Sample records for cardiac sympathetic denervation

  1. 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;


    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...... and macrophage infiltration at day 7. No denervation was detectable at day 14 of double treatment, using subcutaneous AG. Our findings favor a role for ED1+ macrophages and iNOS in the hypertension-induced denervation process....

  2. Renal sympathetic denervation prevents the development of pulmonary arterial hypertension and cardiac dysfunction in dogs. (United States)

    Hu, Wei; Yu, Sheng-Bo; Chen, Liao; Guo, Rui-Qiang; Zhao, Qing-Yan


    The renin-angiotensin-aldosterone system is activated in pulmonary arterial hypertension (PAH) patients, and this activation may have long-term negative effects on the progression of PAH. The purpose of this study was to evaluate the effects of transcatheter renal sympathetic denervation (RSD) on the development of pulmonary arterial hypertension and cardiac dysfunction in dogs using two-dimensional speckle tracking imaging. Twenty-two dogs were randomly divided into three groups: control group (n = 7), PAH group (n = 8), and PAH + RSD group (n = 7). All dogs were assessed using two-dimensional speckle tracking imaging. The ventricular strain, ventricular synchrony, left ventricular (LV) twist, and torsion rate were analyzed to evaluate cardiac function. After 8 weeks, the right ventricular lateral longitudinal strain and the septum longitudinal strain were reduced in the PAH group compared with the control group (p dogs.

  3. Effects of renal sympathetic denervation on post-myocardial infarction cardiac remodeling in rats.

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    Jialu Hu

    Full Text Available OBJECTIVE: To investigate the therapeutic effects of renal denervation (RD on post- myocardial infarction (MI cardiac remodeling in rats, the most optimal time for intervention and the sustainability of these effects. METHODS: One hundred SPF male Wistar rats were randomly assigned to N group (Normal, n=10, MI group(MI, n=20,RD group (RD, n=10, RD3+MI (MI three days after RD, n=20, MI1+RD (RD one day after MI, n=20, MI7+RD (RD seven days after MI, n=20. MI was produced through thoracotomic ligation of the anterior descending artery. RD was performed through laparotomic stripping of the renal arteriovenous adventitial sympathetic nerve. Left ventricular function, hemodynamics, plasma BNP, urine volume, urine sodium excretion and other indicators were measured four weeks after MI. RESULTS: (1 The left ventricular function of the MI group significantly declined (EF<40%, plasma BNP was elevated, urine output was significantly reduced, and 24-hour urine sodium excretion was significantly reduced. (2 Denervation can be achieved by surgically stripping the arteriovenous adventitia, approximately 3 mm from the abdominal aorta. (3 In rats with RD3+MI, MI1+RD and MI7+RD, compared with MI rats respectively, the LVEF was significantly improved (75 ± 8.4%,69 ± 3.8%,73 ± 5.5%, hemodynamic indicators were significantly improved, plasma BNP was significantly decreased, and the urine output was significantly increased (21.3 ± 5 ml,23.8 ± 5.4 ml,25.2 ± 8.7 ml. However, the urinary sodium excretion also increased but without significant difference. CONCLUSIONS: RD has preventive and therapeutic effects on post-MI cardiac remodeling.These effects can be sustained for at least four weeks, but there were no significant differences between denervation procedures performed at different times in the course of illness. Cardiac function, hemodynamics, urine volume and urine sodium excretion in normal rats were not affected by RD.

  4. Cardiac Dysregulation and Myocardial Injury in a 6-Hydroxydopamine-Induced Rat Model of Sympathetic Denervation.

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    Yue-Hua Jiang

    Full Text Available Cardiac sympathetic denervation is found in various cardiac pathologies; however, its relationship with myocardial injury has not been thoroughly investigated.Twenty-four rats were assigned to the normal control group (NC, sympathectomy control group (SC, and a sympathectomy plus mecobalamin group (SM. Sympathectomy was induced by injection of 6-OHDA, after which, the destruction and distribution of sympathetic and vagal nerve in the left ventricle (LV myocardial tissue were determined by immunofluorescence and ELISA. Heart rate variability (HRV, ECG and echocardiography, and assays for myocardial enzymes in serum before and after sympathectomy were examined. Morphologic changes in the LV by HE staining and transmission electron microscope were used to estimate levels of myocardial injury and concentrations of inflammatory cytokines were used to reflect the inflammatory reaction.Injection of 6-OHDA decreased NE (933.1 ± 179 ng/L for SC vs. 3418.1± 443.6 ng/L for NC, P < 0.01 and increased NGF (479.4± 56.5 ng/mL for SC vs. 315.85 ± 28.6 ng/mL for NC, P < 0.01 concentrations. TH expression was reduced, while ChAT expression showed no change. Sympathectomy caused decreased HRV and abnormal ECG and echocardiography results, and histopathologic examinations showed myocardial injury and increased collagen deposition as well as inflammatory cell infiltration in the cardiac tissue of rats in the SC and SM groups. However, all pathologic changes in the SM group were less severe compared to those in the SC group.Chemical sympathectomy with administration of 6-OHDA caused dysregulation of the cardiac autonomic nervous system and myocardial injuries. Mecobalamin alleviated inflammatory and myocardial damage by protecting myocardial sympathetic nerves.

  5. Role of left cardiac sympathetic denervation in the management of congenital long QT syndrome.

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    Wang L


    Full Text Available Congenital long QT syndrome (LQTS is a rare but life-threatening disorder affecting cardiac electrophysiology. It occurs due to mutation in genes encoding for the ion channels in ventricular cell membrane. Syncopal attacks and cardiac arrest are the main symptoms of the disease. Anti-adrenergic therapy with oral beta-blockers has been the mainstay of treatment for LQTS. However, up to 30% of patients fail to respond to medical therapy and remain symptomatic. An alarming 10% of patients still experience cardiac arrest or sudden cardiac death during the course of therapy. Left cardiac sympathetic denervation (LCSD has been used as an alternative therapy in patients who are resistant to beta-blockers. Although LCSD appears effective in reducing the frequency of syncopal attacks and improving the survival rate in both the short and long-term, its use has not gained popularity. The recent advent of minimally invasive thoracoscopic sympathectomy may improve the acceptance of LCSD by physicians and patients in the future. The primary objective of this article was to review the current evidence of the clinical efficacy and safety of LCSD in the management of LQTS. The review was based on Medline search of articles published between 1966 and 2002.

  6. Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability

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    Delahaye, N.; Le Guludec, D. [Department of Nuclear Medicine, Bichat Hospital, Paris (France); Dinanian, S.; Slama, M.S. [Department of Cardiology, A. Beclere Hospital, Paris (France); Mzabi, H.; Samuel, D. [Department of Hepatic Surgery, P. Brousse Hospital, Paris (France); Adams, D. [Department of Neurology, Bicetre Hospital, Paris (France); Merlet, P. [SHFJ, DSV-CEA, Orsay (France)


    Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42{+-}12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36{+-}0.26 versus 1.98{+-}0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac

  7. Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure. (United States)

    Kimura, Kensuke; Kanazawa, Hideaki; Ieda, Masaki; Kawaguchi-Manabe, Haruko; Miyake, Yoshiko; Yagi, Takashi; Arai, Takahide; Sano, Motoaki; Fukuda, Keiichi


    In severe congestive heart failure (CHF), sympathetic overactivity correlates with the exacerbation of cardiac performance. To test the hypothesis that the cardiac sympathetic nerve density dramatically changes with the acceleration of circulating norepinephrine (NE) concentration, we investigated the temporal association of nerve growth factor (NGF) expression in the heart and cardiac sympathetic nerve density during the development of CHF in the continuous NE-infused rats. The animals were analyzed at 0-, 1-, 3-, 7-, 14-, and 28-day after implantation of osmotic pump at a rate of 0.05 mg/kg/hr. The cardiac performance was temporally facilitated in NE-exposed rats at 3-day in accordance with the sympathetic hyper-innervation induced by the augmentation of NGF mRNA expression in the heart. In NE-treated rats, left ventricular end-diastolic pressure was significantly increased after 7-day and marked left ventricular hypertrophy and systemic fluid retention were observed at 28-day. CHF-induced sympathetic overactivity further increased plasma NE concentration in NE-treated rats and finally reached to 16.1+/-5.6 ng/ml at 28-day (control level was 0.39+/-0.1 ng/ml, pcardiac performance. The cardiac sympathetic fiber loss was also confirmed in NE-exposed DBH (dopamine beta-hydroxylase)-Cre/Floxed-EGFP (enhanced green fluorescent protein) mice with severe CHF, in which sympathetic nerve could be traced by EGFP. Our results suggest that the cardiac sympathetic nerve density is strictly regulated by the NGF expression in the heart and long-exposure of high plasma NE concentration caused myocardial NGF reduction, following sympathetic fiber loss in severe CHF animals.

  8. LMI1195 PET imaging in evaluation of regional cardiac sympathetic denervation and its potential role in antiarrhythmic drug treatment

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    Yu, Ming; Bozek, Jody; Lamoy, Melanie; Kagan, Mikhail; Benites, Pedro; Onthank, David; Robinson, Simon P. [Lantheus Medical Imaging, Discovery Research, N. Billerica, MA (United States)


    Regional cardiac sympathetic denervation (RCSD) associated with reduced noradrenaline transporter (NAT) function has been linked to cardiac arrhythmia. This study examined the association of LMI1195, an {sup 18}F-labeled NAT substrate developed for positron emission tomography (PET) imaging, with NAT in vitro, and its imaging to detect RCSD and guide antiarrhythmic drug treatment in vivo. LMI1195 association with NAT was assessed in comparison with other substrates, noradrenaline (NA) and {sup 123}I-metaiodobenzylguanidine (MIBG), in NAT-expressing cells. LMI1195 cardiac imaging was performed for evaluation of RCSD in a rabbit model surgically developed by regional phenol application on the left ventricular (LV) wall. The normal LV areas in images were quantified as regions with radioactivity {>=}50 % maximum. Potential impact of RCSD on dofetilide, an antiarrhythmic drug, induced ECG changes was assessed. NAT blockade with desipramine reduced LMI1195 cell uptake by 90 {+-} 3 %, similar to NA and MIBG. NA, MIBG, or self inhibited LMI1195 cell uptake concentration-dependently with comparable IC{sub 50} values (1.09, 0.21, and 0.90 {mu}M). LMI1195 cardiac imaging differentiated innervated and denervated areas in RCSD rabbits. The surgery resulted in a large denervated LV area at 2 weeks which was partially recovered at 12 weeks. Myocardial perfusion imaging with flurpiridaz F 18 showed normal perfusion in RCSD areas. Dofetilide induced more prominent QTc prolongation in RCSD than control animals. However, changes in heart rate were comparable. LMI1195 exhibits high association with NAT and can be used for imaging RCSD. The detected RCSD increases cardiac risks to the antiarrhythmic drug, dofetilide, by inducing more QTc prolongation. (orig.)

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

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    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)


    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

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

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    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)


    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

  11. Neurohumoral indicators of efficacy radiofrequency cardiac denervation

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    Evtushenko, A. V., E-mail:; Evtushenko, V. V. [National Research Tomsk State University, Tomsk (Russian Federation); Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Saushkina, Yu. V.; Gusakova, A. M.; Suslova, T. E.; Dymbrylova, O. N.; Smyshlyaev, K. A.; Kurlov, I. O. [Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Lishmanov, Yu. B.; Anfinogenova, Ya. D. [National Research Tomsk Polytechnic University, Tomsk (Russian Federation); Federal State Budgetary Scientific Institution “Research Institute for Cardiology”, Tomsk (Russian Federation); Sergeevichev, D. S. [Academician E.N. Meshalkin State Research Institute of Circulation Pathology, Novosibirsk (Russian Federation); Bykov, A. N.; Syryamkin, V. I.; Kistenev, Yu. V. [National Research Tomsk State University, Tomsk (Russian Federation); Lotkov, A. I. [Institute of Strength Physics and Materials Science of the Siberian Branch of the RAS, Tomsk (Russian Federation); Pokushalov, E. A.


    In this study, we compared pre- and postoperative parameters of the cardiac sympathetic innervation. The aim of the study was to examine the approaches to evaluating the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive and laboratory methods. The study included 32 people with long-lasting persistent atrial fibrillation (AF). The patients were divided into 2 groups according to the objectives of the study: group 1 (main) - 21 patients with mitral valve diseases, which simultaneously with radiofrequency ablation (RFA) AF carried out on the effects of the paraganglionic nervous plexuses by C. Pappone (2004) and N. Doll (2008) schemes. The second group (control) contained 11 patients with heart diseases in sinus rhythm (the RF denervation not been performed). All patients, who underwent surgical treatment, were received examination of cardiac sympathetic tone by using {sup 123}I-MIBG. All of them made blood analysis from ascending aorta and coronary sinus to determine the level of norepinephrine and its metabolites before and after cardiac denervation. Data of radionuclide examination are correlating with laboratory data.

  12. Neurohumoral indicators of efficacy radiofrequency cardiac denervation (United States)

    Evtushenko, A. V.; Evtushenko, V. V.; Saushkina, Yu. V.; Lishmanov, Yu. B.; Pokushalov, E. A.; Sergeevichev, D. S.; Gusakova, A. M.; Suslova, T. E.; Dymbrylova, O. N.; Bykov, A. N.; Syryamkin, V. I.; Kistenev, Yu. V.; Anfinogenova, Ya. D.; Smyshlyaev, K. A.; Lotkov, A. I.; Kurlov, I. O.


    In this study, we compared pre- and postoperative parameters of the cardiac sympathetic innervation. The aim of the study was to examine the approaches to evaluating the quality of radiofrequency (RF)-induced cardiac denervation by using non-invasive and laboratory methods. The study included 32 people with long-lasting persistent atrial fibrillation (AF). The patients were divided into 2 groups according to the objectives of the study: group 1 (main) - 21 patients with mitral valve diseases, which simultaneously with radiofrequency ablation (RFA) AF carried out on the effects of the paraganglionic nervous plexuses by C. Pappone (2004) and N. Doll (2008) schemes. The second group (control) contained 11 patients with heart diseases in sinus rhythm (the RF denervation not been performed). All patients, who underwent surgical treatment, were received examination of cardiac sympathetic tone by using 123I-MIBG. All of them made blood analysis from ascending aorta and coronary sinus to determine the level of norepinephrine and its metabolites before and after cardiac denervation. Data of radionuclide examination are correlating with laboratory data.

  13. 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))


    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.

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

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    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)


    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.)

  15. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    LENUS (Irish Health Repository)

    Hutchinson, Barry D


    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  16. Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence. (United States)

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


    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.

  17. Cardiorenal axis and arrhythmias: Will renal sympathetic denervation provide additive value to the therapeutic arsenal? (United States)

    van Brussel, Peter M; Lieve, Krystien V V; de Winter, Robbert J; Wilde, Arthur A M


    Disruption of sympathetic tone may result in the occurrence or maintenance of cardiac arrhythmias. Multiple arrhythmic therapies that intervene by influencing cardiac sympathetic tone are common in clinical practice. These vary from pharmaceutical (β-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists) to percutaneous/surgical (cardiac sympathetic denervation) interventions. In some patients, however, these therapies have insufficient prophylactic and therapeutic capabilities. A safe and effective additional therapy wherein sympathetic drive is further attenuated would be expedient. Recently, renal sympathetic denervation (RSD) has been subject of research for various sympathetic nervous system-related diseases. By its presumed afferent and efferent sympatholytic effects, RSD might indirectly attenuate sympathetic outflow via the brain to the heart but might also reduce systemic catecholamine excretion and might therefore reduce catecholamine-sensitive arrhythmias. RSD is subject of research for various sympathetically driven arrhythmias, both supraventricular and ventricular. In this review, we give an overview of the rationale behind RSD as potential therapy in mediating arrhythmias that are triggered by a disrupted sympathetic nervous system and discuss the presently available results from animal and human studies.

  18. Regional sympathetic denervation after myocardial infarction: a follow-up study using [123I]MIBG. (United States)

    Podio, V; Spinnler, M T; Spandonari, T; Moretti, C; Castellano, G; Bessone, M; Brusca, A


    Previous studies in dogs have shown that experimental infarction produces myocardial sympathetic denervation not only in the infarcted area, but also in a region apical to the infarction. In these dogs MIBG myocardial scintigraphy detected denervation but returned to normal in a few months at which time reinnervation was shown to have occurred. Myocardial sympathetic denervation was studied with MIBG scintigraphy in ten patients after their first acute transmural myocardial infarction; scans were repeated at 4 months, one year and 30 months to follow the time course of possible reinnervation. Except during the first 48 hours following the infarction, no therapy except for antiaggregants was administered to the patients; during this follow-up period no cardiac events were seen. One week after infarction, comparison of MIBG images with perfusion scans revealed that the denervated area was larger than the infarcted area; no difference in MIBG uptake by the infarcted myocardium was found during the 30 months follow-up.

  19. Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart. (United States)

    Patrick, Casey B; McHowat, Jane; Rosenberger, Thad A; Rapoport, Stanley I; Murphy, Eric J


    Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 muCi/kg of either [1-(14)C]palmitic acid ([1-(14)C]16:0) or [1-(14)C]arachidonic acid ([1-(14)C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient lambda was increased in [1-(14)C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-(14)C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-(14)C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60-84%) and turnover value (56-85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A(2) activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A(2) activity.

  20. A Case Report of Renal Sympathetic Denervation for the Treatment of Polymorphic Ventricular Premature Complexes (United States)

    Kiuchi, Márcio Galindo; Vitorio, Frederico Puppim; da Silva, Gustavo Ramalho; Paz, Luis Marcelo Rodrigues; Souto, Gladyston Luiz Lima


    Abstract Premature ventricular complexes are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Recently, Armaganijan et al reported the relevance of sympathetic activation in patients with ventricular arrhythmias and suggested a potential role for catheter-based renal sympathetic denervation in reducing the arrhythmic burden. In this report, we describe a 32-year-old hypertensive male patient presenting with a high incidence of polymorphic premature ventricular complexes on a 24 hour Holter monitor. Beginning 1 year prior, the patient experienced episodes of presyncope, syncope, and tachycardia palpitations. The patient was taking losartan 100 mg/day, which kept his blood pressure (BP) under control, and sotalol 160 mg twice daily. Bisoprolol 10 mg/day was used previously but was not successful for controlling the episodes. The 24 hour Holter performed after the onset of sotalol 160 mg twice daily showed a heart rate ranging between 48 (minimum)–78 (average)–119 (maximum) bpm; 14,286 polymorphic premature ventricular complexes; 3 episodes of nonsustained ventricular tachycardia, the largest composed of 4 beats at a rate of 197 bpm; and 14 isolated atrial ectopic beats. Cardiac magnetic resonance imaging with gadolinium perfusion performed at rest and under pharmacological stress with dipyridamole showed increased left atrial internal volume, preserved systolic global biventricular function, and an absence of infarcted or ischemic areas. The patient underwent bilateral renal sympathetic denervation. The only drug used postprocedure was losartan 25 mg/day. Three months after the patient underwent renal sympathetic denervation, the mean BP value dropped to 132/86 mmHg, the mean systolic/diastolic 24 hour ambulatory BP measurement was reduced to 128/83

  1. Local Sympathetic Denervation of Femoral Artery in a Rabbit Model by Using 6-Hydroxydopamine In Situ

    Directory of Open Access Journals (Sweden)

    Yufei Jin


    Full Text Available Both artery bundle and sympathetic nerve were involved with the metabolism of bone tissues. Whether the enhancing effects of artery bundle result from its accompanying sympathetic nerve or blood supply is still unknown. There is no ideal sympathetic nerve-inhibited method for the in situ denervation of artery bundle. Therefore, we dipped the femoral artery in the 6-hydroxydopamine (6-OHDA locally and observed its effect. Compared with control group, the in situ treatment of 6-OHDA did not damage the normal structure of vascular bundle indicated by hematoxylin-eosin (HE staining. However, the functions of sympathetic nerve was completely inhibited for more than 2 weeks, and only a few function of sympathetic nerve resumed 4 weeks later, evidenced by glyoxylic acid staining and the expression of tyrosine hydroxylase (TH and nerve peptide Y (NPY. Thus, 6-OHDA is promising as an ideal reagent for the local denervation of sympathetic nerve from artery system.

  2. Renal sympathetic nervous system and the effects of denervation on renal arteries

    Institute of Scientific and Technical Information of China (English)

    Arun; Kannan; Raul; Ivan; Medina; Nagapradeep; Nagajothi; Saravanan; Balamuthusamy


    Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal-as well as systemic-level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements.Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.

  3. 肾交感神经去除术对心力衰竭犬心功能的影响%Influence of renal sympathetic denervation on cardiac function of dogs with heart failure

    Institute of Scientific and Technical Information of China (English)

    黄达民; 侯舒心; 罗晓菡; 张金春; 卢英民


    Objective:To study influence of renal sympathetic denervation (RDN)on cardiac function of dogs with heart failure (HF).Methods:A total of 40 dogs were randomly and equally divided into RDN group [received bilat- eral renal artery radiofrequency ablation (RFA)]and model group (only received femoral puncture).Pacemaker was implanted in every dog,and dog HF model was established using rapid right ventricular pacing.Cardiac and re-nal function indexes,BNP and sympathetic activity index levels were observed and compared between two groups be- fore RFA/sham operation,instant and four weeks after model establishment.Results:After operation four weeks, compared with model group,there were significant reductions in levels of epinephrine (E)[(362.69±42.54)ng/ml vs.(290.36±42.32)ng/ml],renin (R)[(305.46± 39.68)ng/ml vs.(230.04±32.80)ng/ml],aldosterone (AD)[(408.00±38.56)ng/ml vs.(246.00± 48.37)ng/ml],angiotensin Ⅱ (ATⅡ)[(280.00±48.08)pg/ml vs.(172.00±25.04)pg/ml]and norepinephrine (NE)[(425.65±50.54)ng/ml vs.(316.76±46.29)ng/ml]in RDN group (P<0.05 all);there were significant reductions in HR,respiratory rate (RR)and BNP level in RDN group,P<0.05 all;there were significant rise in SBP,LVEF,CO,CI,left ventricular pressure maximal rising rate (+dp/dtmax),left ventricular pressure maximal dropping rate (-dp/dtmax)and left ventricular end-systolic pressure (LVESP),and significant reductions in left ventricular end-systolic dimension (LVESd),left ventricular end-diastolic dimension (LVEDd)and left ventricular end-diastolic pressure (LVEDP)in RDN group,P<0.05 all.Conclusion:RDN can decrease renal sympathetic activity,improve heart function,inhibit myocardial remode- ling,its therapeutic effect is significant%目的:研究肾交感神经去除术(RDN)对心力衰竭(HF)犬心功能的影响.方法:选择实验犬40只,随机均分为RDN组(接受双肾动脉射频消融)及模型组(仅予股动脉穿刺).40只犬均安置心脏起搏器,用快速右室起搏的方法

  4. New treatment for old disease: management of resistant hypertension by percutaneous renal sympathetic denervation. (United States)

    Kanai, Takashi; Krum, Henry


    Hypertension is a major contributor to cardiovascular events, such as stroke and myocardial infarction, with accelerated sympathetic nerve activity implicated in its pathogenesis. However, hypertension in many patients is not adequately controlled, despite the availability of numerous medication classes. Novel procedure-as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation therapy-have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation delivers not only a decrease in blood pressure levels but also renal as well as systemic sympathetic nerve activity. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which implies no counterregulatory mechanism or re-innervation of afferent renal sympathetic nerve so far. Renal sympathetic denervation is expected to be a promising treatment for patients with hypertension, congestive heart failure, chronic kidney disease, and metabolic syndrome implicated in the pathogenesis of potentiated sympathetic nerve activity. This review will focus on the current devices and procedures, their outcomes and prospects in the treatment of hypertension.

  5. [Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment]. (United States)

    Mahfoud, F; Vonend, O; Bruck, H; Clasen, W; Eckert, S; Frye, B; Haller, H; Hausberg, M; Hoppe, U C; Hoyer, J; Hahn, K; Keller, T; Krämer, B K; Kreutz, R; Potthoff, S A; Reinecke, H; Schmieder, R; Schwenger, V; Kintscher, U; Böhm, M; Rump, L C


    This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time.

  6. Partial sympathetic denervation of the rat epididymis permits fertilization but inhibits embryo development. (United States)

    Ricker, D D; Crone, J K; Chamness, S L; Klinefelter, G R; Chang, T S


    The rat cauda epididymidis receives sympathetic innervation from the inferior mesenteric ganglion (IMG). We have previously demonstrated that surgical removal of the IMG and proximal hypogastric nerves (IMG denervation) results in significant and cauda-specific changes in epididymal sperm transport, sperm motility, luminal fluid protein composition, and tissue histology. In the present study we used natural mating trials and intrauterine insemination (IUI) techniques to determine whether or not IMG denervation affects male fertility and reproductive capacity. For the initial studies, adult male Sprague Dawley rats were mated with estrous females 1 and 4 weeks following IMG denervation. Nine days after mating, uterine implantation sites and corpora lutea (CL) were counted. In females mated with sham-operated control males, 85.8% of ovulated oocytes were fertilized and subsequently implanted. In contrast, females mated with IMG-denervated males 1 or 4 weeks following surgery had 0% and 3.5%, respectively, of ovulated oocytes fertilized and implanted. For rats maintained 21 days after mating, an average of 13 +/- 1 pups were delivered by each of nine females mated with sham-operated control male rats; whereas, only seven morphologically normal pups were delivered by one of 14 females mated with IMG-denervated male rats. Additional experiments demonstrated that the decrement in offspring was, in part, due to a significant decrease in the number of spermatozoa in the female uterus following mating with IMG-denervated males. To determine whether IMG denervation exerted an additional effect directly on the fertilizing ability of spermatozoa, IUI experiments were performed. Six million cauda epididymal spermatozoa from 1- or 4-week IMG-denervated males were inseminated into the uterine horns of luteinzing hormone-releasing hormone (LHRH)-synchronized females and 9 days later implantation sites and CL were counted. Implantations were observed for 78%, 28%, and 25% of

  7. Renal artery sympathetic denervation: observations from the UK experience


    Sharp, Andrew S. P.; Davies, Justin E.; Lobo, Melvin D.; Bent, Clare L.; Mark, Patrick B.; Burchell, Amy E; Thackray, Simon D.; Martin, Una; McKane, William S.; Gerber, Robert T.; Wilkinson, James R.; Antonios, Tarek F.; Doulton, Timothy W.; Patterson, Tiffany; Clifford, Piers C.


    Background Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response—particularly in those prescribed aldosterone antagonists at the time of RDN. Methods We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres. Results Results from 253 patients treated with five technologies are shown. Pre-proc...

  8. MR-guided Periarterial Ethanol Injection for Renal Sympathetic Denervation: A Feasibility Study in Pigs

    Energy Technology Data Exchange (ETDEWEB)

    Streitparth, F., E-mail:; Walter, A.; Stolzenburg, N.; Heckmann, L.; Breinl, J. [Charite, Humboldt University, Department of Radiology (Germany); Rinnenthal, J. L. [Charite, Humboldt University, Department of Neuropathology (Germany); Beck, A.; De Bucourt, M.; Schnorr, J. [Charite, Humboldt University, Department of Radiology (Germany); Bernhardt, U. [InnoRa GmbH (Germany); Gebauer, B.; Hamm, B.; Guenther, R. W. [Charite, Humboldt University, Department of Radiology (Germany)


    Purpose. To evaluate the feasibility and efficacy of image-guided periarterial ethanol injection as an alternative to transluminal radiofrequency ablation. Methods. Unilateral renal periarterial ethanol injection was performed under general anesthesia in 6 pigs with the contralateral kidney serving as control. All interventions were performed in an open 1.0 T MRI system under real-time multiplanar guidance. The injected volume was 5 ml (95 % ethanol labelled marked MR contrast medium) in 2 pigs and 10 ml in 4 pigs. Four weeks after treatment, the pigs underwent MRI including MRA and were killed. Norepinephrine (NE) concentration in the renal parenchyma served as a surrogate parameter to analyze the efficacy of sympathetic denervation. In addition, the renal artery and sympathetic nerves were examined histologically to identify evidence of vascular and neural injury. Results. In pigs treated with 10 ml ethanol, treatment resulted in neural degeneration. We found a significant reduction of NE concentration in the kidney parenchyma of 53 % (p < 0.02) compared with the untreated contralateral kidney. In pigs treated with 5 ml ethanol, no significant changes in histology or NE were observed. There was no evidence of renal arterial stenosis in MRI, macroscopy or histology in any pig. Conclusion. MR-guided periarterial ethanol injection was feasible and efficient for renal sympathetic denervation in a swine model. This technique may be a promising alternative to the catheter-based approach in the treatment of resistant arterial hypertension.

  9. Revisiting renovascular imaging for renal sympathetic denervation: current techniques and applications

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei; Tan, Cher Heng [Tan Tock Seng Hospital, Department of Diagnostic Radiology, Singapore (Singapore); Ho, Hee Hwa; Tan, Julian Ko Beng; Ong, Paul Jau Leong [Tan Tock Seng Hospital, Department of Cardiology, Singapore (Singapore)


    Renal sympathetic denervation (RDN) is an emerging technique in the treatment of resistant hypertension, most commonly performed using an endovascular approach. Clinical and anatomical criteria for RDN are well established and imaging plays an integral role in selecting patients with suitable anatomy, procedural planning and device selection. Nevertheless, the current body of literature surrounding imaging related to RDN remains limited. The purpose of this article is to illustrate the expectations and limitations of various imaging techniques, including Doppler ultrasound, CT angiography, MR angiography and newer techniques such as non-contrast MR angiography, in the context of RDN. (orig.)

  10. A perspective on sympathetic renal denervation in chronic congestive heart failure. (United States)

    Madanieh, Raef; El-Hunjul, Mohammed; Alkhawam, Hassan; Kosmas, Constantine E; Madanieh, Abed; Vittorio, Timothy J


    Medical therapy has indisputably been the mainstay of management for chronic congestive heart failure. However, a significant percentage of patients continue to experience worsening heart failure (HF) symptoms despite treatment with multiple therapeutic agents. Recently, catheter-based interventional strategies that interrupt the renal sympathetic nervous system have shown promising results in providing better symptom control in patients with HF. In this article, we will review the pathophysiology of HF for better understanding of the interplay between the cardiovascular system and the kidney. Subsequently, we will briefly discuss pivotal renal denervation (RDN) therapy trials in patients with resistant hypertension and then present the available evidence on the role of RDN in HF therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Raffel, David M. E-mail:; Wieland, Donald M


    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.

  12. Renal Sympathetic Denervation by CT-scan-Guided Periarterial Ethanol Injection in Sheep

    Energy Technology Data Exchange (ETDEWEB)

    Firouznia, Kavous, E-mail:; Hosseininasab, Sayed jaber, E-mail: [Tehran University of Medical Sciences (TMUS), Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Amanpour, Saeid, E-mail: [Tehran University of Medical Science, Cancer Models Research Center, Cancer Institute of Iran (Iran, Islamic Republic of); Haj-Mirzaian, Arya, E-mail: [Tehran University of Medical Science, Department of Radiology and Imaging, MIC, Imam Khomeini Hospital (Iran, Islamic Republic of); Miri, Roza, E-mail: [Tehran University of Medical Science, Department of Pathology, Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Muhammadnejad, Ahad, E-mail: [Tehran University of Medical Science, Cancer Research Center, Cancer Institute of Iran (Iran, Islamic Republic of); Muhammadnejad, Samad, E-mail: [Tehran University of Medical Sciences, Research Center for Molecular and Cellular Imaging (Iran, Islamic Republic of); Jalali, Amir H., E-mail: [Tehran University of Medical Sciences (TMUS), Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Ahmadi, Farrokhlagha, E-mail: [Tehran University of Medical Sciences, Nephrology Research Center, Imam Khomeini Hospital Complex (Iran, Islamic Republic of); Rokni-Yazdi, Hadi, E-mail: [Tehran University of Medical Sciences (TMUS), Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Imam Khomeini Hospital Complex (Iran, Islamic Republic of)


    BackgroundRenal nerves are a recent target in the treatment of hypertension. Renal sympathetic denervation (RSD) is currently performed using catheter-based radiofrequency ablation (RFA) and because this method has limitations, percutaneous magnetic resonance (MR)-guided periarterial ethanol injection is a suggested alternative. However, few studies have been conducted on the effectiveness of percutaneous ethanol injection for RSD.AimTo evaluate the feasibility, efficacy, and complications of computed tomography (CT)-guided periarterial ethanol injection.MethodsEthanol (10 ml, 99.6 %) was injected around the right renal artery in six sheep under CT guidance with the left kidney serving as a control. Before and after the intervention, the sheep underwent MR imaging studies and the serum creatinine level was measured. One month after the intervention, the sheep were euthanized and norepinephrine (NE) concentration in the renal parenchyma was measured to evaluate the efficacy of the procedure. The treated tissues were also examined histopathologically to evaluate vascular, parenchymal, and neural injury.ResultsThe right kidney parenchymal NE concentration decreased significantly compared with the left kidney after intervention (average reduction: 40 %, P = 0.0016). Histologic examination revealed apparent denervation with no other vascular or parenchymal injuries observed in the histological and imaging studies.ConclusionEffective and feasible RSD was achieved using CT-guided periarterial ethanol injection. This technique may be a potential alternative to catheter-based RFA in the treatment of hypertension.

  13. Central Sympathetic Inhibition: a Neglected Approach for Treatment of Cardiac Arrhythmias? (United States)

    Cagnoni, Francesca; Destro, Maurizio; Bontempelli, Erika; Locatelli, Giovanni; Hering, Dagmara; Schlaich, Markus P


    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Overactivation of the sympathetic nervous system (SNS) plays an important role in the pathogenesis of comorbidities related to AF such as hypertension, congestive heart failure, obesity, insulin resistance, and obstructive sleep apnea. Methods that reduce sympathetic drive, such as centrally acting sympatho-inhibitory agents, have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. Moxonidine acts centrally to reduce activity of the SNS, and clinical trials indicate that this is associated with a decreased AF burden in hypertensive patients with paroxysmal AF and reduced post-ablation recurrence of AF in patients with hypertension who underwent pulmonary vein isolation (PVI). Furthermore, device-based approaches to reduce sympathetic drive, such as renal denervation, have yielded promising results in the prevention and treatment of cardiac arrhythmias. In light of these recent findings, targeting elevated sympathetic drive with either pharmacological or device-based approaches has become a focus of clinical research. Here, we review the data currently available to explore the potential utility of sympatho-inhibitory therapies in the prevention and treatment of cardiac arrhythmias.

  14. Cardiac impairment evaluated by transesophageal echocardiography and invasive measurements in rats undergoing sinoaortic denervation.

    Directory of Open Access Journals (Sweden)

    Raquel A Sirvente

    Full Text Available BACKGROUND: Sympathetic hyperactivity may be related to left ventricular (LV dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE using intracardiac echocardiographic catheter. METHODS AND RESULTS: We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD. The rats (n = 32 were divided into 4 groups: 16 Wistar (W with (n = 8 or without SAD (n = 8 and 16 spontaneously hypertensive rats (SHR with (n = 8 or without SAD (SHRSAD (n = 8. Blood pressure (BP and heart rate (HR did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. CONCLUSIONS: Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease.

  15. Sustained sympathetic and blood pressure reduction 1 year after renal denervation in patients with resistant hypertension. (United States)

    Hering, Dagmara; Marusic, Petra; Walton, Antony S; Lambert, Elisabeth A; Krum, Henry; Narkiewicz, Krzysztof; Lambert, Gavin W; Esler, Murray D; Schlaich, Markus P


    Renal denervation (RDN) reduces muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in resistant hypertension. Although a persistent BP-lowering effect has been demonstrated, the long-term effect on MSNA remains elusive. We investigated whether RDN influences MSNA over time. Office BP and MSNA were obtained at baseline, 3, 6, and 12 months after RDN in 35 patients with resistant hypertension. Office BP averaged 166±22/88±19 mm Hg, despite the use of an average of 4.8±2.1 antihypertensive drugs. Baseline MSNA was 51±11 bursts/min ≈2- to 3-fold higher than the level observed in healthy controls. Mean office systolic and diastolic BP significantly decreased by -12.6±18.3/-6.5±9.2, -16.1±25.6/-8.6±12.9, and -21.2±29.1/-11.1±12.9 mm Hg (Phypertension and high baseline MSNA. These observations are compatible with the hypothesis of a substantial contribution of afferent renal nerve signaling to increased BP in resistant hypertension and argue against a relevant reinnervation at 1 year after procedure.

  16. Cardiac fibroblasts regulate sympathetic nerve sprouting and neurocardiac synapse stability.

    Directory of Open Access Journals (Sweden)

    Céline Mias

    Full Text Available Sympathetic nervous system (SNS plays a key role in cardiac homeostasis and its deregulations always associate with bad clinical outcomes. To date, little is known about molecular mechanisms regulating cardiac sympathetic innervation. The aim of the study was to determine the role of fibroblasts in heart sympathetic innervation. RT-qPCR and western-blots analysis performed in cardiomyocytes and fibroblasts isolated from healthy adult rat hearts revealed that Pro-Nerve growth factor (NGF and pro-differentiating mature NGF were the most abundant neurotrophins expressed in cardiac fibroblasts while barely detectable in cardiomyocytes. When cultured with cardiac fibroblasts or fibroblast-conditioned medium, PC12 cells differentiated into/sympathetic-like neurons expressing axonal marker Tau-1 at neurites in contact with cardiomyocytes. This was prevented by anti-NGF blocking antibodies suggesting a paracrine action of NGF secreted by fibroblasts. When co-cultured with cardiomyocytes to mimic neurocardiac synapse, differentiated PC12 cells exhibited enhanced norepinephrine secretion as quantified by HPLC compared to PC12 cultured alone while co-culture with fibroblasts had no effect. However, when supplemented to PC12-cardiomyocytes co-culture, fibroblasts allowed long-term survival of the neurocardiac synapse. Activated fibroblasts (myofibroblasts isolated from myocardial infarction rat hearts exhibited significantly higher mature NGF expression than normal fibroblasts and also promoted PC12 cells differentiation. Within the ischemic area lacking cardiomyocytes and neurocardiac synapses, tyrosine hydroxylase immunoreactivity was increased and associated with local anarchical and immature sympathetic hyperinnervation but tissue norepinephrine content was similar to that of normal cardiac tissue, suggesting depressed sympathetic function. Collectively, these findings demonstrate for the first time that fibroblasts are essential for the setting of

  17. Effects of renal sympathetic denervation on 24-hour blood pressure variability

    Directory of Open Access Journals (Sweden)

    Christine Stefanie Zuern


    Full Text Available Background: In patients with arterial hypertension, increased blood pressure (BP variability contributes to end organ damage independently from mean levels of arterial BP. Increased BP variability has been linked to alterations in autonomic function including sympathetic overdrive. We hypothesized that catheter-based renal sympathetic denervation (RDN confers beneficial effects on BPV. Methods and Results: Eleven consecutive patients with therapy-refractory arterial hypertension (age 68.9±7.0 years; baseline systolic BP 189±23mmHg despite medication with 5.6±2.1 antihypertensive drugs underwent bilateral RDN. Twenty-four hour ambulatory blood pressure monitoring (ABPM was performed before RDN and six months thereafter. BPV was primarily assessed by means of standard deviation of 24-hour systolic arterial blood pressures (SDsys. Secondary measures of BPV were maximum systolic blood pressure (MAXsys and maximum difference between two consecutive readings of systolic BP (deltamaxsys over 24 hours. Six months after RDN, SDsys, MAXsys and deltamaxsys were significantly reduced from 16.9±4.6mmHg to 13.5±2.5mmHg (p=0.003, from 190±22mmHg to 172±20mmHg (p<0.001 and from 40±15mmHg to 28±7mmHg (p=0.006, respectively, without changes in concomitant antihypertensive therapy. Reductions of SDsys, MAXsys and deltamaxsys were observed in 10/11 (90.9%, 11/11 (100% and 9/11 (81.8% patients, respectively. Although we noted a significant reduction of systolic office blood pressure by 30.4±27.7mmHg (p=0.007, there was only a trend in reduction of average systolic BP assessed from ABPM (149±19mmHg to 142±18mmHg; p=0.086.Conclusions: In patients with therapy-refractory arterial hypertension, RDN leads to significant reductions of BP variability. Effects of RDN on BPV over 24 hours were more pronounced than on average levels of BP.

  18. The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease. (United States)

    Sata, Yusuke; Schlaich, Markus P


    Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.

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

    DEFF Research Database (Denmark)

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


    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...... system, norepinephrine. Also, positron emission tomography tracers are being developed for the same purpose. With (123) I-MIBG as a starting point, this brief review introduces the modalities used for cardiac sympathetic imaging....

  20. Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique

    Energy Technology Data Exchange (ETDEWEB)

    Ricke, J., E-mail:; Seidensticker, M.; Becker, S. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Schiefer, J. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany); Adamchic, I.; Lohfink, K. [Otto-von-Guericke University Magdeburg, Department of Radiology and Nuclear Medicine, Universitätsklinikum Magdeburg AöR (Germany); Kandulski, M.; Heller, A.; Mertens, P. R. [Universitätsklinikum Magdeburg AöR, Department of Nephrology and Hypertension, Diabetes and Endocrinology (Germany)


    ObjectivesCT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy.Materials and MethodsEleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments.ResultsNo toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease −41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: −9.7 and −6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: −18.3 and −15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06).ConclusionCT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter.

  1. The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats. (United States)

    Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo


    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.

  2. Cardiac sympathetic nerve terminal function in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    Chang-seng LIANG


    Increased cardiac release of norepinephrine (NE) and depleted cardiac stores of NE are two salient features of the human failing heart. Researches from my labo-ratory have shown that these changes are accompanied by a functional defect of NE uptake in the cardiac sympathetic nerve terminals. Our studies have shown that the decrease of NE uptake is caused by reduction of NE transporter density in the sympathetic nerve endings, and this change is responsible, at least in part, for the increased myocardial interstitial NE, decreased myocardial adrenoceptor density, and increased myocyte apoptosis in experimental cardiomyopathies. We have also provided evidence in both intact animals and cultured PC12 cells that the decrease of NE transporter is induced by the actions of oxidative metabolites of exogenous NE, involving endoplasmic reticulum stress and impaired N-glycosylation of the NE transporter. This change in the cardiac sympathetic NE uptake function, as demonstrated by [123I] metaiodobenzylguanidine in human studies, may not only serve as an important prognostic variable in patients with congestive heart failure, but also be used as a surrogate for the efficacies of various therapeutic interventions for heart failure. Finally, increasing evidence suggests and further studies are needed to show that the cardiac sympathetic nerve terminal function may be a direct target for pharmacologic treatment of congestive heart failure.

  3. Analysis of the Total Surgical Cardiac Denervation by Computer Simulation (United States)


    filtration rate and increase vasopressin, plasma renin activity, angiotensin II and aldosteron” [2][3]. It is claimed that these effects weaken...CE: Chemoreceptor Effect OSR: Autonomous System Resp. CK: Potassium Concent PPC: Plasma Osmotic Pressure CNa: Sodium Concentration RAP: Right...receptors respond to hypervolemia by supressing vasopressin, renin - angiotensin-aldosteron axis, thirst and sympathetic traffic to the kidney

  4. Renal denervation for treatment of cardiac arrhythmias: state of the art and future directions. (United States)

    Kosiuk, Jedrzej; Hilbert, Sebastian; Pokushalov, Evgeny; Hindricks, Gerhard; Steinberg, Jonathan S; Bollmann, Andreas


    It has now been more than a quarter of a century since modulation of the sympathetic nervous system was proposed for the treatment of cardiac arrhythmias of different origins. But it has also been some time since some of the early surgical attempts have been abandoned. With the development of ablation techniques, however, new approaches and targets have been recently introduced that have revolutionized our way of thinking about sympathetic modulation. Renal nerve ablation technology is now being successfully used for the treatment of resistant hypertension, but the indication spectrum might broaden and new therapeutic options might arise in the near future. This review focuses on the possible impact of renal sympathetic system modulation on cardiac arrhythmias, the current evidence supporting this approach, and the ongoing trials of this method in electrophysiological laboratories. We will discuss the potential roles that sympathetic modulation may play in the future.

  5. Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study (United States)

    Villacorta, Aline Sterque; Villacorta, Humberto; de Souza, Jenne Serrão; Teixeira, José Antônio Caldas; Muradas, Maria Clara S. S. S.; Alves, Christiane Rodrigues; Precht, Bernardo Campanário; Porto, Pilar; Ubaldo, Letícia; Mesquita, Cláudio Tinoco; da Nóbrega, Antônio Cláudio Lucas


    Background In the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT), heart rate (HR) reduction with ivabradine was associated with improved survival and reduced hospitalizations in patients with heart failure (HF). The mechanisms by which elevated HR increases mortality are not fully understood. Objective To assess the relationship of baseline HR with clinical, neurohormonal and cardiac sympathetic activity in patients with chronic HF and elevated HR. Method Patients with chronic HF who were in sinus rhythm and had resting HR>70 bpm despite optimal medical treatment were included in a randomized, double-blind study comparing ivabradine versus pyridostigmine. This report refers to the baseline data of 16 initial patients. Baseline HR (before randomization to one of the drugs) was assessed, and patients were classified into two groups, with HR below or above mean values. Cardiac sympathetic activity was assessed by 123-iodine-metaiodobenzylguanidine myocardial scintigraphy. Results Mean HR was 83.5±11.5 bpm (range 72 to 104), and seven (43.7%) patients had HR above the mean. These patients had lower 6-min walk distance (292.3±93 vs 465.2±97.1 m, p=0.0029), higher values of N-Terminal-proBNP (median 708.4 vs 76.1, p=0.035) and lower late heart/mediastinum rate, indicating cardiac denervation (1.48±0.12 vs 1.74±0.09, p<0.001). Conclusion Elevated resting HR in patients with HF under optimal medical treatment was associated with cardiac denervation, worse functional capacity, and neurohormonal activation. PMID:27982270

  6. Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study

    Directory of Open Access Journals (Sweden)

    Aline Sterque Villacorta

    Full Text Available Abstract Background: In the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT, heart rate (HR reduction with ivabradine was associated with improved survival and reduced hospitalizations in patients with heart failure (HF. The mechanisms by which elevated HR increases mortality are not fully understood. Objective: To assess the relationship of baseline HR with clinical, neurohormonal and cardiac sympathetic activity in patients with chronic HF and elevated HR. Method: Patients with chronic HF who were in sinus rhythm and had resting HR>70 bpm despite optimal medical treatment were included in a randomized, double-blind study comparing ivabradine versus pyridostigmine. This report refers to the baseline data of 16 initial patients. Baseline HR (before randomization to one of the drugs was assessed, and patients were classified into two groups, with HR below or above mean values. Cardiac sympathetic activity was assessed by 123-iodine-metaiodobenzylguanidine myocardial scintigraphy. Results: Mean HR was 83.5±11.5 bpm (range 72 to 104, and seven (43.7% patients had HR above the mean. These patients had lower 6-min walk distance (292.3±93 vs 465.2±97.1 m, p=0.0029, higher values of N-Terminal-proBNP (median 708.4 vs 76.1, p=0.035 and lower late heart/mediastinum rate, indicating cardiac denervation (1.48±0.12 vs 1.74±0.09, p<0.001. Conclusion: Elevated resting HR in patients with HF under optimal medical treatment was associated with cardiac denervation, worse functional capacity, and neurohormonal activation.

  7. Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial. (United States)

    Verloop, Willemien L; Beeftink, Martine M A; Nap, Alex; Bots, Michiel L; Velthuis, Birgitta K; Appelman, Yolande E; Cramer, Maarten-Jan; Agema, Willem R P; Scholtens, Asbjorn M; Doevendans, Pieter A; Allaart, Cor P; Voskuil, Michiel


    Aim Increasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF. Methods DIASTOLE is a multicentre, randomized controlled trial. Sixty patients, diagnosed with HFNEF and treated for hypertension, will be randomly allocated in a 1:1 ratio to undergo renal denervation on top of medical treatment (n = 30) or to maintain medical treatment alone (n = 30). The primary objective is to investigate the efficacy of pRDN by means of pulsed wave Doppler echocardiographic parameters. Secondary objectives include safety of pRDN and a comparison of changes in the following parameters after pRDN: LV mass, LV volume, LVEF, and left atrial volume as determined by magnetic resonance imaging. Also, MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure, heart rate variability, exercise capacity, and quality of life will be assessed. Perspective DIASTOLE is a randomized controlled trial evaluating renal denervation as a treatment option for HFNEF. The results of the current trial will provide important information regarding the treatment of HFNEF, and therefore may have major impact on future therapeutic strategies. Trail registration NCT01583881.

  8. Estrogen up-regulation of semaphorin 3F correlates with sympathetic denervation of the rat uterus. (United States)

    Richeri, Analía; Chalar, Cora; Martínez, Gaby; Greif, Gonzalo; Bianchimano, Paola; Brauer, M Mónica


    Current evidence indicates that rises in systemic levels of estrogen create in the uterus an inhibitory environment for sympathetic nerves. However, molecular insights of these changes are far from complete. We evaluated if semaphorin 3F mRNA, a sympathetic nerve repellent, was produced by the rat uterus and if its expression was modulated by estrogen. We also analyzed whether uterine nerves express the semaphorin 3F binding receptor, neuropilin-2. Uterine levels of semaphorin 3F mRNA were measured using real time reverse transcriptase-polymerase chain reaction in prepubertal rat controls and following chronic estrogen treatment. Localization of semaphorin 3F transcripts was determined by in situ hybridization and the expression of neuropilin-2 was assessed by immunohistochemistry. These studies showed that: (1) chronic estrogen treatment led to a 5-fold induction of semaphorin 3F mRNA in the immature uterus; (2) estrogen provoked a tissue-specific induction of semaphorin 3F which was particularly localized in the connective tissue that borders muscle bundles and surrounds intrauterine blood vessels; (3) two major cell-types were recognized in the areas where transcripts were concentrated, fibroblast-like cells and infiltrating eosinophil leukocytes; and (4) some delicate nerve terminal profiles present in the estrogenized uterus were immunoreactive for neuropilin-2. Temporal and spatial expression patterns of semaphorin 3F/neuropilin-2 are consistent with a possible role of this guidance cue in the remodeling of uterine sympathetic innervation by estrogen. Though correlative in its nature, these data support a model whereby semaphorin 3F, in combination with other inhibitory molecules, converts the estrogenized myometrium to an inhospitable environment for sympathetic nerves.

  9. Estrogen-induced collagen reorientation correlates with sympathetic denervation of the rat myometrium. (United States)

    Martínez, G F; Bianchimano, P; Brauer, M M


    Estrogen inhibits the growth and causes the degeneration (pruning) of sympathetic nerves supplying the rat myometrium. Previous cryoculture studies evidenced that substrate-bound signals contribute to diminish the ability of the estrogenized myometrium to support sympathetic nerve growth. Using electron microscopy, here we examined neurite-substrate interactions in myometrial cryocultures, observing that neurites grew associated to collagen fibrils present in the surface of the underlying cryosection. In addition, we assessed quantitatively the effects of estrogen on myometrial collagen organization in situ, using ovariectomized rats treated with estrogen and immature females undergoing puberty. Under low estrogen levels, most collagen fibrils were oriented in parallel to the muscle long axis (83% and 85%, respectively). Following estrogen treatment, 89% of fibrils was oriented perpendicularly to the muscle main axis; while after puberty, 57% of fibrils acquired this orientation. Immunohistochemistry combined with histology revealed that the vast majority of fine sympathetic nerve fibers supplying the myometrium courses within the areas where collagen realignment was observed. Finally, to assess whether depending on their orientation collagen fibrils can promote or inhibit neurite outgrowth, we employed cryocultures, now using as substrate tissue sections of rat-tail tendon. We observed that neurites grew extensively in the direction of the parallel-aligned collagen fibrils in the tendon main axis but were inhibited to grow perpendicularly to this axis. Collectively, these findings support the hypothesis that collagen reorientation may be one of the factors contributing to diminish the neuritogenic capacity of the estrogen-primed myometrial substrate.

  10. Effects of Scopolamine on Blood Vessels in Rabbit Ear after Sympathetic and Sensory Denervation

    Institute of Scientific and Technical Information of China (English)

    刘书勤; 臧伟进; 成亮; 李增利; 于晓江; 李宝平


    Objectives To investigate the effects and involved mechanisms of scopolamine (Scop) on rabbit ear blood vessels. Methods Rabbit ear blood vessels were desympathetic and desensory innervation with surgical operation. Diameters of dorsal auricular arterial trunks in vivo were measured with a pair of compasses and the ruler in a dissecting microscope, and effluents from isolated ear under constant perfusion pressure were recorded with a digital drop-recorder. Results Intramuscular injection of Scop 0.1 mg/kg made the diameter of denerved dorsal auricular arterial trunks, as well as that of innerved ones, significantly increased. Scop by itself, at the maximal concentration (Cmax) of 3 μM, 30 μM and 300 μM, did not alter the effluent flow from the isolated denervated rabbit ear, but chlorpromazine (CPZ), at Cmax of 1 μM, acetylcholine (ACh), 0.25μM, all significantly increased the effluent flow, and norepinephrine (NE), 0.1μM, significantly decreased the effluent. Scop, 3 μM, did not affect ACh (0.25μM)-induced the increase of effluent flow, but Scop,30μM, alleviated the increase. Scop, 3μM, did not affect NE (0.1 μM)-induced the decrease of effluent flow, but Scop, 10, 30 and 100 μM, significantly alleviated the decrease. Conclusions The study suggests that Scop has no direct vasodilator effect. The vasodilator effect of Scop is not due to the blockade of muscarinic receptor. However, Scop can dilate blood vessels contracted by α1-adrenoceptor activation.

  11. Cardiac sympathetic imaging with mIBG in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Møller, Søren; Mortensen, Christian; Bendtsen, Flemming


    Autonomic and cardiac dysfunction is frequent in cirrhosis and includes increased sympathetic nervous activity, impaired heart rate variability (HRV), and baroreflex sensitivity (BRS). Quantified (123)I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake, and in pati...

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

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    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: [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)


    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.

  13. Advances in Renal Sympathetic Denervation%肾脏交感神经射频消融术临床效应研究进展

    Institute of Scientific and Technical Information of China (English)



    Renal sympathetic denervation (RSD) is a novel catheter-based approach to directly target renal sympathetic nerves using radiofrequency ablation technology, which can suppress the activation of the sympathetic nervous system. It has been indicated that RSD can not only significantly lower peripheral blood pressure in patients with resistant hypertension, but shows improvement in left ventricular hypertrophy , heart failure, insulin resistance and albuminuria. This review focuses on the clinical effects of renal sympathetic denervation and the prospects of its clinical application.%肾脏交感神经射频消融术是一种新型的、选择性降低肾脏交感神经活性的介入治疗手段,最新研究证实不仅可显著降低顽固性高血压患者血压水平,而且临床研究发现还具有逆转左心室肥厚、改善心功能、改善胰岛素抵抗、降低尿蛋白等临床效应;现主要对肾脏交感神经射频消融术的临床效应及应用前景进行综述.

  14. Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

    Directory of Open Access Journals (Sweden)

    Zhaojie Du

    Full Text Available The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3 in bone marrow mesenchymal stem cells (MSCs, and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2 and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3. Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP, osteocalcin (OCN, and runt-related transcription factor-2 (RUNX2, but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes.

  15. Cardiac sympathetic dysfunction in anti-NMDA receptor encephalitis. (United States)

    Byun, Jung-Ick; Lee, Soon-Tae; Moon, Jangsup; Jung, Keun-Hwa; Shin, Jung-Won; Sunwoo, Jun-Sang; Lim, Jung-Ah; Shin, Yong-Won; Kim, Tae-Joon; Lee, Keon-Joo; Park, Kyung-Il; Jung, Ki-Young; Lee, Sang Kun; Chu, Kon


    Patients with anti-NMDA receptor (anti-NMDAR) encephalitis frequently suffer from autonomic dysfunctions, which can cause substantial morbidity. This study assessed cardiac autonomic functions in patients with anti-NMDAR encephalitis using heart rate variability (HRV) analysis. This was a retrospective single-center case-control study. Eleven patients with anti-NMDAR encephalitis and 15 age- and sex-matched controls were included in this study. To ensure that autonomic dysfunction does not occur in any encephalitis, we additionally analyzed HRV of 9 patients with herpes encephalitis (HSE) and compared with that of NMDAR encephalitis patients and controls. Five minute resting stationary electrocardiogram was collected from each subject, and HRV was analyzed. Total power and low frequency (LF) power were lower in anti-NMDAR encephalitis patients than those in controls (p=0.005, 0.001 respectively), indicating cardiac autonomic dysfunction especially in sympathetic system. Patients with HSE showed no significant difference in HRV parameters compared with that of controls. Cardiac autonomic dysfunction was associated with 3 month functional outcome in anti-NMDAR encephalitis patients.

  16. Reversal of serotonin vasodilatation in the dog external carotid bed by sympathetic denervation. (United States)

    Mena, M A; Vidrio, H


    In view of the conflicting reports of both constrictor and dilator effects of serotonin on the external carotid vascular bed of dogs, the influence of intraarterial infusions of the amine on blood flow through this territory was assessed by electromagnetic flowmeter techniques. In anesthetized intact dogs, serotonin produced dose-related increases in flow. These vasodilator responses were markedly diminished after ipsilateral vagotomy and were followed by delayed vasoconstriction, which then became the predominant response. Pretreatment with atropine did not modify dilator responses, while resection of the ipsilateral stellate ganglion reversed them to pure constriction. In the internal carotid, serotonin elicited constriction, and this effect was unaffected by vagotomy. These results were interpreted in terms of the hypothesis relating serotonin reactivity to vascular tone. The amine would elicit dilatation through an effect on tonically constricted small vessels. Removal of this tone by section of the vagosympathetic trunk or stellectomy would unmask the constrictor effect of serotonin on large vessels. Such reversal of responses would not occur in the internal carotid, a territory normally devoid of important sympathetic tone.

  17. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. (United States)

    Fadl Elmula, Fadl Elmula M; Hoffmann, Pavel; Larstorp, Anne C; Fossum, Eigil; Brekke, Magne; Kjeldsen, Sverre E; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjaer, Vibeke N; Rostrup, Morten; Os, Ingrid; Stenehjem, Aud; Høieggen, Aud


    We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (Pdrug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: Unique identifier: NCT01673516.

  18. Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias. (United States)

    McCully, Belinda H; Hasan, Wohaib; Streiff, Cole T; Houle, Jennifer C; Woodward, William R; Giraud, George D; Brooks, Virginia L; Habecker, Beth A


    Obesity increases the risk of arrhythmias and sudden cardiac death, but the mechanisms are unknown. This study tested the hypothesis that obesity-induced cardiac sympathetic outgrowth and hyperinnervation promotes the development of arrhythmic events. Male Sprague-Dawley rats (250-275 g), fed a high-fat diet (33% kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments showed that both OR and OP rats exhibited hyperinnervation of the heart and high sympathetic outgrowth compared with CON rats, even though OR rats are not obese. Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were less susceptible to arrhythmic events after an intravenous epinephrine challenge compared with OP rats. On examining total and stimulus-evoked neurotransmitter levels in an ex vivo system, we demonstrate that atrial acetylcholine content and release were attenuated in OP compared with OR and CON groups. OP rats also expressed elevated atrial norepinephrine content, while norepinephrine release was suppressed. These findings suggest that the consumption of a high-fat diet, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart. However, normalized cardiac parasympathetic nervous system control may protect the heart from arrhythmic events.

  19. Effects of renal sympathetic denervation on exercise blood pressure, heart rate, and capacity in patients with resistant hypertension. (United States)

    Ewen, Sebastian; Mahfoud, Felix; Linz, Dominik; Pöss, Janine; Cremers, Bodo; Kindermann, Ingrid; Laufs, Ulrich; Ukena, Christian; Böhm, Michael


    Renal denervation reduces office blood pressure in patients with resistant hypertension. This study investigated the effects of renal denervation on blood pressure, heart rate, and chronotropic index at rest, during exercise, and at recovery in 60 patients (renal denervation group=50, control group=10) with resistant hypertension using a standardized bicycle exercise test protocol performed 6 and 12 months after renal denervation. After renal denervation, exercise blood pressure at rest was reduced from 158±3/90±2 to 141±3/84±4 mm Hg (Pblood pressure/P=0.007 for diastolic blood pressure) after 6 months and 139±3/83±4 mm Hg (Pblood pressure tended to be lower at all stages of exercise at 6- and 12-month follow-up in patients undergoing renal denervation, although reaching statistical significance only at mild-to-moderate exercise levels (75-100 W). At recovery after 1 minute, blood pressure decreased from 201±4/95±2 to 177±4/88±2 (Pblood pressure and heart rate during exercise, improved mean workload, and increased exercise time without impairing chronotropic competence.

  20. Expressions of cardiac sympathetic norepinephrine transporter and β1-adrenergic receptor decreased in aged rats

    Institute of Scientific and Technical Information of China (English)

    He LI; Xiao-qing MA; Fan YE; Jing ZHANG; Xin ZHOU; Zhi-hong WANG; Yu-ming LI; Guo-yuan ZHANG


    Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovas-cular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine (NE) transporter (NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleff and maintains the sensitivity of the β-adrenergic receptor (β-AR). In the present study, we investigated NET and β1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and leff ventricular myocardium in 2- and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA, NET protein and β1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%, 26%, and 43%, respectively, in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.

  1. The sympathetic nervous system in obesity hypertension. (United States)

    Lohmeier, Thomas E; Iliescu, Radu


    Abundant evidence supports a role of the sympathetic nervous system in the pathogenesis of obesity-related hypertension. However, the nature and temporal progression of mechanisms underlying this sympathetically mediated hypertension are incompletely understood. Recent technological advances allowing direct recordings of renal sympathetic nerve activity (RSNA) in conscious animals, together with direct suppression of RSNA by renal denervation and reflex-mediated global sympathetic inhibition in experimental animals and human subjects have been especially valuable in elucidating these mechanisms. These studies strongly support the concept that increased RSNA is the critical mechanism by which increased central sympathetic outflow initiates and maintains reductions in renal excretory function, causing obesity hypertension. Potential determinants of renal sympathoexcitation and the differential mechanisms mediating the effects of renal-specific versus reflex-mediated, global sympathetic inhibition on renal hemodynamics and cardiac autonomic function are discussed. These differential mechanisms may impact the efficacy of current device-based approaches for hypertension therapy.

  2. Renal sympathetic denervation as an adjunct to catheter ablation for the treatment of ventricular electrical storm in the setting of acute myocardial infarction. (United States)

    Hoffmann, Boris A; Steven, Daniel; Willems, Stephan; Sydow, Karsten


    We present a case of ventricular storm (VS) in a patient with acute ST-elevation myocardial infarction (STEMI). After initial successful thrombus extraction and percutaneous coronary intervention (PCI) of the proximal left anterior descending (LAD) coronary artery, a 63-year-old male patient showed recurrent monomorphic ventricular tachycardia (VT) and fibrillation (VF) episodes refractory to antiarrhythmic drug therapy. After initial successful VT ablation, fast VT and VF episodes remained an evident problem despite maximum antiarrhythmic drug therapy. Due to an increasing instability, renal sympathetic denervation (RDN) was performed. ICD interrogation and 24-hour Holter monitoring excluded recurrent episodes of VT or VF at a 6-month follow-up (FU) after discharge. This case highlights that RDN was effective and safely performed in a hemodynamically unstable patient with VS after STEMI and adjunct catheter ablation. RDN may open a new avenue for an adjunctive interventional bailout treatment of such highly challenging patients.

  3. Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents. (United States)

    Kanazawa, Hideaki; Ieda, Masaki; Kimura, Kensuke; Arai, Takahide; Kawaguchi-Manabe, Haruko; Matsuhashi, Tomohiro; Endo, Jin; Sano, Motoaki; Kawakami, Takashi; Kimura, Tokuhiro; Monkawa, Toshiaki; Hayashi, Matsuhiko; Iwanami, Akio; Okano, Hideyuki; Okada, Yasunori; Ishibashi-Ueda, Hatsue; Ogawa, Satoshi; Fukuda, Keiichi


    Although several cytokines and neurotrophic factors induce sympathetic neurons to transdifferentiate into cholinergic neurons in vitro, the physiological and pathophysiological roles of this remain unknown. During congestive heart failure (CHF), sympathetic neural tone is upregulated, but there is a paradoxical reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic nervous system (SNS). Here we examined whether cholinergic transdifferentiation can occur in the cardiac SNS in rodent models of CHF and investigated the underlying molecular mechanism(s) using genetically modified mice. We used Dahl salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac SNS clearly acquired cholinergic characteristics. Of the various cholinergic differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1 were strongly upregulated in the ventricles of rats with CHF. Further, LIF and cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced cholinergic transdifferentiation in cultured sympathetic neurons, and this process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with the data in rats, heart-specific overexpression of LIF in mice caused cholinergic transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic transdifferentiation was also observed in the cardiac SNS of autopsied patients with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of the cardiac SNS via gp130-signaling cytokines secreted from the failing myocardium.

  4. Imaging of the autonomic nervous system: focus on cardiac sympathetic innervation. (United States)

    Goldstein, David S


    Symptoms or signs of abnormal autonomic nervous system function occur commonly in several neurological disorders. Clinical evaluations have depended on physiological, pharmacological, and neurochemical approaches. Recently, imaging of sympathetic noradrenergic innervation has been introduced and applied especially in the heart. Most studies have used the radiolabeled sympathomimetic amine, (123)I-metaiodobenzylguanidine. Decreased uptake or increased "washout" of (123)I-metaiodobenzylguanidine-derived radioactivity is associated with worse prognosis or more severe disease in hypertension, congestive heart failure, arrhythmias, and diabetes mellitus. This pattern may reflect a high rate of postganglionic sympathetic nerve traffic to the heart. Many recent studies have agreed on the remarkable finding that all patients with Parkinson's disease and orthostatic hypotension have a loss of cardiac sympathetic innervation, whereas all patients with multiple system atrophy, often difficult to distinguish clinically from Parkinson's disease, have intact cardiac sympathetic innervation. Because Parkinson's disease entails a postganglionic sympathetic noradrenergic lesion, the disease appears to be not only a movement disorder, with dopamine loss in the nigrostriatal system of the brain, but also a dysautonomia, with noradrenaline loss in the sympathetic nervous system of the heart. As new ligands are developed, one may predict further discoveries of involvement of components of the autonomic nervous system in neurological diseases.

  5. Pacemaker current inhibition in experimental human cardiac sympathetic activation: a double-blind, randomized, crossover study

    NARCIS (Netherlands)

    Schroeder, C.; Heusser, K.; Zoerner, A.A.; Grosshennig, A.; Wenzel, D.; May, M.; Sweep, F.C.; Mehling, H.; Luft, F.C.; Tank, J.; Jordan, J.


    Hyperpolarization-activated, cyclic nucleotide-gated 4 (HCN4) channels comprise the final pathway for autonomic heart rate (HR) regulation. We hypothesized that HCN4 inhibition could reverse autonomic imbalance in a human model of cardiac sympathetic activation. Nineteen healthy men ingested oral me

  6. Co-localization of histamine and norepinephrine in sympathetic ganglia and exocytosis of endogenous histamine from cardiac sympathetic nerve endings of macaca mulatto monkey

    Institute of Scientific and Technical Information of China (English)

    Ming-kaiLI; Xiao-xingLUO; Liang-weiCHEN; ZhongCHEN; JiaMENG; JingHU; Yu-meiWU; Jing-ruMENG; ZhengHOU; XueMA


    AIM To provide the evidence about localization, biosynthesis, metabolism and release of histamine from the cardiac sympathetic nerve terminals, and endogenous sympathetic histamine could inhibit itsel frelease from the nerve terminal through the presynaptic histamine H3 receptor. METHODS Using double-labeled immunohistochemistry to observe the co-localization of histamine and NE in the superior cer-vical ganglia (SCG) of macaca mulatto monkey; Different-speed centrifugation to obtain the cardiac sympathetic nerve terminal model (the cardiac synaptosomes), spectrofluorometer and ELISA techniques to detect the release of histamine from the cardiacsynaptosomes. RESULTS ( 1 ) The coexistence of histamine and norepinephrine immunoreactivities was identified in the same neuron within SCG of macaca mulatto monkey. (2) Depolarization of macaca mulatto monkey cardiac synaptosomes with 50 mmol/L potassium caused the release of endogenous histamine,

  7. 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


    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)

  8. Renal sympathetic denervation in patients with treatment-resistant hypertension after witnessed intake of medication before qualifying ambulatory blood pressure. (United States)

    Fadl Elmula, Fadl Elmula Mohamed; Hoffmann, Pavel; Fossum, Eigil; Brekke, Magne; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjær, Vibeke N; Rostrup, Morten; Kjeldsen, Sverre E; Os, Ingrid; Stenehjem, Aud-E; Høieggen, Aud


    It is unknown whether the decline in blood pressure (BP) after renal denervation (RDN) is caused by denervation itself or concomitantly improved drug adherence. We aimed to investigate the BP lowering effect of RDN in true treatment-resistant hypertension by excluding patients with poor drug adherence. Patients with resistant hypertension (n=18) were referred for a thorough clinical and laboratory work-up. Treatment-resistant hypertension was defined as office systolic BP>140 mm Hg, despite maximally tolerated doses of ≥ 3 antihypertensive drugs, including a diuretic. In addition, ambulatory daytime systolic BP>135 mm Hg was required after witnessed intake of antihypertensive drugs to qualify. RDN (n=6) was performed with Symplicity Catheter System. The mean office and ambulatory BPs remained unchanged at 1, 3, and 6 months in the 6 patients, whereas there was no known change in antihypertensive medication. Two patients, however, had a fall in both office and ambulatory BPs. Our findings question whether BP falls in response to RDN in patients with true treatment-resistant hypertension. Additional research must aim to verify potential BP lowering effect and identify a priori responders to RDN before this invasive method can routinely be applied to patients with drug-resistant hypertension. Clinical Trial Registration- URL: Unique identifier: NCT01673516.

  9. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy (United States)

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun


    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

  10. Radionuclide imaging of cardiac sympathetic innervation in heart failure: unlocking untapped potential. (United States)

    Gupta, Shuchita; Amanullah, Aman


    Heart failure (HF) is associated with sympathetic overactivity, which contributes to disease progression and arrhythmia development. Cardiac sympathetic innervation imaging can be performed using radiotracers that are taken up in the presynaptic nerve terminal of sympathetic nerves. The commonly used radiotracers are (123)I-metaiodobenzylguanidine ((123)I-mIBG) for planar and single-photon emission computed tomography imaging, and (11)C-hydroxyephedrine for positron emission tomography imaging. Sympathetic innervation imaging has been used in assessing prognosis, response to treatment, risk of ventricular arrhythmias and sudden death and prediction of response to cardiac resynchronization therapy in patients with HF. Other potential applications of these techniques are in patients with chemotherapy-induced cardiomyopathy, predicting myocardial recovery in patients with left ventricular assist devices, and assessing reinnervation following cardiac transplantation. There is a lack of standardization with respect to technique of (123)I-mIBG imaging that needs to be overcome for the imaging modality to gain popularity in clinical practice.

  11. Quantifying cardiac sympathetic and parasympathetic nervous activities using principal dynamic modes analysis of heart rate variability. (United States)

    Zhong, Yuru; Jan, Kung-Ming; Ju, Ki Hwan; Chon, Ki H


    The ratio between low-frequency (LF) and high-frequency (HF) spectral power of heart rate has been used as an approximate index for determining the autonomic nervous system (ANS) balance. An accurate assessment of the ANS balance can only be achieved if clear separation of the dynamics of the sympathetic and parasympathetic nervous activities can be obtained, which is a daunting task because they are nonlinear and have overlapping dynamics. In this study, a promising nonlinear method, termed the principal dynamic mode (PDM) method, is used to separate dynamic components of the sympathetic and parasympathetic nervous activities on the basis of ECG signal, and the results are compared with the power spectral approach to assessing the ANS balance. The PDM analysis based on the 28 subjects consistently resulted in a clear separation of the two nervous systems, which have similar frequency characteristics for parasympathetic and sympathetic activities as those reported in the literature. With the application of atropine, in 13 of 15 supine subjects there was an increase in the sympathetic-to-parasympathetic ratio (SPR) due to a greater decrease of parasympathetic than sympathetic activity (P=0.003), and all 13 subjects in the upright position had a decrease in SPR due to a greater decrease of sympathetic than parasympathetic activity (Pparasympathetic and sympathetic nervous systems. The culprit is equivalent decreases in both the sympathetic and parasympathetic activities irrespective of the pharmacological blockades. These findings suggest that the PDM shows promise as a noninvasive and quantitative marker of ANS imbalance, which has been shown to be a factor in many cardiac and stress-related diseases.

  12. Relationship between left ventricular diastolic function and myocardial sympathetic denervation measured by {sup 123}I-meta-iodobenzylguanidine imaging in Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Spinelli, Letizia; Giudice, Caterina Anna; Imbriaco, Massimo; Trimarco, Bruno; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Pisani, Antonio; Riccio, Eleonora [University Federico II, Department of Public Health, Naples (Italy); Salvatore, Marco [IRCCS SDN, Naples (Italy)


    Whether cardiac sympathetic nervous function abnormalities may be present in patients with Anderson-Fabry disease (AFD) remains unexplored. We investigated the relationship between left ventricular (LV) function and cardiac sympathetic nervous function in patients with AFD. Twenty-five patients (12 men, mean age 43 ± 13 years) with genetically proved AFD and preserved LV ejection fraction and ten age and gender-matched control subjects underwent speckle tracking echocardiography and {sup 123}I-meta-iodobenzylguanidine (MIBG) imaging from which early and late heart to mediastinum (H/M) ratios and myocardial washout rate values were calculated. In AFD patients, a significant correlation between late H/M ratio and LV mass index (r = -61, p = 0.001), left atrial volume (r = -0.72, p < 0.001), systolic pulmonary artery pressure (r = -0.75, p < 0.001), and early diastolic untwisting rate (r = -0.66, p < 0.001) was found. Ten AFD patients exhibited a late H/M ratio below two fold standard deviation of control subjects (≤1.75). Patients showing late H/M ratio ≤ 1.75 had significantly higher LV mass index, relative wall thickness, left atrial volume and systolic pulmonary artery pressure, lower systolic longitudinal strain and an early diastolic untwisting rate compared to patients with late H/M ratio > 1.75. At multivariable linear regression analysis, early diastolic untwisting rate was the only independent predictor of late H/M ratio ≤ 1.75 (odds ratio 1.15, 95 % confidence interval 1.07-1.31, p < 0.05). The present findings provide the first demonstration of a cardiac sympathetic derangement in AFD patients with preserved LV ejection fraction, which is mostly related to LV diastolic dysfunction. (orig.)

  13. 超声能源在去肾交感治疗中的应用%Application of Ultrasound in Renal Sympathetic Denervation

    Institute of Scientific and Technical Information of China (English)



    Renal sympathetic denervation (RDN) with radiofrequency energy is a novel therapeutic technique for the treatment of patients with resistant hypertension. Nevertheless, radiofrequency ablation of renal sympathetic nerves bears numerous disadvantages, e.g., low efifciency;patient’s suffering from pain during ablation and unresponsiveness to the treatment, as well as successful procedural performance depending on the type of target vessels, etc. While ultrasound, when longitudinally propagating through the biological tissue, may cause the medium molecules to vibrate violently, with subsequent generation of mechanical friction, cavitation and thermal effects; thus, can be applied for RDN. Compared with radiofrequency energy, it has many advantages in terms of safety and efifcacy. This review is about the-state-of-art of ultrasound ablation for renal sympathetic nerves.%以SymplicityTM 为代表的利用射频能量行去肾交感神经术开创了经皮血管介入治疗顽固性高血压的全新途径。但射频能量消融尚存在消融效率较低、消融时患者疼痛明显、部分患者对治疗无反应(约20%)及完成治疗过程依耐于标准的患者血管类型等缺点。而超声作为一种频率高于听阈的机械波,在生物组织中以纵波传播时,其携带的机械能可使介质中的分子剧烈震荡产生机械摩擦、空化和热效应等,因此可用于去肾交感神经术。且与射频能量消融相比,超声能量在安全性和有效性方面有诸多优势。本综述即将对经导管超声消融肾交感神经相关研究进展作一系统阐述。

  14. Differential cardiac responses to unilateral sympathetic nerve stimulation in the isolated innervated rabbit heart. (United States)

    Winter, James; Tanko, Abdul Samed; Brack, Kieran E; Coote, John H; Ng, G André


    The heart receives both a left and right sympathetic innervation. Currently there is no description of an in vitro whole heart preparation for comparing the influence of each sympathetic supply on cardiac function. The aim was to establish the viability of using an in vitro model to investigate the effects of left and right sympathetic chain stimulation (LSS/RSS). For this purpose the upper sympathetic chain on each side was isolated and bipolar stimulating electrodes were attached between T2-T3 and electrically insulated from surrounding tissue in a Langendorff innervated rabbit heart preparation (n=8). Heart rate (HR) was investigated during sinus rhythm, whilst dromotropic, inotropic and ventricular electrophysiological effects were measured during constant pacing (250 bpm). All responses exhibited linear increases with increases in stimulation frequency (2-10 Hz). The change in HR was larger during RSS than LSS (P<0.01), increasing by 78±9 bpm and 49±8 bpm respectively (10 Hz, baseline; 145±7 bpm). Left ventricular pressure was increased from a baseline of 50±4 mmHg, by 22±5 mmHg (LSS, 10 Hz) and 4±1 mmHg (RSS, 10 Hz) respectively (P<0.001). LSS, but not RSS, caused a shortening of basal and apical monophasic action potential duration (MAPD90). We demonstrate that RSS exerts a greater effect at the sinoatrial node and LSS at the left ventricle. The study confirms previous experiments on dogs and cats, provides quantitative data on the comparative influence of right and left sympathetic nerves and demonstrates the feasibility of isolating and stimulating the ipsilateral cardiac sympathetic supply in an in vitro innervated rabbit heart preparation.

  15. Impaired cardiac sympathetic innervation in symptomatic patients with long QT syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kies, Peter; Stegger, Lars; Schober, Otmar [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Paul, Matthias; Moennig, Gerold [University Hospital Muenster, Department for Cardiology and Angiology, Muenster (Germany); Gerss, Joachim [University of Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany); Wichter, Thomas [Marienhospital Osnabrueck, Department of Cardiology, Niels-Stensen-Kliniken, Osnabrueck (Germany); Schaefers, Michael [University of Muenster, European Institute of Molecular Imaging - EIMI, Muenster (Germany); Schulze-Bahr, Eric [University Hospital Muenster, Department for Cardiology and Angiology, Muenster (Germany); University Hospital Muenster, Institute for Genetics of Heart Diseases, Muenster (Germany)


    Increased sympathetic activation is a key modifier for arrhythmogenesis in patients with long QT syndrome (LQTS), a congenital channelopathy. Therefore, we investigated cardiac sympathetic function using {sup 123}I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) in a cohort of symptomatic LQTS patients and correlated these findings with the underlying genotype. [{sup 123}I]MIBG SPECT was performed in 28 LQTS patients. Among these, 18 patients (64%) had a previous syncope and 10 patients (36%) survived sudden cardiac arrest. Patients were characterized in terms of genetic subtypes and QTc interval on surface ECGs. SPECT images were analysed for regional [{sup 123}I]MIBG uptake in a 33-segment bullseye scheme and compared to those obtained from 10 age-matched healthy control subjects (43 {+-} 12 years). An abnormal {sup 123}I-MIBG scan was found in 17 of 28 LQTS patients (61%) with a tracer reduction mainly located in the anteroseptal segments of the left ventricle. This finding was independent of the genetic LQTS subtype. In addition, no differences were found between LQTS patients with a QTc >500 ms vs <500 ms or those suffering from syncope vs VF (p > 0.05). A distinct regional pattern of impaired cardiac sympathetic function was identified in the majority of symptomatic LQTS patients. This innervation defect was independent of the underlying genotype and clinical disease expression. (orig.)

  16. Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control (United States)

    Furlan, R.; Jacob, G.; Snell, M.; Robertson, D.; Porta, A.; Harris, P.; Mosqueda-Garcia, R.


    BACKGROUND: Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). METHODS AND RESULTS: In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75 degrees tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index alpha, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LFSAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced alpha similarly in both groups. CONCLUSIONS: COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

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

    Nakajima, Kenichi; Scholte, Arthur J H A; Nakata, Tomoaki; Dimitriu-Leen, Aukelien C; Chikamori, Taishiro; Vitola, João V; Yoshinaga, Keiichiro


    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, (123)I-meta-iodobenzylguanidine ((123)I-MIBG) was approved by the Japanese Ministry of Health, Labour and Welfare in 1992 and has therefore been widely used since in clinical settings. (123)I-MIBG was also later approved by the Food and Drug Administration (FDA) in the United States of America (USA) and it was expected to achieve broad acceptance. In Europe, (123)I-MIBG is currently used only for clinical research. This review article is based on a joint symposium of the Japanese Society of Nuclear Cardiology (JSNC) and the American Society of Nuclear Cardiology (ASNC), which was held in the annual meeting of JSNC in July 2016. JSNC members and a member of ASNC discussed the standardization of (123)I-MIBG parameters, and clinical aspects of (123)I-MIBG with a view to further promoting (123)I-MIBG imaging in Asia, the USA, Europe, and the rest of the world.

  18. Usefulness of Cardiac Sympathetic Nerve Imaging Using (123)Iodine-Metaiodobenzylguanidine Scintigraphy for Predicting Sudden Cardiac Death in Patients With Heart Failure. (United States)

    Kasama, Shu; Toyama, Takuji; Kurabayashi, Masahiko


    The autonomic nervous system plays an important role in the human heart. Activation of the cardiac sympathetic nervous system is a cardinal pathophysiological abnormality associated with the failing human heart. Myocardial imaging using (123)I-metaiodobenzylguanidine (MIBG), an analog of norepinephrine, can be used to investigate the activity of norepinephrine, the predominant neurotransmitter of the sympathetic nervous system. Many clinical trials have demonstrated that (123)I-MIBG scintigraphic parameters predict cardiac adverse events, especially sudden cardiac death, in patients with heart failure. In this review, we summarize results from published studies that have focused on the use of cardiac sympathetic nerve imaging using (123)I-MIBG scintigraphy for risk stratification of sudden cardiac death in patients with heart failure.

  19. Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia. (United States)

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio


    Familial dysautonomia (Riley-Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement.

  20. Experimental american trypanomiasis in rats: sympathetic denervation, parasitism and inflammatory process Desnervação simpática, parasitismo e processo inflamatório durante a doença de Chagas experimental, em ratos

    Directory of Open Access Journals (Sweden)

    Conceição R. S. Machado


    Full Text Available Tissue parasitism, inflammatory process (histologic methods and sympathetic denervation (glyoxylic acid-induced histofluorescence for demonstration of catecholamines were studied in the heart (atrium and verntricle and the submandibular gland of rats infected with the Y strain of Trypanosoma cruzi. In the heart paralleling intense parasitism and inflammatory process, the sympathetic denervation started at day 6 of infection and at the end of the acute phase (day 20 practically no varicose nerve terminals were found in both myocardium and vessels. In the submandibular gland, in spite of the rarity of anastigote pseudocysts and the scarcity of inflammatory foci, slight to moderate (days 13-15 of infection or moderate to severe denervation (day 20 was found. At day 120 of infection both organs exhibited normal pattern of sympathetic innervation and only the heart showed some inflammatory foci and rare psudocysts (ventricle. Our data suggest the involvement of circulating factors in the sympathetic denervation phenomena but indicate that local inflammatory process is, at least, an aggravating factor.Parasitismo tecidual, processo inflamatório (métodos histológicos e desnervação simpática (histofluorescência induzida por ácido glioxílico para demosntração de catecolaminas foram estudados no coração (átrio e ventrículo e na glândula submandibular de ratos infectados com cepa Y de Trypanosoma cruzi. No coração, em paralelo com intenso parasitismo e processo inglamatório, a desnervação simpática iniciuo-se no 6º dia de infecção e ao fim da fase aguda (20º dia praticamente nenhuma terminação nervosa varicosa foi encontrada tanto no miocárdio como em vasos. Na glândula submandibular, apesar da raridade de ninhos de amastigotas e da escassez de focos inflamatórios, encontram-se discreta e moderada 13º-15º dia de infeccção ou moderada a severa (20º dia desnervação. Aos 120 dias de infecção, ambos os órgãos exibiram

  1. Heart Rate Changes in Response to Mechanical Pressure Stimulation of Skeletal Muscles Are Mediated by Cardiac Sympathetic Nerve Activity (United States)

    Watanabe, Nobuhiro; Hotta, Harumi


    Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm2) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: −56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = −0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: −9 to +3 bpm, p mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = −0.62, p = 0.0066). These results suggest that cardiac sympathetic nerve activity regulates HR responses to muscle mechanical pressure stimulation and the direction of HR

  2. Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction (United States)

    Gavioli, Mariana; Lara, Aline; Almeida, Pedro W. M.; Lima, Augusto Martins; Damasceno, Denis D.; Rocha-Resende, Cibele; Ladeira, Marina; Resende, Rodrigo R.; Martinelli, Patricia M.; Melo, Marcos Barrouin; Brum, Patricia C.; Fontes, Marco Antonio Peliky; Souza Santos, Robson A.; Prado, Marco A. M.; Guatimosim, Silvia


    Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the α2A/α2C-adrenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease. PMID:24992197

  3. Cholinergic signaling exerts protective effects in models of sympathetic hyperactivity-induced cardiac dysfunction.

    Directory of Open Access Journals (Sweden)

    Mariana Gavioli

    Full Text Available Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO, and ii the α2A/α2C-adrenergic receptor knockout (KO mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease.

  4. Selective quantification of the cardiac sympathetic and parasympathetic nervous systems by multisignal analysis of cardiorespiratory variability. (United States)

    Chen, Xiaoxiao; Mukkamala, Ramakrishna


    Heart rate (HR) power spectral indexes are limited as measures of the cardiac autonomic nervous systems (CANS) in that they neither offer an effective marker of the beta-sympathetic nervous system (SNS) due to its overlap with the parasympathetic nervous system (PNS) in the low-frequency (LF) band nor afford specific measures of the CANS due to input contributions to HR [e.g., arterial blood pressure (ABP) and instantaneous lung volume (ILV)]. We derived new PNS and SNS indexes by multisignal analysis of cardiorespiratory variability. The basic idea was to identify the autonomically mediated transfer functions relating fluctuations in ILV to HR (ILV-->HR) and fluctuations in ABP to HR (ABP-->HR) so as to eliminate the input contributions to HR and then separate each estimated transfer function in the time domain into PNS and SNS indexes using physiological knowledge. We evaluated these indexes with respect to selective pharmacological autonomic nervous blockade in 14 humans. Our results showed that the PNS index derived from the ABP-->HR transfer function was correctly decreased after vagal and double (vagal + beta-sympathetic) blockade (P < 0.01) and did not change after beta-sympathetic blockade, whereas the SNS index derived from the same transfer function was correctly reduced after beta-sympathetic blockade in the standing posture and double blockade (P < 0.05) and remained the same after vagal blockade. However, this SNS index did not significantly decrease after beta-sympathetic blockade in the supine posture. Overall, these predictions were better than those provided by the traditional high-frequency (HF) power, LF-to-HF ratio, and normalized LF power of HR variability.

  5. Effects of sympathetic denervation on liver regeneration after partial hepatic resection%去交感神经状态对肝部分切除后肝再生的影响

    Institute of Scientific and Technical Information of China (English)

    夏锋; 何振平; 段恒春; 李昆; 陈莉; 王小丽; 董家鸿


    目的 建立去交感神经状态动物模型并探讨去交感神经状态下对肝切除后肝再生的影响。方法 雄性Wistar大鼠共90只,用6-OHDA制作去交感神经状态动物模型。其中30只大鼠分为实验组和对照组各15例。按Higgins和Anderson方法加以改良,作肝左叶和肝中叶切除(约占全肝的68%)。实验组加做去交感神经模型。术后第7天全部动物经抽血处死,计算相对肝重(HMI)、肝再生率的指数(RLR)和有丝分裂指数(MI)。肝脏DNA合成率用3H标记胸腺嘧啶核苷(3H-TdR)掺入法测得。结果 注射6-OHDA后3~14 d,NE含量明显降低。行肝切除后两组大鼠术后7 d均无死亡,实验组大鼠HMI、RLR、MI和3H-TdR DNA掺入量较对照组均明显下降(P<0.01)。结论 6-OHDA可明显起到化学性去交感神经的效果。交感神经的存在与否对肝切除后肝再生具有明显影响,去交感神经状态可抑制肝再生的进程。%Objective To establish the animal model of denervation of sympathetic nerve and to explore the effects of denervation of the sympathetic nerve on liver regeneration after partial resection. Methods The animal model of denervation of sympathetic nerve was made with 6-OHDA. A total of thirty male Wistar rats were divided equally into experimental and control group. The left and middle lobe of liver were resected with improved Higgins and Anderson's method. Meanwhile, denervation was made in the experimental group. All the rats were killed by haemospasia on the 7 th day after operation. HMI, RLR and MI were measured. The rates of DNA synthesis were detected by 3H-TdR method. Results The concentration of NE decreased extremely on day 3 to day 14 after administration of 6-ONDA. No death happened in all the rats 7 days after liver resection. HMI, RLR, MI and 3H-TdR incorporation significantly decreased in experimental group compared with that in control (P<0.01). Conclusion The chemical

  6. Heart rate complexity and cardiac sympathetic dysinnervation in patients with type 2 diabetes mellitus. (United States)

    Baumert, Mathias; Sacre, Julian W


    Cardiovascular autonomic neuropathy (CAN) is one of the most severe complications of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate associations of cardiac sympathetic dysinnervation (CSD; by (123)I-MIBG scintigraphy) with short-term heart rate variability (HRV) measured by traditional vs. complexity markers. ECG was measured in 31 diabetic patients during rest over a period of 5 minutes and HRV quantified in different domains (time and frequency domain, scaling properties, symbolic dynamics). (123)I-MIBG scintigraphy identified 16 patients with CSD. Resting heart rate was increased and HRV reduced in these patients. In a subgroup of 16 patients ECG was also measured during standing. Changes in several HRV measures upon standing demonstrated cardiac responsiveness to orthostatic stress. Strong correlations between HRV, measured during standing, and CSD were observed with metrics based on symbolic dynamics. In conclusion, HRV assessment during standing may be useful for assessing cardiac sympathetic dysinnervation in patients with type 2 diabetes mellitus.

  7. Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

    Directory of Open Access Journals (Sweden)

    Valerie Joers

    Full Text Available Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg. The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001 and 14 weeks (P<0.01 relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05, epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01 were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia.

  8. 去肾交感神经支配术与高血压%Renal sympathetic denervation for the treatment of hypertension

    Institute of Scientific and Technical Information of China (English)

    杨宁; 程康安; 李拥军


    Although effective antihypertensive drug together with lifestyle intervention has been widely employed in the medical field, essential hypertension remains one of the main diseases affecting human being's health. Because of some reasons such as lower rate of patients' awareness of hypertension, lower rate of receiving treatment, poor tolerance to the antihypertensive drugs, patient'g poor biddable willing, unreasonable medication, etc. about one third of the patients having essential hypertension are not be able to effectively control their blood pressure level and they have been in a high risk status to cardio - cerebral vascular diseases all along. Therefore, it is very urgent to find out a safer and more effective therapy for essential hypertension. Renal sympathetic denervation (RSD) has been recently employed in clinical practice for hypertension. This, therapy is based on the catheterization technique combined with the radiofrequency ablation to selectively destroy the targeted renal nerves in order to treat the intractable essential hypertension. Two clinical trials, Symplicity HTN -1 and HTN -2, have been conducted to evaluate the feasibility and effectiveness of RSD, and the results provide reliable evidence, which indicates that RSD is safe and effective in clinical use. This paper aims to make a brief introduction of the recent research progress concerning the safety and efficacy of RSD technique.(J Intervent Radiol, 2012, 21: 441-446)%目前,原发性高血压及其并发症仍是影响人类健康的主要疾病之一.原发性高血压因其知晓率低和治疗率低、药物不耐受、患者依从性差以及不合理用药等原因,有近1/3患者不能有效控制血压,处在心脑血管疾病高危状态.为此,寻求更为安全和有效的治疗高血压的方法十分迫切.去肾交感神经支配术基于导管方法应用射频消融选择性靶向损毁肾交感神经,以达到治疗顽固性高血压的目的.

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

    Energy Technology Data Exchange (ETDEWEB)

    Manrique, Alain; Hitzel, Anne; Vera, Pierre [Rouen University Hospital - Henri Becquerel Center, Nuclear Medicine, Rouen (France); Bernard, Mathieu; Bauer, Fabrice [Rouen University Hospital, Cardiology, Rouen (France); Menard, Jean-Francois [Rouen University Hospital, Biostatistics, Rouen (France); Sabatier, Remi [Caen University Hospital, Cardiology, Caen (France); Jacobson, Arnold [GE Healthcare, Princeton, NJ (United States); Agostini, Denis [Caen University Hospital, Nuclear Medicine, Caen (France)


    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.)

  10. Basal and hyperaemic myocardial blood flow in regionally denervated canine hearts: an in vivo study with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Rimoldi, Ornella E.; Camici, Paolo G. [Hammersmith Hospital, MRC Clinical Sciences Centre, London (United Kingdom); Imperial College, National Heart and Lung Institute, London (United Kingdom); Drake-Holland, Angela J. [Robert Gordon University, School of Pharmacy, Aberdeen (United Kingdom); Noble, Mark I.M. [University of Aberdeen, Department of Cardiology, Aberdeen (United Kingdom)


    Positron emission tomography (PET) studies in patients with diabetic autonomic neuropathy (DAN) have demonstrated the impact of this disease on cardiac sympathetic innervation and myocardial blood flow (MBF). To investigate the effects of selective partial sympathetic denervation of the left ventricle (LV) on baseline and hyperaemic MBF, we measured myocardial presynaptic catecholamine re-uptake (uptake-1), {beta}-adrenoceptor ({beta}-AR) density and MBF non-invasively by means of PET in a canine model of regional sympathetic denervation. In 11 anaesthetised dogs, the sympathetic nerves of the free wall and septum of the LV were removed by means of dissection and phenol painting. Three weeks later, the animals were studied with PET. MBF was measured at baseline and following i.v. adenosine (140 {mu}g kg{sup -1} min{sup -1}) and dobutamine (20 {mu}g kg{sup -1} min{sup -1}) using{sup 15}O-labelled water. Sympathetic denervation was confirmed by an 80{+-}12% decrease in the volume of distribution (V{sub d}) of [{sup 11}C]hydroxyephedrine (HED) compared with innervated regions. Myocardial {beta}-AR density was measured using [{sup 11}C]CGP12177. Innervated and denervated regions showed no differences in MBF at baseline and during adenosine or dobutamine. [{sup 11}C]HED V{sub d}was inversely correlated with MBF in both regions at baseline, and the correlation was lost during hyperaemia in denervated regions. However, for any given value of MBF, [{sup 11}C]HED V{sub d}was significantly lower in the denervated regions. {beta}-AR density was comparable in denervated and innervated regions (17.9{+-}4.2 vs 18.4{+-}3.3 pmol g{sup -1};p=NS). In this experimental model, selective, regional sympathetic denervation of the LV, which results in a profound reduction in [{sup 11}C]HED V{sub d}, did not affect baseline or hyperaemic MBF. In addition, we demonstrated that, under baseline conditions, there was a significant inverse correlation between [{sup 11}C]HED V{sub d}and MBF in

  11. Norepinephrine transporter (NET) is expressed in cardiac sympathetic ganglia of adult rat

    Institute of Scientific and Technical Information of China (English)


    The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.

  12. Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans (United States)

    Convertino, V. A.; Thompson, C. A.; Benjamin, B. A.; Keil, L. C.; Savin, W. M.; Gordon, E. P.; Haskell, W. L.; Schroeder, J. S.; Sandler, H.


    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

  13. Polycystic Ovary Syndrome Presents Higher Sympathetic Cardiac Autonomic Modulation that is not altered by Strength Training (United States)



    Polycystic ovary syndrome (PCOS) may present important comorbidities, such as cardiovascular and metabolic diseases, which are often preceded by changes in cardiac autonomic modulation. Different types of physical exercises are frequently indicated for the prevention and treatment of PCOS. However, little is known about the effects of strength training on the metabolic, hormonal, and cardiac autonomic parameters. Therefore, our aim was to investigate the effects of strength training on the autonomic modulation of heart rate variability (HRV) and its relation to endocrine-metabolic parameters in women with PCOS. Fifty-three women were divided into two groups: CONTROL (n=26) and PCOS (n=27). The strength training lasted 4 months, which was divided into mesocycles of 4 weeks each. The training load started with 70% of one repetition maximum (1RM). Blood samples were collected before and after intervention for analysis of fasting insulin and glucose, HOMA-IR, testosterone, androstenedione and testosterone/androstenedione (T/A) ratio. Spectral analysis of HRV was performed to assess cardiac autonomic modulation indexes. The PCOS group presented higher insulin and testosterone levels, T/A ratio, along with increased sympathetic cardiac autonomic modulation before intervention. The training protocol used did not cause any change of endocrine-metabolic parameters in the CONTROL group. Interestingly, in the PCOS group, reduced testosterone levels and T/A ratio. Additionally, strength training did not have an effect on the spectral parameter values of HRV obtained in both groups. Strength training was not able to alter HRV autonomic modulation in women with PCOS, however may reduce testosterone levels and T/A ratio. PMID:27990221

  14. Anaesthesia Application for Cardiac Denervation in a Patient with Long QT Syndrome and Cardiomyopathy (United States)

    Karadeniz, Ümit; Demir, Aslı; Koçulu, Rabia


    Long QT syndrome is a congenital disorder that is characterized by a prolongation of the QT interval on electrocardiograms and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest or sudden death. Cardiomyopathy and pulmonary hypertension diseases have additional risks in anaesthesia management. In this study, we emphasize on one lung ventilation, pacemaker-implantable cardioverter–defibrillator and the anaesthesia management process in a patient with long QT syndrome, cardiomyopathy and pulmonary hypertension who underwent thoracic sympathectomy. PMID:27366557

  15. In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-α-methyl-histamine and its prodrug BP 2.94 in the dog


    Mazenot, Catherine; Ribuot, Christophe; Durand, Andrée; Joulin, Yves; Demenge, Pierre; Godin-Ribuot, Diane


    The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog.Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1–4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-α-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP).Cardiac sympathetic stimulation induced a noradr...

  16. Assessment of cardiac sympathetic nerve abnormalities by {sup 123}I-MIBG (metaiodobenzylguanidine) myocardial scintigraphy in diabetic patients undergoing hemodialysis

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Hiroshige; Oda, Hiroshi; Matsuno, Yukihiko [Prefectural Gifu Hospital (Japan)] [and others


    We compared cardiac sympathetic nerve abnormalities in patients hemodialyzed because of diabetic nephropathy (DN, n=18) and chronic glomerulonephritis (CGN, n=21). {sup 123}I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in this study. SPECT and anterior planar myocardial images were obtained 15 minutes after (initial images) and 4 hours after (delayed images) an injection of MIBG. The following results were obtained: (1) SPECT showed more defects in DN than in CGN. (2) The heart to superior mediastinum uptake ratio (H/M) was lower in DN than in CGN. These findings suggest that myocardial uptake of MIBG in DN is significantly impaired because of cardiac sympathetic nerve abnormalities. These abnormalities may affect the prognosis in DN. (author).

  17. Effects of alpha-adrenoceptor and of combined sympathetic and parasympathetic blockade on cardiac performance and vascular resistance

    DEFF Research Database (Denmark)

    Kelbaek, H; Frandsen, Henrik Lund; Hilsted, J


    1. Cardiac performance and vascular resistance was studied in seven healthy men by radionuclide cardiography and venous plethysmography before and after alpha-adrenoceptor blockade with phentolamine and after combined alpha-adrenoceptor, beta-adrenoceptor (propranolol) and parasympathetic (atropine...... propranolol and atropine were added. 3. These results indicate that peripheral vasoconstriction especially that exerted by alpha-adrenoceptor nervous tone in skeletal muscle restricts left ventricular emptying of the intact heart. During pharmacologic blockade of the sympathetic and parasympathetic nervous...

  18. Effect of Renal Sympathetic Denervation on Endothelial Function in Hypertensive Dogs%去肾脏交感神经术对犬高血压及内皮功能的研究

    Institute of Scientific and Technical Information of China (English)

    赵斌; 卢成志; 张欣; 于翔; 王彦欧


    Objective: To explore the relationship between hypertension, renal sympathetic activity and endothelial function in dogs. Methods: Eighteen mongrel dogs were divided into intervention group (n=10) and control group (n=8). The hypertension model was made in dogs of intervention group. The percutaneous catheter-based radiofrequency was given to dogs in two groups. Values of mean blood pressure (MAP) and angiotensin II (Ang II) were detected before operation and at 2, 4 and 10 weeks after operation. The changes of endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected before and 12 weeks after molding, and 10 weeks after denervation. ReSUltSrThe values of MAP and Ang II were significantly lower 2, 4 and 10 weeks after operation than those before operation in two groups (P < 0.05 or P < 0.01). The level of ET-1 was higher after 12 weeks in intervention group, but lower after denervation. The level of CGR was significantly lower after 12 weeks in intervention group (P < 0.01), but was significantly increased after denervation (P < 0.01). Conclusion: Renal sympathetic denervation can significantly decrease blood pressure and improve endothelial dysfunction in dogs.%目的:探讨高血压病与交感神经兴奋及内皮功能的关系.方法:18只杂种犬随机分为高血压模型组(n=10)和对照组(n=8).高血压模型组于全身麻醉下手术分离颈动脉和迷走神经后制作高血压模型,对照组同样操作但不制作高血压模型,造模12周后,2组动物都接受去肾脏交感神经术.测量2组术前和术后2、4、10周的平均动脉压(MAP)和血管紧张素Ⅱ(AngⅡ),测量高血压模型组造模前、造模后12周和去神经术后10周的内皮素-1(ET-1)及降钙素基因相关肽(CGRP).结果:2组术后2、4、10周的MAP和AngⅡ均低于术前,差异有统计学意义(P< 0.05或P<0.01).在高血压模型组,造模后12周ET-1水平较造模前升高,去神经术后又下降;CGRP在造模后12周较造模

  19. Clinical usefulness of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy in diabetic patients with cardiac sympathetic nerve dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Miyanaga, Hajime; Yoneyama, Satoshi; Kamitani, Tadaaki; Kawasaki, Shingo; Takahashi, Toru; Kunishige, Hiroshi [Matsushita Memorial Hospital, Osaka (Japan)


    To assess the clinical utility of {sup 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).

  20. 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.


    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 anti

  1. Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale. (United States)

    Böhm, Michael; Ewen, Sebastian; Mahfoud, Felix


    The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome.

  2. Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure. (United States)

    Wang, Wei-Zhong; Gao, Lie; Wang, Han-Jun; Zucker, Irving H; Wang, Wei


    Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT1R antagonist losartan (10 and 100 pmol) dose-dependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT1R-dependent mechanism.

  3. Cardiac sympathetic activity in chronic heart failure: cardiac (123)I-mIBG scintigraphy to improve patient selection for ICD implantation. (United States)

    Verschure, D O; van Eck-Smit, B L F; Somsen, G A; Knol, R J J; Verberne, H J


    Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with (123)I-meta-iodobenzylguanide ((123)I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with (123)I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation.

  4. The low frequency power of heart rate variability is neither a measure of cardiac sympathetic tone nor of baroreflex sensitivity. (United States)

    Martelli, Davide; Silvani, Alessandro; McAllen, Robin M; May, Clive N; Ramchandra, Rohit


    The lack of noninvasive approaches to measure cardiac sympathetic nerve activity (CSNA) has driven the development of indirect estimates such as the low-frequency (LF) power of heart rate variability (HRV). Recently, it has been suggested that LF HRV can be used to estimate the baroreflex modulation of heart period (HP) rather than cardiac sympathetic tone. To test this hypothesis, we measured CSNA, HP, blood pressure (BP), and baroreflex sensitivity (BRS) of HP, estimated with the modified Oxford technique, in conscious sheep with pacing-induced heart failure and in healthy control sheep. We found that CSNA was higher and systolic BP and HP were lower in sheep with heart failure than in control sheep. Cross-correlation analysis showed that in each group, the beat-to-beat changes in HP correlated with those in CSNA and in BP, but LF HRV did not correlate significantly with either CSNA or BRS. However, when control sheep and sheep with heart failure were considered together, CSNA correlated negatively with HP and BRS. There was also a negative correlation between CSNA and BRS in control sheep when considered alone. In conclusion, we demonstrate that in conscious sheep, LF HRV is neither a robust index of CSNA nor of BRS and is outperformed by HP and BRS in tracking CSNA. These results do not support the use of LF HRV as a noninvasive estimate of either CSNA or baroreflex function, but they highlight a link between CSNA and BRS.

  5. 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


    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)

  6. 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)


    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)

  7. Renal denervation: a new therapeutic approach for resistant hypertension

    Institute of Scientific and Technical Information of China (English)

    Cao Longxing; Fu Qiang; Wang Binghui; Li Zhiliang


    Objective To review the advances in studies on renal denervation.Data sources References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014.Study selection Articles with keywords "renal denervation" and "resistant hypertension" were selected.Results Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity.Renal denervation is a new,catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries.Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases,Symplicity HTN 3 study,the most rigorous clinical trial of renal denervation to date,failed to meet its primary endpoint.The procedure also has other limitations such as the lack of long term,efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure.An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review.Conclusions Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity.In its early stage of clinical application,the efficacy of the procedure is still controversial.Large scale,blind,randomized,controlled clinical trials are still necessary to address the limitations of the procedure.

  8. An electrophysiologist perspective on risk stratification in heart failure: can better understanding of the condition of the cardiac sympathetic nervous system help? (United States)

    Borgquist, Rasmus; Singh, Jagmeet P


    Heart failure is often complicated by arrhythmias that can adversely affect the quality of life and increase the risk for sudden cardiac death. Current risk stratification strategies for sudden cardiac death in the heart failure patient are not ideal, with much potential for further refinement. Overactivation of the sympathetic nervous system has been shown to be associated with worsening heart failure as well as arrhythmic events. Recent advances in our understanding of the autonomic nervous system and new methods for quantification of the pathologic activation of the sympathetic nerves have triggered increasing interest in this field. This viewpoint focuses on the need for and challenges of risk stratification of sudden death in the heart failure patient and discusses the potential value of measuring sympathetic nervous system activity to better stratify risk and to select patients with heart failure for implantable cardioverter defibrillator therapy.

  9. Scintigraphic assessment of regional cardiac sympathetic nervous system in patients with single-vessel coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, Kazuyuki; Yoshida, Hiroshi; Nawada, Ryuzo; Obayashi, Kazuhiko; Tamekiyo, Hiromichi; Mochizuki, Mamoru [Shizuoka General Hospital (Japan)


    In coronary artery disease, the cardiac sympathetic nervous system is closely associated with myocardial ischemia. I-123 metaiodobenzylguanidine (MIBG) imaging allows us to assess the cardiac sympathetic nervous system regionally. One-hundred and eleven patients with single-vessel disease underwent regional quantitative analysis of MIBG imaging before successful percutaneous transluminal coronary angioplasty (PTCA), and repeat angiography 6 months after PTCA. Based on the results of the follow-up left ventriculogram, patients were divided into 3 groups: 39 angina pectoris (AP), 48 prior myocardial infarction without asynergy (MI without asynergy) and 24 prior myocardial infarction with asynergy (Ml with asynergy). AP and MI without asynergy had significant correlations between uptake parameters and regional washout in the territory of diseased vessels, among which the severity score in AP was the most closely correlated with regional washout (r=0.79, p<0.0001). These correlations disappeared in MI with asynergy. To compare regional MIBG parameters in the territory of the diseased vessel as well as in the territories of the other major coronary arteries among the 3 groups, we examined MIBG parameters in 57 patients with left anterior descending artery (LAD) disease selected from among the study patients. Regional washout in the territory of the LAD was significantly higher in the MI without asynergy group than in the other two groups. The left circumflex artery (LCX) region showed significantly reduced MlBG uptake and an increased extent score in the MI with asynergy group compared with the AP group, although only a difference in the extent score existed between the MI with asynergy group and the AP group in the right coronary artery (RCA) region. In addition, the global ejection fraction before PTCA showed a significant negative correlation with each regional washout rate. In this way, regional quantitative analysis of MIBG imaging can detect the regional

  10. Catheter-based renal sympathetic denervation for resistant hypertension in chronic renal failure:recent progress in clinical research%肾交感射频消融术在慢性肾脏病患者高血压治疗的应用研究

    Institute of Scientific and Technical Information of China (English)

    柏雨双; 甘华


    交感神经过度兴奋与慢性肾脏疾病(chronic kidney disease,CKD)患者高血压的发生、发展密切相关.而抗交感药物难以达到降压治疗目标.近年来,肾交感射频消融术(catheter-based renal sympathetic denervation,RSD)迅猛发展,成为了CKD患者治疗高血压新的尝试.本文对此项技术在CKD患者高血压治疗的应用进行探讨.

  11. A vesicular sequestration to oxidative deamination shift in myocardial sympathetic nerves in Parkinson's disease. (United States)

    Goldstein, David S; Sullivan, Patricia; Holmes, Courtney; Miller, Gary W; Sharabi, Yehonatan; Kopin, Irwin J


    In Parkinson's disease (PD), profound putamen dopamine (DA) depletion reflects denervation and a shift from vesicular sequestration to oxidative deamination of cytoplasmic DA in residual terminals. PD also involves cardiac sympathetic denervation. Whether PD entails myocardial norepinephrine (NE) depletion and a sequestration-deamination shift have been unknown. We measured apical myocardial tissue concentrations of NE, DA, and their neuronal metabolites 3,4-dihydroxyphenylglycol (DHPG), and 3,4-dihydroxyphenylacetic acid (DOPAC) from 23 PD patients and 23 controls and ascertained the extent of myocardial NE depletion in PD. We devised, validated in VMAT2-Lo mice, and applied 5 neurochemical indices of the sequestration-deamination shift-concentration ratios of DOPAC:DA, DA:NE, DHPG:NE, DOPAC:NE, and DHPG:DOPAC-and used a kinetic model to estimate the extent of the vesicular storage defect. The PD group had decreased myocardial NE content (p Parkinson's disease (PD) patients have profound (98%) myocardial norepinephrine depletion, because of both cardiac sympathetic denervation and a shift from vesicular sequestration to oxidative deamination of cytoplasmic catecholamines in the residual nerves. This shift may be part of a final common pathogenetic pathway in the loss of catecholaminergic neurons that characterizes PD.

  12. Effect of catheter-based renal sympathetic denervation in pigs with rapid pacing induced heart failure%肾交感神经射频消融术治疗快速起搏致猪心力衰竭的疗效

    Institute of Scientific and Technical Information of China (English)

    谢赟; 刘奇良; 徐佑龙; 郜俊清; 严鹏勇; 张文全; 孙剑光; 王明瑜; 金惠根


    目的 研究经导管射频消融去肾交感神经术(catheter-based renal sympathetic denervation,RDN)对右心室快速起搏导致的心力衰竭猪心功能的改善作用.方法 健康广西巴马小型猪12头,建立快速起搏致心力衰竭模型,以随机数字表法分为消融组(n=6,心室快速起搏1周后接受RDN术)和对照组(n=6,单纯心室快速起搏,不接受RDN术).12头猪分别于建模前及其后每周检查左心室舒张末期内径、左心室收缩末期内径、左心室射血分数(LVEF).建模后1周(RDN术前)及2周检测血肌酐和血肾素、醛固酮等的水平.RDN术后1周复查肾动脉造影.建模2周后处死猪,检查心肾组织病理、肾动脉病理及交感神经染色.结果 12头猪置入起搏器前LVEF平均值为(60.5±6.0)%,快速起搏后1周,平均值为(35.3±9.8)%,表明右心室快速起搏致心衰模型建立成功.随访2周,消融组LVEF高于对照组[(42.8±5.9)%比(33.4±9.7)%,P=0.001 8],左心室收缩末期内径明显小于对照组[(28.4±3.7)mm比(33.0±2.0) mm,P=0.001 6].消融组消融后肾素浓度较消融前下降[(170.75 ±68.94) ng/L比(216.25 ±83.73) ng/L,P=0.046 4],醛固酮水平无明显改变,对照组醛固酮水平则明显上升(P =0.048).消融组血压、肾功能均无明显下降,无肾动脉狭窄、夹层及血栓形成.肾动脉病理及免疫组织化学显示血管外膜交感神经元被破坏.结论 RDN可以显著改善心力衰竭猪的心脏收缩功能,逆转心室重构,抑制肾素-血管紧张素-醛固酮系统活性.%Objective This study investigated the effect of catheter-based renal sympathetic denervation (RDN) in pigs with rapid pacing induced heart failure.Methods Heart failure was induced by rapid right ventricular pacing in 12 pigs and pigs were randomly divided into RDN group(n =6):pacing + RDN at 7 days post pacing; control group (n =6):pacing only.Echocardiography examination (LVEF,LVEDD and LVESD) was performed before pacing and

  13. Regional heterogeneity in cardiac sympathetic innervation in acute myocardial infarction: relationship with myocardial oedema on magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Gimelli, Alessia; Masci, Pier Giorgio; Pasanisi, Emilio Maria; Lombardi, Massimo [Fondazione CNR/Regione Toscana, Pisa (Italy); Liga, Riccardo; Grigoratos, Chrysanthos [University Hospital of Pisa, Pisa (Italy); Marzullo, Paolo [Fondazione CNR/Regione Toscana, Pisa (Italy); Institute of Clinical Physiology, CNR, Pisa (Italy)


    To assess the relationships between myocardial structure and function on cardiac magnetic resonance (CMR) imaging and sympathetic tone on {sup 123}I-metaiodobenzylguanidine ({sup 123}I-MIBG) scintigraphy early after myocardial infarction (MI). Ten patients underwent {sup 123}I-MIBG and {sup 99m}Tc-tetrofosmin rest cadmium zinc telluride scintigraphy 4 ± 1 days after MI. The segmental left ventricular (LV) relative radiotracer uptake of both {sup 99m}Tc-tetrofosmin and early {sup 123}I-MIBG was calculated. The day after scintigraphy, on CMR imaging, the extent of ischaemia-related oedema and of myocardial fibrosis (late gadolinium enhancement, LGE) was assessed. Accordingly, the extent of oedema and LGE was evaluated for each segment and segmental wall thickening determined. Based on LGE distribution, LV segments were categorized as ''infarcted'' (56 segments), ''adjacent'' (66 segments) or ''remote'' (48 segments). Infarcted segments showed a more depressed systolic wall thickening and greater extent of oedema than adjacent segments (p < 0.001) and remote segments (p < 0.001). Interestingly, while uptake of {sup 99m}Tc-tetrofosmin was significantly depressed only in infarcted segments (p < 0.001 vs. both adjacent and remote segments), uptake of {sup 123}I-MIBG was impaired not only in infarcted segments (p < 0.001 vs. remote) but also in adjacent segments (p = 0.024 vs. remote segments). At the regional level, after correction for {sup 99m}Tc-tetrofosmin and LGE distribution, segmental {sup 123}I-MIBG uptake (p < 0.001) remained an independent predictor of ischaemia-related oedema. After acute MI the regional impairment of sympathetic tone extends beyond the area of altered myocardial perfusion and is associated with myocardial oedema. (orig.)

  14. Using Lorenz plot and Cardiac Sympathetic Index of heart rate variability for detecting seizures for patients with epilepsy. (United States)

    Jeppesen, Jesper; Beniczky, Sandor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders


    Tachycardia is often seen during epileptic seizures, but it also occurs during physical exercise. In order to assess whether focal epileptic seizures can be detected by short term moving window Heart Rate Variability (HRV) analysis, we modified the geometric HRV method, Lorenz plot, to consist of only 30, 50 or 100 R-R intervals per analyzed window. From each window we calculated the longitudinal (L) and transverse (T) variability of Lorenz plot to retrieve the Cardiac Sympathetic Index (CSI) as (L/T) and "Modified CSI" (described in methods), and compared the maximum during the patient's epileptic seizures with that during the patient's own exercise and non-seizure sessions as control. All five analyzed patients had complex partial seizures (CPS) originating in the temporal lobe (11 seizures) during their 1-5 days long term video-EEG monitoring. All CPS with electroencephalographic correlation were selected for the HRV analysis. The CSI and Modified CSI were correspondently calculated after each heart beat depicting the prior 30, 50 and 100 R-R intervals at the time. CSI (30, 50 and 100) and Modified CSI (100) showed a higher maximum peak during seizures than exercise/non-seizure (121-296%) for 4 of the 5 patients within 4 seconds before till 60 seconds after seizure onset time even though exercise maximum HR exceeded that of the seizures. The results indicate a detectable, sudden and inordinate shift towards sympathetic overdrive in the sympathovagal balance of the autonomic nervous system just around seizure-onset for certain patients. This new modified moving window Lorenz plot method seems promising way of constructing a portable ECG-based epilepsy alarm for certain patients with epilepsy who needs aid during seizure.

  15. 经导管消融选择性去肾交感神经治疗——未来心力衰竭治疗的热点%Catheter-based Selective Renal Artery Sympathetic Denervation-A Hot Spot of Managing Heart Failure in the Future

    Institute of Scientific and Technical Information of China (English)

    刘晓莉; 肖培林


    心力衰竭是各种心脏疾病的终末阶段.近几十年来,心力衰竭的治疗得到了一定的发展,但仍不能明显改善患者生存率,且需长期大量服药,严重影响患者生活质量.大量的研究显示:交感神经系统激活在心力衰竭的发生发展中扮演着重要角色.自上世纪40、50年代,学者们已开始进行去交感神经治疗心力衰竭的尝试,但碍于当时设备和技术的限制,治疗效果不尽人意.可喜的是,澳大利亚的权威学者近几年在美国心脏病学会/美国心脏协会心血管年会上介绍了一种安全、有效的新型去肾交感神经的方法,即经导管消融选择性去肾交感神经.该研究证实此方法可以明显降低全身交感活性.那么经导管消融去肾交感神经治疗能否成为未来心力衰竭治疗的热点呢?现将对去交感神经治疗心力衰竭的现状和进展做一综述.%Heart failure is the end-stage of serious heart disease. In recent decades, the heart failure treatment has gained some devel -opment, but still can' t significantly improve survival rate. The patients need to take a large amount of medication , and influence seriously the life quality of patients. Some study demonstrated that the somatic sympathetic nerves drive plays an important role in the development of heart failure. The sympathetic nerves denervation therapy has been researched since 1940 ~ 1950s, but the result is not satisfactory because of the restriction of poor technology. On the 2009 ACC/AHA cardiovascular annual conference , Krum MD introduced a new therapeutic method: the catheter-based renal artery ablation renal sympathetic nerves denervation . The HTN-2 Trail prove that the new method is safe and effective. The study (HTN-2) has been confirmed that the method can obviously reduce the whole body sympathetic activity . Will the catheter-based selective renal artery sympathetic denervation be a hot spot of managing heart failure in the future

  16. Percutaneous lumbar sympathectomy: A comparison of radiofrequency denervation versus phenol neurolysis

    Energy Technology Data Exchange (ETDEWEB)

    Haynsworth, R.F. Jr.; Noe, C.E. (Baylor Univ. Medical Center, Dallas, TX (USA))


    A new percutaneous approach to sympathectomy using radiofrequency denervation has seemed to offer longer duration and less incidence of postsympathetic neuralgia as compared to phenol sympathetic blocks. To compare these techniques, 17 patients underwent either phenol lumbar sympathetic blocks (n = 9) or radiofrequency denervation (n = 8). Duration of sympathetic block was followed by a sweat test and temperature measurements. Results indicate that 89% of patients in the phenol group showed signs of sympathetic blockade after 8 weeks, as compared to 12% in the radiofrequency group (P less than 0.05). Although the incidence of post sympathetic neuralgia appears to be less with radiofrequency denervation, further refinement of needle placement to ensure complete lesioning of the sympathetic chain will be required before the technique can offer advantages over current phenol techniques.

  17. Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias (United States)

    Jungen, Christiane; Scherschel, Katharina; Eickholt, Christian; Kuklik, Pawel; Klatt, Niklas; Bork, Nadja; Salzbrunn, Tim; Alken, Fares; Angendohr, Stephan; Klene, Christiane; Mester, Janos; Klöcker, Nikolaj; Veldkamp, Marieke W.; Schumacher, Udo; Willems, Stephan; Nikolaev, Viacheslav O.; Meyer, Christian


    The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis. PMID:28128201

  18. Cardiac spectral power reflects parasympathetic but not sympathetic nervous system activity in a clinical population. (United States)

    Muth, E R; Morrow, G R; Jiang, W; Stern, R M; Dubeshter, B


    The purpose of this short communication is to report our clinical findings regarding the use of the low frequency (LF, 0.02-0.15 Hz) and high frequency (HF, > 0.15 Hz) components of the spectral decomposition of heart-rate as indices of sympathetic (SNS) and parasympathetic nervous system (PNS) activity, respectively. Thirty-two females with histologically confirmed ovarian cancer, ranging in age from 46-72 years, participated in an autonomic assessment protocol consisting of a resting heart rate recording and several ANS function tests. The LF, HF and total power measures from the spectral decomposition were highly correlated with one another. In addition, the spectral components were most highly correlated with measures of PNS activity, i.e. standard deviation of heart rate at rest and the ratio of the six longest to the six shortest R-R intervals during deep breathing (E:I ratio). It is concluded, as other researchers have stated, that the use of the HF component of the HR spectrum as a measure of PNS activity is warranted, but caution must be used when interpreting the LF component.

  19. Effects of Spinal Cord Stimulation on Cardiac Sympathetic Nerve Activity in Patients with Heart Failure

    DEFF Research Database (Denmark)

    Naar, Jan; Jaye, Deborah; Linde, Cecilia


    activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. METHODS: HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week...... intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-μs pulse duration, aiming at T2-T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using (123) I......-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. RESULTS: We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0...

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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

  1. [The state of sympathetic-adrenal system in patients with chronic cardiac insufficiency]. (United States)

    Nigmatullin, R R; Kirillova, V V; Dzhordzhikiia, R K; Kudrin, V S; Klodt, P M


    Activation of sympato-adrenal system plays an important role in the development of chronic cardiac failure (CCF). However, its relation to morpho-functional state of myocardium in CCF patients is virtually unknown. HPLC with electrochemical detection was used to determine plasma noradrenalin, adrenalin, and their precursors, 3,4-dioxyphenylalanine (DOPA) and dopamine, in patients with different morpho-functional changes in myocardium. The study demonstrated enhanced activity of sympato-adrenal system in patients with CCF. It showed for the first time that activity of sympato-adrenal system in CCF patients depends on the morpho-functional status of myocardium.

  2. Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure. (United States)

    Abukar, Yonis; May, Clive N; Ramchandra, Rohit


    Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg(-1)·h(-1)) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep (n = 6) and sheep with pacing-induced HF (n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (-8 ± 4 mmHg and -4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF.

  3. The human sympathetic nervous system: its relevance in hypertension and heart failure. (United States)

    Parati, Gianfranco; Esler, Murray


    Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in

  4. Evaluation of cardiac sympathetic neuronal integrity in diabetic patients using iodine-123 metaiodobenzylguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Jung [Department of Diagnostic Radiology and Nuclear Medicine, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of); Lee, Jong Doo [Department of Diagnostic Radiology and Nuclear Medicine, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of); Ryu, Young Hoon [Department of Diagnostic Radiology and Nuclear Medicine, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of); Jeon, Pyoung [Department of Diagnostic Radiology and Nuclear Medicine, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of); Shim, Yong Woon [Department of Diagnostic Radiology and Nuclear Medicine, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of); Yoo, Hyung Sik [Department of Diagnostic Radiology and Nuclear Medicine, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of); Park, Chang Yun [Department of Diagnostic Radiology and Nuclear Medicine, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of); Lim, Seung Gil [Department of Endocrinology, Yonsei University, College of Medicine, 134 Shincheon-dong, Seodaemun-gu, Seoul, 120-752 (Korea, Republic of)


    Autonomic dysfunction is associated with increased mortality in diabetic patients. To evaluate the cardiac autonomic dysfunction in these patients, a prospective study was undertaken using iodine-123 metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET). The study groups consisted of ten diabetic patients with cardiac autonomic neuropathy (group I) and six without autonomic neuropathy (group II). Autonomic nervous function tests, thallium scan, radionuclide ventriculographic data including ejection fraction and wall motion study, and 24-h urine catecholamine levels were evaluated. {sup 123}I-MIBG SPET was performed at 30 min and 4 h following injection of 3 mCi of {sup 123}I-MIBG in groups I and II and in normal subjects (n=4). On planar images, the heart to mediastinum (H/M) ratio was measured. Defect pattern and severity of MIBG uptake were qualitatively analysed on SPET. Compared with control subjects, diabetic patients had a reduced H/M ratio regardless of the presence of clinical autonomic neuropathy. There was no difference in H/M ratio between groups I and II. On SPET images, focal or diffuse defects were demonstrated in all patients in group I, and in five of the six patients in group II. The extent of defects tended to be more pronounced in group I than in group II. In conclusion, {sup 123}I-MIBG scan was found to be a more sensitive method than clinical autonomic nervous function tests for the detection of autonomic neuropathy in diabetes. (orig.). With 3 figs., 1 tab.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

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


    Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI). We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from {sup 99m}Tc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from {sup 201}Tl scintigraphy 3-5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment. Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from {sup 201}Tl and {sup 123}I-MIBG were significantly lower (26{+-}6 vs 30{+-}5, P<0.01, and 32{+-}8 vs 40{+-}6, P<0.0001, respectively), the H/M ratio significantly higher (1.99{+-}0.16 vs 1.77{+-}0.30, P<0.005) and the WR significantly lower (36%{+-}8% vs 44%{+-}12%, P<0.005) than in group B

  7. Implications of Renal Denervation Therapy in Patients with Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Fernando Jaén-Águila


    Full Text Available Obstructive sleep apnea (OSA syndrome is a prevalent condition characterized by repeated episodes of obstruction of the upper airway, leading to intermittent hypoxemia and important endothelial and anatomical dysfunctions that cause cardiovascular and cerebrovascular disease. The finding of the relationship between OSA and hypertension, especially resistant hypertension (RHT, has increased the interest in therapeutic strategies that affect renal sympathetic activity in these patients. The observational studies published until now demonstrated that renal denervation therapy can reduce the severity of OSA syndrome. Renal sympathetic denervation (RDN could be a future therapeutic possibility for conditions other than RHT, such as atrial fibrillation, heart failure, obesity, and OSA syndrome, where renal sympathetic system plays an important physiological role. The aim of this review was to elucidate the implications of renal sympathetic activity in OSA syndrome.

  8. Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction. (United States)

    Lymperopoulos, Anastasios; Rengo, Giuseppe; Gao, Erhe; Ebert, Steven N; Dorn, Gerald W; Koch, Walter J


    Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2)-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells of the adrenal gland, we crossed PNMTCre mice, expressing Cre recombinase under the chromaffin cell-specific phenylethanolamine N-methyltransferase (PNMT) gene promoter, with floxedGRK2 mice. After confirming a significant ( approximately 50%) reduction of adrenal GRK2 mRNA and protein levels, the PNMT-driven GRK2 knock-out (KO) offspring underwent myocardial infarction (MI) to induce HF. At 4 weeks post-MI, plasma levels of both norepinephrine and epinephrine were reduced in PNMT-driven GRK2 KO, compared with control mice, suggesting markedly reduced post-MI sympathetic activation. This translated in PNMT-driven GRK2 KO mice into improved cardiac function and dimensions as well as amelioration of abnormal cardiac beta-adrenergic receptor signaling at 4 weeks post-MI. Thus, adrenal-targeted GRK2 gene KO decreases circulating CAs, leading to improved cardiac function and beta-adrenergic reserve in post-MI HF. GRK2 inhibition in the adrenal gland might represent a novel sympatholytic strategy that can aid in blocking HF progression.

  9. 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)


    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.)

  10. 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)


    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.)

  11. 消融肾动脉交感神经对肺动脉高压犬心室收缩功能的影响%Evaluation of the ventricular systolic function in dogs with pulmonary artery hypertension after transcatheter ;renal sympathetic denervation

    Institute of Scientific and Technical Information of China (English)

    胡伟; 赵庆彦; 于胜波; 孙彬; 陈辽; 郭瑞强


    目的:应用二维斑点追踪技术评价肾动脉交感神经消融对肺动脉高压犬心脏收缩功能的影响。方法本实验犬分3组:对照组7只,肺高压(PAH)组8只,肾动脉交感神经消融(PAH+RSD)组7只。PAH 组及PAH+RSD组静脉注射脱氢野百合碱,建立肺动脉高压模型,且 PAH+RSD组进一步消融双侧肾动脉交感神经,而对照组及PAH 组做假手术处理。分别于建模前和建模8周后观察比格犬的血压变化及心脏指标变化。测量左室侧壁平均应变、室间隔平均应变、右室侧壁平均应变;通过心尖四腔观左室及右室长轴6个节段二维应变曲线,计算收缩期达峰时间,从而计算左室及右室纵向同步性(LVTsl-6SD、RVTsl-6SD);通过左室心尖水平及二尖瓣水平得到左室扭转曲线,计算左室整体最大扭转角度。结果三组间左室侧壁平均应变无明显变化(P >0.05),PAH+RSD组室间隔平均应变及右室侧壁平均应变明显高于 PAH 组(P <0.01);LVTsl-6SD 和 RVTsl-6SD 在 PAH+RSD 组较 PAH 组明显减低[(25.45±3.59)ms 对(40.40±2.83)ms,P <0.001;(34.16±2.81)ms 对(51.98±3.64)ms,P <0.001];左室整体最大扭转角度在PAH+RSD组明显高于 PAH 组[(10.47±0.73)°对(8.46±1.06)°,P <0.001]。结论肾动脉交感神经消融可以部分抑制肺动脉高压对心室收缩功能的损害作用。%Objective To evaluate the effects of transcatheter renal sympathetic denervation (RSD) on the cardiac systolic function of dogs with pulmonary arterial hypertension(PAH)using two-dimensional speckle tracking imaging (2D-STI).Methods Twenty two dogs were divided in to three groups:control group (n=7),PAH group (n =8),PAH+RSD group(n =7).Pulmonary artery hypertension models were made by monocrotaline injection in PAH group and PAH+RSD group,while bilateral renal artery sympathetic nerve were also ablated in PAH+RSD group.Meanwhile,sham operation treatment were made in the control group and PAH group.The changes

  12. Clinical research progress in percutaneous catheter ablation of renal sympathetic nerve%经导管肾交感神经射频消融术临床研究进展

    Institute of Scientific and Technical Information of China (English)

    潘涛; 郭金和; 滕皋军


    Transcatheter renal sympathetic denervation with radiofrequency ablation has become a new treatment for refractory hypertension.Recent studies have showed that renal sympathetic denervation can also treat the diseases that are related to increased sympathetic nerve activity, such as metabolic diseases, cardiac disfunction, arrhythmia, obstructive sleep apnea syndrome, polycystic ovary syndrome, renal failure, etc. This paper aims to make a general review on the recent clinical research progress about renal sympathetic denervation with radiofrequency ablation.%经导管肾交感神经射频消融术(RDN)是治疗顽固性高血压的新手段,进一步研究发现RDN术还可治疗交感神经活性增高相关疾病,如代谢性疾病、心功能不全、心律失常、阻塞性睡眠呼吸暂停综合征、多囊卵巢综合征和肾功能不全等.本文就RDN术临床研究进展作一综述.

  13. 肾去交感神经对心力衰竭犬心室基质重构的影响%Renal sympathetic denervation suppresses ventricular substrate remodeling in a canine high-rate pacing model

    Institute of Scientific and Technical Information of China (English)

    王晓占; 赵庆彦; 于胜波; 王徐乐; 肖金平; 代子玄; 黄鹤; 唐艳红; 黄从新


    目的 探讨肾去交感神经(RSD)对心力衰竭(心衰,HF)犬心室基质重构的影响.方法 19只犬按照随机数字表法随机分为3组:假手术组(n=7),心衰组(n=6)和RSD组(n=6).假手术组植入起搏器不起搏;心衰组植入起搏器后行右室快速起搏3周;RSD组先行双侧肾动脉消融再行右室快速起搏3周,实验前后监测血流动力学变化,采用Masson染色、ELISA和Western印迹等方法检测心室间质纤维化、脑钠肽(BNP)、血管紧张素Ⅱ(AngⅡ)、醛固酮和转化生长因子-β(TGF-β)的变化.结果 心衰组和RSD组犬的左右心室舒张末期内径均明显增大[左室:(27.0±2.4)mm 比(37.0±2.8) mm,P<0.01和(30.0±2.5) mm比(36.0±2.8) mm,P<0.05;右室:(11.0±1.5)mm比(14.0±1.7) mm,P=0.03和(12.0±1.1) mm比(14.0±1.2) mm,P<0.05].与RSD组相比,心衰组犬左室舒张末期压力升高[(25.0±3.7) mmHg比(3.3±1.6) mmHg,P<0.01],且心室肌组织纤维化程度明显升高(左室:24.1%±4.8%比8.5%±1.9%,P<0.01;右室:17.2%±5.2%比11.8%±3.9%,P<0.01).与假手术组和RSD组相比,心衰组犬心室中TGF-β表达明显增加,心室肌组织及血清中BNP,AngⅡ和醛固酮水平明显升高.结论 RSD可抑制长期快速心室起搏引起的心室肌基质重构.%Objective To explore the role of renal sympathetic denervation (RSD) on ventricular substrate remodeling in dogs with pacing-induced heart failure (HF).Methods A total of 19 dogs were randomized into 3 groups of sham-operated control (n =7),right ventricular pacing induction of HF (n =6) and RSD (n =6).After 8-week pacing induction of HF.Hemodynamic variables were monitored at baseline and after HF.Masson's trichrome staining,enzyme-linked immunosorbent assay (ELISA) and Western blot were used to measure ventricular interstitial fibrosis,brain natriuretic peptide (BNP),angiotensin Ⅱ (Ang Ⅱ),aldosterone and transforming growth factor-beta (TGF-β).Results All dogs in HF and HF + RSD groups


    NARCIS (Netherlands)



    Activity in sympathetic liver nerves has been proposed to be important for glucose production in exercising humans. However, liver denervation does not influence the exercise-induced increase in glucose production in the rat and dog. These species have a poor sympathetic liver innervation in contras

  15. Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

    Directory of Open Access Journals (Sweden)

    Cabral A.M.


    Full Text Available Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc or vehicle (soybean oil, 0.25 ml per animal was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW ratio (2.44 ± 0.09 mg/g and right ventricular weight/body weight (RVW/BW ratio (0.53 ± 0.01 mg/g compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively rats. MAP was significantly higher (39% in DOCA-salt rats. Renal denervation prevented (P>0.05 the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g and RVW/BW (0.52 ± 0.01 mg/g. We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity

  16. 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)


    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.)

  17. Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF). (United States)

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


    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 rat ventricles and superior cervical ganglia were cultured at a close distance. Then, morphological and functional coupling between SNs and VMs was assessed in response to GDNF (10 ng/ml) or nerve growth factor (50 ng/ml). As a result, fractions of neurofilament-M-positive axons and synapsin-I-positive area over the surface of VMs were markedly increased with GDNF by 9-fold and 25-fold, respectively, compared to control without neurotrophic factors. Pre- and post-synaptic stimulation of β1-adrenergic receptors (BAR) with nicotine and noradrenaline, respectively, resulted in an increase of the spontaneous beating rate of VMs co-cultured with SNs in the presence of GDNF. GDNF overexpressing VMs by adenovirus vector (AdGDNF-VMs) attracted more axons from SNs compared with mock-transfected VMs. In vivo, axon outgrowth toward the denervated myocardium in adult rat hearts after cryoinjury was also enhanced significantly by adenovirus-mediated GDNF overexpression. GDNF acts as a potent chemoattractant for sympathetic innervation of ventricular myocytes, and is a promising molecular target for regulation of cardiac function in diseased hearts.

  18. Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF.

    Directory of Open Access Journals (Sweden)

    Keiko Miwa

    Full Text Available 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 rat ventricles and superior cervical ganglia were cultured at a close distance. Then, morphological and functional coupling between SNs and VMs was assessed in response to GDNF (10 ng/ml or nerve growth factor (50 ng/ml. As a result, fractions of neurofilament-M-positive axons and synapsin-I-positive area over the surface of VMs were markedly increased with GDNF by 9-fold and 25-fold, respectively, compared to control without neurotrophic factors. Pre- and post-synaptic stimulation of β1-adrenergic receptors (BAR with nicotine and noradrenaline, respectively, resulted in an increase of the spontaneous beating rate of VMs co-cultured with SNs in the presence of GDNF. GDNF overexpressing VMs by adenovirus vector (AdGDNF-VMs attracted more axons from SNs compared with mock-transfected VMs. In vivo, axon outgrowth toward the denervated myocardium in adult rat hearts after cryoinjury was also enhanced significantly by adenovirus-mediated GDNF overexpression. GDNF acts as a potent chemoattractant for sympathetic innervation of ventricular myocytes, and is a promising molecular target for regulation of cardiac function in diseased hearts.

  19. The posterior vermis of the cerebellum selectively inhibits 10-Hz sympathetic nerve discharge in anesthetized cats. (United States)

    Barman, Susan M; Gebber, Gerard L


    We studied the changes in inferior cardiac sympathetic nerve discharge (SND) and mean arterial pressure (MAP) produced by aspiration or chemical inactivation (muscimol microinjection) of lobule IX (uvula) of the posterior vermis of the cerebellum in baroreceptor-denervated and baroreceptor-innervated cats anesthetized with urethane. Autospectral analysis was used to decompose SND into its frequency components. Special attention was paid to the question of whether the experimental procedures affected the rhythmic (10-Hz and cardiac-related) components of SND. Aspiration or chemical inactivation of lobule IX produced an approximately three-fold increase in the 10-Hz rhythmic component of SND (P cats. Total power (0- to 20-Hz band) was unchanged. Despite the absence of a change in total power in SND, there was a statistically significant increase in MAP. In baroreceptor-innervated cats, neither aspiration nor chemical inactivation of the uvula caused a significant change in cardiac-related or total power in SND or MAP. These results are the first to demonstrate a role of cerebellar cortical neurons of the posterior vermis in regulating the frequency composition of naturally occurring SND. Specifically, these neurons selectively inhibit the 10-Hz rhythm-generating network in baroreceptor-denervated, urethane-anesthetized cats. The functional implications of these findings are discussed.

  20. Eligibility for renal denervation

    DEFF Research Database (Denmark)

    Persu, Alexandre; Jin, Yu; Baelen, Marie;


    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according......Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...

  1. Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by {sup 11}C-hydroxyephedrine

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Rudolf A.; Higuchi, Takahiro [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); Maya, Yoshifumi [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nihon Medi-Physics Co., Ltd., Research Centre, Chiba (Japan); Rischpler, Christoph [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Muenchen (Germany); Javadi, Mehrbod S. [Johns Hopkins University, Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Baltimore, MD (United States); Fukushima, Kazuhito [Hyogo College of Medicine, Department of Radiology, Hyogo (Japan); Lapa, Constantin [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Herrmann, Ken [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States)


    An altered state of the cardiac sympathetic nerves is an important prognostic factor in patients with coronary artery disease. The aim of this study was to investigate regional sympathetic nerve damage and restoration utilizing a rat model of myocardial transient ischemia and a catecholamine analog PET tracer, {sup 11}C-hydroxyephedrine ({sup 11}C-HED). Transient myocardial ischemia was induced by coronary occlusion for 20 min and reperfusion in male Wistar rats. Dual-tracer autoradiography was performed subacutely (7 days) and chronically (2 months) after ischemia, and in control rats without ischemia using {sup 11}C-HED as a marker of sympathetic innervation and {sup 201}TI for perfusion. Additional serial in vivo cardiac {sup 11}C-HED and {sup 18}F-FDG PET scans were performed in the subacute and chronic phases after ischemia. After transient ischemia, the {sup 11}C-HED uptake defect areas in both the subacute and chronic phases were clearly larger than the perfusion defect areas in the midventricular wall. The subacute {sup 11}C-HED uptake defect showed a transmural pattern, whereas uptake recovered in the subepicardial portion in the chronic phase. Tyrosine hydroxylase antibody nerve staining confirmed regional denervation corresponding to areas of decreased {sup 11}C-HED uptake. Serial in vivo PET imaging visualized reductions in the area of the {sup 11}C-HED uptake defects in the chronic phase consistent with autoradiography and histology. Higher susceptibility of sympathetic neurons compared to myocytes was confirmed by a larger {sup 11}C-HED defect with a corresponding histologically identified region of denervation. Furthermore, partial reinnervation was observed in the chronic phase as shown by recovery of subepicardial {sup 11}C-HED uptake. (orig.)

  2. 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


    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.)

  3. Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats (United States)

    Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

  4. Intrapericardial Denervation: Responses to Water Immersion in Rhesus Monkeys (United States)

    McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold


    Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

  5. MRI appearance of muscle denervation

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, S. [University Hospital of Wales, Department of Radiology, Cardiff (United Kingdom); Venkatanarasimha, N.; Walsh, M.A.; Hughes, P.M. [Derriford Hospital, Department of Radiology, Plymouth (United Kingdom)


    Muscle denervation results from a variety of causes including trauma, neoplasia, neuropathies, infections, autoimmune processes and vasculitis. Traditionally, the diagnosis of muscle denervation was based on clinical examination and electromyography. Magnetic resonance imaging (MRI) offers a distinct advantage over electromyography, not only in diagnosing muscle denervation, but also in determining its aetiology. MRI demonstrates characteristic signal intensity patterns depending on the stage of muscle denervation. The acute and subacutely denervated muscle shows a high signal intensity pattern on fluid sensitive sequences and normal signal intensity on T1-weighted MRI images. In chronic denervation, muscle atrophy and fatty infiltration demonstrate high signal changes on T1-weighted sequences in association with volume loss. The purpose of this review is to summarise the MRI appearance of denervated muscle, with special emphasis on the signal intensity patterns in acute and subacute muscle denervation. (orig.)

  6. Exercise-induced increase in dog adipose tissue blood flow before and after denervation

    DEFF Research Database (Denmark)

    Bülow, J; Madsen, J


    Subcutaneous adipose tissue blood flow was examined during rest and exercise in the inguinal fat pads of four female dogs using the Xe wash-out technique. The experiments were performed before and after denervation of one of the pads. No difference between the resting flows in the two pads could...... be demonstrated either before or after denervation. The flow increased about two-fold on average from rest to exercise. This response was similar before and after denervation. It is concluded that direct sympathetic innervation is not involved in the regulation of adipose tissue blood flow during exercise....

  7. Effect of renal sympathetic denervation on the inducibility of ventricular arrhythmia in dogs with pacing-induced heart failure%肾去交感神经对长期右室起搏犬室性心律失常诱发的影响及机制

    Institute of Scientific and Technical Information of China (English)

    赵庆彦; 王晞; 唐艳红; 黄从新; 郭宗文; 代子玄; 王晓占; 于胜波; 王徐乐; 万沛星; 肖金平; 黄鹤


    Objective To investigate the effect of renal sympathetic denervation ( RSD) on the vulnerability of ventric-ular arrhythmia in dogs with pacing-induced heart failure ( HF) . Methods Twenty-one dogs were randomized into con-trol (n=7), HF (n=7) and RSD (n=7) groups. Control dogs were implanted with transvenous cardiac pacemakers with-out pacing. Dogs in the HF group were implanted with pacemakers and underwent right ventricular pacing for 3 weeks at 240 bpm to induce HF. The dogs in the RSD group received bilateral renal artery ablation, subsequently underwent the same HF-inducing procedure. Echocardiography test were performed on all the dogs at the baseline and endpoint of the ex-periment. After 3 weeks, electrophysiological test and the changes of ventricular substrate were measured. Results Two dogs were dead during the experiment. Nineteen dogs completed this study. The QT interval and effective refractory period were higher in HF dogs than in control and RSD dogs. Conduction time ( CT) within the right-ventricle and inter-ventricle was significant longer in HF dogs than that in control and RSD dogs (CT within inter-ventricles:77±9 ms vs 61±7 ms, 65 ±8 ms;P=0. 03). More episodes of ventricular fibrillation were induced in the HF dogs than that in the RSD dogs (19%vs 6. 9%;P<0. 05). The ventricle tissue from HF hearts revealed a large amount of fibrosis and severe heterogeneous ex-pression of Cx43, whereas RSD dogs showed less change when compared with the dogs with HF alone. Conclusions RSD suppress the vulnerability of malignantventricular arrhythmia in dogs with pacing - induced HF and the mechanism maybe have relationship with inhibited ventricular electrical and substrate remodeling.%目的:探讨肾去交感神经( RSD)对长期右室起搏犬室性心律失常诱发的影响及机制。方法21只比格犬随机分为对照组(n=7),心力衰竭(简称心衰)组(n=7)和RSD组(n=7)。对照组植入起搏器不起搏;心衰组植入起搏器后以240

  8. Effect of unilateral incisor tooth amputation on the glucose metabolism in submandibular glands of rats following sympathetic and parasympathetic denervation Efeito da amputação unilateral do incisivo inferior sobre o metabolismo da glicose em glândulas submandibulares de ratos submetidas a desnervação simpática e parassimpática

    Directory of Open Access Journals (Sweden)



    Full Text Available The autonomic nervous system is of major importance in the regulation of physiological functions of the salivary glands, including the sialadenotrophic process. It is well known that the secretory function as well as other functions in the salivary glands depend upon the energy produced in the gland. The acini volume density, some enzymes of the glucose metabolism, such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and lactate dehydrogenase were evaluated following sympathetic and parasympathetic denervation of submandibular glands of rats, submitted to unilateral incisor amputation, five days after denervation. Sympathectomized glands submitted to amputation showed a reduction in the activity of hexokinase and phosphofructokinase-1, varying from 27.5 to 36.7 % for hexokinase and from 22.8 to 38.4 % for phosphofructokinase-1. Although no variation was observed in the enzymatic activity of parasympathectomized animals, the acini volume density showed a significant decrease.O sistema nervoso autônomo é de grande importância na regulação da fisiologia das glândulas salivares, incluindo o processo sialadenotrófico. Já é bem conhecido o fato de que a função secretora, bem como, outras funções desempenhadas pelas glândulas salivares dependem de energia produzida nas glândulas. A histometria dos ácinos, algumas enzimas do metabolismo de carboidratos como, hexoquinase, fosfofrutoquinase-1, piruvato quinase, glicose-6-fosfato desidrogenase e lactato desidrogenase foram avaliados na glândula submandibular de ratos com desnervação simpática e parassimpática, submetidos a amputação unilateral dos dentes incisivos, cinco dias após a desnervação. Nas glândulas simpatectomizadas submetidas a amputação dos incisivos observou-se uma redução nas atividades da hexoquinase (27,5 - 36,7 % e da fosofofrutoquinase-1 (22,8 - 38,4 %. Embora, nehuma variação foi observado nas atividades enzim

  9. Sympathetic reinnervation in cardiac transplants : preliminary results {sup 123}I-MIBG and {sup 201}Tl/{sup 99m}Tc-MIBI scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joug Ho; Oh, Se Jin; Son, Min Soo; Son, Ji Won; Choi, In Seok; Shin, Euk Kyun; Park, Kuk Yang; Kim, Ju E. [International Medicine and Thoraic Surgery, Inchon (Korea, Republic of)


    Iodine-123 metaiodobenzylguanidine ({sup 123}I-MIBG) is a norepinephrine (NE) analogue. To determine whether cardiac sympathetic reinnervation occurs after orthotopic heart transplantation (TPL). Nine patients (M : F=7 :2; mean ages=34{+-}24.1 yr; idiopathic:rheumatic = 8: 1) within 197.{+-}14.3 (4-36) months after TPL performed both {sup 123}I-MIBG scintigraphy and {sup 201}Tl/{sup 99m}Tc-MIBI dipyridamole stress gated myocardial perfusion SPECT (g-MPS). {sup 23}I-MIBG imagings were performed in anterior position 15 minutes, 4 and 24 hours after i.v. injection of 148 MBq {sup 123}I MIBG. Image quantitation was based on the ratio of hear to mediastinal MIBG uptake (HMR). Six subjects with <14 (4.3{+-}1.4) months after TPL had no visible {sup 123}I-MIBG uptake on early 15. min imaging however, three subjects with 26 to 36(32.0{+-}5.3) months had visible cardiac {sup 123}I-MIBG uptake (HMR:1.24{+-}0.09 vs. 1.8{+-}0.2). Correlation was found between plasma NE concentration and HMR(r=0.80: p<0.05). Compared to HMR on 15 min images (1.5{+-}0.3), neither four nor 24 hour delayed images (1.3{+-}0.3 vs. 1.1{+-}0.1 : p<0.05, respectively, ANOVA) showed definite delayed localization of MIBG. The uptakes in the liver, lung, salivary glands and spleen were present. To dipyridamole stress, transplant hearts showed significant subnormal hemodynamic responses of HR, s-BP, d-BP, and rate pressure product (95.4{+-}13.8 to 107.4{+-}14.6, 131.0{+-}16.7 to 123.6{+-}13.4, 79.1{+-}12.7 to 72.2{+-}12.7, 124.5{+-}19.6 to 133.0{+-}23.6 p<0.05, respectively). G-MPS of one patient shod an apicoanterior wall reversible perfusion defect which was confirmed as 90% distal left anterior descending artery stenosis by coronary angiography. MIBG uptake seems to involve mainly the specific sodium and energy dependent uptake-1 pathway, and the non-neuronal uptake-2 involving simple diffusion is not significant. Conclusively, partial sympathetic late reinnervation of the transplant human hearts can

  10. Baroreflex control of sympathetic activity in experimental hypertension

    Directory of Open Access Journals (Sweden)

    M.C.C. Irigoyen


    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.

  11. [Sympathetic nerve activity in chronic renal failure - what are the therapeutic options?]. (United States)

    Hausberg, M; Tokmak, F


    Patients with chronic renal failure are characterized by a tonic elevation of sympathetic tone. This factor largely contributes to their increased cardiovascular risk. The increased sympathetic drive is caused by activiation of renal afferent fibers in the diseased kidneys. Therapeutic options for hypertensive patients with chronic renal failure with respect to their sympathetic overactivity are inhibitors of the renin-angiotensin-system and central sympatholytic drugs. The role of catheter-based renal denervation in these patients is currently under investigation.

  12. Successful accessory renal artery denervation in a patient with resistant hypertension

    Directory of Open Access Journals (Sweden)

    Halil Atas


    Full Text Available Renal sympathetic denervation is safe and effective in patients with resistant hypertension. In all of the studies of renal artery denervation, patients with accessory renal arteries are excluded. So there is not any data regarding renal sympathetic denervation applied to the accessory renal arteries. We present a young female patient with resistant hypertension despite use of five different antihypertensive drugs. The patient had a well developed (diameter >4 mm left renal accessory. We believe that if we omitted the well developed accessory renal artery, we would not have maintained adequate blood pressure control. Thus, we applied radiofrequency ablation to both renal arteries and left accessory artery. Immediately after the procedure, the patient′s blood pressure was reduced to 110/60 mmHg and this effect was continued during the first month of follow-up.

  13. The explore of mechanism,validity and safety of renal sympathetic denervation for hypertensive dogs%去肾脏交感神经术对犬高血压的影响机制及有效性、安全性探讨

    Institute of Scientific and Technical Information of China (English)

    赵斌; 卢成志; 张欣


    目的:通过去肾脏交感神经术(RSD)对犬高血压的治疗,探讨高血压与肾素-血管紧张素-醛固酮系统(RAS)的关系,并评估RSD的有效性与安全性.方法:18只杂种狗随机分为干预组(n=10)和对照组(n=8)两组,干预组为高血压造模组,两组实验动物都接受RSD.观察的主要指标是平均动脉压(MAP)的变化,分别在术前和术后2、4、10周监测血压,同时在术后第2、6、10周监测肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、肌酐(Cr)等指标,通过对这些数据进行方差分析,来评价RSD的有效性与安全性.结果:在干预组,造模后MAP增高明显,由(134.4±4.32)mmHg升至(153.8±7.2)mmHg(P<0.001);在行RSD治疗后,MAP在2、4和10周后分别降至(137.6±8.46)mmHg、(132.3±6.20)mmHg和(125.5±2.87)mmHg,同时PRA、AngⅡ、ALD水平都较术前下降(P<0.05),Cr水平无明显变化(P>0.05).结论:RAS在高血压的发生和发展过程中发挥着重要的作用,RSD能够产生显著和持久的血压下降作用,能有效降低RAS的活性,并且手术过程没有造成严重肾功能受损.%Objective To explore the treatment of renal sympathetic denervation (RSD) for hypertension and assess the validity of the treatment, discussing the relation between hypertension and renin-angiotensin-aldosterone system(RAS) at the same time. Methods Eighteen mongrel dogs were studied as intervention (re = 10) and control (n= 8) groups, Ihe intervention group was made the neurogenic hypertension model, Iwo groups were received RSD. Primary endpoints were changes of mean blood pressure before and at 2,4 and 10 weeks after procedure. We assessed the effectiveness of renal sympathetic denervation with renin activity (PRA), angiotensin II (Ang II ), aldosterone(ALD), and creatinine(Cr) in the intervention group. The changes of PRA, Ang II , ALD, and Cr were detected at 2, 6 and 10 weeks after procedure. We assessed the data changes effectiveness by repeated measures

  14. Treating resistant hypertension: role of renal denervation

    Directory of Open Access Journals (Sweden)

    Urban D


    Full Text Available Daniel Urban, Sebastian Ewen, Christian Ukena, Dominik Linz, Michael Böhm, Felix Mahfoud Department of Internal Medicine III, Cardiology, Angiology and Intensive Care Medicine, University Hospital of Saarland, Homburg, Saarland, Germany Abstract: Arterial hypertension is the most prevalent risk factor associated with increased cardiovascular morbidity and mortality. Although pharmacological treatment is generally well tolerated, 5%–20% of patients with hypertension are resistant to medical therapy, which is defined as blood pressure above goal (>140/90 mmHg in general; >130–139/80–85 mmHg in patients with diabetes mellitus; >130/80 mmHg in patients with chronic kidney disease despite treatment with ≥3 antihypertensive drugs of different classes, including a diuretic, at optimal doses. These patients are at significantly higher risk for cardiovascular events, in particular stroke, myocardial infarction, and heart failure, as compared with patients with nonresistant hypertension. The etiology of resistant hypertension is multifactorial and a number of risk factors have been identified. In addition, resistant hypertension might be due to secondary causes such as primary aldosteronism, chronic kidney disease, renal artery stenosis, or obstructive sleep apnea. To identify patients with resistant hypertension, the following must be excluded: pseudo-resistance, which might be due to nonadherence to medical treatment; white-coat effect; and inaccurate measurement technique. Activation of the sympathetic nervous system contributes to the development and maintenance of hypertension by increasing renal renin release, decreasing renal blood flow, and enhancing tubular sodium retention. Catheter-based renal denervation (RDN is a novel technique specifically targeting renal sympathetic nerves. Clinical trials have demonstrated that RDN significantly reduces blood pressure in patients with resistant hypertension. Experimental studies and small

  15. Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects.

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    Pawel J Winklewski

    Full Text Available Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS that allows for the non-invasive measurement of pial artery pulsation (cc-TQ and subarachnoid width (sas-TQ in humans, we assessed the influence of sympathetic activation on the cardiac and respiratory contribution to blood pressure (BP cc-TQ oscillations in healthy subjects.The pial artery and subarachnoid width response to handgrip (HGT and cold test (CT were studied in 20 healthy subjects. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV was measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR and beat-to-beat mean BP were recorded using a continuous finger-pulse photoplethysmography; respiratory rate (RR, minute ventilation (MV, end-tidal CO2 (EtCO2 and end-tidal O2 (EtO2 were measured using a metabolic and spirometry module of the medical monitoring system. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations.HGT evoked an increase in BP (+15.9%; P<0.001, HR (14.7; P<0.001, SaO2 (+0.5; P<0.001 EtO2 (+2.1; P<0.05 RR (+9.2%; P = 0.05 and MV (+15.5%; P<0.001, while sas-TQ was diminished (-8.12%; P<0.001, and a clear trend toward cc-TQ decline was observed (-11.0%; NS. CBFV (+2.9%; NS and EtCO2 (-0.7; NS did not change during HGT. CT evoked an increase in BP (+7.4%; P<0.001, sas-TQ (+3.5%; P<0.05 and SaO2(+0.3%; P<0.05. HR (+2.3%; NS, CBFV (+2.0%; NS, EtO2 (-0.7%; NS and EtCO2 (+0.9%; NS remained unchanged. A trend toward decreased cc-TQ was observed (-5.1%; NS. The sas-TQ response was biphasic with elevation during the first 40 seconds (+8.8% vs. baseline; P<0.001 and subsequent decline (+4.1% vs. baseline; P<0.05. No change with respect to wavelet coherence and wavelet phase coherence was found between the BP and cc-TQ oscillations.Short sympathetic activation does not affect the cardiac and respiratory contribution to the relationship

  16. A novel electrophilic synthesis and evaluation of medium specific radioactivity (1R,2S)-4-[{sup 18}F]fluorometaraminol, a tracer for the assessment of cardiac sympathetic nerve integrity with PET

    Energy Technology Data Exchange (ETDEWEB)

    Eskola, Olli E-mail:; Groenroos, Tove; Bergman, Joergen; Haaparanta, Merja; Marjamaeki, Paeivi; Lehikoinen, Pertti; Forsback, Sarita; Langer, Oliver; Hinnen, Francoise; Dolle, Frederic; Halldin, Christer; Solin, Olof


    (1R,2S)-4-[{sup 18}F]fluorometaraminol (4-[{sup 18}F]FMR), a tracer for cardiac sympathetic innervation, was synthesized by electrophilic aromatic substitution. A trimethylstannyl precursor, protected with tert-butoxycarbonyl protecting groups, was radiofluorinated with high specific radioactivity [{sup 18}F]F{sub 2}. Specific radioactivity of 4-[{sup 18}F]FMR, in average 11.8 {+-}3.3 GBq/{mu}mol, was improved 40-800-fold in comparison to the previous electrophilic fluorinations. The biodistribution of 4-[{sup 18}F]FMR in rat was in accordance with the known distribution of sympathetic innervation. 4-[{sup 18}F]FMR showed no metabolic degradation in left ventricle of rat heart, where the uptake was high, rapid and specific.

  17. Local denervation of sympathetic nerve from the femoral artery using 6-hydroxydopamine in a rabbit model%6-羟多巴胺去除股动脉交感神经的动物模型建立及相关研究

    Institute of Scientific and Technical Information of China (English)

    靳宇飞; 李富航; 毕龙; 裴国献


    -hydroxydopamine hydrobromide (6-OHDA) and 0.1% ascorbic acid in the experimental group (n =12),but with Krebs buffer only containing 0.1% ascorbic acid in the control group (n =4).To investigate the recovery time of sympathetic nerves after drug intervention,the experimental group was divided into 3 subgroups(n =4 for each) for sampling at 7,14 and 28 days respectively.Hematoxylin-eosin (HE) staining was used to detect the structure changes of the femoral artery while glyoxylic acid staining to observe the distribution of sympathetic nerves.The protein expressions of tyrosine hydroxylase (TH) and nerve peptide Y (NPY) were also investigated with western blot.Results HE staining showed that the treatment of 6-OHDA did not damage the normal structure of vascular bundles,compared with the control group.By glyoxylic acid staining,a massive web of sympathetic nerves was distributed in the femoral artery in the control group.In contrast,the sympathetic nerves were almost invisible at 7 and 14 days,and only few of them were observed at 28 days after the treatment of 6-OHDA.The TH/β-actin ratios were 0.70 ± 0.08,0.19 ± 0.08,0.20 ±0.06 and 0.33 ±0.06 while the NPY/β-actin ratios were 0.68 ±0.14,0.14 ±0.02,0.17 ±0.02 and 0.53 ±0.10 in the control group,7-day,14-day and 28-day sampling subgroups,respectively.At all time points,the TH and NPY expressions in all the experimental sub-groups were significantly lower than in the control group (P < 0.05),though the expressions were significantly higher in the 28-day sampling subgroup than in the other 2 subgroups (P < 0.05).Conclusions Since local application of 6-OHDA can effectively remove the sympathetic nerve from the femoral artery in a rabbit model,it provides an ideal experimental model with which it is a feasible to remove sympathetic nerves from vascular walls to investigate denervated vascular bundles.

  18. 肾去交感神经对心房神经节刺激诱发心房颤动的影响%Effect of renal sympathetic denervation on the inducibility of atrial fibrillation by anterior right ganglionic plexi stimulation

    Institute of Scientific and Technical Information of China (English)

    于胜波; 代子玄; 邹明辉; 王徐乐; 肖金平; 赵庆彦; 黄从新


    Objective To investigate the effect of renal sympathetic denervation on inducibility of atrial fibrillation(AF) by anterior right ganglionic plexi (ARGP)stimulation.Methods Thirteen dogs were used for the study as follows:control group(n =7) and renal artery ablation (RAA) group (n =6).In control group,after right thoracotomy,high-frequency electrical stimulation(20 Hz,0.1 ms duration)was applied to the ARGP for 1 minute by incremental voltages up to the voltage that induced AF.In RAA group,after atrial effective refractory period (AERP) measured,each renal artery was ablated and dogs were raised for 6 weeks.The procedure of ARGP stimulation was same as in the control group.Blood was collected before and after ablation 6 weeks to measure the levels ofangiotensin Ⅱ(Ang Ⅱ)and aldosterone(ALD) in RAA dogs.Results AERP had no significant change before and after renal artery ablation 6 weeks [(134.4±19.2) ms vs (142.0±21.5) ms,P>0.05].Compared with that in control group,dogs had higher voltage in the sinus rate slowing response induced by ARGP stimulation in RAA group[(3.5±1.6)V vs(1.6±0.3)V,P=0.03].Furthermore,the lowest voltage that induce AF was higher in RAA group than that in control group[(5.1±1.0)V vs(2.1±0.7)V,P=0.03].The plasma Ang Ⅱ and aldosterone concentration showed a greatly decreasing after RAA 6 weeks in RAA group [Ang Ⅱ:(142.8±31.7) pg/ml vs(91.7±23.8)pg/ml,P=0.01 ; Aldosterone:(272.2±37.4) pg/ml vs(156.3±17.6)pg/ml,P<0.01].Conclusions Renal sympathetic denervation inhibited the inducibility of AF during ARGP stimulation.This effect might have relationship with decreased activity of renin-angiotensin-aldosterone system(RAAS).%目的 探讨经导管消融肾交感神经后对心房右前神经节(ARGP)刺激诱发心房颤动(房颤)的影响.方法 13只犬随机分为对照组(n=7)和消融组(n=6).对照组犬于右侧第4肋间开胸,采用不同电压高频刺激(20 Hz,0.1 ms) ARGP,观察心率减慢和房颤诱发情况;消

  19. Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves. (United States)

    Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H


    Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation.

  20. 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)


    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.)

  1. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis. (United States)

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias


    Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function.

  2. 经皮导管射频消融去肾交感神经术在顽固性高血压中的临床应用%Clinical application of catheter-based renal sympathetic denervation for the treatment of resistant hypertension

    Institute of Scientific and Technical Information of China (English)

    唐小铁; 周涛


    目的 探讨经皮导管肾交感神经射频消融术(renal sympathetic denervation,RSD)治疗顽固性高血压的有效性和安全性.方法 对32例顽固性高血压患者实施RSD,随访12个月.比较RSD术前与RSD术后第3、6及12个月的血压下降水平、肾功能变化情况以及降压药使用情况;术后行计算机断层扫描(computed tomography,CT)检查肾动脉有无异常.结果 32例患者中,RSD术后第3个月失访1例,术后第6个月失访2例,其余29例患者完成术后12个月的随访.RSD术后第3个月时,患者收缩压和舒张压分别下降为[(18.5±3.6)mm Hg,(P<0.01)]和[(5.8±2.5)mm Hg,(P<0.01)];RSD术后第6个月时,患者收缩压和舒张压分别下降[(24.3±2.2)mm Hg,(P<0.01)]和[(8.7±2.6)mm Hg,(P<0.01)];RSD术后第12个月时,患者收缩压和舒张压分别下降[(20.7±3.2)mm Hg,(P<0.01)]和[(6.6±1.8)mm Hg,(P<0.01)].术后未见严重低血压及并发症出现.在RSD术后第3、6及12个月时,患者合并使用降压药的种类较RSD术前有明显减少[第3、6及12个月时分别减少43.7% (P<0.01)、41.9% (P<0.01)和44.8%(P<0.01)];与RSD术前比较,RSD术后第3、6及12个月时,检测估算肾小球滤过率(estimate glomerular filtration rate,eGFR)水平、血肌酐水平、血清胱抑素C水平均无明显变化(P>0.05);而心率水平在RSD术后第3、6及12个月时均比RSD术前有明显下降(P<0.05).术后随访未见肾动脉以及肾功能异常.结论 RSD对治疗顽固性高血压有一定的有效性和安全性,且介入方法简单,值得在临床上推广应用.

  3. The morphological substrate for Renal Denervation : Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study

    NARCIS (Netherlands)

    van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W


    BACKGROUND: Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of paras

  4. Obesity-Related Metabolic Syndrome: Mechanisms of Sympathetic Overactivity

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    Maria Paola Canale


    Full Text Available The prevalence of the metabolic syndrome has increased worldwide over the past few years. Sympathetic nervous system overactivity is a key mechanism leading to hypertension in patients with the metabolic syndrome. Sympathetic activation can be triggered by reflex mechanisms as arterial baroreceptor impairment, by metabolic factors as insulin resistance, and by dysregulated adipokine production and secretion from visceral fat with a mainly permissive role of leptin and antagonist role of adiponectin. Chronic sympathetic nervous system overactivity contributes to a further decline of insulin sensitivity and creates a vicious circle that may contribute to the development of hypertension and of the metabolic syndrome and favor cardiovascular and kidney disease. Selective renal denervation is an emerging area of interest in the clinical management of obesity-related hypertension. This review focuses on current understanding of some mechanisms through which sympathetic overactivity may be interlaced to the metabolic syndrome, with particular regard to the role of insulin resistance and of some adipokines.

  5. How does renal denervation lower blood pressure and when should this technique be considered for the treatment of hypertension? (United States)

    Leong, Kui Toh Gerard; Krum, Henry


    Resistant hypertension poses significant health concerns. There are strong demands for new safe therapeutics to control resistant hypertension, while addressing its common causes, specifically poor compliance to lifelong polypharmacy, lifestyle modification and physician inertia. The sympathetic nervous system plays a significant pathophysiological role in hypertension. Surgical sympathectomy for blood pressure reduction is an old but extremely efficacious therapeutic concept, since abandoned, with the dawn of safer contemporary pharmacology era. Recently, clinical studies have revealed promising results for safe and sustained blood pressure reduction with percutaneous renal sympathetic denervation. This is a novel, minimally-invasive, device-based therapy, specifically targeting and ablating the renal artery nerves with radiofrequency waves, without permanent implantation. There are also reported additional benefits in related comorbidities, such as impaired glucose metabolism, renal impairment, left ventricular hypertrophy, heart failure, and others. This review will focus on how selective renal sympathetic denervation works, as well as its present and potential therapeutic indications.

  6. Role of the sympathetic nervous system in carbon tetrachloride-induced hepatotoxicity and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Jung-Chun Lin

    Full Text Available Carbon tetrachloride (CCl4 is widely used as an animal model of hepatotoxicity and the mechanisms have been arduously studied, however, the contribution of the sympathetic nervous system (SNS in CCl4-induced acute hepatotoxicity remains controversial. It is also known that either CCl4 or SNS can affect systemic inflammatory responses. The aim of this study was to establish the effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA in a mouse model of CCl4-induced acute hepatotoxicity and systemic inflammatory response. Mice exposed to CCl4 or vehicle were pretreated with 6-OHDA or saline. The serum levels of aminotransferases and alkaline phosphatase in the CCl4-poisoning mice with sympathetic denervation were significantly lower than those without sympathetic denervation. With sympathetic denervation, hepatocellular necrosis and fat infiltration induced by CCl4 were greatly decreased. Sympathetic denervation significantly attenuated CCl4-induced lipid peroxidation in liver and serum. Acute CCl4 intoxication showed increased expression of inflammatory cytokines/chemokines [eotaxin-2/CCL24, Fas ligand, interleukin (IL-1α, IL-6, IL-12p40p70, monocyte chemoattractant protein-1 (MCP-1/CCL2, and tumor necrosis factor-α (TNF-α], as well as decreased expression of granulocyte colony-stimulating factor and keratinocyte-derived chemokine. The overexpressed levels of IL-1α, IL-6, IL-12p40p70, MCP-1/CCL2, and TNF-α were attenuated by sympathetic denervation. Pretreatment with dexamethasone significantly reduced CCl4-induced hepatic injury. Collectively, this study demonstrates that the SNS plays an important role in CCl4-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical- or drug-induced hepatotoxicity and circulating immune response.

  7. [Role of renal sympathetic nerve and oxidative stress in foot shock-induced hypertension in rats]. (United States)

    Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Dong, Tao; Zhang, Guo-Xing


    The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups (the number of each group was 15): control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve + foot shock group, Tempol treatment + foot shock group, denervation of renal sympathetic nerve + Tempol treatment + foot shock group. Rats were received electrical foot shock for 14 days (2-4 mA, 75 V, shocks of 50-100 ms every 30 s, for 4 h each session through an electrified grid floor every day). Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats (rats were allowed to recover for one week before the beginning of the foot shock procedure). The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance (TBARS), renin, angiotensin II (AngII) and glutathione peroxidase (GSH-Px) in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased (P indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced.

  8. The utility of segmental analysis in cardiac I-123 MIBG SPECT in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Soo Hyun; Yoon, Joon Kee; Yoon, Jung Han; Lee, Su Jin; Jo, Kyung Soo; Lee, Dong Hyun; An, Young Sil [Ajou University School of Medicine, Suwon (Korea, Republic of)


    Cardiac images using I-123 metaiodobenzylguanidine (MIBG) are widely used to evaluate cardiac sympathetic denervation in Parkinson’s disease (PD). The aim of this study was to evaluate the utility of segmental analysis on cardiac MIBG SPECT in PD patients. In total, 36 patients with PD (n = 26) or essential tremor (ET, n = 10) who underwent MIBG cardiac SPECT were enrolled. The heart-to-mediastinum (H/M) ratios of MIBG uptake were acquired on planar images. For the segmental analysis of SPECT images, we evaluated the summed defect score (SDS) using a 17-segment model. The diagnostic abilities of H/M ratios and segmental parameters on MIBG SPECT were assessed by ROC curve analysis. The H/M ratios were significantly lower in PD than in ET patients (p < 0.05). On segmental analysis, SDS was significantly higher in PD patients than in the ET group (7.04 ± 4.09 vs. 2.90 ± 2.80; p = 0.006). The defect score of the anteroseptal region showed a significant difference between the groups (p = 0.002). The ROC analysis suggested only SDS (AUC = 0.785, p = 0.0003) and defect scores in the anteroseptal (AUC = 0.800, p < 0.0001) and inferior (AUC = 0.667, p = 0.013) regions showed significant diagnostic ability to differentiate PD from ET. Segmental parameters from cardiac MIBG SPECT images can provide additional information to differentiate PD from ET patients. Beyond H/M ratios from planar images, we recommend an MIBG SPECT study to evaluate sympathetic denervation in PD.

  9. Renal sympathetic denervation inhibites the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs%肾交感神经消融抑制心力衰竭犬左心室机械不同步性的实验研究

    Institute of Scientific and Technical Information of China (English)

    胡伟; 于胜波; 赵庆彦; 孙彬; 陈辽; 郭瑞强


    Objective To investigate whether transcatheter renal sympathetic denervation (RSD) by radiofrequency ablation interfere with the development of left ventricular (LV) mechanical dyssynchrony during the progression of heart failure (HF).Methods Nineteen beagles were randomly divided into sham-operated group (six dogs),control group (seven dogs),and RSD group (six dogs).Sham-operated group were implanted with pacemakers without pacing;Control group were implanted with pacemakers and underwent 3 weeks of rapid right ventricular pacing;and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers.LV dyssynchrony was analyzed via 2D speckle-tracking strain echocardiography to evaluate LV function.Longitudinal dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain on apical 4-and 2-chamber views.Radial and circumferential dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain in mid-and base-LV short-axis views.LV systolic pressure (LVSP) and LV end-diastolic pressure (LVEDP) were measured.The LV interstitial fibrosis was determined by histological analysis.Results After 3 weeks,all of the dogs in both the control and RSD groups showed greater LV end-diastolic volume compared with the sham-operated group;however,the dogs in the RSD group had a higher LV ejection fraction (LVEF) than the dogs in the control group (P <0.001).The LV systolic strains were higher in the RSD group than in the control group (P <0.001 for longitudinal,circumferential and radial strain,respectively).The levels of LV dyssynchrony were lower in the RSD group than in the control group (P < 0.001 for longitudinal,circumferential and radial dyssynchrony,respectively).Compared with control group,RSD group had lower LV end-diastolic pressures and less fibrous tissue.Conclusions RSD inhibites the development of left ventricular mechanical dyssynchrony during the progression of

  10. Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis. (United States)

    Schneider, Johanna; Lother, Achim; Hein, Lutz; Gilsbach, Ralf


    Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development of cardiac hypertrophy and progression of heart failure is less well known. Thus, the aim of the present study was to determine the effect of chronic cardiac pressure overload in mice on adrenal medulla structure and function. Cardiac hypertrophy was induced in wild-type mice by transverse aortic constriction (TAC) for 8 weeks. After TAC, the degree of cardiac hypertrophy correlated significantly with adrenal weight and adrenal catecholamine storage. In the medulla, TAC caused an increase in chromaffin cell size but did not result in chromaffin cell proliferation. Ablation of chromaffin α(2C)-adrenoceptors did not affect adrenal weight or epinephrine synthesis. However, unilateral denervation of the adrenal gland completely prevented adrenal hypertrophy and increased catecholamine synthesis. Transcriptome analysis of microdissected adrenal medulla identified 483 up- and 231 downregulated, well-annotated genes after TAC. Among these genes, G protein-coupled receptor kinases 2 (Grk2) and 6 and phenylethanolamine N-methyltransferase (Pnmt) were significantly upregulated by TAC. In vitro, acetylcholine-induced Pnmt and Grk2 expression as well as enhanced epinephrine content was prevented by inhibition of nicotinic acetylcholine receptors and Ca(2+)/calmodulin-dependent signaling. Thus, activation of preganglionic sympathetic nerves innervating the adrenal medulla plays an essential role in inducing adrenal hypertrophy, enhanced catecholamine synthesis and induction of Grk2 expression after cardiac pressure overload.

  11. Efeito da denervação cardíaca ventral na incidência de fibrilação atrial após revascularização cirúrgica do miocárdio Effect of ventral cardiac denervation in the incidence of atrial fibrilation after coronary artery bypass graft surgery

    Directory of Open Access Journals (Sweden)

    João Roberto Breda


    Full Text Available OBJETIVO: Verificar o efeito da denervação cardíaca ventral na incidência de fibrilação atrial no pós-operatório de revascularização cirúrgica do miocárdio. MÉTODOS: Entre setembro e novembro de 2005, 50 pacientes consecutivos da mesma instituição foram alocados neste estudo prospectivo e randomizado. Foram selecionados pacientes portadores de insuficiência coronariana com indicação de revascularização cirúrgica do miocárdio, sem história ou diagnóstico prévio de arritmia atrial. Os critérios de exclusão foram: idade acima de 75 anos, história prévia de arritmia atrial e operações cardíacas associadas. A denervação era realizada antes do início da circulação extracorpórea pela remoção do tecido gorduroso ao redor da veia cava superior, aorta e artéria pulmonar. Os grupos foram comparados de acordo com as características clínicas, demográficas e variáveis operatórias. RESULTADOS: Não houve mortalidade hospitalar em ambos os grupos. O tempo médio adicional para realização da denervação foi de 7,64 + 2,33 minutos e não houve complicações associadas ao procedimento. Cinco pacientes apresentaram fibrilação atrial no pós-operatório, sendo dois (8% no grupo controle e três (12% no grupo denervação. O risco dos pacientes do grupo denervação apresentarem fibrilação atrial foi 22% maior do que no grupo controle (intervalo de confiança, 0,56-2,66, porém, este resultado não foi estatisticamente significativo (p=0,64. CONCLUSÕES: A denervação cardíaca ventral, apesar de rápida execução e de baixo risco, não apresentou efeito na redução da incidência de fibrilação atrial no pós-operatório de revascularização cirúrgica do miocárdio.OBJECTIVE: To evaluate the effect of ventral cardiac denervation in the incidence of atrial fibrillation after coronary artery bypass surgery. METHODS: Between September and November, 50 patients without history or previous diagnosis of atrial

  12. Next generation renal denervation: chemical “perivascular” renal denervation with alcohol using a novel drug infusion catheter

    Energy Technology Data Exchange (ETDEWEB)

    Fischell, Tim A. [Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI, 49008 (United States); Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025 (United States); Fischell, David R.; Ghazarossian, Vartan E. [Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025 (United States); Vega, Félix [Preclinical Consultation, San Francisco, CA (United States); Ebner, Adrian [Clinics, Ascension (Paraguay)


    the Peregrine™ chemical renal denervation catheter to perform renal sympathetic denervation using micro-doses of alcohol.

  13. Sympathetic radiofrequency neurolysis for unilateral lumbar hyperhidrosis: a case report. (United States)

    Aşik, Züleyha Soytürk; Orbey, Başak Ceyda; Aşik, Ibrahim


    Patients with hyperhidrosis suffer from physical, social and mental discomfort which often cannot be treated sufficiently using conservative measures. A new percutaneous approach to sympathectomy using radiofrequency denervation has seemed to offer longer duration of action and less incidence of post sympathetic neuralgia. This article reports the authors' experience with sympathetic RF neurolysis in a 35 year old male with right unilateral lumbar hyperhidrosis. Under scopy guided localization of the lumbar spine sympathetic blockade with local anesthetics to L2-5 vertebral levels were performed as a diagnostic block. Lesion effectiveness is monitored by bilateral feet skin temperature measurement. Clinical effects produced by the first sympathetic ganglion block were sustained for 1 week and then RF neurolysis of lumbar sympathetic ganglion was performed to the same levels for a longer effect. The procedure was accomplished within 30 minutes and the patient was discharged within 2 hours after the procedure. Hyperhidrosis was relieved after the procedure and there were no postsympathectomy neuralgia and sexual dysfunction. The patient obtained improvement of lumbar hyperhidrosis at his first month of follow- up and was satisfied with the outcome. In conclusion, RF neurolysis of lumbar sympathetic ganglions is a safe and effective palliative procedure with minimal invasiveness for relieving excessive sweat secretion in patients with localized hyperhidrosis.

  14. Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving? (United States)

    Al-Fakhouri, Ahmad; Efeovbokhan, Nephertiti; Nakhla, Rami; Khouzam, Rami N


    Hypertension is one of the most common chronic clinical problems encountered by physicians. The prevalence of resistant hypertension is estimated at 9% in the US. Patients with resistant hypertension have been shown to be at higher risk for adverse cardiovascular events, hence the need for greater efforts in improving the treatment of hypertension. The renal sympathetic nerves play an important role in the development of hypertension, mediated via sodium and water retention, increased renin release and alterations in renal blood flow. The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular, selective, minimally invasive approach to renal denervation; a potential treatment option for resistant hypertension. While the RAPID, Reduce-HTN, EnligHTN, DENERHTN and Symplicity HTN-1 and -2 studies showed significant benefit of renal denervation in the treatment of resistant hypertension, the results of Oslo RDN, Prague-15 and Symplicity HTN-3 were not so favorable. Future well-designed clinical trials are needed to ascertain the benefits or otherwise of renal denervation in treatment-resistant hypertension.

  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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.)

  16. Sympathetic nervous system and chronic renal failure. (United States)

    Boero, R; Pignataro, A; Ferro, M; Quarello, F


    The aim of this work was to review evidence on the role of the sympathetic nervous system (SNS) in chronic renal failure (CRF). Three main points are discussed: 1) SNS and pathogenesis of arterial hypertension; 2) SNS and cardiovascular risk; 3) implication of SNS in arterial hypotension during hemodialysis. Several lines of evidence indicate the presence of a sympathetic hyperactivity in CRF, and its relationship with arterial hypertension. It is suggested that diseased kidneys send afferent nervous signals to central integrative sympathetic nuclei, thus contributing to the development and maintenance of arterial hypertension. The elimination of these impulses with nephrectomy could explain the concomitant reduction of blood pressure. Several experiments confirmed this hypothesis. Regarding SNS and cardiovascular risk, some data suggest that reduced heart rate variability identifies an increased risk for both all causes and sudden death, independently from other recognized risk factors. Symptomatic hypotension is a common problem during hemodialysis treatment, occurring in approximately 20-30% of all hemodialysis sessions and is accompanied by acute withdrawal of sympathetic activity, vasodilation and relative bradicardia. This reflex is thought to be evoked by vigorous contraction of a progressively empty left ventricle, activating cardiac mechanoceptors. This inhibits cardiovascular centers through vagal afferents, and overrides the stimulation by baroreceptor deactivation. Alternative explanations include cerebral ischemia and increased production of nitric oxide, which inhibit central sympathetic activity. It is hoped that therapies aimed at modulating sympathetic nerve activity in patients with CRF will ameliorate their prognosis and quality of life.

  17. Joint UK societies’ 2014 consensus statement on renal denervation for resistant hypertension (United States)

    Lobo, Melvin D; de Belder, Mark A; Cleveland, Trevor; Collier, David; Dasgupta, Indranil; Deanfield, John; Kapil, Vikas; Knight, Charles; Matson, Matthew; Moss, Jonathan; Paton, Julian F R; Poulter, Neil; Simpson, Iain; Williams, Bryan; Caulfield, Mark J


    Resistant hypertension continues to pose a major challenge to clinicians worldwide and has serious implications for patients who are at increased risk of cardiovascular morbidity and mortality with this diagnosis. Pharmacological therapy for resistant hypertension follows guidelines-based regimens although there is surprisingly scant evidence for beneficial outcomes using additional drug treatment after three antihypertensives have failed to achieve target blood pressure. Recently there has been considerable interest in the use of endoluminal renal denervation as an interventional technique to achieve renal nerve ablation and lower blood pressure. Although initial clinical trials of renal denervation in patients with resistant hypertension demonstrated encouraging office blood pressure reduction, a large randomised control trial (Symplicity HTN-3) with a sham-control limb, failed to meet its primary efficacy end point. The trial however was subject to a number of flaws which must be taken into consideration in interpreting the final results. Moreover a substantial body of evidence from non-randomised smaller trials does suggest that renal denervation may have an important role in the management of hypertension and other disease states characterised by overactivation of the sympathetic nervous system. The Joint UK Societies does not recommend the use of renal denervation for treatment of resistant hypertension in routine clinical practice but remains committed to supporting research activity in this field. A number of research strategies are identified and much that can be improved upon to ensure better design and conduct of future randomised studies. PMID:25431461

  18. Reversible bladder denervation in acute polyradiculitis

    DEFF Research Database (Denmark)

    Kamper, A L; Andersen, J T


    A case of reversible bladder denervation in acute polyradiculitis is presented, in which both motor and sensory bladder involvement could be demonstrated using cystometry and denervation-hypersensitivity testing. Attention is drawn to the differential diagnosis to cauda equina syndromes of other ...

  19. Effects of renal sympathetic denervation on the development of atrial fibrillation substrates in dogs with pacing-in-duced heart failure%肾去交感神经对心力衰竭犬心房基质和心房颤动诱发的影响

    Institute of Scientific and Technical Information of China (English)

    代子玄; 赵庆彦; 于胜波; 王徐乐; 肖金平; 唐艳红; 王晞; 黄从新


    摇目的摇探讨经导管介入肾去交感神经对心力衰竭(简称心衰)犬心房基质和心房颤动(简称房颤)诱发的影响。方法摇22只犬随机分为假手术组(n=7),心衰组(n=8)和肾动脉消融组(n=7)。假手术组犬植入起搏器不起搏,喂养3周;心衰组植入起搏器后以240次/分的频率连续右室起搏3周,于起搏前、3周后分别取静脉血检测血管紧张素域( Ang域)和醛固酮水平;消融组先行双侧肾动脉消融,喂养8周,起搏器植入同心衰组。其中血清学指标测3次(消融前、消融8周后、起搏3周后)。所有犬在实验基线期和终点均进行心脏彩超、血压及电生理检测;处死动物后迅速取心房组织检测其基质变化。结果摇心衰组2只死亡,消融组1只未进入试验。淤与基线期相比,心衰组和消融组在起搏3周后股动脉血压均明显下降,且两者无明显差异;②与基线期相比,心衰组起搏3周后左室收缩末期压力(LVESP)降低[(167依21)mmHg vs (123依14) mmHg,P<0.01],左室舒张末期压力(LV鄄EDP)升高[(2.5依1.3) mmHg vs (25依3.7) mmHg,P<0.01]。消融组起搏3周后LVESP也降低,但LVEDP无明显变化;③与基线期相比,心衰组起搏3周后心房有效不应期明显降低,消融组无明显变化。消融组起搏3周后房颤平均诱发次数和时间明显少于心衰组;④与心衰组相比,消融组心房肌胶原容积分数、Ang域和转化生长因子鄄茁水平明显降低,血Ang域和醛固酮水平也明显降低。结论摇肾去交感神经可抑制长期快速心室起搏心房基质的改变和房颤的诱发。%Objective To investigate the role of renal denervation on atrial substrate and inducibility of atrial fibrillation ( AF) in dogs with pacing-induced heart failure( HF) . Methods Twenty-two dogs were randomized into sham-operated (n=7), HF (n=8) and renal artery ablation (RAA,n=7) groups. Sham-operated dogs were implanted with transvenous cardiac

  20. Protein kinase C pathway on cardiac sympathetic nerve neuroplasticity and myocardial interstitial remodeling%心脏交感神经和心肌间质重塑的共同通路——蛋白激酶C途径

    Institute of Scientific and Technical Information of China (English)

    李贺; 周欣; 王坷; 赵丽霞; 王志宏; 李玉明


    Cardiac sympathetic nerve and myocardial interstitium play important roles for preservation of heart function. Different extent of the interstitial remodeling and neuroplasticity commonly occur in many kinds of cardiovascular diseases. The abnormalities interact and contribute to progression and worsening of the diseases. There is accumulating evidence suggesting that protein kinase C activation as a regulator involves in and mediates interaction between the neuroplasticity and remodeling under such conditions, which plays a critical role in the nerve dysfunction and myocardial fibrosis.%心脏交感神经和心肌间质对维持正常心功能有重要作用.心血管患病时,两者均发生不同程度的重塑,并互相影响,这些变化对疾病进展发挥重要影响.研究证据显示,两者间的相互作用可能通过蛋白激酶C介导,对交感神经功能异常和心肌纤维化都发挥重要作用.

  1. Analysis and measurement of the sympathetic and sensory innervation of white and brown adipose tissue. (United States)

    Vaughan, Cheryl H; Zarebidaki, Eleen; Ehlen, J Christopher; Bartness, Timothy J


    Here, we provide a detailed account of how to denervate white and brown adipose tissue (WAT and BAT) and how to measure sympathetic nervous system (SNS) activity to these and other tissues neurochemically. The brain controls many of the functions of WAT and BAT via the SNS innervation of the tissues, especially lipolysis and thermogenesis, respectively. There is no clearly demonstrated parasympathetic innervation of WAT or the major interscapular BAT (IBAT) depot. WAT and BAT communicate with the brain neurally via sensory nerves. We detail the surgical denervation (eliminating both innervations) of several WAT pads and IBAT. We also detail more selective chemical denervation of the SNS innervation via intra-WAT/IBAT 6-hydroxy-dopamine (a catecholaminergic neurotoxin) injections and selective chemical sensory denervation via intra-WAT/IBAT capsaicin (a sensory nerve neurotoxin) injections. Verifications of the denervations are provided (HPLC-EC detection for SNS, ELIA for calcitonin gene-related peptide (proven sensory nerve marker)). Finally, assessment of the SNS drive to WAT/BAT or other tissues is described using the alpha-methyl-para-tyrosine method combined with HPLC-EC, a direct neurochemical measure of SNS activity. These methods have proven useful for us and for other investigators interested in innervation of adipose tissues. The chemical denervation approach has been extended to nonadipose tissues as well.

  2. Renal sympathetic nerve activity during asphyxia in fetal sheep. (United States)

    Booth, Lindsea C; Malpas, Simon C; Barrett, Carolyn J; Guild, Sarah-Jane; Gunn, Alistair J; Bennet, Laura


    The sympathetic nervous system (SNS) is an important mediator of fetal adaptation to life-threatening in utero challenges, such as asphyxia. Although the SNS is active well before term, SNS responses mature significantly over the last third of gestation, and its functional contribution to adaptation to asphyxia over this critical period of life remains unclear. Therefore, we examined the hypotheses that increased renal sympathetic nerve activity (RSNA) is the primary mediator of decreased renal vascular conductance (RVC) during complete umbilical cord occlusion in preterm fetal sheep (101 ± 1 days; term 147 days) and that near-term fetuses (119 ± 0 days) would have a more rapid initial vasomotor response, with a greater increase in RSNA. Causality of the relationship of RSNA and RVC was investigated using surgical (preterm) and chemical (near-term) denervation. All fetal sheep showed a significant increase in RSNA with occlusion, which was more sustained but not significantly greater near-term. The initial fall in RVC was more rapid in near-term than preterm fetal sheep and preceded the large increase in RSNA. These data suggest that although RSNA can increase as early as 0.7 gestation, it is not the primary determinant of RVC. This finding was supported by denervation studies. Interestingly, chemical denervation in near-term fetal sheep was associated with an initial fall in blood pressure, suggesting that by 0.8 gestation sympathetic innervation of nonrenal vascular beds is critical to maintain arterial blood pressure during the rapid initial adaptation to asphyxia.

  3. Sympathetic re-innervation of myocardium after liver transplant in the hereditary amyloid neuropathy; Reinnervation sympathique du myocarde apres transplantation hepatique dans la neuropathie amyloide hereditaire

    Energy Technology Data Exchange (ETDEWEB)

    Delahaye, N.; Le Guludec, D. [Medecine Nucleaire, Hopital Bichat, Paris (France); Slama, M. [Cardiologie, Hopital A.Beclere, Paris (France); Guyen, C.N. [SHFJ, DSV-CEA, Orsay (France); Dinanian, S. [Cardiologie, Hopital A.Beclere, Paris (France); Merlet, P. [SHFJ, DSV-CEA, Orsay (France)


    The hereditary amyloid neuropathy (HAN) is characterized by a progressive sensory-motor poly-neuropathy and a dysautonomia with myocardium sympathetic denervation. This is established by MIBL scintigraphy and may enhance the troubles of conduction and of cardiac rhythm. The amyloid deposits are constituted of anomalous pre-albumin fabricated by liver. The hepatic transplant (HT) is the only known treatment. Four patients (GI: 39 {+-} 5 years) have been studied by MIBG scintigraphy, 2.2 {+-} 0.7 years after HT, and compared with 12 patients (GII: 39 {+-} 12 years) studied before HT. The left ventricular function, the coronary arteries and the at-rest scintigraphy with thallium were normal for all of them. The cardiac capture of MIBG, evaluated by the cardio-mediastinal activity ratio (C/M), measured on an anterior thoracic planar acquisition performed 4 hours after the intravenous injection of 300 MBq, was higher for GI than for GII (1.49 {+-} 0.12 vs 1.29 {+-} 0.13, p 0.02). The washouts (4 h / 20 min) were not different. In tomography, the patients of GI presented focal anomalies with a more-or-less extended apical defect, a satisfying fixation of the basal half of the anterior wall, more-or-less overflowing the septal and lateral walls, and for 2 patients, a satisfying inferior fixation. On the contrary, 9/12 patients of GII have had a diffuse absence of fixation, the other three heaving a satisfying antero-basal fixation ({chi}{sup 2}, p = 0.05). The results are not explained by difference of severity or evolution duration of HAN. Thus, it appears that there exists a sympathetic re-innervation of myocardium after HT in the HAN, debuting by the heart base, similarly with the effect of anatomic interruption of innervation in cardiac transplants

  4. Intrinsic innervation and dopaminergic markers after experimental denervation in rat thymus

    Directory of Open Access Journals (Sweden)

    F. Mignini


    Full Text Available The aim of this study was to examine rat thymus innervation using denervation techniques and to explore the related micro-anatomical localization of dopamine, D1, D2 receptors and dopamine membrane transporter (DAT. In the thymus subcapsular region, the parenchymal cholinergic fibers belong exclusively to phrenic nerve branching. No somatic phrenic nerve branching was detected in any other analysed thymus lobule regions. In rats subjected to sympathetic or parasympathetic ablation, it was observed that catecholaminergic and cholinergic nerve fibers respectively contributed to forming plexuses along vessel walls. In the subcapsular and septal region, no parenchymal nerve branching, belonging to sympathetic or parasympathetic nervous system was noted. Instead, in the deep cortical region, cortico-medullary junction (CM-j and medulla, catecholaminergic and cholinergic nerve fibers were detected along the vessels and parenchyma. Dopamine and dopamine receptors were widely diffused in the lobular cortico-medullary junction region and in the medulla, where the final steps of thymocyte maturation and their trafficking take place. No variation in dopamine and DAT immune reaction was observed following total or partial parasympathectomy or phrenic nerve cutting. After chemical or surgical sympathectomy however, neither dopamine nor DAT immune reaction was noted again. Instead, D1 and D2 dopamine receptor expression was not affected by thymus denervation. In rats subjected to specific denervation, it was observed the direct intraparenchymal branching of the phrenic nerve and sympathetic and parasympathetic fibers into thymus parenchyma along vessels. These findings on the dopaminergic system highlight the importance of neurotransmitter receptor expression in the homeostasis of neuroimmune modulation.

  5. Intrinsic innervation and dopaminergic markers after experimental denervation in rat thymus. (United States)

    Mignini, F; Sabbatini, M; D'Andrea, V; Cavallotti, C


    The aim of this study was to examine rat thymus innervation using denervation techniques and to explore the related micro-anatomical localization of dopamine, D1, D2 receptors and dopamine membrane transporter (DAT). In the thymus subcapsular region, the parenchymal cholinergic fibers belong exclusively to phrenic nerve branching. No somatic phrenic nerve branching was detected in any other analysed thymus lobule regions. In rats subjected to sympathetic or parasympathetic ablation, it was observed that catecholaminergic and cholinergic nerve fibers respectively contributed to forming plexuses along vessel walls. In the subcapsular and septal region, no parenchymal nerve branching, belonging to sympathetic or parasympathetic nervous system was noted. Instead, in the deep cortical region, cortico-medullary junction (CM-j) and medulla, catecholaminergic and cholinergic nerve fibers were detected along the vessels and parenchyma. Dopamine and dopamine receptors were widely diffused in the lobular cortico-medullary junction region and in the medulla, where the final steps of thymocyte maturation and their trafficking take place. No variation in dopamine and DAT immune reaction was observed following total or partial parasympathectomy or phrenic nerve cutting. After chemical or surgical sympathectomy however, neither dopamine nor DAT immune reaction was noted again. Instead, D1 and D2 dopamine receptor expression was not affected by thymus denervation. In rats subjected to specific denervation, it was observed the direct intraparenchymal branching of the phrenic nerve and sympathetic and parasympathetic fibers into thymus parenchyma along vessels. These findings on the dopaminergic system highlight the importance of neurotransmitter receptor expression in the homeostasis of neuroimmune modulation.

  6. Morphology of sympathetic chain in Saguinus niger

    Directory of Open Access Journals (Sweden)



    Full Text Available Saguinus niger popularly known as Sauim, is a Brazilian North primate. Sympathetic chain investigation would support traumatic and/or cancer diagnosis which are little described in wild animals. The aim of this study was to describe the morphology and distribution of sympathetic chain in order to supply knowledge for neurocomparative research. Three female young animals that came death by natural causes were investigated. Animals were fixed in formaldehyde 10% and dissected along the sympathetic chain in neck, thorax and abdomen. Cranial cervical ganglion was located at the level of carotid bifurcation, related to carotid internal artery. In neck basis the vagosympathetic trunk divides into the sympathetic trunk and the parasympathetic vagal nerve. Sympathetic trunk ran in dorsal position and originated the stellate ganglia, formed by the fusion of caudal cervical and first thoracic ganglia. Vagal trunk laid ventrally to heart and formed the cardiac plexus. In abdomen, on the right side, were found the celiac ganglion and cranial mesenteric ganglion; in the left side these ganglia were fusioned into the celiac-mesenteric ganglion displaced closely to the celiac artery. In both sides, the caudal mesenteric ganglion was located near to the caudal mesenteric artery.

  7. Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs. (United States)

    Poncet, M. F.; Damase-Michel, C.; Tavernier, G.; Tran, M. A.; Berlan, M.; Montastruc, J. L.; Montastruc, P.


    1. Plasma levels of noradrenaline (NA) and neuropeptide Y (NPY) were evaluated in two experimental models associated with an increase in sympathetic tone: conscious dogs which were subject to either sinoaortic denervation or acute administration of the alpha 2-adrenoceptor antagonist yohimbine. 2. Dogs that had undergone sinoaortic denervation exhibited a two fold increase in plasma NA without any change in NPY levels. 3. Yohimbine (0.05 mg kg-1 i.v. as a bolus) produced similar effects. A higher dose of yohimbine (0.5 mg kg-1 i.v.) increased both plasma NA (7 fold) and NPY (6.5 fold) levels. 4. The present results indicate that changes in plasma catecholamines and NPY are not always concomitant. They suggest that the simultaneous release of NA and NPY is only observed under in vivo conditions for a marked increase in sympathetic tone. PMID:1596679

  8. Effects of renal sympathetic nerve radiofrequency ablation on norepinephrine spillover rate and sympathetic nerve activity in dogs with hypertension

    Directory of Open Access Journals (Sweden)

    Hang YU


    Full Text Available Objective  To evaluate the validity and explore the mechanism of renal sympathetic denervation (RSD in the treatment of dogs with hypertension reproduced by constriction of abdominal aorta. Methods  The hypertension model was reproduced by constriction of abdominal aorta in 20 adult healthy dogs. These dogs were then randomly divided into the treatment group and control group (10 each. Renal sympathetic nerve radiofrequency ablation was done in treatment group 1 month after modeling. The foreleg blood pressure, sympathetic activity and norepinephrine overflow rate of dogs in two groups were detected before modeling, and 1, 2 and 3 months after modeling, and the trend of the change was also observed. Results  One month after modeling, the systolic blood pressure (SBP, diastolic blood pressure (DBP and mean arterial blood pressure (MAP were elevated significantly in control group (146.7±21.0, 89.0±12.7 and 108.3±14.9mmHg compared with those before modeling (119.5±13.2, 76.5±7.8 and 90.9±8mmHg, P < 0.05. The renal sympathetic activity impulse and norepinephrine spillover rate were also enhanced significantly (P < 0.05. The renal sympathetic nerve activity obviously decreased in the treatment group after the operation, and then increased 2 months after the ablation. The norepinephrine spillover rate in treatment group increased significantly 1 month after modeling (P < 0.05, and decreased after ablation, and it lasted to the end of the experiment (P < 0.05. One and two months after ablation, the norepinephrine spillover rate was lower in treatment group than in control group (P < 0.05. Conclusion  Renal sympathetic nerve radiofrequency ablation significantly inhibits the elevation of norepinephrine spillover rate and sympathetic nerve activity in dogs with hypertension.

  9. Immunopathology of sympathetic ophthalmia. (United States)

    Marak, G E


    The long held notion that sympathetic ophthalmia represents an autoimmune reaction to uveal pigment is no longer tenable. Pigmentation influences the histopathologic picture of sympathetic ophthalmia but no evidence supports the role of uveal pigment as inciting antigen. Several recent studies have confirmed our initial report of the participation of cellular hypersensitivity to ocular tissues in the pathogenesis of this disease. Both clinical and experimental studies implicate retinal tissue as being more immunogenic than uveal antigens. The recent histopathologic observation that eosinophils concentrate near the choriocapillaris suggests that outer retina and retinal pigment epithelium should not be overlooked as a potential source of the stimulating antigen in sympathetic ophthalmia.

  10. Evaluation of cardiac autonomic nerves by iodine-123 metaiodobenzylguanidine scintigraphy and ambulatory electrocardiography in patients after arterial switch operations

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Hajime; Maeda, Masanobu; Miyahara, Ken [Shakaihoken Chukyo Hospital, Nagoya (Japan)] [and others


    The autonomic cardiac nerves reach the heart after passing through the vicinity of the aortic root and the pulmonary trunk. The arterial switch operation (ASO) completely transects the ascending aorta and the pulmonary trunk. Therefore, this surgical procedure virtually denerves the heart. Cardiac sympathetic denervation and reinnervation were evaluated in patients after ASO using iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and parasympathetic denervation and reinnervation using ambulatory electrocardiography [Holter electrocardiogram (ECG)]. MIBG scintigraphy was performed in 14 patients who underwent ASO (ASO group) and 3 patients who underwent other open heart surgery (control group). All patients in the ASO group underwent the operation in the neonatal or infantile period. Planar and single photon emission computed tomography (SPECT) images of the myocardium were obtained. Defect score was determined by the SPECT images as a semi-quantitative index. The mean interval between ASO and MIBG scintigraphy was 25.6{+-}14.6 months. Holter ECG was also performed in 14 patients in the ASO group and 19 age-matched normal children. The Holter ECGs were plotted on a Lorenz plot. The H index, which is related to vagal tone for the cardiovascular system, was calculated from the R-R intervals. The mean interval between the ASO and Holter ECG was 8.3{+-}9.7 months. MIBG scintigraphy in the control group demonstrated an almost normal homogeneous tracer uptake, but showed extremely reduced tracer uptake and significantly higher defect score in the ASO group. The extent and degree of the reduction of MIBG uptake improved with time after the ASO. The heart-to-mediastinum MIBG count ratio tended to increase with time. The H index of the ASO group was lower than that of normal children (<12 months: Control group 0.0280{+-}0.0068 vs ASO group 0.0219{+-}0.0083), and gradually increased with time (1-3 years: 0.0470{+-}0.0157 vs 0.0314{+-}0.0124). (author)

  11. Role of sympathetic nervous system and neuropeptides in obesity hypertension

    Directory of Open Access Journals (Sweden)

    J.E. Hall


    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

  12. Investigation of Sleep Bruxism Relating to Micro-arousals and Cardiac Sympathetic Activities%夜磨牙与微觉醒及心脏交感神经活动的关系

    Institute of Scientific and Technical Information of China (English)

    刘伟才; 王海波; 陈威; 李强


    Objective: To investigate whether rhythmic masticatory muscle activity (RMMA) is associated with sleep micro- arousals (MA), and analyze the association between RMMA of sleep bruxism patients (RMMA/SB) and autonomic cardiac activity. Methods: Thirty SB subjects and thirty control subjects for two consecutive nights were performed by polygraphic recordings. MA index and RMMA index were scored. The mean heart rate from a series of 10 cardiac cycles was calculated at 60, 40, 20 and 5 sec before RMMA onset respectively. To assess a transient beat-to-beat heart rate change in relation to the RMMA onset, heart rate from 5 cardiac cycles before and 5 cycles after the onset were also calculated. Results: Sleep bruxism (SB) subjects showed a higher incidence of rhythmic masticatory muscle activity (RMMA) than control subjects (6.10±1.05 vs. 1.81 ±0.39, P<0.0001). However, no difference was found in according to their micro-arousal index(7.72±1.21 vs.7.53±1.33, P=0.5641). RMMA/SB was associated with sleep micro-arousals. In both groups, transient heart rate acceleration was observed in relation to the onset of RMMA episodes. Conclusion: RMMA is associated with sleep micro-arousals. In SB subjects, a clear increase in sympathetic activity precedes SB onset.%目的:研究夜磨牙(sleep bruxism,SB)患者睡眠期咀嚼肌节律性运动(RMMA)发生的微觉醒机制.方法:对30名夜磨牙患者、30名正常人进行连续2夜的多导睡眠监测,研究RMMA事件与微觉醒(MA)的时间相关性;比较2组间RMMA指数及MA指数的差异;RMMA事件发生前60 s、前40 s、前20 s、前5s,共5个时间点的各连续10个心动周期的平均心率,以及RMMA事件发生前后各5个心动周期的心率变化.结果:夜磨牙症患者微觉醒指数(7.72±1.21)与正常对照相似(7.53±1.33,P=0.5641);但咀嚼肌节律性运动频率,即磨牙指数[(6.10±1.05)次/h]约3倍于正常对照组[(1.81±0.39)次/h,P<0.0001)].RMMA事件与MA存在高度时间相关

  13. Chemical Renal Denervation in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Consigny, Paul M., E-mail:; Davalian, Dariush, E-mail: [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail:; Hu, Jie, E-mail: [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail:; Stolarik, DeAnne, E-mail: [Abbvie, Analytical Pharmacology (United States)


    Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

  14. Sympathetic nervous system promotes hepatocarcinogenesis by modulating inflammation through activation of alpha1-adrenergic receptors of Kupffer cells. (United States)

    Huan, Hong-Bo; Wen, Xu-Dong; Chen, Xue-Jiao; Wu, Lin; Wu, Li-Li; Zhang, Liang; Yang, Da-Peng; Zhang, Xia; Bie, Ping; Qian, Cheng; Xia, Feng


    The sympathetic nervous system (SNS) is known to play a significant role in tumor initiation and metastasis. Hepatocellular carcinoma (HCC) frequently occurs in cirrhotic livers after chronic inflammation, and the SNS is hyperactive in advanced liver cirrhosis. However, it remains unclear whether the SNS promotes hepatocarcinogenesis by modulating chronic liver inflammation. In this study, a retrospective pathological analysis and quantification of sympathetic nerve fiber densities (tyrosine hydroxylase, TH(+)) in HCC patients, and diethylnitrosamine (DEN)-induced hepatocarcinogenesis in rats were performed. Our data showed that high density of sympathetic nerve fibers and α1-adrenergic receptors (ARs) of Kupffer cells (KCs) were associated with a poor prognosis of HCC. Sympathetic denervation or blocking of α1-ARs decreased DEN-induced HCC incidence and tumor development. In addition, synergistic effects of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β) in hepatocarcinogenesis were observed. The suppression of the SNS reduced IL-6 and TGF-β expression, which suppressed hepatocarcinogenesis, and KCs play a key role in this process. After the ablation of KCs, IL-6 and TGF-β expression and the development of HCC were inhibited. This study demonstrates that sympathetic innervation is crucial for hepatocarcinogenesis and that the SNS promotes hepatocarcinogenesis by activating α1-ARs of KCs to boost the activation of KCs and to maintain the inflammatory microenvironment. These results indicate that sympathetic denervation or α1-ARs blockage may represent novel treatment approaches for HCC.

  15. Nitric oxide and the autonomic regulation of cardiac excitability. The G.L. Brown Prize Lecture. (United States)

    Paterson, D


    Cardiac sympathetic imbalance and arrhythmia; Nitric oxide-cGMP pathway and the cholinergic modulation of cardiac excitability; Nitric oxide-cGMP pathway and the sympathetic modulation of cardiac excitability; Functional significance of nitric oxide in the autonomic regulation of cardiac excitability; Summary; References. Experimental Physiology (2001) 86.1, 1-12.

  16. Imaging of denervation in the head and neck

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093 Lisboa (Portugal)], E-mail:


    Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation.

  17. Renal Denervation Using an Irrigated Catheter in Patients with Resistant Hypertension: A Promising Strategy?

    Energy Technology Data Exchange (ETDEWEB)

    Armaganijan, Luciana, E-mail:; Staico, Rodolfo; Moraes, Aline; Abizaid, Alexandre; Moreira, Dalmo; Amodeo, Celso; Sousa, Márcio; Borelli, Flávio; Armaganijan, Dikran; Sousa, J. Eduardo; Sousa, Amanda [Instituto Dante Pazzanese de Cardiologia, São Paulo, SP (Brazil)


    Systemic hypertension is an important public health problem and a significant cause of cardiovascular mortality. Its high prevalence and the low rates of blood pressure control have resulted in the search for alternative therapeutic strategies. Percutaneous renal sympathetic denervation emerged as a perspective in the treatment of patients with resistant hypertension. To evaluate the feasibility and safety of renal denervation using an irrigated catheter. Ten patients with resistant hypertension underwent the procedure. The primary endpoint was safety, as assessed by periprocedural adverse events, renal function and renal vascular abnormalities at 6 months. The secondary endpoints were changes in blood pressure levels (office and ambulatory monitoring) and in the number of antihypertensive drugs at 6 months. The mean age was 47.3 (± 12) years, and 90% of patients were women. In the first case, renal artery dissection occurred as a result of trauma due to the long sheath; no further cases were observed after technical adjustments, thus showing an effect of the learning curve. No cases of thrombosis/renal infarction or death were reported. Elevation of serum creatinine levels was not observed during follow-up. At 6 months, one case of significant renal artery stenosis with no clinical consequences was diagnosed. Renal denervation reduced office blood pressure levels by 14.6/6.6 mmHg, on average (p = 0.4 both for systolic and diastolic blood pressure). Blood pressure levels on ambulatory monitoring decreased by 28/17.6 mmHg (p = 0.02 and p = 0.07 for systolic and diastolic blood pressure, respectively). A mean reduction of 2.1 antihypertensive drugs was observed. Renal denervation is feasible and safe in the treatment of resistant systemic arterial hypertension. Larger studies are required to confirm our findings.

  18. Changes following denervation to the masseter muscle

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang


    BACKGROUND: Masseter muscle nerve is often injured in mandible osteotomy. What changes in food intake and masseter muscle will be brought after masseter muscle nerve injury?OBJECTIVE: This study was designed to selectively establish animal models of denervated masseter muscle and investigate the effects of severing masseter muscular nerve on masseter muscle and animal's food intake. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Laboratory Animal Center, Nanfang Hospital, Southern Medical University from September to November 2005. MATERIALS: A total of 50 healthy, adult, SPF-grade, New Zealand rabbits, of both genders, were used to develop an animal model of selectively denervated masseter muscle.METHODS: Five rabbits were randomly selected as normal controls. According to various mutilation methods, the remaining animals were randomly divided into 3 experimental groups, with 15 rabbits in each group: masseter muscular neural stem denervated, masseter muscular neural superior branch-denervated, and masseter muscular neural inferior branch-denervated groups. Self-control comparison was performed on each animal. The right masseter muscle served as the experimental side, and the left masseter muscle served as the control side. In each group, 3 time points (2, 8, and 24 weeks post-surgery) were allotted for observation. MAIN OUTCOME MEASURES: At the pre-set time points, masseter muscular thickness was measured with a Logic 500 color Doppler ultrasonic diagnostic apparatus. Masseter muscle tissue was resected for hematoxylin eosin staining. Masseter muscular fiber diameter and area were measured with an optical microscope. Masseter muscle tissue was sectioned and nicotinamide adenine dinucleotide tetrazolium oxidoreductase (NADH-TR) and adenosine triphosphatase staining were performed. Following staining, the sections were quantitatively analyzed using an IBAS200 image analyzer.RESULTS: Post-surgery food intake: No abnormal

  19. Sympathetic neural control of indoleamine metabolism in the rat pineal gland (United States)

    Lynch, H. J.; Hsuan, M.; Wurtman, R. J.


    The mechanisms responsible for the acceleration in rat pineal biosynthetic activity in response to prolonged exposure to darkness or to immobilization were investigated in animals whose pineals were surgically denervated. Some animals were adrenalectomized to remove one potential source of circulating catecholamines, and some were subjected to a partial chemical sympathectomy accomplished by a series of intravenous injections of 6-hydroxydopamine. Results suggest that N-acetyltransferase (NAT) activity can be enhanced either by release of norepinephrine from sympathetic terminals within the pineal or from sympathetic nerve terminals elsewhere. The stress of immobilization stimulates the pineal by increasing circulating catecholamines. Photic control of pineal function requires intact pineal sympathetic innervation, since the onset of darkness apparently does not cause a sufficient rise in circulating catecholamines to stimulate the pineal. The present studies suggest that nonspecific stress triggers increased biosynthesis and secretion of melatonin; it is possible that this hormone may participate in mechanisms of adaptation.

  20. Cytokine responses during chronic denervation

    Directory of Open Access Journals (Sweden)

    Olsson Tomas


    Full Text Available Abstract Background The aim of the present study was to examine inflammatory responses during Wallerian degeneration in rat peripheral nerve when the regrowth of axons was prevented by suturing. Methods Transected rat sciatic nerve was sutured and ligated to prevent reinnervation. The samples were collected from the left sciatic nerve distally and proximally from the point of transection. The endoneurium was separated from the surrounding epi- and perineurium to examine the expression of cytokines in both of these compartments. Macrophage invasion into endoneurium was investigated and Schwann cell proliferation was followed as well as the expression of cytokines IL-1β, IL-10, IFN-γ and TNF-α mRNA. The samples were collected from 1 day up to 5 weeks after the primary operation. Results At days 1 to 3 after injury in the epi-/perineurium of the proximal and distal stump, a marked expression of the pro-inflammatory cytokines TNF-α and IL-1β and of the anti-inflammatory cytokine IL-10 was observed. Concurrently, numerous macrophages started to gather into the epineurium of both proximal and distal stumps. At day 7 the number of macrophages decreased in the perineurium and increased markedly in the endoneurium of both stumps. At this time point marked expression of TNF-α and IFN-γ mRNA was observed in the endo- and epi-/perineurium of the proximal stump. At day 14 a marked increase in the expression of IL-1β could be noted in the proximal stump epi-/perineurium and in the distal stump endoneurium. At that time point many macrophages were observed in the longitudinally sectioned epineurium of the proximal 2 area as well as in the cross-section slides from the distal stump. At day 35 TNF-α, IL-1β and IL-10 mRNA appeared abundantly in the proximal epi-/perineurium together with macrophages. Conclusion The present studies show that even during chronic denervation there is a cyclic expression pattern for the studied cytokines. Contrary to the

  1. Use-dependent loss of active sympathetic neurogenic vasodilation after nitric oxide synthase inhibition in conscious rats. Evidence for the presence of preformed stores of nitric oxide-containing factors (United States)

    Davisson, R. L.; Shaffer, R. A.; Johnson, A. K.; Lewis, S. J.


    In this study, we examined whether air-jet stress-induced active sympathetic hindlimb vasodilation in conscious rats involves the release of preformed stores of nitric oxide-containing factors. We determined the effects of repeated episodes of air-jet stress (six episodes given 5 minutes apart) on mean arterial pressure and vascular resistances in the mesenteric bed and intact and sympathetically denervated hindlimb beds of conscious rats treated with saline or the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mumol/kg IV). In saline-treated rats, air-jet stress produced alerting behavior, minor changes in blood pressure, pronounced mesenteric vaso-constriction, and immediate and marked vasodilation in the sympathetically intact hindlimb but a minor vasodilation in the sympathetically denervated hindlimb. Each air-jet stress produced virtually identical responses. In L-NAME-treated rats, the first air-jet stress produced vasodilator responses in the sympathetically intact and sympathetically denervated hindlimbs that were similar to those in the saline-treated rats. However, each subsequent air-jet stress produced progressively smaller vasodilator responses in the sympathetically intact but not the sympathetically denervated hindlimb. There was no loss of air-jet stress-induced alerting behavior or mesenteric vasoconstriction, suggesting that L-NAME did not interfere with the central processing of the air-jet or the resultant changes in autonomic nerve activity. The progressive diminution of air-jet stress-induced vasodilation in the intact hindlimb of L-NAME-treated rats may be due to the use-dependent depletion of preformed stores of nitric oxide-containing factors that cannot be replenished in the absence of nitric oxide synthesis.

  2. [Endovascular radiofrequency denervation of renal arteries as an innovation method of treatment of refractory arterial hypertension. First experience in Russia]. (United States)

    Danilov, N M; Matchin, Iu G; Chazova, I E


    Excessive activation of the sympathetic nervous system forms the basis of pathogenesis of essential arterial hypertension (AH). The present work was aimed at evaluating efficacy and safety of endovascular radiofrequency denervation of renal arteries in patients with AH refractory AH based on the initial first experience in with using this methodology in the Russian Federation. The interventions were carried out on December 14-15th, 2011 in the first five patients presenting with AH refractory to antihypertensive therapy consisting of three and more drugs in therapeutic doses, one of which was a diuretic. The selection criteria were systolic arterial pressure (SAP) ≥160 mm Hg or ≥150 mm Hg in the presence of type 2 diabetes mellitus. The obligatory conditions for selection were the preserved renal function [glomerular filtration rate (GFR) ≥45 ml/min] and the absence of the secondary form of AH. The procedure of denervation was performed in the conditions of roentgen-operating room using special Medtronic Ardian Simplicity Catheter System™. In all cases we managed to perform bilateral denervation of renal arteries with the radiofrequency effect in not less than 4 zones of each of vessels. Efficacy of each of the effect was registered with due regard for reaching certain temperature and values of impedance. The interventions were not accompanied by the development of any complications either in the area of manipulations or the site of puncture. Neither were there any complications from the side of the cardiovascular or excretory systems of the body. Diurnal monitoring of AP (DMAP) registered a significant decrease in SAP averagely from 174±12 to 145±10 mm Hg three days after the intervention. A persistent antihypertensive effect was confirmed by the DMAP findings one month after denervation - the SAP level averagely amounted to 131±6 mm Hg. Endovascular radiofrequency denervation of renal arteries is a safe and efficient method of treatment of AH resistant

  3. PM2.5对大鼠心脏交感神经分布的影响及其与心肌神经生长因子表达的关系%Effect of PM2.5 on sympathetic innervation by stimulating the secretion of cardiac nerve growth factor in healthy rat hearts

    Institute of Scientific and Technical Information of China (English)

    段军; 丛鲁红; 李刚; 易丽; 柯元南; 周益锋


    Objective To assess the effect of PM2.5 on sympathetic innervation and the relationship with cardiac nerve growth factor in healthy rat hearts,identify the ability to the sympathetic nerve reconstruction,and explore the possible arrhythogenic mechanism of PM2.5.Methods Forty healthy SD rats were instilled into trachea with two different solutions twice per week for four weeks:control group with saline and experimental group with PM2.5 25 mg/kg.Then these rats were killed,and biatrial appendages,two ventricular anterior walls were left.Immune cytochemical staining of cardiac nerves was performed using anti-tyrosine hydroxylase antibodies and cardiac nerve growth factor was detected by western blotting.Resuits Compared with the control group,both the density of sympathetic nerves and the expression of cardiac NGF protein in the experimental group were much higher in the left ventricular anterior wall ( P<0.01 and P<0.05) and in the right ventricular anterior wall ( P<0.01 and P<0.05).Conclusions PM2.5 can induce regional sympathetic hyperinnervation in both ventricular anterior walls in healthy rats by stimulating the NGF protein secretion,and the sympathetic nerve reconstruction effect of PM2.5 was confirmed.%目的 研究可吸入颗粒物PM2.5对大鼠心脏交感神经分布的影响及其与心肌神经生长因子表达的关系,明确PM2.5是否具有致交感神经重构作用,探讨PM2.5致心律失常的可能机制.方法 40只SD雄性大鼠,随机分为对照组和实验组,每组20只.实验组大鼠按25 mg/kg剂量经气管内缓慢注入颗粒物悬液染毒,每周染毒2次,连续染毒4周;对照组以生理盐水代替颗粒物悬液;两组大鼠于末次染毒后次日处死,开胸留取双侧心耳和双心室前壁,通过免疫组化方法检测酪氨酸羟化酶染色阳性的交感神经纤维分布密度,同时采用蛋白免疫印迹法检测心肌神经生长因子(NGF)蛋白表达.结果 与对照组比较,实验组大鼠吸入PM2

  4. Angiotensin II, sympathetic nerve activity and chronic heart failure. (United States)

    Wang, Yutang; Seto, Sai-Wang; Golledge, Jonathan


    Sympathetic nerve activity has been reported to be increased in both humans and animals with chronic heart failure. One of the mechanisms believed to be responsible for this phenomenon is increased systemic and cerebral angiotensin II signaling. Plasma angiotensin II is increased in humans and animals with chronic heart failure. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic heart failure. Angiotensin II signaling is enhanced in different brain sites such as the paraventricular nucleus, the rostral ventrolateral medulla and the area postrema. Blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the paraventricular nucleus. Injection of an angiotensin receptor blocker into the area postrema activates the sympathoinhibitory baroreflex. In peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity seen in chronic heart failure. Increased circulating angiotensin II during chronic heart failure may enhance the sympathoexcitatory chemoreflex and inhibit the sympathoinhibitory baroreflex. In addition, increased circulating angiotensin II can directly act on the central nervous system via the subfornical organ and the area postrema to increase sympathetic outflow. Inhibition of angiotensin II formation and its type 1 receptor has been shown to have beneficial effects in chronic heart failure patients.

  5. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension. (United States)

    Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing


    We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥ 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.

  6. Is reduced myocardial sympathetic innervation associated with clinical symptoms of autonomic impairment in idiopathic Parkinson's disease? (United States)

    Guidez, Daniel; Behnke, Stefanie; Halmer, Ramona; Dillmann, Ulrich; Faßbender, Klaus; Kirsch, Carl M; Hellwig, Dirk; Spiegel, Jörg


    Patients with idiopathic Parkinson's disease (IPD) have a reduced myocardial MIBG uptake in MIBG scintigraphy, indicating myocardial sympathetic denervation. We were interested whether this myocardial sympathetic denervation coincides with clinical symptoms of autonomic impairment in IPD patients. We performed MIBG scintigraphy, the SCOPA-AUT scale, a standardized medical history (developed in our clinic) and autonomic nervous system testing in 47 IPD patients (21 female, 26 male patients). We correlated myocardial MIBG uptake with the results of the SCOPA-AUT scale, the standardized medical history and the autonomic nervous system testing through the use of Spearman's correlation. Myocardial MIBG uptake correlated significantly (p autonomic nervous system testing (all patients: sum score, Ewing orthostasis test). Remarkably, we found more significant correlations in male than in female patients. Reduced myocardial sympathetic innervation-as revealed by MIBG scintigraphy-is associated with clinical symptoms of autonomic impairment. This association is more pronounced in male than in female patients. The cause for this gender-specific phenomenon is unclear.

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

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    Marcus May

    Full Text Available UNLABELLED: 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. TRIAL REGISTRATION: NCT01237431.

  8. Spleen vagal denervation inhibits the production of antibodies to circulating antigens.

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    Ruud M Buijs

    Full Text Available BACKGROUND: Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output. METHODOLOGY/PRINCIPAL FINDINGS: This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS, activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA. CONCLUSIONS/SIGNIFICANCE: These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production.

  9. Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

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    J.V.M. Franquini


    Full Text Available Obstructive apnea (OA can exert significant effects on renal sympathetic nerve activity (RSNA and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9, which were compared to sham (S; N = 9 rats. Mean arterial pressure (MAP and heart rate (HR were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg or HR (S: 340 ± 12 vs D: 368 ± 11 bpm. An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01. The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9% during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

  10. Brain {sup 18}F-FDG, {sup 18}F-florbtaben PET/CT, {sup 123}I-FP-CIT SPECT and cardiac {sup 123}I-MBG imaging for diagnosis of a 'cerebral type' of Lewy Body disease

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    Gucht, Axel Van Der; Bélissant, Ophélie; Rabu, Corenti; Cottereau, Anne-Ségolène; Evangelista, Eva; Chalaye, Julia; Bonnot-Lours, Sophie; Fénelon, Gilles; Itti, Emmanuel [Dept. of Nuclear Medicine, AP-HP, Henri-Mondor Teaching Hospital, Crteil (France); De Langavant, Laurent Cleret [Cognitive Neurology Unit, H. Mondor Hospital, Creteil (France)


    A 67-year-old man was referred for fluctuating neuropsychiatric symptoms, featuring depression, delirious episodes, recurrent visual hallucinations and catatonic syndrome associated with cognitive decline. No parkinsonism was found clinically even under neuroleptic treatment. {sup 18}F-FDG PET/CT showed hypometabolism in the posterior associative cortex including the occipital cortex, suggesting Lewy body dementia, but {sup 123}I-FP-CIT SPECT was normal and cardiac {sup 123}I-MIBG imaging showed no signs of sympathetic denervation. Alzheimer's disease was excluded by a normal {sup 18}F-florbetaben PET/CT. This report suggests a rare case of α-synucleinopathy without brainstem involvement, referred to as 'cerebral type' of Lewy body disease.

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

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    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)


    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.


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    Thorat D Kiran


    Full Text Available Physiologically aging refers to the impaired ability to maintain homeostasis during external as wellas internal stresses. The sympathetic nervous system becomes tonically, progressively and markedlyactivated with aging in humans. Study is done to measure the cardiovascular sympatheticdysfunctions in the males and females of the different age groups. Total 80, healthy subjects nothaving any major illness and any chronic addiction, were selected for the study. All the subjects wereevaluated by using “CANWIN cardiac autonomic neuropathy analyzer” using the tests like Pulse rateby Palpatory method, Blood Pressure response to sudden standing and Sustained Handgrip test. In all the elderly subjects the sympathetic system was over activated and this over activation of the sympathetic system became more severe as the age advanced. Aging is accompanied by a greater increase in sympathetic activity in women than in men, independent of menopausal status. The study concludes that there is more marked influence of age on sympathetic nervous system activation and impaired sensitivity of baroreceptors in women than men.

  13. [Psychosomatic aspects of cardiac arrhythmias]. (United States)

    Siepmann, Martin; Kirch, Wilhelm


    Emotional stress facilitates the occurrence of cardiac arrhythmias including sudden cardiac death. The prevalence of anxiety and depression is increased in cardiac patients as compared to the normal population. The risk of cardiovascular mortality is enhanced in patients suffering from depression. Comorbid anxiety disorders worsen the course of cardiac arrhythmias. Disturbance of neurocardiac regulation with predominance of the sympathetic tone is hypothesized to be causative for this. The emotional reaction to cardiac arrhythmias is differing to a large extent between individuals. Emotional stress may result from coping with treatment of cardiac arrhythmias. Emotional stress and cardiac arrhythmias may influence each other in the sense of a vicious circle. Somatoform cardiac arrhythmias are predominantly of psychogenic origin. Instrumental measures and frequent contacts between physicians and patients may facilitate disease chronification. The present review is dealing with the multifaceted relationships between cardiac arrhythmias and emotional stress. The underlying mechanisms and corresponding treatment modalities are discussed.

  14. Selective peripheral denervation : comparison with pallidal stimulation and literature review

    NARCIS (Netherlands)

    Contarino, Maria Fiorella; Van den Munckhof, Pepijn; Tijssen, Marina A. J.; de Bie, Rob M. A.; Bosch, D. Andries; Schuurman, P. Richard; Speelman, Johannes D.


    Patients with cervical dystonia who are non-responders to Botulinum toxin qualify for surgery. Selective peripheral denervation (Bertrand's procedure, SPD) and deep brain stimulation of the globus pallidus (GPi-DBS) are available surgical options. Although peripheral denervation has potential advant

  15. Perlecan and synaptophysin changes in denervated skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Kai Ma; Zhifeng Huang; Jianfeng Ma; Longquan Shao; Huiming Wang; Yanliang Wang


    The present study observed sciatic nerve and gastrocnemius muscle changes in denervated rats using morphology methods, and assessed expression of perlecan, an extracellular matrix com-ponent, which is located at the skeletal muscle cell surface as acetylcholine esterase, as well as synaptophysin, a synaptic marker. Results showed degeneration and inflammation following transection of the sciatic nerve. In addition, the sciatic nerve-dominated skeletal muscle degen-erated with mild inflammation, indicating that skeletal muscle atrophy primarily contributed to denervation-induced nutritional disturbances. With prolonged injury time (1-4 weeks post-injury), perlecan expression gradually decreased and reached the lowest level at 4 weeks, but synap-tophysin expression remained unchanged after denervation. Results suggested that perlecan expression was more sensitive to denervation and reflected regional extracellular matrix changes following denervation.

  16. 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


    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

  17. Capsaicin-mediated denervation of sensory neurons promotes mammary tumor metastasis to lung and heart. (United States)

    Erin, Nuray; Boyer, Philip J; Bonneau, Robert H; Clawson, Gary A; Welch, Danny R


    Capsaicin specifically activates or destroys small diameter nociceptive sensory neurons that contain the capsaicin receptor, also called vanilloid receptor 1. Neurons sensitive to capsaicin mediate inflammatory pain and are important targets for management of chronic pain. These neurons also regulate local tissue homeostasis, inflammation, healing and development, especially under conditions of psychological stress. Stress contributes to increased cancer recurrence and metastasis through as yet undefined mechanisms. Likewise, activity of capsaicin-sensitive neurons is altered by pathological conditions that may lead to metastatic growth (e.g. stress). Therefore, we examined effects of a treatment that induces sensory nerve denervation on breast cancer metastases. Systemic denervation of sensory neurons caused by treatment with 125 mg/kg capsaicin resulted in significantly more lung and cardiac metastases in adult mice injected orthotopically with syngeneic 4T1 mammary carcinoma cells than was observed in vehicle-treated controls. Heart metastases, normally very rare, occurred as pericardial nodules, intra-myocardial nodules, or combined pericardial-myocardial lesions. Since the rate of primary tumor growth was unaffected, effects on metastases appear to be host tissue-specific. Although preliminary, these observations provide one possible explanation for resistance of cardiac tissue to tumor involvement and highlight contributions of host tissue, including sensory neurons, in the efficiency of cancer metastasis.

  18. Renal denervation in chronic kidney disease

    NARCIS (Netherlands)

    Blankestijn, Peter J.; Joles, Jaap A.


    Previous studies have indicated that ablation of renal sympathetic nerves reduces blood pressure in patients with resistant hypertension and preserved renal function. Hering et al. have now investigated the efficacy and safety of this procedure in patients with moderate to severe chronic kidney dise

  19. Mechanisms responsible for postmenopausal hypertension in a rat model: Roles of the renal sympathetic nervous system and the renin-angiotensin system. (United States)

    Maranon, Rodrigo O; Reckelhoff, Jane F


    Hypertension in postmenopausal women is less well controlled than in age-matched men. The aging female SHR is a model of postmenopausal hypertension that is mediated in part by activation of the renin-angiotensin system (RAS) and by the renal sympathetic nervous system. In this study, the hypothesis was tested that renal denervation would lower the blood pressure in old female SHR and would attenuate the antihypertensive effects of AT1 receptor antagonism. Retired breeder female SHR were subjected to right uninephrectomy (UNX) and left renal denervation (RD) or UNX and sham, and 2 weeks later, baseline mean arterial pressure (MAP; radiotelemetry) was measured for 4 days, and then rats were treated with angiotensin (AT1) receptor antagonist, losartan (40 mg/kg/day po) for 6 days. Renal denervation reduced MAP in old females compared to sham (172 ± 6 vs. 193 ± 6 mm Hg; P system and the RAS have independent effects to control the blood pressure in old female SHR. Since the denervated rats treated with losartan remained hypertensive, the data also suggest that other mechanisms than the RAS and renal sympathetic nervous system contribute to the hypertension in old female SHR. The data also suggest that multiple mechanisms may mediate the elevated blood pressure in postmenopausal women.

  20. Protective Effects of Ciliary Neurotrophic Factor on Denervated Skeletal Muscle

    Institute of Scientific and Technical Information of China (English)

    黄仕龙; 王发斌; 洪光祥; 万圣祥; 康皓


    Summary: To study the effects of ciliary neurotrophic factor (CNTF) on denervated skeletal muscle atrophy and to find a new approach to ameliorate atrophy of denervated muscle, a model was estab lished by cutting the right sciatic nerve in 36 Wistar mice, with the left side serving as control. Then they were divided into two groups randomly. CNTF (1 U/ml) 0. 1 ml was injected into the right tib-ial muscle every day in experimental group, and saline was used into another group for comparison.The muscle wet weight, muscle total protein, Ca2+, physiological response and morphology were an alyzed on the 7th, 14th and 28th day after operation. Our results showed that compared to control group, there was a significant increase in muscle wet weight, total protein, Ca2+ , muscle fiber cross section area in CNTF group (P< 0. 05). CNTF could ameliorate the decrease of tetanic tension (PO), post-tetanic twitch potentiation (PTP), and the prolonged muscle relaxation time (RT)caused by denervation (P<0. 05). The motor end-plate areas 7 days and 14 days after denervation was similar (P>0. 05), but significantly larger 28 days after the denervation (P<0.05). Our re-sults suggest that CNTF exerts myotrophic effects by attenuating the morphological and functional changes associated with denervation of rat muscles and has protective effects on denervated muscle and motor end plate.

  1. Recent advances in sympathetic ophthalmia. (United States)

    Marak, G E


    Recent advances in understanding the pathogenesis of sympathetic ophthalmia are helping to remove the pigmented cloud which has obstructed the view of researchers on this disease for many years. Clinical features, diagnostic testing, histopathologic variations and principles of treatment are evaluated in the context of our increasing understanding of the pathogenesis of this disease. The relationship of sympathetic ophthalmia to Harada's disease and phacoantigenic uveitis are reviewed.

  2. Bursting into space: alterations of sympathetic control by space travel (United States)

    Eckberg, D. L.


    AIM: Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average +/- SEM age: 40 +/- 2 years) before, during, and after the 16-day Neurolab space shuttle mission. METHOD: We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt. RESULTS: In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre-syncope during 10 min of post-flight tilting. CONCLUSION: We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post-flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.

  3. Renal denervation: Results of a single-center cohort study; Renale Denervation. Ergebnisse einer Single-Center Kohortenstudie

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    Luetkens, J.A.; Thomas, D.; Doerner, J.; Schild, H.H.; Naehle, C.P. [Bonn Univ. (Germany). Dept. of Radiology; Wilhelm, K. [Johanniter Hospital, Bonn (Germany). Dept. of Radiology; Duesing, R. [Hypertension Center, Bonn (Germany); Woitas, R.P.; Hundt, F. [Bonn Univ. (Germany). Dept. of Internal Medicine I


    To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension. Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation. Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ± 3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ± 20.3/103.8 ± 20.4 mmHg and 155.2 ± 20.5/93.7 ± 14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ± 14.9/89.5 ± 12.1 (p < 0.05). ABPM values remained unchanged (147.9 ± 20.3/90.3 ± 15.6, p > 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ± 2.0 vs. 4.2 ± 1.2, p = 0.18). No renovascular complications were detected in follow-up MRI. After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension.

  4. Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus. (United States)

    Krizsan-Agbas, D; Pedchenko, T; Hasan, W; Smith, P G


    Sympathetic innervation of the adult rodent uterus undergoes cyclic remodelling. Terminal sympathetic axons degenerate when oestrogen levels rise and regenerate when oestrogen levels decline. This study examined the role of neurotrophins in oestrogen-mediated uterine sympathetic nerve remodelling. Oestrogen injection of ovariectomized female rats did not affect uterine NT-3 levels 24 h postinjection, and increased endometrial NGF protein, indicating that reduced NGF or NT-3 is not responsible for the oestrogen-induced denervation. Oestrogen also raised BDNF protein and mRNA in myometrium and endometrium. To assess whether increased BDNF affects uterine receptivity to sympathetic outgrowth, sympathetic ganglion explants were co-cultured with myometrium. Myometrium from ovariectomized rats induced neuritogenesis in oestrogen-free conditions, and this was abolished when BDNF was added to the medium. Neuritogenesis induced by ovariectomized myometrium was suppressed by oestrogen, and restored by a BDNF function-blocking antibody. To determine if target BDNF synthesis is required for oestrogen to suppress sympathetic neurite outgrowth, uteri from wild-type mice and mice homozygous or heterozygous for recombinant mutations of the BDNF gene were cultured with rat sympathetic ganglia. Neuritogenesis induced by wild-type uteri was diminished by oestrogen. Neurite formation in the presence of homozygous BDNF mutant uteri was not affected by oestrogen, but was lower than that of wild-type mice. Uteri from mice heterozygous for the BDNF mutation, who have reduced BDNF synthesis, showed normal neuritogenic properties, but were not affected by oestrogen. These findings suggest that oestrogen alters neuritogenic properties of the rodent uterus by regulating BDNF synthesis, which inhibits sympathetic neurite outgrowth.

  5. Tritiated thymidine autoradiographic study on the influence of sensory and sympathetic innervation on periodontal wound healing in the rat. (United States)

    Wucherpfennig, A L; Chiego, D J; Avery, J K


    Understanding of wound healing mechanisms is important in designing preventive and therapeutic approaches to inflammatory periodontal diseases, which are a major cause of dental morbidity. In this study, cell proliferation was assessed after an experimental gingival wound; this was preceded by either resection of 3 mm of the inferior alveolar nerve, total extirpation of the superior cervical ganglion, trauma to those structures or sham operations. At different times, animals were pulsed with 0.5 microCi/g body weight of tritiated thymidine; histological sections were processed for quantitative autoradiography of different compartments of the periodontium. Wounding led to a significant increase in cell proliferation in the epithelial layer, the fibroblast compartment and the periodontal ligament, but not in the alveolar crest compartment. Sympathetic denervation significantly enhanced this response in the epithelial layer, the fibroblast compartment and the alveolar crest, whereas sensory denervation only modified the response in the fibroblast layer. Thus it appears that sympathetic innervation plays an important role in the regulation of cell proliferation in the periodontium and that pharmacological modulation of sympathetic activity should be further studied as a therapeutic approach in periodontal disease.

  6. Opioid neuronal denervation in Gilles de la Tourette syndrome. (United States)

    Sandyk, R


    Increased striatal dopaminergic functions with heightened postsynaptic receptor sensitivity has been proposed to underlie the major clinical symptoms of Tourette's syndrome (TS). The beneficial response of the majority of TS patients to haloperidol supports the hyperdopaminergic pathophysiological concept of TS. However, in 5 recently encountered TS patients, haloperidol failed to ameliorate self-injurious behavior (SIB) while the opiate antagonist, naloxone, attenuated SIB, implicating deranged endorphinergic mechanisms in the pathophysiology of this disorder. Brain damage is commonly associated with partial neuronal denervation, denervation supersensitivity and neuronal habituation (Cannon's Law). While the motor tics of TS possibly reflect neuronal denervation of striatal dopaminergic neurons. SIB may represent opioid denervation with alterations in opioid receptor sensitivity possibly involving striato-limbic-hypothalamic circuits. The effect of naloxone on SIB in TS could thus be explained on the basis of a modulatory effect of this drug on opioid receptor sensitivity.

  7. Effect of salbutamol on innervated and denervated rat soleus muscle

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    ?oic-Vranic T.


    Full Text Available The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a ß2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10, treated with salbutamol (N = 30, denervated (N = 30, and treated with salbutamol after denervation (N = 30. Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21% in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2% compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other ß2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.

  8. Respiratory neuroplasticity following carotid body denervation Central and peripheral adaptations

    Institute of Scientific and Technical Information of China (English)

    Matthew R. Hodges; Hubert V. Forster


    Historically, the role of the carotid bodies in ventilatory control has been understated, but the current view suggests that the carotid bodies (1) provide a tonic, facilitory input to the respiratory network, (2) serve as the major site of peripheral O2 chemoreception and minor contributor to CO2/H+ chemoreception, and (3) are required for ventilatory adaptation to high altitude. Each of these roles has been demonstrated in studies of ventilation in mammals after carotid body denervation. Following carotid body denervation, many of the compromised ventilatory "functions" show a time-dependent recovery plasticity that varies in the degree of recovery and time required for recovery. Respiratory plasticity following carotid body denervation is also dependent on species, with contributions from peripheral and central sites/mechanisms driving the respiratory plasticity. The purpose of this review is to provide a summary of the data pointing to peripheral and central mechanisms of plasticity following carotid body denervation. We speculate that after carotid body denervation there are altered excitatory and/or inhibitory neuromodulator mechanisms that contribute to the initial respiratory depression and the subsequent respiratory plasticity, and further suggest that the continued exploration of central effects of carotid body denervation might provide useful information regarding the capacity of the respiratory network for plasticity following neurologic injury in humans.

  9. Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

    Directory of Open Access Journals (Sweden)

    F. Xavier


    Full Text Available The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide (NO synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each of male Wistar-Hannover rats weighing 200 to 250 g: 1 sham-operated vehicle-treated, 2 sham-operated L-NAME-treated, 3 denervated vehicle-treated, and 4 denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1 progressively increased arterial pressure from 108 ± 6.0 to 149 ± 12 mmHg (P<0.05 in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 ± 18 to 222 ± 59 µl min-1 100 g body weight-1 (P<0.05 and a rise in fractional urinary sodium excretion from 0.2 ± 0.04 to 1.62 ± 0.35% (P<0.05 and in sodium post-proximal fractional excretion from 0.54 ± 0.09 to 4.7 ± 0.86% (P<0.05. The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 ± 0.04 to 4.5 ± 1.6% and from 0.1 ± 0.015 to 1.21 ± 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an

  10. Characteristic enhancement of blood pressure V-shaped waves in sinoaortic-denervated rats in a conscious and quiet state. (United States)

    Chang, Huan; Gu, Hong-Xia; Gong, Min; Han, Ji-Ju; Wang, Yun; Xia, Zuo-Li; Zhao, Xiao-Min


    A hemodynamic feature of chronic sinoaortic-denervated (SAD) rats is the increase in blood pressure variability (BPV) without significant changes in the average level of blood pressure (BP). The current study was designed to investigate the changes in BP V-shaped waves (V waves) in SAD rats. Sprague-Dawley (SD) rats were divided into 2 groups: SAD rats and sham-operated rats (n=13). Hemodynamics measurements were obtained in conscious, freely moving rats, four weeks after sinoaortic denervation or sham operation. V wave indices were evaluated in rats in both conscious and quiet states. Additionally, normal and high BPV was simulated by the production of V waves with different amplitudes. The results showed that the V wave amplitude was dramatically increased, with a significantly prolonged duration and reduced frequency in SAD rats. V wave BPV in SAD rats was significantly increased, though BP remained unchanged. The twenty-four hour BPV in all rats was positively correlated with amplitude, duration time and V wave BPV and negatively correlated with frequency. The systolic BP spectral powers in the low frequency range (0.38-0.45 Hz) were significantly reduced in the V waves of SAD rats. Moreover, there was a remarkable increase in mean BPV and a normal mean BP after simulating high BPV in SAD rats. These results suggest that enhancement of V waves might be a waveform character of BP in SAD rats in both the conscious and quiet states. These types of V waves appear to be related to a depression of sympathetic regulation of BP induced by sinoaortic denervation.

  11. Blood pressure decrease in spontaneously hypertensive rats folowing renal denervation or dopamine β-hydroxylase inhibition with etamicastat. (United States)

    Pires, Nuno Miguel; Igreja, Bruno; Moura, Eduardo; Wright, Lyndon Christopher; Serrão, Maria Paula; Soares-da-Silva, Patrício


    Overactivity of the sympathetic nervous system has an important role in the development and progression of arterial hypertension. Catheter-based renal nerve ablation for the treatment of drug-resistant hypertension has recently been developed. An alternative strategy for the modulation of sympathetic nerve function is to reduce the biosynthesis of noradrenaline (NA) by inhibiting dopamine β-hydroxylase (DβH), the enzyme that catalyzes the conversion of dopamine (DA) to NA in the sympathetic nerves. Renal denervation (RDN) surgery was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of RDN on the DA and NA levels and on blood pressure over a 28-day period. The selective peripheral DβH inhibitor etamicastat (30 mg kg (-1)day(-1)) was administered to another cohort of SHR. RDN and etamicastat treatment had no effect on the renal function, as assessed by measuring the water balance response, renal function and urinary electrolyte levels. RDN significantly decreased the systolic blood pressure (SBP) and the diastolic blood pressure (DBP). A gradual return of the SBP and the DBP to the high baseline levels was observed over time. Conversely, treatment with etamicastat resulted in a significant decrease in the SBP and the DBP at all time points. On the last day of the assessment, NA levels in renal tissue were significantly decreased in both RDN and etamicastat-treated groups. In contrast, the NA levels in the left ventricle were decreased only in the etamicastat-treated group. Thus, RDN produces transitory decreases in blood pressure, whereas prolonged downregulation of sympathetic drive with the DβH inhibitor etamicastat results in a sustained decrease in the SBP and the DBP.

  12. Maturational changes in sympathetic and sensory innervation of the rat uterus: effects of neonatal capsaicin treatment. (United States)

    Brauer, M M; Lincoln, J; Sarner, S; Blundell, D; Milner, P; Passaro, M; Burnstock, G


    The plasticity of the sympathetic and sensory innervation of the rat uterus was examined, before and after puberty, in controls and in animals where primary sensory nerves had been destroyed by neonatal capsaicin treatment. Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) Puberty was associated with a marked increase in the weight of the uterine horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin treatment. (2) The sympathetic innervation of the uterine horn and parametrial tissue was reduced following puberty as revealed by a decrease in the density of noradrenaline-containing nerves and a marked decrease in the tissue concentration of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the sensory supply of the uterus by substance P and calcitonin gene-related peptide-containing nerves increased in parallel with uterine growth during puberty resulting in no change in nerve density and only a slight reduction in peptide concentration. (4) Neonatal capsaicin treatment caused a long-lasting depletion of substance P- and calcitonin gene-related peptide-containing nerves. In the uterine horn and parametrial tissue, capsaicin-resistant calcitonin gene-related peptide, but not substance P, still increased with tissue weight during puberty, indeed, in the uterine horn, the relative increase was greater than in controls. (5) Sensory denervation resulted in an increase in the non-vascular sympathetic supply of the uterus, although there was a regional variation in the time course of the response. Perivascular sympathetic nerves were unaffected by capsaicin treatment. The pattern of change in non-vascular noradrenaline-containing nerves associated with puberty was similar in nature to controls. Thus, there is considerable plasticity

  13. Effects of Renal Denervation Documented in the Austrian National Multicentre Renal Denervation Registry (United States)

    Lambert, Thomas; Steinwender, Clemens; Weber, Thomas; Suppan, Markus; Brussee, Helmut; Koppelstätter, Christian; Kerschbaum, Julia; Watschinger, Bruno; Hohenstein-Scheibenecker, Katharina; Reindl-Schwaighofer, Roman; Sturmberger, Thomas; Kindslehner, Claudia; Weiss, Thomas Werner; Rohla, Miklos; Gruener, Peter; Maister, Petra; Auer, Johann; Dechant, Cornelia; Sykora, Josef; Krismer, Christoph; Glaser, Stefan; Zweiker, Robert


    Renal denervation (RDN) is a new procedure for treatment-resistant hypertensive patients. In order to monitor all procedures undergone in Austria, the Austrian Society of Hypertension established the investigator-initiated Austrian Transcatheter Renal Denervation (TREND) Registry. From April 2011 to September 2014, 407 procedures in 14 Austrian centres were recorded. At baseline, office and mean 24-h ambulatory blood pressure (ABP) were 171/94 and 151/89 mmHg, respectively, and patients were taking a median of 4 antihypertensive medications. Mean 24-h ABP changes after 2–6 weeks, 3, 6 and 12 months were -11/-6, -8/-4, -8/-5 and -10/-6 mmHg (p<0.05 at all measurements), respectively. The periprocedural complication rate was 2.5%. Incidence of long-term complications during follow-up (median 1 year) was 0.5%. Office BP and ABP responses showed only a weak correlation (Pearson coefficient 0.303). Based on the data from the TREND registry, ambulatory blood pressure monitoring in addition to office BP should be used for patient selection as well as for monitoring response to RDN. Furthermore, criteria for optimal patient selection are suggested. PMID:27529426

  14. Molecular Aspects of Exercise-induced Cardiac Remodeling. (United States)

    Bernardo, Bianca C; McMullen, Julie R


    Exercise-induced cardiac remodeling is typically an adaptive response associated with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers of cardiac remodeling include increased hemodynamic load, increased sympathetic activity, and the release of hormones and growth factors. Prolonged and strenuous exercise may lead to maladaptive exercise-induced cardiac remodeling including cardiac dysfunction and arrhythmia. In addition, this article describes novel therapeutic approaches for the treatment of heart failure that target mechanisms responsible for adaptive exercise-induced cardiac remodeling, which are being developed and tested in preclinical models.

  15. Neurotrophin-3 mRNA expression in rat intrafusal muscle fibres after denervation and reinnervation

    NARCIS (Netherlands)

    Copray, JCVM; Brouwer, N


    We have studied the regulation of the expression of neurotrophin-3 (NT-3) mRNA in neonatal and adult rat muscle spindles after denervation and after denervation followed by reinnervation. Denervation of the intrafusal fibres did not result in an upregulation of the NT-3 mRNA expression but decreased

  16. Multiscale entropy analysis of heart rate variability in heart failure, hypertensive, and sinoaortic-denervated rats: classical and refined approaches. (United States)

    Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; da Silva, Carlos Alberto Aguiar; Valencia, Jose Fernando; Murta, Luiz Otavio; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto


    The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation.

  17. Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy (United States)

    Konagaya, Masaaki; Konagaya, Yoko; Max, Stephen R.


    The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

  18. An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats (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...

  19. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)


    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  20. Removal of half the sympathetic innervation does not reduce vasoconstrictor responses in rat tail artery. (United States)

    Tripovic, Diana; McLachlan, Elspeth M; Brock, James A


    Following reinnervation of denervated rat tail arteries, nerve-evoked contractions are at least as large as those evoked in normally innervated arteries despite a much lower nerve terminal density. Here nerve-evoked contractions have been investigated after transection of half the sympathetic innervation of normal tail arteries. After 1 week, the noradrenergic plexus 50-70 mm along the tail was about half as dense as control. Excitatory junction potentials recorded in smooth muscle cells of arterial segments isolated in vitro were half their normal amplitude. Surprisingly, nerve-evoked contractions of isometrically mounted segments were not reduced in amplitude, as was also the case after only 3 days. After 1 week, enhancement of nerve-evoked contractions by blocking either neuronal re-uptake of noradrenaline with desmethylimipramine or prejunctional α2-adrenoceptors with idazoxan was similar to control, suggesting that these mechanisms are matched to the number of innervating axons. The relative contribution of postjunctional α2-adrenoceptors to contractions evoked by long trains of stimuli was enhanced but that of α1-adrenoceptors was unchanged. Transiently, sensitivity to the α1-adrenoceptor agonist phenylephrine was slightly increased. After 7 weeks, amplitudes of nerve-evoked contractions remained similar to control, and sensitivity to phenylephrine had recovered but that to the α2-adrenoceptor agonist clonidine was slightly raised. The normal amplitude of nerve-evoked contractions after partial denervation is only partly explained by the greater contribution of α2-adrenoceptors. While the post-receptor mechanisms activated by nerve-released transmitter may be modified to amplify the contractions after partial denervation, our findings suggest that these mechanisms are normally saturated, at least in this artery.


    NARCIS (Netherlands)



    Objective-In the absence of an obvious cause for cardiac arrest, patients with idiopathic ventricular fibrillation are difficult to manage. A subset of patients has inducible arrhythmias. In others sympathetic excitation plays a role in the onset of the cardiac arrest. This study evaluates a prospec

  2. Effects of dexamethasone on estrogen- and pregnancy-induced plasticity in rat uterine sympathetic nerves. (United States)

    Bianchimano, P; Frías, A I; Richeri, A; Brauer, M M


    Estrogen and glucocorticoids are known to evoke opposing effects on the uterus. We analyzed the effects of dexamethasone (DEX) on uterine sympathetic denervation elicited by short- and long-term exposure to estrogen of intact prepubertal rats. We also studied the effects of DEX on the physiological degeneration of uterine sympathetic nerves at term pregnancy. Changes in innervation were assessed quantitatively by using computer-assisted methods on uterine cryostat tissue sections stained for tyrosine hydroxylase. At 24 h following treatment of prepubertal rats (25 days of age) with 1 microg or 2.5 microg estrogen, marked increases in uterine size and reductions in the percentage nerve area were observed. Co-administration of DEX (4 mg/kg) attenuated both these short-term estrogen-induced effects. Treatment of 19-day-old rats with a single dose of 25 mug estrogen provoked, at 26 days of age, a 54% reduction in the total nerve area. This reduction was abolished by the co-administration of nine doses of DEX (0.5 mg/kg) at 18-26 days of age. Treatment of rats with the same regime of DEX alone increased the total nerve area by 46% of the control values. Studies of control pregnant rats revealed the unexpected presence of intrauterine nerve fibers at term. Treatment of pregnant rats with six doses of DEX (4 mg/kg) at 16-21 days of age had no effects on the density of uterine sympathetic nerves. These results suggest that DEX has growth-promoting effects on immature uterine sympathetic nerves and may antagonize the degenerative effects elicited by long-term exposure to estrogen.

  3. Modification of motoneuron size after partial denervation in neonatal rats. (United States)

    Tyc, F; Vrbová, G


    Our previous studies have shown that partial denervation of extensor digitorum longus muscle (EDL) in the rat at 3 days of age causes an increase in the activity of the intact motoneurons. The originally phasic pattern of activity of EDL became tonic after partial denervation. These modifications of motoneuron activity were associated with the change in the phenotype of the muscle from fast to slow contracting and with a conversion of the muscle fibres from a fast to a slow type. The present study investigates whether the size of the cell body of the active EDL motoneurons change in parallel with the altered muscular activity. The study involved partial denervation of rat EDL muscle by section of the L4 spinal nerve at 3 days of age. Then the remaining motoneurons from L5 spinal nerve supplying the EDL muscle were retrogradly labelled with horseradish peroxidase two months later. The results show a reduction in motoneuron size in parallel with an increase in activity of the motoneurons after partial denervation of EDL muscle.

  4. 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)


    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.)

  5. The role of the peripheral sympathetic nervous system in the natriuresis following central administration of an I1 imidazoline agonist, moxonidine. (United States)

    Penner, S. B.; Smyth, D. D.


    1. Central administration of the I1-imidazoline receptor agonist moxonidine increases sodium excretion without alteration of blood pressure. In the present study we determined whether this natriuretic action was mediated through a decrease in activity of the sympathetic nervous system, as has been reported for the antihypertensive action of this compound. Interruption of the sympathetic nervous system was achieved with prazosin (alpha 1-adrenoceptor antagonist) and renal denervation. 2. In pentobarbitone-anaesthetized Sprague-Dawley rats, intracerebroventricular (i.c.v.) injection of moxonidine alone increased urine volume and sodium excretion. Prazosin (0.15 mg kg-1, i.v.) alone decreased urine flow rate and sodium excretion as compared to the vehicle controls. In the presence of prazosin, i.c.v. injection of moxonidine failed to increase sodium excretion or urine volume as compared to animals which received the prazosin alone. 3. The administration of moxonide (i.c.v.) to sham renal-denervated animals caused an increase in urine flow rate, urine sodium excretion, osmolar clearance and free water clearance. The increase in sodium excretion and osmolar clearance were completely attenuated in renal denervated rats, however, urine flow rate was still increased and this was secondary to the increase in free water clearance which remained intact. 4. These results indicate the importance of an intact sympathetic nervous system in the renal response to i.c.v. moxonidine. Moreover, the differential antagonism of these interventions on solute and water excretion indicate that they may be mediated at two separate sites and/or receptors following i.c.v. moxonidine. PMID:8590981

  6. Sympathetic crashing acute pulmonary edema. (United States)

    Agrawal, Naman; Kumar, Akshay; Aggarwal, Praveen; Jamshed, Nayer


    Sympathetic crashing acute pulmonary edema (SCAPE) is the extreme end of the spectrum of acute pulmonary edema. It is important to understand this disease as it is relatively common in the emergency department (ED) and has better outcomes when managed appropriately. The patients have an abrupt redistribution of fluid in the lungs, and when treated promptly and effectively, these patients will rapidly recover. Noninvasive ventilation and intravenous nitrates are the mainstay of treatment which should be started within minutes of the patient's arrival to the ED. Use of morphine and intravenous loop diuretics, although popular, has poor scientific evidence.

  7. Sympathetic blocks for visceral cancer pain management

    DEFF Research Database (Denmark)

    Mercadante, Sebastiano; Klepstad, Pal; Kurita, Geana Paula


    The neurolytic blocks of sympathetic pathways, including celiac plexus block (CPB) and superior hypogastric plexus block (SHPB) , have been used for years. The aim of this review was to assess the evidence to support the performance of sympathetic blocks in cancer patients with abdominal visceral...

  8. Sympathetic vasoconstrictor nerve function in alcoholic neuropathy

    DEFF Research Database (Denmark)

    Jensen, K; Andersen, K; Smith, T;


    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 ...

  9. Sympathetic actions on the skeletal muscle. (United States)

    Roatta, Silvestro; Farina, Dario


    The sympathetic nervous system (SNS) modulates several functions in skeletal muscle fibers, including metabolism, ionic transport across the membrane, and contractility. These actions, together with the sympathetic control of other organ systems, support intense motor activity. However, some SNS actions on skeletal muscles may not always be functionally advantageous. Implications for motor control and sport performance are discussed.

  10. Glucose metabolism in rats submitted to skeletal muscle denervation

    Directory of Open Access Journals (Sweden)

    Wilton Marlindo Santana Nunes


    Full Text Available This study analyzed the local and systemic effects of immobilization by denervation of the skeletal muscle on glucose metabolism. The rats were submitted to section of the right paw sciatic nerve. A reduction was observed in glucose uptake by the isolated soleus muscle of the denervated paw after 3 and 7 days, but not after 28 days in relation to the control animals. There was no difference after 3 and 7 days in glucose uptake by the soleus muscle of the opposite intact paw in relation to the control. There was increased glucose uptake in the same paw 28 days after denervation. The rate of glucose removal in response to exogenous insulin after 28 days of denervation was significantly higher than in control animals and those observed after 3 and 7 days of denervation. These results suggest that immobilization by denervation interfered not only in glucose metabolism in the skeletal muscle involved but also in other tissues.O estudo analisou os efeitos locais e sistêmicos da imobilização por desnervação do músculo esquelético sobre o metabolismo glicidico. Ratos foram submetidos à secção do nervo ciático da pata direita. Observou-se redução da captação de glicose pelo músculo sóleo isolado da pata desnervada após 3 e 7 mas não após 28 dias em relação a animais controle. Não houve diferença após 3 e 7 dias na captação de glicose pelo músculo sóleo da pata contralateral intacta em relação ao controle. Houve aumento da captação de glicose nesta mesma pata 28 dias após a desnervação. A taxa de remoção da glicose em resposta à insulina exógena após 28 dias de desnervação foi significantemente superior à do controle e àquelas observadas após 3 e 7 dias da desnervação. Esses resultados sugerem que a imobilização por desnervação interfere não só no metabolismo da glicose no músculo esquelético envolvido como também em outros tecidos.

  11. Adaptive reaction of boys’ sympathetic-adrenal system to physical activity in puberty.

    Directory of Open Access Journals (Sweden)

    Alekcei Anatolevich Zverev


    Full Text Available This paper deals with the study of adaptive reactions of the sympathetic-adrenal system of 11-16-year-old boys to graduated exercise at different pubertal stages. To evaluate the functional state of the cardiovascular system, the heart rate, systolic and cardiac output were determined. The state of the sympathetic-adrenal system was analyzed by the excretion level of catecholamines and DOPA. Cardiac output in response to graduated exercise in boys at pubertal stages 1-2 is substantially ensured by the increased heart rate, and at the other stages of puberty - mainly due to increase in stroke volume, which is estimated as a favorable response to exercise. In mechanisms of urgent adaptation to graduated exercise, the boys of third and fourth pubertal stages show an intensive functioning of the cardiovascular system and a reducing reserve capacity of the sympathetic-adrenal system. The adolescents of fifth pubertal stage show economical response to functional tests, a reduced reactivity of the components of the sympathetic-adrenal system on the background of a significant increase in the excretion of precursors.

  12. Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight (United States)

    Levine, Benjamin D.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Zuckerman, Julie H.; Diedrich, Andre; Biaggioni, Italo; Ray, Chester A.; Smith, Michael L.; Iwase, Satoshi; Saito, Mitsuru; Sugiyama, Yoshiki; Mano, Tadaaki; Zhang, Rong; Iwasaki, Kenichi; Lane, Lynda D.; Buckey, Jay C Jr; Cooke, William H.; Baisch, Friedhelm J.; Eckberg, Dwain L.; Blomqvist, C. Gunnar


    Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

  13. Estimated central blood volume in cirrhosis: relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic factor

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Bendtsen, Flemming; Gerbes, A L


    The estimated central blood volume (i.e., blood volume in the heart cavities, lungs and central arterial tree) was determined by multiplying cardiac output by circulatory mean transit time in 19 patients with cirrhosis and compared with sympathetic nervous activity and circulating level of atrial...

  14. {sup 123}I-MIBG myocardial scintigraphy in diabetic patients. Relationship with {sup 201}Tl uptake and cardiac autonomic function

    Energy Technology Data Exchange (ETDEWEB)

    Nagamachi, Shigeki; Jinnouchi, Seishi; Kurose, Takeshi; Ohnishi, Takashi; Flores, L.G. II; Nakahara, Hiroshi; Futami, Shigemi; Tamura, Shozo; Matsukura, Shigeru [Miyazaki Medical Coll., Kiyotake (Japan)


    The purpose of this paper is to investigate the influence of diabetic myocardial damage (suspected myocardial damage; SMD) diagnosed by {sup 201}Tl-SPECT and diabetic cardiac autonomic neuropathy (AN) on myocardial MIBG uptake in patients with NIDDM. Eighty-seven diabetic patients divided into four subgroups: 23 with SMD (+) AN (+); 19 with SMD (+) AN (-); 27 with SMD (-) AN (+); 18 with SMD (-) AN (-), and 10 controls were studied. Both planar and SPECT images were taken at 30 minutes (early) and 3 hours (delayed) after {sup 123}I-MIBG injection. The heart to mediastinum uptake ratio (H/M) and washout ratio of {sup 123}I-MIBG (WR) were obtained from both planar images. Similarly, the difference between the {sup 201}Tl image and the {sup 123}I-MIBG image in the total uptake score (TUS) was taken as the difference in the total uptake score ({Delta}TUS) representing cardiac sympathetic denervation without SMD. On both early and delayed planar images, the mean H/M value in the subgroups of diabetic patients was significantly lower in the SMD (+) AN (+) group than in the control group, but among those subgroups, there was statistically significant difference between the SMD (+) AN (+) and SMD (-) AN (-) groups only on the delayed images. Regarding the WR value, there was no statistically significant difference among subjects. On SPECT image analysis, the diabetic subgroup with AN or SMD had statistically significant lower values for TUS than those of the control group. Among diabetics, there was a statistically significant differences between SMD [+] AN [+] and SMD [-] AN [-] on both early and delayed images. Similarly, the SMD [+] AN [-] group also had significantly lower values than those of SMD [-] AN [-] on early images. Regarding {Delta}TUS, there was a statistically significant differences between AN [+] subgroups and controls. Similarly, the mean value for {Delta}TUS was much higher in AN [+] subgroups than in AN [-] subgroups with or without SMD in diabetes

  15. [sup 123]I-MIBG myocardial scintigraphy in diabetic patients. Relationship with [sup 201]Tl uptake and cardiac autonomic function

    Energy Technology Data Exchange (ETDEWEB)

    Nagamachi, Shigeki; Jinnouchi, Seishi; Kurose, Takeshi; Ohnishi, Takashi; Flores, L.G. II; Nakahara, Hiroshi; Futami, Shigemi; Tamura, Shozo; Matsukura, Shigeru (Miyazaki Medical Coll., Kiyotake (Japan))


    The purpose of this paper is to investigate the influence of diabetic myocardial damage (suspected myocardial damage; SMD) diagnosed by [sup 201]Tl-SPECT and diabetic cardiac autonomic neuropathy (AN) on myocardial MIBG uptake in patients with NIDDM. Eighty-seven diabetic patients divided into four subgroups: 23 with SMD (+) AN (+); 19 with SMD (+) AN (-); 27 with SMD (-) AN (+); 18 with SMD (-) AN (-), and 10 controls were studied. Both planar and SPECT images were taken at 30 minutes (early) and 3 hours (delayed) after [sup 123]I-MIBG injection. The heart to mediastinum uptake ratio (H/M) and washout ratio of [sup 123]I-MIBG (WR) were obtained from both planar images. Similarly, the difference between the [sup 201]Tl image and the [sup 123]I-MIBG image in the total uptake score (TUS) was taken as the difference in the total uptake score ([Delta]TUS) representing cardiac sympathetic denervation without SMD. On both early and delayed planar images, the mean H/M value in the subgroups of diabetic patients was significantly lower in the SMD (+) AN (+) group than in the control group, but among those subgroups, there was statistically significant difference between the SMD (+) AN (+) and SMD (-) AN (-) groups only on the delayed images. Regarding the WR value, there was no statistically significant difference among subjects. On SPECT image analysis, the diabetic subgroup with AN or SMD had statistically significant lower values for TUS than those of the control group. Among diabetics, there was a statistically significant differences between SMD [+] AN [+] and SMD [-] AN [-] on both early and delayed images. Similarly, the SMD [+] AN [-] group also had significantly lower values than those of SMD [-] AN [-] on early images. Regarding [Delta]TUS, there was a statistically significant differences between AN [+] subgroups and controls. Similarly, the mean value for [Delta]TUS was much higher in AN [+] subgroups than in AN [-] subgroups with or without SMD in diabetes

  16. Nuclear imaging in cardiac amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    Glaudemans, A.W.J.M.; Slart, R.H.J.A.; Veltman, N.C.; Dierckx, R.A.J.O. [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Hanzeplein 1, P.O. Box 30001, Groningen (Netherlands); Zeebregts, C.J. [University Medical Center Groningen, Department of Surgery (Division of Vascular Surgery), Groningen (Netherlands); Tio, R.A. [University Medical Center Groningen, Department of Cardiology, Groningen (Netherlands); Hazenberg, B.P.C. [University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen (Netherlands)


    Amyloidosis is a disease characterized by depositions of amyloid in organs and tissues. It can be localized (in just one organ) or systemic. Cardiac amyloidosis is a debilitating disease and can lead to arrhythmias, deterioration of heart function and even sudden death. We reviewed PubMed/Medline, without time constraints, on the different nuclear imaging modalities that are used to visualize myocardial amyloid involvement. Several SPECT tracers have been used for this purpose. The results with these tracers in the evaluation of myocardial amyloidosis and their mechanisms of action are described. Most clinical evidence was found for the use of {sup 123}I-MIBG. Myocardial defects in MIBG activity seem to correlate well with impaired cardiac sympathetic nerve endings due to amyloid deposits. {sup 123}I-MIBG is an attractive option for objective evaluation of cardiac sympathetic level and may play an important role in the indirect measurement of the effect of amyloid myocardial infiltration. Other, less sensitive, options are {sup 99m}Tc-aprotinin for imaging amyloid deposits and perhaps {sup 99m}Tc-labelled phosphate derivatives, especially in the differential diagnosis of the aetiology of cardiac amyloidosis. PET tracers, despite the advantage of absolute quantification and higher resolution, are not yet well evaluated for the study of cardiac amyloidosis. Because of these advantages, there is still the need for further research in this field. (orig.)

  17. Role of autoinhibitory feedback in cardiac sympathetic transmission

    Energy Technology Data Exchange (ETDEWEB)

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


    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 /sup 3/H-noradrenaline. The relationships between /sup 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 /sup 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 /sup 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.

  18. Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Liggett, S B; Christensen, N J


    by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP...... accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor...... to diabetic autonomic neuropathy. Regardless of the mechanism of adrenergic denervation hypersensitivity in such patients, these data provide further evidence that measurements of cellular adrenergic receptors (and adenylate cyclase) in vitro are a fallible index of sensitivity to catecholamines in vivo....

  19. Efficacy of the "baby-sitter" procedure after prolonged denervation. (United States)

    Mersa, B; Tiangco, D A; Terzis, J K


    This study was undertaken to evaluate whether 40 percent of the hypoglossal nerve, which showed optimal efficacy in restoring orbicularis oculi muscle (OOM) function after different percentages of partial neurectomy in a previous study would be effective after prolonged denervation time. Twenty Sprague-Dawley rats were divided into four groups. In first-stage surgery the left facial nerve of all animals was transected at the level of the stylomastoid foramen and main zygomatic branch. Group A (controls) consisted of animals with only left facial nerves transected (no repair). In Groups B, C, and D the facial nerve was transected and the facial musculature was denervated for a period of 4, 8, and 12 weeks respectively. During a second-stage procedure, a 40 percent neurectomy was performed on the hypoglossal nerve. Subsequently, a nerve transfer was performed by coaptations of a saphenous nerve graft to the neurectomized hypoglossal nerve and the main zygomatic branch of the facial nerve that innervated the OOM. Behavioral analysis of blink reflex, electrophysiology, and axon and motor end-plate counts in Groups B, C, and D showed superior results compared to Group A. There was no statistically significant difference observed among Groups B, C, and D (p > 0.05). Despite the diminished number of axons in the zygomatic branch and motor end-plates in the orbicularis oculi muscle after 12 weeks of denervation, there was still sufficient muscle target recovery to effect some eye closure in all groups except the controls. This study demonstrated in this model that the 40 percent partial neurectomy of the XII to VII component of the "baby-sitter" procedure was effective even after prolonged denervation.

  20. Hemodynamic and neural responses to renal denervation of the nerve to the clipped kidney by cryoablation in two-kidney, one-clip hypertensive rats. (United States)

    Rossi, Noreen F; Pajewski, Russell; Chen, Haiping; Littrup, Peter J; Maliszewska-Scislo, Maria


    Renal artery stenosis is increasing in prevalence. Angioplasty plus stenting has not proven to be better than medical management. There has been a reluctance to use available denervation methodologies in this condition. We studied conscious, chronically instrumented, two-kidney, one-clip (2K-1C) Goldblatt rats, a model of renovascular hypertension, to test the hypothesis that renal denervation by cryoablation (cryo-DNX) of the renal nerve to the clipped kidney decreases mean arterial pressure (MAP), plasma and tissue ANG II, and contralateral renal sympathetic nerve activity (RSNA). Five-week-old male Sprague-Dawley rats underwent sham (ShC) or right renal artery clipping (2K-1C), placement of telemetry transmitters, and pair-feeding with a 0.4% NaCl diet. After 6 wk, rats were randomly assigned to cryo-DNX or sham cryotreatment (sham DNX) of the renal nerve to the clipped kidney. MAP was elevated in 2K-1C and decreased significantly in both ShC cryo-DNX and 2K-1C cryo-DNX. Tissue norepinephrine was ∼85% lower in cryo-DNX kidneys. Plasma ANG II was higher in 2K-1C sham DNX but not in 2K-1C cryo-DNX vs ShC. Renal tissue ANG II in the clipped kidney decreased after cryo-DNX. Baseline integrated RSNA of the unclipped kidney was threefold higher in 2K-1C versus ShC and decreased in 2K-1C cryo-DNX to values similar to ShC. Maximum reflex response of RSNA to baroreceptor unloading in 2K-1C was lower after cryo-DNX. Thus, denervation by cryoablation of the renal nerve to the clipped kidney decreases not only MAP but also plasma and renal tissue ANG II levels and RSNA to the contralateral kidney in conscious, freely moving 2K-1C rats.

  1. CT-guided percutaneous radiofrequency denervation of the sacroiliac joint

    Energy Technology Data Exchange (ETDEWEB)

    Gevargez, A.; Schirp, S.; Braun, M. [Department of Radiology and Microtherapy, University of Witten/Herdecke, Bochum (Germany); Groenemeyer, D. [Department of Radiology and Microtherapy, University of Witten/Herdecke, Bochum (Germany); EFMT Development and Research Center for Microtherapy, Bochum (Germany)


    Defining the origin of low back pain is a challenging task. Among a variety of factors the sacroiliac joint (SIJ) is a possible pain generator, although precise diagnosis is difficult. Joint blocks may reduce pain, but are, in cases, of only temporary effect. This study was conducted to evaluate CT-guided percutaneous radiofrequency denervation of the sacroiliac joint in patients with low back pain. The procedure was performed on 38 patients who only temporarily responded to CT-guided SIJ blocks. The denervation was carried out in the posterior interosseous sacroiliac ligaments and on the dorsal rami of the fifth spinal nerve. All interventions were carried out under CT guidance as out-patient therapies. Three months after the therapy, 13 patients (34.2%) were completely free of pain. Twelve patients (31.6%) reported on a substantial pain reduction, 7 patients (18.4%) had obtained a slight and 3 patients (7.9%) no pain reduction. The data of 3 patients (7.9%) was missing. There were no intra- or postoperative complications. Computed tomography-guided percutaneous radiofrequency denervation of the sacroiliac joint appears safe and effective. The procedure may be a useful therapeutic modality, especially in patients with chronic low back pain, who only temporarily respond to therapeutic blocks. (orig.)

  2. The Role of Lumbar Sympathetic Nerves in Regulation of Blood Flow to Skeletal Muscle during Anaphylactic Hypotension in Anesthetized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Song

    Full Text Available During hypovolemic shock, skeletal muscle blood flow could be redistributed to vital organs via vasoconstriction in part evoked by activation of the innervating sympathetic nerve activity. However, it is not well known whether this mechanism operates during anaphylactic shock. We determined the femoral artery blood flow (FBF and lumbar sympathetic nerve activity (LSNA mainly regulating the hindquater muscle blood flow during anaphylactic hypotension in anesthetized rats. Anesthetized Sprague-Dawley rats were randomly allocated to the following groups (n = 7/group: (1 non-sensitized, (2 anaphylaxis, (3 anaphylaxis-lumbar sympathectomy (LS and (4 anaphylaxis-sinoaortic denervation (SAD groups. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen to the sensitized rats. The systemic arterial pressure (SAP, heart rate (HR, central venous pressure (CVP, FBF and LSNA were continuously measured. In the anaphylaxis group, LSNA and HR increased, while SAP and FBF decreased after antigen injection. In the anaphylaxis-SAD group, LSNA did not significantly change during the early phase, but the responses of SAP and FBF were similar to those in the anaphylaxis group. In the anaphylaxis-LS group, both FBF and SAP decreased similarly to the anaphylaxis group during anaphylactic hypotension. These results indicated that LSNA increased via baroreceptor reflex, but this sympathoexcitation or LS did not affect antigen-induced decreases in FBF or SAP. Lumbar sympathetic nerves are not involved in regulation of the blood flow to the hindlimb or systemic blood pressure during anaphylactic hypotension in anesthetized rats.

  3. Early changes of graft function, cytokines and superoxide dismutase serum levels after donor liver denervation and Kupffer cell depletion in a rat-to-rat liver transplantation model

    Institute of Scientific and Technical Information of China (English)

    Hong Zhu; Catena Marco; Ferla Gianfranco


    BACKGROUND:Hepatic reperfusion injury may cause acute inlfammatory damage, producing signiifcant organ dysfunction, and is an important problem in liver transplantation. This experiment aimed to study early changes of hepatic function after donor liver denervation and Kupffer cell depletion in rat-to-rat liver transplantation and to evaluate the effect of pre-treatment on liver reperfusion injury. METHODS:Donor rats were divided into four groups:control group; group G was pre-treated with gadolinium chloride (G), an inhibitor of Kupffer cells; group H with hexamethonium (H), a sympathetic ganglionic blocking agent; and group HG, with combined H and G pre-treatment. Under the same conditions, serum alanine aminotransferase (ALT), arterial ketone body ratio (AKBR), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and superoxide dismutase (SOD) of recipient rats were assessed at 4, 8, 16 and 24 hours after liver transplantation. Histological studies of the grafts were compared. RESULTS:HG pre-treatment signiifcantly decreased ALT, TNF-α, and IL-6 levels, increased AKBR and SOD levels, and demonstrated less pathological damage at 8, 16 and 24 hours compared with the control group. Similar trends were also found in the other groups (G and H). However, the differences among them were not signiifcant at 4 post-operative hours.CONCLUSIONS:Donor denervation and Kupffer cell depletion had preventive effect on liver reperfusion injury. HG pre-treatment is a feasible and reproducible method to protect grafts from reperfusion injury.

  4. Cardiac Autonomic Nerve Stimulation in the Treatment of Heart Failure


    Kobayashi, Mariko; Massiello, Alex; Karimov, Jamshid H.; Van Wagoner, David R.; Fukamachi, Kiyotaka


    Research on the therapeutic modulation of cardiac autonomic tone by electrical stimulation has yielded encouraging early clinical results. Vagus nerve stimulation has reduced the rates of morbidity and sudden death from heart failure, but therapeutic vagus nerve stimulation is limited by side effects of hypotension and bradycardia. Sympathetic nerve stimulation that has been implemented in the experiment may exacerbate the sympathetic-dominated autonomic imbalance. In contrast, concurrent sti...

  5. Hydralazine tachycardia and sympathetic cardiovascular reactivity in normal subjects. (United States)

    Vidrio, H; Tena, I


    The correlation between hydralazine-induced tachycardia and overall cardiovascular reactivity to sympathetic stimulation was explored in 50 normal subjects. Blood pressure and heart rate changes after standing, immersion of a hand in cold water, the Valsalva maneuver, and moderate exercise were compared with pressure and rate responses to 20 mg oral hydralazine. The drug did not modify blood pressure but increased heart rate, mainly in the standing position. Because plotting the magnitude of this response suggested a two-population distribution, subjects were divided into hyporeactor and hyperreactor groups. Reactivity did not appear to be related to acetylator phenotype. The magnitude of the cardiac response correlated with heart rate responses to standing and to the Valsalva maneuver; when analyzed separately from hyporeactors, correlation was greater among hyperreactors. Because the orthostatic and Valsalva responses are reflex in nature, these results suggest that hydralazine tachycardia is also reflexly induced, that its magnitude depends on individual baroreceptor sensitivity, which is distributed nonnormally, and that it can be predicted by suitable tests of sympathetic responsiveness.

  6. A model for magnetically coupled sympathetic eruptions

    CERN Document Server

    Torok, T; Titov, V S; Mikic, Z; Reeves, K K; Velli, M; Linker, J A; De Toma, G


    Sympathetic eruptions on the Sun have been observed for several decades, but the mechanisms by which one eruption can trigger another one remain poorly understood. We present a 3D MHD simulation that suggests two possible magnetic trigger mechanisms for sympathetic eruptions. We consider a configuration that contains two coronal flux ropes located within a pseudo-streamer and one rope located next to it. A sequence of eruptions is initiated by triggering the eruption of the flux rope next to the streamer. The expansion of the rope leads to two consecutive reconnection events, each of which triggers the eruption of a flux rope by removing a sufficient amount of overlying flux. The simulation qualitatively reproduces important aspects of the global sympathetic event on 2010 August 1 and provides a scenario for so-called twin filament eruptions. The suggested mechanisms are applicable also for sympathetic eruptions occurring in other magnetic configurations.

  7. Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions

    Directory of Open Access Journals (Sweden)

    Estofolete Cássia F


    Full Text Available Abstract Background In this study the effect of myenteric denervation induced by benzalconium chloride (BAC on distribution of fibrillar components of extracellular matrix (ECM and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG. Rats were divided in four experimental groups: non-denervated (I and denervated stomach (II without MNNG treatment; non-denervated (III and denervated stomachs (IV treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF. Results BAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II compared to the non-denervated stomachs (group I. The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV compared to the non-denervated stomachs (group III that showed degradation of these fibers. The development of lesions (groups III and IV was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV. Conclusions The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes

  8. [Denervation of mimic muscles during endoscopic lifting of the upper part of face]. (United States)

    Pinchuk, V D; Tkach, O S


    Endoscopic lifting of the upper part of face carry out in 28 patients Chemical or surgical denervation had been done for decreasing of mimic muscles activity. Medical glue with folic acid had been used for tissues fixation. Use of medical glue in conjunction with preliminary chemical denervation of mimic muscles with botulin toxin application decreases surgery duration, prevents complications and increases satisfaction of patients.

  9. Effect of denervation of the myenteric plexus on gastroduodenal motility in turkeys. (United States)

    Chaplin, S B; Duke, G E


    The effect of denervation of portions of the myenteric plexus on initiation and coordination of gastric and duodenal contractions was examined in domestic turkeys. Three areas of the muscular stomach (MS), the isthmus between the glandular stomach (GS) and MS, and the pylorus were denervated by application of 1% benzalkonium chloride. Motor activity of the gastroduodenal organs was monitored for 1 h every other day for 13 days using strain gauge transducers implanted at selected sites. Denervation of the isthmus reduced the frequency of MS and duodenal contractions by 50% and abolished GS contractions. Pyloric denervation did not affect the frequency of GS or MS contractions but abolished duodenal contractions. These results suggest that 1) a driving pacemaker for the gastroduodenal cycle is located in the isthmus, and 2) the myenteric plexus is essential for conduction from the pacemaker to the GS and to the duodenum. Denervation of the medial commissure of the myenteric plexus of the MS significantly impaired the function of the ventral half of the MS. It caused atrophy of the underlying medial thick muscle and significantly decreased contraction amplitude. Denervation at this site also caused an enlargement and impaction of the adjacent caudal thin muscle with food and a significant decrease in contraction amplitude. In contrast, denervation of the lateral commissure enlarged the underlying lateral thick muscle and significantly increased its contraction amplitude. Denervation of the cranial thin muscle delayed contractions of that muscle, causing an asynchronization of thin muscle pair.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. The effect of acute denervation on the microcirculation of skeletal muscle: rat cremaster model. (United States)

    Chen, L E; Seaber, A V; Bossen, E; Urbaniak, J R


    Although tissue is denervated during replantation of a severed part, tissue transfer, or muscle transplantation, there are few studies concerning the effects of acute denervation on muscle microcirculation. We have described a surgical procedure that totally denervates the rat cremaster muscle. Histological examination of the denervated tissue has given convincing evidence of nerve degeneration and skeletal muscle atrophy, accompanied by electrophysiological evidence of total denervation. The diameters of each component of the microcirculation were measured before and after denervation. Arterioles and arteries ranging in size from 10 to 70 microns in diameter were found to increase significantly in size immediately after acute denervation. Larger arteries and veins did not undergo significant diametrical increases. These findings suggest that total acute denervation significantly increases the diameter of small arteries and arterioles, thereby decreasing the resistance in the arterial bed and increasing blood flow. Since this phenomenon is of limited duration (20 min), it would appear to be ineffective in enhancing reperfusion and oxygenation at the time of reattachment of amputated parts or during vascularized tissue transfers, until methods of prolonging it for several hours or more are found.

  11. The time course of denervation-induced changes is similar in soleus muscles of adult and old rats.

    NARCIS (Netherlands)

    Degens, H.; Kosar, S.N.; Hopman, M.T.E.; Haan, A. de


    Muscle denervation is accompanied by atrophy and a decline in oxidative capacity. We investigated whether the time course of adaptations following denervation of the soleus muscle differs in adult (5 months old) and older adult (25 months old) rats. We denervated the soleus muscle of the left leg, w

  12. Magnitude of blood pressure reduction in the placebo arms of modern hypertension trials: implications for trials of renal denervation. (United States)

    Patel, Hitesh C; Hayward, Carl; Ozdemir, Baris Ata; Rosen, Stuart D; Krum, Henry; Lyon, Alexander R; Francis, Darrel P; di Mario, Carlo


    Early phase studies of novel interventions for hypertension, such as renal sympathetic denervation, are sometimes single-armed (uncontrolled). We explored the wisdom of this by quantifying the blood pressure fall in the placebo arms of contemporary trials of hypertension. We searched Medline up to June 2014 and identified blinded, randomized trials of hypertension therapy in which the control arm received placebo medication or a sham (placebo) procedure. For nonresistant hypertension, we have identified all such trials of drugs licensed by the US Food and Drug Administration since 2000 (5 drugs). This US Food and Drug Administration-related restriction was not applied to resistant hypertension trials. This produced 7451 patients, who were allocated to a blinded control from 52 trials of nonresistant hypertension and 694 patients from 8 trials of resistant hypertension (3 drugs and 2 interventions). Systolic blood pressure fell by 5.92 mm Hg (95% confidence interval, 5.14-6.71; Phypertension, once safety is established, should be performed with a randomized, appropriately controlled, and blinded design.

  13. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy. (United States)

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F


    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

  14. Imaging of muscular denervation secondary to motor cranial nerve dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Connor, S.E.J. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)]. E-mail:; Chaudhary, N. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Fareedi, S. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Woo, E.K. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)


    The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality.

  15. Activation of NTS A2a adenosine receptors differentially resets baroreflex control of renal vs. adrenal sympathetic nerve activity. (United States)

    Ichinose, Tomoko K; O'Leary, Donal S; Scislo, Tadeusz J


    The role of nucleus of solitary tract (NTS) A(2a) adenosine receptors in baroreflex mechanisms is controversial. Stimulation of these receptors releases glutamate within the NTS and elicits baroreflex-like decreases in mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas inhibition of these receptors attenuates HR baroreflex responses. In contrast, stimulation of NTS A(2a) adenosine receptors increases preganglionic adrenal sympathetic nerve activity (pre-ASNA), and the depressor and sympathoinhibitory responses are not markedly affected by sinoaortic denervation and blockade of NTS glutamatergic transmission. To elucidate the role of NTS A(2a) adenosine receptors in baroreflex function, we compared full baroreflex stimulus-response curves for HR, RSNA, and pre-ASNA (intravenous nitroprusside/phenylephrine) before and after bilateral NTS microinjections of selective adenosine A(2a) receptor agonist (CGS-21680; 2.0, 20 pmol/50 nl), selective A(2a) receptor antagonist (ZM-241385; 40 pmol/100 nl), and nonselective A(1) + A(2a) receptor antagonist (8-SPT; 1 nmol/100 nl) in urethane/alpha-chloralose anesthetized rats. Activation of A(2a) receptors decreased the range, upper plateau, and gain of baroreflex-response curves for RSNA, whereas these parameters all increased for pre-ASNA, consistent with direct effects of the agonist on regional sympathetic activity. However, no resetting of baroreflex-response curves along the MAP axis occurred despite the marked decreases in baseline MAP. The antagonists had no marked effects on baseline variables or baroreflex-response functions. We conclude that the activation of NTS A(2a) adenosine receptors differentially alters baroreflex control of HR, RSNA, and pre-ASNA mostly via non-baroreflex mechanism(s), and these receptors have virtually no tonic action on baroreflex control of these sympathetic outputs.

  16. Connexin hemichannels explain the ionic imbalance and lead to atrophy in denervated skeletal muscles. (United States)

    Cisterna, Bruno A; Vargas, Aníbal A; Puebla, Carlos; Sáez, Juan C


    Denervated fast skeletal muscles undergo atrophy, which is associated with an increase in sarcolemma permeability and protein imbalance. However, the mechanisms responsible for these alterations remain largely unknown. Recently, a close association between de novo expression of hemichannels formed by connexins 43 and 45 and increase in sarcolemma permeability of denervated fast skeletal myofibers was demonstrated. However, it remains unknown whether these connexins cause the ionic imbalance of denervates fast myofibers. To elucidate the latter and the role of hemichannels formed by connexins (Cx HCs) in denervation-induced atrophy, skeletal myofibers deficient in Cx43 and Cx45 expression (Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice) and control (Cx43(fl/fl)Cx45(fl/fl) mice) were denervated and several muscle features were systematically analyzed at different post-denervation (PD) times (1, 3, 5, 7 and 14days). The following sequence of events was found in denervated myofibers of Cx43(fl/fl)Cx45(fl/fl) mice: 1) from day 3 PD, increase in sarcolemmal permeability, 2) from day 5 PD, increases of intracellular Ca(2+) and Na(+) signals as well as a significant increase in protein synthesis and degradation, yielding a negative protein balance and 3) from day 7 PD, a fall in myofibers cross-section area. All the above alterations were either absent or drastically reduced in denervated myofibers of Cx43(fl/fl)Cx45(fl/fl):Myo-Cre mice. Thus, the denervation-induced Cx HCs expression is an early event that precedes the electrochemical gradient dysregulation across the sarcolemma and critically contributes to the progression of skeletal muscle atrophy. Consequently, Cx HCs could be a therapeutic target to drastically prevent the denervation-induced atrophy of fast skeletal muscles.

  17. Thin-fiber mechanoreceptors reflexly increase renal sympathetic nerve activity during static contraction. (United States)

    Kim, Jong Kyung; Hayes, Shawn G; Kindig, Angela E; Kaufman, Marc P


    The renal vasoconstriction induced by the sympathetic outflow during exercise serves to direct blood flow from the kidney toward the exercising muscles. The renal circulation seems to be particularly important in this regard, because it receives a substantial part of the cardiac output, which in resting humans has been estimated to be 20%. The role of group III mechanoreceptors in causing the reflex renal sympathetic response to static contraction remains an open question. To shed some light on this question, we recorded the renal sympathetic nerve responses to static contraction before and after injection of gadolinium into the arterial supply of the statically contracting triceps surae muscles of decerebrate unanesthetized and chloralose-anesthetized cats. Gadolinium has been shown to be a selective blocker of mechanogated channels in thin-fiber muscle afferents, which comprise the afferent arm of the exercise pressor reflex arc. In decerebrate (n = 15) and chloralose-anesthetized (n = 12) cats, we found that gadolinium (10 mM; 1 ml) significantly attenuated the renal sympathetic nerve and pressor responses to static contraction (60 s) after a latent period of 60 min; both responses recovered after a latent period of 120 min. We conclude that thin-fiber mechanoreceptors supplying contracting muscle are involved in some of the renal vasoconstriction evoked by the exercise pressor reflex.

  18. Cardiac arrhythmias

    Institute of Scientific and Technical Information of China (English)


    2008407 Effects of sympathetic nerve stimulation on connexin43 and ventricular arrhythmias during acute myocardial ischemia: experiment with rats. HU Xiaorong(胡笑容), et al. Dept Cardiol, Renmin Hosp, Wuhan Univ, Wuhan 430060. Natl Med J China 2008;88(24):1707-1710. Objective To investigate the effects of sympathetic nerve stimulation (SNS) on connexin43 (Cx43) and ventricular arrhythmias during acute myocardial ischemia (MI).

  19. Estimated central blood volume in cirrhosis: relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic factor

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Bendtsen, F; Gerbes, A L


    The estimated central blood volume (i.e., blood volume in the heart cavities, lungs and central arterial tree) was determined by multiplying cardiac output by circulatory mean transit time in 19 patients with cirrhosis and compared with sympathetic nervous activity and circulating level of atrial...... natriuretic factor. Arterial norepinephrine level, an index of overall sympathetic nervous activity (3.08 nmol/L in patients vs. 1.36 nmol/L in controls; p blood volume (mean = 23 ml/kg in patients vs. 27 ml/kg in controls; p ....05). Similarly, renal venous norepinephrine level (an index of renal sympathetic tone; 4.26 nmol/L in patients vs. 1.78 nmol/L in controls; p blood volume (r = -0.53, n = 18, p

  20. Adrenal GRK2 upregulation mediates sympathetic overdrive in heart failure. (United States)

    Lymperopoulos, Anastasios; Rengo, Giuseppe; Funakoshi, Hajime; Eckhart, Andrea D; Koch, Walter J


    Cardiac overstimulation by the sympathetic nervous system (SNS) is a salient characteristic of heart failure, reflected by elevated circulating levels of catecholamines. The success of beta-adrenergic receptor (betaAR) antagonists in heart failure argues for SNS hyperactivity being pathogenic; however, sympatholytic agents targeting alpha2AR-mediated catecholamine inhibition have been unsuccessful. By investigating adrenal adrenergic receptor signaling in heart failure models, we found molecular mechanisms to explain the failure of sympatholytic agents and discovered a new strategy to lower SNS activity. During heart failure, there is substantial alpha2AR dysregulation in the adrenal gland, triggered by increased expression and activity of G protein-coupled receptor kinase 2 (GRK2). Adrenal gland-specific GRK2 inhibition reversed alpha2AR dysregulation in heart failure, resulting in lowered plasma catecholamine levels, improved cardiac betaAR signaling and function, and increased sympatholytic efficacy of a alpha2AR agonist. This is the first demonstration, to our knowledge, of a molecular mechanism for SNS hyperactivity in heart failure, and our study identifies adrenal GRK2 activity as a new sympatholytic target.


    Directory of Open Access Journals (Sweden)

    V. A. Sulimov


    Full Text Available Aim. To study the effect of renal denervation on blood pressure (BP, myocardium function and vegetative status in patients with resistant hypertension (HT.Material and methods. Patients with a provisional resistant HT diagnosis (n=62; 41.3% male were included into the study. 17 patients were selected for renal denervation after correction of previous antihypertensive therapy and examination to exclude symptomatic HT. Two patients refused the procedure, 1 patient hadn’t undergone renal denervation due to anatomical features (renal artery diameter <4 mm. Renal denervation was performed in 14 patients. Office and average daily BP, kidney function, the severity of left ventricular hypertrophy and heart rate variability were assessed initially and after the intervention.Results. Office systolic BP (SBP decreased from 165 to 150 mm Hg (p=0.016, diastolic BP (DBP - from 110 to 95 mm Hg (p=0.019 12 months after the renal denervation. Average daily SBP decreased from 148 to 137 mm Hg (p=0.092, average daily DBP - from 90 to 80 mm Hg (p=0.401. Plasma creatinine level and glomerular filtration rate remained within the reference range at a baseline and in 12 months. Left ventricular hypertrophy measured by echocardiography has not changed significantly. No significant heart rate variability dynamics has been found.Conclusion. Renal denervation is a promising treatment for resistant HT. The effect of renal denervation on the dynamics of left ventricular hypertrophy and heart rate variability requires updating.


    Directory of Open Access Journals (Sweden)

    V. A. Sulimov


    Full Text Available Aim. To study the effect of renal denervation on blood pressure (BP, myocardium function and vegetative status in patients with resistant hypertension (HT.Material and methods. Patients with a provisional resistant HT diagnosis (n=62; 41.3% male were included into the study. 17 patients were selected for renal denervation after correction of previous antihypertensive therapy and examination to exclude symptomatic HT. Two patients refused the procedure, 1 patient hadn’t undergone renal denervation due to anatomical features (renal artery diameter <4 mm. Renal denervation was performed in 14 patients. Office and average daily BP, kidney function, the severity of left ventricular hypertrophy and heart rate variability were assessed initially and after the intervention.Results. Office systolic BP (SBP decreased from 165 to 150 mm Hg (p=0.016, diastolic BP (DBP - from 110 to 95 mm Hg (p=0.019 12 months after the renal denervation. Average daily SBP decreased from 148 to 137 mm Hg (p=0.092, average daily DBP - from 90 to 80 mm Hg (p=0.401. Plasma creatinine level and glomerular filtration rate remained within the reference range at a baseline and in 12 months. Left ventricular hypertrophy measured by echocardiography has not changed significantly. No significant heart rate variability dynamics has been found.Conclusion. Renal denervation is a promising treatment for resistant HT. The effect of renal denervation on the dynamics of left ventricular hypertrophy and heart rate variability requires updating.

  3. Increase in norepinephrine-induced formation of phosphatidic acid in rat vas deferens after denervation. (United States)

    Takenawa, T; Masaki, T; Goto, K


    Surgical denervation of rat vas deferens causes supersensitivity in that the tissue sensitivity and the maximum response to a variety of agonists increase. To understand the molecular mechanism of supersensitivity in smooth muscle, norepinephrine(NE)-induced alteration in phospholipid metabolism was studied using control and denervated vasa deferentia. When the tissue was stimulated by NE, only [32P]Pi incorporation into phosphatidic acid(PA) was increased in proportion to the increase in NE concentration without any significant effect on that into other phospholipids. This PA labeling was significantly accelerated by denervation. In the denervated tissue, PA labeling was stimulated by lower concentrations of NE and the maximum response to NE was increased compared to the control. The breakdown of phosphatidylinositol 4-monophosphate(DPI) and phosphatidylinositol 4,5-diphosphate (TPI) was also accelerated by NE. But the influence of denervation on this NE-induced DPI and TPI was not marked. Therefore, it is likely that denervation clearly enhanced NE-induced PA labeling without an appreciable effect on that of the other phospholipids. Furthermore, the absolute amount of PA was also increased by NE, and this increase was exaggerated by denervation. Considering that PA can behave as a Ca2+ ionophore in the plasma membrane, these results suggest that the stimulated accumulation of PA plays an important role in receptor-linked supersensitivity in smooth muscle.

  4. Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy. (United States)

    Ling, Karen K Y; Gibbs, Rebecca M; Feng, Zhihua; Ko, Chien-Ping


    Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in >20 muscles in the SMNΔ7 SMA mouse model. We found that severe denervation (<50% fully innervated endplates) occurs selectively in many vulnerable axial muscles and several appendicular muscles at the disease end stage. Since these vulnerable muscles were located throughout the body and were comprised of varying muscle fiber types, it is unlikely that muscle location or fiber type determines susceptibility to denervation. Furthermore, we found a similar extent of neurofilament accumulation at NMJs in both vulnerable and resistant muscles before the onset of denervation, suggesting that neurofilament accumulation does not predict subsequent NMJ denervation. Since vulnerable muscles were initially innervated, but later denervated, loss of innervation in SMA may be attributed to defects in synapse maintenance. Finally, we found that denervation was amendable by trichostatin A (TSA) treatment, which increased innervation in clinically relevant muscles in TSA-treated SMNΔ7 mice. Our findings suggest that neuromuscular denervation in vulnerable muscles is a widespread pathology in SMA, and can serve as a preparation for elucidating the biological basis of synapse loss, and for evaluating therapeutic efficacy.

  5. Effect of regional myocardial ischemia on sympathetic nervous system as assessed by fluorine-18-metaraminol

    Energy Technology Data Exchange (ETDEWEB)

    Schwaiger, M.; Guibourg, H.; Rosenspire, K.; McClanahan, T.; Gallagher, K.; Hutchins, G.; Wieland, D.M. (Univ. of Michigan Medical Center, Ann Arbor (USA))


    With the introduction of radiolabeled catecholamine analogues, the noninvasive evaluation of the cardiac sympathetic nervous system has become possible. This study evaluated the effect of regional ischemia on myocardial retention of the new norepinephrine analogue 6-({sup 18}F) fluorometaraminol (FMR) in the open chest dog model. Six dogs were injected intravenously with FMR following 30-min occlusion of the left anterior descending artery. Six sham animals served as control group. Regional myocardial blood flow as determined by microspheres decreased 87% during ischemia (p less than 0.01), but was not significantly different from control myocardium following reperfusion. Regional myocardial 18F activity as determined postmortem was significantly reduced in reperfused myocardium (-34%), which paralleled an 18% reduction of tissue norepinephrine concentration. Thus, short time periods of coronary occlusion affect neuronal function indicating the sensitivity of the sympathetic nerve terminals to ischemia. FMR provides a new tracer approach for the characterization of neuronal integrity in postischemic myocardium.

  6. Central and cerebrovascular effects of leg crossing in humans with sympathetic failure

    DEFF Research Database (Denmark)

    Harms, Mark P M; Wieling, Wouter; Colier, Willy N J M;


    MCA Vmean (middle cerebral artery blood velocity; using transcranial Doppler ultrasound), frontal lobe oxygenation [O2Hb (oxyhaemoglobin)] and MAP (mean arterial pressure), CO (cardiac output) and TPR (total peripheral resistance) in six patients (aged 37-67 years; three women) and age- and gender.......12 (0.52-3.27)] in the patients compared with the controls [0.83 (-0.11 to 2.04) micromol/l]. In the control subjects, CO increased 11% (PTPR. By contrast, in the patients, CO increased 9% (PTPR increased by 13% (P... cerebral perfusion and oxygenation both in patients with sympathetic failure and in healthy subjects. However, in healthy subjects, cerebral perfusion and oxygenation were improved by a rise in CO without significant changes in TPR or MAP, whereas in patients with sympathetic failure, cerebral perfusion...

  7. [Effectiveness of sympathetic block using various technics]. (United States)

    Weissenberg, W


    Blocking of sympathetic conduction aims at permanent or temporary elimination of those pain pathways conducted by the sympathetic nervous system. In order to provide an objective evaluation of sufficient blocking effect, earlier inquiries referred to parameters such as: (1) observation of clinical signs such as Horner's syndrome, Guttman's sign, anhidrosis, extended venous filling; (2) difference in skin temperature of at least 1.5 degrees C between blocked and unblocked side; (3) increase in amplitude of the pulse wave; and (4) depression of the psychogalvanic reflex (PGR) on the blocked side (Fig. 1). In clinical practice, these control parameters are effective because they are time-saving, technically simple, and highly evidential. Further parameters for evaluating sympathetic blockade are examination of hydrosis by means of color indicators such as bromocresol and ninhydrin, oscillometry, and plethysmography. The effectiveness of sympathetic blockade after stellate ganglion and sympathetic trunk blocks has been verified by various authors. In a clinical study, 16 patients were divided into four groups in order to test the effectiveness of sympathetic blockade after spinal anesthesia with 3 ml 0.75% bupivacaine (group I) and 4 ml 0.75% bupivacaine (group II) and after peridural anesthesia with 15 ml 0.75% bupivacaine (group III) and 20 ml 0.75% bupivacaine (group IV) by means of temperature difference, response of pulse wave amplitude and PGR between blocked lower and unblocked upper extremity, and sensory levels of block. The patients were classified as ASA I and II; their ages varied from 20 to 63 years.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 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)


    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 work

  9. Sympathetic hyperactivity in patients with chronic kidney disease

    NARCIS (Netherlands)

    Neumann, N.


    Sympathetic hyperactivity in patients with chronic kidney disease Chronic kidney disease (CKD) is often characterized by the presence of sympathetic hyperactivity. This contributes to the pathogenesis of renal hypertension. It is also associated with cardiovascular (CV) morbidity and mortality indep

  10. Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation (United States)

    Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra


    Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

  11. Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice. (United States)

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


    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.

  12. Estimation of arterial and cardiopulmonary total peripheral resistance baroreflex gain values: validation by chronic arterial baroreceptor denervation. (United States)

    Mukkamala, Ramakrishna; Kim, Jong-Kyung; Li, Ying; Sala-Mercado, Javier; Hammond, Robert L; Scislo, Tadeusz J; O'Leary, Donal S


    Feedback control of total peripheral resistance (TPR) by the arterial and cardiopulmonary baroreflex systems is an important mechanism for short-term blood pressure regulation. Existing methods for measuring this TPR baroreflex mechanism typically aim to quantify only the gain value of one baroreflex system as it operates in open-loop conditions. As a result, the normal, integrated functioning of the arterial and cardiopulmonary baroreflex control of TPR remains to be fully elucidated. To this end, the laboratory of Mukkamala et al. (Mukkamala R, Toska K, and Cohen RJ. Am J Physiol Heart Circ Physiol 284: H947-H959, 2003) previously proposed a potentially noninvasive technique for estimating the closed-loop (dimensionless) gain values of the arterial TPR baroreflex (GA) and the cardiopulmonary TPR baroreflex (GC) by mathematical analysis of the subtle, beat-to-beat fluctuations in arterial blood pressure, cardiac output, and stroke volume. Here, we review the technique with additional details and describe its experimental evaluation with respect to spontaneous hemodynamic variability measured from seven conscious dogs, before and after chronic arterial baroreceptor denervation. The technique was able to correctly predict the group-average changes in GA and GC that have previously been shown to occur following chronic arterial baroreceptor denervation. That is, reflex control by the arterial TPR baroreflex was virtually abolished (GA = -2.1 +/- 0.6 to 0.3 +/- 0.2; P TPR baroreflex more than doubled (GC = -0.7 +/- 0.4 to -1.8 +/- 0.2; P TPR baroreflex functioning in both humans and animals in health and disease.

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

    DEFF Research Database (Denmark)

    Henriksen, O


    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 ...... to collision of normodromically and antidromically conducted impulses in efferent sympathetic vasoconstrictor fibers. The evidence obtained suggests that sympathetic vasoconstrictor reflexes to postural changes are complex and highly differentiated....

  14. Periodic Repolarisation Dynamics: A Natural Probe of the Ventricular Response to Sympathetic Activation (United States)

    Rizas, Konstantinos D; Hamm, Wolfgang; Kääb, Stefan; Schmidt, Georg; Bauer, Axel


    Periodic repolarisation dynamics (PRD) refers to low-frequency (≤0.1Hz) modulations of cardiac repolarisation instability. Spontaneous PRD can be assessed non-invasively from 3D high-resolution resting ECGs. Physiological and experimental studies have indicated that PRD correlates with efferent sympathetic nerve activity, which clusters in low-frequency bursts. PRD is increased by physiological provocations that lead to an enhancement of sympathetic activity, whereas it is suppressed by pharmacological β-blockade. Electrophysiological studies revealed that PRD occurs independently from heart rate variability. Increased PRD under resting conditions is a strong predictor of mortality in post-myocardial infarction (post-MI) patients, yielding independent prognostic value from left-ventricular ejection fraction (LVEF), heart rate variability, the Global Registry of Acute Coronary Events score and other established risk markers. The predictive value of PRD is particularly strong in post-MI patients with preserved LVEF (>35 %) in whom it identifies a new high-risk group of patients. The upcoming Implantable Cardiac Monitors in High-Risk Post-Infarction Patients with Cardiac Autonomic Dysfunction and Moderately Reduced Left Ventricular Ejection Fraction (SMART-MI) trial will test prophylactic strategies in high-risk post-MI patients with LVEF 36–50 % identified by PRD and deceleration capacity of heart rate (NCT02594488). PMID:27403291

  15. Lack of uptake, release and action of UTP at sympathetic perivascular nerve terminals in rabbit ear artery. (United States)

    Saïag, B; Shacoori, V; Bodin, P; Catheline, M; Burnstock, G


    A possible role of uridine 5'-triphosphate (UTP) and uridine at sympathetic nerve terminals was studied in the rabbit ear artery after incubation of isolated vessels with [3H]uridine or [3H]noradrenaline. It was found that [3H]uridine was taken up by rabbit ear artery. This uptake was largely suppressed after the removal of endothelium and was inhibited by ethidium bromide and dipyridamole. Chemical denervation of the vessels with 6-hydroxydopamine did not reduce the uptake. Following pre-incubation of the isolated vessels with [3H]uridine, there was a release of radioactivity from the superfused rabbit ear artery. UTP, UDP, UMP and uridine were detected by thin layer chromatography both in the superfusate and inside the vessels. Transmural electric stimulation (30 V, 5 Hz) induced a contraction of the vessels but did not increase the release of uridine nucleotides into the superfusate. [3H]Noradrenaline was released during electric stimulation and the addition of UTP (100 microM) had no effects on this release. To conclude, this study shows that in contrast to endothelial cells, the sympathetic nerve terminals of the rabbit ear artery do not take up uridine and do not release uridine-derived nucleotides. UTP at 100 microM is also unable to modulate the evoked release of noradrenaline. These results mainly confine the role of UTP in endothelium-derived vasodilatation via P2Y2 and/or P2Y4 receptors.

  16. Trapping and Sympathetic Cooling of Boron Ions

    CERN Document Server

    Rugango, Rene; Shu, Gang; Brown, Kenneth R


    We demonstrate the trapping and sympathetic cooling of B$^{+}$ ions in a Coulomb crystal of laser-cooled Ca$^{+}$, We non-destructively confirm the presence of the both B$^+$ isotopes by resonant excitation of the secular motion. The B$^{+}$ ions are loaded by ablation of boron and the secular excitation spectrum also reveals features consistent with ions of the form B$_{n}^{+}$.

  17. Pigmentation associated histopathological variations in sympathetic ophthalmia. (United States)

    Marak, G E; Ikui, H


    The severity of inflammation in sympathetic ophthalmia is related to the degree of pigmentation, and the granulomatous response seems to be related to pigmentation. Eosinophilia is also associated with pigmentation, but this association appears to be fortuitous and is a result of the association of eosinophilia with severity of the inflammation. PMID:7387955

  18. 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)


    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.

  19. MRI diagnosis of muscle denervation from herpes zoster with discordant distribution of the skin rash

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Amit; Sundaram, Murali [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Winalski, Carl S. [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Cleveland Clinic, Department of Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States)


    Herpes zoster is a common disorder characterized by a painful rash along a dermatome caused by reactivation of the varicella zoster virus (VZV). Muscle denervation injury from motor involvement is an uncommon phenomenon. Discordant distribution of the skin rash and motor nerve involvement, presenting as a skin rash in one body part and muscle weakness or pain from nerve involvement in another body part is an even more uncommonly reported finding. We present an unusual case of muscle denervation injury resulting from motor involvement of a peripheral nerve by VZV diagnosed by magnetic resonance imaging with cutaneous manifestations in a different dermatomal distribution. To the best of our knowledge, there has been no similar case reported in the English radiology literature. We suggest that whenever a radiologist notices MRI findings suggesting denervation injury and a cause not readily identified, VZV-related denervation injury should be included in the differential diagnosis, especially in an older immunocompromised patient. (orig.)

  20. Sphingosine-1-phosphate receptor inhibition prevents denervation-induced dendritic atrophy. (United States)

    Willems, Laurent M; Zahn, Nadine; Ferreirós, Nerea; Scholich, Klaus; Maggio, Nicola; Deller, Thomas; Vlachos, Andreas


    A hallmark of several major neurological diseases is neuronal cell death. In addition to this primary pathology, secondary injury is seen in connected brain regions in which neurons not directly affected by the disease are denervated. These transneuronal effects on the network contribute considerably to the clinical symptoms. Since denervated neurons are viable, they are attractive targets for intervention. Therefore, we studied the role of Sphingosine-1-phosphate (S1P)-receptor signaling, the target of Fingolimod (FTY720), in denervation-induced dendritic atrophy. The entorhinal denervation in vitro model was used to assess dendritic changes of denervated mouse dentate granule cells. Live-cell microscopy of GFP-expressing granule cells in organotypic entorhino-hippocampal slice cultures was employed to follow individual dendritic segments for up to 6 weeks after deafferentation. A set of slice cultures was treated with FTY720 or the S1P-receptor (S1PR) antagonist VPC23019. Lesion-induced changes in S1P (mass spectrometry) and S1PR-mRNA levels (laser microdissection and qPCR) were determined. Denervation caused profound changes in dendritic stability. Dendritic elongation and retraction events were markedly increased, resulting in a net reduction of total dendritic length (TDL) during the first 2 weeks after denervation, followed by a gradual recovery in TDL. These changes were accompanied by an increase in S1P and S1PR1- and S1PR3-mRNA levels, and were not observed in slice cultures treated with FTY720 or VPC23019. We conclude that inhibition of S1PR signaling prevents dendritic destabilization and denervation-induced dendrite loss. These results suggest a novel neuroprotective effect for pharmaceuticals targeting neural S1PR pathways.

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

    DEFF Research Database (Denmark)

    Henriksen, O


    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...

  2. Cardiac autonomic nerve distribution and arrhythmia

    Institute of Scientific and Technical Information of China (English)

    Quan Liu; Dongmei Chen; Yonggang Wang; Xin Zhao; Yang Zheng


    OBJECTIVE: To analyze the distribution characteristics of cardiac autonomic nerves and to explore the correlation between cardiac autonomic nerve distribution and arrhythmia.DATA RETRIEVAL: A computer-based retrieval was performed for papers examining the distribution of cardiac autonomic nerves, using "heart, autonomic nerve, sympathetic nerve, vagus nerve, nerve distribution, rhythm and atrial fibrillation" as the key words.SELECTION CRITERIA: A total of 165 studies examining the distribution of cardiac autonomic nerve were screened, and 46 of them were eventually included.MAIN OUTCOME MEASURES: The distribution and characteristics of cardiac autonomic nerves were observed, and immunohistochemical staining was applied to determine the levels of tyrosine hydroxylase and acetylcholine transferase (main markers of cardiac autonomic nerve distribution). In addition, the correlation between cardiac autonomic nerve distribution and cardiac arrhythmia was investigated.RESULTS: Cardiac autonomic nerves were reported to exhibit a disordered distribution in different sites, mainly at the surface of the cardiac atrium and pulmonary vein, forming a ganglia plexus. The distribution of the pulmonary vein autonomic nerve was prominent at the proximal end rather than the distal end, at the upper left rather than the lower right, at the epicardial membrane rather than the endocardial membrane, at the left atrium rather than the right atrium, and at the posterior wall rather than the anterior wall. The main markers used for cardiac autonomic nerves were tyrosine hydroxylase and acetylcholine transferase. Protein gene product 9.5 was used to label the immunoreactive nerve distribution, and the distribution density of autonomic nerves was determined using a computer-aided morphometric analysis system.CONCLUSION: The uneven distribution of the cardiac autonomic nerves is the leading cause of the occurrence of arrhythmia, and the cardiac autonomic nerves play an important role in the

  3. Diagnostic signs of motor neuropathy in MR neurography: Nerve lesions and muscle denervation

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Daniel; Pham, Mirko; Bendszus, Martin; Baeumer, Philipp [Heidelberg University Hospital, Department of Neuroradiology, Heidelberg (Germany); Weiler, Markus [Heidelberg University Hospital, Department of Neurology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neurooncology, Heidelberg (Germany); Heiland, Sabine [Heidelberg University Hospital, Section of Experimental Radiology, Department of Neuroradiology, Heidelberg (Germany)


    To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. (orig.)

  4. Improved functional recovery of denervated skeletal muscle after temporary sensory nerve innervation. (United States)

    Bain, J R; Veltri, K L; Chamberlain, D; Fahnestock, M


    Prolonged muscle denervation results in poor functional recovery after nerve repair. The possible protective effect of temporary sensory innervation of denervated muscle, prior to motor nerve repair, has been examined in the rat. Soleus and gastrocnemius muscles were denervated by cutting the tibial nerve, and the peroneal nerve was then sutured to the transected distal tibial nerve stump either immediately or after two, four or six months. In half of the animals with delayed repair, the saphenous (sensory) nerve was temporarily attached to the distal nerve stump. Muscles were evaluated three months after the peroneal-to-tibial union, and were compared with each other, with unoperated control muscles and with untreated denervated muscles. After four to six months of sensory "protection", gastrocnemius muscles weighed significantly more than unprotected muscles, and both gastrocnemius and soleus muscles exhibited better preservation of their structure, with less fiber atrophy and connective tissue hyperplasia. The maximum compound action potentials were significantly larger in gastrocnemius and soleus muscles following sensory protection, irrespective of the delay in motor nerve union. Isometric force, although less than in control animals and in those with immediate nerve repair, remained reasonably constant after sensory protection, while in unprotected muscles there was a progressive and significant decline as the period of denervation lengthened. We interpret these results as showing that, although incapable of forming excitable neuromuscular junctions, sensory nerves can nevertheless exert powerful trophic effects on denervated muscle fibers. We propose that these findings indicate a useful strategy for improving the outcome of peripheral nerve surgery.

  5. Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat (United States)

    Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun


    Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

  6. Cardiac arrest (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  7. Abolition of reflex bradycardia by cardiac vagotomy has no effect on the regulation of oxygen uptake by Atlantic cod in progressive hypoxia

    DEFF Research Database (Denmark)

    McKenzie, David; Skov, Peter Vilhelm; Taylor, E.W.T.


    nerve X Cardiac denervation had no effect on oxygen uptake rate (M-O2), gill ventilation rate (f(G)) or opercular pressure amplitude (P-OP) under normoxic conditions, but caused a significant increase in heart rate (f(H)), to 50 +/- 1 beats min(-1) by comparison to 40 +/- 2 beats min(-1) in sham...

  8. Research progress of myocardial ischemia and sympathetic afferent%心肌缺血与交感神经传入的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘俊; 梁尚栋


    心脏的自主神经包括交感神经与副交感神经.支配心脏的交感神经不仅有传出轴突,也有传递心脏感受的传入神经.心肌缺血可激活心交感传入神经并将信息传递到大脑心血管中枢,通过兴奋交感传出神经引起交感兴奋性反射,出现心率加快和血压升高等现象使心肌缺血、缺氧和心绞痛加重.因此,交感神经功能变化可加重心肌缺血损伤.%The heart autonomic nervous system consists of both sympathetic and parasympathetic nerves. The heart sympathetic nerves contain not only efferent axons, but also the afferentnerve( transmitting messages to the heart ). Myocardial ischemia activates cardiac sympathetic afferent nerve and transmits the information to the brain and cardiovascular centre, which resultsin sympathetic reflex excitability by excitatory sympathetic efferent. This causes an increase in heart rate and blood pressure, leading to the development of myocardial ischemia, hypoxia and angina pain. Therefore, the change in sympathetic function is acontributing factor to myocardial ischemia.

  9. The effect of renal denervation on kidney oxygenation as determined by BOLD MRI in patients with hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Vink, E.E.; Boer, A.; Blankestijn, P.J. [University Medical Center Utrecht, Department of Nephrology, P.O. Box 85500, GA, Utrecht (Netherlands); Verloop, W.L.; Voskuil, M. [University Medical Center Utrecht, Department of Cardiology, Utrecht (Netherlands); Spiering, W.; Leiner, T. [University Medical Center Utrecht, Department of Vascular Medicine, Utrecht (Netherlands); Vonken, E.; Hoogduin, J.M. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Bots, M.L. [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands)


    Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m{sup 2}; p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. (orig.)

  10. Effect of percutaneous renal sympathetic nerve radiofrequency ablation in patients with severe heart failure. (United States)

    Dai, Qiming; Lu, Jing; Wang, Benwen; Ma, Genshan


    This study aimed to investigate the clinical feasibility and effects of percutaneous renal sympathetic nerve radiofrequency ablation in patients with heart failure. A total of 20 patients with heart failure were enrolled, aged from 47 to 75 years (63±10 years). They were divided into the standard therapy (n = 10), and renal nerve radiofrequency ablation groups (n = 10). There were 15 males and 5 female patients, including 8 ischemic cardiomyopathy, 8 dilated cardiomyopathy, and 8 hypertensive cardiopathy. All of the patients met the criteria of New York Heart Association classes III-IV cardiac function. Patients with diabetes and renal failure were excluded. Percutaneous renal sympathetic nerve radiofrequency ablation was performed on the renal artery wall under X-ray guidance. Serum electrolytes, neurohormones, and 24 h urine volume were recorded 24 h before and after the operation. Echocardiograms were performed to obtain left ventricular ejection fraction at baseline and 6 months. Heart rate, blood pressure, symptoms of dyspnea and edema were also monitored. After renal nerve ablation, 24 h urine volume was increased, while neurohormone levels were decreased compared with those of pre-operation and standard therapy. No obvious change in heart rate or blood pressure was recorded. Symptoms of heart failure were improved in patients after the operation. No complications were recorded in the study. Percutaneous renal sympathetic nerve radiofrequency ablation may be a feasible, safe, and effective treatment for the patients with severe congestive heart failure.

  11. Effect of postnatal lead exposure on the development of sympathetic innervation of the heart. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, M.E.


    To determine possible mechanisms for this Pb-induced cardiotoxicity, several neutrochemical parameters indicative of cardiac sympathetic innervation were measured in developing rats. Presynaptic indices of nerve terminal development which were studied included steady-state levels of norepinephrine, neuronal uptake and vesicular storage of /sup 3/H-norepinephrine. Analysis of postsynaptic development was accomplished by quantitating the density of ..beta..-adrenergic receptors and by measuring the activity of adenylate cyclase. Rat pups were exposed to Pb from birth to weaning (21 days) via the milk of dams whose drinking water contained 0.2% Pb acetate. This method and level of Pb treatment had no effect on body or heart weight development, however, it did result in a seven-fold increase in the blood Pb content (70-75 of the treated pups during the period of exposure. Pb exposure accelerated the development of sympathetic innervation of the heart as detected by significant increases in the vesicular uptake of /sup 3/H-norepinephrine and the steady-state concentration of norepinephrine measured at postnatal day 4. On the other hand, ontogeny of the neutronal uptake of /sup 3/H-norepinephrine in the heart and in the forebrain was not affected by Pb treatment. The apparent premature development of sympathetic innervation induced by Pb treatment was not reflected in significant alterations in either the density or the affinity of ..beta..-adrenergic receptor sites determined by the binding kinetics of /sup 3/H-dihydroalprenolol.

  12. Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity? (United States)

    Lambert, Elisabeth A; Straznicky, Nora E; Dixon, John B; Lambert, Gavin W


    The sympathetic nervous system (SNS) plays a key role in both cardiovascular and metabolic regulation; hence, disturbances in SNS regulation are likely to impact on both cardiovascular and metabolic health. With excess adiposity, in particular when visceral fat accumulation is present, sympathetic activation commonly occurs. Experimental investigations have shown that adipose tissue releases a large number of adipokines, cytokines, and bioactive mediators capable of stimulating the SNS. Activation of the SNS and its interaction with adipose tissue may lead to the development of hypertension and end-organ damage including vascular, cardiac, and renal impairment and in addition lead to metabolic abnormalities, especially insulin resistance. Lifestyle changes such as weight loss and exercise programs considerably improve the cardiovascular and metabolic profile of subjects with obesity and decrease their cardiovascular risk, but unfortunately weight loss is often difficult to achieve and sustain. Pharmacological and device-based approaches to directly or indirectly target the activation of the SNS may offer some benefit in reducing the cardiometabolic consequences of obesity. Preliminary evidence is encouraging, but more trials are needed to investigate whether sympathetic inhibition could be used in obesity to reverse or prevent cardiometabolic disease development. The purpose of this review article is to highlight the current knowledge of the role that SNS plays in obesity and its associated metabolic disorders and to review the potential benefits of sympathoinhibition on metabolic and cardiovascular functions.

  13. Sympathetic adaptations to one-legged training (United States)

    Ray, C. A.


    The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.

  14. Sympathetic innervation of the upper and lower regions of the uterus and cervix in the rat have different origins and routes. (United States)

    Houdeau, E; Rousseau, A; Meusnier, C; Prud'Homme, M J; Rousseau, J P


    The origins and routes of the postganglionic sympathetic nerve supply to the upper and lower uterus and to the cervix were investigated in the rat by using denervation procedures combined with immunohistochemistry and retrograde tracing. The sympathetic nerve fibers of the upper part of the uterus arise from the ovarian plexus nerve. They mainly originate (90%) from neurons of the suprarenal ganglia (SRG) and of the T10 to L3 ganglia of the paravertebral sympathetic chain. Fluoro-Gold injections into different regions of the upper uterus showed that the SRG neurons mainly provide innervation to the tubal extremity (52%) rather than to the uterine portion below this area (26%). Very few neurons of the celiac ganglion or the aorticorenal ganglia participated in this innervation. Most of the sympathetic innervation of the lower uterus and the cervix (90%) originates from neurons of the paravertebral ganglia T13 to S2, principally at the L2-L4 levels. By using immunocytochemistry, we show that very few tyrosine hydroxylase-positive neurons of the pelvic plexus project to these areas, where they represent only 3% of the sympathetic nerve supply. Again, very few neurons of the inferior mesenteric ganglion (IMG) supply the lower uterus and the cervix. The comparison between retrograde tracing experiments in intact animals and after the removal of the IMG shows that very few sympathetic postganglionic axons from the paravertebral chain pass through the IMG to reach the lower uterus and the cervix. In contrast, these axons mainly project to splanchnic nerves bypassing the IMG to connect with the hypogastric nerves. In addition, some axons supplying the lower uterus follow the superior vesical arteries and then reach the organ. Taken together, these results show that the upper region of the uterus receives a sympathetic innervation that is different in origin and route from that of the lower uterus and the cervix. Such a marked region-specific innervation suggests that nerve

  15. [Sympathetically maintained pain (SMP): phentolamine test vs sympathetic nerve blockade. Comparison of two diagnostic methods]. (United States)

    Wehnert, Y; Müller, B; Larsen, B; Kohn, D


    The objective of our study was to clarify whether the phentolamine test is as suitable as sympathetic blockade in diagnosing cases of sympathetically maintained pain. The specificity and the sensitivity of both procedures were examined within a prospective and randomized study. Both a local sympathetic blockade and an intravenous phentolamine infusion were carried out in 29 patients with persistent pain in the area of the upper or lower extremities. A significant improvement was defined as reduction of pain of at least 50%. There were no complications in either test procedure. The phentolamine test registers sympathetically maintained pain well when it has a positive result (specificity of 83%). However, the phentolamine test shows only a low sensitivity of 69%. The phentolamine test, on the other hand, can be realized very easily and safely. Therefore, based on the results obtained, it is recommended that the phentolamine test be applied for primary diagnosis. In case of a negative result, further diagnosis should follow subsequently, for example with local sympathetic blockade.

  16. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

    Directory of Open Access Journals (Sweden)

    A. Medeiros


    Full Text Available The effect of swimming training (ST on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12 and trained (T, N = 12 male Wistar rats (200-220 g. ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5% body weight load attached to the tail. The effect of the autonomic nervous system in generating training-induced resting bradycardia (RB was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm. RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm, since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13% and myocyte dimension (21% were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52% in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

  17. Denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sharon L Rowan

    Full Text Available Although denervation has long been implicated in aging muscle, the degree to which it is causes the fiber atrophy seen in aging muscle is unknown. To address this question, we quantified motoneuron soma counts in the lumbar spinal cord using choline acetyl transferase immunhistochemistry and quantified the size of denervated versus innervated muscle fibers in the gastrocnemius muscle using the in situ expression of the denervation-specific sodium channel, Nav₁.₅, in young adult (YA and senescent (SEN rats. To gain insights into the mechanisms driving myofiber atrophy, we also examined the myofiber expression of the two primary ubiquitin ligases necessary for muscle atrophy (MAFbx, MuRF1. MN soma number in lumbar spinal cord declined 27% between YA (638±34 MNs×mm⁻¹ and SEN (469±13 MNs×mm⁻¹. Nav₁.₅ positive fibers (1548±70 μm² were 35% smaller than Nav₁.₅ negative fibers (2367±78 μm²; P<0.05 in SEN muscle, whereas Nav₁.₅ negative fibers in SEN were only 7% smaller than fibers in YA (2553±33 μm²; P<0.05 where no Nav₁.₅ labeling was seen, suggesting denervation is the primary cause of aging myofiber atrophy. Nav₁.₅ positive fibers had higher levels of MAFbx and MuRF1 (P<0.05, consistent with involvement of the proteasome proteolytic pathway in the atrophy of denervated muscle fibers in aging muscle. In summary, our study provides the first quantitative assessment of the contribution of denervation to myofiber atrophy in aging muscle, suggesting it explains the majority of the atrophy we observed. This striking result suggests a renewed focus should be placed on denervation in seeking understanding of the causes of and treatments for aging muscle atrophy.

  18. Experimental study on aortic remodeling in sinoaortic denervated rats

    Institute of Scientific and Technical Information of China (English)

    MIAO Chao-yu; TAO Xia; GUAN Yun-feng; YANG You-cai; CHU Zheng-xu; SU Ding-feng


    Objective: To study the aortic remodeling produced by chronic sinoaortic denervation (SAD) and its time course, and to study the role of humoral factor in the SAD-induced aortic remodeling. Methods: In rats with chronic SAD or sham operation, the aortic structure was measured by computer-assisted image analysis, the aortic function by isolated artery preparation, and angiotensin Ⅱ concentration by radioimmunoassay. Results and Conclusion: The aortic structural remodeling developed progressively at 4, 8, 16 and 32 weeks after SAD. Aortic structural remodeling after SAD expressed mainly as aortic hypertrophy due to SMC growth and collagen accumulation. The aortic contraction elicited by norepinephrine (NE) was progressively increased 8, 16 and 32 weeks after SAD. The aortic relaxation elicited by acetylcholine (ACh) was depressed 8, 16 and 32 weeks after SAD. In addition, in 32-week SAD rats the NE-induced contraction was not increased by endothelial denudation. These indicated that the increased contraction and depressed relaxation after SAD were related to the change of endothelium and/or the change of interaction between endothelium and SMC. In 10-week SAD rats, plasma angiotensin Ⅱ concentration remained unchanged, whereas aortic angiotensin Ⅱ concentration was significantly increased, suggesting that activation of tissue renin-angiotensin system may be involved in SAD-induced aortic remodeling.

  19. PET and SPET tracers for mapping the cardiac nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska Hospital, 17176 Stockholm (Sweden)


    The human cardiac nervous system consists of a sympathetic and a parasympathetic branch with (-)-norepinephrine and acetylcholine as the respective endogenous neurotransmitters. Dysfunction of the cardiac nervous system is implicated in various types of cardiac disease, such as heart failure, myocardial infarction and diabetic autonomic neuropathy. In vivo assessment of the distribution and function of cardiac sympathetic and parasympathetic neurones with positron emission tomography (PET) and single-photon emission tomography (SPET) can be achieved by means of a number of carbon-11-, fluorine-18-, bromine-76- and iodine-123-labelled tracer molecules. Available tracers for mapping sympathetic neurones can be divided into radiolabelled catecholamines, such as 6-[{sup 18}F]fluorodopamine, (-)-6-[{sup 18}F]fluoronorepinephrine and (-)-[{sup 11}C]epinephrine, and radiolabelled catecholamine analogues, such as [{sup 123}I]meta-iodobenzylguanidine, [{sup 11}C]meta-hydroxyephedrine, [{sup 18}F]fluorometaraminol, [{sup 11}C]phenylephrine and meta-[{sup 76}Br]bromobenzylguanidine. Resistance to metabolism by monoamine oxidase and catechol-O-methyl transferase simplifies the myocardial kinetics of the second group. Both groups of compounds are excellent agents for an overall assessment of sympathetic innervation. Biomathematical modelling of tracer kinetics is complicated by the complexity of the steps governing neuronal uptake, retention and release of these agents as well as by their high neuronal affinity, which leads to partial flow dependence of uptake. Mapping of cardiac parasympathetic neurones is limited by a low density and focal distribution pattern of these neurones in myocardium. Available tracers are derivatives of vesamicol, a molecule that binds to a receptor associated with the vesicular acetylcholine transporter. Compounds like (-)-[{sup 18}F]fluoroethoxybenzovesamicol display a high degree of non-specific binding in myocardium which restricts their utility

  20. Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism

    DEFF Research Database (Denmark)

    Vagn Nielsen, H; Hasselström, K; Feldt-Rasmussen, U


    Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic vasoconstrict......Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic.......02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment....

  1. The sympathetic nervous system alterations in human hypertension. (United States)

    Grassi, Guido; Mark, Allyn; Esler, Murray


    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

  2. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages. (United States)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo


    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and α-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation.

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

    Directory of Open Access Journals (Sweden)

    Heather L. Bloom


    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.

  4. Heart rate complexity: A novel approach to assessing cardiac stress reactivity. (United States)

    Brindle, Ryan C; Ginty, Annie T; Phillips, Anna C; Fisher, James P; McIntyre, David; Carroll, Douglas


    Correlation dimension (D2), a measure of heart rate (HR) complexity, has been shown to decrease in response to acute mental stress and relate to adverse cardiovascular health. However, the relationship between stress-induced changes in D2 and HR has yet to be established. The present studies aimed to assess this relationship systematically while controlling for changes in respiration and autonomic activity. In Study 1 (N = 25) D2 decreased during stress and predicted HR reactivity even after adjusting for changes in respiration rate, and cardiac vagal tone. This result was replicated in Study 2 (N = 162) and extended by including a measure of cardiac sympathetic activity; correlation dimension remained an independent predictor of HR reactivity in a hierarchical linear model containing measures of cardiac parasympathetic and sympathetic activity and their interaction. These results suggest that correlation dimension may provide additional information regarding cardiac stress reactivity above that provided by traditional measures of cardiac autonomic function.

  5. Myenteric denervation in gastric carcinogenesis: differential modulation of nitric oxide and annexin-A1. (United States)

    Polli-Lopes, Ana Cláudia; Estofolete, Cássia F; Oliani, Sonia M; Zucoloto, Sérgio; Cunha, Fernando Q; Gil, Cristiane D


    This study evaluated the properties of endogenous nitric oxide synthases (NOS) and annexin-A1 (ANXA1) and determined how they can be exploited in the N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and myenteric denervation model. Male Wistar rats were treated with MNNG and/or aminoguanidine (AG) for 20 weeks. In another set of experiments, rats with nondenervated and denervated stomachs were treated with MNNG or water for 28 weeks. Fragments of the pyloric region were processed for histopathology, NOS activity, and immunohistochemistry to explore the activity and expression of constitutive (cNOS) and inducible (iNOS) NO synthase and their relationship with annexin-A1 (ANXA1) expression. NO inhibition by AG increased the percentage of animals with adenocarcinomas (~29%) compared with the untreated MNNG group (~4%). Myenteric denervation did not alter NOS activity. cNOS activity was significantly greater in nondernervated and denervated stomachs with or without lesions (Pactivity (Pactivity in normal stomachs and outside the lesion area was considerably higher than inside it (Pmyenteric denervation. In conclusion, NO protects against the development of gastric adenocarcinomas. The pattern of ANXA1 expression was not associated with NOS activity or expression, suggesting that NO and ANXA1 act in gastric tumors in disparate pathways.

  6. Diffusion-weighted MRI of denervated muscle: a clinical and experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Holl, Nathalie; Bierry, Guillaume; Moser, Thomas; Dietemann, Jean-Louis; Kremer, Stephane [Hopitaux Universitaires de Strasbourg, Service de Radiologie 2, Strasbourg (France); Echaniz-Laguna, Andoni [Hopitaux Universitaires de Strasbourg, Departement de Neurologie, BP 426, Strasbourg (France); Mohr, Michel [Hopitaux Universitaires de Strasbourg, Departement d' Anatomie Pathologique, Strasbourg (France); Loeffler, Jean-Philippe [INSERM U692, Laboratoire de Signalisations Moleculaires et Neurodegenerescence, Faculte de Medecine, Strasbourg (France)


    The aim of this study was to investigate skeletal muscle denervation using diffusion-weighted magnetic resonance imaging (DWMRI). Sciatic nerve axotomy was performed in a group of nine New Zealand White rabbits, and electromyographic (EMG), pathological, and DWMRI studies were conducted on ipsilateral hamstring muscles 1 and 8 days after axotomy. In addition, DWMRI studies were carried out on leg muscles of ten patients with acute and subacute lumbosacral radiculopathy. High intensity signals on short tau inversion recovery (STIR) magnetic resonance imaging and an increased apparent diffusion coefficient (ADC) were observed in denervated muscles of the animals 1 and 8 days after axotomy as well as in denervated muscles of the patients with radiculopathy. In the clinical study, ADC was 1.26{+-}0.18 x 10{sup -9} m{sup 2}/s in normal muscle and increased to 1.56{+-}0.23 x 10{sup -9} m{sup 2}/s in denervated muscles (p =0.0016). In animals, EMG and muscle pathological studies were normal 1 day after axotomy, and the muscles demonstrated spontaneous activity on EMG and neurogenic atrophy on histological studies 7 days later. This DWMRI study demonstrates that enlargement of extracellular fluid space in muscle denervation is an early phenomenon occurring several days before the appearance of EMG and histological abnormalities. (orig.)

  7. Morphological alterations in small intestine of rats with myenteric plexus denervation. (United States)

    Deniz, M; Kilinç, M; Hatipoğlu, E S


    We aimed to investigate the effect of myenteric denervation by benzalkonium chloride (BAC) on small intestine morphology in the rat, and whether segmental myenteric denervation alters morphology elsewhere in the small intestine. Forty male Sprague-Dawley rats were equally divided into 4 groups: control (0.9% NaCl); denervation (0.062% BAC); chemical inflammation (5% acetic acid), and intraluminal stasis produced by partial obstruction. 28 days after operation tissue samples were taken from the treated segment, 10 cm distal to the treated segment, and 20 cm proximal to the treated segment. Morphological changes and the number of ganglion cells were examined under the light microscope. BAC application reduced the number of myenteric neurons by 85% in the treated segment. Denervation increased villus height and crypt depth in the treated and proximal segments. But changes in muscle thickness were seen throughout the intestine. As a result, although myenteric plexus denervation caused mucosa morphology in the treated and proximal segments, it caused smooth muscle changes throughout the small intestine.

  8. Interaction of thyroid state and denervation on skeletal myosin heavy chain expression (United States)

    Haddad, F.; Arnold, C.; Zeng, M.; Baldwin, K.


    The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

  9. Carotid baroreceptor-muscle sympathetic relation in humans. (United States)

    Rea, R F; Eckberg, D L


    The purpose of this study was to define the relation between carotid distending pressure and muscle sympathetic activity in humans. Carotid baroreceptors of nine healthy subjects were compressed or stretched for 5 s with graded neck pressure or suction (+40 to -65 mmHg), and muscle sympathetic nerve activity was recorded. The results delineate several features of human baroreflex function. First, the carotid-muscle sympathetic relation is well described by an inverse sigmoid function. Second, a linear relation exists between carotid distending pressure and sympathetic outflow over a range of approximately 25 mmHg. Third, sympathetic responses to changes of carotid pressures are asymmetric; increases of sympathetic activity during carotid compression are much greater than reductions of sympathetic activity during carotid stretch. Fourth, at rest, normal subjects operate near the threshold level for sympathetic excitation. Thus the carotid-muscle sympathetic baroreflex is poised to oppose reductions more effectively than elevations of arterial pressure, and the range of pressures over which the reflex is active is wider than thought hitherto.

  10. Effects of renal denervation on vascular remodelling in patients with heart failure and preserved ejection fraction: A randomised control trial (United States)

    Hayward, Carl; Keegan, Jennifer; Gatehouse, Peter D; Rajani, Ronak; Khattar, Rajdeep S; Mohiaddin, Raad H; Rosen, Stuart D; Lyon, Alexander R; di Mario, Carlo


    Objective To assess the effect of renal denervation (RDT) on micro- and macro-vascular function in patients with heart failure with preserved ejection fraction (HFpEF). Design A prospective, randomised, open-controlled trial with blinded end-point analysis. Setting A single-centre London teaching hospital. Participants Twenty-five patients with HFpEF who were recruited into the RDT-PEF trial. Main outcome measures Macro-vascular: 24-h ambulatory pulse pressure, aorta distensibilty (from cardiac magnetic resonance imaging (CMR), aorta pulse wave velocity (CMR), augmentation index (peripheral tonometry) and renal artery blood flow indices (renal MR). Micro-vascular: endothelial function (peripheral tonometry) and urine microalbuminuria. Results At baseline, 15 patients were normotensive, 9 were hypertensive and 1 was hypotensive. RDT did not lower any of the blood pressure indices. Though there was evidence of abnormal vascular function at rest, RDT did not affect these at 3 or 12 months follow-up. Conclusions RDT did not improve markers of macro- and micro-vascular function. PMID:28228942

  11. Abnormal Cardiac Autonomic Regulation in Mice Lacking ASIC3

    Directory of Open Access Journals (Sweden)

    Ching-Feng Cheng


    Full Text Available Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3 is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3−/− mice. Asic3−/− mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3−/− mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3−/− mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

  12. Cardiac Sarcoidosis. (United States)

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo


    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  13. Functional Echomyography: thickness, ecogenicity, contraction and perfusion of the LMN denervated human muscle before and during h-bFES

    Directory of Open Access Journals (Sweden)

    Riccardo Zanato


    Full Text Available Permanent denervated muscles were evaluated by ultrasound to monitor changes in morphology, thickness, contraction-relaxation kinetics and perfusion due to the electrical stimulation program of the Rise2-Italy project. In a case of monolateral lesion, morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete denervation-induced muscle atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third of the denervated muscle, reaching the same value as the contralateral innervated muscle. Contraction-relaxation kinetics, measured by recording the muscle movements during electrical stimulation, showed an abnormal behavior of the chronically denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle. The long-term denervated muscles analyzed with Echo Doppler showed at rest a low resistance arterial flow that became pulsed during and after electrical stimulation. As expected, the ultra sound measured electrical stimulation-induced hyperemia lasted longer than the stimulation period. The higher than normal energy of the delivered electrical stimuli of the Vienna home-based Functional Electrical Stimulation strategy (h-b FES demonstrate that the explored muscles were still almost completely denervated during the one-year of training. In conclusion, this pilot study confirms the usefulness of Functional Echomyography in the follow-up and the positive effects of h-b FES of denervated muscles.

  14. Gender differences in sympathetic nervous system regulation. (United States)

    Hinojosa-Laborde, C; Chapa, I; Lange, D; Haywood, J R


    1. Females are protected against the development of hypertension. The purpose of the current review is to present the evidence for gender differences in the regulation of the sympatho-adrenal nervous system and to determine if these differences support the hypothesis that, in females, the regulation of the sympathetic nervous system (SNS) is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented. 2. The central control of sympatho-adrenal function is different in females and responses vary during the oestral and menstrual cycles. Pathways regulating the SNS appear to be less sensitive to excitatory stimuli and more sensitive to inhibitory stimuli in females compared with males. 3. Gender differences in arterial baroreflex sensitivity suggest that females may have a greater baroreflex sensitivity, such that alterations in blood pressure are more efficiently controlled than in males. Cardiopulmonary reflex inhibition of sympathetic nerve activity is greater in females, possibly resulting in a greater renal excretory function. 4. An attenuated sensitivity to adrenergic nerve stimulation, but not to noradrenaline (NA), suggests that gender differences in noradrenergic neurotransmission may protect females against sympathetic hyperactivity. Gender differences in the regulation of NA release via presynaptic alpha 2-adrenoceptors, the vasoconstrictor response to the cotransmitter neuropeptide Y and the clearance of catecholamines are consistent with this hypothesis. 5. Similarly, attenuated stress-induced increases in plasma catecholamines in women suggest that females are less sensitive and/or less responsive to adrenal medullary activation. This is supported by findings of gender differences in adrenal medullary catecholamine content, release and degradation. 6. We conclude that there is strong evidence that supports the hypothesis that, in females, the regulation of the SNS is altered such that sympatho

  15. [Noradrenaline and glycogen content and the activity of several enzymes of carbohydrate metabolism in normal, embryonic, and partly denervated livers and in hepatomas of the rat]. (United States)

    Iljin, S V; Shanigina, K I; Sydow, G; Parfhenova, N S


    The noradrenaline and glycogen contents as well as hexokinase, glucokinase and glucose-6-phosphatase activities were determined in normal, embryonic and partially denervated (bilateral dissection of the Nervus splanchnicus or Nervus vagus) rat liver and in two transplantable hepatomas. In embryonic liver and hepatomas a strong decrease or complete loss of noradrenaline and glycogen levels and glucokinase and glucose-6-phosphatase activities is demonstrable as compared to the livers of adult animals, while the hexokinase activity is enhanced. Following bilateral splanchnicotomy the glycogen content and hexokinase activity are enhanced; the glucose-6-phosphatase activity is reduced, and the liver does not contain any noradrenaline. Bilateral vagotomy causes decrease of the glycogen content, of the hexokinase and glucokinase activities and an enhancement of glucose-6-phosphatase activity. The results lend support to the idea of antagonistic action of the sympathetic and parasympathetic nervous systems upon several partial reactions of carbohydrate metabolism of liver. In addition, it can be assumed that the alterations of the carbohydrate metabolism demonstrable in hepatomas as compared to normal liver are not solely attributable to disturbance or breakdown of the nervous regulation.

  16. High incidence of secondary hypertension in patients referred for renal denervation

    DEFF Research Database (Denmark)

    Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup


    extracted from letters and documents from referring clinics and from our physical examination. Of the 100 patients included, 68 were men and the mean age was 60 (± 12) years. Office blood pressure was 176 (± 28)/99 (± 19) mmHg and 24-h ambulatory blood pressure 156 (± 20)/88 (± 13) mmHg. The mean number......Percutaneous renal denervation is a new treatment option for patients with resistant hypertension and little is known about the eligibility of patients referred. 100 consecutive patients were referred for renal denervation from March 2011 through September 2012. Clinical data were prospectively...... of antihypertensive agents was 4.0 (± 1.6). Nearly four-fifths (82%) of the patients were categorized as having resistant hypertension based on the criteria stated by The American Heart Association's stated criteria. Nine patients declined interest in renal denervation before completing the clinical workup program...

  17. Mechanisms of accelerated proteolysis in rat soleus muscle atrophy induced by unweighting or denervation (United States)

    Tischler, Marc E.; Kirby, Christopher; Rosenberg, Sara; Tome, Margaret; Chase, Peter


    A hypothesis proposed by Tischler and coworkers (Henriksen et al., 1986; Tischler et al., 1990) concerning the mechanisms of atrophy induced by unweighting or denervation was tested using rat soleus muscle from animals subjected to hindlimb suspension and denervation of muscles. The procedure included (1) measuring protein degradation in isolated muscles and testing the effects of lysosome inhibitors, (2) analyzing the lysosome permeability and autophagocytosis, (3) testing the effects of altering calcium-dependent proteolysis, and (4) evaluating in vivo the effects of various agents to determine the physiological significance of the hypothesis. The results obtained suggest that there are major differences between the mechanisms of atrophies caused by unweighting and denervation, though slower protein synthesis is an important feature common for both.

  18. 肾脏去神经支配治疗对顽固性高血压的心血管、肾脏及代谢获益%Renal Denervation Treatment for Resistant Hypertension

    Institute of Scientific and Technical Information of China (English)



    Renal sympathetic efferent and afferent nerves, which lie within and immediately adjacent to the wall of the renal arteries, contribute to the maintenance of hypertension. Because the causative factors of hypertension change over time, denervation of both efferent and afferent renal nerves should result in long-term attenuation of hypertension. The importance of the renal nerves in hypertensive patients can now be defined with the novel development of percutaneous minimally invasive renal denervation from within the renal artery using radio-frequency energy as a therapeutic strategy. This manuscript reviews the results of renal denervation in patients with resistant essential hypertension reported thus far, emphasizes the safety of this minimally invasive technique, notes new insights about the function of the renal nerves in hypertension that have been learned from these initial studies, considers the many cardiovascular disorders for which this therapy may have clinical value, and suggests potential long-term cardiovascular, renal, and metabolic benefits to hypertensive patients who undergo renal denervation.%肾脏交感的传入和传出神经系统毗邻肾动脉血管壁或存在于肾动脉血管壁内部.肾脏传入、传出交感神经系统的激活,对高血压的维持起重要作用.由于高血压的诱发因素随时间流逝而变化,对肾脏传入及传出神经的去神经治疗可以降低高血压程度.现回顾迄今为止对于顽固的原发性高血压患者的去神经治疗的研究,强调最小能量的侵入性治疗方法的安全性.通过这些研究表明肾脏神经在高血压中的地位.强调这项治疗措施对于心血管系统功能紊乱的治疗可能产生的临床价值,阐明采用肾脏去神经治疗对于高血压患者的心血管、肾脏以及代谢系统获益.

  19. Interaction of Xylamine with peripheral sympathetic neurons

    Energy Technology Data Exchange (ETDEWEB)

    Ransom, R.W.; Waggaman, L.A.; Cho, A.K.


    Xylamine (XYL) administered to intact rats caused a 70-80% reduction in norepinephrine (NE) uptake by the vas deferens but had little or no effect on NE content in that tissue. The vas deferens accumulates /sup 3/H-XYL in vitro by a desmethylimipramine (DMI)-sensitive mechanism. Vasa deferentia from 6-hydroxydopamine (60HDA) pretreated animals exhibited a 80% reduction in both NE content and XYL uptake activity. These results indicate that XYL is taken up by sympathetic nerve terminals and can reduce NE uptake activity without depleting terminals of neurotransmitter. 9 references, 4 tables.

  20. Literary ethnographic writing as sympathetic experiment

    DEFF Research Database (Denmark)

    Dalsgaard, Anne Line

    perhaps only implicitly) of research. But we have no direct access to the subjective world of others and can only inhabit their point of view by way of imagination. Writing literary ethnographic text is one way, I will argue, of experimenting with such sympathetic imagination. By putting together observed...... not propose a radical turn towards literary writing in anthropology. Rather, I suggest that we include the courage of imagination inherent to literature and the accompanying doubt into our existing endeavor, if not for anything else, then for the sake of a more human relationship with our so-called informants....

  1. Does Renal Artery Supply Indicate Treatment Success of Renal Denervation?

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, Axel, E-mail: [University of Erlangen-Nuremberg, Department of Radiology (Germany); Ditting, Tilmann, E-mail: [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany); Sobotka, Paul A., E-mail: [Ohio State University (United States); Veelken, Roland, E-mail:; Schmieder, Roland E., E-mail: [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany); Uder, Michael, E-mail: [University of Erlangen-Nuremberg, Department of Radiology (Germany); Ott, Christian, E-mail: [University of Erlangen-Nuremberg, Department of Nephrology and Hypertension (Germany)


    PurposeRenal denervation (RDN) emerged as an innovative interventional antihypertensive therapy. With the exception of pretreatment blood pressure (BP) level, no other clear predictor for treatment efficacy is yet known. We analyzed whether the presence of multiple renal arteries has an impact on BP reduction after RDN.MethodsFifty-three patients with treatment-resistant hypertension (office BP {>=} 140/90 mmHg and 24-h ambulatory BP monitoring ({>=}130/80 mmHg) underwent bilateral catheter-based RDN. Patients were stratified into one-vessel (OV) (both sides) and at least multivessel (MV) supply at one side. Both groups were treated on one vessel at each side; in case of multiple arteries, only the dominant artery was treated on each side.ResultsBaseline clinical characteristics (including BP, age, and estimated glomerular filtration rate) did not differ between patients with OV (n = 32) and MV (n = 21). Office BP was significantly reduced in both groups at 3 months (systolic: OV -15 {+-} 23 vs. MV -16 {+-} 20 mmHg; diastolic: OV -10 {+-} 12 vs. MV -8 {+-} 11 mmHg, both p = NS) as well as 6 months (systolic: OV -18 {+-} 18 vs. MV -17 {+-} 22 mmHg; diastolic: OV -10 {+-} 10 vs. -10 {+-} 12 mmHg, both p = NS) after RDN. There was no difference in responder rate (rate of patients with office systolic BP reduction of at least 10 mmHg after 6 months) between the groups.ConclusionIn patients with multiple renal arteries, RDN of one renal artery-namely, the dominant one-is sufficient to induce BP reduction in treatment-resistant hypertension.

  2. Age-related changes in rhythmic electrical activity in the cervical sympathetic trunk in rats and cats. (United States)

    Maslyukov, P M; Korzina, M B; Emanuilov, A I


    Baseline electrical activity in the cervical sympathetic trunk was studied in neonatal rats and cats and at ages 10, 20, and 30 days and two and six months, using spectral analysis. Rats from the neonatal period to the end of the first month of life and cats to 20 days of life showed increases at the amplitudes of electrical oscillations. From birth, all animals showed oscillations in the respiratory and cardiac rhythms. From day 20, frequencies with a cardiac component in rats dominated the power spectrum. The proportion of other frequencies, not associated with the cardiac or respiratory rhythms, was smaller. In cats, unlike the situation in rats, there were no age-related changes in the spectral composition of baseline electrical activity. High-frequency oscillations were recorded in cats from birth.

  3. The Human Sympathetic Nervous System Response to Spaceflight (United States)

    Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David


    The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

  4. The oestrogenized rat myometrium inhibits organotypic sympathetic reinnervation. (United States)

    Brauer, M M; Chávez-Genaro, R; Richeri, A; Viettro, L; Frias, A I; Burnstock, G; Cowen, T


    Chronic administration of oestrogen to rats during the infantile/prepubertal period provokes, at 28 days of age, complete loss of noradrenaline-labelled intrauterine sympathetic nerves. It is not known whether oestrogen inhibits the growth or causes the degeneration of developing uterine sympathetic nerves, or whether the uterus recovers its innervation following cessation of infantile/prepubertal oestrogen treatment. In the present study, we analysed the time-course of the effects of oestrogen on the development of uterine sympathetic nerves in the rat, using histochemical methods. In addition, the pattern of sympathetic reinnervation of the uterus of intact and ovariectomised females was assessed 3 and 6 months after cessation of chronic oestrogen treatment. The ability of sympathetic nerves to reinnervate the oestrogenized uterine tissue was assessed in intraocular transplants of uterine myometrium into ovariectomised host rats. Early exposure to oestrogen did not inhibit the approach of sympathetic nerves to the uterus, but prevented the normal growth and maturation of intrauterine sympathetic fibres and abolished the innervation that reached the organ before initiation of treatment. Three or six months following cessation of oestrogen treatment, most of the sympathetic nerves were restricted to the mesometrium and mesometrial entrance, whereas intrauterine innervation remained persistently depressed as a consequence of a sustained oestrous-like state provoked by ovarian dysfunction (polycystic ovary). An organotypic regrowth of uterine sympathetic nerves was observed in ovariectomised infantile/prepubertal oestrogen-treated animals. After 5 weeks in oculo, the innervation of oestrogenized myometrial transplants was reduced by 50%, and substantial changes in the pattern of reinnervation were observed. In control transplants, 86% of the nerves were terminal varicose myometrial and perivascular nerve fibres, whereas 14% were preterminal nerve bundles. In

  5. Chronic bilateral renal denervation attenuates renal injury in a transgenic rat model of diabetic nephropathy. (United States)

    Yao, Yimin; Fomison-Nurse, Ingrid C; Harrison, Joanne C; Walker, Robert J; Davis, Gerard; Sammut, Ivan A


    Bilateral renal denervation (BRD) has been shown to reduce hypertension and improve renal function in both human and experimental studies. We hypothesized that chronic intervention with BRD may also attenuate renal injury and fibrosis in diabetic nephropathy. This hypothesis was examined in a female streptozotocin-induced diabetic (mRen-2)27 rat (TGR) shown to capture the cardinal features of human diabetic nephropathy. Following diabetic induction, BRD/sham surgeries were conducted repeatedly (at the week 3, 6, and 9 following induction) in both diabetic and normoglycemic animals. Renal denervation resulted in a progressive decrease in systolic blood pressure from first denervation to termination (at 12 wk post-diabetic induction) in both normoglycemic and diabetic rats. Renal norepinephrine content was significantly raised following diabetic induction and ablated in denervated normoglycemic and diabetic groups. A significant increase in glomerular basement membrane thickening and mesangial expansion was seen in the diabetic kidneys; this morphological appearance was markedly reduced by BRD. Immunohistochemistry and protein densitometric analysis of diabetic innervated kidneys confirmed the presence of significantly increased levels of collagens I and IV, α-smooth muscle actin, the ANG II type 1 receptor, and transforming growth factor-β. Renal denervation significantly reduced protein expression of these fibrotic markers. Furthermore, BRD attenuated albuminuria and prevented the loss of glomerular podocin expression in these diabetic animals. In conclusion, BRD decreases systolic blood pressure and reduces the development of renal fibrosis, glomerulosclerosis, and albuminuria in this model of diabetic nephropathy. The evidence presented strongly suggests that renal denervation may serve as a therapeutic intervention to attenuate the progression of renal injury in diabetic nephropathy.

  6. Chemistry and biology of radiotracers that target changes in sympathetic and parasympathetic nervous systems in heart disease. (United States)

    Eckelman, William C; Dilsizian, Vasken


    Following the discovery of the sympathetic and parasympathetic nervous system, numerous adrenoceptor drugs were radiolabeled and potent radioligands were prepared in order to image the β-adrenergic and the muscarinic systems. But the greatest effort has been in preparing noradrenaline analogs, such as norepinephrine, (11)C-metahydroxyephedrine, and (123)I-metaiodobenzylguanidine that measure cardiac sympathetic nerve varicosities. Given the technical and clinical challenges in designing and validating targeted adrenoceptor-binding radiotracers, namely the heavily weighted flow dependence and relatively low target-to-background ratio, both requiring complicated mathematic analysis, and the inability of targeted adrenoceptor radioligands to have an impact on clinical care of heart disease, the emphasis has been on radioligands monitoring the norepinephrine pathway. The chemistry and biology of such radiotracers, and the clinical and prognostic impact of these innervation imaging studies in patients with heart disease, are examined.

  7. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  8. Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle (United States)

    Henriksen, Erik J.; Rodnick, Kenneth J.; Mondon, Carl E.; James, David E.; Holloszy, John O.


    The study is intended to test the hypothesis that the decreased capacity for glucose transport in the denervated rat soleus and the increased capacity for glucose transport in the unweighted rat soleus are related to changes in the expression of the regulatable glucose transporter protein in skeletal muscle (GLUT-4). Results obtained indicate that altered GLUT-4 expression may be a major contributor to the changes in insulin-stimulated glucose transport that are observed with denervation and unweighting. It is concluded that muscle activity is an important factor in the regulation of the GLUT-4 expression in skeletal muscle.

  9. Myenteric denervation in gastric carcinogenesis: differential modulation of nitric oxide and annexin-A1



    This study evaluated the properties of endogenous nitric oxide synthases (NOS) and annexin-A1 (ANXA1) and determined how they can be exploited in the N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and myenteric denervation model. Male Wistar rats were treated with MNNG and/or aminoguanidine (AG) for 20 weeks. In another set of experiments, rats with nondenervated and denervated stomachs were treated with MNNG or water for 28 weeks. Fragments of the pyloric region we...

  10. Role of the autonomic nervous system in modulating cardiac arrhythmias. (United States)

    Shen, Mark J; Zipes, Douglas P


    The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

  11. Role of Nuclear Medicine in the cardiac resinchronization therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Simone Cristina Soares, E-mail: [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)


    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)

  12. Chain Reconnections observed in Sympathetic Eruptions

    CERN Document Server

    Joshi, Navin Chandra; Magara, Tetsuya; Guo, Yang; Aulanier, Guillaume


    The nature of various plausible causal links between sympathetic events is still a controversial issue. In this work, we present multi-wavelength observations of sympathetic eruptions, associated flares and coronal mass ejections (CMEs) occurring on 2013 November 17 in two close-by active regions. Two filaments i.e., F1 and F2 are observed in between the active regions. Successive magnetic reconnections, caused by different reasons (flux cancellation, shear and expansion) have been identified during the whole event. The first reconnection occurred during the first eruption via flux cancellation between the sheared arcades overlying filament F2, creating a flux rope and leading to the first double ribbon solar flare. During this phase we observed the eruption of overlaying arcades and coronal loops, which leads to the first CME. The second reconnection is believed to occur between the expanding flux rope of F2 and the overlying arcades of the filament F1. We suggest that this reconnection destabilized the equi...

  13. Sympathetic adaptations to one-legged training (United States)

    Ray, C. A.


    The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.

  14. Reflex sympathetic dystrophy: Early treatment and psychological aspects

    NARCIS (Netherlands)

    Geertzen, J.H.B.; De Bruijn, H.; De Bruijn-Kofman, A.T.; Arendzen, J.H.


    We report the results of two prospective studies of early treatment and psychological aspects in a series of 26 patients with sympathetic reflex dystrophy of the hand in which treatment was started within 3 months after diagnosis. Ismelin blocks is an often used therapy in sympathetic reflex dystrop

  15. Sympathetic hyperactivity - A hidden enemy in chronic kidney disease patients

    NARCIS (Netherlands)

    Blankestijn, Peter J.


    Chronic kidney disease is often characterized by the presence of sympathetic hyperactivity. The aim of this brief review is to summarize available knowledge on the pathogenesis of sympathetic hyperactivity and to discuss its clinical relevance, the consequences of this knowledge for the choice of tr

  16. Lower limb pain in sympathetic-sensory coupling

    Institute of Scientific and Technical Information of China (English)

    Hongjun Yang; Kairun Peng; Sanjue Hu; Li Xuan


    Previous studies have shown that sympathetic nerves are related to certain types of pain, and this phenomenon is referred to as sympathetic-sensory coupling. Chronic pain resulting from nerve injury can be exacerbated by sympathetic stimulation or relieved by sympathetic inhibition. In the present study, the correlation between pain and sympathetic nerves was analyzed in patients with severe pain in lower limbs, as well as in a chronically compressed dorsal root ganglion (CCD) rat model (model of low back pain and sciatica). Patients with severe pain in the lower limbs underwent chemical lumbar sympathectomy (CLS), and the analgesic effects of CLS were compared with painkillers. Results demonstrated significantly relieved lower limb pain following CLS, and the analgesic effects of CLS were superior to those seen with painkillers. In the CCD rat model, dorsal root ganglion neuronal activity significantly increased as a result of electrical stimulation to the sympathetic nerves. These results suggest that sympathetic nerves are closely associated with pain and sympathetic-sensory coupling is likely in lower limb pain in both patients and rat models of CCD.

  17. Persistent muscle fiber regeneration in long term denervation. Past, present, future

    Directory of Open Access Journals (Sweden)

    Ugo Carraro


    Full Text Available Despite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES. Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb. Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest

  18. Dynamic Radiographic Analysis of Sympathetic Cervical Spondylosis Instability

    Institute of Scientific and Technical Information of China (English)

    Jun Qian; Ye Tian; Gui-xing Qiu; Jian-hua Hu


    Objective To investigate the correlation between subaxial cervical spine instability and cervical spondylotic sympathetic symptoms as well as the difference of cervical spondylotic subaxial instability between male and female patients. Methods We analyzed retrospectively 318 surgical cases of cervical spondylosis treated at Department of Orthopedic Surgery of Peking Union Medical College Hospital between July 2003 and December 2007. All cases were divided into group A without sympathetic symptoms (n=284) and group B with sympathetic symptoms (n=34). Angular and horizontal translation values between two adjacent vertebral bodies from C2 to C7 were measured separately on hyperflexion and hyperextension lateral cervical spine radiographs. Fisher's exact test was used to evaluate the correlation between subaxial cervical instability and sympathetic symptoms. Intragroup correlation between patient gender and subaxial cervical instability was also evaluated. Results Subaxial instability incidences in groups A and B were 21.8% (62/284) and 55.9% (19/34), respectively. Statistical analysis indicated a definite correlation between subaxial cervical instability and sympathetic symptoms (P=0.000). Among patients without sympathetic symptoms, subaxial instability incidences were 21.4% (37/173) in males and 22.5% (25/111) in females, respectively (P=0.883). While among patients with sympathetic symptoms, subaxial instability incidences were 27.3% (3/11) in males and 69.6% (16/23) in females, respectively, indicating significant difference (P=0.030). Subaxial instability was most commonly seen at C4-C5 intervertebral space in sympathetic cervical spondylosis patients. Conclusions High correlation exists between subaxial cervical spine instability and cervical spondylotic sympathetic symptoms, especially in female patients. Hyperextension and hyperflexion radiographs of cervical spine are important to assess sympathetic cervical spondylotic subaxial instability.

  19. Stimulation of NTS A1 adenosine receptors differentially resets baroreflex control of regional sympathetic outputs. (United States)

    Scislo, Tadeusz J; Ichinose, Tomoko K; O'Leary, Donal S


    Previously we showed that pressor and differential regional sympathoexcitatory responses (adrenal > renal >/= lumbar) evoked by stimulation of A(1) adenosine receptors located in the nucleus of the solitary tract (NTS) were attenuated/abolished by baroreceptor denervation or blockade of glutamatergic transmission in the NTS, suggesting A(1) receptor-elicited inhibition of glutamatergic transmission in baroreflex pathways. Therefore we tested the hypothesis that stimulation of NTS A(1) adenosine receptors differentially inhibits/resets baroreflex responses of preganglionic adrenal (pre-ASNA), renal (RSNA), and lumbar (LSNA) sympathetic nerve activity. In urethane-chloralose-anesthetized male Sprague-Dawley rats (n = 65) we compared baroreflex-response curves (iv nitroprusside and phenylephrine) evoked before and after bilateral microinjections into the NTS of A(1) adenosine receptor agonist (N(6)-cyclopentyladenosine, CPA; 0.033-330 pmol/50 nl). CPA evoked typical dose-dependent pressor and differential sympathoexcitatory responses and similarly shifted baroreflex curves for pre-ASNA, RSNA, and LSNA toward higher mean arterial pressure (MAP) in a dose-dependent manner; the maximal shifts were 52.6 +/- 2.8, 48.0 +/- 3.6, and 56.8 +/- 6.7 mmHg for pre-ASNA, RSNA, and LSNA, respectively. These shifts were not a result of simple baroreceptor resetting because they were two to three times greater than respective increases in baseline MAP evoked by CPA. Baroreflex curves for pre-ASNA were additionally shifted upward: the maximal increases of upper and lower plateaus were 41.8 +/- 16.4% and 45.3 +/- 8.7%, respectively. Maximal gain (%/mmHg) measured before vs. after CPA increased for pre-ASNA (3.0 +/- 0.6 vs. 4.9 +/- 1.3), decreased for RSNA (4.1 +/- 0.6 vs. 2.3 +/- 0.3), and remained unaltered for LSNA (2.1 +/- 0.2 vs. 2.0 +/- 0.1). Vehicle control did not alter the baroreflex curves. We conclude that the activation of NTS A(1) adenosine receptors differentially inhibits

  20. Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation

    Directory of Open Access Journals (Sweden)

    Anna R. Chambers


    Full Text Available Neurons at higher stages of sensory processing can partially compensate for a sudden drop in input from the periphery through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where > 95% of synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore the cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, cortical processing and perception recover despite the absence of an auditory brainstem response (ABR or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC, an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the auditory cortex (ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB of awake mice. Sound-driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory

  1. Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation (United States)

    Chambers, Anna R.; Salazar, Juan J.; Polley, Daniel B.


    Neurons at higher stages of sensory processing can partially compensate for a sudden drop in peripheral input through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where >95% of afferent synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, auditory cortex (ACtx) processing and perception recover despite the absence of an auditory brainstem response (ABR) or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC), an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB) of awake mice. Sound driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory plasticity at the level of the

  2. Sympathetic predominance is associated with impaired endothelial progenitor cells and tunneling nanotubes in controlled-hypertensive patients. (United States)

    de Cavanagh, Elena M V; González, Sergio A; Inserra, Felipe; Forcada, Pedro; Castellaro, Carlos; Chiabaut-Svane, Jorge; Obregón, Sebastián; Casarini, María Jesús; Kempny, Pablo; Kotliar, Carol


    Early endothelial progenitor cells (early EPC) and late EPC are involved in endothelial repair and can rescue damaged endothelial cells by transferring organelles through tunneling nanotubes (TNT). In rodents, EPC mobilization from the bone marrow depends on sympathetic nervous system activity. Indirect evidence suggests a relation between autonomic derangements and human EPC mobilization. We aimed at testing whether hypertension-related autonomic imbalances are associated with EPC impairment. Thirty controlled-essential hypertensive patients [systolic blood pressure/diastolic blood pressure = 130(120-137)/85(61-88) mmHg; 81.8% male] and 20 healthy normotensive subjects [114(107-119)/75(64-79) mmHg; 80% male] were studied. Mononuclear cells were cultured on fibronectin- and collagen-coated dishes for early EPC and late EPC, respectively. Low (LF)- and high (HF)-frequency components of short-term heart rate variability were analyzed during a 5-min rest, an expiration/inspiration maneuver, and a Stroop color-word test. Modulations of cardiac sympathetic and parasympathetic activities were evaluated by LF/HF (%) and HF power (ms(2)), respectively. In controlled-hypertensive patients, the numbers of early EPC, early EPC that emitted TNT, late EPC, and late EPC that emitted TNT were 41, 77, 50, and 88% lower than in normotensive subjects (P hypertensive patients, late EPC number was positively associated with cardiac parasympathetic reserve during the expiration/inspiration maneuver (rho = 0.45, P = 0.031) and early EPC with brachial flow-mediated dilation (rho = 0.655; P = 0.049); also, late TNT number was inversely related to cardiac sympathetic response during the stress test (rho = -0.426, P = 0.045). EPC exposure to epinephrine or norepinephrine showed negative dose-response relationships on cell adhesion to fibronectin and collagen; both catecholamines stimulated early EPC growth, but epinephrine inhibited late EPC growth. In controlled-hypertensive patients

  3. Cardiac autonomic nervous system activity in obesity. (United States)

    Liatis, Stavros; Tentolouris, Nikolaos; Katsilambros, Nikolaos


    The development of obesity is caused by a disturbance of energy balance, with energy intake exceeding energy expenditure. As the autonomic nervous system (ANS) has a role in the regulation of both these variables, it has become a major focus of investigation in the fields of obesity pathogenesis. The enhanced cardiac sympathetic drive shown in most of the studies in obese persons might be due to an increase in their levels of circulating insulin. The role of leptin needs further investigation with studies in humans. There is a blunted response of the cardiac sympathetic nervous system (SNS) activity in obese subjects after consumption of a carbohydrate-rich meal as well as after insulin administration. This might be due to insulin resistance. It is speculated that increased SNS activity in obesity may contribute to the development of hypertension in genetically susceptible individuals. It is also speculated that the increase in cardiac SNS activity under fasting conditions in obesity may be associated with high cardiovascular morbidity and mortality.

  4. Microinjection of glycine into the hypothalamic paraventricular nucleus produces diuresis, natriuresis, and inhibition of central sympathetic outflow. (United States)

    Krowicki, Zbigniew K; Kapusta, Daniel R


    Strychnine-sensitive glycine receptors and glycine-immunoreactive fibers are expressed in the hypothalamic paraventricular nucleus (PVN), yet the functional significance of this innervation is unclear. Therefore, these studies examined the changes in cardiovascular and renal function and renal sympathetic nerve activity (RSNA) produced by the microinjection of glycine (5 and 50 nmol) into the PVN of conscious Sprague-Dawley rats. Microinjection of glycine into, but not outside of, the PVN dose-dependently increased urine flow rate and urinary sodium excretion and decreased RSNA. At the higher dose, PVN glycine also decreased heart rate; neither 5 nor 50 nmol PVN glycine altered mean arterial pressure. The glycine (50 nmol)-evoked diuresis and natriuresis were abolished in rats continuously infused intravenously with [Arg(8)]-vasopressin. Furthermore, chronic bilateral renal denervation prevented the bradycardia and diuresis to PVN glycine and blunted the natriuresis. In other studies, unilateral PVN pretreatment with the glycine receptor antagonist strychnine (1.6 nmol) prevented the effects of PVN glycine (50 nmol) on heart rate, RSNA, and renal excretory function. When microinjected bilaterally, PVN strychnine (1.6 nmol per site) evoked a significant increase in heart rate and RSNA without altering renal excretory function. These findings demonstrate that in conscious rats glycine acts in the PVN to enhance the renal excretion of water and sodium and decrease central sympathetic outflow to the heart and kidneys. Although endogenous PVN glycine inputs elicit a tonic control of heart rate and RSNA, the renal excretory responses to PVN glycine seem to be caused primarily by the inhibition of arginine vasopressin secretion.

  5. Expression of TGF-β1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice. (United States)

    Liu, Fei; Tang, Weifang; Chen, Donghui; Li, Meng; Gao, Yinna; Zheng, Hongliang; Chen, Shicai


    Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis, which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after denervation (p muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

  6. miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy

    Directory of Open Access Journals (Sweden)

    Gang Li


    Full Text Available Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle and a typical fast muscle (tibialis anterior muscle at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the final targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation. Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

  7. Denervation syndromes of the shoulder girdle: MR imaging with electrophysiologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Bredella, M.A.; Wischer, T.K.; Stork, A.; Genant, H.K. [Dept. of Radiology, University of California, San Francisco (United States); Tirman, P.F.J. [San Francisco Magnetic Resonance Center, CA (United States); Fritz, R.C. [National Orthopaedic Imaging Associates, Greenbrae, CA (United States)


    Objective. To investigate the use of MR imaging in the characterization of denervated muscle of the shoulder correlated with electrophysiologic studies.Design and patients. We studied with MR imaging five patients who presented with shoulder weakness and pain and who underwent electrophysiologic studies. On MR imaging the distribution of muscle edema and fatty infiltration was recorded, as was the presence of masses impinging on a regional nerve.Results. Acute/subacute denervation was best seen on T2-weighted fast spin-echo images with fat saturation, showing increased SI related to neurogenic edema. Chronic denervation was best seen on T1-weighted spin-echo images, demonstrating loss of muscle bulk and diffuse areas of increased signal intensity within the muscle. Three patients showed MR imaging and electrophysiologic findings of Parsonage Turner syndrome. One patient demonstrated an arteriovenous malformation within the spinoglenoid notch, impinging on the suprascapular nerve with associated atrophy of the infraspinatus muscle. The fifth patient demonstrated fatty atrophy of the teres minor muscle caused by compression by a cyst of the axillary nerve and electrophysiologic findings of an incomplete axillary nerve block.Conclusion. MR imaging is useful in detecting and characterizing denervation atrophy and neurogenic edema in shoulder muscles. MR imaging can provide additional information to electrophysiologic studies by estimating the age (acute/chronic) and identifying morphologic causes for shoulder pain and atrophy. (orig.)

  8. Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands

    NARCIS (Netherlands)

    Henry, Thea L.; Brouwer, de Bonnie F.E.; Keep, van Marjolein M.L.; Blankestijn, Peter J.; Bots, Michiel L.; Koffijberg, Hendrik


    Objectives: Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the per

  9. Innervation of the elbow joint: Is total denervation possible? A cadaveric anatomic study. (United States)

    De Kesel, Renata; Van Glabbeek, Francis; Mugenzi, Dominique; De Vos, Joris; Vermeulen, Katrien; Van Renterghem, Debbie; Bortier, Hilde; Schuind, Frédéric


    The aim of this anatomical study was to find out if total denervation of the elbow joint is technically feasible. The endbranches of the brachial plexus of eight fresh-frozen upper arm cadavers were dissected with optical loupe magnification. All major nerves of the upper limb (except the axillary and the medial brachial cutaneous nerve) give some terminal articular endbranches to the elbow. The articular endbranches arise from muscular endbranches, cutaneous endbranches, or arise straight from the main nerves of the brachial plexus. A topographic diagram was made of the different nerves innervating the elbow joint. The ulno-posterior part of the elbow is innervated by the ulnar nerve and some branches of medial antebrachial cutaneous nerve. The radial-posterior part of the elbow is innervated exclusively by the radial nerve. The ulno-anterior part of the elbow is innervated by the median nerve and the musculocutaneous nerve. The radio-anterior part of the elbow is innervated by the radial nerve and the musculocutaneous nerve. These elbow innervation findings are relevant to both anatomical and clinical field as they provide evidence that the total denervation of the elbow joint is impossible. Nevertheless, partial denervation, like denervation of the lateral epicondyle or the ulnar part of elbow, is technically possible.

  10. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis

    DEFF Research Database (Denmark)

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting


    ) regulation in the development of hypertension in rats with hydronephrosis. Hydronephrosis was induced by partial unilateral ureteral obstruction (PUUO) in young rats. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high and low salt diets. Renal...

  11. Clinical Results of Carotid Denervation by Adventitial Stripping in Carotid Sinus Syndrome

    NARCIS (Netherlands)

    Toorop, R. J.; Scheltinga, M. R.; Huige, M. C.; Moll, F. L.


    Aims: Older patients with spells of syncope may suffer from a carotid sinus syndrome (CSS). Patients with invalidating CSS routinely receive pacemaker treatment. This study evaluated the safety and early outcome of a surgical technique termed carotid denervation by adventitial stripping for CSS trea

  12. Denervated hippocampus provides a favorable microenvironment for neuronal differentiation of endogenous neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Xiao Han; Xiang Cheng; Xue-feng Tan; He-yan Zhao; Xin-hua Zhang


    Fimbria-fornix transection induces both exogenous and endogenous neural stem cells to differentiate into neurons in the hippocampus. This indicates that the denervated hippocampus provides an environment for neuronal differentiation of neural stem cells. However, the pathways and mechanisms in this process are still unclear. Seven days after ifmbria fornix transection, our reverse transcription polymerase chain reaction, western blot assay, and enzyme linked immunosorbent assay results show a signiifcant increase in ciliary neurotrophic factor mRNA and protein expression in the denervated hippocampus. Moreover, neural stem cells derived from hippocampi of fetal (em-bryonic day 17) Sprague-Dawley rats were treated with ciliary neurotrophic factor for 7 days, with an increased number of microtubule associated protein-2-positive cells and decreased number of glial ifbrillary acidic protein-positive cells detected. Our results show that cili-ary neurotrophic factor expression is up-regulated in the denervated hippocampus, which may promote neuronal differentiation of neural stem cells in the denervated hippocampus.

  13. 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.

  14. PPM1B and P-IKKβ expression levels correlated inversely with rat gastrocnemius atrophy after denervation

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Jian; Liang, Bing-Sheng [Department of Orthopedics, the Second Hospital, Shanxi Medical University, Taiyuan (China)


    Activated inhibitor of nuclear factor-κB kinase β (IKKβ) is necessary and sufficient for denervated skeletal muscle atrophy. Although several studies have shown that Mg{sup 2+}/Mn{sup 2+}-dependent protein phosphatase 1B (PPM1B) inactivated IKKβ, few studies have investigated the role of PPM1B in denervated skeletal muscle. In this study, we aim to explore the expression and significance of PPM1B and phosphorylated IKKβ (P-IKKβ) during atrophy of the denervated gastrocnemius. Thirty young adult female Wistar rats were subjected to right sciatic nerve transection and were sacrificed at 0 (control), 2, 7, 14, and 28 days after denervation surgery. The gastrocnemius was removed from both the denervated and the contralateral limb. The muscle wet weight ratio was calculated as the ratio of the wet weight of the denervated gastrocnemius to that of the contralateral gastrocnemius. RT-PCR and Western blot analysis showed that mRNA and protein levels of PPM1B were significantly lower than those of the control group at different times after the initiation of denervation, while P-IKKβ showed the opposite trends. PPM1B protein expression persistently decreased while P-IKKβ expression persistently increased for 28 days after denervation. PPM1B expression correlated negatively with P-IKKβ expression by the Spearman test, whereas decreasing PPM1B expression correlated positively with the muscle wet weight ratio. The expression levels of PPM1B and P-IKKβ were closely associated with atrophy in skeletal denervated muscle. These results suggest that PPM1B and P-IKKβ could be markers in skeletal muscle atrophy.

  15. Sympathetic cooling of nanospheres with cold atoms (United States)

    Montoya, Cris; Witherspoon, Apryl; Ranjit, Gambhir; Casey, Kirsten; Kitching, John; Geraci, Andrew


    Ground state cooling of mesoscopic mechanical structures could enable new hybrid quantum systems where mechanical oscillators act as transducers. Such systems could provide coupling between photons, spins and charges via phonons. It has recently been shown theoretically that optically trapped dielectric nanospheres could reach the ground state via sympathetic cooling with trapped cold atoms. This technique can be beneficial in cases where cryogenic operation of the oscillator is not practical. We describe experimental advances towards coupling an optically levitated dielectric nanosphere to a gas of cold Rubidium atoms. The sphere and the cold atoms are in separate vacuum chambers and are coupled using a one-dimensional optical lattice. This work is partially supported by NSF, Grant Nos. PHY-1205994,PHY-1506431.

  16. Do sympathetic nerves release noradrenaline in "quanta"? (United States)

    Stjärne, L


    The discovery of excitatory junction potentials (EJPs) in guinea-pig vas deferens by Burnstock and Holman (1960) showed for the first time that a sympathetic transmitter, now known to be ATP, is secreted in "quanta". As it was assumed at the time that EJPS are triggered by noradrenaline, this discovery led to attempts to use the fractional overflow of noradrenaline from sympathetically innervated tissues to assess, indirectly, the number of noradrenaline molecules in the average "quantum". The basic finding was that each pulse released 1/50000 of the tissue content of noradrenaline, when reuptake was blocked and prejunctional alpha(2)-adrenoceptors were intact. This provided the constraints, two extreme alternatives: (i) each pulse releases 0.2-3% of the content of a vesicle from all varicosities, or (ii) each pulse releases the whole content of a vesicle from 0.2 to 3% of the varicosities. New techniques have made it possible to address questions about the release probability in individual sites, or the "quantal" size, more directly. Results by optical (comparison of the labelling of SV2 and synaptotagmin, proteins in the membrane of transmitter vesicles), electrophysiological (excitatory junction currents, EJCs, at single visualized varicosities) and amperometric (the noradrenaline oxidation current at a carbon fibre electrode) methods reveal that transmitter exocytosis in varicosities is intermittent. The EJC and noradrenaline oxidation current responses (in rat arteries) to a train of single pulses were observed to be similar in intermittency and amplitude fluctuation. This suggests that they are caused by exocytosis of single or very few "quanta" of ATP and noradrenaline, respectively, equal to the contents of single vesicles, from a small population of release sites. These findings support, but do not conclusively prove the validity of the "intermittent" model of noradrenaline release. The question if noradrenaline is always secreted in packets of preset size


    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Navin Chandra; Magara, Tetsuya [School of Space Research, Kyung Hee University, Yongin, Gyeonggi-Do, 446-701 (Korea, Republic of); Schmieder, Brigitte; Aulanier, Guillaume [LESIA, Observatoire de Paris, PSL Research University, CNRS Sarbonne Universités, Univ. Paris 06, Univ. Paris Diderot, Sorbonne Paris Cité, 5 place Jules Jansson, F-92195 Meudon (France); Guo, Yang, E-mail:, E-mail: [School of Astronomy and Space Science, Nanjing University, 210023 Nanjing (China)


    The nature of various plausible causal links between sympathetic events is still a controversial issue. In this work, we present multiwavelength observations of sympathetic eruptions, associated flares, and coronal mass ejections (CMEs) occurring on 2013 November 17 in two close active regions. Two filaments, i.e., F1 and F2, are observed in between the active regions. Successive magnetic reconnections, caused for different reasons (flux cancellation, shear, and expansion) have been identified during the whole event. The first reconnection occurred during the first eruption via flux cancellation between the sheared arcades overlying filament F2, creating a flux rope and leading to the first double-ribbon solar flare. During this phase, we observed the eruption of overlying arcades and coronal loops, which leads to the first CME. The second reconnection is believed to occur between the expanding flux rope of F2 and the overlying arcades of filament F1. We suggest that this reconnection destabilized the equilibrium of filament F1, which further facilitated its eruption. The third stage of reconnection occurred in the wake of the erupting filament F1 between the legs of the overlying arcades. This may create a flux rope and the second double-ribbon flare and a second CME. The fourth reconnection was between the expanding arcades of the erupting filament F1 and the nearby ambient field, which produced the bi-directional plasma flows both upward and downward. Observations and a nonlinear force-free field extrapolation confirm the possibility of reconnection and the causal link between the magnetic systems.

  18. Cardiac cameras. (United States)

    Travin, Mark I


    Cardiac imaging with radiotracers plays an important role in patient evaluation, and the development of suitable imaging instruments has been crucial. While initially performed with the rectilinear scanner that slowly transmitted, in a row-by-row fashion, cardiac count distributions onto various printing media, the Anger scintillation camera allowed electronic determination of tracer energies and of the distribution of radioactive counts in 2D space. Increased sophistication of cardiac cameras and development of powerful computers to analyze, display, and quantify data has been essential to making radionuclide cardiac imaging a key component of the cardiac work-up. Newer processing algorithms and solid state cameras, fundamentally different from the Anger camera, show promise to provide higher counting efficiency and resolution, leading to better image quality, more patient comfort and potentially lower radiation exposure. While the focus has been on myocardial perfusion imaging with single-photon emission computed tomography, increased use of positron emission tomography is broadening the field to include molecular imaging of the myocardium and of the coronary vasculature. Further advances may require integrating cardiac nuclear cameras with other imaging devices, ie, hybrid imaging cameras. The goal is to image the heart and its physiological processes as accurately as possible, to prevent and cure disease processes.

  19. Cyclic Adenosine Monophosphate Accumulation and beta-Adrenergic Binding in Unweighted and Denervated Rat Soleus Muscle (United States)

    Kirby, Christopher R.; Woodman, Christopher R.; Woolridge, Dale; Tischler, Marc E.


    Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases beta-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and beta-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a p-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular (IM) injection) to a greater degree (P less than .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased beta-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (B(sub max)) for iodo-125(-)-pindolol in particulate preparations of unweighted (420 x 10(exp -18) mol/mg muscle) than of control or denervated muscles (285 x 10(exp-18) mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished CAMP accumulation in the presence of theophylline in unweighted muscle (-66% +/- 2%) more than in controls (-42% +'- 6%, P less than .001). These results show that insulin affects CAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.

  20. Effect of renal denervation on the compensatory renal growth following nephrectomy in the cat. (United States)

    Wada, T; Matsukawa, K; Murata, J; Matsumoto, M; Nakashima, K


    The purpose of this study was to clarify the effect of denervation on the mass of the remaining kidney with or without unilateral nephrectomy using adult cats. The animals were divided into 4 groups: (1) control group, the weights of the right and left kidneys were measured intact in 5 cats; (2) nephrectomy group (Nx, n = 5 cats), the right kidney was removed and the left kidney was weighed 3-5 d after nephrectomy; (3) nephrectomy and denervation group (Nx+Dx, n = 7 cats), the left kidney was weighed on the 7th day after surgery in which the left kidney was denervated and the right kidney was removed; and (4) denervation group (Dx+Dx, n = 5 cats), both kidneys were weighed on the 7th day after denervation of the kidneys. In the control group, the left and right kidney weights per body weight (LKW and RKW) were the same (LKW, 0.74 +/- 0.06%; RKW, 0. 74 +/- 0.07%). In the Nx group, LKW increased to 0.90 +/- 0.03% 3-5 d after nephrectomy, although RKW of the removed kidney was 0.66 +/- 0.01%. In the Nx+Dx group, LKW increased to 0.97 +/- 0.15%, which was similar to that of the Nx group. In the Dx+Dx group, LKW (0.56 +/- 0.05%) and RKW (0.54 +/- 0.05%) were significantly less than those in the control group. We conclude that the renal nerves may contribute to maintaining the renal mass and that the neural effect on compensatory growth following nephrectomy may be covered by other growth factors.

  1. Ultra structure of the denervated vocal muscle mechanically in hogs (sus scrofa domestica

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    Leão, Henrique Zaquia


    Full Text Available Introduction: The literature is not clear in the ultra-structural manifestations of the vocal wrinkles after neural wound. Objective: To verify the alterations that occur in a vocal fold mechanically denervated. Method: In this prospective study, it were utilized 15 hogs of commercial race (Sus scrofa domesticates, with age of 4 to 12 weeks. The animals were distributed in three groups, chosen at random. Everybody was submitted to the denervation of the right vocal fold, with surgical removal of a segment with three centimeters of the recurring right laryngeal nerve. After 45, 90 and 180 days of the operations, it was proceeded the biopsy of the vocal muscles, it was prosecuted the samples for transmission electron microscopy and, for the ultra-structural study, utilized the transmission electron microscopy Philips, model EM208S. Results: The biopsied groups with 45 and 90 days after operation of mechanical denervation, presented disorganization miofibrilar, only vestigial lines Z in many samples, as well like altered mithochondrions presenting limited sizes, and matrix mithocondrial rarefied with rare mithocondrial cristae present. The biopsied group with 180 days after operation of denervation, presented regular sarcomeres, mithocondrions with sizes and regular number with correct positioning between the sarcomerical units. Conclusion: The finds in the ultra-structure of the vocal muscles suggest to re enervation of the muscle being that the muscular mithochondrions were the most sensible structures to the denervated condition, successions by the cytoarchiteture of the miofibrilas; the finds in the ultra-structure of the vocal muscles suggests to reinervation of the muscle in the period of approximately six months.

  2. Cooled radiofrequency denervation for treatment of sacroiliac joint pain: two-year results from 20 cases

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    Ho KY


    Full Text Available Kok-Yuen Ho,1 Mohamed Abdul Hadi,2 Koravee Pasutharnchat,2 Kian-Hian Tan21Pain Management Centre, Raffles Hospital, 2Pain Management Centre, Singapore General Hospital, SingaporeBackground: Sacroiliac joint pain is a common cause of chronic low back pain. Different techniques for radiofrequency denervation of the sacroiliac joint have been used to treat this condition. However, results have been inconsistent because the variable sensory supply to the sacroiliac joint is difficult to disrupt completely using conventional radiofrequency. Cooled radiofrequency is a novel technique that uses internally cooled radiofrequency probes to enlarge lesion size, thereby increasing the chance of completely denervating the sacroiliac joint. The objective of this study was to evaluate the efficacy of cooled radiofrequency denervation using the SInergyTM cooled radiofrequency system for sacroiliac joint pain.Methods: The charts of 20 patients with chronic sacroiliac joint pain who had undergone denervation using the SInergyTM cooled radiofrequency system were reviewed at two years following the procedure. Outcome measures included the Numeric Rating Scale for pain intensity, Patient Global Impression of Change, and Global Perceived Effect for patient satisfaction.Results: Fifteen of 20 patients showed a significant reduction in pain (a decrease of at least three points on the Numeric Rating Scale. Mean Numeric Rating Scale for pain decreased from 7.4 ± 1.4 to 3.1 ± 2.5, mean Patient Global Impression of Change was "improved" (1.4 ± 1.5, and Global Perceived Effect was reported to be positive in 16 patients at two years following the procedure.Conclusion: Cooled radiofrequency denervation showed long-term efficacy for up to two years in the treatment of sacroiliac joint pain.Keywords: ablation, chronic low back pain, intervention, neurotomy, sacroiliitis

  3. One-year outcomes of percutaneous renal denervation for the treatment of resistant hypertension: the first Chinese experience

    Institute of Scientific and Technical Information of China (English)

    Dong Hui; Jiang Xiongjing; Liang Tuo; Zou Yubao; Guan Ting; Peng Meng; Song Lei


    Background As a novel device-based approach targeting the renal sympathetic nerves,percutaneous renal denervation (RDN) has been shown to be effective and safe for reducing blood pressure.However,while considerable data on RDN have been obtained from Western populations,there is limited findings from East Asian populations.The purpose of this study was to evaluate one-year outcomes of RDN for the treatment of resistant hypertension in Chinese patients.Methods Between February and August 2012,14 patients (mean age 39±8 years,10 males) with resistant hypertension underwent successful RDN at the Fuwai Hospital.All 14 patients were followed up at 1,3,6 and 12 months postprocedure.Blood pressure,use of antihypertensive agents,renal function,and complications were investigated.Results Baseline values included mean office blood pressure of 164/103±14/10 mmHg,mean 3.9±0.6 anti-hypertensive agents,and an estimated glomerular filtration rate of (79±19) mlmin-1.1.73 m-2.Office blood pressure after the procedure was reduced by-14/-10,-17/-11,-21/-12,and-24/-14 mmHg at 1,3,6,and 12 months respectively,and the reduction of the number of antihypertensive agents at the above corresponding time points was-1.3,-1.5,-1.7 and-1.8 respectively (all P <0.001).The mean reduction of 24-hour ambulatory blood pressure was similar to the reduction of office blood pressure at the four corresponding time points.Renal function did not significantly change at any time point (all P >0.05).No clinical complications were observed at 12-month follow-up.Conclusion This study showed that RDN seems to be effective in reducing blood pressure of Chinese patients with resistant hypertension,with minimal adverse events at 12-month follow-up.

  4. Mechanism of relation among heart meridian, referred cardiac pain and heart

    Institute of Scientific and Technical Information of China (English)

    RONG; Peijing(荣培晶); ZHU; Bing(朱兵)


    It has been demonstrated that an important clinical phenomenon often associated with visceral diseases is the referred pain to somatic structures, especially to the body areaof homo-segmental innervation. It is interesting that the somatic foci of cardiac referred pain wereoften and mainly distributed along the heart meridian (HM), whereas the acupoints of HM havebeen applied to treat cardiac disease since ancient times. The purpose of this study was to inves-tigate the neural relationship between the cardiac referred pain and the heart meridian.Fluorescent triple-labeling was injected into the pericardium, some acupoints of HM and lung me-ridian (LM, for control). The responses of the left cardiac sympathetic nerve and of the EMG in left HM and LM were electrophysiologically studied, when the electrical stimuli were applied to the acupoints of left HM and to the left cardiac sympathetic nerve. More double-labeled neurons in HM-heart, not in LM-heart, were observed in the ipsilateral dorsal root ganglia of the spinal segments C8-T3. Electric stimulation of the acupoints of left HM was able to elicit more responses of left cardiac sympathetic nerve than that of the LM-acupoints. Electric stimulation of the left cardiac sympathetic nerve resulted in stronger activities of EMG-response in the acupoints of left HM than in LM-acupoints. We conclude that double-labeling study has provided direct evidence for the existence of dichotomizing afferent fibers that supply both the pericardium and HM. Electrophysiological results show that HM is more closely related functionally to heart. These findings provide a possible morphological and physiological explanation for the referred cardiac pain and HM-heart interrelation.

  5. Glutamate and GABA in vestibulo-sympathetic pathway neurons

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    Gay R Holstein


    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

  6. (123)I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases. (United States)

    Nakajima, Kenichi; Yamada, Masahito


    (123)I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of (123)I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of (123)I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac (123)I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both (123)I-ioflupane for the striatum and (123)I-MIBG. Despite being a simple index, the H/M ratio of (123)I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

  7. Glutamatergic inputs to the CVLM independent of the NTS promote tonic inhibition of sympathetic vasomotor tone in rats. (United States)

    Mandel, Daniel A; Schreihofer, Ann M


    GABAergic neurons in the caudal ventrolateral medulla (CVLM) are driven by baroreceptor inputs relayed via the nucleus tractus solitarius (NTS), and they inhibit neurons in rostral ventrolateral medulla to reduce sympathetic nerve activity (SNA) and arterial pressure (AP). After arterial baroreceptor denervation or lesions of the NTS, inhibition of the CVLM continues to increase AP, suggesting additional inputs also tonically activate the CVLM. This study examined whether the NTS contributes to baroreceptor-independent drive to the CVLM and whether glutamate promotes baroreceptor- and NTS-independent activation of the CVLM to tonically reduce SNA. In addition, we evaluated whether altering central respiratory drive, a baroreceptor-independent regulator of CVLM neurons, influences glutamatergic inputs to the CVLM. Splanchnic SNA and AP were measured in chloralose-anesthetized, ventilated, paralyzed rats. The infusion of nitroprusside decreased AP below threshold for baroreceptor afferent firing (NTS by microinjection of the GABA(A) agonist muscimol did not further increase SNA. In contrast, after inhibition of the NTS, blockade of glutamatergic inputs to CVLM by microinjection of kynurenate increased SNA (274+/-54%; PNTS-mediated excitation of the CVLM. Furthermore, glutamate tonically activates the CVLM to reduce SNA independent of the NTS, and this excitatory input appears to be affected by the strength of central respiratory drive.

  8. Role of the Sympathetic Nervous System in Stress-Mediated Cardiovascular Disease. (United States)

    Hering, Dagmara; Lachowska, Kamila; Schlaich, Markus


    A high incidence of acute cardiovascular events and sudden cardiac death following unexpected acute emotional stress or a natural catastrophic disaster has been well-documented over the past decades. Chronic psychosocial factors have been shown to be directly linked to the development of hypertension, cardiovascular disease and stroke. Activation of various neurogenic pathways is an important mediator of acute and chronic stress-induced hypertension and heart disease. Heightened sympathetic activation has been shown to be a critical contributor linking psychogenic effects on cardiovascular regulation to serious and often fatal CV outcomes. Accordingly, several therapeutic approaches that attenuate autonomic imbalance via modulation of increased sympathetic outflow by either non-pharmacological or interventional means have been shown to alleviate clinical symptoms. Likewise stress reduction per se achieved with transcendental medicine has been linked to improved patient outcomes. Therapies that oppose adrenergic activity and/or have the potential to attenuate negative emotions are likely to reduce cardiovascular risk and its adverse consequences attributable to chronic mental stress.

  9. Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects. (United States)

    Shores, M M; Pascualy, M; Lewis, N L; Flatness, D; Veith, R C


    Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 microg/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions.

  10. Habitual traffic noise at home reduces cardiac parasympathetic tone during sleep

    NARCIS (Netherlands)

    Graham, J.M.A.; Janssen, S.A.; Vos, H.; Miedema, H.M.E.


    The relationships between road and rail traffic noise with pre-ejection period (PEP) and with respiratory sinus arrhythmia (RSA) during sleep, as indices of cardiac sympathetic and parasympathetic nervous system tone, were investigated in the field (36 subjects, with 188 and 192 valid subject nights

  11. Effect of Yoga on migraine: A comprehensive study using clinical profile and cardiac autonomic functions

    Directory of Open Access Journals (Sweden)

    Ravikiran Kisan


    Conclusions: Intervention showed significant clinical improvement in both groups. Headache frequency and intensity were reduced more in Yoga with conventional care than the conventional care group alone. Furthermore, Yoga therapy enhanced the vagal tone and decreased the sympathetic drive, hence improving the cardiac autonomic balance. Thus, Yoga therapy can be effectively incorporated as an adjuvant therapy in migraine patients.

  12. Heart-brain interactions in cardiac arrhythmia. (United States)

    Taggart, P; Critchley, H; Lambiase, P D


    This review examines current knowledge of the effects of higher brain centres and autonomic control loops on the heart with particular relevance to arrhythmogenesis. There is now substantial evidence that higher brain function (cortex), the brain stem and autonomic nerves affect cardiac electrophysiology and arrhythmia, and that these may function as an interactive system. The roles of mental stress and emotion in arrhythmogenesis and sudden cardiac death are no longer confined to the realms of anecdote. Advances in molecular cardiology have identified cardiac cellular ion channel mutations conferring vulnerability to arrhythmic death at the myocardial level. Indeed, specific channelopathies such as long QT syndrome and Brugada syndrome are selectively sensitive to either sympathetic or vagal stimulation. There is increasing evidence that afferent feedback from the heart to the higher centres may affect efferent input to the heart and modulate the cardiac electrophysiology. The new era of functional neuroimaging has identified the central neural circuitry in this brain-heart axis. Since precipitants of sudden fatal arrhythmia are frequently environmental and behavioural, central pathways translating stress into autonomic effects on the heart might be considered as therapeutic targets. These brain-heart interactions help explain the apparent randomness of sudden cardiac events and provide new insights into future novel therapies to prevent sudden death.

  13. Sympathetic Innervation Induced in Engrafted Engineered Cardiomyocyte Sheets by Glial Cell Line Derived Neurotrophic Factor In Vivo

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    Xian-ming Fu


    Full Text Available The aim of myocardial tissue engineering is to repair or regenerate damaged myocardium with engineered cardiac tissue. However, this strategy has been hampered by lack of functional integration of grafts with native myocardium. Autonomic innervation may be crucial for grafts to function properly with host myocardium. In this study, we explored the feasibility of in vivo induction of autonomic innervation to engineered myocardial tissue using genetic modulation by adenovirus encoding glial cell line derived neurotrophic factor (GDNF. GFP-transgene (control group or GDNF overexpressing (GDNF group engineered cardiomyocyte sheets were transplanted on cryoinjured hearts in rats. Nerve fibers in the grafts were examined by immunohistochemistry at 1, 2, and 4 weeks postoperatively. Growth associated protein-43 positive growing nerves and tyrosine hydroxylase positive sympathetic nerves were first detected in the grafts at 2 weeks postoperatively in control group and 1 week in GDNF group. The densities of growing nerve and sympathetic nerve in grafts were significantly increased in GDNF group. No choline acetyltransferase immunopositive parasympathetic nerves were observed in grafts. In conclusion, sympathetic innervation could be effectively induced into engrafted engineered cardiomyocyte sheets using GDNF.

  14. Sympathetic skin response test in essential hypertensive patients

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    Ann Abdel Kader


    Conclusion Although SSR has a low diagnostic value in patients with essential hypertension, it might be a good diagnostic test particularly in the presence of signs and symptoms of sympathetic overactivity such as tachycardia and sweating.

  15. Adipose afferent reflex: sympathetic activation and obesity hypertension. (United States)

    Xiong, X-Q; Chen, W-W; Zhu, G-Q


    Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex (AAR) is a sympatho-excitatory reflex that the afferent activity from white adipose tissue (WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus (PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension.

  16. Cardiac echinococcosis

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    Ivanović-Krstić Branislava A.


    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  17. Schwanomma From Cervical Sympathetic Chain Ganglion - A Rare Presentation. (United States)

    Asma, A Affee; Kannah, E


    Schwanommas arising from cervical sympathetic chain are tumours that are rare in occurrence. These lesions are usually difficult to differentiate from a vagal schwanomma and a carotid body tumour during the initial workup. In this report, a rarely seen huge cervical sympathetic chain schwanomma case with partial Horner's syndrome is being presented in detail, which to our known knowledge, is one of the few cases reported in literature.

  18. Remodelling sympathetic innervation in rat pancreatic islets ontogeny

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    Hiriart Marcia


    Full Text Available Abstract Background Pancreatic islets are not fully developed at birth and it is not clear how they are vascularised and innervated. Nerve Growth Factor (NGF is required to guide sympathetic neurons that innervate peripheral organs and also in cardiovascular system and ovary angiogenesis. Pancreatic beta cells of a transgenic mouse that over-expressed NGF in attracts sympathetic hyper-innervation towards them. Moreover, we have previously demonstrated that adult beta cells synthesize and secrete NGF; however, we do not know how is NGF secreted during development, nor if it might be trophic for sympathetic innervation and survival in the pancreas. We analyzed sympathetic innervation and vasculature development in rat pancreatic islets at different developmental stages; foetal (F19, early postnatal (P1, weaning period (P20 and adults. We temporarily correlated these events to NGF secretion by islet cells. Results Sympathetic fibres reached pancreatic islets in the early postnatal period, apparently following blood vessels. The maximal number of sympathetic fibres (TH immunopositive in the periphery of the islets was observed at P20, and then fibres entered the islets and reached the core where beta cells are mainly located. The number of fibres decreased from that stage to adulthood. At all stages studied, islet cells secreted NGF and also expressed the high affinity receptor TrkA. Foetal and neonatal isolated islet cells secreted more NGF than adults. TrkA receptors were expressed at all stages in pancreatic sympathetic fibres and blood vessels. These last structures were NGF–immunoreactive only at early stages (foetal and P0. Conclusion The results suggest that NGF signalling play an important role in the guidance of blood vessels and sympathetic fibres toward the islets during foetal and neonatal stages and could also preserve innervation at later stages of life.

  19. Sympathetic Nervous System, Hypertension, Obesity and Metabolic Syndrome. (United States)

    Seravalle, Gino; Grassi, Guido


    Experimental and clinical studies have clearly shown the role of the sympathetic nervous system in the pathophysiology of several cardiovascular and non-cardiovascular diseases. This short review will be aimed at focusing and discussing the new information collected on two specific clinical conditions such as obesity and metabolic syndrome. The paper will briefly describe the four main mechanisms that represent the common link between these two pathophysiological conditions and that through the sympathetic nervous system contribute to increase the cardiovascular risk.

  20. Factors influencing the cardiac MIBG accumulation

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    Takatsu, Hisato; Fujiwara, Hisayoshi [Gifu Univ. (Japan). School of Medicine


    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.)

  1. Comparison in regard to myocardial sympathetic denervation between {sup 123}I-MIBG and {sup 201}Tl in patients with vasospastic angina pectoris

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    Ohta, Katsuhisa [Kanazawa Medical Univ., Uchinada (Japan)


    Of the patients who were diagnosed as having vasospastic angina (VSA) with coronary spasm proven by acetylcholine (Ach) on coronary angiograms were used as the subjects. There were 39 males and 15 females. MIBG and Tl were administered to all of the 54 cases before coronary angiography. MIBG in a dose of 111 Mbq was injected intravenously at rest. A photograph was taken after 3 hours for a delayed image. Tl myocardial blood flow image was taken immediately after exercise loading and a redistribution image 3 hours later. Results of administration of MIBG and Tl were restudied 3 to 6 months after inception of the treatment in 14 out of 54 cases. The proportion of positive cases was significantly high with MIBG, with 52 (97%) out of 54 cases found positive with MIBG and 10 (19%) out of 54 cases with Tl (p<0.05). The number of cases which were positive with both MIBG and Tl was 10 (19%) but there was no positive case with Tl alone. 42 (78%) out of 54 cases were found positive with MIBG alone, which was significantly high compared with the Tl positive cases (P<0.01). The sensitivity of MIBG tended to be higher than that of Tl, with the sensitivity 19.6% and specificity 42.8% with Tl against the sensitivity 74.4% and specificity 36.8% with MIBG (P<0.1). A significant improvement (P<0.01) was noted with MIBG, with the defect score after treatment being -8.9{+-}6.0 against -13.5{+-}7.7 before treatment. With Tl no significant difference was found, with -5.2{+-}2.3 after treatment against -8.2{+-}4.3 before administration. In VSA, the frequency of the decline in accumulation was higher with MIBG than with Tl. MIBG is thought to sharply reflect past ischemia. With MIBG, a significant improvement in the defect score was seen before and after treatment. So MIBG considered useful for judging the therapeutic effect as well. (K.H.)


    NARCIS (Netherlands)



    Exercise is known to increase hepatic glucose production. Previous studies have suggested that the sympathetic nerves only marginally contribute to this process. This study examined whether increased catecholamine response or increased adrenoceptor sensitivity might have affected previous results sh

  3. Role of sympathetic nerve activity in the process of fainting

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    Satoshi eIwase


    Full Text Available Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery, and the process of syncope progression will be described with two types of sympathetic change. Simultaneous recordings of microneurographically recorded MSNA and continuous and noninvasive blood pressure measurement have disclose what is going on in the course of progression of the syncope. Vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. The vasovagal syncope is characterized by the sympathoexcitation, followed by vagal overcome via the Bezold-Jarisch reflex. Orthostatic syncope is caused by the response failure or lack of sympathetic nerve activity toward the orthostatic challenge followed by the fluid shift, and subsequent cerebral low perfusion. Four causes are considered for the compensatory failure, which triggers the orthostatic syncope; hypovolemia, increased pooling in the lower body, failure to activate the sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions were described in the viewpoint of 1 exaggerated sympathoexcitation and 2 failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control the cardiovascular function, and its failure resulted syncope, however, responses of the system by microneurographically recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism.

  4. Paroxysmal sympathetic hyperactivity in neurological critical care

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    Rajesh Verma


    Full Text Available Introduction: Paroxysmal sympathetic hyperactivity (PSH is a clinical disorder mainly caused by traumatic brain injury, stroke, encephalitis and other types of brain injury. The clinical features are episodes of hypertension, tachycardia, tachypnea, fever and dystonic postures. In this study, we described clinical profile and outcome of six patients of PSH admitted in neurocritical care unit. Materials and Methods: This was a prospective observational study conducted at neurology critical care unit of a tertiary care center. All patients admitted at neurology critical unit during 6-month period from August 2013 to January 2014 were screened for the occurrence of PSH. The clinical details and outcome was documented. Results: PSH was observed in 6 patients. Male to female ratio was 5:1. Mean age ± SD was 36.67 ± 15.19 years. The leading causes were traumatic brain injury (two patients, stroke (two patients and Japanese encephalitis (JE (one patient and tuberculous meningitis (one patient. Conclusion: PSH is an unusual complication in neurocritical care. It prolonged the hospitalization and hampers recovery. The other life-threatening conditions that mimic PSH should be excluded. The association with JE and tuberculous meningitis was not previously described in literature.

  5. Sympathetic nervous system behavior in human obesity. (United States)

    Davy, Kevin P; Orr, Jeb S


    The sympathetic nervous system (SNS) plays an essential role in the regulation of metabolic and cardiovascular homeostasis. Low SNS activity has been suggested to be a risk factor for weight gain and obesity development. In contrast, SNS activation is characteristic of a number of metabolic and cardiovascular diseases that occur more frequently in obese individuals. Until recently, the relation between obesity and SNS behavior has been controversial because previous approaches for assessing SNS activity in humans have produced inconsistent findings. Beginning in the early 1990s, many studies using state of the art neurochemical and neurophysiological techniques have provided important insight. The purpose of the present review is to provide an overview of our current understanding of the region specific alterations in SNS behavior in human obesity. We will discuss findings from our own laboratory which implicate visceral fat as an important depot linking obesity with skeletal muscle SNS activation. The influence of weight change on SNS behavior and the potential mechanisms and consequences of region specific SNS activation in obesity will also be considered.

  6. Pharmacological characterization of the inhibition by moxonidine and agmatine on the cardioaccelerator sympathetic outflow in pithed rats. (United States)

    Cobos-Puc, Luis E; Villalón, Carlos M; Ramírez-Rosas, Martha B; Sánchez-López, Araceli; Lozano-Cuenca, Jair; Gómez-Díaz, Benjamín; MaassenVanDenBrink, Antoinette; Centurión, David


    This study analysed the inhibition produced by the agonists moxonidine (imidazoline I(1) receptors>alpha(2)-adrenoceptors) and agmatine (endogenous ligand of imidazoline I(1)/I(2) receptors), using B-HT 933 (6-ethyl-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepin-2-amine dihydrochloride; alpha(2)-adrenoceptors) for comparison, on the rat cardioaccelerator sympathetic outflow. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or noradrenaline produced, respectively, frequency-dependent and dose-dependent tachycardic responses. I.v. continuous infusions of moxonidine (3 and 10 microg/kg min), agmatine (1000 and 3000 microg/kg min) and B-HT 933 (30 and 100 microg/kg min) inhibited the tachycardic responses to sympathetic stimulation, but not those to noradrenaline. The cardiac sympatho-inhibition by either moxonidine (3 microg/kg min) or B-HT 933 (30 microg/kg min) was not modified by i.v. injections of saline or the antagonists AGN192403 [(+/-)-2-endo-Amino-3-exo-isopropylbicyclo[2.2.1]heptane hydrochloride; 3000microg/kg; imidazoline I(1) receptors] or BU224 (2-(4,5-dihydroimidazol-2-yl)quinoline hydrochloride; 300 microg/kg; imidazoline I(2) receptors) and abolished by rauwolscine (300 microg/kg; alpha(2)-adrenoceptors). At the same doses of these compounds, the sympatho-inhibition to moxonidine (10 microg/kg min) and agmatine (1000 microg/kg min) was: (1) not modified by saline, AGN192403 or BU224; (2) partially blocked by rauwolscine or the combination of rauwolscine plus BU224; and (3) abolished by the combination of rauwolscine plus AGN192403. These results demonstrate that the cardiac sympatho-inhibition to: (1) 3 microg/kg min moxonidine or 30 microg/kg min B-HT 933 involves alpha(2)-adrenoceptors; and (2) 10 microg/kg min moxonidine or 1000 microg/kg min agmatine involves alpha(2)-adrenoceptors and imidazoline I(1) receptors.

  7. Cardiac Rehabilitation (United States)

    ... your risk of future heart problems, and to improve your health and quality of life. Cardiac rehabilitation programs increase ... exercise routine at home or at a local gym. You may also continue to ... health concerns. Education about nutrition, lifestyle and weight loss ...

  8. Sympathetic-leptin relationship in obesity: effect of weight loss. (United States)

    Quilliot, Didier; Böhme, Philip; Zannad, Faiez; Ziegler, Olivier


    Obese patients have high plasma leptin concentrations that do not induce the expected responses on weight regulation, suggesting a leptin resistance in obesity. Elevated leptin levels are also thought to be related to a high sympathetic nervous system (SNS) activity. This effect could be preserved, lowered, or even abolished in obesity. We planned to investigate the possible association in a longitudinal study. Ninety-five normotensive healthy women, aged 40.4 +/- 11.4 years and body mass index of 33.2 +/- 2.3 kg/m(2), were studied. Baseline leptin, fat mass, and heart rate variability were measured and included in a 6-month longitudinal study. Body composition was measured by dual-energy x-ray absorption. Time domain heart rate variability, QT dynamicity, and spectral components on ambulatory electrocardiographs were analyzed. Dietary advice was given by a dietitian to the patient (maximum caloric reduction of 30%), and subjects were randomized in 3 treatment groups: sibutramine 10 mg, sibutramine 20 mg, or placebo. At baseline, low frequencies (LF) and the LF-high frequencies (HF) ratio, mainly related to the SNS, were negatively correlated to leptin concentration (r = -0.30, P = .002 and r = -0.36, P < .001) and to the leptin-fat mass ratio (r = -0.28, P = .004 and r = - 0.33, P = .0007), thus explaining 38% of the LF variance and 33% of the LF/HF variance. Diastolic blood pressure was also negatively correlated to leptin concentrations (-0.20, P = .04) and to the leptin-fat mass ratio (-0.22, P = .022). In contrast, no consistent correlations between leptin and the time domain components related to vagal activity were observed. At 6 months, after completion of the weight loss program, LF significantly decreased (-7.7% +/- 7.9%, P < .001), whereas HF was higher than the initial value (+20% +/- 5.2%). The leptin-fat mass ratio remained negatively correlated to the LF (r = -0.34, P = .030) and to LF/HF (r = -0.35, P = .021) values, explaining 21% of the LF

  9. Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

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    Fabio Francini


    Full Text Available Skeletal muscle atrophy can be defined as a wasting or decrease in muscle mass and muscle force generation owing lack of use, ageing, injury or disease. Thus, the etiology of atrophy can be different. Atrophy in denervated muscle is a consequence of two factors: 1 the complete lack of motoneuron activity inducing the deficiency of neurotransmitter release and 2 the muscles disuse. The balance of the muscular functions depends on extra- and intra-muscular signals. In the balance are involved the excitation-contraction coupling (ECC, local growth factors, Ca2+-dependent and independent intracellular signals, mechano-sensitivity and mechano-transduction that activate Ca2+-dependent signaling proteins and cytoskeleton- nucleus pathways to the nucleus, that regulate the gene expression. Moreover, retrograde signal from intracellular compartments and cytoskeleton to the sarcolemma are additional factors that regulate the muscle function. Proteolytic systems that operate in atrophic muscles progressively reduce the muscle protein content and so the sarcolemma, ECC and the force generation. In this review we will focus on the more relevant changes of the sarcolemma, excitation-contraction coupling, ECC and mechano-transduction evaluated by electrophysiological methods and observed from early- to long-term denervated skeletal muscles. This review put in particular evidence that long-term denervated muscle maintain a sub-population of fibers with ECC and contractile machinery able to be activated, albeit in lesser amounts, by electrical and mechanical stimulation. Accordingly, this provides a potential molecular explanation of the muscle recovery that occurs in response to rehabilitation strategy as transcutaneous electrical stimulation and passive stretching of denervated muscles, which wre developed as a result of empirical clinical observations.

  10. Catheter-Based Renal Denervation for Resistant Hypertension: Will It Ever Be Ready for "Prime Time"? (United States)

    Laffin, Luke J; Bakris, George L


    The year 2014 was a turning point for the field of renal denervation (RDN) and its potential use to treat resistant hypertension. Tremendous enthusiasm shifted to sober reflection on the efficacy of a technology once touted as the cure to resistant hypertension. The following review highlights 2 major questions: First, does catheter-based RDN lower blood pressure and, second, will RDN using catheter-directed therapy for the treatment of resistant hypertension ever become more than an investigational technology.

  11. Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity? (United States)

    Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik


    Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided.

  12. Ulnar nerve injuries of the hand producing intrinsic muscle denervation of magnetic resonance imaging

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    Barberie, J.E.; Connell, D.G.; Munk, P.L.; Janzen, D.L. [Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, (Canada). Department of Radiology


    Muscle and nerve injuries in the hand may be difficult to detect and diagnose clinically. Two cases are reported in which magnetic resonance imaging showed ulnar nerve injury and intrinsic hand muscle denervation. The clinical, anatomical and radiological features of injury to the deep motor branch of the ulnar nerve and associated muscle denervation are discussed and illustrated. Compression of the deep motor branch of the ulnar nerve is a rare cause of hand dysfunction. This condition produces a clinical syndrome characterized by weakness of the muscles innervated by the deep branch of the ulnar nerve, with normal sensation in the hand. Denervation of the intrinsic hand muscles is variable, depending on the site and severity of the nerve injury. The anatomy of the ulnar nerve is complex and ulnar nerve compression syndrome is difficult to detect and localize clinically. Multiple causes exist, including ganglions; repeated trauma, typically occupationally related; calcification adjacent to the pisiform and the pisotriquetral joint; anomalous muscle bellies; fractures or dislocations affecting the ulnar side of the wrist; vascular anomalies of the ulnar artery; and oedema of the hand, requiring differing surgical treatments. We report two patients who presented with ulnar nerve compression syndrome secondary to post-traumatic neuromas as a result of blunt trauma to the palm. Copyright (1999) Blackwell Science Pty Ltd 12 refs., 2 figs.

  13. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

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    Glowniak, J.V.; Turner, F.E.; Gray, L.L.; Palac, R.T.; Lagunas-Solar, M.C.; Woodward, W.R.


    Iodine-123 metaiodobenzylguanidine ((/sup 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 (/sup 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.

  14. Thoracic sympathetic block reduces respiratory system compliance

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    Fábio Ely Martins Benseñor

    Full Text Available CONTEXT AND OBJECTIVE: Thoracic epidural anesthesia (TEA following thoracic surgery presents known analgesic and respiratory benefits. However, intraoperative thoracic sympathetic block may trigger airway hyperreactivity. This study weighed up these beneficial and undesirable effects on intraoperative respiratory mechanics. DESIGN AND SETTING: Randomized, double-blind clinical study at a tertiary public hospital. METHODS: Nineteen patients scheduled for partial lung resection were distributed using a random number table into groups receiving active TEA (15 ml 0.5% bupivacaine, n = 9 or placebo (15 ml 0.9% saline, n = 10 solutions that also contained 1:200,000 epinephrine and 2 mg morphine. Under general anesthesia, flows and airway and esophageal pressures were recorded. Pressure-volume curves, lower inflection points (LIP, resistance and compliance at 10 ml/kg tidal volume were established for respiratory system, chest wall and lungs. Student’s t test was performed, including confidence intervals (CI. RESULTS: Bupivacaine rose 5 ± 1 dermatomes upwards and 6 ± 1 downwards. LIP was higher in the bupivacaine group (6.2 ± 2.3 versus 3.6 ± 0.6 cmH2O, p = 0.016, CI = -3.4 to -1.8. Respiratory system and lung compliance were higher in the placebo group (respectively 73.3 ± 10.6 versus 51.9 ± 15.5, p = 0.003, CI = 19.1 to 23.7; 127.2 ± 31.7 versus 70.2 ± 23.1 ml/cmH2O, p < 0.001, CI = 61 to 53. Resistance and chest wall compliance showed no difference. CONCLUSION: TEA decreased respiratory system compliance by reducing its lung component. Resistance was unaffected. Under TEA, positive end-expiratory pressure and recruitment maneuvers are advisable.

  15. Development of sympathetic ophthalmia following globe injury

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; ZHANG Mao-nian; JIANG Cai-hui; YAO Yi


    Background Sympathetic ophthalmia (SO), a rare, bilateral, diffuse granulomatous uveitis, usually occurs after open globe injury or intraocular surgery. We sought to identify the risk factors for the development of SO after open globe injury and describe their demographic and clinical features and outcomes of treatments.Methods A retrospective study of inpatients with globe injury in 15 tertiary referral hospitals of China from January 2001 to December 2005 was conducted. The information of demography, nature and mechanism of injury, time and ways of treatments and outcomes was reviewed. Diagnosis of SO was made based on a history of ocular trauma or surgery and subsequent development of bilateral or contralateral uveitis consistent with SO. Any association between related parameters and development of SO was analyzed.Results Among 9103 patients (9776 eyes) of globe injury, SO occurred after open globe injury in 18 cases with an occurrence rate of 0.37%, vitrectomy of closed globe injury in 2 (0.37%) and perforation of burned eyes in another 2. For open globe injury, the median age ((36.72±13.59) years, P=0.01) was higher in patients with SO; there were no significant effects of sexes, injury type, uvea proplaps, once or multi-intraocular surgery, once or multi-vitrectomy and endophthalmitis on incidence of SO; 0.70% endophthalmitis concurred with SO; 83.33% of SO occurred within 1 year after injury or last ocular surgery. SO developed in a fellow eye one week after evisceration of the perforating burned eye. Good final visual acuity was obtained in sympathizing eyes with prompt treatment.Conclusions For open globe injuries, SO sufferers were relatively older and any injury type could induce SO with equal possibility. The initial open globe injury was more likely to be the trigger of SO than subsequent intraocular surgeries including vitrectomy. Prophylactic enucleation after injury is not recommended.

  16. Diffusion-weighted MRI, dynamic susceptibility contrast MRI and ultrasound perfusion quantification of denervated muscle in rabbits

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    Goyault, G.; Beregi, J.P. [University Hospital, Department of Cardiovascular imaging, Cardiologic Hospital, Lille (France); Bierry, G.; Holl, N.; Dietemann, J.L.; Kremer, S. [University Hospital, Department of Neuroradiology, Strasbourg (France); Lhermitte, B. [University Hospital, Department of Pathology, Strasbourg (France)


    The purpose of this study was to assess denervated muscle perfusion using dynamic susceptibility contrast MRI (DSCMRI) and contrast-enhanced ultrasound (CEUS), and to measure denervated muscle apparent diffusion coefficient (ADC) on b1000 diffusion-weighted MRI (DWMRI) at 3 T in order to clarify whether muscle denervation leads to an increase in the extracellular extravascular space, or an increase in blood flow - or both. Axotomy of the right sciatic nerve of six white rabbits was performed at day 0. At day 9, hind limb muscles MRI and CEUS were performed to assess the consequences of denervation and both semimembranosus muscles of each rabbit were explanted for histological studies. Signal intensity on T2- and T1-weighted MRI, ADC on DWMRI, maximum signal drop (MSD) on DSCMRI and the area under the curve (AUC) on CEUS were measured over circular regions of interest (ROI), in both semimembranosus muscles. Non-parametric Wilcoxon matched-pairs tests were used to assess the mean differences between denervated and normal muscles. T2 fat-saturated (FS) MRI studies showed a strong signal in the right semimembranosus muscles compared with the left side, and gadolinium enhancement was observed on T1 FS MRI. Denervated muscles show a significant increase in ADC on DWMRI (p < 0.01) and a significant signal enhancement on DSCMR imaging (p < 0.05) and on first-pass CEUS (p < 0.05). The results of this study - based on perfusion- and diffusion-weighted images - suggest that, after denervation, both increased blood flow through muscle tissue and expansion of the extracellular water volume are present. (orig.)

  17. Effect of quinapril or metoprolol on circadian sympathetic and parasympathetic modulation after acute myocardial infarction. (United States)

    Kontopoulos, A G; Athyros, V G; Papageorgiou, A A; Boudoulas, H


    Abnormal autonomic nervous system impairment in patients with acute myocardial infarction (AMI) has a circadian pattern with the greatest manifestation in the morning hours; it probably plays an important role in the pathogenesis of cardiac arrhythmias and acute ischemic syndromes. Angiotensin-converting enzyme inhibitors improve autonomic function in patients with AMI, but the circadian pattern of this effect has not been studied. Heart rate variability-normalized frequency domain indexes were assessed 5 days (baseline) after the onset of uncomplicated AMI and 30 days after therapy with quinapril (n = 30), metoprolol (n = 30), or placebo (n = 30) with a solid-state digital Holter monitor. Normal subjects (n = 30) were used as controls. Quinapril increased parasympathetic and decreased sympathetic modulation, and improved sympathovagal interactions manifested by an increase in normalized high-frequency power (HFP), and a decrease in normalized low-frequency power (LFP), and their ratio (LFP/HFP) during the entire 24-hour period (pMetoprolol increased HFP and decreased LFP and the LFP/HFP ratio mainly between 08.00 A.M. to 12.00 noon, and 19.00 to 22.00 P.M. (delta% ratio -21%, and -12% respectively, pMetoprolol had a similar effect during the late morning and evening hours, but at a lower level. These effects may prove beneficial in reducing cardiac arrhythmias and acute ischemic syndromes in past-AMI patients.

  18. Cardiac Calcification

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    Morteza Joorabian


    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  19. Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons. (United States)

    Fortuna, Vitor; Pardanaud, Luc; Brunet, Isabelle; Ola, Roxana; Ristori, Emma; Santoro, Massimo M; Nicoli, Stefania; Eichmann, Anne


    The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation.

  20. Propranolol for Paroxysmal Sympathetic Hyperactivity with Lateralizing Hyperhidrosis after Stroke

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    Jason W. Siefferman


    Full Text Available Brain injury can lead to impaired cortical inhibition of the hypothalamus, resulting in increased sympathetic nervous system activation. Symptoms of paroxysmal sympathetic hyperactivity may include hyperthermia, tachycardia, tachypnea, vasodilation, and hyperhidrosis. We report the case of a 41-year-old man who suffered from a left middle cerebral artery stroke and subsequently developed central fever, contralateral temperature change, and hyperhidrosis. His symptoms abated with low-dose propranolol and then returned upon discontinuation. Restarting propranolol again stopped his symptoms. This represents the first report of propranolol being used for unilateral dysautonomia after stroke. Propranolol is a lipophilic nonselective beta-blocker which easily crosses the blood-brain barrier and may be used to treat paroxysmal sympathetic hyperactivity.

  1. Leptin as a mediator between obesity and cardiac dysfunction

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    Joanna Karbowska


    Full Text Available  Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and in­volved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue.These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

  2. Systematic morphology and evolutionary anatomy of the autonomic cardiac nervous system in the lesser apes, gibbons (hylobatidae). (United States)

    Kawashima, Tomokazu; Thorington, Richard W; Kunimatsu, Yutaka; Whatton, James F


    We examined the morphology of the autonomic cardiac nervous system (ACNS) on 20 sides of 10 gibbons (Hylobatidae) of three genera, and we have inferred the evolution of the anatomy of the primate ACNS. We report the following. (1) Several trivial intraspecific and interspecific variations are present in gibbons, but the general arrangement of the ACNS in gibbons is consistent. (2) Although the parasympathetic vagal cardiac nervous system is extremely consistent, the sympathetic cardiac nervous system, such as the composition of the sympathetic ganglia and the range of origin of the sympathetic cardiac nerves, exhibit topographical differences among primates. (3) The vertebral ganglion, seldom observed in the Old World monkeys (Cercopithecidae), was consistently present in gibbons as well as in humans. (4) There are fewer thoracic ganglia contributing to the cervicothoracic ganglion in humans than in gibbons and in gibbons than in Old World monkeys. (5) The superior cardiac nerve originating from the superior cervical ganglion, rarely observed in Old World monkeys but commonly observed in humans, was present in 13 of 20 sides (65%), mostly on the left. Accordingly, the ACNS morphology exhibits evolutionary changes within the primate lineage. These evolutionary differences between Old World monkeys, gibbons, and humans are most parsimoniously interpreted as resulting from regular changes in the lineages leading from their common ancestor to the extant species that we dissected. They include the reduction in the number of thoracic ganglia contributing to the cervicothoracic ganglion and the expansion of the range of the cardiac nervous origin.

  3. Effects of skin-derived precursors on wound healing of denervated skin in a nude mouse model. (United States)

    Shu, Bin; Xie, Ju-Lin; Xu, Ying-Bin; Lai, Wen; Huang, Yong; Mao, Ren-Xiang; Liu, Xu-Sheng; Qi, Shao-Hai


    Denervated skin could result in impaired healing of wounds, such as decubitus ulcers and diabetic foot ulcers. Other studies indicated that cutaneous fiber density is reduced after inner nerve transection and that neuropeptide level depletes after denervation, leading to reduced cell proliferation around the wound and thus wound healing problems. Recent studies have revealed that skin-derived precursors (SKPs), which form a neural crest-related stem cell population in the dermis of skin, participate in cutaneous nerve regeneration. We hypothesized that injecting SKPs into denervated wound promotes healing. A bilateral denervation wound model was established followed by SKP transplantation. The wound healing rate was determined at 7, 14, and 21 d after injury. Cell proliferation activity during wound healing was analyzed by proliferating cell nuclear antigen immunohistochemistry (IHC). Nerve fiber density was measured by S-100 IHC. The contents of nerve growth factor, substance P, and calcitonin gene-related peptide were examined by enzyme-linked immunosorbent assay. The rate of epithelization in the SKP-treated group was faster than that in the control group. Wound cell proliferation and nerve fiber density were obviously higher in the SKP-treated group than in the control group. In addition, the content of neuropeptides was higher in the SKP-treated group than in the control group during wound healing. In conclusion, SKPs can promote denervated wound healing through cell proliferation and nerve fiber regeneration, and can facilitate the release of neuropeptides.

  4. Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

    Directory of Open Access Journals (Sweden)

    Machado Ubiratan F


    Full Text Available Abstract Background The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2 in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP and heart rate variability (spectral analysis one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting. Results Higher glycemia (p vs. nondiabetics (p vs. SHR. Conclusions Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

  5. Sympathetic Vasoconstrictor Responsiveness of the Leg Vasculature During Experimental Endotoxemia and Hypoxia in Humans

    DEFF Research Database (Denmark)

    Brassard, Patrice; Zaar, Morten; Thaning, Pia;


    OBJECTIVE: Sympathetic vasoconstriction regulates peripheral circulation and controls blood pressure, but sepsis is associated with hypotension. We evaluated whether apparent loss of sympathetic vasoconstrictor responsiveness relates to distended smooth muscles or to endotoxemia and/or hypoxia...

  6. Central and cerebrovascular effects of leg crossing in humans with sympathetic failure

    NARCIS (Netherlands)

    M.P. Harms; W. Wieling; W.N. Colier; J.W. Lenders; N.H. Secher; J.J. van Lieshout


    Leg crossing increases arterial pressure and combats symptomatic orthostatic hypotension in patients with sympathetic failure This study compared the central and cerebrovascular effects of leg crossing in patients with sympathetic failure and healthy controls. We addressed the relationship between M

  7. A comparison of sympathetic and conventional training methods on responses to initial horse training

    NARCIS (Netherlands)

    Visser, E.K.; Dierendonck, van M.; Ellis, A.D.; Rijksen, C.; Reenen, van C.G.


    In `sympathetic horsemanship¿ the importance of the natural behaviour of the horse and the use of body language in communication is emphasised. However, it is unclear what effect sympathetic horsemanship has on the welfare of horses. During a 5-week starting period the effect of a sympathetic (ST) v

  8. Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

    DEFF Research Database (Denmark)

    Pedersen, J L; Rung, G W; Kehlet, H


    BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers....

  9. Reduced effect of percutaneous renal denervation on blood pressure in patients with isolated systolic hypertension. (United States)

    Ewen, Sebastian; Ukena, Christian; Linz, Dominik; Kindermann, Ingrid; Cremers, Bodo; Laufs, Ulrich; Wagenpfeil, Stefan; Schmieder, Roland E; Böhm, Michael; Mahfoud, Felix


    Renal denervation can reduce blood pressure in certain patients with resistant hypertension. The effect in patients with isolated systolic hypertension (ISH, ≥140/hypertension (CH, ≥140/≥90 mm Hg) defined as baseline office systolic blood pressure (SBP) ≥140 mm Hg despite treatment with ≥3 antihypertensive agents. Renal denervation significantly reduced office SBP and diastolic blood pressure (DBP) at 3, 6, and 12 months by 17/18/17 and 5/4/4 mm Hg in ISH and by 28/27/30 and 13/16/18 mm Hg in CH, respectively. The reduction in SBP and DBP in ISH was lower compared with patients with CH at all observed time points (P<0.05 for SBP/DBP intergroup comparison). The nonresponder rate (change in office SBP <10 mm Hg) after 6 months was 37% in ISH and 21% in CH (P<0.001). Mean 24-hour ambulatory SBP and DBP after 3, 6, and 12 months were significantly reduced by 10/13/15 and 6/6/9 mm Hg in CH, respectively. In patients with ISH the reduction in systolic ambulatory blood pressure was 4/8/7 mm Hg (P=0.032/P<0.001/P=0.009) and 3/4/2 mm Hg (P=0.08/P<0.001/P=0.130) in diastolic ambulatory blood pressure after 3, 6, and 12 months, respectively. The ambulatory blood pressure reduction was significantly lower after 3 and 12 months in SBP and after 12 months in ambulatory DBP, respectively. In conclusion, renal denervation reduces office and ambulatory blood pressure in patients with ISH. However, this reduction is less pronounced compared with patients with CH.

  10. Sympathetic Nerve Activity Maintains an Anti-Inflammatory State in Adipose Tissue in Male Mice by Inhibiting TNF-α Gene Expression in Macrophages. (United States)

    Tang, Lijun; Okamoto, Shiki; Shiuchi, Tetsuya; Toda, Chitoku; Takagi, Kazuyo; Sato, Tatsuya; Saito, Kumiko; Yokota, Shigefumi; Minokoshi, Yasuhiko


    Adipose tissue macrophages (ATMs) play an important role in the inflammatory response in obese animals. How ATMs are regulated in lean animals has remained elusive, however. We now show that the sympathetic nervous system (SNS) is necessary to maintain the abundance of the mRNA for the proinflammatory cytokine TNF-α at a low level in ATMs of lean mice. Intracerebroventricular injection of agouti-related neuropeptide increased the amount of TNF-α mRNA in epididymal (epi) white adipose tissue (WAT), but not in interscapular brown adipose tissue (BAT), through inhibition of sympathetic nerve activity in epiWAT. The surgical denervation and β-adrenergic antagonist propranolol up-regulated TNF-α mRNA in both epiWAT and BAT in vivo. Signaling by the β2-adrenergic receptor (AR) and protein kinase A down-regulated TNF-α mRNA in epiWAT explants and suppressed lipopolysaccharide-induced up-regulation of TNF-α mRNA in the stromal vascular fraction of this tissue. β-AR-deficient (β-less) mice manifested an increased plasma TNF-α concentration and increased TNF-α mRNA abundance in epiWAT and BAT. TNF-α mRNA abundance was greater in ATMs (CD11b(+) cells of the stromal vascular fraction) from epiWAT or BAT of wild-type mice than in corresponding CD11b(-) cells, and β2-AR mRNA abundance was greater in ATMs than in CD11b(-) cells of epiWAT. Our results show that the SNS and β2-AR-protein kinase A pathway maintain an anti-inflammatory state in ATMs of lean mice in vivo, and that the brain melanocortin pathway plays a role in maintaining this state in WAT of lean mice via the SNS.

  11. Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine. (United States)

    Mobini, Reza; Fu, Michael; Jansson, Per-Anders; Bergh, Claes-Håkan; Scharin Täng, Margareta; Waagstein, Finn; Andersson, Bert


    Although beta-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.6 mg of sustained-release moxonidine or matching placebo. Haemodynamics, NA kinetics and myocardial metabolism were studied over a 2.5 h time period. There was a significant reduction in pulmonary and systemic arterial pressures, together with a decrease in cardiac index in the moxonidine group. Furthermore, there was a simultaneous reduction in systemic and cardiac net spillover of NA in the moxonidine group. Analysis of myocardial consumption of substrates in the moxonidine group showed a significant increase in non-esterified fatty acid consumption and a possible trend towards an increase in myocardial oxygen consumption compared with the placebo group (P=0.16). We conclude that a single dose of moxonidine (0.6 mg) in patients already treated with a beta-blocker reduced cardiac and overall sympathetic activity. The finding of increased lipid consumption without decreased myocardial oxygen consumption indicates a lack of positive effects on myocardial metabolism under these conditions. We suggest this might be a reason for the failure of moxonidine to prevent deaths in long-term studies in CHF.

  12. Computer-based analysis of cardiac state using entropies, recurrence plots and Poincare geometry. (United States)

    Chua, K C; Chandran, V; Acharya, U R; Lim, C M


    Heart rate variability refers to the regulation of the sinoatrial node, the natural pacemaker of the heart by the sympathetic and parasympathetic branches of the autonomic nervous system. Heart rate variability is important because it provides a window to observe the heart's ability to respond to normal regulatory impulses that affect its rhythm. A computer-based intelligent system for analysis of cardiac states is very useful in diagnostics and disease management. Parameters are extracted from the heart rate signals and analysed using computers for diagnostics. This paper describes the analysis of normal and seven types of cardiac abnormal signals using approximate entropy (ApEn), sample entropy (SampEn), recurrence plots and Poincare plot patterns. Ranges of these parameters for various cardiac abnormalities are presented with an accuracy of more than 95%. Among the two entropies, ApEn showed better performance for all the cardiac abnormalities. Typical Poincare and recurrence plots are shown for various cardiac abnormalities.

  13. Sympathetically evoked Ca2+ signaling in arterial smooth muscle

    Institute of Scientific and Technical Information of China (English)

    Wei-jin ZANG; Joseph ZACHARIA; Christine LAMONT; Withrow Gil WIER


    The sympathetic nervous system plays an essential role in the control of total peripheral vascular resistance and blood flow, by controlling the contraction of small arteries. Perivascular sympathetic nerves release ATP, norepinephrine (NE) and neuropeptide Y. This review summarizes our knowledge of the intracellular Ca2+ signals that are activated by ATP and NE, acting respectively on P2X1 and α1 adrenoceptors in arterial smooth muscle. Each neurotransmitter produces a unique type of post-synaptic Ca2+ signal and associated contraction. The neural release of ATP and NE is thought to vary markedly with the pattern of nerve activity, probably reflecting both pre- and post-synaptic mechanisms. Finally, we show that Ca2+ signaling during neurogenic contractions activated by trains of sympathetic nerve fiber action potentials are in fact significantly different from that elicited by simple bath application of exogenous neurotransmitters to isolated arteries (a common experimental technique), and end by identifying important questions remaining in our understanding of sympathetic neurotransmission and the physiological regulation of contraction of small arteries.

  14. Morphine-sensitive paroxysmal sympathetic storm in pontine intracerebral hemorrhage. (United States)

    Ko, Sang-Bae; Kim, Chi Kyung; Lee, Seung-Hoon; Bae, Hee-Joon; Yoon, Byung-Woo


    Paroxysmal sympathetic storm (PSS) is a rare complication of severe traumatic brain injury or cerebrovascular disease. Various medications have been tried in patients with PSS, but the clinical responses of the patients were variable. We report a classic case of PSS after spontaneous pontine hemorrhage in which the patient's fluctuating blood pressure and body temperature were dramatically stabilized using morphine.

  15. Prolonged Paroxysmal Sympathetic Storming Associated with Spontaneous Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Yan Liu


    Full Text Available Paroxysmal sympathetic storming (PSS is a rare disorder characterized by acute onset of nonstimulated tachycardia, hypertension, tachypnea, hyperthermia, external posturing, and diaphoresis. It is most frequently associated with severe traumatic brain injuries and has been reported in intracranial tumors, hydrocephalous, severe hypoxic brain injury, and intracerebral hemorrhage. Although excessive release of catecholamine and therefore increased sympathetic activities have been reported in subarachnoid hemorrhage (SAH, there is no descriptive report of PSS primarily caused by spontaneous SAH up to date. Here, we report a case of prolonged PSS in a patient with spontaneous subarachnoid hemorrhage and consequent vasospasm. The sympathetic storming started shortly after patient was rewarmed from hypothermia protocol and symptoms responded to Labetalol, but intermittent recurrence did not resolve until 3 weeks later with treatment involving Midazolam, Fentanyl, Dexmedetomidine, Propofol, Bromocriptine, and minimizing frequency of neurological and vital checks. In conclusion, prolonged sympathetic storming can also be caused by spontaneous SAH. In this case, vasospasm might be a precipitating factor. Paralytics and hypothermia could mask the manifestations of PSS. The treatment of the refractory case will need both timely adjustment of medications and minimization of exogenous stressors or stimuli.

  16. Sympathetic neuroaxonal dystrophy in the aged rat pineal gland. (United States)

    Schmidt, Robert E; Dorsey, Denise A; Parvin, Curtis A; Beaudet, Lucie N


    Dysfunction of circadian melatonin production by the pineal gland in aged humans and rats is thought to reflect the functional loss of its sympathetic innervation. Our ultrastructural neuropathologic studies of the sympathetic innervation of the pineal gland of aged (24 months old) Fischer-344 and Sprague-Dawley rats showed loss of nerve terminals as well as the development of neuroaxonal dystrophy (NAD), an ultrastructurally distinctive distal axonopathy, far in excess of that in young control rats. Immunolocalization of tyrosine hydroxylase confirmed the age-related loss of normal noradrenergic innervation and development of NAD. NAD was more frequent in aged female rats compared to males and was particularly severe in aged female Sprague-Dawley rats compared to Fischer-344 rats. Pineal NGF content was significantly increased or unchanged in female and male aged Fischer-344 rats, respectively, compared to young controls. The rat pineal is a sensitive experimental model for the quantitative ultrastructural examination of age-related neuropathological changes in nerve terminals of postganglionic noradrenergic sympathetic axons, changes which may reflect similar changes in the diffusely distributed sympathetic innervation of other targeted endorgans.

  17. Causes and consequences of increased sympathetic activity in renal disease

    NARCIS (Netherlands)

    Joles, JA; Koomans, HA


    Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only

  18. 晚钠电流的魅影--从交感性 T 波到Takotsubo 综合征%The appearance of late sodium current:from sympathetic T wave to Takotsubo syndrome

    Institute of Scientific and Technical Information of China (English)



    Sympathetic T wave is a kind of cardiac electrophysiological abnormality related to sympathetic stress.Besides cardiac electrophysiological abnormalities,Takotsubo syndrome includes cardiac mechanical dysfunction.They share the same pathogenesis including sympathetic excitation, late sodium current (ⅠNaL )and electrophysiological abnormalities of myocardial cell mediated by calmodulin,etc.However,they may be different clinical manifestations of the same disease.%交感性 T 波是一类与交感应激有关的心脏电生理异常,而 Takotsubo 综合征包含了心电生理异常和心脏机械功能异常两方面。二者有共同的发病机制,包括交感兴奋、晚钠电流(late sodium current,ⅠNaL )及钙调蛋白介导的心肌细胞电生理异常等。它们可能是同一种疾病不同的临床表现形式。

  19. 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)


    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.

  20. Motor imagery muscle contraction strength influences spinal motor neuron excitability and cardiac sympathetic nerve activity



    [Purpose] The aim of this study was to investigate the changes in spinal motor neuron excitability and autonomic nervous system activity during motor imagery of isometric thenar muscle activity at 10% and 50% maximal voluntary contraction (MVC). [Methods] The F-waves and low frequency/high frequency (LF/HF) ratio were recorded at rest, during motor imagery, and post-trial. For motor imagery trials, subjects were instructed to imagine thenar muscle activity at 10% and 50% MVC while holding the...

  1. The central administration of C75, a fatty acid synthase inhibitor, activates sympathetic outflow and thermogenesis in interscapular brown adipose tissue. (United States)

    Cassolla, Priscila; Uchoa, Ernane Torres; Mansur Machado, Frederico Sander; Guimarães, Juliana Bohnen; Rissato Garófalo, Maria Antonieta; de Almeida Brito, Nilton; Kagohara Elias, Lucila Leico; Coimbra, Cândido Celso; do Carmo Kettelhut, Isis; Carvalho Navegantes, Luiz Carlos


    The present work investigated the participation of interscapular brown adipose tissue (IBAT), which is an important site for thermogenesis, in the anti-obesity effects of C75, a synthetic inhibitor of fatty acid synthase (FAS). We report that a single intracerebroventricular (i.c.v.) injection of C75 induced hypophagia and weight loss in fasted male Wistar rats. Furthermore, C75 induced a rapid increase in core body temperature and an increase in heat dissipation. In parallel, C75 stimulated IBAT thermogenesis, which was evidenced by a marked increase in the IBAT temperature that preceded the rise in the core body temperature and an increase in the mRNA levels of uncoupling protein-1. As with C75, an i.c.v. injection of cerulenin, a natural FAS inhibitor, increased the core body and IBAT temperatures. The sympathetic IBAT denervation attenuated all of the thermoregulatory effects of FAS inhibitors as well as the C75 effect on weight loss and hypophagia. C75 induced the expression of Fos in the paraventricular nucleus, preoptic area, dorsomedial nucleus, ventromedial nucleus, and raphé pallidus, all of which support a central role of FAS in regulating IBAT thermogenesis. These data indicate a role for IBAT in the increase in body temperature and hypophagia that is induced by FAS inhibitors and suggest new mechanisms explaining the weight loss induced by these compounds.

  2. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.


    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  3. Arthroscopic Patelloplasty and Circumpatellar Denervation for the Treatment of Patellofemoral Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Gang Zhao


    Full Text Available Background: Patellofemoral osteoarthritis commonly occurs in older people, often resulting in anterior knee pain and severely reduced quality of life. The aim was to examine the effectiveness of arthroscopic patelloplasty and circumpatellar denervation for the treatment of patellofemoral osteoarthritis (PFOA. Methods: A total of 156 PFOA patients (62 males, 94 females; ages 45-81 years, mean 66 years treated in our department between September 2012 and March 2013 were involved in this study. Clinical manifestations included recurrent swelling and pain in the knee joint and aggravated pain upon ascending/descending stairs, squatting down, or standing up. PFOA was treated with arthroscopic patelloplasty and circumpatellar denervation. The therapeutic effects before and after surgery were statistically evaluated using Lysholm and Kujala scores. The therapeutic effects were graded by classification of the degree of cartilage defect. Results: A total of 149 cases were successfully followed up for 14.8 months, on average. The incisions healed well, and no complications occurred. After surgery, the average Lysholm score improved from 73.29 to 80.93, and the average Kujala score improved from 68.34 to 76.48. This procedure was highly effective for patients with cartilage defects I-III but not for patients with cartilage defect IV. Conclusions: For PFOA patients, this procedure is effective for significantly relieving anterior knee pain, improving knee joint function and quality of life, and deferring arthritic progression.

  4. Chronic refractory myofascial pain and denervation supersensitivity as global public health disease. (United States)

    Chu, J; Bruyninckx, F; Neuhauser, D V


    Chronic pain with a 30.3% global prevalence significantly impacts universal health. Low back pain has a 9.4% prevalence worldwide causing the most widespread disability. Neck pain ranks 4th highest regarding years lived with disability with a 4.9% prevalence worldwide. The principal cause of pain in 85% of patients visiting a tertiary pain clinic has a myofascial origin. The root cause is multifocal neuromuscular ischaemia at myofascial trigger points from muscle tightening and shortening following spondylotic radiculopathy induced partial denervation. Chronic refractory myofascial pain (CRMP) is a neuromusculoskeletal disease needing management innovations. Using electrical twitch-obtaining intramuscular stimulation (eToims), we provide objective evidence of denervation supersensitivity in multiple myotomes as cause, aggravation and maintenance of CRMP. This study underscores our previous findings that eToims is safe and efficacious for long-term use in CRMP. eToims aids potential prevention (pre-rehabilitation), simultaneous diagnosis, treatment (rehabilitation) and prognosis in real time for acute and CRMP management.

  5. P2 receptors in the central and peripheral nervous systems modulating sympathetic vasomotor tone. (United States)

    Ralevic, V


    Arterial pressure depends on the level of activity of sympathetic vasoconstrictor outflow to blood vessels. This activity is generated in the central nervous system, and involves inputs from a variety of brain regions projecting to sympathetic preganglionic neurones. Of especial interest are a group of neurones in the rostral ventrolateral medulla (RVLM), as they have been demonstrated to have a fundamental role in reflex regulation of the cardiovascular system, and in generation of tonic drive to sympathetic outflow. Sympathetic outflow to blood vessels is additionally modulated at sympathetic ganglia, and at the peripheral terminals of sympathetic nerves. This review considers the role of P2 purine receptors in this neural pathway. Ionotropic P2X receptors are expressed in the RVLM, in sympathetic ga