiomyopathy, indicating dysfunction of the sympathetic system. These results show that HED used in combination with PET provides a sophisticated quantitative approach for studying the sympathetic nervous system of the normal and diseased human heart

  6. Influences of lifestyle factors on cardiac autonomic nervous system activity over time

    NARCIS (Netherlands)

    Hu, Mandy Xian; Lamers, Femke; de Geus, Eco J C; Penninx, Brenda W J H

    Physical activity, alcohol use and smoking might affect cardiovascular disease through modifying autonomic nervous system (ANS) activity. We investigated: 1) whether there are consistent relationships between lifestyle factors and cardiac ANS activity over time, and 2) whether 2-year changes in

  7. Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator.

    Science.gov (United States)

    Carlson, Signe; Helterline, Deri; Asbe, Laura; Dupras, Sarah; Minami, Elina; Farris, Stephen; Stempien-Otero, April

    2017-07-01

    Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3±6.5 and 70.3±36, fold change vs UI, n=8, Padopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. The effects of different physical activities on atrial fibrillation in patients with hypertension and chronic kidney disease

    OpenAIRE

    Kiuchi, M?rcio Galindo; Chen, Shaojie; Hoye, Neil Alexander

    2017-01-01

    Background: Atrial fibrillation (AF) is highly common, and is most frequently observed in individuals with hypertension and structural cardiac disease. Sympathetic hyperactivity plays a fundamental role in the progression, maintenance and aggravation of arrhythmia. Endurance exercise training clearly lowers sympathetic activity in sympathoexcitatory disease states, and is well-tolerated by patients with chronic kidney disease (CKD). Methods: We assessed 50 CKD patients with hypertension. Each...

  9. Intrinsic cardiac nervous system in tachycardia induced heart failure.

    Science.gov (United States)

    Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

    2003-11-01

    The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to

  10. Factors influencing the cardiac MIBG accumulation

    International Nuclear Information System (INIS)

    Takatsu, Hisato; Fujiwara, Hisayoshi

    1997-01-01

    Following factors possibly influencing the cardiac MIBG accumulation were examined mainly in mice. 1. The specific activity of the MIBG (meta-iodo-benzyl guanidine) on the neuronal and non-neuronal fractions. 2. Motor restriction stress on MIBG accumulation and washout. 3. Loading and restriction of sodium chloride on the accumulation and effect of suppression of renin-angiotensin system. 4. Examinations in Dahl rats. 125I- or 131I-MIBG was intravenously administered to mice at 74 kBq. At 30 min or 4 hr after administration, mice were sacrificed and their left ventricles were dissected out for measurement of radioactivity in a liquid scintillation counter. Salt-sensitive and -resistant Dahl rats were given with 37 MBq of 123I-MIBG and cardiac radioactivity was measured externally for calculation of washout. Factors examined were found highly correlated with the accumulation of MIBG and measurement of its washout was considered useful for evaluating sympathetic activity. (K.H.)

  11. Nifedipine-sensitive blood pressure component in hypertensive models characterized by high activity of either sympathetic nervous system or renin-angiotensin system

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef; Dobešová, Zdenka; Behuliak, Michal; Pintérová, Mária; Kuneš, Jaroslav; Vaněčková, Ivana

    2014-01-01

    Roč. 63, č. 1 (2014), s. 13-26 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/09/0336; GA ČR(CZ) GAP304/12/0259 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : voltage-gated caclium channels * sympathetic nervous system * renin-angiotensin system * nitric oxide Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.293, year: 2014

  12. Effect of physical activity after a cardiac event on smoking habits and/or Quetelet index.

    Science.gov (United States)

    Huijbrechts, I P A M; Duivenvoorden, H J; Passchier, J; Deckers, J W; Kazemier, M; Erdman, R A M

    2003-02-01

    To further elucidate earlier findings, the present study investigated whether physical activity could serve as a positive stimulus to modify other changeable cardiac risk factors. Participants were 140 patients who had completed a cardiac rehabilitation programme focused on physical activity. Their present level of physical activity, smoking habits and Quetelet index were investigated as well as that before the cardiac event, in retrospect. Current feelings of anxiety and depression were also assessed. Participants were divided into two categories according to their present level of physical activity after finishing the rehabilitation programme, compared with that before the cardiac event. It appeared that the more physically active category contained more smokers. Although many of them had quitted smoking, significantly more persisted in their smoking habits compared with the patients who did not increase their physical activity. Significantly less depression was found in the more active patients. Although it could not be confirmed that physical activity stimulated a positive change in smoking and Quetelet index, the more active patients appeared to be less depressed.

  13. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    International Nuclear Information System (INIS)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj; Schönberger, Tanja; Noegel, Angelika A.; Gawaz, Meinrad; Lang, Florian

    2014-01-01

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca 2+ signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7 −/− ) and wild-type mice (anxa7 +/+ ) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7 −/− mice than in anxa7 +/+ mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions

  14. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj [Department of Physiology, University of Tübingen, Tübingen (Germany); Schönberger, Tanja [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Noegel, Angelika A. [Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln (Germany); Gawaz, Meinrad [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tübingen, Tübingen (Germany)

    2014-02-28

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{sup +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

  15. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study.

    Directory of Open Access Journals (Sweden)

    Tanja G M Vrijkotte

    Full Text Available In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5-6 years.Cross-sectional data from an apparently healthy population (within the ABCD study were collected at age 5-6 years in 1540 children. Heart rate (HR, respiratory sinus arrhythmia (RSA; parasympathetic activity and pre-ejection period (PEP; sympathetic activity were assessed during rest. Metabolic components were waist-height ratio (WHtR, systolic blood pressure (SBP, fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed.In analysis adjusted for child's physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01, higher SBP (p<0.001 and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01. Lower PEP was only associated with higher SBP (p <0.05. Of all children, 5.6% had 3 or more (out of 5 adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001.This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5-6 years.

  16. Biobehavioral Triggers of Cardiac Arrhythmia during Daily Life: The Role of Emotion, Physical Activity, and Heart Rate Variability

    National Research Council Canada - National Science Library

    McCeney, Melissa K

    2004-01-01

    Biobehavioral factors, such as physical activity and emotions, have been associated with adverse cardiac outcomes, including myocardial ischemia and infarction, in individuals with coronary artery disease...

  17. Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Jesse L. Ashton

    2018-03-01

    Full Text Available Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation.

  18. The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study.

    Science.gov (United States)

    Gordin, Daniel; Fadl Elmula, Fadl Elmula M; Andersson, Bert; Gottsäter, Anders; Elf, Johan; Kahan, Thomas; Christensen, Kent Lodberg; Vikatmaa, Pirkka; Vikatmaa, Leena; Bastholm Olesen, Thomas; Groop, Per-Henrik; Olsen, Michael Hecht; Tikkanen, Ilkka

    2017-10-01

    To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of  ≥145 mm Hg, and/or a daytime diastolic ABPM of  ≥95 mm Hg after witnessed drug intake (including  ≥3 antihypertensive drugs, preferably including a diuretic). The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety. This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.

  19. Dysfunctional Hyperpolarization-Activated Cyclic Nucleotide-gated Ion Channels in Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    Xiaoqi Zhao

    Full Text Available Abstract Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are reverse voltage-dependent, and their activation depends on the hyperpolarization of the membrane and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP or other signal-transduction cascades. The distribution, quantity and activation states of HCN channels differ in tissues throughout the body. Evidence exhibits that HCN channels play critical roles in the generation and conduction of the electrical impulse and the physiopathological process of some cardiac diseases. They may constitute promising drug targets in the treatment of these cardiac diseases. Pharmacological treatment targeting HCN channels is of benefit to these cardiac conditions.

  20. Dynamic interaction between the heart and its sympathetic innervation following T5 spinal cord transection.

    Science.gov (United States)

    Lujan, Heidi L; Janbaih, Hussein; DiCarlo, Stephen E

    2012-10-15

    Midthoracic spinal cord injury (SCI) is associated with enhanced sympathetic support of heart rate as well as myocardial damage related to calcium overload. The myocardial damage may elicit an enhanced sympathetic support of contractility to maintain ventricular function. In contrast, the level of inotropic drive may be reduced to match the lower afterload that results from the injury-induced reduction in arterial pressure. Accordingly, the inotropic response to midthoracic SCI may be increased or decreased but has not been investigated and therefore remains unknown. Furthermore, the altered ventricular function may be associated with anatomical changes in cardiac sympathetic innervation. To determine the inotropic drive following midthoracic SCI, a telemetry device was used for repeated measurements of left ventricular (LV) function, with and without beta-adrenergic receptor blockade, in rats before and after midthoracic SCI or sham SCI. In addition, NGF content (ELISA) and dendritic arborization (cholera toxin B immunohistochemistry and Sholl analysis) of cardiac-projecting sympathetic postganglionic neurons in the stellate ganglia were determined. Midthoracic SCI was associated with an enhanced sympathetic support of heart rate, dP/dt(+), and dP/dt(-). Importantly, cardiac function was lower following blockade of the sympathetic nervous system in rats with midthoracic SCI compared with sham-operated rats. Finally, these functional neuroplastic changes were associated with an increased NGF content and structural neuroplasticity within the stellate ganglia. Results document impaired LV function with codirectional changes in chronotropic and inotropic responses following midthoracic SCI. These functional changes were associated with a dynamic interaction between the heart and its sympathetic innervation.

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

    OpenAIRE

    Santos, Marcelo R. dos; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; Souza, Francis R. de; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

    2018-01-01

    OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, ...

  2. Cardiac autonomic profile in different sports disciplines during all-day activity.

    Science.gov (United States)

    Sztajzel, J; Jung, M; Sievert, K; Bayes De Luna, A

    2008-12-01

    Physical training and sport activity have a beneficial effect on cardiac autonomic activity. However, the exact impact of different types of sports disciplines on cardiac autonomic function is still unclear. The aim of this study was to evaluate the cardiac autonomic profile in different sports discplines and to determine their impact on cardiac autonomic function by using heart rate variability (HRV), a noninvasive electrocardiographic (ECG) analysis of the sympatho-vagal balance. Temporal and spectral HRV parameters determined from 24-hour continuous ECG monitoring were studied in 40 subjects, including 12 endurance athletes, 14 hockey players and 14 untrained male volunteers (control group). Each participant had to wear a Holter recorder during 24 hours and to continue his everyday activities. All HRV parameters were compared between the 3 study groups. All heart rate values were lower and all parasympathetic-related time domain indices, including root mean square of successive differences (RMSSD) and pNN50 (NN50 count divided by the total number of all NN intervals), were higher in both athletes groups as compared with controls (PHRV, were significantly higher only in endurance athletes (PHRV (higher SDNN), indicating thereby that this type sports discipline may have a more substantially favorable effect on the cardiac autonomic profile.

  3. Role of sympathetic nervous system and neuropeptides in obesity hypertension

    Directory of Open Access Journals (Sweden)

    J.E. Hall

    2000-06-01

    Full Text Available Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R. However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this

  4. Highly localized interactions between sensory neurons and sprouting sympathetic fibers observed in a transgenic tyrosine hydroxylase reporter mouse

    Directory of Open Access Journals (Sweden)

    Zhang Jun-Ming

    2011-07-01

    Full Text Available Abstract Background Sprouting of sympathetic fibers into sensory ganglia occurs in many preclinical pain models, providing a possible anatomical substrate for sympathetically enhanced pain. However, the functional consequences of this sprouting have been controversial. We used a transgenic mouse in which sympathetic fibers expressed green fluorescent protein, observable in live tissue. Medium and large diameter lumbar sensory neurons with and without nearby sympathetic fibers were recorded in whole ganglion preparations using microelectrodes. Results After spinal nerve ligation, sympathetic sprouting was extensive by 3 days. Abnormal spontaneous activity increased to 15% and rheobase was reduced. Spontaneously active cells had Aαβ conduction velocities but were clustered near the medium/large cell boundary. Neurons with sympathetic basket formations had a dramatically higher incidence of spontaneous activity (71% and had lower rheobase than cells with no sympathetic fibers nearby. Cells with lower density nearby fibers had intermediate phenotypes. Immunohistochemistry of sectioned ganglia showed that cells surrounded by sympathetic fibers were enriched in nociceptive markers TrkA, substance P, or CGRP. Spontaneous activity began before sympathetic sprouting was observed, but blocking sympathetic sprouting on day 3 by cutting the dorsal ramus in addition to the ventral ramus of the spinal nerve greatly reduced abnormal spontaneous activity. Conclusions The data suggest that early sympathetic sprouting into the sensory ganglia may have highly localized, excitatory effects. Quantitatively, neurons with sympathetic basket formations may account for more than half of the observed spontaneous activity, despite being relatively rare. Spontaneous activity in sensory neurons and sympathetic sprouting may be mutually re-enforcing.

  5. Alterations in cardiac autonomic control in spinal cord injury.

    Science.gov (United States)

    Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan; Malmqvist, Lasse; Wecht, Jill Maria; Krassioukov, Andrei

    2018-01-01

    A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure.

    Science.gov (United States)

    Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun

    2017-07-07

    A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Effects of short-term food deprivation on interoceptive awareness, feelings and autonomic cardiac activity.

    Science.gov (United States)

    Herbert, Beate M; Herbert, Cornelia; Pollatos, Olga; Weimer, Katja; Enck, Paul; Sauer, Helene; Zipfel, Stephan

    2012-01-01

    The perception of internal bodily signals (interoception) plays a relevant role for emotion processing and feelings. This study investigated changes of interoceptive awareness and cardiac autonomic activity induced by short-term food deprivation and its relationship to hunger and affective experience. 20 healthy women were exposed to 24h of food deprivation in a controlled setting. Interoceptive awareness was assessed by using a heartbeat tracking task. Felt hunger, cardiac autonomic activity, mood and subjective appraisal of interoceptive sensations were assessed before and after fasting. Results show that short-term fasting intensifies interoceptive awareness, not restricted to food cues, via changes of autonomic cardiac and/or cardiodynamic activity. The increase of interoceptive awareness was positively related to felt hunger. Additionally, the results demonstrate the role of cardiac vagal activity as a potential index of emotion related self-regulation, for hunger, mood and the affective appraisal of interoceptive signals during acute fasting. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Renal sympathetic denervation in hypertension.

    Science.gov (United States)

    Doumas, Michael; Faselis, Charles; Papademetriou, Vasilios

    2011-11-01

    Despite the abundance of antihypertensive drugs, resistant hypertension remains a major clinical problem. Recent technological advances render interventional management of resistant hypertension one of the hottest topics in the hypertension field. The aim of this review is to present the pathophysiologic background and the mechanisms mediating blood pressure reduction after renal sympathetic denervation, to analyze recent findings with this fascinating approach and to critically suggest future research directions. Catheter-based, ablation-induced renal sympathetic denervation was initially studied in 45 patients with resistant hypertension in a proof-of-concept study. Impressive blood pressure reductions of about 30/15  mmHg were achieved at 6 months, without serious complications. A second, controlled, randomized (but not blinded) study confirmed the results, verifying the efficacy and safety of the procedure. A recent report revealed the 2-year durability of blood pressure reduction. Data published so far indicate that ablation-induced renal denervation is a feasible, effective, and well tolerated interventional approach for the management of resistant hypertension. The groundbreaking studies of renal denervation in drug-resistant hypertension pave the way for further research in other disease conditions in which sympathetic overactivity seems to play a critical role. This initial wave of enthusiasm needs to be followed by rigorous investigation, for the proper identification of the potential and the limitations, indications, and contraindications of this approach.

  9. Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes.

    Science.gov (United States)

    Sultana, Md Razia; Bagul, Pankaj K; Katare, Parameshwar B; Anwar Mohammed, Soheb; Padiya, Raju; Banerjee, Sanjay K

    2016-11-01

    Cardiac complications are major contributor in the mortality of diabetic people. Mitochondrial dysfunctioning is a crucial contributor for the cardiac complications in diabetes, and SIRT-3 remains the major mitochondrial deacetylase. We hypothesized whether garlic has any role on SIRT-3 to prevent mitochondrial dysfunction in diabetic heart. Rats with developed hyperglycemia after STZ injection were divided into two groups; diabetic (Dia) and diabetic+garlic (Dia+Garl). Garlic was administered at a dose of 250mg/kg/day, orally for four weeks. An additional group was maintained to evaluate the effect of raw garlic administration on control rat heart. We have observed altered functioning of cardiac mitochondrial enzymes involved in metabolic pathways, and increased levels of cardiac ROS with decreased activity of catalase and SOD in diabetic rats. Cardiac mRNA expression of TFAM, PGC-1α, and CO1 was also altered in diabetes. In addition, reduced levels of electron transport chain complexes that observed in Dia group were normalized with garlic administration. This indicates the presence of increased oxidative stress with mitochondrial dysfunctioning in diabetic heart. We have observed reduced activity of SIRT3 and increased acetylation of MnSOD. Silencing SIRT-3 in cells also revealed the same. However, administration of garlic improved the SIRT-3 and MnSOD activity, by deacetylating MnSOD. Increased SOD activity was correlated with reduced levels of ROS in garlic-administered rat hearts. Collectively, our results provide an insight into garlic's protection to T1DM heart through activation of SIRT3-MnSOD pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Cancer-induced cardiac cachexia: Pathogenesis and impact of physical activity (Review).

    Science.gov (United States)

    Belloum, Yassine; Rannou-Bekono, Françoise; Favier, François B

    2017-05-01

    Cachexia is a wasting syndrome observed in many patients suffering from several chronic diseases including cancer. In addition to the progressive loss of skeletal muscle mass, cancer cachexia results in cardiac function impairment. During the severe stage of the disease, patients as well as animals bearing cancer cells display cardiac atrophy. Cardiac energy metabolism is also impeded with disruption of mitochondrial homeostasis and reduced oxidative capacity, although the available data remain equivocal. The release of inflammatory cytokines by tumor is a key mechanism in the initiation of heart failure. Oxidative stress, which results from the combination of chemotherapy, inadequate antioxidant consumption and chronic inflammation, will further foster heart failure. Protein catabolism is due to the concomitant activation of proteolytic systems and inhibition of protein synthesis, both processes being triggered by the deactivation of the Akt/mammalian target of rapamycin pathway. The reduction in oxidative capacity involves AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1α dysregulation. The nuclear factor-κB transcription factor plays a prominent role in the coordination of these alterations. Physical exercise appears as an interesting non-pharmaceutical way to counteract cancer cachexia-induced-heart failure. Indeed, aerobic training has anti-inflammatory effects, increases anti-oxidant defenses, prevents atrophy and promotes oxidative metabolism. The present review points out the importance of better understanding the concurrent structural and metabolic changes within the myocardium during cancer and the protective effects of exercise against cardiac cachexia.

  11. Sympathetic skin responses in patients with hyperthyroidism.

    Science.gov (United States)

    Gozke, E; Ozyurt, Z; Dortcan, N; Ore, O; Kocer, A; Ozer, E

    2007-01-01

    The aim of this study was to investigate the disorders of sympathetic nervous system in patients with hyperthyroidism using sympathetic skin response (SSR). Twenty-two newly diagnosed cases with hyperthyroidism were included in the study. The results were compared with those of 20 healthy controls. SSR was recorded with the contralateral electrical stimulation of the median nerve (of the upper extremities) and tibial nerve (of the lower extremities) with active electrodes placed on palms and soles and reference electrodes attached on the dorsal aspects of hands and feet. Ages of the cases with hyperthyroidism and controls ranged between 15-65 years (mean: 46.7 +/- 15.0 years) and 24-62 years (mean: 39.6 +/- 9.8 years) respectively (p > 0.05). In all the control subjects SSR could be obtained, while from the lower extremities of 4 cases with hyperthyroidism (18.0%) SSR could not be elicited. Mean SSR latencies of lower extremities were found significantly longer than control group (p nervous system involvement in cases with hyperthyroidism.

  12. Vitamin A is a necessary factor for sympathetic-independent rhythmic activation of mitogen-activated protein kinase in the rat pineal gland.

    Science.gov (United States)

    Guillaumond, F; Giraudet, F; Becquet, D; Sage, D; Laforge-Anglade, G; Bosler, O; François-Bellan, A M

    2005-02-01

    The circadian clock in the suprachiasmatic nucleus (SCN) controls day-to-day physiology and behavior by sending timing messages to multiple peripheral oscillators. In the pineal gland, a major SCN target, circadian events are believed to be driven exclusively by the rhythmic release of norepinephrine from superior cervical ganglia (SCG) neurons relaying clock messages through a polysynaptic pathway. Here we show in rat an SCN-driven daily rhythm of pineal MAPK activation that is not dependent on the SCG and whose maintenance requires vitamin A as a blood-borne factor. This finding challenges the dogma that SCG-released norepinephrine is an exclusive mediator of SCN-pineal communication and allows the assumption that humoral mechanisms are involved in pineal integration of temporal messages.

  13. Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

    International Nuclear Information System (INIS)

    Dubois, E.A.; Kam, K.L.; Somsen, G.A.; Boer, G.J.; Bruin, K. de; Batink, H.D.; Pfaffendorf, M.; Royen, E.A. van; Zwieten, P.A. van

    1996-01-01

    The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([ 123 I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 μCi [ 123 I]MIBG. Initial myocardial uptake and washout rates of [ 123 I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular β-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of β-adrenoceptors, indicative of increased sympathetic activity. Cardiac [ 123 I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [ 123 I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity noninvasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in β-adrenoceptor density were found, whereas [ 123 I]MIBG wash-out rate was increased. Thus, either [ 123 I]MIBG washout or β-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. (orig./MG)

  14. Differential effects of high-fat and high-carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in lean and obese women.

    Science.gov (United States)

    Tentolouris, N; Tsigos, C; Perea, D; Koukou, E; Kyriaki, D; Kitsou, E; Daskas, S; Daifotis, Z; Makrilakis, K; Raptis, S A; Katsilambros, N

    2003-11-01

    Food ingestion can influence autonomic nervous system activity. This study compares the effects of 2 different isoenergetic meals on sympathetic nervous system (SNS) activity, assessed by heart rate variability (HRV) and plasma norepinephrine (NE) levels, in lean and obese women. Fifteen lean and 15 obese healthy women were examined on 2 occasions: after a carbohydrate (CHO)-rich and after a fat-rich test meal. Measurements of blood pressure, heart rate, resting energy expenditure, plasma glucose, lipids, insulin, leptin, and NE, as well as spectral analysis of the HRV, were performed at baseline and every 1 hour for 3 hours after meals. At baseline, obese women had higher SNS activity than lean controls (higher values of low-to-high frequency ratio [LF/HF], 1.52 +/- 0.31 v 0.78 +/- 0.13, P=.04; and plasma NE levels, 405.6 +/- 197.9 v 240.5 +/- 95.8 pg/mL, Pmeal a greater increase in LF/HF and in plasma NE levels was observed in lean, compared to obese women (1.21 +/- 0.6 v 0.32 +/- 0.06, P=.04; and 102.9 +/- 35.4 v 38.7 +/- 12.3 pg/mL, P=.01, respectively), while no differences were observed after the fat-rich meal. Meal-induced thermogenesis was higher after the CHO-rich as compared to the fat-rich meal and was comparable between lean and obese women. Changes in HRV were not associated with the thermogenic response to the test meals. In conclusion, consumption of a CHO-rich meal causes greater cardiac SNS activation in lean than in obese women, while fat ingestion does not result in any appreciable change in either group. SNS activation does not appear to influence the thermic effect of the food in either lean or obese women.

  15. Tansig activation function (of MLP network) for cardiac abnormality detection

    Science.gov (United States)

    Adnan, Ja'afar; Daud, Nik Ghazali Nik; Ishak, Mohd Taufiq; Rizman, Zairi Ismael; Rahman, Muhammad Izzuddin Abd

    2018-02-01

    Heart abnormality often occurs regardless of gender, age and races. This problem sometimes does not show any symptoms and it can cause a sudden death to the patient. In general, heart abnormality is the irregular electrical activity of the heart. This paper attempts to develop a program that can detect heart abnormality activity through implementation of Multilayer Perceptron (MLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP network by using several training algorithms with Tansig activation function.

  16. Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.

    Science.gov (United States)

    Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

    2016-01-01

    The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

  17. Pharmacological modulations of cardiac ultra-rapid and slowly activating delayed rectifier currents: potential antiarrhythmic approaches.

    Science.gov (United States)

    Islam, Mohammed A

    2010-01-01

    Despite the emerging new insights into our understandings of the cellular mechanisms underlying cardiac arrhythmia, medical therapy for this disease remains unsatisfactory. Atrial fibrillation (AF), the most prevalent arrhythmia, is responsible for significant morbidity and mortality. On the other hand, ventricular fibrillation results in sudden cardiac deaths in many instances. Prolongation of cardiac action potential (AP) is a proven principle of antiarrhythmic therapy. Class III antiarrhythmic agents prolong AP and QT interval by blocking rapidly activating delayed rectifier current (I(Kr)). However, I(Kr) blocking drugs carry the risk of life-threatening proarrhythmia. Recently, modulation of atrial-selective ultra-rapid delayed rectifier current (I(Kur)), has emerged as a novel therapeutic approach to treat AF. A number of I(Kur) blockers are being evaluated for the treatment of AF. The inhibition of slowly activating delayed rectifier current (I(Ks)) has also been proposed as an effective and safer antiarrhythmic approach because of its distinguishing characteristics that differ in remarkable ways from other selective class III agents. Selective I(Ks) block may prolong AP duration (APD) at rapid rates without leading to proarrhythmia. This article reviews the pathophysiological roles of I(Kur) and I(Ks) in cardiac repolarization and the implications of newly developed I(Kur) and I(Ks) blocking agents as promising antiarrhythmic approaches. Several recent patents pertinent to antiarrhythmic drug development have been discussed. Further research will be required to evaluate the efficacy and safety of these agents in the clinical setting.

  18. Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy

    International Nuclear Information System (INIS)

    Koyama, Keiko; Inoue, Tomio; Hasegawa, Akira; Oriuchi, Noboru; Okamoto, Eiichi; Tomaru, Yumi; Endo, Keigo

    2001-01-01

    Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p<0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p<0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r=0.80, p<0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart. (author)

  19. Hypothalamus-pituitary-thyroid axis activity and function of cardiac muscle in energy deficit

    Directory of Open Access Journals (Sweden)

    Katarzyna Lachowicz

    2017-12-01

    Full Text Available Frequently repeated statement that energy restriction is a factor that improves cardiovascular system function seems to be not fully truth. Low energy intake modifies the hypothalamus-pituitary-thyroid axis activity and thyroid hormone peripheral metabolism. Thyroid hormones, as modulators of the expression and activity of many cardiomyocyte proteins, control heart function. Decreased thyroid hormone levels and their disturbanced conversion and action result in alternation of cardiac remodeling, disorder of calcium homeostasis and diminish myocardial contractility. This review provides a summary of the current state of knowledge about the mechanisms of energy restriction effects on thyroidal axis activity, thyroid hormone peripheral metabolism and action in target tissues, especially in cardiac myocytes. We also showed the existence of energy restriction-thyroid-heart pathway.

  20. Peptidergic modulation of efferent sympathetic neurons in intrathoracic ganglia regulating the canine heart.

    Science.gov (United States)

    Armour, J A

    1989-05-01

    When either substance P or vasoactive intestinal peptide was injected into an acutely decentralized intrathoracic sympathetic ganglion, short-lasting augmentation of cardiac chronotropism and inotropism was induced. These augmentations were induced before the fall in systemic arterial pressure occurred which was a consequence of these peptides leaking into the systemic circulation in enough quantity to alter peripheral vascular resistance directly. When similar volumes of normal saline were injected into an intrathoracic ganglion, no significant cardiac changes were induced. When substance P or vasoactive intestinal peptide was administered into an intrathoracic ganglion, similar cardiac augmentations were induced either before or after the intravenous administration of hexamethonium. In contrast, when these peptides were injected into an intrathoracic ganglion in which the beta-adrenergic blocking agent timolol (0.1 mg/0.1 ml of normal saline) had been administered no cardiac augmentation occurred. These data imply that in the presence of beta-adrenergic blockade intraganglionic administration of substance P or vasoactive intestinal peptide does not modify enough intrathoracic neurons to alter cardiac chronotropism and inotropism detectably. When neuropeptide Y was injected into an intrathoracic ganglion, no cardiac changes occurred. However, when cardiac augmentations were induced by sympathetic preganglionic axon stimulation these were enhanced following the intraganglionic administration of neuropeptide Y. As this effect occurred after timolol was administered into the ipsilateral ganglia, but not after intravenous administration of hexamethonium, it is proposed that the effects of neuropeptide Y are dependent upon functioning intrathoracic ganglionic nicotinic cholinergic synaptic mechanisms. Intravenous administration of either morphine or [D-ala2,D-leu5]enkephalin acetate did not alter the capacity of the preganglionic sympathetic axons to augment the heart

  1. False alarm reduction in BSN-based cardiac monitoring using signal quality and activity type information.

    Science.gov (United States)

    Tanantong, Tanatorn; Nantajeewarawat, Ekawit; Thiemjarus, Surapa

    2015-02-09

    False alarms in cardiac monitoring affect the quality of medical care, impacting on both patients and healthcare providers. In continuous cardiac monitoring using wireless Body Sensor Networks (BSNs), the quality of ECG signals can be deteriorated owing to several factors, e.g., noises, low battery power, and network transmission problems, often resulting in high false alarm rates. In addition, body movements occurring from activities of daily living (ADLs) can also create false alarms. This paper presents a two-phase framework for false arrhythmia alarm reduction in continuous cardiac monitoring, using signals from an ECG sensor and a 3D accelerometer. In the first phase, classification models constructed using machine learning algorithms are used for labeling input signals. ECG signals are labeled with heartbeat types and signal quality levels, while 3D acceleration signals are labeled with ADL types. In the second phase, a rule-based expert system is used for combining classification results in order to determine whether arrhythmia alarms should be accepted or suppressed. The proposed framework was validated on datasets acquired using BSNs and the MIT-BIH arrhythmia database. For the BSN dataset, acceleration and ECG signals were collected from 10 young and 10 elderly subjects while they were performing ADLs. The framework reduced the false alarm rate from 9.58% to 1.43% in our experimental study, showing that it can potentially assist physicians in diagnosing a vast amount of data acquired from wireless sensors and enhance the performance of continuous cardiac monitoring.

  2. False Alarm Reduction in BSN-Based Cardiac Monitoring Using Signal Quality and Activity Type Information

    Directory of Open Access Journals (Sweden)

    Tanatorn Tanantong

    2015-02-01

    Full Text Available False alarms in cardiac monitoring affect the quality of medical care, impacting on both patients and healthcare providers. In continuous cardiac monitoring using wireless Body Sensor Networks (BSNs, the quality of ECG signals can be deteriorated owing to several factors, e.g., noises, low battery power, and network transmission problems, often resulting in high false alarm rates. In addition, body movements occurring from activities of daily living (ADLs can also create false alarms. This paper presents a two-phase framework for false arrhythmia alarm reduction in continuous cardiac monitoring, using signals from an ECG sensor and a 3D accelerometer. In the first phase, classification models constructed using machine learning algorithms are used for labeling input signals. ECG signals are labeled with heartbeat types and signal quality levels, while 3D acceleration signals are labeled with ADL types. In the second phase, a rule-based expert system is used for combining classification results in order to determine whether arrhythmia alarms should be accepted or suppressed. The proposed framework was validated on datasets acquired using BSNs and the MIT-BIH arrhythmia database. For the BSN dataset, acceleration and ECG signals were collected from 10 young and 10 elderly subjects while they were performing ADLs. The framework reduced the false alarm rate from 9.58% to 1.43% in our experimental study, showing that it can potentially assist physicians in diagnosing a vast amount of data acquired from wireless sensors and enhance the performance of continuous cardiac monitoring.

  3. Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients.

    Directory of Open Access Journals (Sweden)

    Yuki Fujimura

    Full Text Available Xanthine oxidoreductase (XOR, which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients.Plasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI, alanine aminotransferase (ALT, HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD, those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF and increased plasma B-type natriuretic peptide (BNP levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages.Among cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.

  4. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    Science.gov (United States)

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle.

  5. Risk and Protective Factors for Sudden Cardiac Death During Leisure Activities in the Mountains: An Update.

    Science.gov (United States)

    Burtscher, Martin

    2017-08-01

    Annually, more than 100 million tourists with widely varying health and fitness status are attracted by the mountainous areas around the world. Whereas mountaineering activities may contribute to the well established beneficial effects of regular exercise, for certain individuals these activities are also associated with a relatively high risk of death. This manuscript presents an updated overview of risk and protective factors for sudden cardiac death during leisure activities in the mountains. Sudden cardiac death (SCD) has been proven to be the most frequent cause of non traumatic death in males aged over 34 years, e.g. during mountain hiking, cross country skiing or downhill skiing. Risk factors for cardiovascular diseases and, in particular, prior myocardial infarction, are the most important risk factors for SCD, predominantly relevant in downhill skiers. The unusual physical exertion on the first day at altitude, the late morning hours and the prolonged abstinence from food and fluid intake during exercise at altitude are most important triggers. Acute hypoxia may represent a trigger for SCD on the one hand but might also evoke beneficial effects by preconditioning on the other hand. The identification of high-risk subjects and SCD triggers, evidence-based therapy of treatable risk factors, the appropriate individual preparation by physical training, and considering behavioural aspects, especially at the beginning of the physically active altitude sojourn will help to prevent SCD and increase the health benefits generated by mountaineering activities. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  6. Effect of PPAR γ activators on hypertrophic cardiac myocytes in vitro

    International Nuclear Information System (INIS)

    Wu Shimin; Zhou Xin; Ye Ping; Wang Qiong; Gao Yue; Liu Yongxue

    2004-01-01

    Objective: To investigate the effects of peroxisome proliferator-activated receptor γ (PPAR γ) activators pioglitazone and 15-deoxy-Δ 12,14 prostaglandin J 2 (15d-PGJ 2 ) on hypertrophic cardiac myocytes (MC) of neonatal rats in vitro. Methods; With the stimulation of angiotensin II(Ang II), a model of hypertrophy of MC was established. With the method of reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was amplified; with the aid of NIH Image J software the surface area of MC was analyzed and with 3 H-leucine incorporation, the synthesizing rate of protein in MC was measured. Results: Increases in surface area of MC, mRNA expression of ANP and BNP and 3 H-leucine incorporation in MC were observed in the model of cardiac hypertrophy. Pioglitazone and 15d-PGJ 2 , two kinds of PPAR γ activators, inhibited the above changes in a dose-dependent manner. Conclusion: It is suggested that PPAR γ activators inhibit hypertrophy of cardiac myocytes and PPAR γ-dependent pathway be involved in the inhibitory course

  7. Autonomic cardiac innervation

    Science.gov (United States)

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  8. Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress.

    Science.gov (United States)

    Giuliano, Ryan J; Gatzke-Kopp, Lisa M; Roos, Leslie E; Skowron, Elizabeth A

    2017-08-01

    The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher-order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high-frequency heart rate variability, HF-HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high-risk women. HF-HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within-person fluctuations in WM performance throughout the task concurrently with HF-HRV and PEP, as well as between-person differences as a function of resting HF-HRV and PEP levels. Results indicate that resting PEP moderated the association between HF-HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow-up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation. © 2017 Society for Psychophysiological Research.

  9. Chronic sympathetic activation promotes downregulation of ß-adrenoceptor-mediated effects in the guinea pig heart independently of structural remodeling and systolic dysfunction

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Thiele, Stefanie; Osadchiy, Oleg

    2011-01-01

    pathway upon chronic infusion of isoproterenol, a ß-adrenoceptor agonist, at a dose producing no structural left ventricular (LV) remodeling and systolic dysfunction. Subcutaneous isoproterenol infusion (400 µg kg(-1) h(-1) over 16 days) to guinea pigs using osmotic minipumps produced no change in cardiac...... weights, LV internal dimensions, myocyte cross-sectional area, extent of interstitial fibrosis, and basal contractile function. Isolated, perfused heart preparations from isoproterenol-treated guinea pigs exhibited attenuated responsiveness to acute ß-adrenoceptor stimulation, as evidenced by reduced LV...

  10. Renal sympathetic nerve, blood flow, and epithelial transport responses to thermal stress.

    Science.gov (United States)

    Wilson, Thad E

    2017-05-01

    Thermal stress is a profound sympathetic stress in humans; kidney responses involve altered renal sympathetic nerve activity (RSNA), renal blood flow, and renal epithelial transport. During mild cold stress, RSNA spectral power but not total activity is altered, renal blood flow is maintained or decreased, and epithelial transport is altered consistent with a sympathetic stress coupled with central volume loaded state. Hypothermia decreases RSNA, renal blood flow, and epithelial transport. During mild heat stress, RSNA is increased, renal blood flow is decreased, and epithelial transport is increased consistent with a sympathetic stress coupled with a central volume unloaded state. Hyperthermia extends these directional changes, until heat illness results. Because kidney responses are very difficult to study in humans in vivo, this review describes and qualitatively evaluates an in vivo human skin model of sympathetically regulated epithelial tissue compared to that of the nephron. This model utilizes skin responses to thermal stress, involving 1) increased skin sympathetic nerve activity (SSNA), decreased skin blood flow, and suppressed eccrine epithelial transport during cold stress; and 2) increased SSNA, skin blood flow, and eccrine epithelial transport during heat stress. This model appears to mimic aspects of the renal responses. Investigations of skin responses, which parallel certain renal responses, may aid understanding of epithelial-sympathetic nervous system interactions during cold and heat stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes.

    OpenAIRE

    Siwik Deborah A; Kuster Gabriela M; Brahmbhatt Jamin V; Zaidi Zaheer; Malik Julia; Ooi Henry; Ghorayeb Ghassan

    2008-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricu...

  12. Myofibril ATPase activity of cardiac and skeletal muscle of exhaustively exercised rats.

    Science.gov (United States)

    Belcastro, A N; Turcotte, R; Rossiter, M; Secord, D; Maybank, P E

    1984-01-01

    The activation characteristics of Mg-ATP and Ca2+ on cardiac and skeletal muscle myofibril ATPase activity were studied in rats following a run to exhaustion. In addition, the effect of varying ionic strength was determined on skeletal muscle from exhausted animals. The exhausted group (E) ran at a speed of 25 m min-1 with an 8% incline. Myofibril ATPase activities for control (C) and E were determined with 1, 3 and 5 mM Mg-ATP and 1 and 10 microM Ca2+ at pH 7.0 and 30 degrees C. For control skeletal muscle, at 1 and 10 microM Ca2+, there was an increase in ATPase activity from 1 to 5 mM Mg-ATP (P less than 0.05). For E animals the myofibril ATPase activities at 10 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ and all Mg-ATP concentrations were similar to C (P greater than 0.05). At 1.0 microM Ca2+ the activities at 3 and 5 mM Mg-ATP were greater for the E animals (P less than 0.05). Increasing KCl concentrations resulted in greater inhibition for E animals. With cardiac muscle, the myofibril ATPase activities at 1.0 microM free Ca2+ were lower for E at all Mg-ATP levels (P less than 0.05). In contrast, at 10 microM Ca2+, the E group exhibited an elevated myofibril ATPase activity. The results indicate that Mg-ATP and Ca2+ activation of cardiac and skeletal muscle myofibril ATPase is altered with exhaustive exercise.

  13. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons

    OpenAIRE

    Hasan, Wohaib; Smith, Peter G

    2013-01-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is a...

  14. Sympathetic Overactivity in Chronic Kidney Disease: Consequences and Mechanisms

    Directory of Open Access Journals (Sweden)

    Jasdeep Kaur

    2017-08-01

    Full Text Available The incidence of chronic kidney disease (CKD is increasing worldwide, with more than 26 million people suffering from CKD in the United States alone. More patients with CKD die of cardiovascular complications than progress to dialysis. Over 80% of CKD patients have hypertension, which is associated with increased risk of cardiovascular morbidity and mortality. Another common, perhaps underappreciated, feature of CKD is an overactive sympathetic nervous system. This elevation in sympathetic nerve activity (SNA not only contributes to hypertension but also plays a detrimental role in the progression of CKD independent of any increase in blood pressure. Indeed, high SNA is associated with poor prognosis and increased cardiovascular morbidity and mortality independent of its effect on blood pressure. This brief review will discuss some of the consequences of sympathetic overactivity and highlight some of the potential pathways contributing to chronically elevated SNA in CKD. Mechanisms leading to chronic sympathoexcitation in CKD are complex, multifactorial and to date, not completely understood. Identification of the mechanisms and/or signals leading to sympathetic overactivity in CKD are crucial for development of effective therapeutic targets to reduce the increased cardiovascular risk in this patient group.

  15. Netrin-1 controls sympathetic arterial innervation.

    Science.gov (United States)

    Brunet, Isabelle; Gordon, Emma; Han, Jinah; Cristofaro, Brunella; Broqueres-You, Dong; Liu, Chun; Bouvrée, Karine; Zhang, Jiasheng; del Toro, Raquel; Mathivet, Thomas; Larrivée, Bruno; Jagu, Julia; Pibouin-Fragner, Laurence; Pardanaud, Luc; Machado, Maria J C; Kennedy, Timothy E; Zhuang, Zhen; Simons, Michael; Levy, Bernard I; Tessier-Lavigne, Marc; Grenz, Almut; Eltzschig, Holger; Eichmann, Anne

    2014-07-01

    Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

  16. Subacute cardiac sympathetic dys-innervation, evaluated by the tomo-scintigraphy with {sup 123}I-Mibg in the Takotsubo syndrome: about one case; Dysinnervation sympathique cardiaque subaigue, evaluee par la tomoscintigraphie a l'123I-MIBG dans le syndrome de Takotsubo: a propos d'un cas

    Energy Technology Data Exchange (ETDEWEB)

    Costo, S.; Agostini, D. [Service de medecine nucleaire, CHU Cote-de-Nacre, Caen, (France); Sabatier, R. [service de cardiologie, CHU Cote-de-Nacre, Caen, (France)

    2009-05-15

    The association of perfusion imaging and myocardium innervation showed a major mismatch of fixation attesting of a sympathetic default of innervation contemporary of a left ventricle dysfunction without perfusion troubles, for a patient with a Takotsubo cardiomyopathy. (N.C.)

  17. Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Courtney M. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Hu, Jianxin [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Thomas, Reuben [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Gainous, T. Blair [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Celona, Barbara [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Sinha, Tanvi [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Dickel, Diane E. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Heidt, Analeah B. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Xu, Shan-Mei [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Bruneau, Benoit G. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pollard, Katherine S. [Univ. of California, San Francisco, CA (United States). Gladstone Inst.; Pennacchio, Len A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Black, Brian L. [Univ. of California, San Francisco, CA (United States). Cardiovascular Research Inst.; Univ. of California, San Francisco, CA (United States). Dept. of

    2017-03-28

    Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by the SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.

  18. Desipramine increases cardiac parasympathetic activity via α2-adrenergic mechanism in rats.

    Science.gov (United States)

    Kawada, Toru; Akiyama, Tsuyoshi; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

    2017-07-01

    Desipramine (DMI) is a blocker of neuronal norepinephrine (NE) uptake transporter. Although intravenous DMI has been shown to cause centrally-mediated sympathoinhibition and peripheral NE accumulation, its parasympathetic effect remains to be elucidated. We hypothesized that intravenous DMI activates the cardiac vagal nerve via an α 2 -adrenergic mechanism. Using a cardiac microdialysis technique, changes in myocardial interstitial acetylcholine (ACh) levels in the left ventricular free wall in response to intravenous DMI (1mg·kg -1 ) were examined in anesthetized rats. In rats with intact vagi (n=7), intravenous DMI increased ACh from 1.67±0.43 to 2.48±0.66nM (Padrenergic stimulation in experimental settings in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Efficient solution of ordinary differential equations modeling electrical activity in cardiac cells.

    Science.gov (United States)

    Sundnes, J; Lines, G T; Tveito, A

    2001-08-01

    The contraction of the heart is preceded and caused by a cellular electro-chemical reaction, causing an electrical field to be generated. Performing realistic computer simulations of this process involves solving a set of partial differential equations, as well as a large number of ordinary differential equations (ODEs) characterizing the reactive behavior of the cardiac tissue. Experiments have shown that the solution of the ODEs contribute significantly to the total work of a simulation, and there is thus a strong need to utilize efficient solution methods for this part of the problem. This paper presents how an efficient implicit Runge-Kutta method may be adapted to solve a complicated cardiac cell model consisting of 31 ODEs, and how this solver may be coupled to a set of PDE solvers to provide complete simulations of the electrical activity.

  20. Does reducing unnecessary right ventricular pacing improve sympathetic activity and innervation of heart in sinus node disease patients? MVP and SafeR study.

    Science.gov (United States)

    Miyamoto, Mihoko; Kimura, Yuichiro; Hosoda, Junya; Matsumoto, Katsumi; Matsushita, Kohei; Ishikawa, Toshiyuki; Umemura, Satoshi

    2012-01-01

    Ventricular desynchronization imposed by ventricular pacing causes regional disturbances of adrenergic innervation in the left ventricular myocardium and increases the risk of heart failure and atrial fibrillation (AF) in patients with sinus node disease (SND). As a result, decreased iodine-123 metaiodobenzylguanidine (I-(123 )MIBG) uptake occurs in patients with an implanted permanent pacemaker. Fourteen SND patients with an implanted pacemaker equipped with an algorithm for reducing unnecessary right ventricular pacing (RURVP) were enrolled. Pacemakers were programmed to RURVP mode for the first 12 weeks, and then reprogrammed to DDD for the last 12 weeks. At the end of each mode, data on cumulative percent ventricular pacing (%Vp), atrial high rate episodes (%AHR), I-(123 )MIBG myocardial scintigraphy, brain natriuretic peptide (BNP), human atrial natriuretic peptide (hANP), and myocardial damage indices typified by troponin T and C-reactive protein (CRP) were collected. %Vp was lower in RURVP than in DDD (0.2% versus 95.7%, P = 0.00098). BNP, hANP, troponin T, and CRP did not differ significantly between the pacing modes. However, I-(123 )MIBG findings of patients with full ventricular pacing in DDD improved in RURVP. In contrast, among patients without full ventricular pacing in DDD, their I-(123 )MIBG findings did not differ significantly between the pacing modes. In SND patients with normal cardiac function and intact atrioventricular conduction, the reduction of %Vp in RURVP was due to the reduction of ineffective pacing and fusion pacing in DDD. Therefore, these 2 types of pacing do not affect cardiac pump function.

  1. Regular physical exercise improves cardiac autonomic and muscle vasodilatory responses to isometric exercise in healthy elderly

    Directory of Open Access Journals (Sweden)

    Sarmento AO

    2017-06-01

    Full Text Available Adriana de Oliveira Sarmento,1–3 Amilton da Cruz Santos,1,4 Ivani Credidio Trombetta,2,5 Marciano Moacir Dantas,1 Ana Cristina Oliveira Marques,1,4 Leone Severino do Nascimento,1,4 Bruno Teixeira Barbosa,1,2 Marcelo Rodrigues Dos Santos,2 Maria do Amparo Andrade,3 Anna Myrna Jaguaribe-Lima,3,6 Maria do Socorro Brasileiro-Santos1,3,4 1Laboratory of Physical Training Studies Applied to Health, Department of Physical Education, Federal University of Paraiba, João Pessoa, Brazil; 2Unit of Cardiovascular Rehabilitation and Exercise Physiology – Heart Institute (InCor/HC-FMUSP, University of São Paulo, São Paulo, Brazil; 3Graduate Program in Physiotherapy, Federal University of Pernambuco, Recife, Brazil; 4Associate Graduate Program in Physical Education UPE/UFPB, João Pessoa, Brazil; 5Graduate Program in Medicine, Universidade Nove de Julho (UNINOVE, São Paulo, Brazil; 6Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco, Recife, Brazil Abstract: The objective of this study was to evaluate cardiac autonomic control and muscle vasodilation response during isometric exercise in sedentary and physically active older adults. Twenty healthy participants, 10 sedentary and 10 physically active older adults, were evaluated and paired by gender, age, and body mass index. Sympathetic and parasympathetic cardiac activity (spectral and symbolic heart rate analysis and muscle blood flow (venous occlusion plethysmography were measured for 10 minutes at rest (baseline and during 3 minutes of isometric handgrip exercise at 30% of the maximum voluntary contraction (sympathetic excitatory maneuver. Variables were analyzed at baseline and during 3 minutes of isometric exercise. Cardiac autonomic parameters were analyzed by Wilcoxon and Mann–Whitney tests. Muscle vasodilatory response was analyzed by repeated-measures analysis of variance followed by Tukey’s post hoc test. Sedentary older adults had higher cardiac

  2. Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction

    Directory of Open Access Journals (Sweden)

    Leiner Tim

    2011-05-01

    Full Text Available Abstract Background Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients. Methods Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 ± 0.9 years, BMI: 29.9 ± 0.01 kg/m2 followed a 12-week training program (combination endurance/strength training, three sessions/week. Before and after training, maximal whole body oxygen uptake (VO2max and insulin sensitivity (by hyperinsulinemic, euglycemic clamp was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy. Results VO2max increased (from 27.1 ± 1.5 to 30.1 ± 1.6 ml/min/kg, p = 0.001 and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose improved from 5.8 ± 1.9 to 10.3 ± 2.0 μmol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 ± 2.0 to 55.6 ± 1.5%, p = 0.01 as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 ± 0.22% to 0.95 ± 0.21%, p = 0.15. Conclusions Twelve weeks of progressive endurance/strength training was effective in improving VO2max, insulin sensitivity

  3. Quantitatively accurate activity measurements with a dedicated cardiac SPECT camera: Physical phantom experiments

    Energy Technology Data Exchange (ETDEWEB)

    Pourmoghaddas, Amir, E-mail: apour@ottawaheart.ca; Wells, R. Glenn [Physics Department, Carleton University, Ottawa, Ontario K1S 5B6, Canada and Cardiology, The University of Ottawa Heart Institute, Ottawa, Ontario K1Y4W7 (Canada)

    2016-01-15

    Purpose: Recently, there has been increased interest in dedicated cardiac single photon emission computed tomography (SPECT) scanners with pinhole collimation and improved detector technology due to their improved count sensitivity and resolution over traditional parallel-hole cameras. With traditional cameras, energy-based approaches are often used in the clinic for scatter compensation because they are fast and easily implemented. Some of the cardiac cameras use cadmium-zinc-telluride (CZT) detectors which can complicate the use of energy-based scatter correction (SC) due to the low-energy tail—an increased number of unscattered photons detected with reduced energy. Modified energy-based scatter correction methods can be implemented, but their level of accuracy is unclear. In this study, the authors validated by physical phantom experiments the quantitative accuracy and reproducibility of easily implemented correction techniques applied to {sup 99m}Tc myocardial imaging with a CZT-detector-based gamma camera with multiple heads, each with a single-pinhole collimator. Methods: Activity in the cardiac compartment of an Anthropomorphic Torso phantom (Data Spectrum Corporation) was measured through 15 {sup 99m}Tc-SPECT acquisitions. The ratio of activity concentrations in organ compartments resembled a clinical {sup 99m}Tc-sestamibi scan and was kept consistent across all experiments (1.2:1 heart to liver and 1.5:1 heart to lung). Two background activity levels were considered: no activity (cold) and an activity concentration 1/10th of the heart (hot). A plastic “lesion” was placed inside of the septal wall of the myocardial insert to simulate the presence of a region without tracer uptake and contrast in this lesion was calculated for all images. The true net activity in each compartment was measured with a dose calibrator (CRC-25R, Capintec, Inc.). A 10 min SPECT image was acquired using a dedicated cardiac camera with CZT detectors (Discovery NM530c, GE

  4. The Effects of Sympathetic Inhibition on Metabolic and Cardiopulmonary Responses to Exercise in Hypoxic Conditions.

    Science.gov (United States)

    Scalzo, Rebecca L; Peltonen, Garrett L; Binns, Scott E; Klochak, Anna L; Szallar, Steve E; Wood, Lacey M; Larson, Dennis G; Luckasen, Gary J; Irwin, David; Schroeder, Thies; Hamilton, Karyn L; Bell, Christopher

    2015-12-01

    Pre-exertion skeletal muscle glycogen content is an important physiological determinant of endurance exercise performance: low glycogen stores contribute to premature fatigue. In low-oxygen environments (hypoxia), the important contribution of carbohydrates to endurance performance is further enhanced as glucose and glycogen dependence is increased; however, the insulin sensitivity of healthy adult humans is decreased. In light of this insulin resistance, maintaining skeletal muscle glycogen in hypoxia becomes difficult, and subsequent endurance performance is impaired. Sympathetic inhibition promotes insulin sensitivity in hypoxia but may impair hypoxic exercise performance, in part due to suppression of cardiac output. Accordingly, we tested the hypothesis that hypoxic exercise performance after intravenous glucose feeding in a low-oxygen environment will be attenuated when feeding occurs during sympathetic inhibition. On 2 separate occasions, while breathing a hypoxic gas mixture, 10 healthy men received 1 hour of parenteral carbohydrate infusion (20% glucose solution in saline; 75 g), after which they performed stationary cycle ergometer exercise (~65% maximal oxygen uptake) until exhaustion. Forty-eight hours before 1 visit, chosen randomly, sympathetic inhibition via transdermal clonidine (0.2 mg/d) was initiated. The mean time to exhaustion after glucose feeding both with and without sympathetic inhibition was not different (22.7 ± 5.4 minutes vs 23.5 ± 5.1 minutes; P = .73). Sympathetic inhibition protects against hypoxia-mediated insulin resistance without influencing subsequent hypoxic endurance performance. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  5. Sympathetic nerves: How do they affect angiogenesis, particularly during wound healing of soft tissues?

    Science.gov (United States)

    Pan, Liangli; Tang, Jianbing; Liu, Hongwei; Cheng, Biao

    2016-01-01

    Angiogenesis is essential for wound healing, and angiogenesis impairment can result in chronic ulcers. Studies have shown that the sympathetic nervous system has an important role in angiogenesis. In recent years, researchers have focused on the roles of sympathetic nerves in tumor angiogenesis. In fact, sympathetic nerves can affect angiogenesis in the wound healing of soft tissues, and may have a similar mechanism of action as that seen in tumorigenesis. Sympathetic nerves act primarily through interactions between the neurotransmitters released from nerve endings and receptors present in target organs. Among this, activation or inhibition of adrenergic receptors (mainly β-adrenergic receptors) influence formation of new blood vessels considerably. As sympathetic nerves locate near pericytes in microvessel, go along the capillaries and there are adrenergic receptors present in endothelial cells and pericytes, sympathetic nerves may participate in angiogenesis by influencing the endothelial cells and pericytes of new capillaries. Studying the roles of sympathetic nerves on the angiogenesis of wound healing can contribute to understanding the mechanisms of tissue repair, tissue regeneration, and tumorigenesis, thereby providing new therapeutic perspectives.

  6. Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats.

    Science.gov (United States)

    Brailoiu, G Cristina; Deliu, Elena; Tica, Andrei A; Rabinowitz, Joseph E; Tilley, Douglas G; Benamar, Khalid; Koch, Walter J; Brailoiu, Eugen

    2013-09-01

    Nesfatin-1, a peptide whose receptor is yet to be identified, has been involved in the modulation of feeding, stress, and metabolic responses. More recently, increasing evidence supports a modulatory role for nesfatin-1 in autonomic and cardiovascular activity. This study was undertaken to test if the expression of nesfatin-1 in the nucleus ambiguus, a key site for parasympathetic cardiac control, may be correlated with a functional role. As we have previously demonstrated that nesfatin-1 elicits Ca²⁺ signaling in hypothalamic neurons, we first assessed the effect of this peptide on cytosolic Ca²⁺ in cardiac pre-ganglionic neurons of nucleus ambiguus. We provide evidence that nesfatin-1 increases cytosolic Ca²⁺ concentration via a Gi/o-coupled mechanism. The nesfatin-1-induced Ca²⁺ rise is critically dependent on Ca²⁺ influx via P/Q-type voltage-activated Ca²⁺ channels. Repeated administration of nesfatin-1 leads to tachyphylaxis. Furthermore, nesfatin-1 produces a dose-dependent depolarization of cardiac vagal neurons via a Gi/o-coupled mechanism. In vivo studies, using telemetric and tail-cuff monitoring of heart rate and blood pressure, indicate that microinjection of nesfatin-1 into the nucleus ambiguus produces bradycardia not accompanied by a change in blood pressure in conscious rats. Taken together, our results identify for the first time that nesfatin-1 decreases heart rate by activating cardiac vagal neurons of nucleus ambiguus. Our results indicate that nesfatin-1, one of the most potent feeding peptides, increases cytosolic Ca²⁺ by promoting Ca²⁺ influx via P/Q channels and depolarizes nucleus ambiguus neurons; both effects are Gi/o-mediated. In vivo studies indicate that microinjection of nesfatin-1 into nucleus ambiguus produces bradycardia in conscious rats. This is the first report that nesfatin-1 increases the parasympathetic cardiac tone. © 2013 International Society for Neurochemistry.

  7. An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats

    Science.gov (United States)

    Background: Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) is an ubiquitous air pollutant believed to provoke cardiac events partly through imbalance of the sympathetic and parasympathetic branches of the autonomic nervo...

  8. Cardiac-specific activation of Cre expression at late fetal development

    International Nuclear Information System (INIS)

    Opherk, Jan P.; Yampolsky, Peter; Hardt, Stefan E.; Schoels, Wolfgang; Katus, Hugo A.; Koenen, Michael; Zehelein, Joerg

    2007-01-01

    In a first step towards dissecting molecular mechanisms that contribute to the development of cardiac diseases, we have generated transgenic mice that express a Cre-GFP fusion protein under the transcriptional control of a 4.3 kb murine cardiac Troponin I gene (cTnI) promoter. Cre-GFP expression, similar in three transgenic lines, is described in one line. In mouse embryos, transgenic for the Cre-GFP and ROSA lacZ reporter allele, first Cre-mediated recombination appeared at 16.5 dpc selectively at the heart. Like the endogenous cTnI gene, transgenic Cre expression showed a slow rise through fetal development that increased neonatally. Bitransgenic hearts, stained at 30 days of age, showed intense signals in ventricular and atrial myocytes while no recombination occurred in other tissues. The delayed onset of Cre activity in cTnI-Cre mice could provide a useful genetic tool to evaluate the function of loxP targeted cardiac genes without interference of recombination during early heart development

  9. Large-deflection statics analysis of active cardiac catheters through co-rotational modelling.

    Science.gov (United States)

    Peng Qi; Chen Qiu; Mehndiratta, Aadarsh; I-Ming Chen; Haoyong Yu

    2016-08-01

    This paper presents a co-rotational concept for large-deflection formulation of cardiac catheters. Using this approach, the catheter is first discretized with a number of equal length beam elements and nodes, and the rigid body motions of an individual beam element are separated from its deformations. Therefore, it is adequate for modelling arbitrarily large deflections of a catheter with linear elastic analysis at the local element level. A novel design of active cardiac catheter of 9 Fr in diameter at the beginning of the paper is proposed, which is based on the contra-rotating double helix patterns and is improved from the previous prototypes. The modelling section is followed by MATLAB simulations of various deflections when the catheter is exerted different types of loads. This proves the feasibility of the presented modelling approach. To the best knowledge of the authors, it is the first to utilize this methodology for large-deflection static analysis of the catheter, which will enable more accurate control of robot-assisted cardiac catheterization procedures. Future work would include further experimental validations.

  10. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest

    Science.gov (United States)

    Vincentz, Joshua W.; Firulli, Beth A.; Lin, Andrea; Spicer, Douglas B.; Howard, Marthe J.; Firulli, Anthony B.

    2013-01-01

    Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. PMID:23555309

  11. Imaging cardiac activation sequence during ventricular tachycardia in a canine model of nonischemic heart failure.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Yu, Long; Zhou, Zhaoye; Killingsworth, Cheryl R; He, Bin

    2015-01-15

    Noninvasive cardiac activation imaging of ventricular tachycardia (VT) is important in the clinical diagnosis and treatment of arrhythmias in heart failure (HF) patients. This study investigated the ability of the three-dimensional cardiac electrical imaging (3DCEI) technique for characterizing the activation patterns of spontaneously occurring and norepinephrine (NE)-induced VTs in a newly developed arrhythmogenic canine model of nonischemic HF. HF was induced by aortic insufficiency followed by aortic constriction in three canines. Up to 128 body-surface ECGs were measured simultaneously with bipolar recordings from up to 232 intramural sites in a closed-chest condition. Data analysis was performed on the spontaneously occurring VTs (n=4) and the NE-induced nonsustained VTs (n=8) in HF canines. Both spontaneously occurring and NE-induced nonsustained VTs initiated by a focal mechanism primarily from the subendocardium, but occasionally from the subepicardium of left ventricle. Most focal initiation sites were located at apex, right ventricular outflow tract, and left lateral wall. The NE-induced VTs were longer, more rapid, and had more focal sites than the spontaneously occurring VTs. Good correlation was obtained between imaged activation sequence and direct measurements (averaged correlation coefficient of ∼0.70 over 135 VT beats). The reconstructed initiation sites were ∼10 mm from measured initiation sites, suggesting good localization in such a large animal model with cardiac size similar to a human. Both spontaneously occurring and NE-induced nonsustained VTs had focal initiation in this canine model of nonischemic HF. 3DCEI is feasible to image the activation sequence and help define arrhythmia mechanism of nonischemic HF-associated VTs. Copyright © 2015 the American Physiological Society.

  12. Sympathetic vasoconstrictor nerve function in alcoholic neuropathy

    DEFF Research Database (Denmark)

    Jensen, K; Andersen, K; Smith, T

    1984-01-01

    (18% and 48% decrease respectively). However, in three patients with moderate neuropathy, and in one patient with no signs of neuropathy, this veno-arteriolar reflex was absent, indicating dysfunction of the peripheral sympathetic adrenergic nerve fibres. The three patients also showed a lesser degree......The peripheral sympathetic vasomotor nerve function was investigated in 18 male chronic alcoholics admitted for intellectual impairment or polyneuropathy. By means of the local 133Xenon washout technique, the sympathetic veno-arteriolar axon-reflex was studied. This normally is responsible for a 50...... comprise not only the peripheral sensory and motor nerve fibres, but also the thin pseudomotor and vasomotor nerves....

  13. Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats

    International Nuclear Information System (INIS)

    Pereira, Susana P.; Pereira, Gonçalo C.; Pereira, Cláudia V.; Carvalho, Filipa S.; Cordeiro, Marília H.; Mota, Paula C.; Ramalho-Santos, João; Moreno, António J.; Oliveira, Paulo J.

    2013-01-01

    The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure. -- Highlights: •Acute TCDD treatment of Wistar rats causes cardiac oxidative stress. •Acute TCDD treatment causes cardiac mitochondrial alterations. •Mitochondrial liver vs. heart alterations are distinct. •TCDD treatment resulted in altered activity of cardiac mitochondrial K-ATP channels. -- Dioxin alters the regulation of cardiac mitochondrial ATP-sensitive potassium channels and disturbs mitochondrial physiology

  14. RAGE-dependent activation of gene expression of superoxide dismutase and vanins by AGE-rich extracts in mice cardiac tissue and murine cardiac fibroblasts.

    Science.gov (United States)

    Leuner, Beatrice; Ruhs, Stefanie; Brömme, Hans-Jürgen; Bierhaus, Angelika; Sel, Saadettin; Silber, Rolf-Edgar; Somoza, Veronika; Simm, Andreas; Nass, Norbert

    2012-10-01

    Advanced glycation end products (AGEs) are stable compounds formed from initial Maillard reaction products. They are considered as markers for ageing and often associated with age-related, degenerative diseases. Bread crust represents an established model for nutritional compounds rich in AGEs and is able to induce antioxidative defense genes such as superoxide dismutases and vanins in cardiac cells. The aim of this study was to investigate to what extend the receptor for AGEs (RAGE) contributes to this response. Signal transduction in response to bread crust extract was analysed in cardiac fibroblasts derived from C57/B6-NCrl (RAGE +/+) and the corresponding RAGE-knock out C57/B6-NCrl mouse strain (RAGE -/-). Activation of superoxide dismutases in animals was then analysed upon bread crust feeding in these two mice strains. Cardiac fibroblasts from RAGE -/- mice did not express RAGE, but the expression of AGER-1 and AGER-3 was up-regulated, whereas the expression of SR-B1 was down-regulated. RAGE -/- cells were less sensitive to BCE in terms of MAP-kinase phosphorylation and NF-κB reporter gene activation. Bread crust extract induced mRNA levels of MnSOD and Vnn-1 were also reduced in RAGE -/- cells, whereas Vnn-3 mRNA accumulation seemed to be RAGE receptor independent. In bread crust feeding experiments, RAGE -/- mice did not exhibit an activation of MnSOD-mRNA and -protein accumulation as observed for the RAGE +/+ animals. In conclusion, RAGE was clearly a major factor for the induction of antioxidant defense signals derived from bread crust in cardiac fibroblast and mice. Nevertheless higher doses of bread crust extract could overcome the RAGE dependency in cell cultures, indicating that additional mechanisms are involved in BCE-mediated activation of SOD and vanin expression.

  15. Noninvasive imaging of three-dimensional cardiac activation sequence during pacing and ventricular tachycardia.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; He, Bin

    2011-08-01

    Imaging cardiac excitation within ventricular myocardium is important in the treatment of cardiac arrhythmias and might help improve our understanding of arrhythmia mechanisms. This study sought to rigorously assess the imaging performance of a 3-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of 3D intracardiac mapping from up to 216 intramural sites during paced rhythm and norepinephrine (NE)-induced ventricular tachycardia (VT) in the rabbit heart. Body surface potentials and intramural bipolar electrical recordings were simultaneously measured in a closed-chest condition in 13 healthy rabbits. Single-site pacing and dual-site pacing were performed from ventricular walls and septum. VTs and premature ventricular complexes (PVCs) were induced by intravenous NE. Computed tomography images were obtained to construct geometry models. The noninvasively imaged activation sequence correlated well with invasively measured counterpart, with a correlation coefficient of 0.72 ± 0.04, and a relative error of 0.30 ± 0.02 averaged over 520 paced beats as well as 73 NE-induced PVCs and VT beats. All PVCs and VT beats initiated in the subendocardium by a nonreentrant mechanism. The averaged distance from the imaged site of initial activation to the pacing site or site of arrhythmias determined from intracardiac mapping was ∼5 mm. For dual-site pacing, the double origins were identified when they were located at contralateral sides of ventricles or at the lateral wall and the apex. 3DCEI can noninvasively delineate important features of focal or multifocal ventricular excitation. It offers the potential to aid in localizing the origins and imaging activation sequences of ventricular arrhythmias, and to provide noninvasive assessment of the underlying arrhythmia mechanisms. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  16. Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

    Science.gov (United States)

    Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

    2010-09-01

    Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

  17. Left cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia

    NARCIS (Netherlands)

    Wilde, Arthur A. M.; Bhuiyan, Zahurul A.; Crotti, Lia; Facchini, Mario; de Ferrari, Gaetano M.; Paul, Thomas; Ferrandi, Chiara; Koolbergen, Dave R.; Odero, Attilio; Schwartz, Peter J.

    2008-01-01

    Catecholaminergic polymorphic ventricular tachycardia is a potentially lethal disease characterized by adrenergically mediated ventricular arrhythmias manifested especially in children and teenagers. Beta-blockers are the cornerstone of therapy, but some patients do not have a complete response to

  18. Clonidine, an alpha2-receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Philbin, Kerry E; Bateman, Ryan J; Mendelowitz, David

    2010-08-06

    In hypertension, there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Presympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these presympathetic neurons are catecholaminergic. In addition to their projection to the spinal cord, many of these presympathetic neurons have axon collaterals that arborize into neighboring cardiorespiratory locations and likely release norepinephrine onto nearby neurons. Activation of alpha(2)-adrenergic receptors in the central nervous system evokes a diverse range of physiological effects, including reducing blood pressure. This study tests whether clonidine, an alpha(2)-adrenergic receptor agonist, alters excitatory glutamatergic, and/or inhibitory GABAergic or glycinergic synaptic neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Cardiac vagal neurons were identified in an in vitro brainstem slice preparation, and synaptic events were recording using whole cell voltage clamp methodologies. Clonidine significantly inhibited GABAergic neurotransmission but had no effect on glycinergic or glutamatergic pathways to cardiac vagal neurons. This diminished inhibitory GABAergic neurotransmission to cardiac vagal neurons would increase parasympathetic activity to the heart, decreasing heart rate and blood pressure. The results presented here provide a cellular substrate for the clinical use of clonidine as a treatment for hypertension as well as a role in alleviating posttraumatic stress disorder by evoking an increase in parasympathetic cardiac vagal activity, and a decrease in heart rate and blood pressure. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Objectively measured daily physical activity related to cardiac size in young children

    DEFF Research Database (Denmark)

    Dencker, M; Thorsson, O; Karlsson, M K

    2009-01-01

    Training studies in children have suggested that endurance training can give enlargement of cardiac dimensions. This relationship has not been studied on a population-based level in young children with objective methods. A cross-sectional study was made of 248 children (140 boys and 108 girls...... activity per day (VPA) was calculated. Acceptable accelerometer and echocardiography measurements were obtained in 228 children (boys=127, girls=101). Univariate correlations between VPA and LVDD were indexed for BSA in boys (r=0.27, Pgirls (r=0.10, NS). Multiple regression analysis showed...

  20. Cardiac-specific overexpression of insulin-like growth factor I (IGF-1) rescues lipopolysaccharide-induced cardiac dysfunction and activation of stress signaling in murine cardiomyocytes.

    Science.gov (United States)

    Zhao, Peng; Turdi, Subat; Dong, Feng; Xiao, Xiaoyan; Su, Guohai; Zhu, Xinglei; Scott, Glenda I; Ren, Jun

    2009-07-01

    Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, plays a key role in cardiac dysfunction in sepsis. Low circulating levels of insulin-like growth factor 1 (IGF-1) are found in sepsis, although the influence of IGF-1 on septic cardiac defect is unknown. This study was designed to examine the impact of IGF-1 on LPS-induced cardiac contractile and intracellular Ca2+ dysfunction, activation of stress signal and endoplasmic reticulum (ER) stress. Mechanical and intracellular Ca2+ properties were examined in cardiomyocytes from Fast Violet B and cardiac-specific IGF-1 overexpression mice treated with or without LPS (4 mg kg(-1), 6 h). Reactive oxygen species (ROS), protein carbonyl formation and apoptosis were measured. Activation of mitogen-activated protein kinase pathways (p38, c-jun N-terminal kinase [JNK] and extracellular signal-related kinase [ERK]), ER stress and apoptotic markers were evaluated using Western blot analysis. Our results revealed decreased peak shortening and maximal velocity of shortening/relengthening and prolonged duration of relengthening in LPS-treated Fast Violet B cardiomyocytes associated with reduced intracellular Ca2+ decay. Accumulation of ROS protein carbonyl and apoptosis were elevated after LPS treatment. Western blot analysis revealed activated p38 and JNK, up-regulated Bax, and the ER stress markers GRP78 and Gadd153 in LPS-treated mouse hearts without any change in ERK and Bcl-2. Total protein expression of p38, JNK, and ERK was unaffected by either LPS or IGF-1. Interestingly, these LPS-induced changes in mechanical and intracellular Ca2+ properties, ROS, protein carbonyl, apoptosis, stress signal activation, and ER stress markers were effectively ablated by IGF-1. In vitro LPS exposure (1 microg mL(-1)) produced cardiomyocyte mechanical dysfunction reminiscent of the in vivo setting, which was alleviated by exogenous IGF-1 (50 nM). These data collectively suggested a beneficial of IGF-1 in

  1. Older Adults' Music Listening Preferences to Support Physical Activity Following Cardiac Rehabilitation.

    Science.gov (United States)

    Clark, Imogen N; Baker, Felicity A; Taylor, Nicholas F

    2016-01-01

    Music listening during exercise is thought to increase physiological arousal and enhance subjective experience, and may support physical activity participation among older adults with cardiac disease. However, little is known about how music preferences, or perceptions of music during exercise, inform clinical practice with this population. Identify predominant musical characteristics of preferred music selected by older adults, and explore participants' music listening experiences during walking-based exercise following cardiac rehabilitation. Twenty-seven participants aged 60 years and older (21 men, 6 women; mean age = 67.3 years) selected music to support walking over a 6-month intervention period, and participated in post-intervention interviews. In this two-phase study, we first identified predominant characteristics of participant-selected music using the Structural Model of Music Analysis. Second, we used inductive thematic analysis to explore participant experiences. Predominant characteristics of participant-selected music included duple meter, consistent rhythm, major key, rounded melodic shape, legato articulation, predictable harmonies, variable volume, and episodes of tension with delayed resolution. There was no predominant tempo, with music selections ranging from slow through to medium and fast. Four themes emerged from thematic analysis of participant interviews: psycho-emotional responses, physical responses, influence on exercise behavior, and negative experiences. Findings are consistent with theory and research explaining influences from music listening on physiological arousal and subjective experience during exercise. Additionally, for older adults with cardiac disease, a holistic approach to music selection considering general well-being and adjustment issues, rather than just exercise performance, may improve long-term lifestyle changes and compliance with physical activity guidelines. © the American Music Therapy Association 2016. All

  2. Factitious lymphoedema as a psychiatric condition mimicking reflex sympathetic dystrophy: a case report

    Directory of Open Access Journals (Sweden)

    Nwaejike Nnamdi

    2008-06-01

    Full Text Available Abstract Introduction Reflex sympathetic dystrophy can result in severe disability with only one in five patients able to fully resume prior activities. Therefore, it is important to diagnose this condition early and begin appropriate treatment. Factitious lymphoedema can mimic reflex sympathetic dystrophy and is caused by self-inflicted tourniquets, blows to the arm or repeated skin irritation. Patients with factitious lymphoedema have an underlying psychiatric disorder but usually present to emergency or orthopaedics departments. Factitious lymphoedema can then be misdiagnosed as reflex sympathetic dystrophy. The treatment for factitious lymphoedema is dealing with the underlying psychiatric condition. Case presentation We share our experience of treating a 33-year-old man, who presented with factitious lymphoedema, initially diagnosed as reflex sympathetic dystrophy. Conclusion Awareness of this very similar differential diagnosis allows early appropriate treatment to be administered.

  3. The biophysics of renal sympathetic denervation using radiofrequency energy.

    Science.gov (United States)

    Patel, Hitesh C; Dhillon, Paramdeep S; Mahfoud, Felix; Lindsay, Alistair C; Hayward, Carl; Ernst, Sabine; Lyon, Alexander R; Rosen, Stuart D; di Mario, Carlo

    2014-05-01

    Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radiofrequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter's active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

  4. Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism

    DEFF Research Database (Denmark)

    Vagn Nielsen, H; Hasselström, K; Feldt-Rasmussen, U

    1987-01-01

    vasoconstriction normally seen after lowering the forearm 40 cm below heart level was absent since SBF only decreased by 4% (+/- 7%, P greater than 0.1) during these conditions. In head-up vertical position we noticed a diminished baroreceptor response as SBF at heart level was reduced by 11% (+/- 7%, P greater...... than 0.1) compared to supine position. After proximal local anaesthesia SBF increased by 351% (+/- 81%, P less than 0.01) and disclosed a normal vasoconstrictor response as SBF was reduced by 53% (+/- 5%, P less than 0.01) during arm lowering. Five of the treated patients were restudied.......02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment....

  5. Cardiac glycoside activities link Na(+)/K(+) ATPase ion-transport to breast cancer cell migration via correlative SAR.

    Science.gov (United States)

    Magpusao, Anniefer N; Omolloh, George; Johnson, Joshua; Gascón, José; Peczuh, Mark W; Fenteany, Gabriel

    2015-02-20

    The cardiac glycosides ouabain and digitoxin, established Na(+)/K(+) ATPase inhibitors, were found to inhibit MDA-MB-231 breast cancer cell migration through an unbiased chemical genetics screen for cell motility. The Na(+)/K(+) ATPase acts both as an ion-transporter and as a receptor for cardiac glycosides. To delineate which function is related to breast cancer cell migration, structure-activity relationship (SAR) profiles of cardiac glycosides were established at the cellular (cell migration inhibition), molecular (Na(+)/K(+) ATPase inhibition), and atomic (computational docking) levels. The SAR of cardiac glycosides and their analogs revealed a similar profile, a decrease in potency when the parent cardiac glycoside structure was modified, for each activity investigated. Since assays were done at the cellular, molecular, and atomic levels, correlation of SAR profiles across these multiple assays established links between cellular activity and specific protein-small molecule interactions. The observed antimigratory effects in breast cancer cells are directly related to the inhibition of Na(+)/K(+) transport. Specifically, the orientation of cardiac glycosides at the putative cation permeation path formed by transmembrane helices αM1-M6 correlates with the Na(+) pump activity and cell migration. Other Na(+)/K(+) ATPase inhibitors that are structurally distinct from cardiac glycosides also exhibit antimigratory activity, corroborating the conclusion that the antiport function of Na(+)/K(+) ATPase and not the receptor function is important for supporting the motility of MDA-MB-231 breast cancer cells. Correlative SAR can establish new relationships between specific biochemical functions and higher-level cellular processes, particularly for proteins with multiple functions and small molecules with unknown or various modes of action.

  6. Is it time for cardiac innervation imaging?

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, J. [Turku Univ., Turku (Finland) Turku PET Center; Sipola, P. [Kuopio Univ., Kuopio (Finland)

    2005-03-01

    The autonomic nervous system plays an important role in the regulation of cardiac function and the regional distribution of cardiac nerve terminals can be visualized using scintigraphic techniques. The most commonly used tracer is iodine-123-metaiodobenzylguanidine (MIBG) but C-11-hydroxyephedrine has also been used with PET. When imaging with MIBG, the ratio of heart-to-mediastinal counts is used as an index of tracer uptake, and regional distribution is also assessed from tomographic images. The rate of clearance of the tracer can also be measured and indicates the function of the adrenergic system. Innervation imaging has been applied in patients with susceptibility to arrythmias, coronary artery disease, hypertrophic and dilated cardiomyopathy and anthracycline induced cardiotoxicity. Abnormal adrenergic innervation or function appear to exist in many pathophysiological conditions indicating that sympathetic neurons are very susceptible to damage. Abnormal findings in innervation imaging also appear to have significant prognostic value especially in patients with cardiomyopathy. Recently, it has also been shown that innervation imaging can monitor drug-induced changes in cardiac adrenergic activity. Although innervation imaging holds great promise for clinical use, the method has not received wider clinical acceptance. Larger randomized studies are required to confirm the value of innervation imaging in various specific indications.

  7. The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

    Science.gov (United States)

    Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

    2013-08-01

    The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

  8. Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    2008-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

  9. Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

    Science.gov (United States)

    Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

    1999-01-01

    We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

  10. Exercise improves cardiac autonomic function in obesity and diabetes.

    Science.gov (United States)

    Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

    2013-05-01

    Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. The effect of space microgravity on the physiological activity of mammalian resident cardiac stem cells

    Science.gov (United States)

    Belostotskaya, Galina; Zakharov, Eugeny

    Prolonged exposure to weightlessness during space flights is known to cause depression of heart function in mammals. The decrease in heart weight and its remodeling under the influence of prolonged weightlessness (or space microgravity) is assumed to be due to both morphological changes of working cardiomyocytes and their progressive loss, as well as to possible depletion of resident cardiac stem cells (CSCs) population, or their inability to self-renewal and regeneration of muscle tissue under conditions of weightlessness. We have previously shown that the presence of different maturity clones formed by resident CSCs not only in culture but also in the mammalian myocardium can be used as an indicator of the regenerative activity of myocardial cells [Belostotskaya, et al., 2013: 2014]. In this study, we were interested to investigate whether the 30-day near-Earth space flight on the spacecraft BION-M1 affects the regenerative potential of resident CSCs. Immediately after landing of the spacecraft, we had examined the presence of resident c-kit+, Sca-1+ and Isl1+ CSCs and their development in suspension of freshly isolated myocardial cells of C57BL mice in comparison to controls. Cardiac cell suspension was obtained by enzymatic digestion of the heart [Belostotskaya and Golovanova, 2014]. Immunocytochemically stained preparations of fixed cells were analyzed with confocal microscope Leica TCS SP5 (Germany) in the Resource Center of St-Petersburg State University. CSCs were labeled with appropriate antibodies. CSCs differentiation into mature cardiomyocytes was verified using antibodies to Sarcomeric α-Actinin and Cardiac Troponin T. Antibodies to Connexin43 were used to detect cell-cell contacts. All antibodies were conjugated with Alexa fluorochromes (488, 532, 546, 568, 594 and/or 647 nm), according to Zenon-technology (Invitrogen). It has been shown that, under identical conditions of cell isolation, more complete digestion of heart muscle was observed in

  12. Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity.

    Science.gov (United States)

    Leifheit-Nestler, Maren; Wagner, Nana-Maria; Gogiraju, Rajinikanth; Didié, Michael; Konstantinides, Stavros; Hasenfuss, Gerd; Schäfer, Katrin

    2013-07-11

    The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels. The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepRdb/db) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepRS1138) were also analyzed. Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepRS1138 animals. LepRS1138 mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepRdb/db and LepRS1138 mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis. Our findings suggest that hearts from obese mice

  13. NEWBORNS OF HIGH RISK GROUPS AND ELECTROPHYSIOLOGICAL CARDIAC ACTIVITY DURING THE PERIOD OF EARLY ADAPTATION

    Directory of Open Access Journals (Sweden)

    T. S. Tumaeva

    2014-01-01

    Full Text Available Aim: to study characteristics of electrophysiological cardiac activity in children of risk groups and to assess possibilities of Holter-electrocardiography (H-ECG in revealing of cardiac dysfunction during the period of early adaptation. Patients and methods: 250 newborns were examined. The main group consisted of 200 children with cerebral ischemia (CI. This group was divided into 2 subgroups: 100 full-term and 100 premature (at various gestation age infants. Control group contained 50 children born at 38–40th weeks of gestation with physiological course of pregnancy and delivery, APGAR score of 8–9 points. Complex examination included H-ECG according the standard technic with evaluation of the hearth rate (HR during sleep and wakefulness; HRmin, HRmax; arrhythmias, conductivity disorders, duration of the intervals; rhythm variability. Results: according to the ECG children with CI, especially premature ones, and children delivered via Cesarean section more often had ST-T disturbances, arrhythmias (sinus tachycardia, less often — sinus bradycardia and conductivity disorders, Q-Tc prolongation. H-EGC revealed decrease of sleep HR, HRmin and HRmax in children with CI especially in delivered via Cesarean section. The most common arrhythmia was supraventricular extrasystole.  Pauses in rhythms and variability were the highest in premature children delivered via Cesarean section. Conclusions: hypoxia/ischemia is a trigger for development of cardiovascular dysfuncion in newborns. Premature and children delivered via Cesarean section form a group of high risk. H-ECG widens possibilities of revealing of symptoms of cardiac dysfunction (disturbances at the basal level of functioning, of adaptation resources of the sinus node, electric instability of the myocardium and heart rate variability in children of risk group for development of cardiovascular disorders. 

  14. Repetitive Transient Ischemia-Induced Cardiac Angiogenesis is Mediated by Camkii Activation

    Directory of Open Access Journals (Sweden)

    Zhuobin Chen

    2018-05-01

    Full Text Available Background/Aims: Coronary angiogenesis is an important protective mechanism in response to myocardial ischemia in coronary artery disease. However, the underlying mechanisms remain largely unclear. Here, we investigated the role of CaMKII activation in ischemia-induced cardiac angiogenesis. Methods: Repetitive transient ischemia model was established in C57/BL6 mice by daily multiple episodes (3 times/day of short time (5 min occlusion of the left anterior descending coronary artery for 7 days. Coronary angiogenesis was detected by immunofluorescent staining. RT-qPCR and Western blot analyses were used to detect the mRNA and protein levels of CaMKII, p-CaMKII and VEGF. Primary cardiac microvascular endothelial cells (CMECs were isolated to investigate the effects of KN93 on cell proliferation and migration in hypoxic condition. Results: We found that angiogenesis was induced in the ischemic myocardium and suppressed by chronic intraperitoneal injection of CaMKII inhibitor KN93. RT-qPCR and Western blot analyses showed that myocardial ischemia induced an increased expression and autophosphorylation of CaMKII. VEGF expression was increased in the ischemia model but blunted by KN93. Moreover, KN93 suppressed the proliferation and migration of cardiac endothelial cells in hypoxic condition in which the protein expression of CaMKII, p-CaMKII and VEGF was increased. Conclusion: CaMKII is an important mediator for the ischemia-induced coronary angiogenesis, in which CaMKII-triggered VEGF expression plays a key role.

  15. Activation of protein kinase C alters the intracellular distribution and mobility of cardiac Na+ channels.

    Science.gov (United States)

    Hallaq, Haifa; Wang, Dao W; Kunic, Jennifer D; George, Alfred L; Wells, K Sam; Murray, Katherine T

    2012-02-01

    Na(+) current derived from expression of the cardiac isoform SCN5A is reduced by receptor-mediated or direct activation of protein kinase C (PKC). Previous work has suggested a possible role for loss of Na(+) channels at the plasma membrane in this effect, but the results are controversial. In this study, we tested the hypothesis that PKC activation acutely modulates the intracellular distribution of SCN5A channels and that this effect can be visualized in living cells. In human embryonic kidney cells that stably expressed SCN5A with green fluorescent protein (GFP) fused to the channel COOH-terminus (SCN5A-GFP), Na(+) currents were suppressed by an exposure to PKC activation. Using confocal microscopy, colocalization of SCN5A-GFP channels with the plasma membrane under control and stimulated conditions was quantified. A separate population of SCN5A channels containing an extracellular epitope was immunolabeled to permit temporally stable labeling of the plasma membrane. Our results demonstrated that Na(+) channels were preferentially trafficked away from the plasma membrane by PKC activation, with a major contribution by Ca(2+)-sensitive or conventional PKC isoforms, whereas stimulation of protein kinase A (PKA) had the opposite effect. Removal of the conserved PKC site Ser(1503) or exposure to the NADPH oxidase inhibitor apocynin eliminated the PKC-mediated effect to alter channel trafficking, indicating that both channel phosphorylation and ROS were required. Experiments using fluorescence recovery after photobleaching demonstrated that both PKC and PKA also modified channel mobility in a manner consistent with the dynamics of channel distribution. These results demonstrate that the activation of protein kinases can acutely regulate the intracellular distribution and molecular mobility of cardiac Na(+) channels in living cells.

  16. Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease : A prospective randomized controlled study on putative involvement of sympathetic activity

    NARCIS (Netherlands)

    Jessurun, GAJ; DeJongste, MJL; Hautvast, RWM; Tio, RA; Brouwer, J; Van Lelieveld, S; Crijns, HJGM

    1999-01-01

    The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. in the

  17. Self-reported physical activity and lung function two months after cardiac surgery--a prospective cohort study.

    Science.gov (United States)

    Jonsson, Marcus; Urell, Charlotte; Emtner, Margareta; Westerdahl, Elisabeth

    2014-03-28

    Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health's national survey. Formal lung function testing was performed preoperatively and two months postoperatively. The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results.

  18. Brain renin angiotensin system in cardiac hypertrophy and failure

    Directory of Open Access Journals (Sweden)

    Luciana eCampos

    2012-01-01

    Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

  19. An efficient cardiac mapping strategy for radiofrequency catheter ablation with active learning.

    Science.gov (United States)

    Feng, Yingjing; Guo, Ziyan; Dong, Ziyang; Zhou, Xiao-Yun; Kwok, Ka-Wai; Ernst, Sabine; Lee, Su-Lin

    2017-07-01

    A major challenge in radiofrequency catheter ablation procedures is the voltage and activation mapping of the endocardium, given a limited mapping time. By learning from expert interventional electrophysiologists (operators), while also making use of an active-learning framework, guidance on performing cardiac voltage mapping can be provided to novice operators or even directly to catheter robots. A learning from demonstration (LfD) framework, based upon previous cardiac mapping procedures performed by an expert operator, in conjunction with Gaussian process (GP) model-based active learning, was developed to efficiently perform voltage mapping over right ventricles (RV). The GP model was used to output the next best mapping point, while getting updated towards the underlying voltage data pattern as more mapping points are taken. A regularized particle filter was used to keep track of the kernel hyperparameter used by GP. The travel cost of the catheter tip was incorporated to produce time-efficient mapping sequences. The proposed strategy was validated on a simulated 2D grid mapping task, with leave-one-out experiments on 25 retrospective datasets, in an RV phantom using the Stereotaxis Niobe ® remote magnetic navigation system, and on a tele-operated catheter robot. In comparison with an existing geometry-based method, regression error was reduced and was minimized at a faster rate over retrospective procedure data. A new method of catheter mapping guidance has been proposed based on LfD and active learning. The proposed method provides real-time guidance for the procedure, as well as a live evaluation of mapping sufficiency.

  20. Sympathetic neural modulation of the immune system

    International Nuclear Information System (INIS)

    Madden, K.S.

    1989-01-01

    One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of 125 iododeoxyuridine ( 125 IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated 125 IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining 51 Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function

  1. [A basis for application of cardiac contractility variability in the Evaluation and assessment of exercise and fitness].

    Science.gov (United States)

    Bu, Bin; Wang, Aihua; Han, Haijun; Xiao, Shouzhong

    2010-06-01

    Cardiac contractility variability (CCV) is a new concept which is introduced in the research field of cardiac contractility in recent years, that is to say, there are some disparities between cardiac contractilities when heart contracts. The changing signals of cardiac contractility contain a plenty of information on the cardiovascular function and disorder. In order to collect and analyze the message, we could quantitatively evaluate the tonicity and equilibrium of cardiac sympathetic nerve and parasympathetic nerve, and the effects of bio-molecular mechanism on the cardiovascular activities. By analyzing CCV, we could further understand the background of human being's heritage characteristics, nerve types, the adjusting mechanism, the molecular biology, and the adjustment of cardiac automatic nerve. With the development of the computing techniques, the digital signal processing method and its application in medical field, this analysis has been progressing greatly. By now, the assessment of CCV, just like the analysis of heart rate variability, is mainly via time domain and frequency domain analysis. CCV is one of the latest research fields in human cardiac signals being scarcely reported in the field of sports medicine; however, its research progresses are of important value for cardiac physiology and pathology in sports medicine and rehabilitation medicine.

  2. Recruitment pattern of sympathetic muscle neurons during premature ventricular contractions in heart failure patients and controls.

    Science.gov (United States)

    Maslov, Petra Zubin; Breskovic, Toni; Brewer, Danielle N; Shoemaker, J Kevin; Dujic, Zeljko

    2012-12-01

    Premature ventricular contractions (PVC) elicit larger bursts of multiunit muscle sympathetic nerve activity (MSNA), reflecting the ability to increase postganglionic axonal recruitment. We tested the hypothesis that chronic heart failure (CHF) limits the ability to recruit postganglionic sympathetic neurons as a response to PVC due to the excessive sympathetic activation in these patients. Sympathetic neurograms of sufficient signal-to-noise ratio were obtained from six CHF patients and from six similarly aged control individuals. Action potentials (APs) were extracted from the multiunit sympathetic neurograms during sinus rhythm bursts and during the post-PVC bursts. These APs were classified on the basis of the frequency per second, the content per burst, and the peak-to-peak amplitude, which formed the basis of binning the APs into active clusters. Compared with controls, CHF had higher APs per burst and higher number of active clusters per sinus rhythm burst (P < 0.05). Compared with sinus rhythm bursts, both groups increased AP frequency and the number of active clusters in the post-PVC burst (P < 0.05). However, compared with controls, the increase in burst integral, AP frequency, and APs per burst during the post-PVC burst was less in CHF patients. Nonetheless, the PVC-induced increase in active clusters per burst was similar between the groups. Thus, these CHF patients retained the ability to recruit larger APs but had a diminished ability to increase overall AP content.

  3. Effect of 3-Day Bed Rest on the Basal Sympathetic Activity and Responsiveness of this System to Physiological Stimuli In Athletes and Sedentary Subjects

    Science.gov (United States)

    Smorawinski, Jerzy; Adrian, Jacek; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Greenleaf, John E.; Dalton, P. Bonnie (Technical Monitor)

    2002-01-01

    The aims of this study were: (1) to examine the effect of three days of bed rest (BR) on basal plasma epinephrine [E] and norepinephrine [NE] and the catecholamine responses to various physiological stimuli, and (2) to find out whether previous physical activity modifies effects of BR. In the first series, 29 young men (11 sedentary students, 8 endurance and 10 strength trained athletes) were submitted to oral glucose tolerance test in supine position and to active orthostatic test before and after 3 days of BR. Plasma [E] and [NE] were measured after overnight fast (basal condition), at 60, 120 and 180 min after glucose ingestion (70 a), and at the 8th min of unsupported standing. In the second series, other 22 subjects (12 sedentary students, 10 endurance and 10 strength trained athletes) were submitted to 2 min cold pressor test (CPT) and exercise. Plasma E and NE were determined in the supine position after overnight fast and at 60th and 120th s of hand cooling. Then, after breakfast followed by 2-3 hour sitting, the subjects performed cycle ergometer exercise with workload increasing until volitional exhaustion. Plasma [E] and [NE] were determined at the end of each load. Plasma catecholamines were determined made radioenzymatically. After BR, basal plasma [NE] was decreased in endurance and strength athletes (psedentary subjects. In neither group BR affected the basal [E]. Responses of both catecholamines to glucose load were diminished after BR in all three groups (pwork intensity after than before BR (p<0.05).

  4. Sympathetic neurons modulate the beat rate of pluripotent cell-derived cardiomyocytes in vitro.

    Science.gov (United States)

    Takeuchi, Akimasa; Shimba, Kenta; Mori, Masahide; Takayama, Yuzo; Moriguchi, Hiroyuki; Kotani, Kiyoshi; Lee, Jong-Kook; Noshiro, Makoto; Jimbo, Yasuhiko

    2012-12-01

    Although stem cell-derived cardiomyocytes have great potential for the therapy of heart failure, it is unclear whether their function after grafting can be controlled by the host sympathetic nervous system, a component of the autonomic nervous system (ANS). Here we demonstrate the formation of functional connections between rat sympathetic superior cervical ganglion (SCG) neurons and pluripotent (P19.CL6) cell-derived cardiomyocytes (P19CMs) in compartmentalized co-culture, achieved using photolithographic microfabrication techniques. Formation of synapses between sympathetic neurons and P19CMs was confirmed by immunostaining with antibodies against β-3 tubulin, synapsin I and cardiac troponin-I. Changes in the beat rate of P19CMs were triggered after electrical stimulation of the co-cultured SCG neurons, and were affected by the pulse frequency of the electrical stimulation. Such changes in the beat rate were prevented when propranolol, a β-adrenoreceptor antagonist, was added to the culture medium. These results suggest that the beat rate of differentiated cardiomyocytes can be modulated by electrical stimulation of connected sympathetic neurons.

  5. Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance.

    Directory of Open Access Journals (Sweden)

    Chunhu Gu

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