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Sample records for studying cardiac adrenergic

  1. Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation

    Science.gov (United States)

    Baker, Candice N.; Gidus, Sarah A.; Price, George F.; Peoples, Jessica N. R.

    2014-01-01

    As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh−/− embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. PMID:25516547

  2. Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation.

    Science.gov (United States)

    Baker, Candice N; Gidus, Sarah A; Price, George F; Peoples, Jessica N R; Ebert, Steven N

    2015-03-01

    As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh-/- embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. Copyright © 2015 the American Physiological Society.

  3. Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

    Science.gov (United States)

    Duncan, Dallas; Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

    2018-03-06

    The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied

  4. β adrenergic receptor modulation of neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Bateman, R J; Boychuk, C R; Philbin, K E; Mendelowitz, D

    2012-05-17

    β-adrenergic receptors are a class of G protein-coupled receptors that have essential roles in regulating heart rate, blood pressure, and other cardiorespiratory functions. Although the role of β adrenergic receptors in the peripheral nervous system is well characterized, very little is known about their role in the central nervous system despite being localized in many brain regions involved in autonomic activity and regulation. Since parasympathetic activity to the heart is dominated by cardiac vagal neurons (CVNs) originating in the nucleus ambiguus (NA), β adrenergic receptors localized in the NA represent a potential target for modulating cardiac vagal activity and heart rate. This study tests the hypothesis that activation of β adrenergic receptors alters the membrane properties and synaptic neurotransmission to CVNs. CVNs were identified in brainstem slices, and membrane properties and synaptic events were recorded using the whole-cell voltage-clamp technique. The nonselective β agonist isoproterenol significantly decreased inhibitory GABAergic and glycinergic as well as excitatory glutamatergic neurotransmission to CVNs. In addition, the β(1)-selective receptor agonist dobutamine, but not β(2) or β(3) receptor agonists, significantly decreased inhibitory GABAergic and glycinergic and excitatory glutamatergic neurotransmission to CVNs. These decreases in neurotransmission to CVNs persisted in the presence of tetrodotoxin (TTX). These results provide a mechanism by which activation of adrenergic receptors in the brainstem can alter parasympathetic activity to the heart. Likely physiological roles for this adrenergic receptor activation are coordination of parasympathetic-sympathetic activity and β receptor-mediated increases in heart rate upon arousal. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

    Science.gov (United States)

    O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

    2014-01-01

    Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

  6. Modeling the Effects of β1-Adrenergic Receptor Blockers and Polymorphisms on Cardiac Myocyte Ca2+ Handling

    Science.gov (United States)

    Amanfu, Robert K.

    2014-01-01

    β-Adrenergic receptor blockers (β-blockers) are commonly used to treat heart failure, but the biologic mechanisms governing their efficacy are still poorly understood. The complexity of β-adrenergic signaling coupled with the influence of receptor polymorphisms makes it difficult to intuit the effect of β-blockers on cardiac physiology. While some studies indicate that β-blockers are efficacious by inhibiting β-adrenergic signaling, other studies suggest that they work by maintaining β-adrenergic responsiveness. Here, we use a systems pharmacology approach to test the hypothesis that in ventricular myocytes, these two apparently conflicting mechanisms for β-blocker efficacy can occur concurrently. We extended a computational model of the β1-adrenergic pathway and excitation-contraction coupling to include detailed receptor interactions for 19 ligands. Model predictions, validated with Ca2+ and Förster resonance energy transfer imaging of adult rat ventricular myocytes, surprisingly suggest that β-blockers can both inhibit and maintain signaling depending on the magnitude of receptor stimulation. The balance of inhibition and maintenance of β1-adrenergic signaling is predicted to depend on the specific β-blocker (with greater responsiveness for metoprolol than carvedilol) and β1-adrenergic receptor Arg389Gly polymorphisms. PMID:24867460

  7. Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, C.; Acar, P.; Sidi, D.

    2006-01-01

    I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 ± 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 ± 49% vs 162 ± 26%, p < 0.0001 and LVEF = 43 ± 17% vs 26 ± 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

  8. Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.

    Science.gov (United States)

    Khalilimeybodi, Ali; Daneshmehr, Alireza; Sharif-Kashani, Babak

    2018-07-01

    The chronic stimulation of β-adrenergic receptors plays a crucial role in cardiac hypertrophy and its progression to heart failure. In β-adrenergic signaling, in addition to the well-established classical pathway, Gs/AC/cAMP/PKA, activation of non-classical pathways such as Gi/PI3K/Akt/GSK3β and Gi/Ras/Raf/MEK/ERK contribute in cardiac hypertrophy. The signaling network of β-adrenergic-induced hypertrophy is very complex and not fully understood. So, we use a computational approach to investigate the dynamic response and contribution of β-adrenergic mediators in cardiac hypertrophy. The proposed computational model provides insights into the effects of β-adrenergic classical and non-classical pathways on the activity of hypertrophic transcription factors CREB and GATA4. The results illustrate that the model captures the dynamics of the main signaling mediators and reproduces the experimental observations well. The results also show that despite the low portion of β2 receptors out of total cardiac β-adrenergic receptors, their contribution in the activation of hypertrophic mediators and regulation of β-adrenergic-induced hypertrophy is noticeable and variations in β1/β2 receptors ratio greatly affect the ISO-induced hypertrophic response. The model results illustrate that GSK3β deactivation after β-adrenergic receptor stimulation has a major influence on CREB and GATA4 activation and consequent cardiac hypertrophy. Also, it is found through sensitivity analysis that PKB (Akt) activation has both pro-hypertrophic and anti-hypertrophic effects in β-adrenergic signaling.

  9. β1-adrenergic regulation of rapid component of delayed rectifier K+ currents in guinea-pig cardiac myocytes.

    Science.gov (United States)

    Wang, Sen; Xu, Di; Wu, Ting-Ting; Guo, Yan; Chen, Yan-Hong; Zou, Jian-Gang

    2014-05-01

    Human ether-à-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG‑associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between β1-adrenergic stimulation and IKr in guinea-pig left ventricular myocytes and to analyze how IKr is regulated following activation of the β1-adrenergic signaling pathway. The IKr current was measured using a whole-cell patch-clamp technique. A selective β1-adrenergic receptor agonist, xamoterol, at concentrations of 0.01-100 µM decreased IKr in a concentration-dependent manner. The 10 µM xamoterol-induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in β1-adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the β1-adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.

  10. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

  11. Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylp ropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

    International Nuclear Information System (INIS)

    Samnick, Samuel; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin

    2004-01-01

    In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the 99m Tc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylpropylamino)-piperidine ( 99m Tc-FBPBAT) with those of the clinically established meta-[ 123 I]iodobenzylguanidine ( 123 I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various α- and β-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of 99m Tc-FBPBAT and 123 I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 minutes. Radioactivity uptake after a 60-minute incubation at 37 degree sign C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, 99m Tc-FBPBAT showed the higher uptake, relative to 123 I-MIBG, at any given cell concentration. The cellular uptake of 99m Tc-FBPBAT was lower at 4 degree sign C and 20 degree sign C than at 37 degree sign C. In contrast, the 123 I-MIBG uptake was only slightly temperature dependent. Inhibition experiments confirmed that the cellular uptake of 123 I-MIBG is mediated by the uptake-I carrier, whereas α 1 - and β 1 -adrenoceptors were predominantly involved in the uptake of 99m Tc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that 99m Tc-FBPBAT accumulated in myocardium after intravenous injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per gram at 15 and 60 minutes postinjection, compared with 3.10% and 2.21% injected dose per gram of tissue (%ID/g) in the experiment with 123 I-MIBG, respectively. Prazosin, urapidil, and metoprolol were as effective as treatment with other adrenergic

  12. Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylp ropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

    Energy Technology Data Exchange (ETDEWEB)

    Samnick, Samuel E-mail: rassam@uniklinik-saarland.de; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin

    2004-05-01

    In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the {sup 99m}Tc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylpropylamino)-piperidine ({sup 99m}Tc-FBPBAT) with those of the clinically established meta-[{sup 123}I]iodobenzylguanidine ({sup 123}I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various {alpha}- and {beta}-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of {sup 99m}Tc-FBPBAT and {sup 123}I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 minutes. Radioactivity uptake after a 60-minute incubation at 37 degree sign C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, {sup 99m}Tc-FBPBAT showed the higher uptake, relative to {sup 123}I-MIBG, at any given cell concentration. The cellular uptake of {sup 99m}Tc-FBPBAT was lower at 4 degree sign C and 20 degree sign C than at 37 degree sign C. In contrast, the {sup 123}I-MIBG uptake was only slightly temperature dependent. Inhibition experiments confirmed that the cellular uptake of {sup 123}I-MIBG is mediated by the uptake-I carrier, whereas {alpha}{sub 1}- and {beta}{sub 1}-adrenoceptors were predominantly involved in the uptake of {sup 99m}Tc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that {sup 99m}Tc-FBPBAT accumulated in myocardium after intravenous injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per gram at 15 and 60 minutes postinjection, compared with 3.10% and 2.21% injected dose per gram of tissue (%ID/g) in the experiment with {sup 123}I

  13. Cardiac β-adrenergic responsiveness of obese Zucker rats: The role of AMPK.

    Science.gov (United States)

    Bussey, Carol T; Thaung, Hp Aye; Hughes, Gillian; Bahn, Andrew; Lamberts, Regis R

    2018-06-05

    What is the central question of the study? What is the main finding and its importance? 1. Is the reduced signalling of AMPK, a key regulator of energy homeostasis in the heart, responsible for the reduced β-adrenergic responsiveness of the heart in obesity? 2. Inhibition of AMPK in isolated hearts prevented the reduced cardiac β-adrenergic responsiveness of obese rats, which was accompanied by reduced phosphorylation of AMPK, a proxy of AMPK activity. This suggests a direct functional link between β-adrenergic responsiveness and AMPK signalling in the heart, and that AMPK might be an important target to restore the β-adrenergic responsiveness in the heart in obesity. The obesity epidemic impacts heavily on cardiovascular health, in part due to changes in cardiac metabolism. AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis in the heart, and is regulated by β-adrenoceptors (AR) under normal conditions. In obesity, chronic sympathetic overactivation leads to impaired cardiac β-AR responsiveness, although it is unclear whether AMPK signalling, downstream of β-AR, contributes to this dysfunction. Therefore, we aimed to determine whether reduced AMPK signalling is responsible for the reduced β-AR responsiveness in obesity. In isolated hearts of lean and obese Zucker rats, we tested β-AR responsiveness to β 1 -AR agonist isoproterenol (ISO, 1 × 10 -10 - 5 × 10 -8  M) in the absence and presence of the AMPK inhibitor compound C (CC, 10 μM). β 1 -AR expression and AMPK phosphorylation were assessed by Western blot. β-Adrenergic responsiveness was reduced in the hearts of obese rats (LogEC50 of ISO-developed pressure dose-response curves: lean -8.53 ± 0.13 vs. obese -8.35 ± 0.10 10 x M; p  0.05, n = 6 per group). β 1 -AR expression and AMPK phosphorylation were reduced in hearts of obese rats (AMPK at Thr 172 : lean 1.73 ± 0.17 vs. lean CC 0.81 ± 0.13, and obese 1.18 ± 0.09 vs. obese CC 0.81 ± 0

  14. PET measures of pre- and post-synaptic cardiac beta adrenergic function

    Energy Technology Data Exchange (ETDEWEB)

    Link, Jeanne M.; Stratton, John R.; Levy, Wayne; Poole, Jeanne E.; Shoner, Steven C.; Stuetzle, Werner; Caldwell, James H. E-mail: jcald@u.washington.edu

    2003-11-01

    Positron Emission Tomography was used to measure global and regional cardiac {beta}-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [{sup 11}C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [{sup 11}C]-CGP12177 was used to measure cell surface {beta}-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.

  15. In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

    DEFF Research Database (Denmark)

    Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

    2013-01-01

    β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We...

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

    Science.gov (United States)

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

    2018-03-01

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

  17. Remodeling of intrinsic cardiac neurons: effects of β-adrenergic receptor blockade in guinea pig models of chronic heart disease.

    Science.gov (United States)

    Hardwick, Jean C; Southerland, E Marie; Girasole, Allison E; Ryan, Shannon E; Negrotto, Sara; Ardell, Jeffrey L

    2012-11-01

    Chronic heart disease induces remodeling of cardiac tissue and associated neuronal components. Treatment of chronic heart disease often involves pharmacological blockade of adrenergic receptors. This study examined the specific changes in neuronal sensitivity of guinea pig intrinsic cardiac neurons to autonomic modulators in animals with chronic cardiac disease, in the presence or absence of adrenergic blockage. Myocardial infarction (MI) was produced by ligature of the coronary artery and associated vein on the dorsal surface of the heart. Pressure overload (PO) was induced by a banding of the descending dorsal aorta (∼20% constriction). Animals were allowed to recover for 2 wk and then implanted with an osmotic pump (Alzet) containing either timolol (2 mg·kg(-1)·day(-1)) or vehicle, for a total of 6-7 wk of drug treatment. At termination, intracellular recordings from individual neurons in whole mounts of the cardiac plexus were used to assess changes in physiological responses. Timolol treatment did not inhibit the increased sensitivity to norepinephrine seen in both MI and PO animals, but it did inhibit the stimulatory effects of angiotensin II on the norepinephrine-induced increases in neuronal excitability. Timolol treatment also inhibited the increase in synaptically evoked action potentials observed in PO animals with stimulation of fiber tract bundles. These results demonstrate that β-adrenergic blockade can inhibit specific aspects of remodeling within the intrinsic cardiac plexus. In addition, this effect was preferentially observed with active cardiac disease states, indicating that the β-receptors were more influential on remodeling during dynamic disease progression.

  18. Beta-Adrenergic Receptor Polymorphisms and Cardiac Graft Function in Potential Organ Donors

    Science.gov (United States)

    Khush, K.K.; Pawlikowska, L.; Menza, R.L.; Goldstein, B.A.; Hayden, V.; Nguyen, J.; Kim, H.; Poon, A.; Sapru, A.; Matthay, M.A.; Kwok, P.Y.; Young, W.L.; Baxter-Lowe, L.A.; Zaroff, J.G.

    2012-01-01

    Prior studies have demonstrated associations between β-adrenergic receptor polymorphisms and left ventricular dysfunction—an important cause of allograft non-utilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. 1,043 organ donors managed from 2001-2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg), and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fractiondonor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 mcg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts. PMID:22994654

  19. Use of {sup 123}I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, Christophe [Service de Medecine Nucleaire, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743, Paris Cedex 15 (France); Acar, Philippe; Sidi, Daniel [Service de Cardiologie Pediatrique, Hopital Necker-Enfants Malades, Paris (France)

    2003-12-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using {sup 123}I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39{+-}57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent {sup 123}I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of {sup 123}I-MIBG. Cardiac neuronal uptake of {sup 123}I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%{+-}49% vs 162%{+-}26%, P<0.0001, and LVEF=43%{+-}17% vs 26%{+-}11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  20. Use of 123I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Christophe; Acar, Philippe; Sidi, Daniel

    2003-01-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using 123 I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent 123 I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of 123 I-MIBG. Cardiac neuronal uptake of 123 I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  1. Developmental changes in the role of a pertussis toxin sensitive guanine nucleotide binding protein in the rat cardiac alpha1-adrenergic system

    International Nuclear Information System (INIS)

    Han, H.M.

    1989-01-01

    During development, the cardiac alpha 1 -adrenergic chronotropic response changes from positive in the neonate to negative in the adult. This thesis examined the possibility of a developmental change in coupling of a PT-sensitive G-protein to the alpha 1 -adrenergic receptor. Radioligand binding experiments performed with the iodinated alpha 1 -selective radioligand [ 125 I]-I-2-[β-(4-hydroxphenyl)ethylaminomethyl]tetralone ([ 125 I]-IBE 2254) demonstrated that the alpha 1 -adrenergic receptor is coupled to a G-protein in both neonatal and adult rat hearts. However, in the neonate the alpha 1 -adrenergic receptor is coupled to a PT-insensitive G-protein, whereas in the adult the alpha 1 -adrenergic receptor is coupled to both a PT-insensitive and a PT-sensitive G-protein. Consistent with the results from binding experiments, PT did not have any effect on the alpha 1 -mediated positive chronotropic response in the neonate, whereas in the adult the alpha 1 -mediated negative chronotropic response was completely converted to a positive one after PT-treatment. This thesis also examined the possibility of an alteration in coupling of the alpha 1 -adrenergic receptor to its effector under certain circumstances such as high potassium (K + ) depolarization in nerve-muscle (NM) co-cultures, a system which has been previously shown to be a convenient in vitro model to study the mature inhibitory alpha 1 -response

  2. Effect of age on upregulation of the cardiac adrenergic beta receptors

    International Nuclear Information System (INIS)

    Tumer, N.; Houck, W.T.; Roberts, J.

    1990-01-01

    Radioligand binding studies were performed to determine whether upregulation of postjunctional beta receptors occurs in sympathectomized hearts of aged animals. Fischer 344 rats 6, 12, and 24 months of age (n = 10) were used in these experiments. To produce sympathectomy, rats were injected with 6-hydroxydopamine hydrobromide (6-OHDA; 2 x 50 mg/kg iv) on days 1 and 8; the animals were decapitated on day 15. The depletion of norepinephrine in the heart was about 86% in each age group. 125I-Iodopindolol (IPIN), a beta adrenergic receptor antagonist, was employed to determine the affinity and total number of beta adrenergic receptors in the ventricles of the rat heart. The maximal number of binding sites (Bmax) was significantly elevated by 37%, 48%, and 50% in hearts from sympathectomized 6-, 12-, and 24-month-old rats, respectively. These results indicate that beta receptor mechanisms in older hearts can respond to procedures that cause upregulation of the beta adrenergic receptors

  3. Desipramine increases cardiac parasympathetic activity via α2-adrenergic mechanism in rats.

    Science.gov (United States)

    Kawada, Toru; Akiyama, Tsuyoshi; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

    2017-07-01

    Desipramine (DMI) is a blocker of neuronal norepinephrine (NE) uptake transporter. Although intravenous DMI has been shown to cause centrally-mediated sympathoinhibition and peripheral NE accumulation, its parasympathetic effect remains to be elucidated. We hypothesized that intravenous DMI activates the cardiac vagal nerve via an α 2 -adrenergic mechanism. Using a cardiac microdialysis technique, changes in myocardial interstitial acetylcholine (ACh) levels in the left ventricular free wall in response to intravenous DMI (1mg·kg -1 ) were examined in anesthetized rats. In rats with intact vagi (n=7), intravenous DMI increased ACh from 1.67±0.43 to 2.48±0.66nM (Padrenergic stimulation in experimental settings in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Thermal, cardiac and adrenergic responses to repeated local cooling.

    Science.gov (United States)

    Janský, L; Matousková, E; Vávra, V; Vybíral, S; Janský, P; Jandová, D; Knízková, I; Kunc, P

    2006-01-01

    The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.

  5. The AKAP Cypher/Zasp contributes to β-adrenergic/PKA stimulation of cardiac CaV1.2 calcium channels.

    Science.gov (United States)

    Yu, Haijie; Yuan, Can; Westenbroek, Ruth E; Catterall, William A

    2018-06-04

    Stimulation of the L-type Ca 2+ current conducted by Ca V 1.2 channels in cardiac myocytes by the β-adrenergic/protein kinase A (PKA) signaling pathway requires anchoring of PKA to the Ca V 1.2 channel by an A-kinase anchoring protein (AKAP). However, the AKAP(s) responsible for regulation in vivo remain unknown. Here, we test the role of the AKAP Cypher/Zasp in β-adrenergic regulation of Ca V 1.2 channels using physiological studies of cardiac ventricular myocytes from young-adult mice lacking the long form of Cypher/Zasp (LCyphKO mice). These myocytes have increased protein levels of Ca V 1.2, PKA, and calcineurin. In contrast, the cell surface density of Ca V 1.2 channels and the basal Ca 2+ current conducted by Ca V 1.2 channels are significantly reduced without substantial changes to kinetics or voltage dependence. β-adrenergic regulation of these L-type Ca 2+ currents is also significantly reduced in myocytes from LCyphKO mice, whether calculated as a stimulation ratio or as net-stimulated Ca 2+ current. At 100 nM isoproterenol, the net β-adrenergic-Ca 2+ current conducted by Ca V 1.2 channels was reduced to 39 ± 12% of wild type. However, concentration-response curves for β-adrenergic stimulation of myocytes from LCyphKO mice have concentrations that give a half-maximal response similar to those for wild-type mice. These results identify Cypher/Zasp as an important AKAP for β-adrenergic regulation of cardiac Ca V 1.2 channels. Other AKAPs may work cooperatively with Cypher/Zasp to give the full magnitude of β-adrenergic regulation of Ca V 1.2 channels observed in vivo. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

  6. α-2 adrenergic receptor: a radiohistochemical study

    International Nuclear Information System (INIS)

    Unnerstall, J.R.

    1984-01-01

    α-2 adrenergic agents have been shown to influence blood pressure, heart rate and other physiological and behavioral functions through interactions with adrenergic pathways within the central nervous system. Pharmacologically relevant α-1 adrenergic receptors were biochemically characterized and radiohistochemically analyzed in intact tissue sections of the rat and human central nervous system. The anatomical distribution of the α-2 receptors, labeled with the agonist [ 3 H]para-aminoclonidine, verified the concept that α-2 receptors are closely associated with adrenergic nerve terminals and that α-2 agents can influence autonomic and endocrine function through an action in the central nervous system. Since α-2 agonists can influence sympathetic outflow, α-2 binding sites were closely analyzed in the intermediolateral cell column of the thoracic spinal cord. The transport of putative presynaptic α-2 binding sites in the rat sciatic nerve was analyzed by light microscopic radiohistochemical techniques. Finally, in intact tissue section of the rat central nervous system, the biochemical characteristics of [ 3 H]rauwolscine binding were analyzed. Data were also shown which indicates that the synthetic α-2 antagonist [ 3 H]RX781094 also binds to α-2 receptors with high-affinity. Further, the distribution of [ 3 H]RX781094 binding sites in the rat central nervous system was identical to the distribution seen when using [ 3 H]para-aminoclonidine

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fangyun Tian

    2018-02-01

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

  9. Changes in cardiac adrenergic nervous system in patients submitted to transmyocardial laser revascularisation - assessment with I-123-MIBG SPECT

    International Nuclear Information System (INIS)

    Teresinska, A.; Sliwinski, M.; Konieczna, S.; Szymanska, M.; Hendzel, P.; Juraszynski, Z.; Wojnowski, A.; Debski, A.; Szumilak, B.

    2002-01-01

    Meta-iodobenzylguanidine [MIBG] is an analogue of guanethidine, which, after labelling with iodine-123, has been used for cardiac neuronal imaging in conditions such as coronary artery disease, myocardial infarction, heart failure, cardiac arrhythmia, diabetes mellitus, heart transplantation. The aim of our program using I-123-Mibg is: 1) to study the range of influence of the laser energy (CO 2 -high power laser) during trans myocardial laser revascularisation [Tml] on cardiac adrenergic nervous system, and 2) to assess if disruption of this system can be one of the mechanisms responsible for clinical improvement observed early after Tml. Methods: The patients with high pre-operative probability of having sole TMLR or TMLR combined with only 1 bypass are studied before the operation for neuronal activity with I-123-MIBG SPECT [MIBG-0]. The patients (if they were operated according to the assumption) are studied postoperatively with I-123-MIBG SPECT as early as possible from clinical point of view [MIBG-early] and 6 months after operation [MIBG-6m]. Up to now, in 27 pts the preoperative and early postoperative (7-39 days, av. 13±7 days) tests were performed and in 15 pts - also MIBG-6m was performed. The group characteristics: 21M (78%); age: 43-76y, av. 64±10y; all the patients in III/IV CCS class; 20 pts (74%) after 1-2 MI; 5 pts (19%) after earlier CABG or PTCA. Registration of I-123-MIBG SPECT images was started 4 hrs after injection of the radiopharmaceutical. All SPECT studies were assessed in 17 segments (seg) of the LV. The bypassed seg and the septal seg were excluded from the assessment (as not submitted to the laser). Results: In 22 studies (32%), the evaluation of MIBG uptake was not possible because of very low heart uptake and/or very high extra cardiac uptake. Finally, 18 of the preoperative, 18 of the early postoperative and 11 of the late postoperative studies were submitted to segmental analysis. In MIBG-0, there were 172 uptake defects in

  10. Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

    Science.gov (United States)

    Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

    2018-02-01

    Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression.

    Science.gov (United States)

    Knowlton, K U; Baracchini, E; Ross, R S; Harris, A N; Henderson, S A; Evans, S M; Glembotski, C C; Chien, K R

    1991-04-25

    To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.

  12. Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy; Interet de la scintigraphie cardiaque a l'I-123 MIBG pour evaluer l'impact du carvedilol sur la fonction neuronale adrenergique cardiaque dans les myocardiopathies dilatees de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, C. [Hopital Europeen Georges Pompidou (HEGP), Dept. de Physiologie et Radio-Isotopes, 75 - Paris (France); Acar, P. [Centre Hospitalier Universitaire, Service de Cardiologie Pediatrique, Hopital des Enfants, 31 - Toulouse (France); Sidi, D. [Centre Hospitalier Universitaire Necker-Enfants-Malades, 75 - Paris (France)

    2006-04-15

    I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 {+-} 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 {+-} 49% vs 162 {+-} 26%, p < 0.0001 and LVEF = 43 {+-} 17% vs 26 {+-} 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

  13. Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

    Science.gov (United States)

    Hu, L W; Benvenuti, L A; Liberti, E A; Carneiro-Ramos, M S; Barreto-Chaves, M L M

    2003-12-01

    The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

  14. β-Adrenergic receptors desensitization is not involved in exercise-induced cardiac fatigue: NADPH oxidase-induced oxidative stress as a new trigger.

    Science.gov (United States)

    Vitiello, Damien; Boissière, Julien; Doucende, Grégory; Gayrard, Sandrine; Polge, Anne; Faure, Patrice; Goux, Aurélie; Tanguy, Stéphane; Obert, Philippe; Reboul, Cyril; Nottin, Stéphane

    2011-11-01

    Prolonged strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Previous studies suggest that β-adrenergic pathway desensitization could be involved in this phenomenon, but it remains to be confirmed. Moreover, other underlying mechanisms involving oxidative stress have been recently proposed. The present study aimed to evaluate the involvement of both the β-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative stress in myocardial dysfunction in rats following PSE. Rats were divided into 4 groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO, respectively). We evaluated cardiac function in vivo and ex vivo during basal conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI) release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in LV developed pressure, intrinsic myocardial contractility, and relaxation associated with an increase in plasma cTnI release. Our in vivo and ex vivo results demonstrated no differences in myocardial response to isoproterenol and of effective dose 50 between control and PSE rats. Interestingly, the LV dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units (au): 1.98 ± 0.07 vs. 1.35 ± 0.10; P stress from the Nox enzyme.

  15. β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo.

    Directory of Open Access Journals (Sweden)

    Jennifer A Talarico

    Full Text Available β-adrenergic receptor (βAR-mediated transactivation of epidermal growth factor receptor (EGFR has been shown to promote cardioprotection in a mouse model of heart failure and we recently showed that this mechanism leads to enhanced cell survival in part via regulation of apoptotic transcript expression in isolated primary rat neonatal cardiomyocytes. Thus, we hypothesized that this process could regulate cardiac transcript expression in vivo. To comprehensively assess cardiac transcript alterations in response to acute βAR-dependent EGFR transactivation, we performed whole transcriptome analysis of hearts from C57BL/6 mice given i.p. injections of the βAR agonist isoproterenol in the presence or absence of the EGFR antagonist gefitinib for 1 hour. Total cardiac RNA from each treatment group underwent transcriptome analysis, revealing a substantial number of transcripts regulated by each treatment. Gefitinib alone significantly altered the expression of 405 transcripts, while isoproterenol either alone or in conjunction with gefitinib significantly altered 493 and 698 distinct transcripts, respectively. Further statistical analysis was performed, confirming 473 transcripts whose regulation by isoproterenol were significantly altered by gefitinib (isoproterenol-induced up/downregulation antagonized/promoted by gefinitib, including several known to be involved in the regulation of numerous processes including cell death and survival. Thus, βAR-dependent regulation of cardiac transcript expression in vivo can be modulated by the EGFR antagonist gefitinib.

  16. β-Adrenergic regulation of the cardiac Na+-K+ ATPase mediated by oxidative signaling

    DEFF Research Database (Denmark)

    Galougahi, Keyvan Karimi; Liu, Chia-Chi; Bundgaard, Henning

    2012-01-01

    Activation of β-adrenergic receptors (ARs) elicits responses arising from protein kinase A (PKA)-mediated phosphorylation of target proteins that regulate Ca(2+)-dependent excitation-contraction coupling. Some important targets for β-AR- and PKA-dependent pathways, including the sarcolemmal Na(+)...

  17. Cardiac Function in Patients with Early Cirrhosis during Maximal Beta-Adrenergic Drive

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Dahl, Emilie Kristine

    2014-01-01

    BACKGROUND AND AIM: Cardiac dysfunction in patients with early cirrhosis is debated. We investigated potential cardiac dysfunction by assessing left ventricular systolic performance during a dobutamine stress test in patients with early cirrhosis. PATIENTS AND METHODS: Nineteen patients with Chil...

  18. Overexpression Myocardial Inducible Nitric Oxide Synthase Exacerbates Cardiac Dysfunction and Beta-Adrenergic Desensitization in Experimental Hypothyroidism☆,☆☆

    Science.gov (United States)

    Shao, Qun; Cheng, Heng-Jie; Callahan, Michael F.; Kitzman, Dalane W; Li, Wei-Min; Cheng, Che Ping

    2015-01-01

    Background Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cadiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca2+]i transient ([Ca2+]iT), and β-adrenergic hyporesponsiveness. Methods and Results We simultaneously evaluated LV functional performance and compared myocyte three NOS, β-adrenergic receptors (AR) and SERCA2a expressions and assessed cardiomyocyte contractile and [Ca2+]iT responses to β-AR stimulation with and without pretreatment of iNOS inhibitor (1400W, 10−5 mol/L) in 26 controls and 26 rats with hypothyroidism induced by methimazole (~30 mg/kg/day for 8 weeks in the drinking water). Compared with controls, in hypothyroidism, total serum T3 and T4 were significantly reduced followed by significantly decreased LV contractility (EES) with increased LV time constant of relaxation. These LV abnormalities were accompanied by concomitant significant decreases in myocyte contraction (dL/dtmax), relaxation (dR/dtmax), and [Ca2+]iT. In hypothyroidism, isoproterenol (10−8 M) produced significantly smaller increases in dL/dtmax, dR/dtmax and [Ca2+]iT. These changes were associated with decreased β1-AR and SERCA2a, but significantly increased iNOS. Moreover, only in hypothyroidism, pretreatment with iNOS inhibitor significantly improved basal and isoproterenol-stimulated myocyte contraction, relaxation and [Ca2+]iT. Conclusions Hypothyroidism produces intrinsic defects of LV myocyte force-generating capacity and relaxation with β-AR desensitization. Up-regulation of cadiomyocyte iNOS may promote progressive cardiac dysfunction in

  19. Evaluation of cardiac adrenergic neuronal damage in rats with doxorubicin-induced cardiomyopathy using iodine-131 MIBG autoradiography and PGP 9.5 immunohistochemistry

    International Nuclear Information System (INIS)

    Jeon, T.J.; Lee, J.D.; Ha, J.-W.; Yang, W.I.; Cho, S.H.

    2000-01-01

    Doxorubicin is one of the most useful anticancer agents, but its repeated administration can induce irreversible cardiomyopathy as a major complication. The purpose of this study was to investigate doxorubicin toxicity on cardiac sympathetic neurons using iodine-131-metaiodobenzylguanidine (MIBG) and protein gene product (PGP) 9.5 immunohistochemistry, which is a marker of cardiac innervation. Wistar rats were treated with doxorubicin (2 mg/kg, i.v.) once a week for 4 (n=5), 6 (n=6) or 8 (n=7) weeks consecutively. Left ventricular ejection fraction (LVEF), calculated by M-mode echocardiography, was used as an indicator of cardiac function. Plasma noradrenaline (NA) concentration was measured by high-performance liquid chromatography (HPLC). 131 I-MIBG uptake of the left ventricular wall (24 ROIs) was measured by autoradiography. 131 I-MIBG uptake pattern was compared with histopathological results, the neuronal population on PGP 9.5 immunohistochemistry and the degree of myocyte damage assessed using a visual scoring system on haematoxylin and eosin and Masson's trichrome staining. LVEF was significantly decreased in the 8-week group (P 131 I-MIBG uptake ratio of subepicardium to subendocardium were significantly increased (P<0.05) in the 8-week group as compared with the control group. It may be concluded that radioiodinated MIBG is a reliable marker for the detection of cardiac adrenergic neuronal damage in doxorubicin-induced cardiomyopathy; it detects such damage earlier than do other clinical parameters and in this study showed a good correlation with the reduction in the neuronal population on PGP 9.5 stain. The subendocardial layer appeared to be more vulnerable to doxorubicin than the subepicardium. (orig.)

  20. MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors.

    Science.gov (United States)

    Ogata, Takehiro; Naito, Daisuke; Nakanishi, Naohiko; Hayashi, Yukiko K; Taniguchi, Takuya; Miyagawa, Kotaro; Hamaoka, Tetsuro; Maruyama, Naoki; Matoba, Satoaki; Ikeda, Koji; Yamada, Hiroyuki; Oh, Hidemasa; Ueyama, Tomomi

    2014-03-11

    The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as "caveolae." Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR-induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

  1. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  2. Arg16Gly and Gln27Glu β2 adrenergic polymorphisms influence cardiac autonomic modulation and baroreflex sensitivity in healthy young Brazilians

    Science.gov (United States)

    Atala, Magda M; Goulart, Alessandra; Guerra, Grazia M; Mostarda, Cristiano; Rodrigues, Bruno; Mello, Priscila R; Casarine, Dulce E; Irigoyen, Maria-Claudia; Pereira, Alexandre C; Consolim-Colombo, Fernanda M

    2015-01-01

    The association between functional β2 adrenergic receptor (β2-AR) polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common polymorphisms in the β2-AR gene (Gln27Glu β2 and Arg16Gly β2) were studied to determine whether they might affect tonic and reflex cardiac sympathetic activity in healthy young subjects. A total of 213 healthy young white subjects of both genders (53% female), aged 18-30 years (23.5±3.4 y), had their continuous blood pressure curves noninvasively recorded by Finometer at baseline, and other hemodynamic parameters, as cardiac autonomic modulation, baroreflex sensitivity, and allele, genotype, and diplotype frequencies calculated. Associations were made between Arg16Gly β2 and Gln27Glu β2 polymorphisms and between β2-AR diplotypes and all variables. The heart rate was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles (60.9±1.5 bpm) than in that of Arg/Gly heterozygotes (65.9±1.0 bpm) or Gly/Gly homozygotes (66.3±1.2 bpm). Homozygous carriers of Arg16 allele had an alpha index (19.2±1.3) significantly higher (P<0.001) than that of the subjects with the Gly allele Gly/Gly (14.5±0.7) or Arg/Gly (14.6±0.7). Furthermore, the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1% vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the presence of β2-AR Arg16 allele in a recessive model was associated with higher baroreflex sensitivity, and increased parasympathetic modulation in studied individuals. PMID:25755837

  3. EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes.

    OpenAIRE

    Siwik Deborah A; Kuster Gabriela M; Brahmbhatt Jamin V; Zaidi Zaheer; Malik Julia; Ooi Henry; Ghorayeb Ghassan

    2008-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricu...

  4. G16R single nucleotide polymorphism but not haplotypes of the ß2-adrenergic receptor gene alters cardiac output in humans

    DEFF Research Database (Denmark)

    Rokamp, Kim Z; Staalsø, Jonatan M; Gartmann, Martin

    2013-01-01

    Variation in genes encoding the ß2-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q¿ (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with ß2-mediated vasodilation, but the effect of ADRB2 haplotypes on Q¿ has not been...... studied. Five SNPs within ADRB2 (46G>A, 79C>G, 491C>T, 523C>A and 1053G>C by a pairwise tagging principle) and the I/D (insertion/deletion) polymorphism in ACE were genotyped in 143 subjects. Cardiovascular variables were evaluated by the Model flow method at rest and during incremental cycling exercise...... V¿O2 (oxygen uptake) in G16G subjects, but the increase was 0.5 (0.0-0.9) l/min lower in Arg16 carriers (P=0.035). A similar effect size was observed for the Arg16 haplotypes ACCCG and ACCCC. No interaction was found between ADRB2 and ACE polymorphisms. During exercise, the increase in Q¿ was 0...

  5. Cardiac function studies

    International Nuclear Information System (INIS)

    Horn, H.J.

    1986-01-01

    A total of 27 patients were subjected tointramyocardial sequential scintiscanning (first pass) using 99m-Tc human serum albumin. A refined method is described that is suitable to analyse clinically relevant parameters like blood volume, cardiac output, ejection fraction, stroke volume, enddiastolic and endsystolic volumes as well as pulmonal transition time and uses a complete camaracomputer system adapted to the requirements of a routine procedure. Unless there is special hardware available, the method does not yet appear mature enough to be put into general practice. Its importance recently appeared in a new light due to the advent of particularly shortlived isotopes. For the time being, however, ECG-triggered equilibrium studies are to be preferred for cardiac function tests. (TRV) [de

  6. β(3) adrenergic stimulation of the cardiac Na+-K+ pump by reversal of an inhibitory oxidative modification.

    Science.gov (United States)

    Bundgaard, Henning; Liu, Chia-Chi; Garcia, Alvaro; Hamilton, Elisha J; Huang, Yifei; Chia, Karin K M; Hunyor, Stephen N; Figtree, Gemma A; Rasmussen, Helge H

    2010-12-21

    inhibition of L-type Ca(2+) current contributes to negative inotropy of β(3) adrenergic receptor (β(3) AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na(+)-K(+) pump is of particular interest because of adverse effects attributed to high cardiac myocyte Na(+) levels and upregulation of the β(3) AR in heart failure. we voltage clamped rabbit ventricular myocytes and identified electrogenic Na(+)-K(+) pump current (I(p)) as the shift in holding current induced by ouabain. The synthetic β(3) AR agonists BRL37344 and CL316,243 and the natural agonist norepinephrine increased I(p). Pump stimulation was insensitive to the β(1)/β(2) AR antagonist nadolol and the protein kinase A inhibitor H-89 but sensitive to the β(3) AR antagonist L-748,337. Blockade of nitric oxide synthase abolished pump stimulation and an increase in fluorescence of myocytes loaded with a nitric oxide-sensitive dye. Exposure of myocytes to β(3) AR agonists decreased β(1) Na(+)-K(+) pump subunit glutathionylation, an oxidative modification that causes pump inhibition. The in vivo relevance of this was indicated by an increase in myocardial β(1) pump subunit glutathionylation with elimination of β(3) AR-mediated signaling in β(3) AR(-/-) mice. The in vivo effect of BRL37344 on contractility of the nonfailing and failing heart in sheep was consistent with a beneficial effect of Na(+)-K(+) pump stimulation in heart failure. the β(3) AR mediates decreased β(1) subunit glutathionylation and Na(+)-K(+) pump stimulation in the heart. Upregulation of the receptor in heart failure may be a beneficial mechanism that facilitates the export of excess Na(+).

  7. Renal albumin excretion: twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism

    DEFF Research Database (Denmark)

    Rao, Fangwen; Wessel, Jennifer; Wen, Gen

    2007-01-01

    biosynthesis (tyrosine hydroxylase), catabolism (monoamine oxidase A), storage/release (chromogranin A), receptor target (dopamine D1 receptor), and postreceptor signal transduction (sorting nexin 13 and rho kinase). Epistasis (gene-by-gene interaction) occurred between alleles at rho kinase, tyrosine...... hydroxylase, chromogranin A, and sorting nexin 13. Dopamine D1 receptor polymorphism showed pleiotropic effects on both albumin and dopamine excretion. These studies establish new roles for heredity and environment in albumin excretion. Urinary excretions of albumin and catecholamines are highly heritable......, and their parallel suggests adrenergic mediation of early glomerular permeability alterations. Albumin excretion is influenced by multiple adrenergic pathway genes and is, thus, polygenic. Such functional links between adrenergic activity and glomerular injury suggest novel approaches to its prediction, prevention...

  8. Adverse Effects on β-Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long-Term Cardiac Function.

    Science.gov (United States)

    Schreckenberg, Rolf; Bencsik, Péter; Weber, Martin; Abdallah, Yaser; Csonka, Csaba; Gömöri, Kamilla; Kiss, Krisztina; Pálóczi, János; Pipis, Judit; Sárközy, Márta; Ferdinandy, Péter; Schulz, Rainer; Schlüter, Klaus-Dieter

    2017-12-22

    Ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury. However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor-mediated signaling of the postischemic heart. The current article examines the effect of IPC or IPoC on the regulation and coupling of β-adrenergic receptors and their effects on postischemic left ventricular function. The β-adrenergic signal transduction was analyzed in 3-month-old Wistar rats for each of the intervention strategies (Sham, ischemia/reperfusion, IPC, IPoC) immediately and 7 days after myocardial infarction. Directly after the infarction a cardioprotective potential was demonstrated for both IPC and IPoC: the infarct size was reduced, apoptosis and production of reactive oxygen species were lowered, and the myocardial tissue was preserved. Seven days after myocardial ischemia, only IPC hearts showed significant functional improvement. Along with a deterioration in fractional shortening, IPoC hearts no longer responded adequately to β-adrenergic stimulation. The stabilization of β-adrenergic receptor kinase-2 via increased phosphorylation of Mdm2 (an E3-ubiquitin ligase) was responsible for desensitization of β-adrenergic receptors and identified as a characteristic specific to IPoC hearts. Immediately after myocardial infarction, rapid and transient activation of β-adrenergic receptor kinase-2 may be an appropriate means to protect the injured heart from excessive stress. In the long term, however, induction and stabilization of β-adrenergic receptor kinase-2, with the resultant loss of positive inotropic function, leads to the functional picture of heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  9. Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons

    NARCIS (Netherlands)

    Southerland, E. M.; Milhorn, D. M.; Foreman, R. D.; Linderoth, B.; DeJongste, M. J. L.; Armour, J. A.; Subramanian, V.; Singh, M.; Singh, K.; Ardell, J. L.

    2007-01-01

    Our objective was to determine whether electrical neuromodulation using spinal cord stimulation ( SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of

  10. β(3) adrenergic stimulation of the cardiac Na+-K+ pump by reversal of an inhibitory oxidative modification

    DEFF Research Database (Denmark)

    Bundgaard, Henning; Liu, Chia-Chi; Garcia, Alvaro

    2010-01-01

    inhibition of L-type Ca(2+) current contributes to negative inotropy of β(3) adrenergic receptor (β(3) AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na(+)-K(+) pump is of particular interest because of adverse effects attributed ...

  11. ß(3) adrenergic stimulation of the cardiac Na+-K+ pump by reversal of an inhibitory oxidative modification

    DEFF Research Database (Denmark)

    Bundgaard, Henning; Liu, Chia-Chi; Garcia, Alvaro

    2010-01-01

    inhibition of L-type Ca(2+) current contributes to negative inotropy of ß(3) adrenergic receptor (ß(3) AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na(+)-K(+) pump is of particular interest because of adverse effects attributed ...

  12. Mouse models for the study of postnatal cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    A. Del Olmo-Turrubiarte

    2015-06-01

    Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

  13. Adrenergic regulation of conduction velocity in cultures of immature cardiomyocytes

    NARCIS (Netherlands)

    de Boer, T. P.; van Rijen, H. V. M.; van der Heyden, M. A. G.; de Bakker, J. M. T.; van Veen, T. A. B.

    2008-01-01

    During cardiac maturation, increased exposure of the heart to circulating catecholamines correlates with increased conduction velocity and growth of the heart. We used an in vitro approach to study the underlying mechanisms of adrenergic stimulation induced changes in conduction velocity. By

  14. Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

    Science.gov (United States)

    Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R

    2014-01-01

    Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is

  15. 2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R-2-((2-(1H-Indol-2-ylethylamino-1-Phenylethan-1-ol with Human β3-Adrenergic Activity

    Directory of Open Access Journals (Sweden)

    Gastón Apablaza

    2017-03-01

    Full Text Available The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration in USA and the MHRA (Medicines and Healthcare products Regulatory Agency in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.

  16. 2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human β₃-Adrenergic Activity.

    Science.gov (United States)

    Apablaza, Gastón; Montoya, Luisa; Morales-Verdejo, Cesar; Mellado, Marco; Cuellar, Mauricio; Lagos, Carlos F; Soto-Delgado, Jorge; Chung, Hery; Pessoa-Mahana, Carlos David; Mella, Jaime

    2017-03-05

    The β₃ adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β₃ adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β₃ adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β₃ adrenergic activity is given.

  17. Beta 2-adrenergic receptors on eosinophils. Binding and functional studies

    International Nuclear Information System (INIS)

    Yukawa, T.; Ukena, D.; Kroegel, C.; Chanez, P.; Dent, G.; Chung, K.F.; Barnes, P.J.

    1990-01-01

    We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand [125I]pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed

  18. Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

    Science.gov (United States)

    2014-01-01

    Background Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats. Methods Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days. Results Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4. Conclusions Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats. PMID:24521405

  19. Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.

    OpenAIRE

    Ping, P; Gelzer-Bell, R; Roth, D A; Kiel, D; Insel, P A; Hammond, H K

    1995-01-01

    To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta-adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G-protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling as...

  20. ß-adrenergic regulation of ion transport in pancreatic ducts: Patch-clamp study of isolated rat pancreatic ducts

    DEFF Research Database (Denmark)

    Novak, I

    1998-01-01

    BACKGROUND & AIMS: In the intact pancreas, bicarbonate secretion is thought to be controlled by a number of regulators, including adrenergic agonists. The aim of this study was to investigate the effects of adrenergic agonists on pancreatic ducts, which are the site of bicarbonate secretion....... METHODS: Small intralobular ducts were isolated from rat pancreas and studied in vitro by the whole-cell patch clamp technique. Cell membrane voltages and currents were indicators of cellular ion transport. In some ducts, intracellular Ca2+ activity was measured by fluorescence optical methods. RESULTS...

  1. 451 Case studies Cardiac

    African Journals Online (AJOL)

    Marinda

    Case Studies. 29 ... A case of a 26-year-old ASA I physical status male undergoing septoplasty had an abrupt ... myocardial infarction, severe hypertensive crisis, cerebral .... or no formal management is required in an ASA I patient.8 One.

  2. β-adrenergic receptor responsiveness in aging heart and clinical implications

    Science.gov (United States)

    Ferrara, Nicola; Komici, Klara; Corbi, Graziamaria; Pagano, Gennaro; Furgi, Giuseppe; Rengo, Carlo; Femminella, Grazia D.; Leosco, Dario; Bonaduce, Domenico

    2014-01-01

    Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called “β-adrenergic desensitization”). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the β-adrenergic receptor density reduction and to the β-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of β-adrenergic system with heart failure pathogenesis. In particular it is well known that: (a) levels of cathecolamines are directly correlated with mortality and functional status in heart failure, (b) β1-adrenergic receptor subtype is down-regulated in heart failure, (c) heart failure-dependent cardiac adrenergic responsiveness reduction is related to changes in G proteins activity. In this review we focus on the cardiovascular β-adrenergic changes involvement in the aging process and on similarities and differences between aging heart and heart failure. PMID:24409150

  3. Synthesis and biological evaluation of [11C]MK-912 as an α2-adrenergic receptor radioligand for PET studies

    International Nuclear Information System (INIS)

    Shiue Chyngyann; Pleus, Richard C.; Shiue, Grace G.; Rysavy, Joseph A.; Sunderland, John J.; Cornish, Kurtis G.; Young, Steven D.; Bylund, David B.

    1998-01-01

    ABSTRACT. In vitro studies showed that MK-912 ((2S, 12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2H-benzo[b]furo [2,3-a]quinolizine)-2,4'-pyrimidin-2'-one) is a potent α 2 -adrenergic receptor antagonist with high affinity (K i = 0.42, 0.26 and 0.03 nM to α 2A , α 2B and α 2C , respectively) and high selectivity (α 2A /α 1A = 240; α 2A /D-1 = 3600; α 2A /D-2 3500; α 2A /5-HT 1 = 700; α 2A /5-HT 2 = 4100). The compound was labeled with 11 C and evaluated in rodents and monkey as a specific radioligand for studying α 2 -adrenergic receptors using PET. [ 11 C]MK-912 was synthesized by methylation of its desmethyl precursor, L-668,929, with [ 11 C]CH 3 I in (Bu 3 O)P=O at 85 deg. C for 8 min followed by purification with HPLC in 18% yield in a synthesis time of 45 min from end of bombardment (EOB). The specific activity was 0.83-0.93 Ci/μmol and the radiochemical purity was 97%. The initial uptake of [ 11 C]MK-912 in mouse brain, heart, lung, liver and kidney was high (5%, 4%, 5%, 17% and 8% per gram of organ, respectively, at 5 min postinjection) and the activities were then slowly cleared from these organs. The uptake of [ 11 C]MK-912 in rat olfactory tubercle, a brain region with high density of α 2 -adrenergic receptors, was reduced by 30%, and the ratio of radioactivity in olfactory tubercle/cerebellum was reduced from 2:1 to 1:1 by coinjection of [ 11 C]MK-912 with a potent α 2 -adrenergic receptor antagonist, atipamezole (3 mg/kg), indicating that compound 2 binds to α 2 -adrenergic receptors. However, a PET study in a rhesus monkey revealed that the initial influx of [ 11 C]MK-912 into various brain regions (cerebellum, cortex, olfactory tubercle and striatum) was high (0.02%/cc), and the radioactivity was then washed out slowly and without significantly differential retention in these brain regions. This, coupled with the fact that none of the high-density α 2 -adrenergic receptor brain regions exceeds a few millimeters in diameter

  4. Angiotensin II potentiates adrenergic and muscarinic modulation of guinea pig intracardiac neurons.

    Science.gov (United States)

    Girasole, Allison E; Palmer, Christopher P; Corrado, Samantha L; Marie Southerland, E; Ardell, Jeffrey L; Hardwick, Jean C

    2011-11-01

    The intrinsic cardiac plexus represents a major peripheral integration site for neuronal, hormonal, and locally produced neuromodulators controlling efferent neuronal output to the heart. This study examined the interdependence of norepinephrine, muscarinic agonists, and ANG II, to modulate intrinsic cardiac neuronal activity. Intracellular voltage recordings from whole-mount preparations of the guinea pig cardiac plexus were used to determine changes in active and passive electrical properties of individual intrinsic cardiac neurons. Application of either adrenergic or muscarinic agonists induced changes in neuronal resting membrane potentials, decreased afterhyperpolarization duration of single action potentials, and increased neuronal excitability. Adrenergic responses were inhibited by removal of extracellular calcium ions, while muscarinic responses were inhibited by application of TEA. The adrenergic responses were heterogeneous, responding to a variety of receptor-specific agonists (phenylephrine, clonidine, dobutamine, and terbutaline), although α-receptor agonists produced the most frequent responses. Application of ANG II alone produced a significant increase in excitability, while application of ANG II in combination with either adrenergic or muscarinic agonists produced a much larger potentiation of excitability. The ANG II-induced modulation of firing was blocked by the angiotensin type 2 (AT(2)) receptor inhibitor PD 123319 and was mimicked by the AT(2) receptor agonist CGP-42112A. AT(1) receptor blockade with telmasartin did not alter neuronal responses to ANG II. These data demonstrate that ANG II potentiates both muscarinically and adrenergically mediated activation of intrinsic cardiac neurons, doing so primarily via AT(2) receptor-dependent mechanisms. These neurohumoral interactions may be fundamental to regulation of neuronal excitability within the intrinsic cardiac nervous system.

  5. Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Patel Mayur B

    2012-09-01

    the Extended Glasgow Outcome Scale and Quality of Life after Brain Injury scale. Safety parameters evaluated will include cardiac complications. Discussion The DASH After TBI Study is the first randomized, double-blinded, placebo-controlled trial powered to determine feasibility and investigate safety and outcomes associated with adrenergic blockade in patients with severe TBI. If the study results in positive trends, this could provide pilot evidence for a larger multicenter randomized clinical trial. If there is no effect of therapy, this trial would still provide a robust prospective description of sympathetic hyperactivity after TBI. Trial registration ClinicalTrials.gov NCT01322048

  6. Pet measurements of postsynaptic muscarinic and beta adrenergic receptors in the heart

    International Nuclear Information System (INIS)

    Syrota, A.

    1991-01-01

    There is ample evidence from both experimental and clinical studies that changes in β-adrenergic and muscarinic receptor density can be associated with such cardiac diseases as congestive heart failure, myocardial ischemia and infarction, cardiomyopathy, diabetes, or thyroid-induced muscle disease. Changes in B-adrenergic density also have been shown in the denervated transplanted heart. These alterations of cardiac receptors have been demonstrated in vitro on homogenates from samples collected mainly during surgery or post mortem. Recent developments of Positron Emission Tomography (PET) techniques and of radioligands suitable for cardiac receptor binding studies in vivo have made possible both the imaging and the measurement of receptor density. From these studies, important information is now available concerning physiologic and pathologic conditions, as well as alterations induced by treatment. For the investigation of myocardial B-adrenergic receptors we have used [ 11 C] CGP 12177, a potent hydrophilic antagonist of the 3-adrenergic receptor. The quantification of myocardial muscarinic receptors in vivo has been obtained with [ 11 C] MQNB, a nonmetabolized hydrophilic antagonist of the muscarinic receptor. Receptor density and affinity have been measured by a kinetic, nonequilibrium approach in an experimental protocol that provides sufficient data to determine values for all parameters from a single experiment

  7. Adrenergic bronchodilator overdose

    Science.gov (United States)

    Adrenergic bronchodilators are inhaled medicines that help open up the airways. They are used to treat asthma and chronic bronchitis. Adrenergic bronchodilator overdose occurs when someone accidentally or intentionally ...

  8. Effects of adrenergic agents on the expression of zebrafish (Danio rerio) vitellogenin Ao1

    International Nuclear Information System (INIS)

    Yin Naida; Jin Xia; He Jiangyan; Yin Zhan

    2009-01-01

    Teleost vitellogenins (VTGs) are large multidomain apolipoproteins, traditionally considered to be estrogen-responsive precursors of the major egg yolk proteins, expressed and synthesized mainly in hepatic tissue. The inducibility of VTGs has made them one of the most frequently used in vivo and in vitro biomarkers of exposure to estrogen-active substances. A significant level of zebrafish vtgAo1, a major estrogen responsive form, has been unexpectedly found in heart tissue in our present studies. Our studies on zebrafish cardiomyopathy, caused by adrenergic agonist treatment, suggest a similar protective function of the cardiac expressed vtgAo1. We hypothesize that its function is to unload surplus intracellular lipids in cardiomyocytes for 'reverse triglyceride transportation' similar to that found in lipid transport proteins in mammals. Our results also demonstrated that zebrafish vtgAo1 mRNA expression in heart can be suppressed by both α-adrenergic agonist, phenylephrine (PE) and β-adrenergic agonist, isoproterenol (ISO). Furthermore, the strong stimulation of zebrafish vtgAo1 expression in plasma induced by the β-adrenergic antagonist, MOXIsylyl, was detected by Enzyme-Linked ImmunoSorbent Assay (ELISA). Such stimulation cannot be suppressed by taMOXIfen, an antagonist to estrogen receptors. Thus, our present data indicate that the production of teleost VTG in vivo can be regulated not only by estrogenic agents, but by adrenergic signals as well.

  9. Association of myocardial inotropic reserve and adrenergic nerve alterations in idiopathic dilated cardiomyopathy. A dobutamine stress echocardiographic and 123-I-MIBG scintigraphic study

    International Nuclear Information System (INIS)

    Prassopoulos, V.P.; Koukouraki, S.; Velidaki, A.; Karkavitsas, N.; Parthenakis, F.; Patrianakos, A.; Kochiadakis, G.; Papadimitriou, E.; Vardas, P.

    2002-01-01

    patients with idiopathic dilated cardiomyopathy the left ventricular contractile reserve is related to cardiac adrenergic nerve activity. MIBG scintigraphy and Dobutamine stress Echocardiography, which are both associated with b-adrenergic receptor mechanisms, may evaluate this association and predict the cardiopulmonary exercise tolerance in these patients

  10. New β-adrenergic agonists used illicitly as growth promoters in animal breeding: chemical and pharmacodynamic studies

    International Nuclear Information System (INIS)

    Mazzanti, Gabriela; Daniele, Claudia; Boatto, Gianpiero; Manca, Giuliana; Brambilla, Gianfranco; Loizzo, Alberto

    2003-01-01

    Clenbuterol and β-adrenergic receptor agonist drugs are illegally used as growth promoters in animal production. Pharmacologically active residues in edible tissues led to intoxication outbreaks in several countries. Pressure of official controls pulsed synthesis of new compounds to escape analytical procedures. We report two new compounds named 'A' and 'G4', found in feeding stuffs. Chemical structure was studied through nuclear magnetic resonance-imaging and infrared spectroscopy, and β 1 - and β 2 -adrenergic activity was evaluated on isolated guinea-pig atrium and trachea in comparison with clenbuterol. Both compounds share with clenbuterol an halogenated aromatic ring with a primary amino group. Main modifications consisted of substitution of secondary amino group with an alkyl chain in compound A and substitution of the ter-butyl group with a benzene ring in compound G4. In guinea-pig trachea these compounds showed myorelaxant potency lower than clenbuterol (EC 50 was 43.8 nM for clenbuterol, 11700 nM for compound A, 2140 nM for G4). On the contrary, in the guinea-pig atrium (heart-beat rate stimulant effect) the compounds were more potent than clenbuterol (EC 50 was 15.2 nM for clenbuterol, 3.4 nM for compound A, 2.8 nM for G4). These pharmacodynamic properties, and stronger lipophilic properties shown by the two compounds may result in increased cardiovascular risk for consumers of illicitly treated animals

  11. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Konstantinos Drosatos

    2016-08-01

    Full Text Available Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging.

  12. Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

    Science.gov (United States)

    Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

    2010-08-01

    Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

  13. The influence of adrenergic stimulation on sex differences in left ventricular twist mechanics.

    Science.gov (United States)

    Williams, Alexandra M; Shave, Rob E; Cheyne, William S; Eves, Neil D

    2017-06-15

    Sex differences in left ventricular (LV) mechanics occur during acute physiological challenges; however, it is unknown whether sex differences in LV mechanics are fundamentally regulated by differences in adrenergic control. Using two-dimensional echocardiography and speckle tracking analysis, this study compared LV mechanics in males and females matched for LV length during post-exercise ischaemia (PEI) and β 1 -adrenergic receptor blockade. Our data demonstrate that while basal rotation was increased in males, LV twist was not significantly different between the sexes during PEI. In contrast, during β 1 -adrenergic receptor blockade, LV apical rotation, twist and untwisting velocity were reduced in males compared to females. Significant relationships were observed between LV twist and LV internal diameter and sphericity index in females, but not males. These findings suggest that LV twist mechanics may be more sensitive to alterations in adrenergic stimulation in males, but more highly influenced by ventricular structure and geometry in females. Sex differences in left ventricular (LV) mechanics exist at rest and during acute physiological stress. Differences in cardiac autonomic and adrenergic control may contribute to sex differences in LV mechanics and LV haemodynamics. Accordingly, this study aimed to investigate sex differences in LV mechanics with altered adrenergic stimulation achieved through post-handgrip-exercise ischaemia (PEI) and β 1 -adrenergic receptor (AR) blockade. Twenty males (23 ± 5 years) and 20 females (22 ± 3 years) were specifically matched for LV length (males: 8.5 ± 0.5 cm, females: 8.2 ± 0.6 cm, P = 0.163), and two-dimensional speckle-tracking echocardiography was used to assess LV structure and function at baseline, during PEI and following administration of 5 mg bisoprolol (β 1 -AR antagonist). During PEI, LV end-diastolic volume and stroke volume were increased in both groups (P adrenergic stimulation

  14. Antinociceptive activity of Astragalus gummifer gum (gum tragacanth) through the adrenergic system: A in vivo study in mice.

    Science.gov (United States)

    Bagheri, Seyyed Majid; Keyhani, Leila; Heydari, Mehrangiz; Dashti-R, Mohammad Hossein

    2015-01-01

    In Iranian traditional medicine, gum obtained from Astragalus gummifer and some other species of Astragalus was used as analgesic agent. In this study, we investigated the antinociceptive effect of several concentrations (125, 250, and 500 μg/kg body weight) of Astragalus gummifer gum (AGG) on thermal and acetic acid induced pain in mice. AGG was dissolved in distillated water and injected i.p to male mice 15 minute before the onset of experiment. Writhing and hot-plate tests were applied to study the analgesic effect of AGG and compared with that of diclofenac sodium (30 mg/kg, i.p.) or morphine (8 mg/kg, i.p). To investigate the mechanisms involved in antinociception, yohimbine, naloxone, glibenclamide, and theophylline were used in writhing test. These drugs were injected intraperitoneally 15 min before the administration of AGG. The number of writhes were counted in 30 minutes and analyzed. AGG exhibited a significant antinociceptive effect and the most effective dose of AGG was 500 μg/kg. The most maximum possible effect (%MPE) was observed (117.4%) 15 min after drug administration. The %inhibition of acetic acid-induced writhing in AGG 125, 250 and 500 was 47%, 50% and 54% vs %15 of control and 66.3% of diclofenac sodium group. The antinociceptive effect induced by this gum in the writhing test was reversed by the systemic administration of yohimbine (α2-adrenergic antagonist), but naloxone, glibenclamide, and theophylline did not reverse this effect. The findings of this study indicated that AGG induced its antinociceptive through the adrenergic system.

  15. Antinociceptive activity of Astragalus gummifer gum (gum tragacanth through the adrenergic system: A in vivo study in mice

    Directory of Open Access Journals (Sweden)

    Seyyed Majid Bagheri

    2015-01-01

    Full Text Available Background: In Iranian traditional medicine, gum obtained from Astragalus gummifer and some other species of Astragalus was used as analgesic agent. Objective: In this study, we investigated the antinociceptive effect of several concentrations (125, 250, and 500 μg/kg body weight of Astragalus gummifer gum (AGG on thermal and acetic acid induced pain in mice. Materials and Methods: AGG was dissolved in distillated water and injected i.p to male mice 15 minute before the onset of experiment. Writhing and hot-plate tests were applied to study the analgesic effect of AGG and compared with that of diclofenac sodium (30 mg/kg, i.p. or morphine (8 mg/kg, i.p. To investigate the mechanisms involved in antinociception, yohimbine, naloxone, glibenclamide, and theophylline were used in writhing test. These drugs were injected intraperitoneally 15 min before the administration of AGG. The number of writhes were counted in 30 minutes and analyzed. Results: AGG exhibited a significant antinociceptive effect and the most effective dose of AGG was 500 μg/kg. The most maximum possible effect (%MPE was observed (117.4% 15 min after drug administration. The %inhibition of acetic acid-induced writhing in AGG 125, 250 and 500 was 47%, 50% and 54% vs %15 of control and 66.3% of diclofenac sodium group. The antinociceptive effect induced by this gum in the writhing test was reversed by the systemic administration of yohimbine (α2 -adrenergic antagonist, but naloxone, glibenclamide, and theophylline did not reverse this effect. Conclusions: The findings of this study indicated that AGG induced its antinociceptive through the adrenergic system.

  16. Radionuclide methods application in cardiac studies

    International Nuclear Information System (INIS)

    Kotina, E.D.; Ploskikh, V.A.; Babin, A.V.

    2013-01-01

    Radionuclide methods are one of the most modern methods of functional diagnostics of diseases of the cardio-vascular system that requires the use of mathematical methods of processing and analysis of data obtained during the investigation. Study is carried out by means of one-photon emission computed tomography (SPECT). Mathematical methods and software for SPECT data processing are developed. This software allows defining physiologically meaningful indicators for cardiac studies

  17. Adrenergic regulation of cytoplasmic structures related to secretory processes in pig pinealocytes-an ultrastructural, quantitative study.

    Science.gov (United States)

    Przybylska-Gornowicz, Barbara; Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena

    2017-10-01

    Two structures, considered as secretory in nature, are present in the pinealocytes in of the domestic pig show the presence of two structures, which are considered as secretory in nature - the dense core vesicles (DCV) and the membrane bounded (dense) bodies (MBB). The latter are extremely numerous in pig pinealocytes (they occupy 6-20% of the cytoplasm), and the number of MBB changes under different physiological and experimental conditions. Norepinephrine is the main neurotransmitter that regulates the secretion of pineal melatonin. The present study was carried out to 1) clarify whether the DCV and their source - the Golgi apparatus (GA) - as well as the MBB are controlled by norepinephrine, 2) determine the effect of adrenergic stimulation on these structures, and 3) identify the receptors involved in the regulation of these structures. The studies were performed using a static organ culture of pig pineal explants. The explants were incubated in a control medium between 08:00 and 20:00 and in a medium with 10μM norepinephrine or alpha- or beta-adrenoceptor agonists between 20:00 and 08:00 on five consecutive days. The tissues were subsequently prepared for ultrastructural analysis. The results distinctly showed that the DCV, GA and MBB in pig pinealocytes are under adrenergic control. The stimulation of the beta-adrenoceptors resulted in an increase in the numerical density of the DCV and a decrease in the relative volume of the GA in the perikarya, while the incubation with agonists of the alpha1-adrenoceptors was ineffective. The relative volume of the MBB in the perikarya significantly decreased after treatment with both beta-agonists and alpha1-agonists, which suggested the involvement of two types of adrenoceptors in the regulation of these structures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis

    Directory of Open Access Journals (Sweden)

    Yifeng Chai

    2012-01-01

    Full Text Available Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol were studied by capillary electrophoresis using six cyclodextrins (CDs as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the –OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy.

  19. Studies on the characterization and regulation of alpha-1 adrenergic receptors and [3H]WB4101 binding sites in the central nervous system

    International Nuclear Information System (INIS)

    Morrow, A.L.

    1985-01-01

    The purpose of these studies has been to resolve the anomalous binding characteristics of two alpha adrenergic receptor ligands, [ 3 H]WB4101 and [ 3 H]prazosin and to study the regulation of the receptors labeled by these compounds after surgical denervation and chronic drug treatments. Preliminary studies indicated that [ 3 H]WB4101 binding sites, which were believed to represent alpha-1 adrenergic receptors, were increased in number following removal of the fimbrial afferents to the hippocampus. This increase was not due to removal of the adrenergic input into this structure since destruction of the locus coeruleus or the dorsal noradrenergic bundle did not produce the up-regulation. Characterization of alpha-1 adrenergic receptors using [ 3 H]prazosin and [ 3 H]WB4101 revealed evidence for subtypes of alpha-1 receptors designated alpha-1A and alpha-1B. The nanomolar affinity component of [ 3 H]WB4101 binding is not adrenergic but serotonergic. The serotonergic agonists, serotonin and 8-hydroxy-dipropylaminotetraline have affinities of 1.5 and 3.0 nM for this site, when studied in the presence of a 30 nM prazosin mask of the alpha-1 component of [ 3 H]WB4101 binding. Fimbria transection or 5,7 dihydroxytryptamine injections produced increases in the Bmax of the nanomolar affinity component of [ 3 H]WB4101 binding in the presence of a prazosin mask. The up-regulated site showed identical serotonergic pharmacology compared to control tissue. Thus, the author concluded that serotonergic denervation of the hippocampus produces the increase in serotonergic binding sites labeled by [ 3 H]WB4101

  20. [Studies on the relationship between beta-adrenergic receptor density on cell wall lymphocytes, total serum catecholamine level and heart rate in patients with hyperthyroidism].

    Science.gov (United States)

    Gajek, J; Zieba, I; Zyśko, D

    2000-08-01

    Hyperthyreosis mimics the hyperadrenergic state and its symptoms were though to be dependent on increased level of catecholamines. Another reason for the symptoms could be the increased density or affinity of beta-adrenergic receptors to catecholamines. The aim of the study was to examine the elements of sympathetic nervous system, thyroid hormones level and their influence on heart rate control in patients with hyperthyreosis. The study was carried out in 18 women, mean age 48.9 +/- 8.7 yrs and 6 men, mean age 54.2 +/- 8.7 yrs. The control group consisted of 30 healthy persons matched for age and sex. We examined the density of beta-adrenergic receptors using radioligand labelling method with 125I-cyanopindolol, serum total catecholamines level with radioenzymatic assay kit, the levels of free thyroid hormones using radioimmunoassays and thyreotropine level with immunoradiometric assay. Maximal, minimal and mean heart rate were studied using Holter monitoring system. The density of beta-adrenergic receptors in hyperthyreosis was 37.3 +/- 21.7 vs 37.2 +/- 18.1 fmol/mg in the control group (p = NS). Total catecholamines level was significantly decreased in hyperthyreosis group: 1.5 +/- 0.89 vs 1.9 +/- 0.73 pmol/ml (p < 0.05). There was significantly higher minimal, maximal and mean heart rate in hyperthyreosis group (p < 0.0001, p < 0.0001 and p < 0.05 respectively). There was a weak inverse correlation between minimum heart rate and triiodothyronine level (r = -0.38, p < 0.05). An inverse correlation between triiodothyronine and catecholamines level (r = -0.49, p < 0.05) was observed. Beta-adrenergic receptors density is unchanged and catecholamines level is decreased in hyperthyreosis when compared to normal subjects. There is no correlation between minimal heart rate and adrenergic receptors density or catecholamines level in hyperthyreosis.

  1. Adrenergic blockade in diabetic and uninephrectomized rats

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Jørgensen, P E

    1999-01-01

    The present study reports on the effects of adrenergic blocking agents on the renal growth and on the renal content and urinary excretion of epidermal growth factor (EGF) in streptozotocin-induced diabetic or uninephrectomized rats. Diabetic and uninephrectomized rats were allocated to groups...... treated with either saline or adrenergic antagonists and compared to controls and sham-operated controls, respectively. 24-hour urine samples were obtained on days 7, 14, and 21 and renal tissue samples on day 21. The 24-hour urinary excretion of EGF from controls and saline-treated diabetic rats...... was comparable. In adrenergic antagonist treated diabetic rats, it was reduced by at least 40% throughout the study period. Uninephrectomy caused a 50% reduction in the urinary excretion of EGF. This was not influenced by treatment with an adrenergic antagonist. After 3 weeks, saline-treated diabetic rats had...

  2. The Role of Reactive Oxygen Species in β-Adrenergic Signaling in Cardiomyocytes from Mice with the Metabolic Syndrome.

    Directory of Open Access Journals (Sweden)

    Monica Llano-Diez

    Full Text Available The metabolic syndrome is associated with prolonged stress and hyperactivity of the sympathetic nervous system and afflicted subjects are prone to develop cardiovascular disease. Under normal conditions, the cardiomyocyte response to acute β-adrenergic stimulation partly depends on increased production of reactive oxygen species (ROS. Here we investigated the interplay between beta-adrenergic signaling, ROS and cardiac contractility using freshly isolated cardiomyocytes and whole hearts from two mouse models with the metabolic syndrome (high-fat diet and ob/ob mice. We hypothesized that cardiomyocytes of mice with the metabolic syndrome would experience excessive ROS levels that trigger cellular dysfunctions. Fluorescent dyes and confocal microscopy were used to assess mitochondrial ROS production, cellular Ca2+ handling and contractile function in freshly isolated adult cardiomyocytes. Immunofluorescence, western blot and enzyme assay were used to study protein biochemistry. Unexpectedly, our results point towards decreased cardiac ROS signaling in a stable, chronic phase of the metabolic syndrome because: β-adrenergic-induced increases in the amplitude of intracellular Ca2+ signals were insensitive to antioxidant treatment; mitochondrial ROS production showed decreased basal rate and smaller response to β-adrenergic stimulation. Moreover, control hearts and hearts with the metabolic syndrome showed similar basal levels of ROS-mediated protein modification, but only control hearts showed increases after β-adrenergic stimulation. In conclusion, in contrast to the situation in control hearts, the cardiomyocyte response to acute β-adrenergic stimulation does not involve increased mitochondrial ROS production in a stable, chronic phase of the metabolic syndrome. This can be seen as a beneficial adaptation to prevent excessive ROS levels.

  3. Gated cardiac blood pool studies in arrhythmias

    International Nuclear Information System (INIS)

    Itti, R.; Casset, D.; Philippe, L.; Cosnay, P.; Fauchier, J.P.

    1988-01-01

    Biventricular phase analysis a gated blood pool studies may help to solve two fundamental questions raised by patients suffering from arrhythmias: localization of an electrical cardiac activation abnormality by means of contraction mapping and assesment of an underlying organic disease using the phase histograms and their standard deviations. Three groups of patients have been evaluated to demonstrate the usefulness of radioisotopic techniques in arrhythmias: 36 patients with a Wolff-Parkinson-White syndrom, 27 patients studied during a ventricular tachycardia attack and 32 patients suspected of arrhythmogenic ventricular dysplasia. Correlations with invasive electrophysiologic studies are presented and the diagnostic and therapeutic implications of these results are discussed [fr

  4. Gated cardiac blood pool studies in arrhythmias

    Energy Technology Data Exchange (ETDEWEB)

    Itti, R.; Casset, D.; Philippe, L.; Cosnay, P.; Fauchier, J.P.

    1988-01-01

    Biventricular phase analysis a gated blood pool studies may help to solve two fundamental questions raised by patients suffering from arrhythmias: localization of an electrical cardiac activation abnormality by means of contraction mapping and assesment of an underlying organic disease using the phase histograms and their standard deviations. Three groups of patients have been evaluated to demonstrate the usefulness of radioisotopic techniques in arrhythmias: 36 patients with a Wolff-Parkinson-White syndrom, 27 patients studied during a ventricular tachycardia attack and 32 patients suspected of arrhythmogenic ventricular dysplasia. Correlations with invasive electrophysiologic studies are presented and the diagnostic and therapeutic implications of these results are discussed.

  5. Human myometrial adrenergic receptors: identification of the beta-adrenergic receptor by [3H]dihydroalprenolol binding

    International Nuclear Information System (INIS)

    Hayashida, D.N.; Leung, R.; Goldfien, A.; Roberts, J.M.

    1982-01-01

    The radioactive beta-adrenergic antagonist [ 3 H] dihydroalprenolol (DHA) binds to particulate preparations of human myometrium in a manner compatible with binding to the beta-adrenergic receptor. The binding of DHA is rapid (attaining equilibrium in 12 minutes), readily reversible (half time = 16 minutes), high affinity (K/sub D/ = 0.50 nM), low capacity (Bmax = 70 fmoles/mg of protein), and stereoselective ([-]-propranolol is 100 times as potent as [+] -propranolol in inhibiting DHA binding). Adrenergic agonists competed for DHA binding sites in a manner compatible with beta-adrenergic interactions and mirrored β 2 pharmacologic potencies: isoproterenol > epinephrine >> norepinephrine. Studies in which zinterol, a β 2 -adrenergic agonist, competed for DHA binding sites in human myometrial particulate indicated that at least 87% of the beta-adrenergic receptors present are β 2 -adrenergic receptors. Binding of DHA to human myometrial beta-adrenergic receptors provides a tool which may be used in the examination of gonadal hormonal modification of adrenergic response in human uterus as well as in the analysis of beta-adrenergic agents as potentially useful tocolytic agents

  6. Reductions in the Cardiac Transient Outward K+ Current Ito Caused by Chronic β-Adrenergic Receptor Stimulation Are Partly Rescued by Inhibition of Nuclear Factor κB.

    Science.gov (United States)

    Panama, Brian K; Korogyi, Adam S; Aschar-Sobbi, Roozbeh; Oh, Yena; Gray, Charles B B; Gang, Hongying; Brown, Joan Heller; Kirshenbaum, Lorrie A; Backx, Peter H

    2016-02-19

    The fast transient outward potassium current (Ito,f) plays a critical role in the electrical and contractile properties of the myocardium. Ito,f channels are formed by the co-assembly of the pore-forming α-subunits, Kv4.2 and Kv4.3, together with the accessory β-subunit KChIP2. Reductions of Ito,f are common in the diseased heart, which is also associated with enhanced stimulation of β-adrenergic receptors (β-ARs). We used cultured neonatal rat ventricular myocytes to examine how chronic β-AR stimulation decreases Ito,f. To determine which downstream pathways mediate these Ito,f changes, adenoviral infections were used to inhibit CaMKIIδc, CaMKIIδb, calcineurin, or nuclear factor κB (NF-κB). We observed that chronic β-AR stimulation with isoproterenol (ISO) for 48 h reduced Ito,f along with mRNA expression of all three of its subunits (Kv4.2, Kv4.3, and KChIP2). Inhibiting either CaMKIIδc nor CaMKIIδb did not prevent the ISO-mediated Ito,f reductions, even though CaMKIIδc and CaMKIIδb clearly regulated Ito,f and the mRNA expression of its subunits. Likewise, calcineurin inhibition did not prevent the Ito,f reductions induced by β-AR stimulation despite strongly modulating Ito,f and subunit mRNA expression. In contrast, NF-κB inhibition partly rescued the ISO-mediated Ito,f reductions in association with restoration of KChIP2 mRNA expression. Consistent with these observations, KChIP2 promoter activity was reduced by p65 as well as β-AR stimulation. In conclusion, NF-κB, and not CaMKIIδ or calcineurin, partly mediates the Ito,f reductions induced by chronic β-AR stimulation. Both mRNA and KChIP2 promoter data suggest that the ISO-induced Ito,f reductions are, in part, mediated through reduced KChIP2 transcription caused by NF-κB activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Proteolytic cleavage and PKA phosphorylation of α1C subunit are not required for adrenergic regulation of CaV1.2 in the heart.

    Science.gov (United States)

    Katchman, Alexander; Yang, Lin; Zakharov, Sergey I; Kushner, Jared; Abrams, Jeffrey; Chen, Bi-Xing; Liu, Guoxia; Pitt, Geoffrey S; Colecraft, Henry M; Marx, Steven O

    2017-08-22

    Calcium influx through the voltage-dependent L-type calcium channel (Ca V 1.2) rapidly increases in the heart during "fight or flight" through activation of the β-adrenergic and protein kinase A (PKA) signaling pathway. The precise molecular mechanisms of β-adrenergic activation of cardiac Ca V 1.2, however, are incompletely known, but are presumed to require phosphorylation of residues in α 1C and C-terminal proteolytic cleavage of the α 1C subunit. We generated transgenic mice expressing an α 1C with alanine substitutions of all conserved serine or threonine, which is predicted to be a potential PKA phosphorylation site by at least one prediction tool, while sparing the residues previously shown to be phosphorylated but shown individually not to be required for β-adrenergic regulation of Ca V 1.2 current (17-mutant). A second line included these 17 putative sites plus the five previously identified phosphoregulatory sites (22-mutant), thus allowing us to query whether regulation requires their contribution in combination. We determined that acute β-adrenergic regulation does not require any combination of potential PKA phosphorylation sites conserved in human, guinea pig, rabbit, rat, and mouse α 1C subunits. We separately generated transgenic mice with inducible expression of proteolytic-resistant α 1C Prevention of C-terminal cleavage did not alter β-adrenergic stimulation of Ca V 1.2 in the heart. These studies definitively rule out a role for all conserved consensus PKA phosphorylation sites in α 1C in β-adrenergic stimulation of Ca V 1.2, and show that phosphoregulatory sites on α 1C are not redundant and do not each fractionally contribute to the net stimulatory effect of β-adrenergic stimulation. Further, proteolytic cleavage of α 1C is not required for β-adrenergic stimulation of Ca V 1.2.

  8. Cardiac Auscultation Using Smartphones: Pilot Study.

    Science.gov (United States)

    Kang, Si-Hyuck; Joe, Byunggill; Yoon, Yeonyee; Cho, Goo-Yeong; Shin, Insik; Suh, Jung-Won

    2018-02-28

    Cardiac auscultation is a cost-effective, noninvasive screening tool that can provide information about cardiovascular hemodynamics and disease. However, with advances in imaging and laboratory tests, the importance of cardiac auscultation is less appreciated in clinical practice. The widespread use of smartphones provides opportunities for nonmedical expert users to perform self-examination before hospital visits. The objective of our study was to assess the feasibility of cardiac auscultation using smartphones with no add-on devices for use at the prehospital stage. We performed a pilot study of patients with normal and pathologic heart sounds. Heart sounds were recorded on the skin of the chest wall using 3 smartphones: the Samsung Galaxy S5 and Galaxy S6, and the LG G3. Recorded heart sounds were processed and classified by a diagnostic algorithm using convolutional neural networks. We assessed diagnostic accuracy, as well as sensitivity, specificity, and predictive values. A total of 46 participants underwent heart sound recording. After audio file processing, 30 of 46 (65%) heart sounds were proven interpretable. Atrial fibrillation and diastolic murmur were significantly associated with failure to acquire interpretable heart sounds. The diagnostic algorithm classified the heart sounds into the correct category with high accuracy: Galaxy S5, 90% (95% CI 73%-98%); Galaxy S6, 87% (95% CI 69%-96%); and LG G3, 90% (95% CI 73%-98%). Sensitivity, specificity, positive predictive value, and negative predictive value were also acceptable for the 3 devices. Cardiac auscultation using smartphones was feasible. Discrimination using convolutional neural networks yielded high diagnostic accuracy. However, using the built-in microphones alone, the acquisition of reproducible and interpretable heart sounds was still a major challenge. ClinicalTrials.gov NCT03273803; https://clinicaltrials.gov/ct2/show/NCT03273803 (Archived by WebCite at http://www.webcitation.org/6x6g1f

  9. Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia.

    Science.gov (United States)

    Spalink, Christy L; Barnes, Erin; Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

    2017-08-01

    To report the use of intranasal dexmedetomidine, an α 2 -adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia. Case series. Three patients with genetically confirmed familial dysautonomia (case 1: 20-year-old male; case 2: 43-year-old male; case 3: 26-year-old female) received intranasal dexmedetomidine 2 mcg/kg, half of the dose in each nostril, for the acute treatment of adrenergic crisis. Within 8-17 min of administering the intranasal dose, the adrenergic crisis symptoms abated, and blood pressure and heart rate returned to pre-crises values. Adrenergic crises eventually resumed, and all three patients required hospitalization for investigation of the cause of the crises. Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia. Further controlled studies are required to confirm the safety and efficacy in this population.

  10. Identification of an endogenous alpha-adrenergic receptor antagonist: studies on its possible role in endocrine and cardiovascular function

    International Nuclear Information System (INIS)

    Dunbar, J.C.; Wider, M.; House, F.; Campbell, R.

    1986-01-01

    The concept of α and β adrenergic receptors that are regulated by epinephrine or norepinephrine (NE) is well established. The reported receptor antagonists have been synthetic. A peptide extracted from the duodenal mucosa with α-2 antagonist properties has been identified. It specifically inhibits 3 H-yohimbine binding (α-2) but not 3 H dihydroalprenolol (β) binding in whole brain membranes. Partially purified preparations of the alpha receptor binding inhibitor (ABI) were tested for endocrine pancreatic and cardiovascular effects. When isolated islets were incubated in the presence of ABI with and without NE, ABI along did not alter insulin secretion but completely reversed the NE suppression of glucose stimulated insulin release. Glucagon secretion by these same islets was enhanced by ABI and augmented the stimulatory effect of NE. Intravenous (I.V.) infusion of ABI increased serum insulin in the presence of NE and decreased the serum glucose response to a glucose load. Infusion of ABI into the 4th ventricle, or I.V. resulted in a decrease (50-60%) in systolic and diastolic blood pressure as well as a decrease (10-20%) in heart rate. From these studies the authors conclude that a duodenal peptide with the capacity to inhibit α-2 agonist binding may play a role in endocrine and cardiovascular functions

  11. Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

    Science.gov (United States)

    Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

    2014-03-01

    Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

  12. A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure.

    Science.gov (United States)

    Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

    2016-10-01

    Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease.

  13. The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

    Science.gov (United States)

    Clément, Olivier; Valencia Garcia, Sara; Libourel, Paul-Antoine; Arthaud, Sébastien; Fort, Patrice; Luppi, Pierre-Hervé

    2014-01-01

    GABAergic neurons specifically active during paradoxical sleep (PS) localized in the dorsal paragigantocellular reticular nucleus (DPGi) are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

  14. The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

    Directory of Open Access Journals (Sweden)

    Olivier Clément

    Full Text Available GABAergic neurons specifically active during paradoxical sleep (PS localized in the dorsal paragigantocellular reticular nucleus (DPGi are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

  15. Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

    1986-08-01

    The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid /sup 14/C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.

  16. Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

    International Nuclear Information System (INIS)

    Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

    1986-01-01

    The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid 14 C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides. (orig.)

  17. An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Ju Youn Beak, PhD

    2017-02-01

    Full Text Available Summary: Alpha-1 adrenergic receptors (α1-ARs play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, the authors administered dabuzalgron to mice treated with doxorubicin (DOX, a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to heart failure (HF. Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF. Key Words: alpha adrenergic receptors, anthracyclines, cardioprotection, catecholamines, heart failure

  18. Influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission

    NARCIS (Netherlands)

    Vercruysse, P.; Bossuyt, P.; Verbeuren, T. J.; Vanhoutte, P. M.; Hanegreefs, G.

    1979-01-01

    The influence of gallamine, pancuronium, d-tubocurarine and succinylcholine on adrenergic neurotransmission was studied in the isolated saphenous vein of the dog. Pancuronium increased the response of vascular smooth muscle to adrenergic nerve stimulation and to exogenous norepinephrine; gallamine,

  19. The role of adrenergic receptors in nicotine-induced hyperglycemia ...

    African Journals Online (AJOL)

    The role of adrenergic receptors in nicotine-induced hyperglycaemia has not been well studied in amphibians. Thus, this study investigates the effects of alpha and beta adrenergic receptor blockers in nicotine-induced hyperglycaemia in the common African toad Bufo regularis. Toads fasted for 24 h were anaesthetized with ...

  20. Intact calcium signaling in adrenergic-deficient embryonic mouse hearts.

    Science.gov (United States)

    Peoples, Jessica N; Taylor, David G; Katchman, Alexander N; Ebert, Steven N

    2018-01-22

    Mouse embryos that lack the ability to produce the adrenergic hormones, norepinephrine (NE) and epinephrine (EPI), due to disruption of the dopamine beta-hydroxylase (Dbh -/- ) gene inevitably perish from heart failure during mid-gestation. Since adrenergic stimulation is well-known to enhance calcium signaling in developing as well as adult myocardium, and impairments in calcium signaling are typically associated with heart failure, we hypothesized that adrenergic-deficient embryonic hearts would display deficiencies in cardiac calcium signaling relative to adrenergic-competent controls at a developmental stage immediately preceding the onset of heart failure, which first appears beginning or shortly after mouse embryonic day 10.5 (E10.5). To test this hypothesis, we used ratiometric fluorescent calcium imaging techniques to measure cytosolic calcium transients, [Ca 2+ ] i in isolated E10.5 mouse hearts. Our results show that spontaneous [Ca 2+ ] i oscillations were intact and robustly responded to a variety of stimuli including extracellular calcium (5 mM), caffeine (5 mM), and NE (100 nM) in a manner that was indistinguishable from controls. Further, we show similar patterns of distribution (via immunofluorescent histochemical staining) and activity (via patch-clamp recording techniques) for the major voltage-gated plasma membrane calcium channel responsible for the L-type calcium current, I Ca,L , in adrenergic-deficient and control embryonic cardiac cells. These results demonstrate that despite the absence of vital adrenergic hormones that consistently leads to embryonic lethality in vivo, intracellular and extracellular calcium signaling remain essentially intact and functional in embryonic mouse hearts through E10.5. These findings suggest that adrenergic stimulation is not required for the development of intracellular calcium oscillations or extracellular calcium signaling through I Ca,L and that aberrant calcium signaling does not likely contribute

  1. STUDY OF CARDIAC INVOLVEMENT IN DIPHTHERIA

    Directory of Open Access Journals (Sweden)

    Bala Raju Gundam

    2016-07-01

    Full Text Available BACKGROUND Diphtheria still endemic in many developing countries and is responsible for high case fatality. Myocardial involvement is a serious complication of diphtheria and diphtheria myocarditis frequently complicated by arrhythmias causes sudden death if not managed properly. So, early and adequate administration of Anti-Diphtheritic Serum (ADS and frequent monitoring particularly 24 hrs. ECG monitoring is helpful to detect any serious cardiac arrhythmias. METHODS A prospective study on patients who were culture positive diagnosed on the basis of WHO definition were treated and analysed in respect to homographic details, immunisation strategy, and clinical features with particular attention to myocarditis. RESULTS In the study, common age group affected by diphtheria was 5 to 10 years. Incidence of myocarditis more in same age group. Out of 64 patients with myocarditis, 23 patients died. CONCLUSION Incidence of diphtheria has increased in the recent years. Commonly effected age group is 5 to 10 years and most of them are presented with asymptomatic myocarditis. Symptomatic diphtheritic myocarditis has high mortality rate even with aggressive management. Patient who presented with either LBBB alone are with combination of other conduction of abnormalities has high mortality rate.

  2. Is it time for cardiac innervation imaging?

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, J. [Turku Univ., Turku (Finland) Turku PET Center; Sipola, P. [Kuopio Univ., Kuopio (Finland)

    2005-03-01

    The autonomic nervous system plays an important role in the regulation of cardiac function and the regional distribution of cardiac nerve terminals can be visualized using scintigraphic techniques. The most commonly used tracer is iodine-123-metaiodobenzylguanidine (MIBG) but C-11-hydroxyephedrine has also been used with PET. When imaging with MIBG, the ratio of heart-to-mediastinal counts is used as an index of tracer uptake, and regional distribution is also assessed from tomographic images. The rate of clearance of the tracer can also be measured and indicates the function of the adrenergic system. Innervation imaging has been applied in patients with susceptibility to arrythmias, coronary artery disease, hypertrophic and dilated cardiomyopathy and anthracycline induced cardiotoxicity. Abnormal adrenergic innervation or function appear to exist in many pathophysiological conditions indicating that sympathetic neurons are very susceptible to damage. Abnormal findings in innervation imaging also appear to have significant prognostic value especially in patients with cardiomyopathy. Recently, it has also been shown that innervation imaging can monitor drug-induced changes in cardiac adrenergic activity. Although innervation imaging holds great promise for clinical use, the method has not received wider clinical acceptance. Larger randomized studies are required to confirm the value of innervation imaging in various specific indications.

  3. Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to "Biased Opioids"?

    Science.gov (United States)

    Root-Bernstein, Robert; Turke, Miah; Subhramanyam, Udaya K Tiruttani; Churchill, Beth; Labahn, Joerg

    2018-01-17

    Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists.

  4. Human myometrial adrenergic receptors during pregnancy: identification of the alpha-adrenergic receptor by [3H] dihydroergocryptine binding

    International Nuclear Information System (INIS)

    Jacobs, M.M.; Hayashida, D.; Roberts, J.M.

    1985-01-01

    The radioactive alpha-adrenergic antagonist [ 3 H] dihydroergocryptine binds to particulate preparations of term pregnant human myometrium in a manner compatible with binding to the alpha-adrenergic receptor (alpha-receptor). [ 3 H] Dihydroergocryptine binds with high affinity (KD = 2 nmol/L and low capacity (receptor concentration = 100 fmol/mg of protein). Adrenergic agonists compete for [ 3 H] dihydroergocryptine binding sites stereo-selectively ([-]-norepinephrine is 100 times as potent as [+]-norepinephrine) and in a manner compatible with alpha-adrenergic potencies (epinephrine approximately equal to norepinephrine much greater than isoproterenol). Studies in which prazosin, an alpha 1-antagonist, and yohimbine, and alpha 2-antagonist, competed for [ 3 H] dihydroergocryptine binding sites in human myometrium indicated that approximately 70% are alpha 2-receptors and that 30% are alpha 1-receptors. [ 3 H] dihydroergocryptine binding to human myometrial membrane particulate provides an important tool with which to study the molecular mechanisms of uterine alpha-adrenergic response

  5. Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

    International Nuclear Information System (INIS)

    Mirbolooki, M. Reza; Upadhyay, Sanjeev Kumar; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

    2014-01-01

    Objective: Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. Methods: A β 3 -adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [ 18 F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Results: Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [ 18 F]FDG PET images. CL 316243 increased the total [ 18 F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [ 18 F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [ 18 F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU

  6. GSK-3α directly regulates β-adrenergic signaling and the response of the heart to hemodynamic stress in mice

    Science.gov (United States)

    Zhou, Jibin; Lal, Hind; Chen, Xiongwen; Shang, Xiying; Song, Jianliang; Li, Yingxin; Kerkela, Risto; Doble, Bradley W.; MacAulay, Katrina; DeCaul, Morgan; Koch, Walter J.; Farber, John; Woodgett, James; Gao, Erhe; Force, Thomas

    2010-01-01

    The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, α and β. Although GSK-3β has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3α in the mouse heart using gene targeting. Gsk3a–/– mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. Surprisingly, markedly impaired β-adrenergic responsiveness was found at both the organ and cellular level. This phenotype was reproduced by acute treatment of WT cardiomyocytes with a small molecule GSK-3 inhibitor, confirming that the response was not due to a chronic adaptation to LV dysfunction. Thus, GSK-3α appears to be the central regulator of a striking range of essential processes, including acute and direct positive regulation of β-adrenergic responsiveness. In the absence of GSK-3α, the heart cannot respond effectively to hemodynamic stress and rapidly fails. Our findings identify what we believe to be a new paradigm of regulation of β-adrenergic signaling and raise concerns given the rapid expansion of drug development targeting GSK-3. PMID:20516643

  7. Adrenergic innervation of the rat hypothalamus

    NARCIS (Netherlands)

    Palkovits, M.; Mezey, E.; Záborszky, L.; Feminger, A.; Versteeg, D.H.G.; Wijnen, H.J.L.M.; Jong, Wybren de; Fekete, M.I.K.; Herman, J.P.; Kanyicska, B.

    The adrenergic innervation of the hypothalamus was studied by measuring hypothalamic adrenaline levels following surgical transection of the lower brain stem or electrolytic lesion of the medullary adrenaline-containing cell groups. The adrenaline levels in some hypothalamic nuclei and in the median

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

    DEFF Research Database (Denmark)

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

    1991-01-01

    In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... 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...

  9. Beta adrenergic receptors in human cavernous tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

    1985-04-01

    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  10. 164Ile allele in the beta2-Adrenergic receptor gene is associated with risk of elevated blood pressure in women. The Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Sethi, AA; Tybjærg-Hansen, A; Jensen, Gorm Boje

    2005-01-01

    Since beta2-adrenergic receptors are important regulators of blood pressure, genetic variation in this receptor could explain risk of elevated blood pressure in selected individuals. We tested the hypothesis that Gly16Arg, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor gene associated w...

  11. [Experimental therapy of cardiac remodeling with quercetin-containing drugs].

    Science.gov (United States)

    Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

    2013-01-01

    It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

  12. Dual-gated cardiac PET-clinical feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Teraes, Mika; Kokki, Tommi; Noponen, Tommi; Hoppela, Erika; Sipilae, Hannu T.; Knuuti, Juhani [Turku PET Centre, PO BOX 52, Turku (Finland); Durand-Schaefer, Nicolas [General Electric Medical Systems, Buc (France); Pietilae, Mikko [Turku University Hospital, Department of Internal Medicine, Turku (Finland); Kiss, Jan [Turku University Hospital, Department of Surgery, Turku (Finland)

    2010-03-15

    Both respiratory and cardiac motions reduce image quality in myocardial imaging. For accurate imaging of small structures such as vulnerable coronary plaques, simultaneous cardiac and respiratory gating is warranted. This study tests the feasibility of a recently developed robust method for cardiac-respiratory gating. List-mode data with triggers from respiratory and cardiac cycles are rearranged into dual-gated segments and reconstructed with standard algorithms of a commercial PET/CT scanner. Cardiac gates were defined as three fixed phases and one variable diastolic phase. Chest motion was measured with a respiratory gating device and post-processed to determine gates. Preservation of quantification in dual-gated images was tested with an IEC whole-body phantom. Minipig and human studies were performed to evaluate the feasibility of the method. In minipig studies, a coronary catheter with radioactive tip was guided in coronary artery for in vivo and ex vivo acquisitions. Dual gating in humans with suspected cardiac disorders was performed using 18-F-FDG as a tracer. The method was found feasible for in vivo imaging and the radioactive catheter tip was better resolved in gated images. In human studies, the dual gating was found feasible and easy for clinical routine. Maximal movement of myocardial surface in cranio-caudal direction was over 20 mm. The shape of myocardium was clearly different between the gates and papillary muscles become more visible in diastolic images. The first clinical experiences using robust cardiac-respiratory dual gating are encouraging. Further testing in larger clinical populations using tracers designed especially for plaque imaging is warranted. (orig.)

  13. Dual-gated cardiac PET-clinical feasibility study

    International Nuclear Information System (INIS)

    Teraes, Mika; Kokki, Tommi; Noponen, Tommi; Hoppela, Erika; Sipilae, Hannu T.; Knuuti, Juhani; Durand-Schaefer, Nicolas; Pietilae, Mikko; Kiss, Jan

    2010-01-01

    Both respiratory and cardiac motions reduce image quality in myocardial imaging. For accurate imaging of small structures such as vulnerable coronary plaques, simultaneous cardiac and respiratory gating is warranted. This study tests the feasibility of a recently developed robust method for cardiac-respiratory gating. List-mode data with triggers from respiratory and cardiac cycles are rearranged into dual-gated segments and reconstructed with standard algorithms of a commercial PET/CT scanner. Cardiac gates were defined as three fixed phases and one variable diastolic phase. Chest motion was measured with a respiratory gating device and post-processed to determine gates. Preservation of quantification in dual-gated images was tested with an IEC whole-body phantom. Minipig and human studies were performed to evaluate the feasibility of the method. In minipig studies, a coronary catheter with radioactive tip was guided in coronary artery for in vivo and ex vivo acquisitions. Dual gating in humans with suspected cardiac disorders was performed using 18-F-FDG as a tracer. The method was found feasible for in vivo imaging and the radioactive catheter tip was better resolved in gated images. In human studies, the dual gating was found feasible and easy for clinical routine. Maximal movement of myocardial surface in cranio-caudal direction was over 20 mm. The shape of myocardium was clearly different between the gates and papillary muscles become more visible in diastolic images. The first clinical experiences using robust cardiac-respiratory dual gating are encouraging. Further testing in larger clinical populations using tracers designed especially for plaque imaging is warranted. (orig.)

  14. Beta-Adrenergic gene therapy for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Koch Walter J

    2000-10-01

    Full Text Available Abstract Gene therapy using in vivo recombinant adenovirus-mediated gene transfer is an effective technique that offers great potential to improve existing drug treatments for the complex cardiovascular diseases of heart failure and vascular smooth muscle intimal hyperplasia. Cardiac-specific adenovirus-mediated transfer of the carboxyl-terminus of the β-adrenergic receptor kinase (βARKct, acting as a Gβγ-β-adrenergic receptor kinase (βARK1 inhibitor, improves basal and agonist-induced cardiac performance in both normal and failing rabbit hearts. In addition, βARKct adenovirus infection of vascular smooth muscle is capable of significantly diminishing neointimal proliferation after angioplasty. Therefore, further investigation is warranted to determine whether inhibition of βARK1 activity and sequestration of Gβγ via an adenovirus that encodes the βARKct transgene might be a useful clinical tool for the treatment of cardiovascular pathologies.

  15. Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase.

    OpenAIRE

    Klein, D C; Sugden, D; Weller, J L

    1983-01-01

    The role played by postsynaptic alpha-adrenergic receptors in the stimulation of pineal N-acetyltransferase (EC 2.3.1.5) and [3H]melatonin production was investigated in the rat. In vivo studies indicated that phenylephrine, an alpha-adrenergic agonist, potentiated and prolonged the effects of isoproterenol, a beta-adrenergic agonist. Similar observations were made in organ culture with glands devoid of functional nerve endings. In addition, a combination of 1 microM prazosin, an alpha 1-adre...

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

    DEFF Research Database (Denmark)

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

    1991-01-01

    In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... densities (and binding affinities), measured with 3H-labelled yohimbine, and adrenaline-induced suppression of cyclic AMP contents did not differ among the three groups. Thus, in contrast to idiopathic autonomic failure, there is no generalized increase in adrenergic receptors in autonomic failure due...

  17. Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

    Directory of Open Access Journals (Sweden)

    Fatima Dumas Cintra

    2014-11-01

    Full Text Available Background: The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective: To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods: Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart® system. Results: A total of 767 participants (461 men with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001. After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia. Conclusion: Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample.

  18. Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

    Science.gov (United States)

    Kamenický, Peter; Redheuil, Alban; Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

    2014-11-01

    Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

  19. Impact of the β-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study.

    Science.gov (United States)

    Lee, Hae-Young; Chung, Wook-Jin; Jeon, Hui-Kyung; Seo, Hong-Seog; Choi, Dong-Ju; Jeon, Eun-Seok; Kim, Jae-Joong; Shin, Joon Han; Kang, Seok-Min; Lim, Sung Cil; Baek, Sang-Hong

    2016-03-01

    We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 ± 14.3 to 70.0 ± 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 ± 2.62 mg vs. 3.96 ± 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring β-blocker therapy according to genotype.

  20. An ethical framework for cardiac report cards: a qualitative study.

    Science.gov (United States)

    Richard, Shawn A; Rawal, Shail; Martin, Douglas K

    2005-03-28

    The recent proliferation of health care report cards, especially in cardiac care, has occurred in the absence of an ethical framework to guide in their development and implementation. An ethical framework is a consistent and comprehensive theoretical foundation in ethics, and is formed by integrating ethical theories, relevant literature, and other critical information (such as the views of stakeholders). An ethical framework in the context of cardiac care provides guidance for developing cardiac report cards (CRCs) that are relevant and legitimate to all stakeholders. The purpose of this study is to develop an ethical framework for CRCs. Delphi technique - 13 panelists: 2 administrators, 2 cardiac nurses, 5 cardiac patients, 2 cardiologists, 1 member of the media, and 1 outcomes researcher. Panelists' views regarding the ethics of CRCs were analyzed and organized into themes. We have organized panelists' views into ten principles that emerged from the data: 1) improving quality of care, 2) informed understanding, 3) public accountability, 4) transparency, 5) equity, 6) access to information 7) quality of information, 8) multi-stakeholder collaboration, 9) legitimacy, and 10) evaluation and continuous quality improvement. We have developed a framework to guide the development and dissemination of CRCs. This ethical framework can provide necessary guidance for those generating CRCs and may help them avoid a number of difficult issues associated with existing ones.

  1. An ethical framework for cardiac report cards: a qualitative study

    Directory of Open Access Journals (Sweden)

    Rawal Shail

    2005-03-01

    Full Text Available Abstract Background The recent proliferation of health care report cards, especially in cardiac care, has occurred in the absence of an ethical framework to guide in their development and implementation. An ethical framework is a consistent and comprehensive theoretical foundation in ethics, and is formed by integrating ethical theories, relevant literature, and other critical information (such as the views of stakeholders. An ethical framework in the context of cardiac care provides guidance for developing cardiac report cards (CRCs that are relevant and legitimate to all stakeholders. The purpose of this study is to develop an ethical framework for CRCs. Methods Delphi technique – 13 panelists: 2 administrators, 2 cardiac nurses, 5 cardiac patients, 2 cardiologists, 1 member of the media, and 1 outcomes researcher. Panelists' views regarding the ethics of CRCs were analyzed and organized into themes. Results We have organized panelists' views into ten principles that emerged from the data: 1 improving quality of care, 2 informed understanding, 3 public accountability, 4 transparency, 5 equity, 6 access to information 7 quality of information, 8 multi-stakeholder collaboration, 9 legitimacy, and 10 evaluation and continuous quality improvement. Conclusion We have developed a framework to guide the development and dissemination of CRCs. This ethical framework can provide necessary guidance for those generating CRCs and may help them avoid a number of difficult issues associated with existing ones.

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

    Science.gov (United States)

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

    2015-02-01

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

  3. Adrenergic nerve fibres and mast cells: correlation in rat thymus.

    Science.gov (United States)

    Artico, Marco; Cavallotti, Carlo; Cavallotti, Daniela

    2002-10-21

    The interactions between adrenergic nerve fibres and mast cells (MCs) were studied in the thymus of adult and old rats by morphological methods and by quantitative analysis of images (QAIs). The whole thymus was drawn in adult (12 months old) rats: normal, sympathectomized or electrostimulated. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for detection of microanatomical details and with Bodian's method for identification of the whole nerve fibres. Thymic MCs were stained with Astrablau. Histofluorescence microscopy was used for staining of adrenergic nerve fibres. Finally, all morphological results were submitted to the QAIs and statistical analysis of data. Our results suggest that after surgical sympathectomy, the greater part of adrenergic nerve fibres disappear while related MCs appear to show less evident fluorescence and few granules. On the contrary, electrostimulation of the cervical superior ganglion induced an increase in the fluorescence of adrenergic nerve fibres and of related MCs.

  4. 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)

    2015-09-15

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

  5. Temperature effects on aerobic scope and cardiac performance of European perch (Perca fluviatilis).

    Science.gov (United States)

    Jensen, Denise Lyager; Overgaard, Johannes; Wang, Tobias; Gesser, Hans; Malte, Hans

    2017-08-01

    Several recent studies have highlighted how impaired cardiac performance at high temperatures and in hypoxia may compromise the capacity for oxygen transport. Thus, at high temperatures impaired cardiac capacity is proposed to reduce oxygen transport to a degree that lowers aerobic scope and compromises thermal tolerance (the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis). To investigate this hypothesis, we measured aerobic and cardiac performance of a eurythermal freshwater teleost, the European perch (Perca fluviatilis). Rates of oxygen consumption were measured during rest and activity at temperatures between 5°C and 27°C, and we evaluated cardiac function by in vivo measurements of heart rate and in vitro studies to determine contractility of myocardial strips. Aerobic scope increased progressively from 5°C to 21°C, after which it levelled off. Heart rate showed a similar response. We found little difference between resting and active heart rate at high temperature suggesting that increased cardiac scope during activity is primarily related to changes in stroke volume. To examine the effects of temperature on cardiac capacity, we measured isometric force development in electrically paced myocardial preparations during different combinations of temperature, pacing frequency, oxygenation and adrenergic stimulation. The force-frequency product increased markedly upon adrenergic stimulation at 21 and 27°C (with higher effects at 21°C) and the cardiac preparations were highly sensitive to hypoxia. These findings suggest that at (critically) high temperatures, cardiac output may diminish due to a decreased effect of adrenergic stimulation and that this effect may be further exacerbated if the heart becomes hypoxic. Hence cardiac limitations may contribute to the inability to increase aerobic scope at high temperatures in the European perch (Perca fluviatilis). Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Peripheral adrenergic receptors in hypertension

    NARCIS (Netherlands)

    Michel, M. C.; Brodde, O. E.; Insel, P. A.

    1990-01-01

    Increased sympathoadrenal activity appears to play an important role in the development or maintenance of elevated blood pressure in hypertensive patients and various animal models of hypertension. Alterations of adrenergic receptor number or responsiveness might contribute to this increased

  7. Studies of the associations between functional beta2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects

    DEFF Research Database (Denmark)

    Gjesing, A P; Andersen, G; Burgdorf, K S

    2007-01-01

    Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results.......Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results....

  8. Amiloride interacts with renal α- and β-adrenergic receptors

    International Nuclear Information System (INIS)

    Howard, M.J.; Mullen, M.D.; Insel, P.A.

    1987-01-01

    The authors have used radioligand binding techniques to assess whether amiloride and certain analogues of amiloride (ethylisopropyl amiloride and benzamil) can bind to adrenergic receptors in the kidney. They found that amiloride could compete for [ 3 H]rauwolscine (α 2 -adrenergic receptors), [ 3 H]prazosin (α 1 -adrenergic receptors), and [ 125 I]iodocyanopindolol (β-adrenergic receptors) binding in rat renal cortical membranes with inhibitor constants of 13.6 /plus minus/ 5.7, 24.4 /plus minus/ 7.4, and 8.36 /plus minus/ 13.5 μM, respectively. Ethylisopropyl amiloride and benzamil were from 2- to 25-fold more potent than amiloride in competing for radioligand binding sites in studies with these membranes. In addition, amiloride and the two analogues competed for [ 3 H]prazosin sites on intact Madin-Darby canine kidney cells and amiloride blocked epinephrine-stimulated prostaglandin E 2 production in these cells. They conclude that amiloride competes for binding to several classes of renal adrenergic receptors with a rank order of potency of α 2 > α 1 > β. Binding to, and antagonism of, adrenergic receptors occurs at concentrations of amiloride that are lower than previously observed nonspecific interactions of this agent

  9. Study on clinical symptoms in canine cardiac diseases

    Directory of Open Access Journals (Sweden)

    F. Karlette Anne

    Full Text Available Cardiac diseases in canines are an extensively studied phenomenon all over the world but meagre information has been reported in India. Certain problems, including historical, physical, and laboratory abnormalities, are associated with cardiovascular or pulmonary disease. In India however, the recognition of canine cardiac diseases has been delayed, and ignored on account of lack of awareness and knowledge by the owner and inadequate diagnostic facility to a field veterinarian. Considering the above facts, the present study was undertaken in Gujarat to survey the prevalence of common cardiac diseases in hospital population of dogs along with the clinical symptoms which often goes undetected due to lack of proper diagnostic techniques to be implied and the most forms of heart disease may be present for many years before any evidence of failure develops. In the present study most of the clinical cases of cardiac diseases were presented with a history of nocturnal coughing (seven cases; 2.55%, exercise intolerance (five cases; 1.82%, partial or complete anorexia (five cases; 1.82%, swelling in abdominal area (four cases; 1.45%, dullness and depression (two cases; 0.72%, cachexia and hepatojugular pulsation (one case each; 0.36% each at times. [Vet World 2009; 2(8.000: 307-309

  10. Cardiac pathology in chronic alcoholics: A preliminary study

    Directory of Open Access Journals (Sweden)

    P Vaideeswar

    2014-01-01

    Full Text Available Background: Ethyl alcohol exerts both positive and negative effects on the cardiovascular system. Alcoholic cardiomyopathy, produced by direct or indirect mechanisms, is well-documented. An important, but seldom appreciated effect is an increase in iron deposition in the myocardium, which can add to the cardiac dysfunction. The present study was planned to document the pathological features and iron levels in the cardiac tissue of patients who were chronic alcoholics and correlate these characteristics with the liver pathology and iron content. Materials and Methods: An autopsy-based prospective study of 40 consecutive patients compared with ten age matched controls (no history of alcohol intake. Histopathological changes like the morphology of the cardiac myocytes, degree of fibrosis (interstitial, interfiber, perivascular, and replacement, presence of inflammatory cells, increased capillary network, and adipose tissue deposition were noted and graded. These were also correlated with the liver pathology. The iron content in the heart and liver were measured by using calorimetry. Results: All cases had increased epicardial adipose tissue with epicardial and endocardial fibrosis, prominence of interstitial and interfiber fibrosis, myofiber degeneration, and increased capillary network; this was particularly prominent in patients with cirrhosis. Elemental iron level in heart tissue was raised in the cases relative to controls. Conclusions: Alcohol produces subclinical changes in the myocardium, with an increased iron content, which may be the forerunner for subsequent clinical cardiac dysfunction.

  11. The adrenergic retulation of the cardiovascular system in the South American rattlesnake, Crotalus durissus

    DEFF Research Database (Denmark)

    Galli, G.L.J.; Jensen, Nini Skovgaard; Abe, A.S.

    2007-01-01

    The present study investigates adrenergic regulation of the systemic and pulmonary circulations of the anaesthetised South American rattlesnake, Crotalus durissus. Haemodynamic measurements were made following bolus injections of adrenaline and adrenergic antagonists administered through a systemic...... arterial catheter. Adrenaline caused a marked systemic vasoconstriction that was abolished by phentolamine, indicating this response was mediated through α-adrenergic receptors. Injection of phentolamine gave rise to a pronounced vasodilatation (systemic conductance (Gsys) more than doubled), while...... injection of propranolol caused a systemic vasoconstriction, pointing to a potent α-adrenergic, and a weaker β-adrenergic tone in the systemic vasculature of Crotalus. Overall, the pulmonary vasculature was far less responsive to adrenergic stimulation than the systemic circulation. Adrenaline caused...

  12. Synthesis of fluorine-18 fluoroalkyl pindolol derivatives: Ligands for the β-adrenergic receptor

    International Nuclear Information System (INIS)

    Tewson, T.J.; Kinsey, B.M.; Franceschini, M.P.

    1990-01-01

    [I-125]Iodocyanopindolol, an antagonist for the β-adrenergic receptor, has been shown to accumulate in vivo in areas rich in β-adrenergic receptors, presumably through saturable receptor mediated binding. In order to perform PET studies of the β-adrenergic receptor in the heart and lung the authors have prepared fluoroalkyl analogs of iodocyanopindolol and are evaluating these compounds for this purpose

  13. β1-adrenergic receptor stimulation by agonist Compound 49b restores insulin receptor signal transduction in vivo

    Science.gov (United States)

    Jiang, Youde; Zhang, Qiuhua; Ye, Eun-Ah

    2014-01-01

    Purpose Determine whether Compound 49b treatment ameliorates retinal changes due to the lack of β2-adrenergic receptor signaling. Methods Using retinas from 3-month-old β2-adrenergic receptor-deficient mice, we treated mice with our novel β1-/β2-adrenergic receptor agonist, Compound 49b, to assess the effects of adrenergic agonists acting only on β1-adrenergic receptors due to the absence of β2-adrenergic receptors. Western blotting or enzyme-linked immunosorbent assay (ELISA) analyses were performed for β1- and β2-adrenergic receptors, as well as key insulin resistance proteins, including TNF-α, SOCS3, IRS-1Ser307, and IRTyr960. Analyses were also performed on key anti- and proapoptotic proteins: Akt, Bcl-xL, Bax, and caspase 3. Electroretinogram analyses were conducted to assess functional changes, while histological assessment was conducted for changes in retinal thickness. Results A 2-month treatment of β2-adrenergic receptor-deficient mice with daily eye drops of 1 mM Compound 49b, a novel β1- and β2-adrenergic receptor agonist, reversed the changes in insulin resistance markers (TNF-α and SOCS3) observed in untreated β2-adrenergic receptor-deficient mice, and concomitantly increased morphological integrity (retinal thickness) and functional responses (electroretinogram amplitude). These results suggest that stimulating β1-adrenergic receptors on retinal endothelial cells or Müller cells can compensate for the loss of β2-adrenergic receptor signaling on Müller cells, restore insulin signal transduction, reduce retinal apoptosis, and enhance retinal function. Conclusions Since our previous studies with β1-adrenergic receptor knockout mice confirmed that the reverse also occurs (β2-adrenergic receptor stimulation can compensate for the loss of β1-adrenergic receptor activity), it appears that increased activity in either of these pathways alone is sufficient to block insulin resistance–based retinal cell apoptosis. PMID:24966659

  14. Adrenergic manipulation inhibits pavlovian conditioned approach behaviors.

    Science.gov (United States)

    Pasquariello, Kyle Z; Han, Marina; Unal, Cagla; Meyer, Paul J

    2018-02-26

    Environmental rewards and Pavlovian reward cues can acquire incentive salience, thereby eliciting incentive motivational states and instigate reward-seeking. In rats, the incentive salience of food cues can be measured during a Pavlovian conditioned approach paradigm, in which rats engage in cue-directed approach ("sign-tracking") or approach the food delivery location ("goal-tracking"). While it has been shown that dopamine signaling is necessary for sign-tracking, some studies have suggested that norepinephrine is involved in learning to sign-track as well. Thus, in order to investigate the influence of norepinephrine in Pavlovian conditioned approach, we administered three adrenergic drugs while rats learned that a food cue (an illuminated, retractable lever) preceded the delivery of banana-flavored food pellets into a food-cup. We found that pre-session injections of disulfiram (a dopamine-β-hydroxylase inhibitor) inhibited the development of sign-tracking, but goal-tracking was only affected at the high dose. In one experiment, post-session injections of disulfiram blocked the development of sign-tracking, although this effect was not replicated in a separate set of rats. Post-session injections of prazosin (an α1-adrenergic receptor antagonist) and propranolol (a β-adrenergic receptor antagonist) also blocked the development of sign-tracking but not goal-tracking. Taken together, these results suggest that adrenergic transmission mediates the acquisition of sign-tracking but not goal-tracking, and thus plays a selective role in the attribution of incentive salience food cues. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

    Science.gov (United States)

    Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

    2014-01-01

    Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

  16. Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

    Science.gov (United States)

    Turke, Miah; Subhramanyam, Udaya K. Tiruttani; Churchill, Beth; Labahn, Joerg

    2018-01-01

    Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists. PMID:29342106

  17. Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to “Biased Opioids”?

    Directory of Open Access Journals (Sweden)

    Robert Root-Bernstein

    2018-01-01

    Full Text Available Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists.

  18. Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

    Directory of Open Access Journals (Sweden)

    Yuya Makiguchi

    Full Text Available Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

  19. Association between ß2-adrenergic receptor gene polymorphisms and adverse events of ritodrine in the treatment of preterm labor: a prospective observational study.

    Science.gov (United States)

    Chung, Jee Eun; Choi, Soo An; Hwang, Han Sung; Park, Jin Young; Lee, Kyung Eun; Yee, Jeong; Kim, Young Ju; Gwak, Hye Sun

    2017-11-13

    Ritodrine, a tocolytic β2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between β2-adrenergic receptor (ADRB2) polymorphisms and adverse drug events (ADEs) in patients with preterm labor treated with ritodrine. This follow-up study was prospectively conducted at Ewha Womans University Mokdong Hospital in Korea. Five single nucleotide polymorphisms (SNPs) of the ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) were analyzed in 186 pregnant women with preterm labor. Patients with the AA genotype of rs1042717 had significantly lower incidence of ADEs compared to those with the G allele (p = 0.009). In multivariate analysis, one of the predictors of ADEs was the maximum infusion rate of ritodrine (AOR 4.47, 95% CI 1.31-15.25). Rs1042719 was also a significant factor for ritodrine-induced ADEs. The CC genotype carriers had 78% decreased risk of ADEs compared to those with other genotypes. This study demonstrates that ADEs induced by ritodrine are associated with ADRB2 gene polymorphisms, as well as the infusion rate of ritodrine in pregnant women with preterm labor.

  20. The Relationship between Birthweight and Longitudinal Changes of Blood Pressure Is Modulated by Beta-Adrenergic Receptor Genes: The Bogalusa Heart Study

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2010-01-01

    Full Text Available This study examines the genetic influence of β-adrenergic receptor gene polymorphisms (β2-AR Arg16Gly and β3-AR Trp64Arg on the relationship of birthweight to longitudinal changes of blood pressure (BP from childhood to adulthood in 224 black and 515 white adults, aged 21–47 years, enrolled in the Bogalusa Heart Study. Blacks showed significantly lower birthweight and frequencies of β2-AR Gly16 and β3-AR Trp64 alleles and higher BP levels and age-related trends than whites. In multivariable regression analyses using race-adjusted BP and birthweight, low birthweight was associated with greater increase in age-related trend of systolic BP (standardized regression coefficient β=−0.09, P=.002 and diastolic BP (β=−0.07, P=.037 in the combined sample of blacks and whites, adjusting for the first BP measurement in childhood, sex, age, and gestational age. Adjustment for the current body mass index strengthened the birthweight-BP association. Importantly, the strength of the association, measured as regression coefficients, was modulated by the combination of β2-AR and β3-AR genotypes for systolic (P=.042 for interaction and diastolic BP age-related trend (P=.039 for interaction, with blacks and whites showing a similar trend in the interaction. These findings indicate that the intrauterine programming of BP regulation later in life depends on β-AR genotypes.

  1. In vitro study on the effects of some selected agonists and antagonists of alpha(1)-adrenergic receptors on the contractility of the aneurysmally-changed aortic smooth muscle in humans.

    Science.gov (United States)

    Gnus, J; Czerski, A; Ferenc, S; Zawadzki, W; Witkiewicz, W; Hauzer, W; Rusiecka, A; Bujok, J

    2012-02-01

    The study included 18 sections of the aneurysmally-changed abdominal aortas, obtained from patients of the Provincial Specialist Hospital in Wroclaw and 18 sections of normal abdominal aortas obtained from swine. The collected samples were placed horizontally in the incubation chamber. Changes in their transverse section area were registered. They were stretched to a tension of 5 mN. Krebs-Henseleit buffer was used as the incubatory environment. Incubation of the sections was performed at a temperature of 37°C, in the gaseous mixture of oxygen and carbon dioxide used in the following proportion: 95% of O(2) and 5% of CO(2). Contractions of the aorta were registered with isotonic transducers (Letica Scientific Instruments). In the studies, we examined the influence of α(1)-adrenergic receptors (and their subtypes α(1A), α(1B), α(1D)) on the contractility of the aortic muscle in humans and swine by their stimulation or inhibition with some selected agonists or antagonists. This time, it was shown that the stimulation of α(1)-adrenergic receptors leads to contractions of the human and swine aortic muscle; the observed increase in the muscle tone may follow from the stimulation of all subtypes of alpha-1 receptor (α(1A), α(1B), α(1D)). All three subtypes of 1-adrenergic receptor are engaged in vasoconstriction, especially of α(1A) and α(1D) subtypes; the α(1B) subtype is less significant for aortic contractility. The contractile response of the aneurysmally-changed abdominal aorta in humans to agonists of α-adrenergic receptors was significantly less intense than that of the normal porcine aorta. It can be concluded that aneurysms influence the contractile response of the aorta.

  2. Regulation of cardiac C-protein phosphorylation

    International Nuclear Information System (INIS)

    Titus, F.L.

    1985-01-01

    Molecular mechanisms of cardiac sympathetic and parasympathetic responses were addressed by studying subcellular changes in protein phosphorylation, cAMP-dependent protein kinase activity and protein phosphatase activity in frog hearts. B-adrenergic agonists increased and muscarinic cholinergic agonists decreased [ 32 P]phosphate incorporation into C-protein, a thick filament component. Regulation of protein phosphatase activity by Iso and methacholine (MCh) was assayed using extracts of drug treated frog hearts and [ 32 P]phospho-C-protein as substrate. Total phosphatase activity decreased 21% in extracts from hearts perfused with 0.1 μM Iso and 17% in hearts exposed to Iso plus 1 μM methacholine. This decrease reflected decreased phosphatase-2A activity. No changes in total phosphatase activity were measurable in broken cells treated with Iso or MCh. The results suggest adrenergic stimulation changes contractile activity in frog hearts by activating cAMP-dependent protein kinase associated with particulate cellular elements and inactivating soluble protein phosphatase-2A. This is the first demonstration of coordinated regulation of these enzymes by B-adrenergic agonists favoring phosphorylation of effector proteins. Coordinated regulation by methacholine in the presence of Iso was not observed

  3. Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity

    International Nuclear Information System (INIS)

    Oliveira, Paulo J.; Bjork, James A.; Santos, Maria S.; Leino, Richard L.; Froberg, M. Kent; Moreno, Antonio J.; Wallace, Kendall B.

    2004-01-01

    The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a β-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its β-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a β-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its β-adrenergic receptor antagonism

  4. Intrinsic cardiac nervous system in tachycardia induced heart failure.

    Science.gov (United States)

    Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

    2003-11-01

    The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to

  5. Antagonism of Lateral Amygdala Alpha1-Adrenergic Receptors Facilitates Fear Conditioning and Long-Term Potentiation

    Science.gov (United States)

    Lazzaro, Stephanie C.; Hou, Mian; Cunha, Catarina; LeDoux, Joseph E.; Cain, Christopher K.

    2010-01-01

    Norepinephrine receptors have been studied in emotion, memory, and attention. However, the role of alpha1-adrenergic receptors in fear conditioning, a major model of emotional learning, is poorly understood. We examined the effect of terazosin, an alpha1-adrenergic receptor antagonist, on cued fear conditioning. Systemic or intra-lateral amygdala…

  6. On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats

    NARCIS (Netherlands)

    Michel, M. C.; Jäger, S.; Casto, R.; Rettig, R.; Graf, C.; Printz, M.; Insel, P. A.; Philipp, T.; Brodde, O. E.

    1992-01-01

    We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor

  7. Neurohumoral activation in heart failure: the role of adrenergic receptors

    Directory of Open Access Journals (Sweden)

    Patricia C. Brum

    2006-09-01

    Full Text Available Heart failure (HF is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality. The development of end-stage HF often involves an initial insult to the myocardium that reduces cardiac output and leads to a compensatory increase in sympathetic nervous system activity. Acutely, the sympathetic hyperactivity through the activation of beta-adrenergic receptors increases heart rate and cardiac contractility, which compensate for decreased cardiac output. However, chronic exposure of the heart to elevated levels of catecholamines released from sympathetic nerve terminals and the adrenal gland may lead to further pathologic changes in the heart, resulting in continued elevation of sympathetic tone and a progressive deterioration in cardiac function. On a molecular level, altered beta-adrenergic receptor signaling plays a pivotal role in the genesis and progression of HF. beta-adrenergic receptor number and function are decreased, and downstream mechanisms are altered. In this review we will present an overview of the normal beta-adrenergic receptor pathway in the heart and the consequences of sustained adrenergic activation in HF. The myopathic potential of individual components of the adrenergic signaling will be discussed through the results of research performed in genetic modified animals. Finally, we will discuss the potential clinical impact of beta-adrenergic receptor gene polymorphisms for better understanding the progression of HF.A insuficiência cardíaca (IC é a via final comum da maioria das doenças cardiovasculares e uma das maiores causas de morbi-mortalidade. O desenvolvimento do estágio final da IC freqüentemente envolve um insulto inicial do miocárdio, reduzindo o débito cardíaco e levando ao aumento compensatório da atividade do sistema nervoso simpático (SNS. Existem evidências de que apesar da exposição aguda ser benéfica, exposições crônicas a elevadas concentra

  8. The role of adrenaline as a modulator of cardiac performance in three Notothenioid fishes

    DEFF Research Database (Denmark)

    Skov, Peter Vilhelm; Bushnell, P.; Tirsgaard, Bjørn

    2008-01-01

    The present work was performed to test the hypothesis that Antarctic teleosts rely mostly on cholinergic inhibition to modulate cardiac performance. Isometric muscle preparations were used to examine the inotropic and chronotropic properties of the ventricle and atrium in three Antarctic teleosts...... adrenaline appear to enhance force of contraction for atrial muscle. The study finds that adrenaline modulates ventricular inotropic properties in all species. For Notothenia coriiceps the regulation of power production purely by adrenergic stimulation appeared most beneficial, while for N. microlepidota...

  9. Coronary atherosclerosis in sudden cardiac death: An autopsy study

    Directory of Open Access Journals (Sweden)

    Sudha M

    2009-10-01

    Full Text Available Background: The incidence of ischemic heart disease (IHD has markedly increased in India over the past few years. Considering the variations in racial, dietary and lifestyle patterns in our population, it is essential to study the biology of coronary atherosclerosis in our patients. Vulnerable plaques have a large number of foam cells, extracellular lipid, thin fibrous caps and clusters of inflammatory cells and are more prone to rupture. These plaques are nourished by the microvessels arising from the vasa vasorum of the blood vessels and by lumen-derived microvessels through the fibrous cap. This autopsy study was designed to analyse the coronary arterial tree in cases of sudden cardiac death, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification and microvascular density. Materials and Methods: Seven cases of sudden cardiac death were included in the study. The hearts were perfusion-fixed and the coronary arteries along with their main branches were dissected and studied. The location of the plaques, type of plaques, presence of inflammation and calcification were assessed. The cap thickness and microvessel density per 1000um 2 were assessed. The statistical significance was estimated. Results and Conclusions: Extensive high-grade coronary atherosclerotic disease was seen in all sudden cardiac death cases. Majority of the plaques were vulnerable. High-grade inflammation was seen in most of the vulnerable and ruptured plaques. All the ruptured plaques were uncalcified indicating that calcification probably stabilizes the plaques and protects against rupture. Increased microvessel density was noted in ruptured plaques compared to vulnerable plaques. However, it was not statistically significant.

  10. β2-Adrenergic Receptor Knockout Mice Exhibit A Diabetic Retinopathy Phenotype

    Science.gov (United States)

    Jiang, Youde; Zhang, Qiuhua; Liu, Li; Tang, Jie; Kern, Timothy S.; Steinle, Jena J.

    2013-01-01

    There is considerable evidence from our lab and others for a functional link between β-adrenergic receptor and insulin receptor signaling pathways in retina. Furthermore, we hypothesize that this link may contribute to lesions similar to diabetic retinopathy in that the loss of adrenergic input observed in diabetic retinopathy may disrupt normal anti-apoptotic insulin signaling, leading to retinal cell death. Our studies included assessment of neural retina function (ERG), vascular degeneration, and Müller glial cells (which express only β1 and β2-adrenergic receptor subtypes). In the current study, we produced β2-adrenergic receptor knockout mice to examine this deletion on retinal neurons and vasculature, and to identify specific pathways through which β2-adrenergic receptor modulates insulin signaling. As predicted from our hypothesis, β2-adrenergic receptor knockout mice display certain features similar to diabetic retinopathy. In addition, loss of β2-adrenergic input resulted in an increase in TNFα, a key inhibitor of insulin receptor signaling. Increased TNFα may be associated with insulin-dependent production of the anti-apoptotic factor, Akt. Since the effects occurred in vivo under normal glucose conditions, we postulate that aspects of the diabetic retinopathy phenotype might be triggered by loss of β2-adrenergic receptor signaling. PMID:23894672

  11. Mapping genetic variants associated with beta-adrenergic responses in inbred mice.

    Directory of Open Access Journals (Sweden)

    Micha Hersch

    Full Text Available β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS addressing the values and susceptibility of cardiovascular-related traits to a selective β(1-blocker, Atenolol (ate, and a β-agonist, Isoproterenol (iso. The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA, a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8. An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6. Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD. Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

  12. Adrenergic effects on exocrine secretion of rat submandibular epidermal growth factor

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1984-01-01

    The present study was undertaken to investigate the effect of alpha- and beta-adrenergic agonists on secretion of epidermal growth factor (EGF) from the rat submandibular glands and to test the possibility of intestinal absorption of EGF. Alpha-adrenergic agonists increased the concentration...... of salivary EGF by approximately a hundred times, while the serum concentration of EGF was unchanged. The contents of EGF in the submandibular glands decreased upon administration of the alpha-adrenergic agonist noradrenaline, and this was confirmed on immunohistochemical investigation of the glands. Beta-adrenergic....... This study shows that alpha-adrenergic agonists stimulate exocrine secretion of submandibular EGF and that EGF in physiological amounts are not absorbed in the gastrointestinal tract....

  13. Adrenergic effects on renal secretion of epidermal growth factor in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1985-01-01

    Urinary epidermal growth factor (EGF) has been demonstrated recently to originate from the kidneys. The present study was undertaken to investigate the adrenergic and cholinergic influence on secretion of renal EGF. beta-Adrenergic agonists increased the level of urinary EGF, while propranolol......, a beta-adrenergic blocking agent, decreased basal and beta-adrenergic stimulated total output of urinary EGF. Acetylcholine and the anticholinergic agent atropine had no effect on the output of EGF in urine. Also chemical sympathectomy induced by 6-hydroxydopamine reduced the urinary output of EGF. None...... of the experimental groups had a median serum concentration above the detection limit of the assay. The present study shows that secretion of renal EGF is under the influence of the sympathetic nervous system and release of EGF is stimulated by activation of beta-adrenergic receptors in the kidneys....

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

    Directory of Open Access Journals (Sweden)

    Pascal H Colson

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. IGF-1 Prevents Diastolic and Systolic Dysfunction Associated with Cardiomyopathy and Preserves Adrenergic Sensitivity

    Science.gov (United States)

    Roof, Steve R.; Boslett, James; Russell, Duncan; del Rio, Carlos; Alecusan, Joe; Zweier, Jay L.; Ziolo, Mark T.; Hamlin, Robert; Mohler, Peter J.; Curran, Jerry

    2015-01-01

    Aims Insulin-like growth factor 1 (IGF-1)-dependent signaling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here we test the potential therapeutic benefits of IGF-1 on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy. Methods Rats were perfused with isoproterenol via osmotic pump (1 mg/kg/day) and treated with 2 mg/kg IGF-1 (2 mg/kg/day, 6 days a week) for 2 or 4 weeks. Echocardiography, ECG, and blood pressure were assessed. In vivo pressure-volume loop studies were conducted at 4 weeks. Heart sections were analyzed for fibrosis and apoptosis, and relevant biochemical signaling cascades were assessed. Results After 4 weeks, diastolic function (EDPVR, EDP, tau, E/A ratio), systolic function (PRSW, ESPVR, dP/dtmax), and structural remodeling (LV chamber diameter, wall thickness) were all adversely affected in isoproterenol-treated rats. All these detrimental effects were attenuated in rats treated with Iso+IGF-1. Isoproterenol-dependent effects on BP were attenuated by IGF-1 treatment. Adrenergic sensitivity was blunted in isoproterenol-treated rats but was preserved by IGF-1 treatment. Immunoblots indicate that cardioprotective p110α signaling and activated Akt are selectively upregulated in Iso+IGF-1 treated hearts. Expression of iNOS was significantly increased in both the Iso and Iso+IGF-1 groups, however tetrahydrobiopterin (BH4) levels were decreased in the Iso group and maintained by IGF-1 treatment. Conclusion IGF-1 treatment attenuates diastolic and systolic dysfunction associated with chronic catecholamine-induced cardiomyopathy while preserving adrenergic sensitivity and promoting BH4 production. These data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies. PMID:26399932

  17. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and {beta}-adrenergic desensitization in heart failure after myocardial infarction in rats

    Energy Technology Data Exchange (ETDEWEB)

    Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro [Toyama Medical and Pharmaceutical Univ. (Japan)] [and others

    2002-11-01

    One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of {beta}-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by {sup 131}I-metaiodobenzylguanidine (MIBG), {beta}-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to {beta}-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of {beta}-adrenergic pathway in this model of heart failure. (author)

  18. Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and β-adrenergic desensitization in heart failure after myocardial infarction in rats

    International Nuclear Information System (INIS)

    Igawa, Akihiko; Nozawa, Takashi; Yoshida, Naohiro

    2002-01-01

    One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of β-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131 I-metaiodobenzylguanidine (MIBG), β-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation. Decreased LV function in the MI rats was associated with reduced cardiac NE content and MIBG uptake, and severely blunted responses of non-infarcted papillary muscle to isoproterenol, forskolin, and calcium. Enalapril attenuated LV remodeling in association with a reduction of the ventricular loading condition and restored baseline developed tension of non-infarcted papillary muscle to the level of sham-operated rats. However, enalapril did not improve cardiac NE content, MIBG uptake, or inotropic responsiveness to β-agonists. These results suggest that the major effect of the ACE inhibitor enalapril in the treatment of heart failure is not due to sympathoinhibition or restoration of β-adrenergic pathway in this model of heart failure. (author)

  19. Alpha and beta adrenergic effects on metabolism in contracting, perfused muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Ruderman, N B; Galbo, H

    1982-01-01

    The role of alpha- and beta-adrenergic receptor stimulation for the effect of epinephrine on muscle glycogenolysis, glucose- and oxygen uptake and muscle performance was studied in the perfused rat hindquarter at rest and during electrical stimulation (60 contractions/min). Adrenergic stimulation...... was obtained by epinephrine in a physiological concentration (2.4 X 10(-8) M) and alpha- and beta-adrenergic blockade by 10(-5) M phentolamine and propranolol, respectively. Epinephrine enhanced net glycogenolysis during contractions most markedly in slow-twitch red fibers. In these fibers the effect...... was mediated by alpha- as well as by beta-adrenergic stimulation, the latter involving production of cAMP, phosphorylase activation and synthase inactivation. In contrast, in fast-twitch fibers only beta-adrenergic mechanisms were involved in the glycogenolytic effect of epinephrine. Moreover, inactivation...

  20. Frequency and echocardiographic study of dilated cardiomyopathy in children presenting with cardiac failure

    International Nuclear Information System (INIS)

    Khan, M.A.; Mohammad, J.; Hussain, M.

    2004-01-01

    Objective: To evaluate the role of echocardiography in diagnosis of dilated cardiomyopathy as a cause of cardiac failure in children. Design: This was descriptive study. Children presenting with cardiac failure from indoor patients were selected and echocardiography along with chest X- ray, ECG, cardiac enzymes and ASO titre was performed in all patients. Subject: Fifty hospitalized patients with congestive heart failure were selected consecutively from hospitalized patients. Main Outcome: Role of echocardiography in the diagnosis of dilated cardiomyopathy in children presenting with cardiac failure. Results: Out of fifty patients admitted with cardiac failure 27 (54%) cases were found to be dilated cardiomyopathy while congenital heart disease, myocarditis and rheumatic heart disease were found in 12 (24%), 8 (16%) and 3 (6%) cases respectively. Conclusion: Dilated cardiomyopathy is an important cause of cardiac failure in children and echocardiography is an important tool to diagnose and differentiate dilated cardiomyopathy from other causes of cardiac failure. (author)

  1. Blunt Cardiac Injury in the Severely Injured - A Retrospective Multicentre Study.

    Directory of Open Access Journals (Sweden)

    Marc Hanschen

    Full Text Available Blunt cardiac injury is a rare trauma entity. Here, we sought to evaluate the relevance and prognostic significance of blunt cardiac injury in severely injured patients.In a retrospective multicentre study, using data collected from 47,580 patients enrolled to TraumaRegister DGU (1993-2009, characteristics of trauma, prehospital / hospital trauma management, and outcome analysis were correlated to the severity of blunt cardiac injury. The severity of cardiac injury was assessed according to the abbreviated injury score (AIS score 1-6, the revised injury severity score (RISC allowed comparison of expected outcome with injury severity-dependent outcome. N = 1.090 had blunt cardiac trauma (AIS 1-6 (2.3% of patients.Predictors of blunt cardiac injury could be identified. Sternal fractures indicate a high risk of the presence of blunt cardiac injury (AIS 0 [control]: 3.0%; AIS 1: 19.3%; AIS 2-6: 19.1%. The overall mortality rate was 13.9%, minor cardiac injury (AIS 1 and severe cardiac injury (AIS 2-6 are associated with higher rates. Severe blunt cardiac injury (AIS 4 and AIS 5-6 is associated with a higher mortality (OR 2.79 and 4.89, respectively as compared to the predicted average mortality (OR 2.49 of the study collective.Multiple injured patients with blunt cardiac trauma are at high risk to be underestimated. Careful evaluation of trauma patients is able to predict the presence of blunt cardiac injury. The severity of blunt cardiac injury needs to be stratified according to the AIS score, as the patients' outcome is dependent on the severity of cardiac injury.

  2. The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions.

    Science.gov (United States)

    Suárez, M M; Rivarola, M A; Molina, S M; Levin, G M; Enders, J; Paglini, P

    2004-09-01

    Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or

  3. Cardiac cAMP: production, hydrolysis, modulation and detection

    Directory of Open Access Journals (Sweden)

    Cédric eBOULARAN

    2015-10-01

    Full Text Available Cyclic adenosine 3’,5’-monophosphate (cAMP modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability.

  4. Cardiac Patients’ Experiences and Perceptions of Social Media: Mixed-Methods Study

    Science.gov (United States)

    Partridge, Stephanie R; Grunseit, Anne C; Gallagher, Patrick; Freeman, Becky; O'Hara, Blythe J; Neubeck, Lis; Due, Sarah; Paull, Glenn; Ding, Ding; Bauman, Adrian; Phongsavan, Philayrath; Roach, Kellie; Sadler, Leonie; Glinatsis, Helen

    2017-01-01

    Background Traditional in-person cardiac rehabilitation has substantial benefits for cardiac patients, which are offset by poor attendance. The rapid increase in social media use in older adults provides an opportunity to reach patients who are eligible for cardiac rehabilitation but unable to attend traditional face-to-face groups. However, there is a paucity of research on cardiac patients’ experiences and perspectives on using social media to support their health. Objective The aim of this study was to describe cardiac rehabilitation patients’ experiences in using social media in general and their perspective on using social media, particularly Facebook, to support their cardiac health and secondary prevention efforts. Methods A mixed-methods study was undertaken among cardiac rehabilitation patients in both urban and rural areas. First, this study included a survey (n=284) on social media use and capability. Second, six focus group interviews were conducted with current Facebook users (n=18) to elucidate Facebook experience and perspectives. Results Social media use was low (28.0%, 79/282) but more common in participants who were under 70 years of age, employed, and had completed high school. Social media users accessed Web-based information on general health issues (65%, 51/79), medications (56%, 44/79), and heart health (43%, 34/79). Participants were motivated to invest time in using Facebook for “keeping in touch” with family and friends and to be informed by expert cardiac health professionals and fellow cardiac participants if given the opportunity. It appeared that participants who had a higher level of Facebook capability (understanding of features and the consequences of their use and efficiency in use) spent more time on Facebook and reported higher levels of “liking,” commenting, or sharing posts. Furthermore, higher Facebook capability appeared to increase a participants’ willingness to participate in a cardiac Facebook support group

  5. Left and right ventricle assessment with Cardiac CT: validation study vs. Cardiac MR

    Energy Technology Data Exchange (ETDEWEB)

    Maffei, Erica; Seitun, Sara [Giovanni XXIII Hospital, Cardiovascular Radiology Unit, Monastier di Treviso (Italy); Messalli, Giancarlo; Catalano, Onofrio [SDN Foundation - IRCCS, Naples (Italy); Martini, Chiara; Cademartiri, Filippo [Giovanni XXIII Hospital, Cardiovascular Radiology Unit, Monastier di Treviso (Italy); Erasmus Medical Center, Department of Radiology and Cardiology, Rotterdam (Netherlands); Nieman, Koen; Rossi, Alexia; Mollet, Nico R. [Erasmus Medical Center, Department of Radiology and Cardiology, Rotterdam (Netherlands); Guaricci, Andrea I. [Azienda Ospedaliero-Universitaria di Foggia, Department of Cardiology, Foggia (Italy); Tedeschi, Carlo [Ospedale San Gennaro, Department of Cardiology, Naples (Italy)

    2012-05-15

    To compare Magnetic Resonance (MR) and Computed Tomography (CT) for the assessment of left (LV) and right (RV) ventricular functional parameters. Seventy nine patients underwent both Cardiac CT and Cardiac MR. Images were acquired using short axis (SAX) reconstructions for CT and 2D cine b-SSFP (balanced-steady state free precession) SAX sequence for MR, and evaluated using dedicated software. CT and MR images showed good agreement: LV EF (Ejection Fraction) (52 {+-} 14% for CT vs. 52 {+-} 14% for MR; r = 0.73; p > 0.05); RV EF (47 {+-} 12% for CT vs. 47 {+-} 12% for MR; r = 0.74; p > 0.05); LV EDV (End Diastolic Volume) (74 {+-} 21 ml/m{sup 2} for CT vs. 76 {+-} 25 ml/m{sup 2} for MR; r = 0.59; p > 0.05); RV EDV (84 {+-} 25 ml/m{sup 2} for CT vs. 80 {+-} 23 ml/m{sup 2} for MR; r = 0.58; p > 0.05); LV ESV (End Systolic Volume)(37 {+-} 19 ml/m{sup 2} for CT vs. 38 {+-} 23 ml/m{sup 2} for MR; r = 0.76; p > 0.05); RV ESV (46 {+-} 21 ml/m{sup 2} for CT vs. 43 {+-} 18 ml/m{sup 2} for MR; r = 0.70; p > 0.05). Intra- and inter-observer variability were good, and the performance of CT was maintained for different EF subgroups. Cardiac CT provides accurate and reproducible LV and RV volume parameters compared with MR, and can be considered as a reliable alternative for patients who are not suitable to undergo MR. circle Cardiac-CT is able to provide Left and Right Ventricular function. circle Cardiac-CT is accurate as MR for LV and RV volume assessment. (orig.)

  6. EFFECTS OF EXERCISE TRAINING ON CARDIOVASCULAR ADRENERGIC SYSTEM

    Directory of Open Access Journals (Sweden)

    Dario eLeosco

    2013-11-01

    Full Text Available In heart failure (HF, exercise has been shown to modulate cardiac sympathetic hyperactivation which is one of the earliest features of neurohormonal derangement in this syndrome and correlates with adverse outcome. An important molecular alteration related to chronic sympathetic overstimulation in HF is represented by cardiac β-adrenergic receptor (β-AR dysfunction . It has been demonstrated that exercise reverses β-AR dysfunction by restoring cardiac receptor membrane density and G-protein-dependent adenylyl cyclase activation. In particular, several evidence indicate that exercise reduces levels of cardiac G-protein coupled receptor kinase-2 (GRK2 which is known to be involved in both β1-AR and β2-AR dysregulation in HF. Similar alterations of β-AR system have been described also in the senescent heart. It has also been demonstrated that exercise training restores adrenal GRK2/α-2AR/cathecolamine (CA production axis. At vascular level, exercise shows a therapeutic effect on age-related impairment of vascular reactivity to adrenergic stimulation and restores β-AR-dependent vasodilatation by increasing vascular β-AR responsiveness and reducing endothelial GRK2 activity. Sympathetic nervous system overdrive is thought to account for >50 % of all cases of hypertension and a lack of balance between parasympathetic and sympathetic modulation has been observed in hypertensive subjects. Non-pharmacological, lifestyle interventions have been associated with reductions in SNS overactivity and blood pressure in hypertension. Several evidence have highlighted the blood pressure lowering effects of aerobic endurance exercise in patients with hypertension and the significant reduction in sympathetic neural activity has been reported as one of the main mechanisms explaining the favourable effects of exercise on blood pressure control.

  7. Effects of exercise training on cardiovascular adrenergic system.

    Science.gov (United States)

    Leosco, Dario; Parisi, Valentina; Femminella, Grazia D; Formisano, Roberto; Petraglia, Laura; Allocca, Elena; Bonaduce, Domenico

    2013-11-28

    In heart failure (HF), exercise has been shown to modulate cardiac sympathetic hyperactivation which is one of the earliest features of neurohormonal derangement in this syndrome and correlates with adverse outcome. An important molecular alteration related to chronic sympathetic overstimulation in HF is represented by cardiac β-adrenergic receptor (β-AR) dysfunction. It has been demonstrated that exercise reverses β-AR dysfunction by restoring cardiac receptor membrane density and G-protein-dependent adenylyl cyclase activation. In particular, several evidence indicate that exercise reduces levels of cardiac G-protein coupled receptor kinase-2 (GRK2) which is known to be involved in both β1-AR and β2-AR dysregulation in HF. Similar alterations of β-AR system have been described also in the senescent heart. It has also been demonstrated that exercise training restores adrenal GRK2/α-2AR/catecholamine (CA) production axis. At vascular level, exercise shows a therapeutic effect on age-related impairment of vascular reactivity to adrenergic stimulation and restores β-AR-dependent vasodilatation by increasing vascular β-AR responsiveness and reducing endothelial GRK2 activity. Sympathetic nervous system overdrive is thought to account for >50% of all cases of hypertension and a lack of balance between parasympathetic and sympathetic modulation has been observed in hypertensive subjects. Non-pharmacological, lifestyle interventions have been associated with reductions in SNS overactivity and blood pressure in hypertension. Several evidence have highlighted the blood pressure lowering effects of aerobic endurance exercise in patients with hypertension and the significant reduction in sympathetic neural activity has been reported as one of the main mechanisms explaining the favorable effects of exercise on blood pressure control.

  8. Brain α1-adrenergic receptors: suitability of [125I]HEAT as a radioligand for in vitro autoradiography

    International Nuclear Information System (INIS)

    Jones, L.S.; Gauger, L.L.; Davis, J.N.

    1983-01-01

    [2-(β-4-Hydroxyphenyl)-ethylaminomethyl)-tetralone] (BE 2254, HEAT) is a new potent α 1 -adrenergic receptor blocker. The iodinated radioligand, [ 125 I]HEAT appears to be even more potent than HEAT (Engel and Hoyer, 1981; Glossman et al., 1981) and has proved useful for the studying of α 1 -adrenergic receptors in membrane preparations of rat brain. The authors report the suitability of [ 125 I]HEAT for α 1 -adrenergic binding site autoradiography and a degree of localization of α 1 -adrenergic receptor binding sites that has not been possible with [ 3 H]WB 4101 and [ 3 H]prazosin autoradiography. (Auth.)

  9. Adrenergic receptors and gastric secretion in dogs. Is a "tonic balance" relationship between vagal and beta 2-adrenergic activity a possibility?

    DEFF Research Database (Denmark)

    Gottrup, F; Hovendal, C; Bech, K

    1984-01-01

    The relative influence of adrenergic receptors on gastric acid secretion in the dog stomach with different vagal activity or "tone" is almost unknown. beta-adrenoceptors seem to be most important for the direct effect of adrenergic stimulation on acid secretion. In this study the effects...... acid secretion was not influenced significantly by beta-blockade. Similar dose-response curves were found for non-vagotomized dogs with high beta 2-adrenergic tone and dogs with low vagal tone (vagotomy) after pentagastrin and histamine stimulated acid secretion. This study indicates...... that a counterbalance between beta 2-adrenergic and cholinergic vagal tone exists. A "tonic balance theory" is suggested and is probably involved in the resulting acid secretion after vagotomy....

  10. An experimental study and mathematical simulation of adrenergic control of hindlimb vessels in rats after 3-week tail suspension

    DEFF Research Database (Denmark)

    Rodionov, Ivan M; Timin, Eugeny N; Matchkov, Vladimir

    1999-01-01

    Adrenoreactivity of rat hindlimb vessels was studied in experiments with constant-pressure saline perfusion. An original mathematical model was applied to evaluate the mechanism of changes in vascular tone regulation. A 3-week suspension resulted in decreased responses to sympathetic nerve stimul...

  11. A dosimetric study during cardiac angiography in young children

    International Nuclear Information System (INIS)

    Amiel, M.; Clermont, A.; Jocteur-Monrozier, D.; Moroni, J.P.; Brun, P.

    1976-01-01

    A dosimetric study was carried out in collaboration with the SCPRI in 30 infants during cardiac catheterization for a congenital cardiopathy. As far as the doctor is concerned, the results show that the dose received by the right hand of the operator is the only one that is relatively high and notably higher than in the adult; the other results are in agreement with those published in the literature. For the manipulator the doses received are practically negligible. This finding does not agree with those of certain publications in the literature and it emphasizes the importance of the working conditions for these personnel. For infants, the gonadal dose is much higher than in the adult and the magnitude of the dose relative to the dose at the place of entry of the incident beam, taking into account the weight of the infant, certaintly represents a long-term risk, in particular, in patients who must undergo repeated examinations [fr

  12. [Mutation in the beta3-adrenergic receptor gene (Trp64Arg) does not influence insulin resistence, energy metabolism, fat distribution and lipid spectrum in young people. Pilot study].

    Science.gov (United States)

    Bendlová, B; Mazura, I; Vcelák, J; Pelikánová, T; Kunesová, M; Hainer, V; Obenberger, J; Palyzová, D

    1999-05-01

    A missence mutation Trp64Arg in the beta3-adrenergic receptor gene is associated with obesity, insulin resistance, a lower metabolic rate and the earlier onset of NIDDM but the published results are controversial. We investigated the effect of this mutation on insulin resistance (euglycemic hyperinsulinemic clamp), on fat mass and fat distribution (anthropometry, bioimpedance, CT) and resting metabolic rate (indirect calorimetry), lipid spectrum and other metabolic disturbances in Czech juveniles recruited from juvenile hypertensives (H, n = 68) and controls (C, n = 81). The frequency of this mutation (determined by digestion of 210 bp PCR product with MvaI) was double in H than in C (14.7%, vs. 7.4%) and the carriers of Arg64 allele had sig. higher fasting glucose (H: p = 0.002. C: p = 0.025). Four Trp64/Arg64 and six Trp64/Trp64 men (age 23 +/- 4.2, vs. 22.5 +/- 1.9 y, BMI 26 +/- 5.5, vs. 22.9 +/- 5.1 kg/m2) took part in a detailed pilot study. But no signif. differences (Horn's method) in fasting glucose (4.6 +/- 0.6, vs. 4.9 +/- 0.4 mmol/l), in parameters of insulin resistance (M-value150-180 min. 9.1 +/- 1.1, vs. 8.9 +/- 1.5 mg glucose/kg.min(-1)), resting metabolic rate/lean body mass (RMR/kg LBM: 78.6 +/- 4.6, vs. 85.6 +/- 23.2 kJ/kg), lipid spectrum and other screened parameters were found. The lowest resting metabolic rate (RMR/kg LBM 55.4; 62.6 kJ/kg) was found in brothers (both C, Trp64/Trp64) who highly differ in body constitution (BMI 19.0 resp. 32.4 kg/m2). We suppose that in this case the energy metabolism is probably determined by other genetic loci and does not correlate with body fat mass. Our pilot study does not confirm the influence of Trp64Arg mutation in heterozygous carriers on insulin resistance, energy metabolism and lipid spectrum.

  13. β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study.

    Science.gov (United States)

    Wu, Pingsheng; Larkin, Emma K; Reiss, Sara S; Carroll, Kecia N; Summar, Marshall L; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Islam, Jessica Y; Hartert, Tina V; Moore, Paul E

    2015-09-14

    Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95% confidence

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

    Science.gov (United States)

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

    2008-01-01

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

  15. Myocardial adrenergic nerve activity in valvular diseases assessed by iodine-123-metaiodobenzylguanidine myocardial scintigraphy

    International Nuclear Information System (INIS)

    Imamura, Yoshihiro; Fukuyama, Takaya

    1997-01-01

    Iodine-123-metaiodobenzylguanidine (MIBG) imaging was used to assess myocardial adrenergic nerve activity in patients with heart failure. MIBG planar images were obtained in 94 patients. The uptake of MIBG, calculated as the heart-to-mediastinum activity ratio in the immediate image (15 min), showed a significant decrease only in patients with severe heart failure due to cardiomyopathy, but was not changed in those with valvular diseases. Storage and release of MIBG, calculated as the percentage myocardial MIBG washout from 15 min to 4 hours after isotope injection, was substantially accelerated in both patients with cardiomyopathy and valvular diseases in proportion to the severity of heart failure. These data suggest that, in severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. Also, myocardial adrenergic nerve activity is accelerated in proportion to the severity of heart failure independent of the underlying cause. MIBG images were analyzed in 20 patients with mitral stenosis with the same methods to clarify whether myocardial adrenergic nerve activity is different in patients with heart failure without left ventricular volume or pressure overload. Myocardial uptake of MIBG did not show any significant difference. The percentage myocardial MIBG washout was increased in patients with severe heart failure. The closest correlation was between myocardial washout and cardiac output. In heart failure due to mitral stenosis, myocardial adrenergic nerve activity is intensified. Decrease in cardiac output associated with mitral stenosis acts as a potent stimulus for this intensification. (author)

  16. Sex differences and the effects of ovariectomy on the β-adrenergic contractile response

    Science.gov (United States)

    McIntosh, Victoria J.; Chandrasekera, P. Charukeshi

    2011-01-01

    The presence of sex differences in myocardial β-adrenergic responsiveness is controversial, and limited studies have addressed the mechanism underlying these differences. Studies were performed using isolated perfused hearts from male, intact female and ovariectomized female mice to investigate sex differences and the effects of ovarian hormone withdrawal on β-adrenergic receptor function. Female hearts exhibited blunted contractile responses to the β-adrenergic receptor agonist isoproterenol (ISO) compared with males but not ovariectomized females. There were no sex differences in β1-adrenergic receptor gene or protein expression. To investigate the role of adenylyl cyclase, phosphodiesterase, and the cAMP-signaling cascade in generating sex differences in the β-adrenergic contractile response, dose-response studies were performed in isolated perfused male and female hearts using forskolin, 3-isobutyl-1-methylxanthine (IBMX), and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (CPT-cAMP). Males showed a modestly enhanced contractile response to forskolin at 300 nM and 5 μM compared with females, but there were no sex differences in the response to IBMX or CPT-cAMP. The role of the A1 adenosine receptor (A1AR) in antagonizing the β-adrenergic contractile response was investigated using both the A1AR agonist 2-chloro-N6-cyclopentyl-adenosine and A1AR knockout (KO) mice. Intact females showed an enhanced A1AR anti-adrenergic effect compared with males and ovariectomized females. The β-adrenergic contractile response was potentiated in both male and female A1ARKO hearts, with sex differences no longer present above 1 nM ISO. The β-adrenergic contractile response is greater in male hearts than females, and minor differences in the action of adenylyl cyclase or the A1AR may contribute to these sex differences. PMID:21685268

  17. The change of β-adrenergic system after cessation of lead exposure

    International Nuclear Information System (INIS)

    Chang, H.-R.; Tsao, D.-A.; Yu, H.-S.; Ho, C.-K.

    2005-01-01

    For understanding a reversible or irreversible harm of β-adrenergic system in lead induced cardiovascular disease (hypertension), We set up animal model to estimate the change of blood pressure and sympathetic nervous system after lead exposure withdrawn in the study. We address three topics in this study: (a) the relationship between withdrawal time of lead exposure and β-adrenergic receptor, plasma catecholamine level, blood pressure, and lead level in heart, aorta, and kidney in lead-induced hypertensive rats after lead exposure stopped; (b) the relationship between blood pressure and β-adrenergic receptor in heart, aorta, and kidney; (c) the estimation of relationship between lead withdrawn and the variation of β-adrenergic system. Wistar rats were chronically fed with 2% lead acetate (experimental group) and water (control group) for 2 months. The rats were divided into 8 groups by withdrawal time of lead exposure stopped. Plasma catecholamine level was measured by high-performance liquid chromatography. Radioligand binding assay was measured by a method that fulfilled strict criteria of β-adrenergic receptor using the ligand [ 125 I]iodocyanopindolol. The levels of lead were determined by electrothermal atomic absorption spectrometry. The results showed that a close relation between reduced lead level and the plasma catecholamine level decreased, aorta β-adrenergic receptor increased, kidney β-adrenergic receptor diminished, heart β-adrenergic receptor increased, and blood pressure dropped after lead exposure withdrawn. The study on the regulation of β-adrenergic system in lead-induced hypertension after lead withdrawn might also provide insight about the nature of this disease state

  18. Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

    International Nuclear Information System (INIS)

    Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu

    2001-01-01

    We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52±15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m 2 or higher were assigned to the high dose group and those given doses under 300 mg/m 2 to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3±218.2 mg/m 2 . In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m 2 appeared to be the borderline dose beyond which there were

  19. Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu [Tokyo Medical Coll. (Japan)

    2001-05-01

    We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52{+-}15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m{sup 2} or higher were assigned to the high dose group and those given doses under 300 mg/m{sup 2} to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3{+-}218.2 mg/m{sup 2}. In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m{sup 2} appeared to be the borderline dose beyond

  20. Cardiac spheroids as promising in vitro models to study the human heart microenvironment

    DEFF Research Database (Denmark)

    Polonchuk, Liudmila; Chabria, Mamta; Badi, Laura

    2017-01-01

    Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart ("cardiac spheroids", CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells an...

  1. The diagnostic relevance of an integrated approach to gated cardiac studies

    International Nuclear Information System (INIS)

    Pavel, D.G.

    1982-01-01

    Evolution of Nuclear Medicine hardware and software has opened the way towards maximizing the amount of information of gated cardiac studies. The clinical use of cardiac functional images started with stroke volume image, paradoxis images and regional ejection fraction images, followed later by slope images, variation images and others. Especially the introduction of phase analysis has opened a variety of new perspectives. (WU)

  2. Hemodynamic and tissue oxygenation responses to exercise and beta-adrenergic blockade in patients with hyperthyroidism.

    Science.gov (United States)

    Monachini, Maristela C; Lage, Silvia G; Ran, Miguel A N; Cardoso, Rita H A; Medeiros, Caio; Caramelli, Bruno; Sposito, Andrei C; Ramires, José A F

    2004-07-01

    Exercise-induced dyspnea is a frequent feature in patients with hyperthyroidism. Data from clinical studies to elucidate the origin of this symptom are lacking. In the current study, we examined the hemodynamic and oxygenation responses to exercise and beta-adrenergic blockade in patients with hyperthyroidism and their relationship with dyspnea. Hemodynamic studies were performed under resting conditions and after isotonic exercise in 15 patients with hyperthyroidism and 11 control subjects. Exercise was applied using a bicycle ergometer, with progressive loads. In the hyperthyroid group, measurements were repeated at rest and during supine exercise after administering 15 mg of intravenous metoprolol. End-diastolic pulmonary artery pressure and cardiac index were higher in the hyperthyroid group than in controls (18.6 +/- 5.3 vs. 11.2 +/- 4.9 mmHg; p = 0.02, and 6.0 +/- 1.7 vs. 2.8 +/- 0.5 l/min/m2; p = 0.0001, respectively). After exercise, there was an increase in end-diastolic pulmonary artery pressure in the hyperthyroid group (18.6 +/- 5.3 to 25.5 +/- 9.9 mmHg; p = 0.02), revealing impaired cardiocirculatory reserve. Pulmonary arteriolar resistance increased significantly in parallel with end-diastolic pulmonary artery pressure after drug administration, suggesting an inadequate cardiovascular response after beta blockade in patients with hyperthyroidism. We observed that functional left ventricular reserve is impaired in patients with hyperthyroidism, suggesting an explanation for the frequent symptom of dyspnea and impaired exercise tolerance. Moreover, we also suggest that beta-adrenergic blockade may adversely affect cardiovascular function in patients with hyperthyroidism.

  3. Wave Reflection and Characteristic Impedance in the Conscious Dog as Influenced by Adrenergic Intervention

    National Research Council Canada - National Science Library

    Kerkhof, P

    2001-01-01

    .... Therefore, the specific aims of this study are first to delineate the characteristics of the systemic circulation and second to analyze the influence of adrenergic agonists and blockers on C and Zo...

  4. Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists.

    Directory of Open Access Journals (Sweden)

    Gunnar Kleinau

    Full Text Available Trace amine-associated receptors (TAAR are rhodopsin-like G-protein-coupled receptors (GPCR. TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR, phenylethylamine (PEA, octopamine (OA, but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1 and 2 (ADRB2 have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR octopamine (OAR, ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes.

  5. The Metabolic Syndrome and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study.

    Science.gov (United States)

    Hess, Paul L; Al-Khalidi, Hussein R; Friedman, Daniel J; Mulder, Hillary; Kucharska-Newton, Anna; Rosamond, Wayne R; Lopes, Renato D; Gersh, Bernard J; Mark, Daniel B; Curtis, Lesley H; Post, Wendy S; Prineas, Ronald J; Sotoodehnia, Nona; Al-Khatib, Sana M

    2017-08-23

    Prior studies have demonstrated a link between the metabolic syndrome and increased risk of cardiovascular mortality. Whether the metabolic syndrome is associated with sudden cardiac death is uncertain. We characterized the relationship between sudden cardiac death and metabolic syndrome status among participants of the ARIC (Atherosclerosis Risk in Communities) Study (1987-2012) free of prevalent coronary heart disease or heart failure. Among 13 168 participants, 357 (2.7%) sudden cardiac deaths occurred during a median follow-up of 23.6 years. Participants with the metabolic syndrome (n=4444) had a higher cumulative incidence of sudden cardiac death than those without it (n=8724) (4.1% versus 2.3%, P metabolic syndrome, the metabolic syndrome was independently associated with sudden cardiac death (hazard ratio, 1.70, 95% confidence interval, 1.37-2.12, P metabolic syndrome criteria components. The risk of sudden cardiac death varied according to the number of metabolic syndrome components (hazard ratio 1.31 per additional component of the metabolic syndrome, 95% confidence interval, 1.19-1.44, P metabolic syndrome was associated with a significantly increased risk of sudden cardiac death irrespective of sex or race. The risk of sudden cardiac death was proportional to the number of metabolic syndrome components. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  6. Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine

    International Nuclear Information System (INIS)

    Taouis, M.; Berlan, M.; Lafontan, M.

    1987-01-01

    The recovery of post- and extrasynaptic alpha 2-adrenergic receptor-binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites. The kidney alpha 2-adrenergic receptor number was measured with [ 3 H]yohimbine, whereas [ 3 H]clonidine was used for fat cell and brain membrane alpha 2-binding site identification. Benextramine treatment of fat cell, kidney, and brain membranes reduced or completely suppressed, in an irreversible manner, [ 3 H] clonidine and [ 3 H]yohimbine binding without modifying adenosine (A1-receptor) and beta-adrenergic receptor sites. This irreversible binding was also found 1 and 2 hr after intraperitoneal administration of benextramine to the hamsters. Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg). After the irreversible blockade, alpha 2-binding sites reappeared in kidney and adipose tissue following a monoexponential time course. Recovery of binding sites was more rapid in kidney than in adipose tissue; the half-lives of the receptor were 31 and 46 hr, respectively in the tissues. The rates of receptor production were 1.5 and 1.8 fmol/mg of protein/hr in kidney and adipose tissue. Reappearance of alpha 2-binding sites was associated with a rapid recovery of function (antilipolytic potencies of alpha 2-agonists) in fat cells inasmuch as occupancy of 15% of [ 3 H]clonidine-binding sites was sufficient to promote 40% inhibition of lipolysis. Benextramine is a useful tool to estimate turnover of alpha 2-adrenergic receptors under normal and pathological situations

  7. Improvement of cardiac contractile function by peptide-based inhibition of NF-κB in the utrophin/dystrophin-deficient murine model of muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Guttridge Denis C

    2011-05-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain, targeted at blunting Nuclear Factor κB (NF-κB signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted β-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as β-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice. Results At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to β-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice. Conclusions We conclude

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-15

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

  9. Assessment of cardiac neuronal function with iodine-123 MIBG scintigraphy in children with idiopathic dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Ch.; Sebahoun, St.; Hallaj, I.; Barritault, L.; Acar, Ph.; Sidi, D.; Kachaner, J.; Agostini, D.; Bouvard, G.

    2000-01-01

    The I-123 MIBG cardiac scintigraphy can assess norepinephrine uptake. It has been showed that cardiac adrenergic neuronal function was impaired in adults with dilated cardiomyopathy. The aim of this prospective study was to assess cardiac neuronal function in children with idiopathic dilated cardiomyopathy (DCM) and to compare cardiac uptake of I-123 MIBG with left ventricular ejection fraction (LVEF). We studied 26 consecutive patients with idiopathic DCM, aged 44 ± 50 months, and 12 controls, aged 49 ±65 months. A planar scintigraphy was performed in all children 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. A static anterior view was acquired for 10 minutes. Cardiac uptake of I-123 MIBG was expressed as the heart to mediastinum count ratio (HMR). Equilibrium radionuclide angiography was performed following a standard protocol. Cardiac uptake of I-123 MIBG was significantly decreased in patients with idiopathic DCM when compared with cardiac uptake in controls (172±34% vs 277±14%, P<0.0001. There was a good correlation between RCM and LVEF in patients with idiopathic DCM (y = 2.5 x +113.3, r = 0.80, P < 0.0001). In conclusion, cardiac neuronal function was impaired in children with idiopathic DCM and related to impairment of left ventricular function. (author)

  10. Radionuclide study for cardiac lesion in Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Oguni, Hirokazu; Osawa, Makiko; Shishikura, Keiko

    1985-12-01

    Tl-201 myocardial scintigraphy and radionuclide ventriculography with Tc-99m were performed in 10 patients with Duchenne muscular dystropohy (DMD) and 2 siblings with Becker muscular dystrophy (BMD). Perfusion defect especially in the left ventricular posterolateral wall (LVPLW) and cardiac apex was seen on Tl-201 imaging in 6 of the DMD patients and one of the BMD patients. For these patients, Tc-99m imaging also showed left ventricular local wall motion abnormality in 5 patients and a decreased left ventricular ejection fraction in 4 patients. These findings coincided well with fibrosis of the LVPLW found on autopsy. There were individual differences regarding the occurrence of cardiac complications. One of the BMD patients, as well as DMD patients, had also cardiac complications which have long been considered less common. (Namekawa, K.).

  11. Radionuclide study for cardiac lesion in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Oguni, Hirokazu; Osawa, Makiko; Shishikura, Keiko

    1985-01-01

    Tl-201 myocardial scintigraphy and radionuclide ventriculography with Tc-99m were performed in 10 patients with Duchenne muscular dystropohy (DMD) and 2 siblings with Becker muscular dystrophy (BMD). Perfusion defect especially in the left ventricular posterolateral wall (LVPLW) and cardiac apex was seen on Tl-201 imaging in 6 of the DMD patients and one of the BMD patients. For these patients, Tc-99m imaging also showed left ventricular local wall motion abnormality in 5 patients and a decreased left ventricular ejection fraction in 4 patients. These findings coincided well with fibrosis of the LVPLW found on autopsy. There were individual differences regarding the occurrence of cardiac complications. One of the BMD patients, as well as DMD patients, had also cardiac complications which have long been considered less common. (Namekawa, K.)

  12. β-Adrenergic receptor stimulation inhibits proarrhythmic alternans in postinfarction border zone cardiomyocytes: a computational analysis.

    Science.gov (United States)

    Tomek, Jakub; Rodriguez, Blanca; Bub, Gil; Heijman, Jordi

    2017-08-01

    The border zone (BZ) of the viable myocardium adjacent to an infarct undergoes extensive autonomic and electrical remodeling and is prone to repolarization alternans-induced cardiac arrhythmias. BZ remodeling processes may promote or inhibit Ca 2+ and/or repolarization alternans and may differentially affect ventricular arrhythmogenesis. Here, we used a detailed computational model of the canine ventricular cardiomyocyte to study the determinants of alternans in the BZ and their regulation by β-adrenergic receptor (β-AR) stimulation. The BZ model developed Ca 2+ transient alternans at slower pacing cycle lengths than the control model, suggesting that the BZ may promote spatially heterogeneous alternans formation in an infarcted heart. β-AR stimulation abolished alternans. By evaluating all combinations of downstream β-AR stimulation targets, we identified both direct (via ryanodine receptor channels) and indirect [via sarcoplasmic reticulum (SR) Ca 2+ load] modulation of SR Ca 2+ release as critical determinants of Ca 2+ transient alternans. These findings were confirmed in a human ventricular cardiomyocyte model. Cell-to-cell coupling indirectly modulated the likelihood of alternans by affecting the action potential upstroke, reducing the trigger for SR Ca 2+ release in one-dimensional strand simulations. However, β-AR stimulation inhibited alternans in both single and multicellular simulations. Taken together, these data highlight a potential antiarrhythmic role of sympathetic hyperinnervation in the BZ by reducing the likelihood of alternans and provide new insights into the underlying mechanisms controlling Ca 2+ transient and repolarization alternans. NEW & NOTEWORTHY We integrated, for the first time, postmyocardial infarction electrical and autonomic remodeling in a detailed, validated computer model of β-adrenergic stimulation in ventricular cardiomyocytes. Here, we show that β-adrenergic stimulation inhibits alternans and provide novel insights

  13. A comparative study of electronic stethoscopes for cardiac auscultation.

    Science.gov (United States)

    Pinto, C; Pereira, D; Ferreira-Coimbra, J; Portugues, J; Gama, V; Coimbra, M

    2017-07-01

    There are several electronic stethoscopes available on the market today, with a very high potential for healthcare namely telemedicine, assisted decision and education. However, there are no recent comparatives studies published about the recording quality of auscultation sounds. In this study we aim to: a) define a ranking, according to experts opinion of 6 of the most relevant electronic stethoscopes on the market today; b) verify if there are any relations between a stethoscope's performance and the type of pathology present; c) analyze if some pathologies are more easily identified than others when using electronic auscultation. Our methodology consisted in creating two study groups: the first group included 18 cardiologists and cardiology house officers, acting as the gold standard of this work. The second included 30 medical students. Using a database of heart sounds recorded in real hospital environments, we applied questionnaires to observers from each group. The first group listened to 60 cardiac auscultations recorded by the 6 stethoscopes, and each one was asked to identify the pathological sound present: aortic stenosis, mitral regurgitation or normal. The second group was asked to choose, between two auscultation recordings, using as criteria the best sound quality for the identification of pathological sounds. Results include a total of 1080 evaluations, in which 72% of cases were correctly diagnosed. A detailed breakdown of these results is presented in this paper. As conclusions, results showed that the impact of the differences between stethoscopes is very small, given that we did not find statistically significant differences between all pairs of stethoscopes. Normal sounds showed to be easier to identify than pathological sounds, but we did not find differences between stethoscopes in this identification.

  14. Age-dependent changes in expression of alpha1-adrenergic receptors in rat myocardium

    International Nuclear Information System (INIS)

    Schaffer, W.; Williams, R.S.

    1986-01-01

    The expression of alpha 1 -adrenergic receptors within ventricular myocardium of rats ranging in age from 21 days of fetal life to 24 months after birth was measured from [ 125 I] 2-(β hydroxy phenyl) ethylaminomethyl tetralone binding isotherms. No difference was observed in binding affinity between any of the age groups studied. The number of alpha 1 -adrenergic receptors was found to be 60-120% higher in membranes from fetal or immature rats up to 25 days of age when compared with adult animals. The increased expression of alpha 1 -adrenergic receptors in the developing heart relative to that observed in adult heart is consistent with the hypothesis that alpha 1 -adrenergic receptor stimulation may modulate protein synthesis and growth in mammalian myocardium

  15. Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

    Science.gov (United States)

    Smiley, R M; Finster, M

    1996-01-01

    In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

  16. Beta-Adrenergic Receptor Blockers in Hypertension: Alive and Well.

    Science.gov (United States)

    Frishman, William H

    Beta-adrenergic receptor blockers (β-blockers) are an appropriate treatment for patients having systemic hypertension (HTN) who have concomitant ischemic heart disease (IHD), heart failure, obstructive cardiomyopathy, aortic dissection or certain cardiac arrhythmias. β-Blockers can be used in combination with other antiHTN drugs to achieve maximal blood pressure control. Labetalol can be used in HTN emergencies and urgencies. β-Blockers may be useful in HTN patients having a hyperkinetic circulation (palpitations, tachycardia, HTN, and anxiety), migraine headache, and essential tremor. β-Blockers are highly heterogeneous with respect to various pharmacologic properties: degree of intrinsic sympathomimetic activity, membrane stabilizing activity, β 1 selectivity, α 1 -adrenergic blocking effects, tissue solubility, routes of systemic elimination, potencies and duration of action, and specific properties may be important in the selection of a drug for clinical use. β-Blocker usage to reduce perioperative myocardial ischemia and cardiovascular (CV) complications may not benefit as many patients as was once hoped, and may actually cause harm in some individuals. Currently the best evidence supports perioperative β-blocker use in two patient groups: patients undergoing vascular surgery with known IHD or multiple risk factors for it, and for those patients already receiving β-blockers for known CV conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  18. β-adrenergic relaxation of smooth muscle: differences between cells and tissues

    International Nuclear Information System (INIS)

    Scheid, C.R.

    1987-01-01

    The present studies were carried out in an attempt to resolve the controversy about the Na + dependence of β-adrenergic relaxation in smooth muscle. Previous studies on isolated smooth muscle cells from the toad stomach had suggested that at least some of the actions of β-adrenergic agents, including a stimulatory effect on 45 Ca efflux, were dependent on the presence of a normal transmembrane Na + gradient. Studies by other investigators using tissues derived from mammalian sources had suggested that the relaxing effect of β-adrenergic agents was Na + independent. Uncertainty remained as to whether these discrepancies reflected differences between cells and tissues or differences between species. Thus, in the present studies, the authors utilized both tissues and cells from the same source, the stomach muscle of the toad Bufo marinus, and assessed the Na + dependence of β-adrenergic relaxation. They found that elimination of a normal Na + gradient abolished β-adrenergic relaxation of isolated cells. In tissues, however, similar manipulations had no effect on relaxation. The reasons for this discrepancy are unclear but do not appear to be attributable to changes in smooth muscle function following enzymatic dispersion. Thus the controversy concerning the mechanisms of β-adrenergic relaxation may reflect inherent differences between tissues and cells

  19. Incorporating cardiopulmonary resuscitation training into a cardiac rehabilitation programme: A feasibility study.

    Science.gov (United States)

    Cartledge, Susie; Finn, Judith; Bray, Janet E; Case, Rosalind; Barker, Lauren; Missen, Diane; Shaw, James; Stub, Dion

    2018-02-01

    Patients with a cardiac history are at future risk of cardiac events, including out-of-hospital cardiac arrest. Targeting cardiopulmonary resuscitation (CPR) training to family members of cardiac patients has long been advocated, but is an area in need of contemporary research evidence. An environment yet to be investigated for targeted training is cardiac rehabilitation. To evaluate the feasibility of providing CPR training in a cardiac rehabilitation programme among patients, their family members and staff. A prospective before and after study design was used. CPR training was delivered using video self-instruction CPR training kits, facilitated by a cardiac nurse. Data was collected pre-training, post-training and at one month. Cardiac patient participation rates in CPR classes were high ( n = 56, 72.7% of eligible patients) with a further 27 family members attending training. Patients were predominantly male (60.2%), family members were predominantly female (81.5%), both with a mean age of 65 years. Confidence to perform CPR and willingness to use skills significantly increased post-training (both ptraining participants demonstrated a mean compression rate of 112 beats/min and a mean depth of 48 mm. Training reach was doubled as participants shared the video self-instruction kit with a further 87 people. Patients, family members and cardiac rehabilitation staff had positive feedback about the training. We demonstrated that cardiac rehabilitation is an effective and feasible environment to provide CPR training. Using video self-instruction CPR training kits enabled further training reach to the target population.

  20. Enhanced Striatal β1-Adrenergic Receptor Expression Following Hormone Loss in Adulthood Is Programmed by Both Early Sexual Differentiation and Puberty: A Study of Humans and Rats

    Science.gov (United States)

    Perry, Adam N.; Westenbroek, Christel; Hedges, Valerie L.; Becker, Jill B.; Mermelstein, Paul G.

    2013-01-01

    After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function. The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood. To investigate this, we measured changes in gene expression the dorsal striatum, where 17β-estradiol modulates catecholamine signaling. In human caudate, quantitative PCR determined a significant elevation in β1-adrenergic receptor (β1AR) expression in menopausal females when compared with similarly aged males. No differences were detected in β2-adrenergic and D1- and D2-dopamine receptor expression. Consistent with humans, adult ovariectomized female rats exhibited a similar increase in β1AR expression when compared with gonadectomized males. No sex difference in β1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy. Additionally, increased β1AR expression in adult ovariectomized females was not observed if animals were masculinized/defeminized with testosterone injections as neonates. To generate a model system for assessing functional impact, increased β1AR expression was induced in female-derived cultured striatal neurons via exposure to and then removal of hormone-containing serum. Increased β1AR action on cAMP formation, cAMP response element-binding protein phosphorylation and gene expression was observed. This up-regulation of β1AR action was eliminated with 17β-estradiol addition to the media, directly implicating this hormone as a regulator of β1AR expression. Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence. PMID:23533220

  1. Prospective study of cardiac troponin I release in patients with upper gastrointestinal bleeding.

    Science.gov (United States)

    Iser, David M; Thompson, Alexander J V; Sia, Koon Ket; Yeomans, Neville D; Chen, Robert Y M

    2008-06-01

    The rate of cardiac injury in upper gastrointestinal hemorrhage is unclear. The aims of this study were to determine prospectively the risk of cardiac troponin I release and associated adverse cardiac events in patients with acute upper gastrointestinal hemorrhage. From January to September 2003, we prospectively studied patients with documented hematemesis and melena referred to the gastroenterology unit in a tertiary teaching hospital in Melbourne, Australia. Serial assays for cardiac troponin I were performed at 0, 12 and 24 h. Serial creatine kinase levels and electrocardiographs were also performed. Clinical and biochemical data were collected. The primary endpoint was a troponin level >0.5 microg/L within 24 h of recruitment. Various clinical variables were then compared between the groups of patients with or without troponin rise. A total of 156 patients were included in the study. The mean age was 67 years (range 19-96). There were 104 (67%) male patients. A troponin level of greater than 0.5 microg/L was found in 30/156 (19%); 126 (81%) patients had normal troponin levels. Age greater than 65 years, signs of hemodynamic instability at presentation, a recent history of cardiac disease, cardiovascular compromise following endoscopy, and re-bleeding were associated with troponin release. Upper gastrointestinal bleeding is associated with a risk of cardiac injury of up to 19%. Troponin assay could be used to screen for cardiac damage, especially in elderly patients who present with hemodynamic instability.

  2. Hyperpolarized C-13 MRS Cardiac Metabolism Studies in Pigs

    DEFF Research Database (Denmark)

    Giovannetti, G.; Hartwig, V.; Frijia, F.

    2012-01-01

    Cardiac metabolism assessment with hyperpolarized 13C magnetic resonance spectroscopy in pig models requires the design of dedicated coils capable of providing large field of view with high signal-to-noise ratio (SNR) data. This work presents a comparison between a commercial 13C quadrature...

  3. Cardiac Arrhythmia: Atrial Flutter in a Newborn. Case Study

    Directory of Open Access Journals (Sweden)

    T.M. Klimenko

    2014-09-01

    Full Text Available The article gives case report of rare in neonatal period cardiac arrhythmia — atrial flutter. The disease is one of the manifestations of life-threatening heart rhythm disorders, has no characteristic clinical picture, is diagnosed only by means of an electrocardiogram.

  4. Role of alpha- and beta-adrenergic receptors in cardiomyocyte differentiation from murine-induced pluripotent stem cells.

    Science.gov (United States)

    Li, Xiao-Li; Zeng, Di; Chen, Yan; Ding, Lu; Li, Wen-Ju; Wei, Ting; Ou, Dong-Bo; Yan, Song; Wang, Bin; Zheng, Qiang-Sun

    2017-02-01

    Induced pluripotent stem cell (iPSC)-derived cardiomyocytes are a promising source of cells for regenerative heart disease therapies, but progress towards their use has been limited by their low differentiation efficiency and high cellular heterogeneity. Previous studies have demonstrated expression of adrenergic receptors (ARs) in stem cells after differentiation; however, roles of ARs in fate specification of stem cells, particularly in cardiomyocyte differentiation and development, have not been characterized. Murine-induced pluripotent stem cells (miPSCs) were cultured in hanging drops to form embryoid bodies, cells of which were then differentiated into cardiomyocytes. To determine whether ARs regulated miPSC differentiation into cardiac lineages, effects of the AR agonist, epinephrine (EPI), on miPSC differentiation and underlying signalling mechanisms, were evaluated. Treatment with EPI, robustly enhanced miPSC cardiac differentiation, as indicated by increased expression levels of cardiac-specific markers, GATA4, Nkx2.5 and Tnnt2. Although β-AR signalling is the foremost signalling pathway in cardiomyocytes, EPI-enhanced cardiac differentiation depended more on α-AR signalling than β-AR signalling. In addition, selective activation of α 1 -AR signalling with specific agonists induced vigorous cardiomyocyte differentiation, whereas selective activation of α 2 - or β-AR signalling induced no or less differentiation, respectively. EPI- and α 1 -AR-dependent cardiomyocyte differentiation from miPSCs occurred through specific promotion of CPC proliferation via the MEK-ERK1/2 pathway and regulation of miPS cell-cycle progression. These results demonstrate that activation of ARs, particularly of α 1 -ARs, promoted miPSC differentiation into cardiac lineages via MEK-ERK1/2 signalling. © 2016 John Wiley & Sons Ltd.

  5. Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

    International Nuclear Information System (INIS)

    Adler, C.H.

    1986-01-01

    The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

  6. β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

    International Nuclear Information System (INIS)

    Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

    1987-01-01

    Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

  7. Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Wu, Qin; Sun, Jin-Xia; Song, Xiang-He; Wang, Jing; Xiong, Cun-Quan; Teng, Fei-Xiang; Gao, Cui-Xiang

    2017-09-01

    Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β 2 -adrenergic receptor antagonist, ICI 118551 (ICI), on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic (TG) mice treated with ICI (AD-TG/ICI) was significantly poorer compared with NaCl-treated AD-TG mice (AD-TG/NaCl), suggesting that β 2 -adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β 2 -adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β 2 -adrenergic receptor increased amyloid-β accumulation by downregulating hippocampal α-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β 2 -adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.

  8. Cardiac Patients' Experiences and Perceptions of Social Media: Mixed-Methods Study.

    Science.gov (United States)

    Partridge, Stephanie R; Grunseit, Anne C; Gallagher, Patrick; Freeman, Becky; O'Hara, Blythe J; Neubeck, Lis; Due, Sarah; Paull, Glenn; Ding, Ding; Bauman, Adrian; Phongsavan, Philayrath; Roach, Kellie; Sadler, Leonie; Glinatsis, Helen; Gallagher, Robyn

    2017-09-15

    Traditional in-person cardiac rehabilitation has substantial benefits for cardiac patients, which are offset by poor attendance. The rapid increase in social media use in older adults provides an opportunity to reach patients who are eligible for cardiac rehabilitation but unable to attend traditional face-to-face groups. However, there is a paucity of research on cardiac patients' experiences and perspectives on using social media to support their health. The aim of this study was to describe cardiac rehabilitation patients' experiences in using social media in general and their perspective on using social media, particularly Facebook, to support their cardiac health and secondary prevention efforts. A mixed-methods study was undertaken among cardiac rehabilitation patients in both urban and rural areas. First, this study included a survey (n=284) on social media use and capability. Second, six focus group interviews were conducted with current Facebook users (n=18) to elucidate Facebook experience and perspectives. Social media use was low (28.0%, 79/282) but more common in participants who were under 70 years of age, employed, and had completed high school. Social media users accessed Web-based information on general health issues (65%, 51/79), medications (56%, 44/79), and heart health (43%, 34/79). Participants were motivated to invest time in using Facebook for "keeping in touch" with family and friends and to be informed by expert cardiac health professionals and fellow cardiac participants if given the opportunity. It appeared that participants who had a higher level of Facebook capability (understanding of features and the consequences of their use and efficiency in use) spent more time on Facebook and reported higher levels of "liking," commenting, or sharing posts. Furthermore, higher Facebook capability appeared to increase a participants' willingness to participate in a cardiac Facebook support group. More capable users were more receptive to the use

  9. Data on cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results

    OpenAIRE

    Giulio Calcagni; Giuseppe Limongelli; Angelo D'Ambrosio; Francesco Gesualdo; Maria Cristina Digilio; Anwar Baban; Sonia B. Albanese; Paolo Versacci; Enrica De Luca; Giovanni B. Ferrero; Giuseppina Baldassarre; Gabriella Agnoletti; Elena Banaudi; Jan Marek; Juan P. Kaski

    2018-01-01

    A comprehensive description of morbidity and mortality in patients affected by mutations in genes encoding for signal transducers of the RAS-MAPK cascade (RASopathies) was performed in our study recently published in the International Journal of Cardiology. Seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET), collaborated in this multicentric, observational, retrospective data analysis and collection. In this study, clinical records of 371 patients with conf...

  10. Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver

    International Nuclear Information System (INIS)

    Katz, M.S.; Boland, S.R.; Schmidt, S.J.

    1985-01-01

    beta-Adrenergic agonist-sensitive adenylate cyclase activity and binding of the beta-adrenergic antagonist(-)-[ 125 I]iodopindolol were studied in rat liver during development of male Fischer 344 rats ages 6-60 days. In liver homogenates maximum adenylate cyclase response to beta-adrenergic agonist (10(-5) M isoproterenol or epinephrine) decreased by 73% (P less than 0.01) between 6 and 60 days, with most of the decrease (56%; P less than 0.01) occurring by 20 days. beta-adrenergic receptor density (Bmax) showed a corresponding decrease of 66% (P less than 0.01) by 20 days without subsequent change. Binding characteristics of stereospecificity, pharmacological specificity, saturability with time, and reversibility were unchanged with age. GTP-, fluoride-, forskolin-, and Mn2+-stimulated adenylate cyclase activities also decreased during development, suggesting a decrease of activity of the catalytic component and/or guanine nucleotide regulatory component of adenylate cyclase. These results indicate that the developmental decrease of beta-adrenergic agonist-sensitive adenylate cyclase activity may result from decreased numbers of beta-adrenergic receptors. Developmental alterations of nonreceptor components of the enzyme may also contribute to changes of catecholamine-sensitive adenylate cyclase

  11. Beta Adrenergic Regulation of Intrapulmonary Arteriovenous Anastomoses in Intact Rat and Isolated Rat Lungs

    Directory of Open Access Journals (Sweden)

    Melissa L. Bates

    2017-04-01

    Full Text Available Intrapulmonary arteriovenous anastomoses (IPAVA allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol. We also evaluated IPAVA recruitment in intact rats with hypoxia and the beta-adrenergic receptor blocker propranolol. We found that IPAVA are recruited in the intact rat by isoproterenol and their recruitment by hypoxia can be minimized by propranolol, suggesting a role for the adrenergic system in the recruitment of IPAVA by hypoxia. IPAVA recruitment is completely abolished by ventilation with 100% oxygen. Isoproterenol also recruits IPAVA in isolated rat lungs. The fact that isoproterenol can recruit IPAVA in isolated lungs, without increased pulmonary flow, suggests that elevated cardiac output is not required for IPAVA recruitment.

  12. Molecular Mechanisms of β2-Adrenergic Receptor Function and Regulation

    OpenAIRE

    McGraw, Dennis W.; Liggett, Stephen B.

    2005-01-01

    It is now clear that the β2-adrenergic receptor continuously oscillates between various conformations in the basal state, and that agonists act to stabilize one or more conformations. It is conceivable that synthetic agonists might be engineered to preferentially confine the receptor to certain conformations deemed clinically important while having a less stabilizing effect on unwanted conformations. In addition, studies of genetically engineered mice have revealed previously unrecognized cro...

  13. Treatment of resting tremor by beta-adrenergic blockade.

    Science.gov (United States)

    Foster, N L; Newman, R P; LeWitt, P A; Gillespie, M M; Chase, T N

    1984-10-01

    The effect of nadolol, a peripherally acting beta-adrenergic blocker, on resting tremor was examined in eight patients with idiopathic Parkinson's disease. With the use of a double-blind, placebo-controlled study of crossover design, patients received 80 to 320 mg of nadolol for 6 weeks while continuing their previous treatment regimen. Accelerometer readings showed a progressive reduction in tremor amplitude, but no change in tremor frequency, with increasing nadolol dosage. Maximum benefit was achieved at 240 mg, when resting tremor improved 50% (p less than 0.01). Physician ratings confirmed these findings. The results suggest that response to beta-adrenergic blockade may not be limited to postural or intention tremor and that such agents may not reliably differentiate between the tremor of Parkinson's disease and essential tremor.

  14. Echocardiographic study of the cardiac state in systemic scleroderma

    International Nuclear Information System (INIS)

    Kotel'nikova, G.P.; Guseva, N.G.

    1986-01-01

    Echocardiographic investigation in 65 patients with systemic scleroderma showed that the left ventricular syes and indices of central hemodynamics were frequently lowered in them; an increase in sizes was observed mainly in the patients with stage 2-3 of disease. Echocardiography made it possible to specify the nature of cardiac pathology and brought to light some additional features of the involvement of different heart membranes in systemic scleroderma

  15. Absence of age-related changes in the binding of the beta adrenergic antagonist 125I-iodohydroxybenzylpindolol in rat heart

    International Nuclear Information System (INIS)

    Tumer, N.; Bender, J.; Roberts, J.

    1987-01-01

    The effect of age on the density and the affinity of beta adrenergic receptors was determined in the hearts of Fischer 344 rats at three ages, 6, 12, and 24 months old. The binding of the beta adrenergic antagonist 125 I-iodohydroxybenzylpindolol (IHYP), was used to quantitate and characterize cardiac beta adrenergic receptors. The maximal number of binding sites (B/sub max/ = F moles/mg of protein) were 26.3 +/- 2.5, 25.4 +/- 0.99, and 24.5 +/- 2.4 and the dissociation constants (K/sub d/ = nM) were 0.166 +/- 0.014, 0.126 +/- 0.006, and 0.135 +/- 0.015 for 6, 12, and 24 months old animals, respectively. There were no significant differences among the three ages. These results support the contention that neither beta adrenergic receptor density of affinity changes with age in the ventricles of the rat heart

  16. Effects of therapeutic touch on anxiety, vital signs, and cardiac dysrhythmia in a sample of Iranian women undergoing cardiac catheterization: a quasi-experimental study.

    Science.gov (United States)

    Zolfaghari, Mitra; Eybpoosh, Sana; Hazrati, Maryam

    2012-12-01

    To investigate the effects of Therapeutic Touch (TT) on anxiety, vital signs, and cardiac dysrhythmia in women undergoing cardiac catheterization. It was a quasi-experimental study. The participants had no history of hallucination, anxiety, or other psychological problems. Participants had to be conscious and have attained at least sixth-grade literacy level. Participants were randomly assigned into an intervention group (n = 23; received 10-15 minutes TT), a placebo group (n = 23; received 10-15 minutes simulated touch), and a control group (n = 23; did not receive any therapy). Data were collected using Spielberger's anxiety test, cardiac dysrhythmia checklist, and vital signs recording sheet. Statistical analyses were considered to be significant at α = .05 levels. Sixty-nine women ranging in age from 35 to 65 years participated. TT significantly decreased state anxiety p < 0.0001 but not trait anxiety (p = .88), decreased the incidence of all cardiac dysrhythmias p < 0.0001 except premature ventricular contraction (p = .01), and regulated vital signs p < 0.0001 in the intervention group versus placebo and control group. TT is an effective approach for managing state anxiety, regulating vital signs, and decreasing the incidence of cardiac dysrhythmia during stressful situations, such as cardiac catheterization, in Iranian cardiac patients.

  17. Basal and β-Adrenergic Cardiomyocytes Contractility Dysfunction Induced by Dietary Protein Restriction is Associated with Downregulation of SERCA2a Expression and Disturbance of Endoplasmic Reticulum Ca2+ Regulation in Rats

    Directory of Open Access Journals (Sweden)

    Arlete R. Penitente

    2014-07-01

    Full Text Available Background: The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and β-adrenergic contractility in murine ventricular cardiomyocytes. Methods: After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20 and a protein-restricted group (PRG, n = 20, receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca2+sparks analysis. Results: PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after β-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca2+sparks were observed in PRG cardiomyocytes. Conclusion: The observations reveal that protein restriction induces marked myocardial morphofunctional damage. The pathological changes of cardiomyocyte mechanics suggest the potential involvement of the β-adrenergic system, which is possibly associated with changes in SERCA2a expression and disturbances in Ca2+ intracellular kinetics.

  18. Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Sharp, Douglas B; Wang, Xin; Mendelowitz, David

    2014-07-29

    Dexmedetomidine, an α2 adrenergic agonist, is a useful sedative but can also cause significant bradycardia. This decrease in heart rate may be due to decreased central sympathetic output as well as increased parasympathetic output from brainstem cardiac vagal neurons. In this study, using whole cell voltage clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac vagal neurons in the rat nucleus ambiguus was determined. The results indicate that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to cardiac vagal neurons, with no significant effect on excitatory input. These results provide a mechanism for dexmedetomidine induced bradycardia and has implications for the management of this potentially harmful side effect. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  20. Dynamic MR cardiac perfusion studies in patients with acquired heart diseases

    International Nuclear Information System (INIS)

    Finelli, D.A.; Adler, L.P.; Paschal, C.B.; Haacke, E.M.

    1990-01-01

    The combination of ultrafast scanning techniques with contrast administration has opened new venues for MR imaging relating to the physiology of organ perfusion. Regional cardiac perfusion determinations lend important additional information to the morphologic and functional data provided by conventional cardiac MR imaging. The authors of this paper studied 10 patients with acquired heart diseases, including ischemic heart disease, cardiomyopathy, ventricular hypertrophy, and cardiac tumor, using conventional spin-echo imaging, cine gradient-echo imaging, and dynamic Gd-DTPA--enhanced perfusion imaging with an ultrafast, inversion-recovery, Turbo-fast low-angle shot sequence. This technique enables analysis of the first pass and early biodistribution phases following contrast administration, information that has been correlated with cardiac catheterization, single photo emission CT (SPECT), and administration emission tomographic (PET) data

  1. Experimental and clinical study of cardiac hypertrophy by thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Torii, Yukio

    1983-01-01

    I studied experimentally the myocardial uptake of 201 Tl in cardiac hypertrophy in rat, and clinically evaluated cardiac shape and dimension in the patients with various types of cardiac hypertrophy. Experimentally, both myocardial blood flow (MBF) and Tl uptake were increased with cardiac weight. There were negative correlations between the extraction fraction and MBF. Tl uptake in Hypertrophy is not always dependent on MBF and affected by the altered metabolism of hypertrophied myocardium. Clinical study was performed in 29 normal subjects and in 90 patients with heart disease. The measurements of left ventricular (LV) size by Tl scintigraphy were well correlated with them by echocardiography. Aortic stenosis and hypertensive heart disease showed thick wall and spherical shape. Both mitral (MR) and aortic (AR) regurgitation showed ventricular dilatation, spherical shape (in chronic MR) and ellipsoid shape (in acute MR and in AR). Decreased ventricular size but normal shape was observed in mitral stenosis and cor pulmonale. Hypertrophic cardiomyopathy showed thick wall with asymmetric septal hypertrophy, while congestive cardiomyopathy showed thin wall with marked ventricular dilatation and spherical shape. I conclude that heart disease has characteristic figures in dimension and shape which may be reflecting cardiac performance or compensating for the load to the heart, and that 201 Tl scintigraphy is useful evaluating cardiac morphology as well as in diagnosing myocardial ischemia. (J.P.N.)

  2. Cardiac involvement in myotonic muscular dystrophy (Steinert's disease): a prospective study of 25 patients

    International Nuclear Information System (INIS)

    Perloff, J.K.; Stevenson, W.G.; Roberts, N.K.; Cabeen, W.; Weiss, J.

    1984-01-01

    The presence, degree and frequency of disorders of cardiac conduction and rhythm and of regional or global myocardial dystrophy or myotonia have not previously been studied prospectively and systematically in the same population of patients with myotonic dystrophy. Accordingly, 25 adults with classic Steinert's disease underwent electrocardiography, 24-hour ambulatory electrocardiography, vectorcardiography, chest x-rays, echocardiography, electrophysiologic studies, and technetium-99m angiography. Clinically important cardiac manifestations of myotonic dystrophy reside in specialized tissues rather than in myocardium. Involvement is relatively specific, primarily assigned to the His-Purkinje system. The cardiac muscle disorder takes the form of dystrophy rather than myotonia, and is not selective, appearing with approximately equal distribution in all 4 chambers. Myocardial dystrophy seldom results in clinically overt ventricular failure, but may be responsible for atrial and ventricular arrhythmias. Since myotonic dystrophy is genetically transmitted, a primary biochemical defect has been proposed with complete expression of the gene toward striated muscle tissue, whether skeletal or cardiac. Specialized cardiac tissue and myocardium have close, if not identical, embryologic origins, so it is not surprising that the genetic marker affects both. Cardiac involvement is therefore an integral part of myotonic dystrophy, targeting particularly the infranodal conduction system, to a lesser extent the sinus node, and still less specifically, the myocardium

  3. The cardiac patients' perceptions of their responsibilities in adherence to care: a qualitative interview study.

    Science.gov (United States)

    Kangasniemi, Mari; Hirjaba, Marina; Kohonen, Katja; Vellone, Ercole; Moilanen, Tanja; Pietilä, Anna-Maija

    2017-09-01

    To describe cardiac patients' perceptions of their responsibilities in adherence to care. The responsibilities of cardiac patients' adherence to care is a topical issue because of the increasing prevalence of noncommunicable diseases in Western countries, including cardiovascular disease (CVD). Responsibilities for cardiac patients' care have been studied, but little is described about patients' perspectives in this study. A qualitative, hermeneutic inquiry. We used face-to-face individual semistructured interviews with 21 cardiac patients (76% male) aged 58-86 in an urban area of Finland in winter 2013. The data were analysed hermeneutically with inductive content analysis. Based on our results, patients with cardiac disease understood that autonomy provided a basis for their responsibility in adherence to care. It included being able to make independent decisions, in collaboration with health professionals, or even to entrust that responsibility to healthcare professionals. Responsibilities were understood to be an expression of adherence, perceived to benefit the patient and included the duty to adopt a healthy lifestyle and care for their own medical condition. The main factors that influenced patients' responsibilities around adherence to care were their individual resources and motivation, relationships with healthcare professionals and the resources of the healthcare system. Autonomy is an inherent part of cardiac patients' adherence to care, but there has been little focus on their responsibilities in the literature. More attention needs to be paid to the healthcare providers' abilities to support patients' duties and responsibilities in clinical practice and to future research. © 2016 John Wiley & Sons Ltd.

  4. β-adrenergic receptor binding characteristics and responsiveness in cultured Wistar-Kyoto rat arterial smooth muscle cells

    International Nuclear Information System (INIS)

    Jazayeri, A.; Meyer, W.J. III

    1988-01-01

    The tone of arterial blood vessels is regulated by the catecholamines through their receptors on arterial smooth muscle cells (ASMC). β- 2 -adrenergic receptors of ASMC mediate vasodilation through agonist mediated c-AMP production. Previous reports have described these receptors on freshly isolated blood vessels. This study demonstrates the presence of β 2 -adrenergic receptors on cultured rat ASMC and that these receptors are functional. β-adrenergic receptor binding was measured using [ 3 H]-dihydroalprenolol (DHA) binding to the membrane of cultured ASMC from normotensive Wistar-Kyoto rats. The ASMC β-adrenergic receptors have a Kd of 0.56 +/- 0.16 nM and a Bmax of 57.2 +/- 21.7 fmol/mg protein. Competition binding studies revealed a much greater affinity of these receptors for epinephrine than norepinephrine, indicating the preponderance of a β 2 -adrenergic receptor subtype. Isoproterenol stimulation of cultured ASMC resulted in a 14 +/- 7 fold increase in intracellular c-AMP content of these cells indicating these receptors are functional. β-adrenergic receptors of cultured ASMC provide an excellent system in which the association between hypertension and observed β-adrenergic receptor differences can be further explored

  5. β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

    Science.gov (United States)

    Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

    2016-01-01

    β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1–M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1–M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1–M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1–M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1–M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  6. Species differences in the localization and number of CNS beta adrenergic receptors: Rat versus guinea pig

    International Nuclear Information System (INIS)

    Booze, R.M.; Crisostomo, E.A.; Davis, J.N.

    1989-01-01

    The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of [125I]cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in the thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions (1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, (2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and (3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species

  7. Smartphone-Based Cardiac Rehabilitation Program: Feasibility Study.

    Science.gov (United States)

    Chung, Heewon; Ko, Hoon; Thap, Tharoeun; Jeong, Changwon; Noh, Se-Eung; Yoon, Kwon-Ha; Lee, Jinseok

    2016-01-01

    We introduce a cardiac rehabilitation program (CRP) that utilizes only a smartphone, with no external devices. As an efficient guide for cardiac rehabilitation exercise, we developed an application to automatically indicate the exercise intensity by comparing the estimated heart rate (HR) with the target heart rate zone (THZ). The HR is estimated using video images of a fingertip taken by the smartphone's built-in camera. The introduced CRP app includes pre-exercise, exercise with intensity guidance, and post-exercise. In the pre-exercise period, information such as THZ, exercise type, exercise stage order, and duration of each stage are set up. In the exercise with intensity guidance, the app estimates HR from the pulse obtained using the smartphone's built-in camera and compares the estimated HR with the THZ. Based on this comparison, the app adjusts the exercise intensity to shift the patient's HR to the THZ during exercise. In the post-exercise period, the app manages the ratio of the estimated HR to the THZ and provides a questionnaire on factors such as chest pain, shortness of breath, and leg pain during exercise, as objective and subjective evaluation indicators. As a key issue, HR estimation upon signal corruption due to motion artifacts is also considered. Through the smartphone-based CRP, we estimated the HR accuracy as mean absolute error and root mean squared error of 6.16 and 4.30bpm, respectively, with signal corruption due to motion artifacts being detected by combining the turning point ratio and kurtosis.

  8. Smartphone-Based Cardiac Rehabilitation Program: Feasibility Study.

    Directory of Open Access Journals (Sweden)

    Heewon Chung

    Full Text Available We introduce a cardiac rehabilitation program (CRP that utilizes only a smartphone, with no external devices. As an efficient guide for cardiac rehabilitation exercise, we developed an application to automatically indicate the exercise intensity by comparing the estimated heart rate (HR with the target heart rate zone (THZ. The HR is estimated using video images of a fingertip taken by the smartphone's built-in camera. The introduced CRP app includes pre-exercise, exercise with intensity guidance, and post-exercise. In the pre-exercise period, information such as THZ, exercise type, exercise stage order, and duration of each stage are set up. In the exercise with intensity guidance, the app estimates HR from the pulse obtained using the smartphone's built-in camera and compares the estimated HR with the THZ. Based on this comparison, the app adjusts the exercise intensity to shift the patient's HR to the THZ during exercise. In the post-exercise period, the app manages the ratio of the estimated HR to the THZ and provides a questionnaire on factors such as chest pain, shortness of breath, and leg pain during exercise, as objective and subjective evaluation indicators. As a key issue, HR estimation upon signal corruption due to motion artifacts is also considered. Through the smartphone-based CRP, we estimated the HR accuracy as mean absolute error and root mean squared error of 6.16 and 4.30bpm, respectively, with signal corruption due to motion artifacts being detected by combining the turning point ratio and kurtosis.

  9. Law enforcement duties and sudden cardiac death among police officers in United States: case distribution study.

    Science.gov (United States)

    Varvarigou, Vasileia; Farioli, Andrea; Korre, Maria; Sato, Sho; Dahabreh, Issa J; Kales, Stefanos N

    2014-11-18

    To assess the association between risk of sudden cardiac death and stressful law enforcement duties compared with routine/non-emergency duties. Case distribution study (case series with survey information on referent exposures). United States law enforcement. Summaries of deaths of over 4500 US police officers provided by the National Law Enforcement Officers Memorial Fund and the Officer Down Memorial Page from 1984 to 2010. Observed and expected sudden cardiac death counts and relative risks for sudden cardiac death events during specific strenuous duties versus routine/non-emergency activities. Independent estimates of the proportion of time that police officers spend across various law enforcement duties obtained from surveys of police chiefs and front line officers. Impact of varying exposure assessments, covariates, and missing cases in sensitivity and stability analyses. 441 sudden cardiac deaths were observed during the study period. Sudden cardiac death was associated with restraints/altercations (25%, n=108), physical training (20%, n=88), pursuits of suspects (12%, n=53), medical/rescue operations (8%, n=34), routine duties (23%, n=101), and other activities (11%, n=57). Compared with routine/non-emergency activities, the risk of sudden cardiac death was 34-69 times higher during restraints/altercations, 32-51 times higher during pursuits, 20-23 times higher during physical training, and 6-9 times higher during medical/rescue operations. Results were robust to all sensitivity and stability analyses. Stressful law enforcement duties are associated with a risk of sudden cardiac death that is markedly higher than the risk during routine/non-emergency duties. Restraints/altercations and pursuits are associated with the greatest risk. Our findings have public health implications and suggest that primary and secondary cardiovascular prevention efforts are needed among law enforcement officers. © Varvarigou et al 2014.

  10. Muscle Plasticity and β2-Adrenergic Receptors: Adaptive Responses of β2-Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

    OpenAIRE

    Shogo Sato; Ken Shirato; Kaoru Tachiyashiki; Kazuhiko Imaizumi

    2011-01-01

    We discuss the functional roles of β2-adrenergic receptors in skeletal muscle hypertrophy and atrophy as well as the adaptive responses of β2-adrenergic receptor expression to anabolic and catabolic conditions. β2-Adrenergic receptor stimulation using anabolic drugs increases muscle mass by promoting muscle protein synthesis and/or attenuating protein degradation. These effects are prevented ...

  11. Clonidine, an alpha2-receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

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

    2010-08-06

    In hypertension, there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Presympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these presympathetic neurons are catecholaminergic. In addition to their projection to the spinal cord, many of these presympathetic neurons have axon collaterals that arborize into neighboring cardiorespiratory locations and likely release norepinephrine onto nearby neurons. Activation of alpha(2)-adrenergic receptors in the central nervous system evokes a diverse range of physiological effects, including reducing blood pressure. This study tests whether clonidine, an alpha(2)-adrenergic receptor agonist, alters excitatory glutamatergic, and/or inhibitory GABAergic or glycinergic synaptic neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Cardiac vagal neurons were identified in an in vitro brainstem slice preparation, and synaptic events were recording using whole cell voltage clamp methodologies. Clonidine significantly inhibited GABAergic neurotransmission but had no effect on glycinergic or glutamatergic pathways to cardiac vagal neurons. This diminished inhibitory GABAergic neurotransmission to cardiac vagal neurons would increase parasympathetic activity to the heart, decreasing heart rate and blood pressure. The results presented here provide a cellular substrate for the clinical use of clonidine as a treatment for hypertension as well as a role in alleviating posttraumatic stress disorder by evoking an increase in parasympathetic cardiac vagal activity, and a decrease in heart rate and blood pressure. Copyright 2010 Elsevier B.V. All rights reserved.

  12. β-Adrenergic Receptor Mediation of Stress-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Roles for β1 and β2 Adrenergic Receptors

    Science.gov (United States)

    Vranjkovic, Oliver; Hang, Shona; Baker, David A.

    2012-01-01

    Stress can trigger the relapse of drug use in recovering cocaine addicts and reinstatement in rodent models through mechanisms that may involve norepinephrine release and β-adrenergic receptor activation. The present study examined the role of β-adrenergic receptor subtypes in the stressor-induced reinstatement of extinguished cocaine-induced (15 mg/kg i.p.) conditioned place preference in mice. Forced swim (6 min at 22°C) stress or activation of central noradrenergic neurotransmission by administration of the selective α2 adrenergic receptor antagonist 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL-44,408) (10 mg/kg i.p.) induced reinstatement in wild-type, but not β- adrenergic receptor-deficient Adrb1/Adrb2 double-knockout, mice. In contrast, cocaine administration (15 mg/kg i.p.) resulted in reinstatement in both wild-type and β-adrenergic receptor knockout mice. Stress-induced reinstatement probably involved β2 adrenergic receptors. The β2 adrenergic receptor antagonist -(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI-118,551) (1 or 2 mg/kg i.p.) blocked reinstatement by forced swim or BRL-44,408, whereas administration of the nonselective β-adrenergic receptor agonist isoproterenol (2 or 4 mg/kg i.p.) or the β2 adrenergic receptor-selective agonist clenbuterol (2 or 4 mg/kg i.p.) induced reinstatement. Forced swim-induced, but not BRL-44,408-induced, reinstatement was also blocked by a high (20 mg/kg) but not low (10 mg/kg) dose of the β1 adrenergic receptor antagonist betaxolol, and isoproterenol-induced reinstatement was blocked by pretreatment with either ICI-118,551 or betaxolol, suggesting a potential cooperative role for β1 and β2 adrenergic receptors in stress-induced reinstatement. Overall, these findings suggest that targeting β-adrenergic receptors may represent a promising pharmacotherapeutic strategy for preventing drug relapse, particularly in cocaine addicts whose drug use is stress

  13. Adrenergic effects on secretion of amylase from the rat salivary glands

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1988-01-01

    The present study was undertaken to investigate the effect of adrenergic agents on secretion of amylase from the salivary glands in vivo. Saliva was collected from the distal oesophagus in conscious rats. Adrenaline increased the concentration of amylase in saliva and serum significantly. The res......The present study was undertaken to investigate the effect of adrenergic agents on secretion of amylase from the salivary glands in vivo. Saliva was collected from the distal oesophagus in conscious rats. Adrenaline increased the concentration of amylase in saliva and serum significantly....... The result of infusion of alpha- and beta-adrenergic antagonists as well as noradrenaline and isoproterenol showed that secretion of salivary amylase is predominantly mediated by stimulation of beta-adrenergic receptors, especially of the beta 1-subtype. Investigation of the isoenzyme pattern in saliva......, pancreatic juice and serum demonstrated that the major component in serum is salivary amylase. This study has shown that beta-adrenergic agents stimulate secretion of amylase from the salivary glands in rats. Though the secretion is mainly exocrine small amounts of amylase is found in serum, which seems...

  14. Nebivolol protects against myocardial infarction injury via stimulation of beta 3-adrenergic receptors and nitric oxide signaling.

    Directory of Open Access Journals (Sweden)

    Zheng Zhang

    Full Text Available Nebivolol, third-generation β-blocker, may activate β3-adrenergic receptor (AR, which has been emerged as a novel and potential therapeutic targets for cardiovascular diseases. However, it is not known whether nebivolol administration plays a cardioprotective effect against myocardial infarction (MI injury. Therefore, the present study was designed to clarify the effects of nebivolol on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD artery ligation. Nebivolol, β3-AR antagonist (SR59230A, Nitro-L-arginine methylester (L-NAME or vehicle was administered for 4 weeks after MI operation. Cardiac function was monitored by echocardiography. Moreover, the fibrosis and the apoptosis of myocardium were assessed by Masson's trichrome stain and TUNEL assay respectively 4 weeks after MI. Nebivolol administration reduced scar area by 68% compared with MI group (p<0.05. Meanwhile, nebivolol also decreased the myocardial apoptosis and improved the heart function after MI (p<0.05 vs. MI. These effects were associated with increased β3-AR expression. Moreover, nebivolol treatment significantly increased the phosphorylation of endothelial NOS (eNOS and the expression of neuronal NOS (nNOS. Conversely, the cardiac protective effects of nebivolol were abolished by SR and L-NAME. These results indicate that nebivolol protects against MI injury. Furthermore, the cardioprotective effects of nebivolol may be mediated by β3-AR-eNOS/nNOS pathway.

  15. Cardiac arrest while exercising on mountains in national or provincial parks: A national observational study from 2012 to 2015.

    Science.gov (United States)

    Jung, Eujene; Park, Jeong Ho; Kong, So Yeon; Hong, Ki Jeong; Ro, Young Sun; Song, Kyoung Jun; Ryu, Hyun Ho; Shin, Sang Do

    2017-12-20

    Previous studies on cardiac arrest in mountainous areas were focused on environmental features such as altitude and temperature. However, those are limited to factors affecting the prognosis of patients after cardiac arrest. We analyzed the cardiac arrests in national or provincial parks located in the mountains and determined the factors affecting the prognosis of patients after cardiac arrest. This study included all emergency medical service (EMS) treated patients over the age of 40 experiencing out-of-hospital cardiac arrests (OHCAs) of presumed cardiac etiology during exercise, between January 2012 and December 2015. The main focus of interest was the location of cardiac arrest occurrence (national mountain parks and provincial parks vs. other sites). The main outcome was survival to discharge and multivariable logistic regression was performed to adjust for possible confounding effects. A total 1835 patients who suffered a cardiac arrest while exercising were included. From these, 68 patients experienced cardiac arrest in national or provincial parks, and 1767 occurred in other locations. The unadjusted and adjusted ORs (95% CI) for a good cerebral performance scale (CPC) were 0.09 (0.01-0.63) and 0.08(0.01-0.56), survival discharges were 0.13(0.03-0.53) and 0.11 (0.03-0.48). Cardiac arrests occurring while exercising in the mountainous areas have worse prognosis compared to alternative locations. Copyright © 2017. Published by Elsevier Inc.

  16. A Numerical Study of Scalable Cardiac Electro-Mechanical Solvers on HPC Architectures

    Directory of Open Access Journals (Sweden)

    Piero Colli Franzone

    2018-04-01

    Full Text Available We introduce and study some scalable domain decomposition preconditioners for cardiac electro-mechanical 3D simulations on parallel HPC (High Performance Computing architectures. The electro-mechanical model of the cardiac tissue is composed of four coupled sub-models: (1 the static finite elasticity equations for the transversely isotropic deformation of the cardiac tissue; (2 the active tension model describing the dynamics of the intracellular calcium, cross-bridge binding and myofilament tension; (3 the anisotropic Bidomain model describing the evolution of the intra- and extra-cellular potentials in the deforming cardiac tissue; and (4 the ionic membrane model describing the dynamics of ionic currents, gating variables, ionic concentrations and stretch-activated channels. This strongly coupled electro-mechanical model is discretized in time with a splitting semi-implicit technique and in space with isoparametric finite elements. The resulting scalable parallel solver is based on Multilevel Additive Schwarz preconditioners for the solution of the Bidomain system and on BDDC preconditioned Newton-Krylov solvers for the non-linear finite elasticity system. The results of several 3D parallel simulations show the scalability of both linear and non-linear solvers and their application to the study of both physiological excitation-contraction cardiac dynamics and re-entrant waves in the presence of different mechano-electrical feedbacks.

  17. Beta-Adrenergic Receptors and Mechanisms in Asthma: The New Long-Acting Beta-Agonists

    Directory of Open Access Journals (Sweden)

    Robert G Townley

    1996-01-01

    Full Text Available The objective is to review β-adrenergic receptors and mechanisms in the immediate and late bronchial reaction in asthma and the new long-acting β-agonist. This will be discussed in light of the controversy of the potential adverse effect of regular use of long-acting β-agonists. We studied the effect of formoterol on the late asthmatic response (LAR and airway inflammation in guinea-pigs. Formoterol suppressed the LAR, antigen-induced airway inflammation and hyperresponsiveness, although isoproterenol failed to inhibit these parameters. β-Adrenergic hyporesponsiveness, and cholinergic and a- adrenergic hyperresponsiveness have been implicated in the pathogenesis of asthma. A decrease in β-adrenoreceptor function can result either from exogenously administered β-agonist or from exposure to allergens resulting in a late bronchial reaction. There is increasing evidence that eosinophils, macrophages, and lymphocytes which are of primary importance in the late bronchial reaction are also modulated by β2- adrenoreceptors. In functional studies of guinea-pig or human isolated trachea and lung parenchyma, PAF and certain cytokines significantly reduced the potency of isoproterenol to reverse methacholine- or histamine-induced contraction. The effect of glucocorticoids on pulmonary β-adrenergic receptors and responses suggests an important role for glucocorticoids to increase β-adrenergic receptors and responsiveness.

  18. Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder.

    Science.gov (United States)

    Zhang, Xiaobin; Norton, Joanna; Carrière, Isabelle; Ritchie, Karen; Chaudieu, Isabelle; Ryan, Joanne; Ancelin, Marie-Laure

    2017-02-15

    Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (ADRs) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped; adrenergic receptors alpha(1A) (ADRA1A), alpha(2A) (ADRA2A), and beta2 (ADRB2) and transcription factor TCF7L2. Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with ADRA1A rs17426222 and rs573514, and ADRB2 rs1042713 which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger samples is needed due to the small case number. This is the first study showing that ADR variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.

  19. [Non-invasive evaluation of the cardiac autonomic nervous system by PET

    International Nuclear Information System (INIS)

    1992-01-01

    C-11 hydroxy ephedrine, introduced as the first clinically usable norepinephrine analogue, studies employing normal volunteers and patients with various cardiac disorders was found to valuable as a nonadreneric tracer. Simultaneously, animal studies been used to assess its use following ischemic injury in order to define neuronal damage. Current research focuses on the comparison of C-11 hydroxyephedrine with other neurotransmitters such as C-11 epinephrine and C-11 threohydroxyephedrine. Epinephrine is primarily stored in vesicles of the nerve terminal, while threo-hydroxyephedrine is only substrate to uptake I mechanism. Such a combination of radiotracers may allow the dissection of uptake I mechanism as well as vesicular storage. In parallel to the refinement of presynaptic tracers for the sympathetic nervous system, we are developing radiopharmaceuticals to delineate the adrenergic receptors in the heart. The combined evaluation of pre- and postsynaptic nerve function will improve our ability to identify abnormalides. We are currently developing a new radiosynthesis of the hydrophilic adrenergic receptor antagonist C-11 CGP-12177 which has been used by others for the visualization of adrenergic receptors in the heart. We are developing radiopharmaceuticals, for the delineation of presynaptic cholinergic nerve terminals. Derivatives of benzovesamicol have been labeled in our institution and are currently under investigation. The most promising agent is F-18 benzovesamicol (FEBOBV) which allows the visualization of parasympathetic nerve terminals in the canine heart as demonstrated by, preliminary PET data

  20. Regional variations in baseline characteristics of cardiac rhythm device recipients: The PANORAMA observational cohort study.

    Science.gov (United States)

    Al Kandari, Fawziah; Erglis, Andrejs; Sweidan, Raed; Dannheimer, Ingrid; Sepsi, Milan; Bénézet, Juan; Padour, Michal; Naik, Ajay; Escudero, Jaime; West, Teena; Holbrook, Reece; Lorgat, Faizel

    2014-09-01

    The PANORAMA study was designed to collect concurrent data on subjects from different worldwide regions implanted with CRM devices. In this prospective, multi-center study, we analyzed baseline data on 8586 subjects implanted with CRM devices with no additional selection criteria (66% pacemaker (IPG), 16% implantable cardiac defibrillators (ICD), 17% cardiac resynchronization therapy (CRT) and CRM devices from a range of geographies that are not typically reported in literature. We found significant variations in clinical characteristics and implant practices. Long term follow-up data will help evaluate if these variations require adjustments to outcome expectations.

  1. Central venous pressure and mean circulatory filling pressure in the dogfish Squalus acanthias: adrenergic control and role of the pericardium.

    Science.gov (United States)

    Sandblom, Erik; Axelsson, Michael; Farrell, Anthony P

    2006-11-01

    Subambient central venous pressure (Pven) and modulation of venous return through cardiac suction (vis a fronte) characterizes the venous circulation in sharks. Venous capacitance was estimated in the dogfish Squalus acanthias by measuring the mean circulatory filling pressure (MCFP) during transient occlusion of cardiac outflow. We tested the hypothesis that venous return and cardiac preload can be altered additionally through adrenergic changes of venous capacitance. The experiments involved the surgical opening of the pericardium to place a perivascular occluder around the conus arteriosus. Another control group was identically instrumented, but lacked the occluder, and was subjected to the same pharmacological protocol to evaluate how pericardioectomy affected cardiovascular status. Routine Pven was negative (-0.08+/-0.02 kPa) in control fish but positive (0.09+/-0.01 kPa) in the pericardioectomized group. Injections of 5 microg/kg body mass (Mb) of epinephrine and phenylephrine (100 microg/kg Mb) increased Pven and MCFP, whereas isoproterenol (1 microg/kg Mb) decreased both variables. Thus, constriction and relaxation of the venous vasculature were mediated through the respective stimulation of alpha- and beta-adrenergic receptors. Alpha-adrenergic blockade with prazosin (1 mg/kg Mb) attenuated the responses to phenylephrine and decreased resting Pven in pericardioectomized animals. Our results provide convincing evidence for adrenergic control of the venous vasculature in elasmobranchs, although the pericardium is clearly an important component in the modulation of venous function. Thus active changes in venous capacitance have previously been underestimated as an important means of modulating venous return and cardiac performance in this group.

  2. NORADRENERGIC AND ADRENERGIC FUNCTIONING IN AUTISM

    NARCIS (Netherlands)

    MINDERAA, RB; ANDERSON, GM; VOLKMAR, FR; AKKERHUIS, GW; COHEN, DJ

    1994-01-01

    A neurochemical assessment of noradrenergic and adrenergic functioning was carried out with autistic patients and normal control individuals. Norepinephrine and related compounds were measured in autistic (n = 17 unmedicated, 23 medicated; age range 9-29 years old) and normal controls (n = 27; age

  3. Impact of the Tamsulosin in Alpha Adrenergic Receptor of Airways at Patients with Increased Bronchial Reactibility.

    Science.gov (United States)

    Mustafa, Lirim; Ilazi, Ali; Dauti, Arta; Islami, Pellumb; Kastrati, Bashkim; Islami, Hilmi

    2015-08-01

    In this work, effect of tamsulosin as antagonist of alpha1A and alpha1B adrenergic receptor and effect of agonists of beta2 adrenergic receptor-salbutamol in patients with increased bronchial reactibility was studied. Parameters of the lung function are determined with Body plethysmography six (6) hours after administration of tamsulosin. Raw and ITGV were registered and specific resistance (SRaw) was calculated as well. Tamsulosin was administered in per os manner as a preparation in the shape of the capsules with a brand name of "Prolosin", produced by Niche Generics Limited, Hitchin, Herts. After six (6) hours of administration of tamsulosin, results gained indicate that blockage of alpha1A and alpha1B-adrenergic receptor (0.8 mg per os) has not changed significantly (p > 0.1) the bronchomotor tonus of tracheobronchial tree in comparison to the check-up that has inhaled salbutamol agonist of adrenergic beta2 receptor (2 inh. x 0.2 mg), (p tamsulosin. This suggests that even after six hours of administration of tamsulosin, and determining of lung function parameters, the activity of alpha1A and alpha1B-adrenergic receptor in the smooth bronchial musculature has not changed in patients with increased bronchial reactibility.

  4. The price of donation after cardiac death in liver transplantation : a prospective cost-effectiveness study

    NARCIS (Netherlands)

    van der Hilst, Christian S.; IJtsma, Alexander J. C.; Bottema, Jan T.; van Hoek, Bart; Dubbeld, Jeroen; Metselaar, Herold J.; Kazemier, Geert; van den Berg, Aad P.; Porte, Robert J.; Slooff, Maarten J. H.

    This study aims to perform a detailed prospective observational multicenter cost-effectiveness study by comparing liver transplantations with Donation after Brain Death (DBD) and Donation after Cardiac Death (DCD) grafts. All liver transplantations in the three Dutch liver transplant centers between

  5. Clinical evaluation of unselected cardiac arrest survivors in a tertiary center over a 1-yearperiod (the LAZARUZ study)

    DEFF Research Database (Denmark)

    Marstrand, P.; Corell, P; Henriksen, F. L.

    2016-01-01

    Objectives: When the cause of an aborted cardiac arrest is unclear the initiation of therapy, counseling and family screening is challenging. Methods: We included 43 unselected, prospectively identified cardiac arrest survivors with or without a diagnosis. Family history for cardiac disease...... of the electrocardiogram. We suggest that these ECG derived clues be investigated in future studies including genetic test results and data from relatives. (C) 2016 Elsevier Inc. All rights reserved....

  6. Investigations of new cardiac functional imaging using Fourier analysis of gated blood-pool study

    International Nuclear Information System (INIS)

    Maeda, H.; Takeda, K.; Nakagawa, T.; Yamaguchi, N.; Taguchi, M.; Konishi, T.; Hamada, M.

    1982-01-01

    A new cardiac functional imaging, using temporal Fourier analysis of 28-frame gated cardiac blood-pool studies, was developed. A time-activity curve of each pixel was approximated by its Fourier series. Approximation by the sum for terms to the 3rd frequency of its Fourier series was considered to be most reasonable because of having the least aberration due to statistical fluctuation and close agreement between the global left ventricular curve and the regional fitted curves in normal subjects. To evaluate the ventricular systolic and diastolic performances, 9 parameters were analyzed from thus fitted curves on a pixel-by-pixel basis and displayed on a colour CRT in 64x64 matrix form. In patients with hypertrophic obstructive cardiomyopathy and other cardiac lesions, detailed information on the regional ventricular systolic and diastolic performances was clearly visualized by this method, which was difficult to obtain from the usual functional images of phase and amplitude at the fundamental frequency alone

  7. Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase.

    Science.gov (United States)

    Dal-Secco, Daniela; DalBó, Silvia; Lautherbach, Natalia E S; Gava, Fábio N; Celes, Mara R N; Benedet, Patricia O; Souza, Adriana H; Akinaga, Juliana; Lima, Vanessa; Silva, Katiussia P; Kiguti, Luiz Ricardo A; Rossi, Marcos A; Kettelhut, Isis C; Pupo, André S; Cunha, Fernando Q; Assreuy, Jamil

    2017-07-01

    G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor binding. GRK2 was determined by immunofluorescence and Western blot analysis in the heart and isolated cardiac myocytes. Sepsis increased NOS2 expression in the heart, increased plasma nitrite + nitrate levels, and reduced isoproterenol-induced isolated ventricle contraction, whole heart tension development, and β-adrenergic receptor density. Treatment with 1400W or with GRK2 inhibitor prevented CLP-induced cardiac hyporesponsiveness 12 and 24 h after CLP. Increased labeling of total and phosphorylated GRK2 was detected in hearts after CLP. With treatment of 1400W or in hearts taken from septic NOS2 knockout mice, the activation of GRK2 was reduced. 1400W or GRK2 inhibitor reduced mortality, improved echocardiographic cardiac parameters, and prevented organ damage. Therefore, during sepsis, NOS2-derived NO increases GRK2, which leads to a reduction in β-adrenergic receptor density, contributing to the heart dysfunction. Isolated cardiac myocyte data indicate that NO acts through the soluble guanylyl cyclase/cGMP/PKG pathway. GRK2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction. NEW & NOTEWORTHY The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore

  8. Catheter-Malposition-Induced Cardiac Tamponade via Contrast Media Leakage During Computed Tomography Study

    International Nuclear Information System (INIS)

    Liang, C.-D.; Ko, S.-F.; Huang, C.-F.; Chien, S.J.; Tiao, M.M.

    2005-01-01

    We present a rare case of a central venous catheter-malposition-induced life-threatening cardiac tamponade as a result of computed tomography (CT) with contrast enhancement in an infant with a ventricular septal defect and pulmonary atresia after a modified Blalock-Taussig shunt. The diagnosis was confirmed by chest radiographs and CT study with catheter perforation through the right atrial wall and extravasation of the contrast medium into the pericardium, leading to cardiac tamponade and subsequent circulatory collapse. Two hours after successful cardiopulmonary resuscitation, the patient gradually resumed normal hemodynamic status

  9. Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.

    Science.gov (United States)

    Miyanishi, Hiroshi; Okubo, Kataaki; Nobata, Shigenori; Takei, Yoshio

    2013-01-01

    Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.

  10. A comparison of dobutamine and levosimendan on hepatic blood flow in patients with a low cardiac output state after cardiac surgery: a randomised controlled study.

    Science.gov (United States)

    Alvarez, J; Baluja, A; Selas, S; Otero, P; Rial, M; Veiras, S; Caruezo, V; Taboada, M; Rodriguez, I; Castroagudin, J; Tome, S; Rodriguez, A; Rodriguez, J

    2013-11-01

    Liver dysfunction due to a low cardiac output state after cardiac surgery is associated with a poor prognosis, but whether one inotrope is superior to another in improving hepatic perfusion remains uncertain. This study compared the systemic and hepatic haemodynamic effects of levosimendan to dobutamine in patients with a low cardiac output state (cardiac index flow (ml/min): 614.0±124.7, 585.9±144.8; pulsatility index: 2.02±0,28, 2.98±0.27 versus the levosimendan group: cardiac index: 3.02± 0.27, 2.98± 0.30; portal vein flow: 723.0± 143.5, 702.9±117.8; pulsatility index: 1.71±0.26, 1.73±0.27). The improvement in portal vein blood flow at 48 hours was significantly better after levosimendan than dobutamine (41% vs. 11% increment from baseline, Pflow through both the hepatic artery and portal venous system, whereas dobutamine can only improve the portal venous blood flow without vasodilating the hepatic artery.

  11. α1A-Subtype adrenergic agonist therapy for the failing right ventricle.

    Science.gov (United States)

    Cowley, Patrick M; Wang, Guanying; Joshi, Sunil; Swigart, Philip M; Lovett, David H; Simpson, Paul C; Baker, Anthony J

    2017-12-01

    Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α 1 -adrenergic receptors (α 1 -ARs), in particular the α 1A -subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α 1A -subtype agonist A61603 improves function and survival in a model of left ventricular failure. The goal of the present study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk. Some mice were chronically treated with a low dose of A61603 (10 ng·kg -1 ·day -1 ). In the bleomycin model of RV failure, chronic A61603 treatment was associated with improved RV fractional shortening and greater in vitro force development by RV muscle preparations. Cell injury markers were reduced with A61603 treatment (serum cardiac troponin I, RV fibrosis, and expression of matrix metalloproteinase-2). RV oxidative stress was reduced (using the probes dihydroethidium and 4-hydroxynonenal). Consistent with lowered RV oxidative stress, A61603 was associated with an increased level of the cellular antioxidant superoxide dismutase 1 and a lower level of the prooxidant NAD(P)H oxidase isoform NOX4. In summary, in the bleomycin model of RV failure, chronic A61603 treatment reduced RV oxidative stress, RV myocyte necrosis, and RV fibrosis and increased both RV function and in vitro force development. These findings suggest that in the context of pulmonary fibrosis, the α 1A -subtype is a potential therapeutic target to treat the failing RV. NEW & NOTEWORTHY Right ventricular (RV) failure is a serious disease with a poor prognosis and no effective treatments. In the mouse bleomycin model of RV failure, we tested the efficacy of a treatment using the α 1A -adrenergic receptor subtype

  12. Immunohistochemical characterization of glandular elements in glandular cardiac myxoma: Study of six cases

    Directory of Open Access Journals (Sweden)

    Devajit Nath

    2017-01-01

    Full Text Available Back ground: Glandular cardiac myxoma has varying clinical presentation with uncertain histogenesis and debatable immunohistochemical profile. Glandular epithelial differentiations are rare phenomenon known to be present as an intrinsic component of the tumor. The origin of the glands has been attributed to epithelial differentiation of a totipotent cardiomyogenic precursor cells or the entrapped foregut rests in the tumor. Materials and Methods: Retrospective study includes six cases of glandular cardiac myxoma collected over a perior of 4 years. Sections were examined to define the histogenesis, histological and immunohistochemical profile of the glandular elements. Results: Incidence of glandular cardiac myxoma was 6.6% with a male to female ratio of 1:2.Mean age was 49.9 years. Left atrium was the commonest site. Five were sporadic and one was familial. Chest pain and dyspnea were the commonest clinical symptoms. Histologically all myxoma showed well formed glandular structures with typical myxomatous area. No atypia, mitosis or necrosis was identified in the glandular elements. Markers in six cases of glandular cardiac myxoma were immunopositive for CK7, CK 19, EMA, CEA, focally for E-cadherin while immunonegative for CK20, Chromogranin, Synaptophysin, calretenin, vimentin, B-catenin, TTF-1 and GCDFP-15 favoring enteric differentiation. Conclusion: Glandular cardiac myxoma is a rare entity which shows characteristics similar to those of classical cardiac myxoma with benign glandular elements showing enteric differentiation. Complete surgical excision is the treatment of choice with good prognosis. It is important to recognize this entity to avoid an erroneous diagnosis of metastatic adenocarcinoma.

  13. Cardioprotective Action of Ginkgo biloba Extract against Sustained β-Adrenergic Stimulation Occurs via Activation of M2/NO Pathway

    Directory of Open Access Journals (Sweden)

    Thássio R. R. Mesquita

    2017-05-01

    Full Text Available Ginkgo biloba is the most popular phytotherapic agent used worldwide for treatment of several human disorders. However, the mechanisms involved in the protective actions of Ginkgo biloba on cardiovascular diseases remain poorly elucidated. Taking into account recent studies showing beneficial actions of cholinergic signaling in the heart and the cholinergic hypothesis of Ginkgo biloba-mediated neuroprotection, we aimed to investigate whether Ginkgo biloba extract (GBE promotes cardioprotection via activation of cholinergic signaling in a model of isoproterenol-induced cardiac hypertrophy. Here, we show that GBE treatment (100 mg/kg/day for 8 days, v.o. reestablished the autonomic imbalance and baroreflex dysfunction caused by chronic β-adrenergic receptor stimulation (β-AR, 4.5 mg/kg/day for 8 days, i.p.. Moreover, GBE prevented the upregulation of muscarinic receptors (M2 and downregulation of β1-AR in isoproterenol treated-hearts. Additionally, we demonstrated that GBE prevents the impaired endothelial nitric oxide synthase activity in the heart. GBE also prevented the pathological cardiac remodeling, electrocardiographic changes and impaired left ventricular contractility that are typical of cardiac hypertrophy. To further investigate the mechanisms involved in GBE cardioprotection in vivo, we performed in vitro studies. By using neonatal cardiomyocyte culture we demonstrated that the antihypertrophic action of GBE was fully abolished by muscarinic receptor antagonist or NOS inhibition. Altogether, our data support the notion that antihypertrophic effect of GBE occurs via activation of M2/NO pathway uncovering a new mechanism involved in the cardioprotective action of Ginkgo biloba.

  14. Participation in sports groups for patients with cardiac problems : An experimental study

    NARCIS (Netherlands)

    Schaperclaus, G; deGreef, M; Rispens, P; deCalonne, D; Landsman, M; Lie, KI; Oudhof, J

    1997-01-01

    An experimental study was carried out to determine the influence of participation in Sports Groups for Patients with Cardiac Problems (SPCP) on physical and mental fitness and on risk factor level after myocardial infarction. SPCP members (n = 74; 67 men and 7 women) were compared with Nonsporting

  15. Platelet alpha-2 adrenergic receptor-mediated phosphoinositide responses in endogenous depression

    International Nuclear Information System (INIS)

    Mori, Hideki; Koyama, Tsukasa; Yamashita, Itaru

    1991-01-01

    We have previously indicated that epinephrine stimulates phosphoinositide (PI) hydrolysis by activating alpha-2 adrenergic receptors in human platelets. This method involves the measurement of the accumulation of [ 3 H]-inositol-1-phosphate (IP-1) as an index of Pl hydrolysis; lithium is added to inhibit the metabolism of IP-1, thus giving an enhanced signal. In the present study, we assessed the platelet alpha-2 adrenergic receptor-mediated PI responses in samples from 15 unmedicated patients with endogenous depression and 15 age- and sex-matched control subjects. The responses to epinephrine in the depressed patients were significantly higher than those of the controls, whereas the basal values did not differ significantly. These results support the hypothesis that platelet alpha-2 adrenergic receptors may be supersensitive in patients with endogenous depression

  16. Anxiety and beta-adrenergic receptor function in a normal population.

    Science.gov (United States)

    Kang, Eun-Ho; Yu, Bum-Hee

    2005-06-01

    Many studies have shown a close relationship between anxiety and beta-adrenergic receptor function in patients with anxiety disorders. This study examined the relationship between beta-adrenergic receptor function and anxiety levels in a normal population. Subjects for this study included 36 men and 44 women between the ages of 20 and 40 years whose Body Mass Index (BMI) was between 18 and 26. All of them were healthy subjects who had no previous history of medical or psychiatric illnesses. The authors measured the Spielberger State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Chronotropic 25 Dose (CD25) of isoproterenol, previously developed to assess in vivo beta-adrenergic receptor sensitivity. We also examined correlations between log normalized CD25 and mood states. The mean of CD25 was 2.64+/-1.37 mug and the mean of CD25 in men was significantly higher (i.e., lower beta-adrenergic receptor sensitivity) than that of women (3.26+/-1.35 vs. 2.14+/-1.17 microg; t = 3.99, p anxiety (r = -0.344, p = 0.002), trait anxiety (r = -0.331, p = 0.003), and BDI (r = -0.283, p = 0.011). CD25 was positively correlated with BMI (r = 0.423, p anxiety, and BMI. The sensitivity of beta-adrenergic receptors increased as anxiety levels became higher in a normal population. Thus, the relationship between anxiety and beta-adrenergic receptor function in healthy subjects may be different from that of patients with anxiety disorders.

  17. Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study.

    Science.gov (United States)

    Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-Ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

    2017-01-01

    It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension-Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes

  18. Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study*

    Science.gov (United States)

    Zhan, He-qing; Xia, Ling; Shou, Guo-fa; Zang, Yun-liang; Liu, Feng; Crozier, Stuart

    2014-01-01

    In this study, the effects of cardiac fibroblast proliferation on cardiac electric excitation conduction and mechanical contraction were investigated using a proposed integrated myocardial-fibroblastic electromechanical model. At the cellular level, models of the human ventricular myocyte and fibroblast were modified to incorporate a model of cardiac mechanical contraction and cooperativity mechanisms. Cellular electromechanical coupling was realized with a calcium buffer. At the tissue level, electrical excitation conduction was coupled to an elastic mechanics model in which the finite difference method (FDM) was used to solve electrical excitation equations, and the finite element method (FEM) was used to solve mechanics equations. The electromechanical properties of the proposed integrated model were investigated in one or two dimensions under normal and ischemic pathological conditions. Fibroblast proliferation slowed wave propagation, induced a conduction block, decreased strains in the fibroblast proliferous tissue, and increased dispersions in depolarization, repolarization, and action potential duration (APD). It also distorted the wave-front, leading to the initiation and maintenance of re-entry, and resulted in a sustained contraction in the proliferous areas. This study demonstrated the important role that fibroblast proliferation plays in modulating cardiac electromechanical behaviour and which should be considered in planning future heart-modeling studies. PMID:24599687

  19. Cardiac Effects of Attenuating Gsα - Dependent Signaling.

    Directory of Open Access Journals (Sweden)

    Marcus R Streit

    Full Text Available Inhibition of β-adrenergic signalling plays a key role in treatment of heart failure. Gsα is essential for β-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing β-adrenergic signalling in the heart at the level of Gsα is a promising option.We analyzed the influence of Gsα on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice overexpressing a dominant negative Gsα-mutant under control of the α-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic β-adrenergic stimulation. At rest, Gsα-DN-mice showed bradycardia (602 ± 13 vs. 660 ± 17 bpm, p<0.05 and decreased dp/dtmax (5037 ± 546- vs. 6835 ± 505 mmHg/s, p = 0.02. No significant differences were found regarding ejection fraction, heart weight and cardiomyocyte size. β-blockade by propranolol revealed no baseline differences of hemodynamic parameters between wildtype and Gsα-DN-mice. Acute adrenergic stimulation resulted in decreased β-adrenergic responsiveness in Gsα-DN-mice. Under chronic adrenergic stimulation, wildtype mice developed myocardial hypertrophy associated with increase of LV/BW-ratio by 23% (4.4 ± 0.2 vs. 3.5 ± 0.1 mg/g, p<0.01 and cardiac myocyte size by 24% (14927 ± 442 px vs. 12013 ± 583 px, p<0.001. In contrast, both parameters were unchanged in Gsα-DN-mice after chronic isoproterenol stimulation.Overexpression of a dominant negative mutant of Gsα leads to decreased β-adrenergic responsiveness and is protective against isoproterenol-induced hypertrophy. Thus, Gsα-DN-mice provide novel insights into β-adrenergic signal transduction and its modulation in myocardial overload and failure.

  20. Identification and characterization of alpha 1 adrenergic receptors in the canine prostate using [125I]-Heat

    International Nuclear Information System (INIS)

    Lepor, H.; Baumann, M.; Shapiro, E.

    1987-01-01

    We have recently utilized radioligand receptor binding methods to characterize muscarinic cholinergic and alpha adrenergic receptors in human prostate adenomas. The primary advantages of radioligand receptor binding methods are that neurotransmitter receptor density is quantitated, the affinity of unlabelled drugs for receptor sites is determined, and receptors can be localized using autoradiography on slide-mounted tissue sections. Recently, [ 125 I]-Heat, a selective and high affinity ligand with high specific activity (2200 Ci/mmole) has been used to characterize alpha 1 adrenergic receptors in the brain. In this study alpha 1 adrenergic receptors in the dog prostate were characterized using [ 125 I]-Heat. The Scatchard plots were linear indicating homogeneity of [ 125 I]-Heat binding sites. The mean alpha 1 adrenergic receptor density determined from these Scatchard plots was 0.61 +/- 0.07 fmol/mg. wet wt. +/- S.E.M. The binding of [ 125 I]-Heat to canine prostate alpha 1 adrenergic binding sites was of high affinity (Kd = 86 +/- 19 pM). Steady state conditions were reached following an incubation interval of 30 minutes and specific binding and tissue concentration were linear within the range of tissue concentrations assayed. The specificity of [ 125 I]-Heat for alpha 1 adrenergic binding sites was confirmed by competitive displacement assays using unlabelled clonidine and prazosin. Retrospective analysis of the saturation experiments demonstrated that Bmax can be accurately calculated by determining specific [ 125 I]-Heat binding at a single ligand concentration. [ 125 I]-Heat is an ideal ligand for studying alpha 1 adrenergic receptors in the prostate and its favorable properties should facilitate the autoradiographic localization of alpha 1 adrenergic receptors in the prostate

  1. Intractable diarrhea in hyperthyroidism: management with beta-adrenergic blockade.

    Science.gov (United States)

    Bricker, L A; Such, F; Loehrke, M E; Kavanaugh, K

    2001-01-01

    To describe a patient with intractable diarrhea and thyrotoxic Graves' disease, for whom b-adrenergic blockade ultimately proved to be effective therapy for the diarrhea, and to review the types of hyperthyroidism-associated diarrhea. We present the clinical course of a young man with a prolonged siege of diarrhea that proved elusive to diagnostic inquiries and resistant to all means of management until its endocrine basis was discovered. Control of such cases with b-adrenergic blockade is discussed, as are the pathophysiologic bases of intestinal hypermotility in hyperthyroidism. A 26-year-old man with Down syndrome, and no prior gastrointestinal disorder, had insidious, chronic, constant diarrhea, which was associated with loss of 14 kg during a 5-month period. Numerous laboratory and imaging studies and endoscopic examinations failed to disclose the cause of the diarrhea. Furthermore, a broad range of antibiotics and other empiric remedies failed to control the problem. No other symptoms of hyperthyroidism were reported, but when the endocrinopathy was suspected and identified, the diarrhea was promptly controlled by treatment with propranolol. In patients with hyperthyroidism, two types of diarrheal disorders have been described-secretory diarrhea and steatorrhea; bile acid malabsorption may have a role in either of these settings. In addition to its capacity for blocking the peripheral effects of thyroid hormone on the heart and central nervous system, b-adrenergic blockade is effective in slowing intestinal transit time and ameliorating the uncommon diarrhea associated with hyperthyroidism. Thyroid hormone in excess, among its other possible effects on the gastrointestinal tract, may exert a stimulatory effect by means of intermediary sympathetic activation, as it does with the heart. Thus, sympathetic blockade can mimic the salutary effects on the gastrointestinal tract conventionally brought about by direct antithyroid therapy, and well before the

  2. FIASCO II failure to achieve a satisfactory cardiac outcome study: the elimination of system errors.

    Science.gov (United States)

    Farid, Shakil; Page, Aravinda; Jenkins, David; Jones, Mark T; Freed, Darren; Nashef, Samer A M

    2013-07-01

    Death in low-risk cardiac surgical patients provides a simple and accessible method by which modifiable causes of death can be identified. In the first FIASCO study published in 2009, local potentially modifiable causes of preventable death in low-risk patients with a logistic EuroSCORE of 0-2 undergoing cardiac surgery were inadequate myocardial protection and lack of clarity in the chain of responsibility. As a result, myocardial protection was improved, and a formalized system introduced to ensure clarity of the chain of responsibility in the care of all cardiac surgical patients. The purpose of the current study was to re-audit outcomes in low-risk patients to see if improvements have been achieved. Patients with a logistic EuroSCORE of 0-2 who had cardiac surgery from January 2006 to August 2012 were included. Data were prospectively collected and retrospectively analysed. The case notes of patients who died in hospital were subject to internal and external review and classified according to preventability. Two thousand five hundred and forty-nine patients with a logistic EuroSCORE of 0-2 underwent cardiac surgery during the study period. Seven deaths occurred in truly low-risk patients, giving a mortality of 0.27%. Of the seven, three were considered preventable and four non-preventable. Mortality was marginally lower than in our previous study (0.37%), and no death occurred as a result of inadequate myocardial protection or communication failures. We postulate that the regular study of such events in all institutions may unmask systemic errors that can be remedied to prevent or reduce future occurrences. We encourage all units to use this methodology to detect any similarly modifiable factors in their practice.

  3. Synthesis and characterization of arylamine derivatives of rauwolscine as molecular probes for alpha 2-adrenergic receptors

    International Nuclear Information System (INIS)

    Lanier, S.M.; Graham, R.M.; Hess, H.J.; Grodski, A.; Repaske, M.G.; Nunnari, J.M.; Limbird, L.E.; Homcy, C.J.

    1987-01-01

    The selective alpha 2-adrenergic receptor antagonist rauwolscine was structurally modified to yield a series of arylamine carboxamide derivatives, which were investigated as potential molecular probes for the localization and structural characterization of alpha 2-adrenergic receptors. The arylamine carboxamides differ in the number of carbon atoms separating the reactive phenyl moiety from the fused ring structure of the parent compound, rauwolscine carboxylate. Competitive inhibition studies with [ 3 H]rauwolscine in rat kidney membranes indicate that the affinity for the carboxamide derivatives is inversely related to the length of the carbon spacer arm with rauwolscine 4-aminophenyl carboxamide exhibiting the highest affinity (Kd = 2.3 +/- 0.2 nM). Radioiodination of rau-AMPC yields a ligand, 125 I-rau-AMPC, which binds to rat kidney alpha 2-adrenergic receptors with high affinity, as determined by both kinetic analysis (Kd = k2/k1 = 0.016 min-1/2.1 X 10(7) M-1 min-1 = 0.76 nM) and equilibrium binding studies (Kd = 0.78 +/- 0.16 nM). 125 I-rau-AMPC was quantitatively converted to the photolabile arylazide derivative 17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-azido-3-[ 125 I]iodophenyl) carboxamide ( 125 I-rau-AZPC). In a partially purified receptor preparation from porcine brain, this compound photolabels a major (Mr = 62,000) peptide. The labeling of this peptide is inhibited by adrenergic agonists and antagonists with a rank order of potency consistent with an alpha 2-adrenergic receptor binding site. Both 125 I-rau-AMPC and the photolabile arylazide derivative, 125 I-rau-AZPC, should prove useful as molecular probes for the structural and biochemical characterization of alpha 2-adrenergic receptors

  4. Cardiac failure due to arteriovenous fistula with brachiocephalic stenosis: a gated heart case study

    International Nuclear Information System (INIS)

    Abel, G.; Irish, A.; Henderson, A.; Lenzo, N.

    2003-01-01

    Full text: There are numerous causes of cardiac failure of which the commonest in our community include ischaemic cardiomyopathy, post-viral cardiomyopathy, alcohol-induced cardiomyopathy and drug-induced cardiomyopathy. All these entities cause low output cardiac failure however high output cardiac failure is also well recognised. This includes heart failure related to such conditions as hyperthyroidism, anaemia, pregnancy, beri-beri, and Paget's disease. A rare cause of high output cardiac failure is an arteriovenous fistula. We present an unusual case of a patient with end-stage renal failure on haemodialysis who developed extensive dilatation of their left arm arteriovenous fistula secondary to bachiocephalic vein stenosis. The labelled red blood cell gated heart blood pool study demonstrated decreased left ventricular function and extensive pooling of blood within the tortuous dilated left arm vessels. A follow-up study post-ligation of the arteriovenous fistula showed improvement of the left ventricular ejection fraction. The associated contrast venography findings are also demonstrated. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  5. Efficacy of cardiac resynchronization with defibrillator insertion in patients undergone coronary artery bypass graft: A cohort study of cardiac function

    Directory of Open Access Journals (Sweden)

    Reza Karbasi Afshar

    2015-01-01

    Full Text Available Introduction: Cardiac resynchronization therapy (CRT is a proven therapeutic method in selected patients with heart failure and systolic dysfunction which increases left ventricular function and patient survival. We designed a study that included patients undergoing coronary artery bypass graft (CABG, with and without CRT-defibrillator (CRT-D inserting and then measured its effects on these two groups. Patients and Methods: Between 2010 and 2013, we conducted a prospective cohort study on 100 coronary artery disease patients where candidate for CABG. Then based on the receiving CRT-D, the patients were categorized in two groups; Group 1 ( n = 48, with CRT-D insertion before CABG and Group 2 ( n = 52 without receiving CRT-D. Thereafter both of these groups were followed-up at 1-3 months after CABG for mortality, hospitalization, atrial fibrillation (AF, echocardiographic assessment, and New York Heart Association (NYHA class level. Results: The mean age of participants in Group 1 (48 male and in Group 2 (52 male was 58 ± 13 and 57 ± 12 respectively. Difference between Groups 1 and 2 in cases of mean left ventricular ejection fraction (LVEF changes and NYHA class level was significant ( P > 0.05. Hospitalization ( P = 0.008, mortality rate ( P = 0.007, and AF were significantly different between these two groups. Conclusions: The results showed that the increase in LVEF and patient′s improvement according to NYHA-class was significant in the first group, and readmission, mortality rate and AF was increased significantly in the second group.

  6. {beta}-adrenergic receptor density and adenylate cyclase activity in lead-exposed rat brain after cessation of lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Huoy-Rou [I-Shou University, Department of Biomedical Engineering, Dashu Shiang, Kaohsiung County (Taiwan); Tsao, Der-An [Fooyin University of Technology, Department of Medical Technology (Taiwan); Yu, Hsin-Su [Taiwan University, Department of Dermatology, College of Medicine (Taiwan); Ho, Chi-Kung [Kaohsiung Medical University, Occupational Medicine (Taiwan); Kaohsiung Medical University, Graduate Institute of Medicine, Research Center for Occupational Disease (Taiwan)

    2005-01-01

    To understanding the reversible or irreversible harm to the {beta}-adrenergic system in the brain of lead-exposed rats, this study sets up an animal model to estimate the change in the sympathetic nervous system of brain after lead exposure was withdrawn. We address the following topics in this study: (a) the relationship between withdrawal time of lead exposure and brain {beta}-adrenergic receptor, blood lead level, and brain lead level in lead-exposed rats after lead exposure was stopped; and (b) the relationship between lead level and {beta}-adrenergic receptor and cyclic AMP (c-AMP) in brain. Wistar rats were chronically fed with 2% lead acetate and water for 2 months. Radioligand binding was assayed by a method that fulfilled strict criteria of {beta}-adrenergic receptor using the ligand [{sup 125}I]iodocyanopindolol. The levels of lead were determined by electrothermal atomic absorption spectrometry. The c-AMP level was determined by radioimmunoassay. The results showed a close relationship between decreasing lead levels and increasing numbers of brain {beta}-adrenergic receptors and brain adenylate cyclase activity after lead exposure was withdrawn. The effect of lead exposure on the {beta}-adrenergic system of the brain is a partly reversible condition. (orig.)

  7. Cardiac patients' perception of patient-centred care: a qualitative study.

    Science.gov (United States)

    Esmaeili, Maryam; Cheraghi, Mohammad A; Salsali, Mahvash

    2016-03-01

    The aim of this study was to explore cardiac patients' perception of patient-centred care. Despite patient's importance in the process of care, less attention has been paid to experiences and expectations of patients in definitions of patient-centred care. As patients are an important element in process of patient-centred care, organizing care programs according to their perceptions and expectations will lead to enhanced quality of care and greater patient satisfaction. This study is a descriptive qualitative study. Content analysis approach was performed for data analysis. Participants were 18 cardiac patients (10 women and 8 men) hospitalized in coronary care units of teaching hospitals affiliated to Tehran University of Medical Sciences. We collected the study data through conducting personal face-to-face semi-structured interviews. The participants' perceptions of patient-centred care fell into three main themes including managing patients uncertainty, providing care with more flexibility and establishing a therapeutic communication. The second theme consisted of two sub-themes: empathizing with patients and having the right to make independent decisions. Receiving patient-centred care is essential for cardiac patients. Attention to priorities and preferences of cardiac patients and making decisions accordingly is among effective strategies for achieving patient-centred care. Cardiac care unit nurses ought to be aware that in spite of technological developments and advances, it is still important to pay attention to patients' needs and expectations in order to achieve patient satisfaction. In planning care programs, they should consider accountability towards patients' needs, flexibility in process of care and establishing medical interactions as an effective strategy for improving quality of care. © 2014 British Association of Critical Care Nurses.

  8. Practolol in Hyperthyroid Cardiac Failure | Epstein | South African ...

    African Journals Online (AJOL)

    Practolol (Eraldint), a recently developed beta-adrenergic blocking agent, has been found useful in conjunction with digitalis and diuretics in 6 patients with thyrocardiac disease who had been refractory to therapy. In all cases cardiac failure improved dramatically, suggesting better myocardial efficiency and a return of ...

  9. Patients with cardiac arrest are ventilated two times faster than guidelines recommend : An observational prehospital study using tracheal pressure measurement

    NARCIS (Netherlands)

    Maertens, Vicky L.; De Smedt, Lieven E. G.; Lemoyne, Sabine; Huybrechts, Sofie A. M.; Wouters, Kristien; Kalmar, Alain F.; Monsieurs, Koenraad G.

    Aim: To measure ventilation rate using tracheal airway pressures in prehospitally intubated patients with and without cardiac arrest. Methods: Prospective observational study. In 98 patients (57 with and 41 without cardiac arrest) an air-filled catheter was inserted into the endotracheal tube and

  10. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Aude Carillion

    Full Text Available In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes.β-adrenergic responses were investigated in vivo (echocardiography and ex vivo (left ventricular papillary muscles in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1. Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD.Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4. Nitric oxide synthase (NOS inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response.Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

  11. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.

    Science.gov (United States)

    Carillion, Aude; Feldman, Sarah; Na, Na; Biais, Matthieu; Carpentier, Wassila; Birenbaum, Aurélie; Cagnard, Nicolas; Loyer, Xavier; Bonnefont-Rousselot, Dominique; Hatem, Stéphane; Riou, Bruno; Amour, Julien

    2017-01-01

    In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes. β-adrenergic responses were investigated in vivo (echocardiography) and ex vivo (left ventricular papillary muscles) in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1). Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD. Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4). Nitric oxide synthase (NOS) inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response. Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

  12. Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects.

    Science.gov (United States)

    Wofford, M R; Anderson, D C; Brown, C A; Jones, D W; Miller, M E; Hall, J E

    2001-07-01

    The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) > or =28 kg/m2 (obese) and nine lean patients with a BMI lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the alpha-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session. There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5+/-2.4 v 76.8+/-4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0+/-2.5 v 138.9+/-2.1 mm Hg, P = .02) and MAP (99.6+/-2.3 v 107.0+/-1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3+/-2.5 v 90.9+/-1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade. These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.

  13. Feasibility of a Facebook Intervention for Exercise Motivation and Cardiac Rehabilitation Adherence: Study Protocol.

    Science.gov (United States)

    Siegmund, Lee Anne; Ahmed, Haitham M; Crawford, Michael Todd; Bena, James Frank

    2017-08-18

    While cardiac rehabilitation has been shown to be effective at improving coronary heart disease (CHD), participation is generally poor. Attempts to increase uptake and adherence often fail. Use of a Facebook intervention for this population may be a unique opportunity to support self-determined motivation and affect adherence. To evaluate the impact of a Facebook intervention on motivation for exercise and adherence to cardiac rehabilitation in patients with CHD during a 12-week, Phase II cardiac rehabilitation program. A prospective, randomized controlled pilot study, grounded in Self-Determination Theory, will be conducted. Participants will be recruited from inpatient, or the intake visit to outpatient, cardiac rehabilitation, and then randomly assigned to the intervention or comparison group. Participants in the intervention group will take part in a private Facebook group. Weekly posts will be designed to support self-determined motivation, measured at baseline and postcardiac rehabilitation by the Behavioral Regulation in Exercise Questionnaire-3 (BREQ-3). The Psychological Need Satisfaction for Exercise (PNSE) scale will measure fulfillment of needs that affect motivation. Participants in the comparison group will be given the same materials, but these will be supplied via handouts and email. The number of sessions attended will be tallied and analyzed using t tests. Overall motivation will be evaluated using analysis of covariance (ANCOVA) models. Multivariate analysis of variance models will be used to evaluate differences in the change across motivation subtypes. If significant, ANCOVA models for each subtype will be fit. ANCOVA models will be used to compare changes in needs satisfaction, overall and separately among the three subscales, between groups. Engagement in the Facebook group will be measured by number of "likes" and self-report of weekly visits to the group. This project was funded in July 2017 and recruitment is currently underway. The

  14. Clinical experience and skills of physicians in hospital cardiac arrest teams in Denmark: a nationwide study

    Directory of Open Access Journals (Sweden)

    Lauridsen KG

    2017-03-01

    Full Text Available Kasper G Lauridsen,1–3 Anders S Schmidt,1–3 Philip Caap,3,4 Rasmus Aagaard,2,3,5 Bo Løfgren1,3,4 1Department of Internal Medicine, 2Clinical Research Unit, Regional Hospital of Randers, Randers, 3Research Center for Emergency Medicine, Aarhus University Hospital, 4Institute of Clinical Medicine, Aarhus University, Aarhus, 5Department of Anesthesiology, Randers Regional Hospital, Denmark Background: The quality of in-hospital resuscitation is poor and may be affected by the clinical experience and cardiopulmonary resuscitation (CPR training. This study aimed to investigate the clinical experience, self-perceived skills, CPR training and knowledge of the guidelines on when to abandon resuscitation among physicians of cardiac arrest teams. Methods: We performed a nationwide cross-sectional study in Denmark. Telephone interviews were conducted with physicians in the cardiac arrest teams in public somatic hospitals using a structured questionnaire. Results: In total, 93 physicians (53% male from 45 hospitals participated in the study. Median age was 34 (interquartile range: 30–39 years. Respondents were medical students working as locum physicians (5%, physicians in training (79% and consultants (16%, and the median postgraduate clinical experience was 48 (19–87 months. Most respondents (92% felt confident in treating a cardiac arrest, while fewer respondents felt confident in performing intubation (41% and focused cardiac ultrasound (39% during cardiac arrest. Median time since last CPR training was 4 (2–10 months, and 48% had attended a European Resuscitation Council (ERC Advanced Life Support course. The majority (84% felt confident in terminating resuscitation; however, only 9% were able to state the ERC guidelines on when to abandon resuscitation. Conclusion: Physicians of Danish cardiac arrest teams are often inexperienced and do not feel competent performing important clinical skills during resuscitation. Less than half have

  15. Paediatric traumatic cardiac arrest: a Delphi study to establish consensus on definition and management.

    Science.gov (United States)

    Rickard, Annette C; Vassallo, James; Nutbeam, Tim; Lyttle, Mark D; Maconochie, Ian K; Enki, Doyo G; Smith, Jason E

    2018-04-28

    Paediatric traumatic cardiac arrest (TCA) is associated with low survival and poor outcomes. The mechanisms that underlie TCA are different from medical cardiac arrest; the approach to treatment of TCA may therefore also need to differ to optimise outcomes. The aim of this study was to explore the opinion of subject matter experts regarding the diagnosis and treatment of paediatric TCA, and to reach consensus on how best to manage this group of patients. An online Delphi study was conducted over three rounds, with the aim of achieving consensus (defined as 70% agreement) on statements related to the diagnosis and management of paediatric TCA. Participants were invited from paediatric and adult emergency medicine, paediatric anaesthetics, paediatric ICU and paediatric surgery, as well as Paediatric Major Trauma Centre leads and representatives from the Resuscitation Council UK. Statements were informed by literature reviews and were based on elements of APLS resuscitation algorithms as well as some concepts used in the management of adult TCA; they ranged from confirmation of cardiac arrest to the indications for thoracotomy. 73 experts completed all three rounds between June and November 2016. Consensus was reached on 14 statements regarding the diagnosis and management of paediatric TCA; oxygenation and ventilatory support, along with rapid volume replacement with warmed blood, improve survival. The duration of cardiac arrest and the lack of a response to intervention, along with cardiac standstill on ultrasound, help to guide the decision to terminate resuscitation. This study has given a consensus-based framework to guide protocol development in the management of paediatric TCA, though further work is required in other key areas including its acceptability to clinicians. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Differential expression and role of hyperglycemia induced oxidative stress in epigenetic regulation of β1, β2 and β3-adrenergic receptors in retinal endothelial cells

    Science.gov (United States)

    2014-01-01

    Background Aberrant epigenetic profiles are concomitant with a spectrum of developmental defects and diseases. Role of methylation is an increasingly accepted factor in the pathophysiology of diabetes and its associated complications. This study aims to examine the correlation between oxidative stress and methylation of β1, β2 and β3-adrenergic receptors and to analyze the differential variability in the expression of these genes under hyperglycemic conditions. Methods Human retinal endothelial cells were cultured in CSC complete medium in normal (5 mM) or high (25 mM) glucose to mimic a diabetic condition. Reverse transcription PCR and Western Blotting were performed to examine the expression of β1, β2 and β3-adrenergic receptors. For detections, immunocytochemistry was used. Bisulfite sequencing method was used for promoter methylation analysis. Apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to measure reactive oxygen species (ROS) production in the cells. Results β1 and β3-adrenergic receptors were expressed in retinal endothelial cells while β2-adrenergic receptor was not detectable both at protein and mRNA levels. Hyperglycemia had no significant effect on β1 and β2-adrenergic receptors methylation and expression however β3-adrenergic receptors showed a significantly higher expression (p adrenergic receptors methylation with no significant effect on β1 and β2-adrenergic receptors. β2-adrenergic receptor was hypermethylated with halted expression. Conclusion Our study demonstrates that β1 and β3-adrenergic receptors expressed in human retinal endothelial cells. Oxidative stress and apoptosis are inversely proportional to the extent of promoter methylation, suggesting that methylation loss might be due to oxidative stress-induced DNA damage. PMID:24885710

  17. Predictors of red blood cell transfusion after cardiac surgery: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Camila Takao Lopes

    2015-12-01

    Full Text Available Abstract OBJECTIVE To identify predictors of red blood cell transfusion (RBCT after cardiac surgery. METHOD A prospective cohort study performed with 323 adults after cardiac surgery, from April to December of 2013. A data collection instrument was constructed by the researchers containing factors associated with excessive bleeding after cardiac surgery, as found in the literature, for investigation in the immediate postoperative period. The relationship between risk factors and the outcome was assessed by univariate analysis and logistic regression. RESULTS The factors associated with RBCT in the immediate postoperative period included lower height and weight, decreased platelet count, lower hemoglobin level, higher prevalence of platelet count <150x10 3/mm3, lower volume of protamine, longer duration of anesthesia, higher prevalence of intraoperative RBCT, lower body temperature, higher heart rate and higher positive end-expiratory pressure. The independent predictor was weight <66.5Kg. CONCLUSION Factors associated with RBCT in the immediate postoperative period of cardiac surgery were found. The independent predictor was weight.

  18. Cardiac chamber quantification using magnetic resonance imaging at 7 Tesla - a pilot study

    International Nuclear Information System (INIS)

    Knobelsdorff-Brenkenhoff, Florian von; Schulz-Menger, Jeanette; Frauenrath, Tobias; Hezel, Fabian; Prothmann, Marcel; Dieringer, Matthias A.; Niendorf, Thoralf; Renz, Wolfgang; Kretschel, Kerstin

    2010-01-01

    Interest in cardiovascular magnetic resonance (CMR) at 7 T is motivated by the expected increase in spatial and temporal resolution, but the method is technically challenging. We examined the feasibility of cardiac chamber quantification at 7 T. A stack of short axes covering the left ventricle was obtained in nine healthy male volunteers. At 1.5 T, steady-state free precession (SSFP) and fast gradient echo (FGRE) cine imaging with 7 mm slice thickness (STH) were used. At 7 T, FGRE with 7 mm and 4 mm STH were applied. End-diastolic volume, end-systolic volume, ejection fraction and mass were calculated. All 7 T examinations provided excellent blood/myocardium contrast for all slice directions. No significant difference was found regarding ejection fraction and cardiac volumes between SSFP at 1.5 T and FGRE at 7 T, while volumes obtained from FGRE at 1.5 T were underestimated. Cardiac mass derived from FGRE at 1.5 and 7 T was larger than obtained from SSFP at 1.5 T. Agreement of volumes and mass between SSFP at 1.5 T and FGRE improved for FGRE at 7 T when combined with an STH reduction to 4 mm. This pilot study demonstrates that cardiac chamber quantification at 7 T using FGRE is feasible and agrees closely with SSFP at 1.5 T. (orig.)

  19. A STUDY ON CARDIAC MYXOMA OF POPULATION IN NORTH EAST INDIA

    Directory of Open Access Journals (Sweden)

    Jyoti Prasad Kalita

    2016-06-01

    Full Text Available BACKGROUND Cardiac myxomas are the most common primary cardiac tumors. A high degree of suspicion is required for diagnosing myxomas clinically and often leads to grave consequence if missed. Though surgical resection is the definitive treatment, but if not treated with the right surgical technique recurrence occurs. OBJECTIVES To describe clinical presentations, age and sex distribution, anatomical location and morbidity, mortality and recurrence rate following surgery of patients of North Eastern part of India who have presented in our Cardiothoracic Unit with cardiac myxomas. METHOD All consecutive patients over a period of 5 years who underwent surgical excision of cardiac myxoma at our Cardiothoracic Unit and histologically proven as cardiac myxoma were included in this study. Data were collected from the operation data base and the patient records. Echocardiography was the the diagnostic tool in all cases. The historical longitudinal study was performed. All patients underwent operation soon after the diagnosis of a myxoma was made. Complete tumour excision were done in all cases. All cases were followed up for a mean period of 32 months. RESULTS Of total 28 patients who underwent surgery for cardiac tumor over that period, 25(89.25% patients had histologically proven cardiac myxomas. Their age ranged from 15 to 55 years with a mean of 35 years. Majority patients were female (n-16, 64%. Most of the patients had clinical presentations similar to obstructive mitral valve. A small group of patients presented with embolic and constitutional symptoms. All patients underwent operation via right atrial approach. Left atrium (n-20, 80% is the commonest location followed by the right atrium (n-3, 12%. One patient had myxoma originating from tricuspid valve annulus, one from right ventricle and another one patient had mitral valve annulus origin. There was no death after surgery or recurrence was noted after mean 32 moths of follow-up. DISCUSSION

  20. Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Blanck, Oliver, E-mail: oliver.blanck@uksh.de [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Bode, Frank [Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Gebhard, Maximilian [Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Hunold, Peter [Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Brandt, Sebastian [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Bruder, Ralf [Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Grossherr, Martin [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Vonthein, Reinhard [Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Rades, Dirk [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Dunst, Juergen [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); University Copenhagen (Denmark)

    2014-07-01

    Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

  1. Stimulation of postsynapse adrenergic α2A receptor improves attention/cognition performance in an animal model of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Kawaura, Kazuaki; Karasawa, Jun-ichi; Chaki, Shigeyuki; Hikichi, Hirohiko

    2014-08-15

    A 5-trial inhibitory avoidance test using spontaneously hypertensive rat (SHR) pups has been used as an animal model of attention deficit hyperactivity disorder (ADHD). However, the roles of noradrenergic systems, which are involved in the pathophysiology of ADHD, have not been investigated in this model. In the present study, the effects of adrenergic α2 receptor stimulation, which has been an effective treatment for ADHD, on attention/cognition performance were investigated in this model. Moreover, neuronal mechanisms mediated through adrenergic α2 receptors were investigated. We evaluated the effects of both clonidine, a non-selective adrenergic α2 receptor agonist, and guanfacine, a selective adrenergic α2A receptor agonist, using a 5-trial inhibitory avoidance test with SHR pups. Juvenile SHR exhibited a shorter transfer latency, compared with juvenile Wistar Kyoto (WKY) rats. Both clonidine and guanfacine significantly prolonged the transfer latency of juvenile SHR. The effects of clonidine and guanfacine were significantly blocked by pretreatment with an adrenergic α2A receptor antagonist. In contrast, the effect of clonidine was not attenuated by pretreatment with an adrenergic α2B receptor antagonist, or an adrenergic α2C receptor antagonist, while it was attenuated by a non-selective adrenergic α2 receptor antagonist. Furthermore, the effects of neither clonidine nor guanfacine were blocked by pretreatment with a selective noradrenergic neurotoxin. These results suggest that the stimulation of the adrenergic α2A receptor improves the attention/cognition performance of juvenile SHR in the 5-trial inhibitory avoidance test and that postsynaptic, rather than presynaptic, adrenergic α2A receptor is involved in this effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Role of adrenergic receptors in the caffeine-induced increase in ...

    African Journals Online (AJOL)

    The present study was designed to investigate the effects of alpha and beta adrenergic receptor blockers on caffeine-induced increase in canine hindlimb glucose uptake. The study was carried out on fasted male anaesthetized dogs divided into five groups (5dogs per group). Each dog was given a bolus injection of normal ...

  3. Effects of chronic delta-9-THC treatment on cardiac beta-adrenoceptors in rats

    Energy Technology Data Exchange (ETDEWEB)

    Evans, E.B.; Seifen, E.; Kennedy, R.H.; Kafiluddi, R.; Paule, M.G.; Scallet, A.C.; Ali, S.F.; Slikker, W. Jr.

    1987-10-01

    This study was designed to determine if chronic treatment with delta-9-tetrahydrocannabinol (THC) alters cardiac beta-adrenoceptors in the rat. Following daily oral administration of 10 or 20 mg/kg THC or an equivalent volume of control solvent for 90 days, rats were sacrificed, and sarcolemmal membranes were prepared from ventricular myocardium. Beta-adrenoceptor density and binding affinity estimated with (-)(/sup 3/H)dihydroalprenolol; a beta-adrenergic antagonist, were not significantly affected by treatment with THC when compared to vehicle controls. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.

  4. Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart.

    Science.gov (United States)

    Herrmann, Stefan; Layh, Beate; Ludwig, Andreas

    2011-12-01

    HCN pacemaker channels (I(f) channels) are believed to contribute to important functions in the heart; thus these channels became an attractive target for generating transgenic mouse mutants to elucidate their role in physiological and pathophysiological cardiac conditions. A full understanding of cardiac I(f) and the interpretation of studies using HCN mouse mutants require detailed information about the expression profile of the individual HCN subunits. Here we investigate the cardiac expression pattern of the HCN isoforms at the mRNA as well as at the protein level. The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals. We find a low, but highly differential HCN expression profile outside the cardiac conduction pathway including left and right atria and ventricles. Additionally HCN distribution was investigated in tissue slices of the sinoatrial node, the atrioventricular node, the bundle of His and the bundle branches. The conduction system was marked by acetylcholine esterase staining. HCN4 was confirmed as the predominant isoform of the primary pacemaker followed by a distinct expression of HCN1. In contrast HCN2 shows only a confined expression to individual pacemaker cells. Immunolabeling of the AV-node reveals also a pronounced specificity for HCN1 and HCN4. Compared to the SN and AVN we found a low but selective expression of HCN4 as the only isoform in the atrioventricular bundle. However in the bundle branches HCN1, HCN4 and also HCN2 show a prominent and selective expression pattern. Our results display a characteristic distribution of individual HCN isoforms in several cardiac compartments and reveal that beside HCN4, HCN1 represents the isoform which is selectively expressed in most parts of the conduction system suggesting a substantial contribution of HCN1 to pacemaking. 2011 Elsevier Ltd. All rights reserved.

  5. Physical inactivity at leisure and work: a 12-month study of cardiac patients.

    Science.gov (United States)

    Rogerson, Michelle C; Murphy, Barbara M; Le Grande, Michael R; Worcester, Marian U C

    2013-01-01

    Physical inactivity has been identified as a distinct health risk. However, little is known about how this can vary at leisure and work in cardiac patients. The aim of this study was to examine the prevalence and predictors of inactivity during leisure and work in the 12 months following a cardiac event in Australian cardiac patients. A total of 346 patients consecutively admitted to hospital with acute coronary syndrome or to undergo coronary artery bypass graft surgery were interviewed in hospital, and 4 and 12 months later. Leisure and occupational physical activity was measured using the Stanford Brief Activity Survey. Sociodemographic, psychosocial, and clinical data were also collected. The prevalence of leisure-time physical inactivity declined over time, with 52% inactive preevent and 29% inactive at 12 months. Approximately 50% of participants were physically inactive in their work, regardless of whether this was measured before or after the cardiac event. Logistic regression revealed that the significant predictors of leisure-time physical inactivity at 12 months were non-home ownership (OR = 2.19; P = .007) and physical inactivity in leisure-time prior to the event (OR = 2.44; P = .001). The significant predictors of occupational physical inactivity at 12 months were white-collar occupation (OR = 3.10; P physical inactivity at work prior to the event (OR = 12.99; P physical inactivity, socioeconomic, and clinical factors predicted both leisure and work inactivity after an acute cardiac event. Effective interventions could be designed and implemented to target those most at risk of being physically inactive at work or leisure.

  6. A Study on Oral Health of Children with Cardiac Diseases in Mashhad, Iran in 2004

    Directory of Open Access Journals (Sweden)

    Mohammad Mahmoudi

    2007-12-01

    Full Text Available

    Background and aims. Preventing oral disease is the most desirable way of ensuring good dental health for children with heart disease. Dental and gingival infections in patients with cardiac problems may lead to infective endocarditis. The aim of this study was to evaluate oral and dental health status in children with heart disease referred to a cardiac center compared with the control group.

    Materials and Methods. In this descriptive cross-sectional study, case group consisting of 100 patients 2-12 years old with heart disease were examined for oral and dental status in Pediatric Cardiac Center in Mashhad, Iran, in 2004. Fifty healthy children with the same age as the case group referring to the Department of Pedodontics, Mashhad Faculty of Dentistry served as the control group. For each patient, dental and medical history, dmft, DMFT, debris index, tooth brushing status as well as parental knowledge of infective endocarditis and their economic status was registered on a questionnaire. Statistical analysis was performed using Kruskal-Wallis, chi-square and t-tests.

    Results. There were no significant differences between case and control groups in dmft (3.92 ± 3.99 and 3.54 ± 3.33, respectively, DMFT (3.7 ± 4 and 1.47 ± 1.72, respectively and their components. Tooth brushing status and debris index were significantly worse in the study group (P = 0.001 and P = 0.008, respectively. 35% of parents were aware of the importance of good oral health in cardiac children although none of them knew about infective endocarditis. Most of the parents in study group had low (30% to medium (53% economic status.

    Conclusion. In this study, the children with cardiac disease did not have a good oral and dental health status. Developing strategies toward preventive dental care of children with cardiac problems and informing their parents is suggested.

  7. Advantages of a cohort study on cardiac arrest conducted by nurses

    Directory of Open Access Journals (Sweden)

    Cássia Regina Vancini Campanharo

    2015-10-01

    Full Text Available AbstractOBJECTIVEIdentifying factors associated to survival after cardiac arrest.METHODAn experience report of a cohort study conducted in a university hospital, with a consecutive sample comprised of 285 patients. Data were collected for a year by trained nurses. The training strategy was conducted through an expository dialogue lecture. Collection monitoring was carried out by nurses via telephone calls, visits to the emergency room and by medical record searches. The neurological status of survivors was evaluated at discharge, after six months and one year.RESULTSOf the 285 patients, 16 survived until hospital discharge, and 13 remained alive after one year, making possible to identify factors associated with survival. There were no losses in the process.CONCLUSIONCohort studies help identify risks and disease outcomes. Considering cardiac arrest, they can subsidize public policies, encourage future studies and training programs for CPR, thereby improving the prognosis of patients.

  8. Echocardiographic study of cardiac dysfunction in patients of chronic kidney disease on hemodialysis

    International Nuclear Information System (INIS)

    Arshi, S.; Butt, G.U.D.; Mian, F.A.

    2016-01-01

    Objective: The objective of this study was to see echocardiographic findings of cardiac dysfunction in patients of chronic kidney disease (CKD) on hemodialysis. Study Design: Comparative cross sectional study. Place and Duration of Study: Department of nephrology, Pakistan Institute of Medical Sciences. Islamabad from September 2014 to February 2015. Patients and Methods: One hundred patients of either gender were included in this study. Fifty patients of chronic kidney disease stage V on hemodialysis were taken for echocardiography and fifty were normal. Echocardiography was done for cardiac dysfunction. Systolic function was measured by ejection fraction (EF) and fractional shortening (FS). Diastolic function was measured by E/A ratio. Results: Out of 100 patients included in the study, 50 patients were on hemodialysis and 50 were control. Left ventricular end systolic and end diastolic volumes were higher in patients on hemodialysis than controls as well as left atrial enlargement and inter ventricular septum which was statistically significant. Ejection fraction, although normal and fractional shortening decreased in patients on hemodialysis (p<0.05). Diastolic dysfunction was present in 36 patients on hemodialysis, while absent in the control group. Conclusion: Patients with chronic kidney disease on hemodialysis have higher prevalence of cardiac dysfunction. (author)

  9. A secondary meta-synthesis of qualitative studies of gender and access to cardiac rehabilitation.

    Science.gov (United States)

    Angus, Jan E; King-Shier, Kathryn M; Spaling, Melisa A; Duncan, Amanda S; Jaglal, Susan B; Stone, James A; Clark, Alexander M

    2015-08-01

    To discuss issues in the theorization and study of gender observed during a qualitative meta-synthesis of influences on uptake of secondary prevention and cardiac rehabilitation services. Women and men can equally benefit from secondary prevention/cardiac rehabilitation and there is a need to understand gender barriers to uptake. Meta-method analysis secondary to meta-synthesis. For the meta-synthesis, a systematic search was performed to identify and retrieve studies published as full papers during or after 1995 and contained: a qualitative research component wholly or in a mixed method design, extractable population specific data or themes for referral to secondary prevention programmes and adults ≥18 years. Databases searched between January 1995-31 October 2011 included: CSA Sociological Abstracts, EBSCOhost CINAHL, EBSCOhost Gender Studies, EBSCOhost Health Source Nursing: Academic Edition, EBSCOhost SPORTDiscus, EBSCOhost SocINDEX. Studies were reviewed against inclusion/exclusion criteria. Included studies were subject to quality appraisal and standardized data extraction. Of 2264 screened articles, 69 were included in the meta-method analysis. Only four studies defined gender or used gender theories. Findings were mostly presented as inherently the characteristic of gendered worldviews of participants. The major themes suggest a mismatch between secondary prevention/cardiac rehabilitation services and consumers' needs, which are usually portrayed as differing according to gender but may also be subject to intersecting influences such as age or socioeconomic status. There is a persistent lack of theoretically informed gender analysis in qualitative literature in this field. Theory-driven gender analysis will improve the conceptual clarity of the evidence base for gender-sensitive cardiac rehabilitation programme development. © 2015 John Wiley & Sons Ltd.

  10. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    Fiandra, O.; Espasandin, W.; Fiandra, H.

    1984-01-01

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  11. a-Adrenergic vasoconstrictor responsiveness is preserved in the heated human leg

    DEFF Research Database (Denmark)

    Keller, David M; Sander, Mikael; Stallknecht, Bente Merete

    2010-01-01

    This study tested the hypothesis that passive leg heating attenuates a-adrenergic vasoconstriction within that limb. Femoral blood flow (FBF, femoral artery ultrasound Doppler) and femoral vascular conductance (FVC, FBF/mean arterial blood pressure), as well as calf muscle blood flow (Calf...

  12. Astrocytic beta 2 Adrenergic Receptor Gene Deletion Affects Memory in Aged Mice

    NARCIS (Netherlands)

    Jensen, Cathy Joanna; Demol, Frauke; Bauwens, Romy; Kooijman, Ron; Massie, Ann; Villers, Agnes; Ris, Laurence; De Keyser, Jacques

    2016-01-01

    In vitro and in vivo studies suggest that the astrocytic adrenergic signalling enhances glycogenolysis which provides energy to be transported to nearby cells and in the form of lactate. This energy source is important for motor and cognitive functioning. While it is suspected that the beta

  13. Substrate utilization and thermogenic responses to beta-adrenergic stimulation in obese subjects with NIDDM.

    NARCIS (Netherlands)

    Blaak, E.E.; Saris, W.H.M.; Wolffenbuttel, B.H.R.

    1999-01-01

    OBJECTIVE: This study intended to investigate disturbances in beta-adrenergically-mediated substrate utilization and thermogenesis in obese subjects with mild non insulin-dependent diabetes mellitus (NIDDM). DESIGN: Following a baseline period of 30 min, the beta-agonist isoproterenol (ISO) was

  14. Substrate utilization and thermogenic responses to beta-adrenergic stimulation in obese subjects with NIDDM

    NARCIS (Netherlands)

    Blaak, E E; Saris, W H; Wolffenbuttel, B H

    OBJECTIVE: This study intended to investigate disturbances in beta-adrenergically-mediated substrate utilization and thermogenesis in obese subjects with mild non insulin-dependent diabetes mellitus (NIDDM). DESIGN: Following a baseline period of 30 min, the beta-agonist isoproterenol (ISO) was

  15. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function

    DEFF Research Database (Denmark)

    Rosenbaum, Daniel M; Cherezov, Vadim; Hanson, Michael A

    2007-01-01

    The beta2-adrenergic receptor (beta2AR) is a well-studied prototype for heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the beta2AR and to facilitate its cr...

  16. An elevated respiratory quotient predicts complications after cardiac surgery under extracorporeal circulation: an observational pilot study.

    Science.gov (United States)

    Piot, J; Hébrard, A; Durand, M; Payen, J F; Albaladejo, P

    2018-04-17

    Following cardiac surgery, hyperlactatemia due to anaerobic metabolism is associated with an increase in both morbidity and mortality. We previously found that an elevated respiratory quotient (RQ) predicts anaerobic metabolism. In the present study we aimed to demonstrate that it is also associated with poor outcome following cardiac surgery. This single institution, prospective, observational study includes all those patients that were consecutively admitted to the intensive care unit (ICU) after cardiac surgery with cardiopulmonary bypass, that had also been monitored using pulmonary artery catheter. Data were recorded at admission (H0) and after one hour (H1) including: oxygen consumption ([Formula: see text]), carbon dioxide production ([Formula: see text]), RQ ([Formula: see text]), lactate levels and mixed venous oxygen saturation ([Formula: see text]). The primary endpoint was defined as mortality at 30 days. Comparison of the area under the curve (AUC) for receiver operating characteristic curves was used to analyze the prognostic predictive value of RQ, lactate levels and [Formula: see text], in terms of patient outcome. We studied 151 patients admitted to the ICU between May 2015 and February 2016. Seventy eight patients experienced a worse than expected outcome in the post-operative period, and among those seven died. RQ at H1 in non-survivors ([Formula: see text]) was higher than in survivors ([Formula: see text]; p = 0.02). The AUC for RQ to predict mortality was 0.77 (IC 95% [0.70-0.84]), with a threshold value of 0.76 (sensitivity 64%, specificity 100%). By comparison, the AUC for lactate levels was significantly superior (AUClact 0.89, IC 95% [0.83-0.93], p = 0.02). In this study, elevated RQ appeared to be predictive of mortality after cardiac surgery with CPB.

  17. β-Adrenergic signaling is required for the induction of a labile state during memory reconsolidation.

    Science.gov (United States)

    Lim, Chae-Seok; Kim, Jae-Ick; Kwak, Chuljung; Lee, Jaehyun; Jang, Eun Hae; Oh, Jihae; Kaang, Bong-Kiun

    2018-04-20

    Memory reconsolidation is the process by which previously consolidated memories reenter a labile state through reactivation of the memory trace and are actively consolidated through de novo protein synthesis. Although extensive studies have shown that β-adrenergic signaling plays a critical role in the restabilization of reactivated memory, its role in the destabilization of long-term memory is not well-studied. In this study, we found that membrane excitability increased in hippocampal CA1 neurons immediately after the retrieval of contextual fear memory. Interestingly, this increase in membrane excitability diminished after treatment with propranolol (a β-adrenergic receptor antagonist), an NMDA receptor antagonist, and a PKA inhibitor. In addition, we found that administration of propranolol prior to, but not after, the retrieval of fear memory ameliorated the memory impairment caused by anisomycin, indicating that inhibition of β-adrenergic signaling blocks the destabilization of contextual fear memory. Taken together, these results indicate that β-adrenergic signaling via NMDA receptors and PKA signaling pathway induces a labile state of long-term memory through increased neuronal membrane excitability. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. The role of adrenergic activation on murine luteal cell viability and progesterone production.

    Science.gov (United States)

    Wang, Jing; Tang, Min; Jiang, Huaide; Wu, Bing; Cai, Wei; Hu, Chuan; Bao, Riqiang; Dong, Qiming; Xiao, Li; Li, Gang; Zhang, Chunping

    2016-09-15

    Sympathetic innervations exist in mammalian CL. The action of catecholaminergic system on luteal cells has been the focus of a variety of studies. Norepinephrine (NE) increased progesterone secretion of cattle luteal cells by activating β-adrenoceptors. In this study, murine luteal cells were treated with NE and isoprenaline (ISO). We found that NE increased the viability of murine luteal cells and ISO decreased the viability of luteal cells. Both NE and ISO promoted the progesterone production. Nonselective β-adrenergic antagonist, propranolol reversed the effect of ISO on cell viability but did not reverse the effect of NE on cell viability. Propranolol blocked the influence of NE and ISO on progesterone production. These results reveal that the increase of luteal cell viability induced by NE is not dependent on β-adrenergic activation. α-Adrenergic activation possibly contributes to it. Both NE and ISO increased progesterone production through activating β-adrenergic receptor. Further study showed that CyclinD2 is involved in the increase of luteal cell induced by NE. 3β-Hydroxysteroid dehydrogenase, LHR, steroidogenic acute regulatory protein (StAR), and PGF2α contribute to the progesterone production induced by NE and ISO. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Self-gated fetal cardiac MRI with tiny golden angle iGRASP: A feasibility study.

    Science.gov (United States)

    Haris, Kostas; Hedström, Erik; Bidhult, Sebastian; Testud, Frederik; Maglaveras, Nicos; Heiberg, Einar; Hansson, Stefan R; Arheden, Håkan; Aletras, Anthony H

    2017-07-01

    real-time images, albeit not statistically significant in this feasibility study (P > 0.99 and P = 0.12, respectively). Fetal cardiac cine MRI can be performed with iGRASP using tiny golden angles and CSG. Comparison with other fetal cardiac cine MRI methods showed that the proposed method produces high-quality fetal cardiac reconstructions. 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:207-217. © 2017 International Society for Magnetic Resonance in Medicine.

  20. New radioiodinated methyl-branched fatty acids for cardiac studies

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Ambrose, K.R.; Goodman, M.M.

    1985-01-01

    The effects of 3-methyl-substitution on the heart retention and metabolism of 3-R,S-methyl-(BMIPP) and 3,3-dimethyl-(DMIPP) analogues of 15-(p-iodophenyl)-pentadecanoic acid (IPP) have been studied in rats. Methyl-substitution considerably increased the myocardial half-time values in fasted rats: IPP, 5 to 10 min; BMIPP, 30 to 45 min; DMIPP, 6 to 7 h. Because of the observed differences in the relative myocardial uptake and retention of these agents, an evaluation of the subcellular distribution profiles and the distribution of radioactivity within various lipid pools extracted from cell components was performed. Studies with DMIPP in fasted rats have shown high levels of the free fatty acid and only slow conversion to triglycerides. These data are in contrast to the rapid clearance of the straight chain IPP analogue and rapid incorporation into triglycerides. These data suggest that the prolonged myocardial retention observed with DMIPP in vivo may result from inhibition of β-oxidation. Subcellular distribution studies have shown predominate association of DMIPP and BMIPP with the mitochondrial and microsomal fractions, while IPP was primarily found in the cytoplasm. Because of the unique ''trapping'' properties and the high heart:blood ratios, [ 123 I]DMIPP should be useful for evaluation of aberrations in regional myocardial uptake. 7 refs., 9 figs., 1 tab

  1. New radioiodinated methyl-branched fatty acids for cardiac studies

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Ambrose, K.R.; Goodman, M.M.

    1986-01-01

    The effects of 3-methyl substitution on the heart retention and metabolism of 3-R,S-methyl-(BMIPP) and 3,3-dimethyl-(DMIPP) analogues of 15-(p-iodophenyl)-pentadecanoic acid (IPP) were studied in rats. Methyl substitution considerably increased the myocardial half-time values in fasted rats: IPP, 5-10 min; BMIPP, 30-45 min; DMIPP, 6-7 h. Because of the observed differences in the relative myocardial uptake and retention of these agents, an evaluation of the subcellular distribution profiles and the distribution of radioactivity within various lipid pools extracted from cell components was performed. Studies with DMIPP in food-deprived rats have shown high levels of the free fatty acid and only slow conversion to triglycerides. These data are in contrast to the rapid clearance of the straight chain IPP analogue and rapid incorporation into triglycerides, and suggest that the prolonged myocardial retention observed with DMIPP in vivo may result from inhibition of β oxidation. Subcellular distribution studies have shown predominant association of DMIPP and BMIPP with the mitochondrial and microsomal fractions, while IPP was primarily found in the cytoplasm. Because of the unique ''trapping'' properties and the high heart: blood ratios, [ 123 I]DMIPP should be useful for evaluation of aberrations in regional myocardial uptake. (orig.)

  2. Iodine-123 metaiodobenzylguanidine in the assessment of late cardiac effects from cancer therapy

    International Nuclear Information System (INIS)

    Valdes Olmos, R.A.; Bokkel Huinink, W.W. ten; Dewit, L.G.H.; Hoefnagel, C.A.; Liem, I.H.; Tinteren, H. van

    1996-01-01

    Recognition of adverse late cardiac effects from cancer therapy may enable identification of patients with risk of cardiotoxicity upon cancer retreatment. In this study the feasibility of using iodine-123 metaiodobenzylguanidine ( 123 I-MIBG) heart scintigraphy to detect abnormalities of the myocardial adrenergic neurone function in the late period after cancer therapy was evaluated in relation to the left ventricle ejection fraction (LVEF) in 18 cancer patients: 11 had undergone thoracic irradiation involving the heart, in five cases in combination with anthracycline therapy, 11-228 months (median 60 months) before radionuclide tests, while seven had not received previous anthracycline and/or radiotherapy (controls). The 123 I-MIBG cardiac uptake, expressed as a heart-to-mediastinum ratio on planar images after 4 h, ranged from 1.21 to 1.76 (median 1.56) in cancer therapy patients, which was significantly decreased (P=0.0006) in comparison with controls (range 1.81-2.06, median 1.9). The myocardial 123 I-MIBG washout, calculated from planar images after 15 min and 4 h, and LVEF also showed significant differences, but with some overlap in individual cases. In cancer therapy patients, cardiac abnormalities seen on planar images and additional single-photon emission tomographic images varied from focal defects to diffusely reduced myocardial uptake. It is concluded that 123 I-MIBG heart scintigraphy, which is able to identify cardiac adrenergic neurone abnormalities in the follow-up period after cancer therapy, may help to identify relapsed patients who are at increased risk of developing cardiotoxicity during retreatment with cardiotoxic therapy modalities. (orig.). With 4 figs., 2 tabs

  3. Rheumatic heart disease- a study of surgically excised cardiac valves and biopsies

    International Nuclear Information System (INIS)

    Khalil Ullah; Badsha, S.; Khan, A.; Kiani, M.R.; Ahmed, S.A.

    2002-01-01

    Objective: To examine the prevalence, age, sex and topographical distribution of the rheumatic heart diseases and its morphology. Design: A cross sectional descriptive study. Place and Duration of Study: Pathology Department, Army Medical College, Rawalpindi between 1981-1990. Patients and Methods: Five hundred and twenty six surgically excised cardiac valves and biopsies were studied in the laboratory in the light of clinical data. Results: Carditis constituted 87.4 % of the cardiac valvular disease with 23.5% active and 71% healed rheumatic lesions. About 5.5% had morphological appearances consistent with RHD. The lesions affected mitral valves (37.0%), aortic valve (22.1%), mitral and aortic valves together (21.0%) and atrial appendages (19.0%). Presentation was mostly as mitral stenosis either isolated (49.2% ) or combined (31.0%), aortic stenosis (11.7% ) and aortic incompetence with regurgitation (7.3%). Conclusion: Rheumatic carditis constitutes a significant proportion of cardiac valvular disease and affects comparatively younger age, with slight male preponderance and primarily affects mitral valve. (author)

  4. Noise removal using factor analysis of dynamic structures: application to cardiac gated studies.

    Science.gov (United States)

    Bruyant, P P; Sau, J; Mallet, J J

    1999-10-01

    Factor analysis of dynamic structures (FADS) facilitates the extraction of relevant data, usually with physiologic meaning, from a dynamic set of images. The result of this process is a set of factor images and curves plus some residual activity. The set of factor images and curves can be used to retrieve the original data with reduced noise using an inverse factor analysis process (iFADS). This improvement in image quality is expected because the inverse process does not use the residual activity, assumed to be made of noise. The goal of this work is to quantitate and assess the efficiency of this method on gated cardiac images. A computer simulation of a planar cardiac gated study was performed. The simulated images were added with noise and processed by the FADS-iFADS program. The signal-to-noise ratios (SNRs) were compared between original and processed data. Planar gated cardiac studies from 10 patients were tested. The data processed by FADS-iFADS were subtracted to the original data. The result of the substraction was studied to evaluate its noisy nature. The SNR is about five times greater after the FADS-iFADS process. The difference between original and processed data is noise only, i.e., processed data equals original data minus some white noise. The FADS-iFADS process is successful in the removal of an important part of the noise and therefore is a tool to improve the image quality of cardiac images. This tool does not decrease the spatial resolution (compared with smoothing filters) and does not lose details (compared with frequential filters). Once the number of factors is chosen, this method is not operator dependent.

  5. Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats.

    Directory of Open Access Journals (Sweden)

    Peter Nordbeck

    Full Text Available BACKGROUND: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. METHODS: Female Wistar rats (n = 6 per group were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. RESULTS: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05 and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05 after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw, such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05, or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05. Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass, but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. CONCLUSION: Cardio-thoracic surgical procedures in experimental myocardial infarction

  6. Model-based estimation for dynamic cardiac studies using ECT

    International Nuclear Information System (INIS)

    Chiao, P.C.; Rogers, W.L.; Clinthorne, N.H.; Fessler, J.A.; Hero, A.O.

    1994-01-01

    In this paper, the authors develop a strategy for joint estimation of physiological parameters and myocardial boundaries using ECT (Emission Computed Tomography). The authors construct an observation model to relate parameters of interest to the projection data and to account for limited ECT system resolution and measurement noise. The authors then use a maximum likelihood (ML) estimator to jointly estimate all the parameters directly from the projection data without reconstruction of intermediate images. The authors also simulate myocardial perfusion studies based on a simplified heart model to evaluate the performance of the model-based joint ML estimator and compare this performance to the Cramer-Rao lower bound. Finally, model assumptions and potential uses of the joint estimation strategy are discussed

  7. Model-based estimation for dynamic cardiac studies using ECT.

    Science.gov (United States)

    Chiao, P C; Rogers, W L; Clinthorne, N H; Fessler, J A; Hero, A O

    1994-01-01

    The authors develop a strategy for joint estimation of physiological parameters and myocardial boundaries using ECT (emission computed tomography). They construct an observation model to relate parameters of interest to the projection data and to account for limited ECT system resolution and measurement noise. The authors then use a maximum likelihood (ML) estimator to jointly estimate all the parameters directly from the projection data without reconstruction of intermediate images. They also simulate myocardial perfusion studies based on a simplified heart model to evaluate the performance of the model-based joint ML estimator and compare this performance to the Cramer-Rao lower bound. Finally, the authors discuss model assumptions and potential uses of the joint estimation strategy.

  8. Nationwide study of sudden cardiac death in persons aged 1-35 years

    DEFF Research Database (Denmark)

    Winkel, Bo Gregers; Holst, Anders Gaarsdal; Theilade, Juliane

    2011-01-01

    Aims The aim of this investigation was to study the incidence of sudden cardiac death (SCD) in persons aged 1-35 years in a nationwide setting (5.38 million people) by systematic evaluation of all deaths. Methods and results All deaths in persons aged 1-35 years in Denmark in 2000-06 were included....... Death certificates were read independently by two physicians. The National Patient Registry was used to retrieve information on prior medical history. All autopsy reports were read and the cause of death was revised based on autopsy findings. We identified 625 cases of sudden unexpected death (10......% of all deaths), of which 156 (25%) were not autopsied. Of the 469 autopsied cases, 314 (67%) were SCD. The most common cardiac cause of death was ischaemic heart disease (13%); 29% of autopsied sudden unexpected death cases were unexplained. In 45% of SCD cases, the death was witnessed; 34% died during...

  9. Electro-resistive bands for non-invasive cardiac and respiration monitoring, a feasibility study

    International Nuclear Information System (INIS)

    Gargiulo, Gaetano D; Breen, Paul P; O’Loughlin, Aiden

    2015-01-01

    Continuous unobtrusive monitoring of tidal volume, particularly for critical care patients (i.e. neonates and patients in intensive care) during sleep studies and during daily activities, is still an unresolved monitoring need. Also a successful monitoring solution is yet to be proposed for continuous non-invasive cardiac stroke volume monitoring that is a novel clinical need. In this paper we present the feasibility study for a wearable, non-invasive, non-contact and unobtrusive sensor (embedded in a standard T-shirt) based on four electro-resistive bands that simultaneously monitors tidal volume and cardiac stroke volume changes. This low power sensor system (requires only 100 mW and accepts a wide power supply range up to ±18 V); thus the sensor can be easily embedded in existing wearable solutions (i.e. Holter monitors). Moreover, being contactless, it can be worn over bandages or electrodes, and as it does not rely over the integrity of the garment to work, it allows practitioners to perform procedures during monitoring. For this preliminary evaluation, one subject has worn the sensor over the period of 24 h (removing it only to shower); the accuracy of the tidal volume tested against a portable spirometer reported a precision of ±10% also during physical activity; accuracy tests for cardiac output (as it may require invasive procedure) have not been carried out in this preliminary trial. (note)

  10. Data on cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results.

    Science.gov (United States)

    Calcagni, Giulio; Limongelli, Giuseppe; D'Ambrosio, Angelo; Gesualdo, Francesco; Digilio, Maria Cristina; Baban, Anwar; Albanese, Sonia B; Versacci, Paolo; De Luca, Enrica; Ferrero, Giovanni B; Baldassarre, Giuseppina; Agnoletti, Gabriella; Banaudi, Elena; Marek, Jan; Kaski, Juan P; Tuo, Giulia; Russo, Maria Giovanna; Pacileo, Giuseppe; Milanesi, Ornella; Messina, Daniela; Marasini, Maurizio; Cairello, Francesca; Formigari, Roberto; Brighenti, Maurizio; Dallapiccola, Bruno; Tartaglia, Marco; Marino, Bruno

    2018-02-01

    A comprehensive description of morbidity and mortality in patients affected by mutations in genes encoding for signal transducers of the RAS-MAPK cascade (RASopathies) was performed in our study recently published in the International Journal of Cardiology. Seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET), collaborated in this multicentric, observational, retrospective data analysis and collection. In this study, clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Cardiac defects, crude mortality, survival rate of patients with 1) hypertrophic cardiomyopathy (HCM) and age Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations; 3) biventricular obstruction and PTPN11 mutations; 4) Costello syndrome or cardiofaciocutaneous syndrome were analysed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. In particular, with this Data In Brief (DIB) paper, the authors aim to report specific statistic highlights of the multivariable regression analysis that was used to assess the impact of mutated genes on number of interventions and overall prognosis.

  11. Can Tranexamic Acid Reduce Blood Loss during Major Cardiac Surgery? A Pilot Study.

    Science.gov (United States)

    Compton, Frances; Wahed, Amer; Gregoric, Igor; Kar, Biswajit; Dasgupta, Amitava; Tint, Hlaing

    2017-09-01

    We examined the effectiveness of tranexamic acid in preventing intraoperative blood loss during major cardiac surgery. Out of initial 81 patients undergoing major cardiac surgery (both coronary artery bypass and valve repair procedures) at our teaching hospital, sixty-seven patients were selected for this study. We compared estimated blood loss, decrease in percent hemoglobin and hematocrit following surgery between two groups of patients (none of them received any blood product during surgery), one group receiving no tranexamic acid (n=17) and another group receiving tranexamic acid (n=25). In the second study, we combined these patients with patients receiving modest amounts of blood products (1-2 unit) and compared these parameters between two groups of patients (25 patients received no tranexamic acid, 42 patients received tranexamic acid). In patients who received no blood product during surgery, those who received no tranexamic acid showed statistically significant (independent t-test two tailed at p tranexamic acid (mean: 987.2 mL, SD: 459.9, n=25). We observed similar results when the patients receiving no blood products and patients receiving modest amount of blood products were combined based on the use of tranexamic acid or not. No statistically significant difference was observed in percent reduced hemoglobin or hematocrit following surgery in any group of patients. We conclude that intraoperative antifibrinolytic therapy with tranexamic acid does not reduce intraoperative blood loss during major cardiac surgery which contradicts popular belief. © 2017 by the Association of Clinical Scientists, Inc.

  12. Barriers to nurse-patient communication in cardiac surgery wards: a qualitative study.

    Science.gov (United States)

    Shafipour, Vida; Mohammad, Eesa; Ahmadi, Fazlollah

    2014-08-15

    An appropriate and effective nurse-patient communication is of the most important aspect of caring. The formation and continuation of such a relationship depends on various factors such as the conditions and context of communication and a mutual understanding between the two. A review of the literature shows that little research is carried out on identification of such barriers in hospital wards between the patients and the healthcare staff. The present study was therefore conducted to explore the experiences of nurses and patients on communication barriers in hospital cardiac surgery wards. This qualitative research was carried out using a content analysis method (Graneheim & Lundman, 2004). The participants were selected by a purposeful sampling and consist of 10 nurses and 11 patients from the cardiac surgery wards of three teaching hospitals in Tehran, Iran. Data was gathered by unstructured interviews. All interviews were audio-taped and transcribed verbatim. Findings were emerged in three main themes including job dissatisfaction (with the sub-themes of workload tension and decreased motivation), routine-centered care (with the sub-themes of habitual interventions, routinized and technical interventions, and objective supervision), and distrust in competency of nurses (with the sub-themes of cultural contrast, less responsible nurses, and their apathy towards the patients). Compared to other studies, our findings identified different types of communication barriers depending on the nursing settings. These findings can be used by the ward clinical nursing managers at cardiac surgery wards to improve the quality of nursing care.

  13. Data on cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results

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    Giulio Calcagni

    2018-02-01

    Full Text Available A comprehensive description of morbidity and mortality in patients affected by mutations in genes encoding for signal transducers of the RAS-MAPK cascade (RASopathies was performed in our study recently published in the International Journal of Cardiology. Seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET, collaborated in this multicentric, observational, retrospective data analysis and collection. In this study, clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Cardiac defects, crude mortality, survival rate of patients with 1 hypertrophic cardiomyopathy (HCM and age <2 years or young adults; 2 individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations; 3 biventricular obstruction and PTPN11 mutations; 4 Costello syndrome or cardiofaciocutaneous syndrome were analysed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. In particular, with this Data In Brief (DIB paper, the authors aim to report specific statistic highlights of the multivariable regression analysis that was used to assess the impact of mutated genes on number of interventions and overall prognosis.

  14. Circulating histones for predicting prognosis after cardiac surgery: a prospective study.

    Science.gov (United States)

    Gao, Hongxiang; Zhang, Naipu; Lu, Fangfang; Yu, Xindi; Zhu, Limin; Mo, Xi; Wang, Wei

    2016-11-01

    The objective of this study was to assess the perioperative changes in circulating histones and their relationships with other biomarkers and clinical outcomes after cardiac surgery with cardiopulmonary bypass (CPB) in patients. Forty-eight patients with congenital cardiac diseases undergoing corrective procedure with CPB were prospectively enrolled in this study. Circulating histones, N-terminal pro-brain natriuretic peptide (NT-proBNP), procalcitonin (PCT) and C-reactive protein (CRP) were measured preoperatively (T0) and at 0 (T1), 24 (T2), 48 (T3) and 72 (T4) h postoperatively. The relationships between biomarkers and clinical outcomes were analysed. Circulating histones, NT-proBNP, PCT and CRP increased significantly postoperatively, with histones reaching the peak value earliest at T1. Circulating histone levels were higher in patients with adverse events. Receiver operating characteristic curve analysis showed that peak histone levels had a better predictive value for adverse events postoperatively. Peak histone levels correlated with the peak level of NT-proBNP (r = 0.563, P histones reached peak levels faster than NT-proBNP, PCT and CRP. Furthermore, peak histone levels correlated with biomarkers and postoperative clinical outcomes. Circulating histones may be used as a prognostic indicator for patients after cardiac surgery with CPB. ClinicalTrials.gov (ID: NCT02325765). © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  15. Cardiac events in patients with positive exercise ECG and normal myocardial perfusion scan - a retrospective study

    International Nuclear Information System (INIS)

    Marshman, K.; Thomson, L.E.J.; Rowe, C.C.; Burns, A.J.; Woon, F.S.

    2002-01-01

    Full text: The low risk of future cardiac events following a normal myocardial perfusion study with normal stress ECG has been well documented. However, there is little literature regarding the prognosis in patients with a positive stress ECG (PosETT) and normal myocardial perfusion scan (MPS). A search of our database over an eighteen month period identified 21 patients who fitted study criteria. A PosETT was defined as stress induced horizontal or downsloping ST depression > 1mm in one or more leads with a normal baseline 12 lead ECG. Patients were divided into two subgroups depending on the severity of ST depression. A mildly PosETT was defined as ST depression of 1-1.5mm (n=10) and strongly PosETT was defined as ST depression of >2mm in at least one lead with depression in other leads (n=l 1). A normal MPS was defined as absence of reversible perfusion defects on SPECT imaging. Technetium 99m Tetrofosmin was the imaging agent used in 18/21 patients. All 21 patients exercised using the Bruce protocol for 3-12 minutes, and 9 experienced chest pain 12 months after the MPS, referring physicians were contacted. Cardiac events were defined as cardiac death, myocardial infarction, unstable angina, cardiac failure, revascularisation or a coronary angiogram demonstrating >70% stenosis. To date, follow up is complete in 11 patients with one confirmed case of single vessel revascularisation 3 months post MPS. Full follow up data will be presented. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  16. Electrophysiological evaluation of phrenic nerve injury during cardiac surgery – a prospective, controlled, clinical study

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    Ege Turan

    2004-01-01

    Full Text Available Abstract Background According to some reports, left hemidiaphragmatic paralysis due to phrenic nerve injury may occur following cardiac surgery. The purpose of this study was to document the effects on phrenic nerve injury of whole body hypothermia, use of ice-slush around the heart and mammary artery harvesting. Methods Electrophysiology of phrenic nerves was studied bilaterally in 78 subjects before and three weeks after cardiac or peripheral vascular surgery. In 49 patients, coronary artery bypass grafting (CABG and heart valve replacement with moderate hypothermic (mean 28°C cardiopulmonary bypass (CPB were performed. In the other 29, CABG with beating heart was performed, or, in several cases, peripheral vascular surgery with normothermia. Results In all patients, measurements of bilateral phrenic nerve function were within normal limits before surgery. Three weeks after surgery, left phrenic nerve function was absent in five patients in the CPB and hypothermia group (3 in CABG and 2 in valve replacement. No phrenic nerve dysfunction was observed after surgery in the CABG with beating heart (no CPB or the peripheral vascular groups. Except in the five patients with left phrenic nerve paralysis, mean phrenic nerve conduction latency time (ms and amplitude (mV did not differ statistically before and after surgery in either group (p > 0.05. Conclusions Our results indicate that CPB with hypothermia and local ice-slush application around the heart play a role in phrenic nerve injury following cardiac surgery. Furthermore, phrenic nerve injury during cardiac surgery occurred in 10.2 % of our patients (CABG with CPB plus valve surgery.

  17. Pediatric cardiac surgery Parent Education Discharge Instruction (PEDI) program: a pilot study.

    Science.gov (United States)

    Staveski, Sandra L; Zhelva, Bistra; Paul, Reena; Conway, Rosalind; Carlson, Anna; Soma, Gouthami; Kools, Susan; Franck, Linda S

    2015-01-01

    In developing countries, more children with complex cardiac defects now receive treatment for their condition. For successful long-term outcomes, children also need skilled care at home after discharge. The Parent Education Discharge Instruction (PEDI) program was developed to educate nurses on the importance of discharge teaching and to provide them with a structured process for conducting parent teaching for home care of children after cardiac surgery. The aim of this pilot study was to generate preliminary data on the feasibility and acceptability of the nurse-led structured discharge program on an Indian pediatric cardiac surgery unit. A pre-/post-design was used. Questionnaires were used to evaluate role acceptability, nurse and parent knowledge of discharge content, and utility of training materials with 40 nurses and 20 parents. Retrospective audits of 50 patient medical records (25 pre and 25 post) were performed to evaluate discharge teaching documentation. Nurses' discharge knowledge increased from a mean of 81% to 96% (P = .001) after participation in the training. Nurses and parents reported high levels of satisfaction with the education materials (3.75-4 on a 4.00-point scale). Evidence of discharge teaching documentation in patient medical records improved from 48% (12 of 25 medical records) to 96% (24 of 25 medical records) six months after the implementation of the PEDI program. The structured nurse-led parent discharge teaching program demonstrated feasibility, acceptability, utility, and sustainability in the cardiac unit. Future studies are needed to examine nurse, parent, child, and organizational outcomes related to this expanded nursing role in resource-constrained environments. © The Author(s) 2014.

  18. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

    Science.gov (United States)

    Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

    2016-01-01

    Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

  19. A STUDY ON ASYMPTOMATIC CARDIAC CHANGES IN TYPE 2 DIABETES PATIENTS

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    Ramchandra Rao

    2015-06-01

    Full Text Available INTRODUCTION: Majority of the time the patient of Diabetes presents with complications like Myocardial infarction, heart failure, being end stages of cardiovascular 2 disease associated with other macro and microvascular complications. If patients are screened at an early stage of Diabetes before the onset of symptoms the cardiovascular complications can be delayed and mortality can be reduced . There are only few studies in India done to screen asymptomatic diabetic individuals for cardiovascular compli cations. This study is done in view of screening the asymptomatic individuals in our area to prevent complications. With the available infrastructure, ECG, 2D ECHO were done in 50 patients who met inclusion, exclusion criterias, the changes were noted and the cardiac status was evaluated. AIM AND OBJECTIVES : “To study the asymptomatic cardiac changes in type2 Diabetes patients”. To observe the ECG changes in patients of type2 Diabetes without any symptoms of cardiac disease. To evaluate the ECG changes along with 2DECHO findings in asymptomatic cardiac patients of type 2 Diabetes. To study the correlation between these two investigations and evaluate the cardiac status of the individual. CONCLUSIONS : M ost of the patients in study group belong to 5 th decade , Males with Diabetes were almost double that of females , Most of the patients had duration of Diabetes as 5yrs , Less than half of patients had family history of Diabetes , Half of the group had alcohol, smoking habits , More than half of patients were overweight , Only 20% had good control of Diabetes , Total cholesterol is above normal in almost all of the patients, LDL is elevated in half of the patients, triglycerides in most of them, there is significant dyslipidemia in patients of Diabetes , Only 6 had normal ECG. Rest of them have LVH, ischemia , 18 patients had changes in echo including LVD, regional and global hypokinesias , t hus the present study shows patients with type 2

  20. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study

    NARCIS (Netherlands)

    Janssens, Karin A. M.; Riese, Harriette; Van Roon, Arie M.; Hunfeld, Joke A. M.; Groot, Paul F. C.; Oldehinkel, Albertine J.; Rosmalen, Judith G. M.

    2016-01-01

    Objective Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac

  1. Outcome after resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia : Dutch nationwide retrospective cohort study

    NARCIS (Netherlands)

    Kieboom, J. K.; Verkade, H. J.; Burgerhof, J. G.; Bierens, J. J.; van Rheenen, P. F.; Kneyber, M. C.; Albers, M. J.

    2015-01-01

    OBJECTIVES To evaluate the outcome of drowned children with cardiac arrest and hypothermia, and to determine distinct criteria for termination of cardiopulmonary resuscitation in drowned children with hypothermia and absence of spontaneous circulation. DESIGN Nationwide retrospective cohort study.

  2. Interaction between Ca++-channel antagonists and α2-adrenergic receptors in rabbit ileal cell membrane

    International Nuclear Information System (INIS)

    Homeidan, F.R.; Wicks, J.; Cusolito, S.; El-Sabban, M.E.; Sharp, G.W.G.; Donowitz, M.

    1986-01-01

    An interaction between Ca ++ -channel antagonists and the α 2 -adrenergic receptor on active electrolyte transport was demonstrated in rabbit ileum. Clonidine, an α 2 -agonist, stimulated NaCl absorption apparently by Ca ++ -channel antagonism since it inhibited 45 Ca ++ uptake across the basolateral membrane and decreased total ileal calcium content. This stimulation was inhibited by the Ca ++ -channel antagonists dl- and l-verapamil and cadmium but not by nifedipine. The binding of 3 H-yohimbine, a specific α 2 -adrenergic antagonist, was studied on purified ileal cell membranes using a rapid filtration technique. dl-Verapamil and Cd ++ inhibited the specific binding of 3 H-yohimbine over the same concentration range in which they affected transport. In contrast, nifedipine had no effect on binding, just as it had no effect on clonidine-stimulated NaCl absorption. These data demonstrate that there is an interaction between Ca ++ -channels and α 2 -adrenergic receptors in ileal basolateral membranes. Some Ca ++ -channel antagonists alter α 2 -adrenergic binding to the receptor and α 2 -agonist binding leads to changes in Ca ++ entry. A close spatial relationship between the Ca ++ -channel and the α 2 -receptor could explain the data

  3. Patient management after noninvasive cardiac imaging results from SPARC (Study of myocardial perfusion and coronary anatomy imaging roles in coronary artery disease).

    NARCIS (Netherlands)

    Hachamovitch, R.; Nutter, B.; Hlatky, M.A.; Shaw, L.J.; Ridner, M.L.; Dorbala, S.; Beanlands, R.S.; Chow, B.J.; Branscomb, E.; Chareonthaitawee, P.; Weigold, W.G.; Voros, S.; Abbara, S.; Yasuda, T.; Jacobs, J.E.; Lesser, J.; Berman, D.S.; Thomson, L.E.; Raman, S.; Heller, G.V.; Schussheim, A.; Brunken, R.; Williams, K.A.; Farkas, S.; Delbeke, D.; Schoepf, U.J.; Reichek, N.; Rabinowitz, S.; Sigman, S.R.; Patterson, R.; Corn, C.R.; White, R.; Kazerooni, E.; Corbett, J.; Bokhari, S.; Machac, J.; Guarneri, E.; Borges-Neto, S.; Millstine, J.W.; Caldwell, J.; Arrighi, J.; Hoffmann, U.; Budoff, M.; Lima, J.; Johnson, J.R.; Johnson, B.; Gaber, M.; Williams, J.A.; Foster, C.; Hainer, J.; Carli, M.F. Di

    2012-01-01

    OBJECTIVES: This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. BACKGROUND: Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear. METHODS: We assessed the 90-day

  4. Protective head-cooling during cardiac arrest and cardiopulmonary resuscitation: the original animal studies

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    Eric W. Brader

    2010-02-01

    Full Text Available Prolonged standard cardiopulmonary resuscitation (CPR does not reliably sustain brain viability during cardiac arrest. Pre-hospital adjuncts to standard CPR are needed in order to improve outcomes. A preliminary dog study demonstrated that surface cooling of the head during arrest and CPR can achieve protective levels of brain hypothermia (30°C within 10 minutes. We hypothesized that protective head-cooling during cardiac arrest and CPR improves neurological outcomes. Twelve dogs under light ketamine-halothane-nitrous oxide anesthesia were arrested by transthoracic fibrillation. The treated group consisted of six dogs whose shaven heads were moistened with saline and packed in ice immediately after confirmation of ventricular fibrillation. Six control dogs remained at room temperature. All 12 dogs were subjected to four minutes of ventricular fibrillation and 20 minutes of standard CPR. Spontaneous circulation was restored with drugs and countershocks. Intensive care was provided for five hours post-arrest and the animals were observed for 24 hours. In both groups, five of the six dogs had spontaneous circulation restored. After three hours, mean neurological deficit was significantly lower in the treated group (P=0.016, with head-cooled dogs averaging 37% and the normothermic dogs 62%. Two of the six head-cooled dogs survived 24 hours with neurological deficits of 9% and 0%, respectively. None of the control group dogs survived 24 hours. We concluded that head-cooling attenuates brain injury during cardiac arrest with prolonged CPR. We review the literature related to the use of hypothermia following cardiac arrest and discuss some promising approaches for the pre-hospital setting.

  5. Development and Validation of a Heart Atlas to Study Cardiac Exposure to Radiation Following Treatment for Breast Cancer

    International Nuclear Information System (INIS)

    Feng, Mary; Moran, Jean M.; Koelling, Todd; Chughtai, Aamer; Chan, June L.; Freedman, Laura; Hayman, James A.; Jagsi, Reshma; Jolly, Shruti; Larouere, Janice; Soriano, Julie; Marsh, Robin; Pierce, Lori J.

    2011-01-01

    Purpose: Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. Methods and Materials: A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. Results: The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. Conclusions: This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.

  6. Acute effects of sex steroid hormones on susceptibility to cardiac arrhythmias: a simulation study.

    Directory of Open Access Journals (Sweden)

    Pei-Chi Yang

    2010-01-01

    Full Text Available Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females. However, the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear. Here we use a computational modeling approach to incorporate experimentally measured effects of physiological concentrations of testosterone, estrogen and progesterone on cardiac ion channel targets. We then study the hormone effects on ventricular cell and tissue dynamics comprised of Faber-Rudy computational models. The "female" model predicts changes in action potential duration (APD at different stages of the menstrual cycle that are consistent with clinically observed QT interval fluctuations. The "male" model predicts shortening of APD and QT interval at physiological testosterone concentrations. The model suggests increased susceptibility to drug-induced arrhythmia when estradiol levels are high, while testosterone and progesterone are apparently protective. Simulations predict the effects of sex steroid hormones on clinically observed QT intervals and reveal mechanisms of estrogen-mediated susceptibility to prolongation of QT interval. The simulations also indicate that acute effects of estrogen are not alone sufficient to cause arrhythmia triggers and explain the increased risk of females to Torsades de Pointes. Our results suggest that acute effects of sex steroid hormones on cardiac ion channels are sufficient to account for some aspects of gender specific susceptibility to long-QT linked arrhythmias.

  7. Interference of neodymium magnets with cardiac pacemakers and implantable cardioverter-defibrillators: an in vitro study.

    Science.gov (United States)

    Ryf, Salome; Wolber, Thomas; Duru, Firat; Luechinger, Roger

    2008-01-01

    Permanent magnets may interfere with the function of cardiac pacemakers and implantable cardioverter-defibrillators (ICDs). Neodymium-iron-boron (NdFeB) magnets have become widely available in recent years and are incorporated in various articles of daily life. We conducted an in-vitro study to evaluate the ability of NdFeB magnets for home and office use to cause interference with cardiac pacemakers and ICDs. The magnetic fields of ten NdFeB magnets of different size and shape were measured at increasing distances beginning from the surface until a field-strength (B-field) value of 0.5 mT was reached. Furthermore, for each magnet the distance was determined at which a sample pacemaker switched from magnet mode to normal mode. Depending on the size and remanence of individual magnets, a B-field value of 0.5 mT was found at distances ranging from 1.5 cm to 30 cm and a value of 1 mT at distances from 1 cm to 22 cm. The pacemaker behavior was influenced at distances from 1 cm to 24 cm. NdFeB magnets for home and office use may cause interference with cardiac pacemakers and ICDs at distances up to 24 centimeters. Patient education and product declarations should include information about the risk associated with these magnets.

  8. An Echocardiographic Study of Left Ventricular Size and Cardiac Function in Adolescent Females with Anorexia Nervosa.

    Science.gov (United States)

    Escudero, Carolina A; Potts, James E; Lam, Pei-Yoong; De Souza, Astrid M; Mugford, Gerald J; Sandor, George G S

    2016-01-01

    This retrospective case-control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls. Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and >10th percentile (AN > 10th). Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN > 10th. Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  9. Risk-taking attitudes and their association with process and outcomes of cardiac care: a cohort study

    Directory of Open Access Journals (Sweden)

    Knudtson Merril L

    2009-08-01

    Full Text Available Abstract Background Prior research reveals that processes and outcomes of cardiac care differ across sociodemographic strata. One potential contributing factor to such differences is the personality traits of individuals within these strata. We examined the association between risk-taking attitudes and cardiac patients' clinical and demographic characteristics, the likelihood of undergoing invasive cardiac procedures and survival. Methods We studied a large inception cohort of patients who underwent cardiac catheterization between July 1998 and December 2001. Detailed clinical and demographic data were collected at time of cardiac catheterization and through a mailed survey one year post-catheterization. The survey included three general risk attitude items from the Jackson Personality Inventory. Patients' (n = 6294 attitudes toward risk were categorized as risk-prone versus non-risk-prone and were assessed for associations with baseline clinical and demographic characteristics, treatment received (i.e., medical therapy, coronary artery bypass graft (CABG surgery, percutaneous coronary intervention (PCI, and survival (to December 2005. Results 2827 patients (45% were categorized as risk-prone. Having risk-prone attitudes was associated with younger age (p Conclusion These exploratory findings suggest that patient attitudes toward risk taking may contribute to some of the documented differences in use of invasive cardiac procedures. An awareness of these associations could help healthcare providers as they counsel patients regarding cardiac care decisions.

  10. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography

    International Nuclear Information System (INIS)

    Dorbala, Sharmila; Vangala, Divya; Semer, James; Strader, Christopher; Bruyere, John R.; Moore, Stephen C.; Di Carli, Marcelo F.; Falk, Rodney H.

    2014-01-01

    Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of 18 F-florbetapir for imaging cardiac amyloidosis. We performed a pilot study of cardiac 18 F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of 18 F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A 18 F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated. Left and right ventricular myocardial uptake of 18 F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min -1 , IQR 0.034 - 0.051 min -1 , vs. 0.023 min -1 , IQR 0.015 - 0.025 min -1 , P = 0.002; TBR 1.84, 1.64 - 2.50, vs. 1.26, IQR 0.91 - 1.36, P = 0.001; LV myocardial SUV 3.84, IQR 1.87 - 5.65, vs. 1.35, IQR 1.17 - 2.28, P = 0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 - 1.64, vs. 0.18, IQR 0.15 - 0.35, P = 0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid. 18 F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied. (orig.)

  11. Peculiarities of the effect of prolonged gamma-irradiation on the functional state of heart and its adrenergic regulation at hypothyroidism

    International Nuclear Information System (INIS)

    Lobanok, L.M.; Antonenko, A.N.

    2001-01-01

    Effect of prolonged gamma radiation on the functional state of heart and its adrenergic regulation in case of hypothyroidism is studied. Rats-females were irradiated during 992 h at the dose of 1.0 Gy, dose rate - 2.8x10 -7 Gy/s. Gammarid - 192/120 plant was used for exposure. Mercazolyl was incorporated into rats before irradiation for modelling hypothyroidism. It is shown that in delayed times, after exposure the contraction function of heart is decreased, but modification of the adrenergic regulation became essentially earlier. Radiation effect on the hyperthyroid organism results in more considerable alterations in biochemical heart function and its adrenergic regulation [ru

  12. Evidence for β-adrenergic modulation of sweating during incremental exercise in habitually trained males.

    Science.gov (United States)

    Amano, Tatsuro; Shitara, Yosuke; Fujii, Naoto; Inoue, Yoshimitsu; Kondo, Narihiko

    2017-07-01

    The aim of the present study was to determine the β-adrenergic contribution to sweating during incremental exercise in habitually trained males. Nine habitually trained and 11 untrained males performed incremental cycling until exhaustion (20 W/min). Bilateral forearm sweat rates (ventilated capsule) were measured at two skin sites that were transdermally administered via iontophoresis with either 1% propranolol (Propranolol, a nonselective β-adrenergic receptor antagonist) or saline (Control). The sweat rate was evaluated as a function of both relative (percentage of maximum workload) and absolute exercise intensities. The sweat rate at the Propranolol site was lower than the control during exercise at 80 (0.57 ± 0.21 and 0.45 ± 0.19 mg·cm -2 ·min -1 for Control and Propranolol, respectively) and 90% (0.74 ± 0.22 and 0.65 ± 0.17 mg·cm -2 ·min -1 , respectively) of maximum workload in trained males (all P 0.05). At the same absolute intensity, higher sweat rates on the control site were observed in trained males relative to the untrained during exercise at 160 (0.23 ± 0.20 and 0.04 ± 0.05 mg·cm -2 ·min -1 for trained and untrained, respectively) and 180 W (0.40 ± 0.20 and 0.13 ± 0.13 mg·cm -2 ·min -1 , respectively) (all P 0.05). We show that the β-adrenergic mechanism does modulate sweating during exercise at a submaximal high relative intensity in habitually trained males. The β-adrenergic mechanism may in part contribute to the greater sweat production in habitually trained males than in untrained counterparts during exercise. NEW & NOTEWORTHY We demonstrated for the first time that the β-adrenergic mechanism does modulate sweating (i.e., β-adrenergic sweating) during exercise using a localized β-adrenoceptor blockade in humans in vivo. β-Adrenergic sweating was evident in habitually trained individuals during exercise at a submaximal high relative intensity (80-90% maximal work). This observation advances

  13. Modelling cardiac signal as a confound in EEG-fMRI and its application in focal epilepsy studies

    DEFF Research Database (Denmark)

    Liston, A. D.; Ellegaard Lund, Torben; Salek-Haddadi, A

    2006-01-01

    effects to be modelled, as effects of no interest. Our model is based on an over-complete basis set covering a linear relationship between cardiac-related MR signal and the phase of the cardiac cycle or time after pulse (TAP). This method showed that, on average, 24.6 +/- 10.9% of grey matter voxels......Cardiac noise has been shown to reduce the sensitivity of functional Magnetic Resonance Imaging (fMRI) to an experimental effect due to its confounding presence in the blood oxygenation level-dependent (BOLD) signal. Its effect is most severe in particular regions of the brain and a method is yet...... to take it into account in routine fMRI analysis. This paper reports the development of a general and robust technique to improve the reliability of EEG-fMRI studies to BOLD signal correlated with interictal epileptiform discharges (IEDs). In these studies, ECG is routinely recorded, enabling cardiac...

  14. Phosphoinositide metabolism and adrenergic receptors in astrocytes

    International Nuclear Information System (INIS)

    Noble, E.P.; Ritchie, T.; de Vellis, J.

    1986-01-01

    Agonist-induced phosphoinositide (PI) breakdown functions as a signal generating system. Diacylglycerol, one breakdown product of phosphotidylinositol-4,5-diphosphate hydrolysis, can stimulate protein kinase C, whereas inositol triphosphate, the other product, has been proposed to be a second messenger for Ca ++ mobilization. Using purified astrocyte cultures from neonatal rat brain, the effects of adrenergic agonists and antagonists at 10 -5 M were measured on PI breakdown. Astrocytes grown in culture were prelabeled with ( 3 H)inositol, and basal ( 3 H) inositol phosphate (IP 1 ) accumulation was measured in the presence of Li + . Epinephrine > norepinephrine (NE) were the most active stimulants of IP 1 production. The α 1 adrenoreceptor blockers, phentolamine and phenoxybenzamine, added alone had no effect on IP 1 production was reduced below basal levels. Propranolol partially blocked the effects of NE. Clonidine and isoproterenol, separately added, reduced IP 1 below basal levels and when added together diminished IP 1 accumulation even further. The role of adrenergic stimulation in the production of c-AMP

  15. Decreased α1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain

    International Nuclear Information System (INIS)

    Feldstein, J.B.; Gonzales, R.A.; Baker, S.P.; Sumners, C.; Crews, F.T.; Raizada, M.K.

    1986-01-01

    The expression of α 1 -adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125 I-1-[β-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125 I-HEAT bound selectively to α 1 -adrenergic receptors. Specific binding of 125 I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of α 1 -adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the α 1 -adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of α 1 -adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain

  16. Guanine nucleotide regulation of α1-adrenergic receptors of muscle and kidney eptihelial cells

    International Nuclear Information System (INIS)

    Terman, B.I.; Hughes, R.J.; Slivka, S.R.; Insel, P.A.

    1986-01-01

    The authors have examined the effect of guanine nucleotides on the interaction of adrenergic agents with α 1 -adrenergic receptors of two cell lines, the Madin-Darby Canine Kidney (MDCK) and BC3H-1 muscle cells. While gaunylylimidodiphosphoate (Gpp(NH)p) had no effect on the affinity or the total number of [ -3 H]prazosin binding sites in membranes prepared from these cells, the nucleotide decreased the apparent affinity of the agonist epinephrine in competing for [ 3 H]prazosin binding sites in both cell types. The EC 50 of Gpp(NH)p was ∼100 μM, and a maximal effect was seen at 500 μM. In contrast, 100 μM Gpp(NH)p yielding maximal shifts in binding of epinephrine to β-adrenergic receptors in BC3H-1 cell membranes. Guanine nucleotides were significantly more effective than adenine nucleotides in shifting agonist affinity for the α 1 -receptor and Mg ++ was required to observe a maximal effect. α 1 -receptor agonists activated phosphatidylinositol (PI) hydrolysis in both cell types, but have no direct effect on membrane adenylate cyclase activity. In intact BC3H-1 cells, α 1 -agonists inhibited β-adrenergic cAMP production, an effect which appears in preliminary studies not to result from enhanced phosphodieterase activity. These results show that agonist binding to α 1 -adrenergic receptors in mammalian kidney and muscle cells is regulated by guanine nucleotides. This regulation and inturn transmembrane signalling (PI hydrolysis) by these receptors appear to involve a guanine nucleotide binding (G) protein, which may be different than G/sub s/ and G/sub i/

  17. beta-Adrenergic and cholinergic receptors in hypertension-induced hypertrophy

    International Nuclear Information System (INIS)

    Vatner, D.E.; Kirby, D.A.; Homcy, C.J.; Vatner, S.F.

    1985-01-01

    Perinephritic hypertension was produced in dogs by wrapping one kidney with silk and removing the contralateral kidney 1 week later. Mean arterial pressure rose from 104 +/- 3 to 156 +/- 11 mm Hg, while left ventricular free wall weight, normalized for body weight, was increased by 49%. Muscarinic, cholinergic receptor density measured with [ 3 H]-quinuclidinyl benzilate, fell in hypertensive left ventricles (181 +/- 19 fmol/mg, n = 6; p less than 0.01) as compared with that found in normal left ventricles (272 +/- 16 fmol/mg, n = 8), while receptor affinity was not changed. The beta-adrenergic receptor density, measured by binding studies with [ 3 H]-dihydroalprenolol, rose in the hypertensive left ventricles (108 +/- 10 fmol/mg, n = 7; p less than 0.01) as compared with that found in normal left ventricles (68.6 +/- 5.2 fmol/mg, n = 15), while beta-adrenergic receptor affinity decreased in the hypertensive left ventricles (10.4 +/- 1.2 nM) compared with that found in the normal left ventricles (5.0 +/- 0.7 nM). Plasma norepinephrine levels were similar in the two groups, but myocardial norepinephrine levels were depressed (p less than 0.05) in dogs with hypertension. Moderate left ventricular hypertrophy induced by long-term aortic banding in dogs resulted in elevations in beta-adrenergic receptor density (115 +/- 14 fmol/mg) and decreases in affinity (10.4 +/- 2.2 nM) similar to those observed in the dogs with left ventricular hypertrophy induced by hypertension. Thus, these results suggest that perinephritic hypertension in the dog induces divergent effects on cholinergic and beta-adrenergic receptor density. The increased beta-adrenergic receptor density and decreased affinity may be a characteristic of left ventricular hypertrophy rather than hypertension

  18. Astrocytic β2 Adrenergic Receptor Gene Deletion Affects Memory in Aged Mice.

    Directory of Open Access Journals (Sweden)

    Cathy Joanna Jensen

    Full Text Available In vitro and in vivo studies suggest that the astrocytic adrenergic signalling enhances glycogenolysis which provides energy to be transported to nearby cells and in the form of lactate. This energy source is important for motor and cognitive functioning. While it is suspected that the β2-adrenergic receptor on astrocytes might contribute to this energy balance, it has not yet been shown conclusively in vivo. Inducible astrocyte specific β2-adrenergic receptor knock-out mice were generated by crossing homozygous β2-adrenergic receptor floxed mice (Adrb2flox and mice with heterozygous tamoxifen-inducible Cre recombinase-expression driven by the astrocyte specific L-glutamate/L-aspartate transporter promoter (GLAST-CreERT2. Assessments using the modified SHIRPA (SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment test battery, swimming ability test, and accelerating rotarod test, performed at 1, 2 and 4 weeks, 6 and 12 months after tamoxifen (or vehicle administration did not reveal any differences in physical health or motor functions between the knock-out mice and controls. However deficits were found in the cognitive ability of aged, but not young adult mice, reflected in impaired learning in the Morris Water Maze. Similarly, long-term potentiation (LTP was impaired in hippocampal brain slices of aged knock-out mice maintained in low glucose media. Using microdialysis in cerebellar white matter we found no significant differences in extracellular lactate or glucose between the young adult knock-out mice and controls, although trends were detected. Our results suggest that β2-adrenergic receptor expression on astrocytes in mice may be important for maintaining cognitive health at advanced age, but is dispensable for motor function.

  19. Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy.

    Science.gov (United States)

    Oelkrug, Rebecca; Herrmann, Beate; Geissler, Cathleen; Harder, Lisbeth; Koch, Christiane; Lehnert, Hendrik; Oster, Henrik; Kirchner, Henriette; Mittag, Jens

    2017-10-01

    Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments. We sought to test the consequences of maternal α1-adrenergic antagonism during pregnancy, which can occur e.g. during hypertension treatment, for the endocrine and metabolic phenotype of the offspring. We treated C57BL/6NCrl female mice with the α1-adrenergic antagonist prazosin during pregnancy and analyzed the male and female offspring for endocrine and metabolic abnormalities. Our data revealed that maternal α1-adrenergic blockade caused dwarfism, elevated body temperature, and insulin resistance in male offspring, accompanied by reduced IGF-1 serum concentrations as the result of reduced hepatic growth hormone receptor (Ghr) expression. We subsequently identified increased CpG DNA methylation at the transcriptional start site of the alternative Ghr promotor caused by the maternal treatment, which showed a strong inverse correlation to hepatic Ghr expression. Our results demonstrate that maternal α1-adrenergic blockade can constitute an epigenetic cause for dwarfism and insulin resistance. The findings are of immediate clinical relevance as combined α/β-adrenergic blockers are first-line treatment of maternal hypertension. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  20. Late Causes of Death After Pediatric Cardiac Surgery: A 60-Year Population-Based Study.

    Science.gov (United States)

    Raissadati, Alireza; Nieminen, Heta; Haukka, Jari; Sairanen, Heikki; Jokinen, Eero

    2016-08-02

    Comprehensive information regarding causes of late post-operative death following pediatric congenital cardiac surgery is lacking. The study sought to analyze late causes of death after congenital cardiac surgery by era and defect severity. We obtained data from a nationwide pediatric cardiac surgery database and Finnish population registry regarding patients who underwent cardiac surgery at Causes of death were determined using International Classification of Diseases diagnostic codes. Deaths among the study population were compared to a matched control population. Overall, 10,964 patients underwent 14,079 operations, with 98% follow-up. Early mortality (death rates correlated with defect severity. Heart failure was the most common mode of CHD-related death, but decreased after surgeries performed between 1990 and 2009. Sudden death after surgery for atrial septal defect, ventricular septal defect, tetralogy of Fallot, and transposition of the great arteries decreased to zero following operations from 1990 to 2009. Deaths from neoplasms, respiratory, neurological, and infectious disease were significantly more common among study patients than controls. Pneumonia caused the majority of non-CHD-related deaths among the study population. CHD-related deaths have decreased markedly but remain a challenge after surgery for severe cardiac defects. Premature deaths are generally more common among patients than the control population, warranting long-term follow-up after congenital cardiac surgery. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Rat hepatic β2-adrenergic receptor: structural similarities to the rat fat cell β1-adrenergic receptor

    International Nuclear Information System (INIS)

    Graziano, M.P.

    1984-01-01

    The mammalian β 2 -adrenergic receptor from rat liver has been purified by sequential cycles of affinity chromatography followed by steric-exclusion high performance liquid chromatography. Electrophoresis of highly purified receptor preparations on polyacrylamide gels in the presence of sodium dodecyl sulfate under reducing conditions reveals a single peptide M/sub r/ = 67,000, as judged by silver staining. Purified β 2 -adrenergic receptor migrates on steric-exclusion high performance liquid chromatography in two peaks, with M/sub r/ = 140,000 and 67,000. Specific binding of the high affinity, β-adrenergic receptor antagonists (-)[ 3 H]dihydroalprenolol and (-)[ 125 I]iodocyanopindolol to purified rat liver β-adrenergic receptor preparations displays stereoselectivity for (-)isomers of agonists and a rank order of potencies for agonists characteristics of a β 2 -adrenergic receptor. Radioiodinated, β 1 -adrenergic receptors from rat fat cells and β 2 -adrenergic receptors from rat liver purified in the presence of protease inhibitors comigrate in electrophoretic separations on polyacrylamide gels in the presence of sodium dodecyl sulfate as 67,000-M/sub r/ peptides. Autoradiograms of two dimensional partial proteolytic digests of the purified, radioiodinated rat liver β 2 -adrenergic receptor, generated with α-chymotrypsin, S. aureus V8 protease and elastase reveal a pattern of peptide fragments essentially identical to those generated by partial proteolytic digests of the purified, radioiodinated β 1 -adrenergic receptor from rat fat cells, by these same proteases. These data indicate that a high degree of homology exists between these two pharmacologically distinct mammalian β-adrenergic receptor proteins

  2. Right and left ventricular cardiac function in a developed world population with human immunodeficiency virus studied with radionuclide ventriculography

    DEFF Research Database (Denmark)

    Lebech, Anne-Mette; Gerstoft, Jan; Hesse, Birger

    2004-01-01

    . No correlations were found between reduced cardiac function and levels of the 3 peptides measured. CONCLUSIONS: No major dysfunction of the left ventricle is present in a developed world HIV population. However, a small but significant part of this population has modestly reduced right-sided systolic function.......-associated morbidity and mortality rates. Accordingly, the prevalence of HIV-associated cardiac dysfunction may also have changed. The aim of the study was to establish the prevalence of right- and left-sided cardiac dysfunction in a Danish HIV population, most of whom were undergoing HAART, with radionuclide...... ventricular ejection fraction and 6 (7%) had a reduced right ventricle ejection fraction (0.35-0.42) compared with reference values from the age- and sex-matched reference population. Patients with HIV and reduced cardiac function did not differ in the duration of HIV, CD4 count, CD4 nadir, or HIV RNA load...

  3. Association of the beta3-adrenergic receptor Trp64Arg polymorphism with common metabolic traits: studies of 7605 middle-aged white people

    DEFF Research Database (Denmark)

    Gjesing, A. P.; Andersen, G; Borch-Johnsen, K

    2008-01-01

    , the Arg-allele was associated with a slightly increased risk of type 2 diabetes (OR1.15 (CI: 1.01-1.31); p=0.04), increased insulin resistance estimated by homeostasis model assessment (p=0.01), higher fasting serum insulin levels (p=0.01), and higher levels of plasma glucose 2-h after glucose ingestion...... does not confer an increased risk of obesity among Danes. Yet, in the present study of 7605 Danes the variant is associated with type 2 diabetes and quantitative traits related to type 2 diabetes....

  4. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    International Nuclear Information System (INIS)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj; Schönberger, Tanja; Noegel, Angelika A.; Gawaz, Meinrad; Lang, Florian

    2014-01-01

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca 2+ signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7 −/− ) and wild-type mice (anxa7 +/+ ) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7 −/− mice than in anxa7 +/+ mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions

  5. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj [Department of Physiology, University of Tübingen, Tübingen (Germany); Schönberger, Tanja [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Noegel, Angelika A. [Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln (Germany); Gawaz, Meinrad [Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen (Germany); Lang, Florian, E-mail: florian.lang@uni-tuebingen.de [Department of Physiology, University of Tübingen, Tübingen (Germany)

    2014-02-28

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{sup +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

  6. Adrenergic receptors in frontal cortex in human brain.

    Science.gov (United States)

    Cash, R; Raisman, R; Ruberg, M; Agid, Y

    1985-02-05

    The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

  7. QT and JT dispersion and cardiac performance in children with neonatal Bartter syndrome: a pilot study.

    Science.gov (United States)

    Hacihamdioglu, Duygu Ovunc; Fidanci, Kursat; Kilic, Ayhan; Gok, Faysal; Topaloglu, Rezan

    2013-10-01

    QT dispersion and JT dispersion are simple noninvasive arrhythmogenic markers that can be used to assess the homogeneity of cardiac repolarization. The aim of this study was to assess QT and JT dispersion and their relation with left ventricular systolic and diastolic functions in children with Bartter syndrome (BS). Nine neonatal patients with BS (median age 9.7 years) and 20 controls (median age 8 years) were investigated at rest. Both study and control subjects underwent electrocardiography (ECG) in which the interval between two R waves and QT intervals, corrected QT, QT dispersion, corrected QT dispersion, JT, corrected JT, JT dispersion and corrected JT dispersion were measured with 12-lead ECG. Two-dimensional, Doppler echocardiographic examinations were performed. Patients and controls did not differ for gender and for serum levels of potassium, magnesium, and calcium (p > 0.05). Both study and control subjects had normal echocardiographic examination and baseline myocardial performance indexes. The QT dispersion and JT dispersion were significantly prolonged in patients with BS compared to those of the controls {37.5 ms [interquartile range (IQR) 32.5-40] vs. 25.5 ms (IQR 20-30), respectively, p = 0.014 and 37.5 ms (IQR 27.5-40) vs. 22.5 ms (IQR 20-30), respectively, p = 0.003}. Elevated QT and JT dispersion during asymptomatic and normokalemic periods may be risk factors for the development of cardiac complications and arrhythmias in children with BS. In these patients the need for systematic cardiac screening and management protocol is extremely important for effective prevention.

  8. The consequence of colour in the accurate interpretation of Sestamibi cardiac studies

    International Nuclear Information System (INIS)

    Dojcinovska, S.

    2001-01-01

    This research project is aimed at investigating the effect of colour in the accurate interpretation of Sestamibi cardiac studies. This project looks at the way the chosen colour for display may influence the final diagnosis. Four patient studies were chosen for this study, and each patient's films were displayed in three different colours, these include 'cool' - a combination of purples, reds, blues and yellow, 'smart' (mainly red and orange), and 'black and white' - consisting of various shades of grey. Subjects were AS/Ked to answer a questionnaire related to the studies. The subjects surveyed were from four different groups: Nuclear Medicine physicians, Nuclear Medicine technologists, general practitioners and members of the public. The results support the use of 'cool' colours for display, especially when reports with films are sent to general practitioners. Researches into the human visual system found that colours in the low wavelength end of spectrum seemed to be more easily detected by human eye. This study showed that there was a possible link between colour and the accuracy of diagnosis for Sestamibi cardiac films

  9. A compartmentalized mathematical model of the β1-adrenergic signaling system in mouse ventricular myocytes.

    Directory of Open Access Journals (Sweden)

    Vladimir E Bondarenko

    Full Text Available The β1-adrenergic signaling system plays an important role in the functioning of cardiac cells. Experimental data shows that the activation of this system produces inotropy, lusitropy, and chronotropy in the heart, such as increased magnitude and relaxation rates of [Ca(2+]i transients and contraction force, and increased heart rhythm. However, excessive stimulation of β1-adrenergic receptors leads to heart dysfunction and heart failure. In this paper, a comprehensive, experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is developed, which includes major subcellular functional compartments (caveolae, extracaveolae, and cytosol. The model describes biochemical reactions that occur during stimulation of β1-adrenoceptors, changes in ionic currents, and modifications of Ca(2+ handling system. Simulations describe the dynamics of major signaling molecules, such as cyclic AMP and protein kinase A, in different subcellular compartments; the effects of inhibition of phosphodiesterases on cAMP production; kinetics and magnitudes of phosphorylation of ion channels, transporters, and Ca(2+ handling proteins; modifications of action potential shape and duration; magnitudes and relaxation rates of [Ca(2+]i transients; changes in intracellular and transmembrane Ca(2+ fluxes; and [Na(+]i fluxes and dynamics. The model elucidates complex interactions of ionic currents upon activation of β1-adrenoceptors at different stimulation frequencies, which ultimately lead to a relatively modest increase in action potential duration and significant increase in [Ca(2+]i transients. In particular, the model includes two subpopulations of the L-type Ca(2+ channels, in caveolae and extracaveolae compartments, and their effects on the action potential and [Ca(2+]i transients are investigated. The presented model can be used by researchers for the interpretation of experimental data and for the developments of

  10. Timing of renal replacement therapy after cardiac surgery: a retrospective multicenter Spanish cohort study.

    Science.gov (United States)

    García-Fernández, Nuria; Pérez-Valdivieso, José Ramón; Bes-Rastrollo, Maira; Vives, Marc; Lavilla, Javier; Herreros, Jesús; Monedero, Pablo

    2011-01-01

    The optimal time to initiate renal replacement therapy (RRT) in cardiac surgery-associated acute kidney injury (CSA-AKI) is unknown. Evidence suggests that the early use of RRT in critically ill patients is associated with improved outcomes. We studied the effects of time to initiation of RRT on outcome in patients with CSA-AKI. This was a retrospective observational multicenter study (24 Spanish hospitals). We analyzed data on 203 patients who required RRT after cardiac surgery in 2007. The cohort was divided into 2 groups based on the time at which RRT was initiated: in the early RRT group, therapy was initiated within the first 3 days after cardiac surgery; in the late group, RRT was begun after the 3rd day. Multivariate nonconditional logistic and linear regression models were used to adjust for potential confounders. In-hospital mortality was significantly higher in the late RRT group compared with early RRT patients (80.4 vs. 53.2%; p < 0.001; adjusted odds ratio of 4.1, 95% CI: 1.6-10.0). Also, patients in the late RRT group had longer adjusted hospital stays by 11.6 days (95% CI: 1.4-21.9) and higher adjusted percentage increases in creatinine at discharge compared with baseline by 67.7% (95% CI: 28.5-106.4). Patients who undergo early initiation of RRT after CSA-AKI have improved survival rates and renal function at discharge and decreased lengths of hospital stay. Copyright © 2011 S. Karger AG, Basel.

  11. Tetralogy of fallot (cyanotic cardiac malformation), trends and variation in a population based study

    International Nuclear Information System (INIS)

    Arif, A.; Zehra, S.; Qamarunnisa, S.; Azhar, A.

    2012-01-01

    Congenital heart diseases (CHDs) are a major threat worldwide for children below the age of five. It has high mortality and morbidity ratio. CHDs can be classified as cyanotic and acyanotic. Cyanotic cardiac malformation accounts 25% of all congenital heart diseases and Tetralogy of Fallot (TOF) is .the most common form of cyanotic CHD. Tetralogy of Fallot is a combination of four anatomical abnormalities. These include a large ventricular septal defect (VSD), right ventricular outflow tract and pulmonary valve obstruction, right ventricular hypertrophy, and over-riding of the aorta. The current investigation was conducted over the span of 2.5 years on the patients presented in OPD and hospitalized at various pediatric cardiology centers. A detailed family history was taken to elucidate the genetic and environmental factors. Diagnosis was confirmed by the cardiologist based on examination of cardiac murmur, chest X-ray, fetal echocardiography (ECG), complete blood count (CBC), echocardiograms and/or echocardiogram (ECHO) reports, cardiac catherization reports, operative notes and MRI of heart, if applicable. This study recruited a cohort of 268 patients and 140 controls, healthy unrelated individuals. The mean age for patients was 2.97+-1.21 and that for controls was 3.14+-2.44 years. Males were shown to have a higher rate of incidence than females (1.26:1) in our population. The genes that are mainly involved are NKX 2.5, GAT A 4, TBX5, JAGI, ZFPM2 and VEGF. The present study focuses on NKX 2.5 and its mutations in our population. (author)

  12. Association between depression and heart rate variability in patients after cardiac surgery: a pilot study.

    Science.gov (United States)

    Patron, Elisabetta; Messerotti Benvenuti, Simone; Favretto, Giuseppe; Valfrè, Carlo; Bonfà, Carlotta; Gasparotto, Renata; Palomba, Daniela

    2012-07-01

    Depression is a risk factor for cardiovascular diseases. Reduced heart rate variability (HRV), which reflects altered autonomic nervous system activity, has been suggested as one of the mechanisms linking depression to cardiovascular diseases. However, the relationship between depression and HRV has not yet been investigated in patients undergone cardiac surgery. Therefore, the main aim of this study was to examine whether postoperative depression could be related to reduced HRV. Eleven patients with depression and 22 patients without depression, who had undergone cardiac surgery, were enrolled postoperatively. In all patients, HRV was derived from a four-minute blood volume pulse recording at rest. Analyses of covariance and partial correlations, while controlling for anxiety, were used to examine the associations between postoperative depression and each HRV parameter. Compared to non-depressed patients, patients with depression showed significantly lower standard deviation of N-to-N intervals (SDNN) (p=.02), root mean square successive difference of N-to-N intervals (rMSSD) (p=.001), and high-frequency power (p=.002). Partial correlation analyses showed that depression was inversely related to SDNN (r=-.49, p=.005), rMSSD (r=-.58, p=.001), and high-frequency power (r=-.41, p=.02), whereas it was unrelated to other HRV parameters (p's>.09). The current findings extend the depression-reduced HRV relationship to the patients after cardiac surgery. Also, our study suggests that postoperative depression is more likely to be associated with reduced vagal modulation on the heart than with excessive sympathetic activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Barriers to Nurse-Patient Communication in Cardiac Surgery Wards: A Qualitative Study

    Science.gov (United States)

    Shafipour, Vida; Mohammad, Eesa; Ahmadi, Fazlollah

    2014-01-01

    Background: An appropriate and effective nurse-patient communication is of the most important aspect of caring. The formation and continuation of such a relationship depends on various factors such as the conditions and context of communication and a mutual understanding between the two. A review of the literature shows that little research is carried out on identification of such barriers in hospital wards between the patients and the healthcare staff. Objectives: The present study was therefore conducted to explore the experiences of nurses and patients on communication barriers in hospital cardiac surgery wards. Design and Methods: This qualitative research was carried out using a content analysis method (Graneheim & Lundman, 2004). The participants were selected by a purposeful sampling and consist of 10 nurses and 11 patients from the cardiac surgery wards of three teaching hospitals in Tehran, Iran. Data was gathered by unstructured interviews. All interviews were audio-taped and transcribed verbatim. Results: Findings were emerged in three main themes including job dissatisfaction (with the sub-themes of workload tension and decreased motivation), routine-centered care (with the sub-themes of habitual interventions, routinized and technical interventions, and objective supervision), and distrust in competency of nurses (with the sub-themes of cultural contrast, less responsible nurses, and their apathy towards the patients). Conclusions: Compared to other studies, our findings identified different types of communication barriers depending on the nursing settings. These findings can be used by the ward clinical nursing managers at cardiac surgery wards to improve the quality of nursing care. PMID:25363126

  14. Dual cardiac-respiratory gated PET: implementation and results from a feasibility study

    International Nuclear Information System (INIS)

    Martinez-Moeller, Axel; Zikic, Darko; Navab, Nassir; Botnar, Rene M.; Bundschuh, Ralph A.; Ziegler, Sibylle I.; Schwaiger, Markus; Nekolla, Stephan G.; Howe, William

    2007-01-01

    Spatial resolution in myocardial imaging is impaired by both cardiac and respiratory motion owing to motional blurring. We investigated the feasibility of a dual cardiac-respiratory gated positron emission tomography (PET) acquisition using a clinical PET/computer tomography (CT) scanner. We describe its implementation and present results on the respiratory motion observed. The correlation between diaphragmatic excursion measured by real-time magnetic resonance imaging (MRI) and the expansion of the chest measured with an elastic belt was studied in six subjects. PET list mode acquisitions were then performed in 12 patients, six of them injected with 13 N-ammonia and six with 18 F-FDG. In parallel, the ECG and respiratory signals of the patients were recorded and the list mode file correspondingly sorted using a dual gated approach. Respiratory motion of the heart was quantified by measuring the displacement between the inspiratory and expiratory images in the diastolic phase by means of intensity-based non-rigid image registration. The correlation between diaphragmatic excursion and expansion of the chest was excellent (R 2 = 0.91), validating the ability of the elastic belt to provide an adequate respiratory trigger. Respiratory signals corresponding to the chest expansion showed a large inter-patient variability, requiring adapted algorithms in order to define suitable respiratory gates. Dual gated PET series were successfully acquired for both groups of patients, showing better resolved myocardial walls. The average respiratory motion of the heart measured by PET was 4.8 mm, with its largest component in the craniocaudal direction. Moreover, a deformation of the heart with respiration was observed, with the inferior wall moving significantly more than the anterior. Dual gated cardiac PET studies were performed successfully and showed better resolved myocardial walls as compared with ungated acquisitions. The respiratory motion of the heart presented a

  15. Preoperative predictive model for acute kidney injury after elective cardiac surgery: a prospective multicentre cohort study.

    Science.gov (United States)

    Callejas, Raquel; Panadero, Alfredo; Vives, Marc; Duque, Paula; Echarri, Gemma; Monedero, Pablo

    2018-05-11

    Predictive models of CS-AKI include emergency surgery and patients with haemodynamic instability. Our objective was to evaluate the performance of validated predictive models (Thakar and Demirjian) in elective cardiac surgery and to propose a better score in the case of poor performance. A prospective, multicentre, observational study was designed. Data were collected from 942 patients undergoing cardiac surgery, after excluding emergency surgery and patients with an intraaortic balloon pump. The main outcome measure was CS-AKI defined by the composite of requiring dialysis or doubling baseline creatinine values. Both models showed poor discrimination in elective surgery (Thakar's model, AUROC = 0.57, 95% CI = 0.50-0.64 and Demirjian's model, AUROC= 0.64, 95% CI = 0.58-0.71). We generated a new model whose significant independent predictors were: anaemia, age, hypertension, obesity, congestive heart failure, previous cardiac surgery and type of surgery. It classifies patients with scores 0-3 as low risk ( 8 as high risk (>30%) of developing CS-AKI with a statistically significant correlation (p <0.001). Our model reflects acceptable discriminatory ability (AUC = 0.72, 95% CI = 0.66-0.78) which is significantly better than Thakar and Demirjian's models (p<0.01). We developed a new simple predictive model of CS-AKI in elective surgery based on available preoperative information. Our new model is easy to calculate and can be an effective tool for communicating risk to patients and guiding decision-making in the perioperative period. The study requires external validation.

  16. Feasibility, safety and image quality of cardiac FDG studies during hyperinsulinaemic-euglycaemic clamping

    International Nuclear Information System (INIS)

    Bax, Jeroen J.; Visser, Frans C.; Lingen, Arthur van; Visser, Cees A.; Poldermans, Don; Elhendy, Abdou; Boersma, Eric

    2002-01-01

    Fluorine-18 fluorodeoxyglucose (FDG) imaging for the assessment of myocardial viability has become an integral part of the diagnostic and prognostic work-up of patients with ischaemic cardiomyopathy. To ensure good image quality, in particular in patients with diabetes mellitus, hyperinsulinaemic-euglycaemic clamping has been proposed. In this study we evaluated the safety and the image quality of cardiac FDG imaging during clamping in a large group of patients, including a subgroup with diabetes mellitus. The incidence of viability (on both a segment and a patient basis) was also determined for patients with and without diabetes mellitus. The safety and image quality of cardiac FDG studies during clamping were evaluated in 131 patients, including 19 with diabetes mellitus. Image quality was assessed visually and quantitatively using heart-to-lung (H/L), heart-to-liver (H/Li) and myocardium-to-background (M/B) ratios. Blood samples were drawn at baseline and at the time of FDG injection to determine levels of glucose, free fatty acids and insulin. The metabolic circumstances were optimal for FDG imaging: high insulin levels, low free fatty acid levels and glucose levels in the normal range (levels of substrates were comparable between patients with and patients without diabetes mellitus). No serious side-effects occurred in any patient. Image quality (assessed visually) was good in all patients. The quantitative parameters of image quality (H/L, H/Li and M/B) were comparable between patients with and patients without diabetes mellitus. The incidence of viability was high: 38% of patients without and 58% of patients with diabetes mellitus had substantial viability despite contractile dysfunction. It is concluded that cardiac FDG imaging during clamping is safe and provides excellent image quality, including in patients with diabetes mellitus. The incidence of viability is high, in particular in patients with diabetes mellitus. (orig.)

  17. Association of Central Adiposity With Adverse Cardiac Mechanics: Findings from the HyperGEN Study

    Science.gov (United States)

    Selvaraj, Senthil; Martinez, Eva E.; Aguilar, Frank G.; Kim, Kwang-Youn A.; Peng, Jie; Sha, Jin; Irvin, Marguerite R.; Lewis, Cora E.; Hunt, Steven C.; Arnett, Donna K.; Shah, Sanjiv J.

    2016-01-01

    Background Central obesity, defined by increased waist circumference (WC) or waist-hip ratio (WHR), is associated with increased cardiovascular (CV) events, including heart failure. However, the pathophysiological link between central obesity and adverse CV outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular [LV] strain and systolic [s’] and early diastolic [e’] tissue velocities). Methods and Results We performed speckle-tracking analysis of echocardiograms from participants in the HyperGEN study, a population- and family-based epidemiologic study (N=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were female, and 47% were African-American. Mean body-mass index (BMI) was 30.8±7.1 kg/m2, WC 102±17 cm, WHR 0.91±0.08, and 80% had central obesity based on WC and WHR criteria. After adjusting for multiple potential confounders, including age, sex, race, physical activity, BMI, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, anti-hypertensive medication use, glomerular filtration rate, LV mass index, wall motion abnormalities, and ejection fraction, central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s’ velocity, and e’ velocity (P mechanics. PMID:27307550

  18. The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Höglund, A Urban

    2004-01-01

    Cholinergic agonists produce spinal antinociception via mechanisms involving an increased release of intraspinal acetylcholine. The cholinergic receptor system interacts with several other receptor types, such as alpha2-adrenergic receptors. To fully understand these interactions, the effects...... of various receptor ligands on the cholinergic system must be investigated in detail. This study was initiated to investigate the effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine and the alpha2-adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors......, all ligands possessed affinity for nicotinic receptors. Clonidine and yohimbine binding was best fit to a one site binding curve and rilmenidine and efaroxan to a two site binding curve. The present study demonstrates that the tested alpha2-adrenergic receptor ligands affect intraspinal acetylcholine...

  19. Ubiquitous health monitoring and real-time cardiac arrhythmias detection: a case study.

    Science.gov (United States)

    Li, Jian; Zhou, Haiying; Zuo, Decheng; Hou, Kun-Mean; De Vaulx, Christophe

    2014-01-01

    As the symptoms and signs of heart diseases that cause sudden cardiac death, cardiac arrhythmia has attracted great attention. Due to limitations in time and space, traditional approaches to cardiac arrhythmias detection fail to provide a real-time continuous monitoring and testing service applicable in different environmental conditions. Integrated with the latest technologies in ECG (electrocardiograph) analysis and medical care, the pervasive computing technology makes possible the ubiquitous cardiac care services, and thus brings about new technical challenges, especially in the formation of cardiac care architecture and realization of the real-time automatic ECG detection algorithm dedicated to care devices. In this paper, a ubiquitous cardiac care prototype system is presented with its architecture framework well elaborated. This prototype system has been tested and evaluated in all the clinical-/home-/outdoor-care modes with a satisfactory performance in providing real-time continuous cardiac arrhythmias monitoring service unlimitedly adaptable in time and space.

  20. Plasma glutamine levels before cardiac surgery are related to post-surgery infections; an observational study

    Directory of Open Access Journals (Sweden)

    Hanneke Buter

    2016-11-01

    Full Text Available Abstract Background A low plasma glutamine level was found in 34% of patients after elective cardiothoracic surgery. This could be a result of the inflammation caused by surgical stress or the use of extracorporeal circulation (ECC. But it is also possible that plasma glutamine levels were already lowered before surgery and reflect an impaired metabolic state and a higher likelihood to develop complications. In the present study plasma glutamine levels were measured before and after cardiac surgery and we questioned whether there is a relation between plasma glutamine levels and duration of ECC and the occurrence of postoperative infections. Methods We performed a single-centre prospective, observational study in a closed-format, 20-bed, mixed ICU in a tertiary teaching hospital. We included consecutive patients after elective cardiac surgery with use of extracorporeal circulation. Blood samples were collected on the day prior to surgery and at admission on the ICU. The study was approved by the local Medical Ethics Committee (Regional Review Committee Patient-related Research, Medical Centre Leeuwarden, nWMO 115, April 28th 2015. Results Ninety patients were included. Pre-operative plasma glutamine level was 0.42 ± 0.10 mmol/l and post-operative 0.38 ± 0.09 mmol/l (p < 0.001. There was no relation between duration of extracorporeal circulation or aortic occlusion time and changes in plasma glutamine levels. A logistic regression analysis showed a significant correlation between the presence of a positive culture during the post-operative course and pre-operative plasma glutamine levels (p = 0.04. Conclusion Plasma glutamine levels are significantly lower just after cardiac surgery compared to pre-operative levels. We did not find a relation between the decrease in plasma glutamine levels and the duration of extracorporeal circulation or aortic clamp time. There was a correlation between pre-operative plasma glutamine levels

  1. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: A prospective study

    Directory of Open Access Journals (Sweden)

    Storm Christian

    2012-01-01

    Full Text Available Abstract Background Neuron specific enolase (NSE has repeatedly been evaluated for neurological prognostication in patients after cardiac arrest. However, it is unclear whether current guidelines for NSE cutoff levels also apply to cardiac arrest patients treated with hypothermia. Thus, we investigated the prognostic significance of absolute NSE levels and NSE kinetics in cardiac arrest patients treated with hypothermia. Methods In a prospective study of 35 patients resuscitated from cardiac arrest, NSE was measured daily for four days following admission. Outcome was assessed at ICU discharge using the CPC score. All patients received hypothermia treatment for 24 hours at 33°C with a surface cooling device according to current guidelines. Results The cutoff for absolute NSE levels in patients with unfavourable outcome (CPC 3-5 72 hours after cardiac arrest was 57 μg/l with an area under the curve (AUC of 0.82 (sensitivity 47%, specificity 100%. The cutoff level for NSE kinetics in patients with unfavourable outcome (CPC 3-5 was an absolute increase of 7.9 μg/l (AUC 0.78, sensitivity 63%, specificity 100% and a relative increase of 33.1% (AUC 0.803, sensitivity 67%, specificity 100% at 48 hours compared to admission. Conclusion In cardiac arrest patients treated with hypothermia, prognostication of unfavourable outcome by NSE kinetics between admission and 48 hours after resuscitation may be superior to prognostication by absolute NSE levels.

  2. Potential diagnostic value of regional myocardial adrenergic imaging using {sup 123}I-MIBG SPECT to identify patients with Lewy body diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lebasnier, Adrien; Peyronnet, Damien; Bouvard, Gerard [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Lamotte, Guillaume; Defer, Gilles [University Hospital Center of Caen, Department of Neurology, Caen (France); Manrique, Alain [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Cyceron PET Centre, Caen (France); Normandie Universite, Caen (France); Agostini, Denis [University Hospital Center of Caen, Department of Nuclear Medicine, Caen (France); Normandie Universite, Caen (France)

    2015-01-28

    The aim of this study was to determine the potential diagnostic value of regional myocardial adrenergic {sup 123}I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) imaging to identify patients with Lewy body diseases (LBD+). Sixty-four consecutive patients who underwent cardiac {sup 123}I-MIBG SPECT to differentiate LBD+, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), from patients without LBD (LBD-) were retrospectively reviewed. A neurologist expert in memory disorders determined the final clinical diagnosis by using international clinical diagnostic criteria. Planar [heart to mediastinum ratio (HMR)] and {sup 123}I-MIBG SPECT[innervation defect score (IDS)] using the 17-segment left ventricular model (five-point scale) were obtained 4 h after the injection of {sup 123}I-MIBG on a low-energy high-resolution (LEHR) collimator. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal HMR and IDS cut-off values to discriminate LBD+ from LBD-. Of the 64 patients, 45 (70 %) were diagnosed LBD+ (DLB, n = 27; PD, n = 18) and 19 were diagnosed LBD- (5 other dementias, 14 other parkinsonisms). The HMR and IDS of LBD+ were significantly different from those of LBD- (1.30 ± 0.21 vs 1.65 ± 0.26, p < 0.001; 39 ± 28 vs 8 ± 16, p = 0.001). The optimal HMR and IDS cut-off values to discriminate LBD+ (n = 45) from LBD- (n = 19) were 1.47 and 6/68, providing a sensitivity and specificity of 82.2 and 84.2 % and 86.7 and 73.7 %, respectively. Regional myocardial adrenergic {sup 123}I-MIBG imaging SPECT has a potential diagnostic value to identify LBD+. (orig.)

  3. Beta-adrenergic blockade for the treatment of hyperthyroidism.

    Science.gov (United States)

    Geffner, D L; Hershman, J M

    1992-07-01

    To review the clinical and biochemical effects of beta-adrenergic blocking drugs on hyperthyroidism. Studies published since 1972 were identified through a computerized search of MEDLINE and extensive searching of the bibliographies of the articles identified. Based on an understanding of the differences in beta-blocker metabolism in euthyroid and hyperthyroid patients, we reviewed the differences in pharmacokinetics and metabolic and clinical outcomes during their use in hyperthyroidism, as reported in the articles reviewed. beta Blockers have been used to modify the severity of the hyperadrenergic symptoms of hyperthyroidism for the past 20 years. The clinical efficacy of these agents is affected by hyperthyroid-induced alterations in their gastrointestinal absorption, hepatic metabolism, and renal excretion. The mechanisms whereby these clinical changes are effected is unknown. The agents differ in their beta 1 cardioselectivity, membrane-stabilizing activity, intrinsic sympathomimetic activity, and lipid solubility. They do not appear to alter synthesis or secretion of thyroid hormone by the thyroid gland. Their effects on thyroxine metabolism are contradictory. Decreased thyroxine to triiodothyronine conversion is caused by some, but not all, beta blockers, and this appears to correlate with membrane-stabilizing activity. There does not appear to be any alteration in catecholamine sensitivity during beta-adrenergic blockade. The principal mechanism of action of beta blockers in hyperthyroidism is to antagonize beta-receptor-mediated effects of catecholamines. beta Blockers are effective in treating hypermetabolic symptoms in a variety of hyperthyroid states. Used alone, they offer significant symptomatic relief. They are also useful adjuvants to antithyroid medications, surgery, and radioactive iodide treatment in patients with Graves' disease and toxic nodular goiters.

  4. Downregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR.

    Directory of Open Access Journals (Sweden)

    Qian Yin

    Full Text Available β-adrenergic receptors (β-ARs play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO at the dose of 0.25 mg·kg(-1·d(-1 for 7 days. We found that the expression of β1- and β2-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMP-response element binding protein(CREB is a well-known transcription factor of β-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR, a RNA binding protein, which binds to the 3'-untranslated region of the β-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of β-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of β-AR expression in ISO induced cardiac remodeling.

  5. A systemic evaluation of cardiac differentiation from mRNA reprogrammed human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Ashish Mehta

    Full Text Available Genetically unmodified cardiomyocytes mandated for cardiac regenerative therapy is conceivable by "foot-print free" reprogramming of somatic cells to induced pluripotent stem cells (iPSC. In this study, we report generation of foot-print free hiPSC through messenger RNA (mRNA based reprograming. Subsequently, we characterize cardiomyocytes derived from these hiPSC using molecular and electrophysiological methods to characterize their applicability for regenerative medicine. Our results demonstrate that mRNA-iPSCs differentiate ontogenetically into cardiomyocytes with increased expression of early commitment markers of mesoderm, cardiac mesoderm, followed by cardiac specific transcriptional and sarcomeric structural and ion channel genes. Furthermore, these cardiomyocytes stained positively for sarcomeric and ion channel proteins. Based on multi-electrode array (MEA recordings, these mRNA-hiPSC derived cardiomyocytes responded predictably to various pharmacologically active drugs that target adrenergic, sodium, calcium and potassium channels. The cardiomyocytes responded chronotropically to isoproterenol in a dose dependent manner, inotropic activity of nifidipine decreased spontaneous contractions. Moreover, Sotalol and E-4031 prolonged QT intervals, while TTX reduced sodium influx. Our results for the first time show a systemic evaluation based on molecular, structural and functional properties of cardiomyocytes differentiated from mRNA-iPSC. These results, coupled with feasibility of generating patient-specific iPSCs hold great promise for the development of large-scale generation of clinical grade cardiomyocytes for cardiac regenerative medicine.

  6. A Prospective Multi-Institutional Cohort Study of Mediastinal Infections After Cardiac Operations.

    Science.gov (United States)

    Perrault, Louis P; Kirkwood, Katherine A; Chang, Helena L; Mullen, John C; Gulack, Brian C; Argenziano, Michael; Gelijns, Annetine C; Ghanta, Ravi K; Whitson, Bryan A; Williams, Deborah L; Sledz-Joyce, Nancy M; Lima, Brian; Greco, Giampaolo; Fumakia, Nishit; Rose, Eric A; Puskas, John D; Blackstone, Eugene H; Weisel, Richard D; Bowdish, Michael E

    2018-02-01

    Mediastinal infections are a potentially devastating complication of cardiac operations. This study analyzed the frequency, risk factors, and perioperative outcomes of mediastinal infections after cardiac operations. In 2010, 5,158 patients enrolled in a prospective study evaluating infections after cardiac operations and their effect on readmissions and mortality for up to 65 days after the procedure. Clinical and demographic characteristics, operative variables, management practices, and outcomes were compared for patients with and without mediastinal infections, defined as deep sternal wound infection, myocarditis, pericarditis, or mediastinitis. There were 43 mediastinal infections in 41 patients (cumulative incidence, 0.79%; 95% confidence interval [CI] 0.60% to 1.06%). Median time to infection was 20.0 days, with 65% of infections occurring after the index hospitalization discharge. Higher body mass index (hazard ratio [HR] 1.06; 95% CI, 1.01 to 1.10), higher creatinine (HR, 1.25; 95% CI, 1.13 to 1.38), peripheral vascular disease (HR, 2.47; 95% CI, 1.21 to 5.05), preoperative corticosteroid use (HR, 3.33; 95% CI, 1.27 to 8.76), and ventricular assist device or transplant surgery (HR, 5.81; 95% CI, 2.36 to 14.33) were associated with increased risk of mediastinal infection. Postoperative hyperglycemia (HR, 3.15; 95% CI, 1.32 to 7.51) was associated with increased risk of infection in nondiabetic patients. Additional length of stay attributable to mediastinal infection was 11.5 days (bootstrap 95% CI, 1.88 to 21.11). Readmission rates and mortality were five times higher in patients with mediastinal infection than in patients without mediastinal infection. Mediastinal infection after a cardiac operation is associated with substantial increases in length of stay, readmissions, and death. Reducing these infections remains a high priority, and improving post-operative glycemic management may reduce their risk in patients without diabetes. Copyright © 2018 The

  7. Effect of cardiopulmonary bypass on beta adrenergic receptor-adenylate cyclase system on surfaces of peripheral lymphocytes.

    Science.gov (United States)

    Luo, A; Tian, Y; Jin, S

    2000-01-01

    The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after cardiopulmonary bypass (CPB) were significantly lower than those before anesthetics in the patients undergoing cardiac surgery with CPB. These findings suggested that CPB could cause serious damage to adrenergic beta receptor-adenylate cyclase system on circulating lymphocytes surfaces, which might be one of the mechanisms resulting in immunosuppression after open heart surgery with CPB.

  8. Mobile Technology Use Across Age Groups in Patients Eligible for Cardiac Rehabilitation: Survey Study.

    Science.gov (United States)

    Gallagher, Robyn; Roach, Kellie; Sadler, Leonie; Glinatsis, Helen; Belshaw, Julie; Kirkness, Ann; Zhang, Ling; Gallagher, Patrick; Paull, Glenn; Gao, Yan; Partridge, Stephanie Ruth; Parker, Helen; Neubeck, Lis

    2017-10-24

    Emerging evidence indicates mobile technology-based strategies may improve access to secondary prevention and reduce risk factors in cardiac patients. However, little is known about cardiac patients' use of mobile technology, particularly for health reasons and whether the usage varies across patient demographics. This study aimed to describe cardiac patients' use of mobile technology and to determine variations between age groups after adjusting for education, employment, and confidence with using mobile technology. Cardiac patients eligible for attending cardiac rehabilitation were recruited from 9 hospital and community sites across metropolitan and rural settings in New South Wales, Australia. Participants completed a survey on the use of mobile technology devices, features used, confidence with using mobile technology, willingness and interest in learning, and health-related use. The sample (N=282) had a mean age of 66.5 (standard deviation [SD] 10.6) years, 71.9% (203/282) were male, and 79.0% (223/282) lived in a metropolitan area. The most common diagnoses were percutaneous coronary intervention (33.3%, 94/282) and myocardial infarction (22.7%, 64/282). The majority (91.1%, 257/282) used at least one type of technology device, 70.9% (200/282) used mobile technology (mobile phone/tablet), and 31.9% (90/282) used all types. Technology was used by 54.6% (154/282) for health purposes, most often to access information on health conditions (41.4%, 117/282) and medications (34.8%, 98/282). Age had an important independent association with the use of mobile technology after adjusting for education, employment, and confidence. The youngest group (mobile technology than the oldest (>69 years) age group (odds ratio [OR] 4.45, 95% CI 1.46-13.55), 5 times more likely to use mobile apps (OR 5.00, 95% CI 2.01-12.44), and 3 times more likely to use technology for health-related reasons (OR 3.31, 95% CI 1.34-8.18). Compared with the older group, the middle age group (56

  9. Beta-adrenergic receptor sensitivity, autonomic balance and serotonergic activity in practitioners of Transcendental Meditation

    International Nuclear Information System (INIS)

    Hill, D.A.

    1989-01-01

    The aim of this thesis was to investigate the acute autonomic effects of the Transcendental Meditation Program (TM) and resolve the conflict arising from discrepant neurochemical and psychophysiological data. Three experimental investigations were performed. The first examined beta 2 -adrenergic receptors (AR's) on peripheral blood lymphocytes, via [I 125 ]iodocyanopindolol binding, in 10 male mediating and 10 age matched non-meditating control subjects, to test the hypothesis that the long-term practice of TM and the TM Sidhi Program (TMSP) reduces end organ sensitivity to adrenergic agonists. The second investigated respiratory sinus arrhythmia (an indirect measure of cardiac Parasympathetic Nervous System tone), and skin resistance (a measure of Sympathetic Nervous System tone) during periods of spontaneous respiratory apneusis, a phenomenon occurring during TM that is known to mark the subjective experience of transcending. The third was within subject investigation of the acute effects of the TMSP on 5-hydroxytryptamine (5-HT) activity. Platelet 5-HT was assayed by high pressure liquid chromatography with electrochemical detection, plasma prolactin (PL) and lutenizing hormone (LH) by radioimmunoassay, tryptophan by spectrofluorimetry, and alpha-1-acid glycoprotein (AGP, a modulator of 5-HT uptake) by radial immunodiffusion assay

  10. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  11. NADPH- Diaphorase positive cardiac neurons in the atria of mice. A morphoquantitative study

    Directory of Open Access Journals (Sweden)

    Castelucci Patrícia

    2006-02-01

    Full Text Available Abstract Background The present study was conducted to determine the location, the morphology and distribution of NADPH-diaphorase positive neurons in the cardiac nerve plexus of the atria of mice (ASn. This plexus lies over the muscular layer of the atria, dorsal to the muscle itself, in the connective tissue of the subepicardium. NADPH- diaphorase staining was performed on whole-mount preparations of the atria mice. For descriptive purposes, all data are presented as means ± SEM. Results The majority of the NADPH-diaphorase positive neurons were observed in the ganglia of the plexus. A few single neurons were also observed. The number of NADPH-d positive neurons was 57 ± 4 (ranging from 39 to 79 neurons. The ganglion neurons were located in 3 distinct groups: (1 in the region situated cranial to the pulmonary veins, (2 caudally to the pulmonary veins, and (3 in the atrial groove. The largest group of neurons was located cranially to the pulmonary veins (66.7%. Three morphological types of NADPH-diaphorase neurons could be distinguished on the basis of their shape: unipolar cells, bipolar cells and cells with three processes (multipolar cells. The unipolar neurons predominated (78.9%, whereas the multipolar were encountered less frequently (5,3%. The sizes (area of maximal cell profile of the neurons ranged from about 90 μm2to about 220 μm2. Morphometrically, the three types of neurons were similar and there were no significant differences in their sizes. The total number of cardiac neurons (obtained by staining the neurons with NADH-diaphorase method was 530 ± 23. Therefore, the NADPH-diaphorase positive neurons of the heart represent 10% of the number of cardiac neurons stained by NADH. Conclusion The obtained data have shown that the NADPH-d positive neurons in the cardiac plexus of the atria of mice are morphologically different, and therefore, it is possible that the function of the neurons may also be different.

  12. Cardiac magnetic resonance radiofrequency tissue tagging for diagnosis of constrictive pericarditis: A proof of concept study.

    Science.gov (United States)

    Power, John A; Thompson, Diane V; Rayarao, Geetha; Doyle, Mark; Biederman, Robert W W

    2016-05-01

    Invasive cardiac catheterization is the venerable "gold standard" for diagnosing constrictive pericarditis. However, its sensitivity and specificity vary dramatically from center to center. Given the ability to unequivocally define segments of the pericardium with the heart via radiofrequency tissue tagging, we hypothesize that cardiac magnetic resonance has the capability to be the new gold standard. All patients who were referred for cardiac magnetic resonance evaluation of constrictive pericarditis underwent cardiac magnetic resonance radiofrequency tissue tagging to define visceral-parietal pericardial adherence to determine constriction. This was then compared with intraoperative surgical findings. Likewise, all preoperative cardiac catheterization testing was reviewed in a blinded manner. A total of 120 patients were referred for clinical suspicion of constrictive pericarditis. Thirty-nine patients were defined as constrictive pericarditis positive solely via radiofrequency tissue-tagging cardiac magnetic resonance, of whom 21 were positive, 4 were negative, and 1 was equivocal for constrictive pericarditis, as defined by cardiac catheterization. Of these patients, 16 underwent pericardiectomy and were surgically confirmed. There was 100% agreement between cardiac magnetic resonance-defined constrictive pericarditis positivity and postsurgical findings. No patients were misclassified by cardiac magnetic resonance. In regard to the remaining constrictive pericarditis-positive patients defined by cardiac magnetic resonance, 10 were treated medically, declined, were ineligible for surgery, or were lost to follow-up. Long-term follow-up of those who were constrictive pericarditis negative by cardiac magnetic resonance showed no early or late crossover to the surgery arm. Cardiac magnetic resonance via radiofrequency tissue tagging offers a unique, efficient, and effective manner of defining clinically and surgically relevant constrictive pericarditis

  13. Renal content and output of epidermal growth factor in long-term adrenergic agonist-treated rats

    DEFF Research Database (Denmark)

    Thulesen, J; Nexø, Ebba; Poulsen, Steen Seier

    2000-01-01

    This study investigates the renal and urinary levels of epidermal growth factor (EGF) in rats under long-term treatment with alpha- or beta-adrenergic agonists. Urine samples were obtained on days 7, 14 and 21, and renal tissue samples on day 21. EGF was quantified by ELISA and tissue sections were...... material in the distal tubules. Concomitantly, reduced levels of EGF and EGF mRNA were observed, and also the urinary levels of EGF were reduced. Together, these observations indicate alpha-adrenergic treatment to affect the distal tubules. Treatment with the beta-adrenergic agonist did not change...... fractional kidney weight, but initially the urinary excretion of EGF was reduced. The data add further evidence to the suggestion that activity of the sympathetic nervous system influences renal homeostasis of EGF, either directly or indirectly through renal histopathological changes....

  14. Functional response of white rats isolated heart to the stimulation of adrenergic receptors after gamma-irradiation in low doses

    International Nuclear Information System (INIS)

    Antonenko, A.N.; Lobanok, L.M.

    1999-01-01

    It was investigated the effects of acute gamma-irradiation on bio mechanical activity of rats heart isolated by Langendorf's method in early and delayed terms after exposure to gamma-rays. Intra ventricle pressure and the rate of its growth, volumetric rate of coronal flow, frequency of heart contraction were registered. Stimulation of alpha-adrenergic receptors was conducted by means of specific agonist mesatone and stimulation of beta-adrenergic receptors was made by means of isoprenaline. The study has shown that acute irradiation of rats caused the decrease of both contractile ability and relaxation of myocardium in a 10 days after exposure. In delayed period bio mechanical activity of isolated heart was restored. Functional response of heart to the stimulation of alpha- and beta-adrenergic receptors was decreased in all terms of investigation

  15. Cardiac supporting device using artificial rubber muscle: preliminary study to active dynamic cardiomyoplasty.

    Science.gov (United States)

    Saito, Yoshiaki; Suzuki, Yasuyuki; Goto, Takeshi; Daitoku, Kazuyuki; Minakawa, Masahito; Fukuda, Ikuo

    2015-12-01

    Dynamic cardiomyoplasty is a surgical treatment that utilizes the patient's skeletal muscle to support circulation. To overcome the limitations of autologous skeletal muscles in dynamic cardiomyoplasty, we studied the use of a wrapped-type cardiac supporting device using pneumatic muscles. Four straight rubber muscles (Fluidic Muscle, FESTO, Esslingen, Germany) were used and connected to pressure sensors, solenoid valves, a controller and an air compressor. The driving force was compressed air. A proportional-integral-derivative system was employed to control the device movement. An overflow-type mock circulation system was used to analyze the power and the controllability of this new device. The device worked powerfully with pumped flow against afterload of 88 mmHg, and the beating rate and contraction/dilatation time were properly controlled using simple software. Maximum pressure inside the ventricle and maximum output were 187 mmHg and 546.5 ml/min, respectively, in the setting of 50 beats per minute, a contraction/dilatation ratio of 1:2, a preload of 18 mmHg, and an afterload of 88 mmHg. By changing proportional gain, contraction speed could be modulated. This study showed the efficacy and feasibility of a pneumatic muscle for use in a cardiac supporting device.

  16. Patient perspectives on the Hula Empowering Lifestyle Adaptation Study: benefits of dancing hula for cardiac rehabilitation.

    Science.gov (United States)

    Maskarinec, Gregory G; Look, Mele; Tolentino, Kalehua; Trask-Batti, Mililani; Seto, Todd; de Silva, Mapuana; Kaholokula, Joseph Keawe'aimoku

    2015-01-01

    The Hula Empowering Lifestyle Adaption Study, funded by the National Institute on Minority Health and Health Disparities, was a 5-year research trial evaluating the impact of the traditional Native Hawaiian dance form, hula, as an exercise modality for cardiac rehabilitation, compared with usual care, on individuals recently hospitalized for a cardiac event or who had recently undergone coronary artery bypass surgery. Seeking to learn what physical, mental, spiritual, and social effects the intervention may have had for participants, we interviewed 20 of a total of 35 patients who were enrolled in the dance arm of the study. Classical thematic triangulation analysis was used. Participants recognized that hula's coordination of body, mind, and spirit as a group activity deepened their appreciation of and connections to Hawaiian culture. This was true for those who were Native Hawaiian, connecting to their own cultural heritage, as well as for non-Native Hawaiians, who found that it improved their appreciation of the surrounding cultural traditions of the host culture where they now live. Not only was hula a safe activity that improved functional capacity, participants also regarded its significant sociocultural aspects-even for participants who are not Native Hawaiian -as enhancing its value and meaningfulness. Learning the words of well-known Hawaiian songs provided additional long-term cues that encouraged "ownership" of the therapy and acted as practical reminders of the importance of exercise and lifestyle moderation while also offering new spiritual connections to the surrounding social environment. © 2014 Society for Public Health Education.

  17. Computational study of ‘HUB’ microRNA in human cardiac diseases

    Science.gov (United States)

    Krishnan, Remya; Nair, Achuthsankar S.; Dhar, Pawan K.

    2017-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs ~22 nucleotides long that do not encode for proteins but have been reported to influence gene expression in normal and abnormal health conditions. Though a large body of scientific literature on miRNAs exists, their network level profile linking molecules with their corresponding phenotypes, is less explored. Here, we studied a network of 191 human miRNAs reported to play a role in 30 human cardiac diseases. Our aim was to study miRNA network properties like hubness and preferred associations, using data mining, network graph theory and statistical analysis. A total of 16 miRNAs were found to have a disease node connectivity of >5 edges (i.e., they were linked to more than 5 diseases) and were considered hubs in the miRNAcardiac disease network. Alternatively, when diseases were considered as hubs, >10 of miRNAs showed up on each ‘disease hub node’. Of all the miRNAs associated with diseases, 19 miRNAs (19/24= 79.1% of upregulated events) were found to be upregulated in atherosclerosis. The data suggest micro RNAs as early stage biological markers in cardiac conditions with potential towards microRNA based therapeutics. PMID:28479745

  18. Prospective cohort study on noise levels in a pediatric cardiac intensive care unit.

    Science.gov (United States)

    Garcia Guerra, Gonzalo; Joffe, Ari R; Sheppard, Cathy; Pugh, Jodie; Moez, Elham Khodayari; Dinu, Irina A; Jou, Hsing; Hartling, Lisa; Vohra, Sunita

    2018-04-01

    To describe noise levels in a pediatric cardiac intensive care unit, and to determine the relationship between sound levels and patient sedation requirements. Prospective observational study at a pediatric cardiac intensive care unit (PCICU). Sound levels were measured continuously in slow A weighted decibels dB(A) with a sound level meter SoundEarPro® during a 4-week period. Sedation requirement was assessed using the number of intermittent (PRNs) doses given per hour. Analysis was conducted with autoregressive moving average models and the Granger test for causality. 39 children were included in the study. The average (SD) sound level in the open area was 59.4 (2.5) dB(A) with a statistically significant but clinically unimportant difference between day/night hours (60.1 vs. 58.6; p-value noise levels were > 90 dB. There was a significant association between average (p-value = 0.030) and peak sound levels (p-value = 0.006), and number of sedation PRNs. Sound levels were above the recommended values with no differences between day/night or open area/single room. High sound levels were significantly associated with sedation requirements. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Adjustments in cholinergic, adrenergic and purinergic control of cardiovascular function in snapping turtle embryos (Chelydra serpentina) incubated in chronic hypoxia.

    Science.gov (United States)

    Eme, John; Rhen, Turk; Crossley, Dane A

    2014-10-01

    Adenosine is an endogenous nucleoside that acts via G-protein coupled receptors. In vertebrates, arterial or venous adenosine injection causes a rapid and large bradycardia through atrioventricular node block, a response mediated by adenosine receptors that inhibit adenylate cyclase and decrease cyclic AMP concentration. Chronic developmental hypoxia has been shown to alter cardioregulatory mechanisms in reptile embryos, but adenosine's role in mediating these responses is not known. We incubated snapping turtle embryos under chronic normoxic (N21; 21 % O2) or chronic hypoxic conditions (H10; 10 % O2) beginning at 20 % of embryonic incubation. H10 embryos at 90 % of incubation were hypotensive relative to N21 embryos in both normoxic and hypoxic conditions. Hypoxia caused a hypotensive bradycardia in both N21 and H10 embryos during the initial 30 min of exposure; however, f H and P m both trended towards increasing during the subsequent 30 min, and H10 embryos were tachycardic relative to N21 embryos in hypoxia. Following serial ≥1 h exposure to normoxic and hypoxic conditions, a single injection of adenosine (1 mg kg(-1)) was given. N21 and H10 embryos responded to adenosine injection with a rapid and large hypotensive bradycardia in both normoxia and hypoxia. Gene expression for adenosine receptors were quantified in cardiac tissue, and Adora1 mRNA was the predominant receptor subtype with transcript levels 30-82-fold higher than Adora2A or Adora2B. At 70 % of incubation, H10 embryos had lower Adora1 and Adora2B expression compared to N21 embryos. Expression of Adora1 and Adora2B decreased in N21 embryos during development and did not differ from H10 embryos at 90 % of incubation. Similar to previous results in normoxia, H10 embryos in hypoxia were chronically tachycardic compared to N21 embryos before and after complete cholinergic and adrenergic blockade. Chronic hypoxia altered the development of normal cholinergic and adrenergic tone, as well as

  20. Cardiopulmonary resuscitation of out-of-hospital traumatic cardiac arrest in Qatar: A nationwide population-based study.

    Science.gov (United States)

    Irfan, Furqan B; Consunji, Rafael; El-Menyar, Ayman; George, Pooja; Peralta, Ruben; Al-Thani, Hassan; Thomas, Stephen Hodges; Alinier, Guillaume; Shuaib, Ashfaq; Al-Suwaidi, Jassim; Singh, Rajvir; Castren, Maaret; Cameron, Peter A; Djarv, Therese

    2017-08-01

    Traumatic cardiac arrest studies have reported improved survival rates recently, ranging from 1.7-7.5%. This population-based nationwide study aims to describe the epidemiology, interventions and outcomes, and determine predictors of survival from out-of-hospital traumatic cardiac arrest (OHTCA) in Qatar. An observational retrospective population-based study was conducted on OHTCA patients in Qatar, from January 2010 to December 2015. Traumatic cardiac arrest was redefined to include out-of-hospital traumatic cardiac arrest (OHTCA) and in-hospital traumatic cardiac arrest (IHTCA). A total of 410 OHTCA patients were included in the 6-year study period. The mean annual crude incidence rate of OHTCA was 4.0 per 100,000 population, in Qatar. OHTCA mostly occurred in males with a median age of 33. There was a preponderance of blunt injuries (94.3%) and head injuries (66.3%). Overall, the survival rate was 2.4%. Shockable rhythm, prehospital external hemorrhage control, in-hospital blood transfusion, and surgery were associated with higher odds of survival. Adrenaline (Epinephrine) lowered the odds of survival. The incidence of OHTCA was less than expected, with a low rate of survival. Thoracotomy was not associated with improved survival while Adrenaline administration lowered survival in OHTCA patients with majority blunt injuries. Interventions to enable early prehospital control of hemorrhage, blood transfusion, thoracostomy and surgery improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly

    DEFF Research Database (Denmark)

    Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E

    2016-01-01

    of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. METHODS AND RESULTS: The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who...... on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). OBJECTIVE: The aim...... and sustainability. CONCLUSION: The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR....

  2. Organ donation in cardiac arrest patients treated with extracorporeal CPR: A single centre observational study.

    Science.gov (United States)

    Casadio, Maria Chiara; Coppo, Anna; Vargiolu, Alessia; Villa, Jacopo; Rota, Matteo; Avalli, Leonello; Citerio, Giuseppe

    2017-09-01

    In a consecutive cohort of cardiac arrest (CA) treated with extracorporeal cardiopulmonary resuscitation (eCPR), we describe the incidence of brain death (BD), the eligibility for organ donation and the short-term follow-up of the transplanted organs. All refractory in- and out-of-hospital CA admitted to our Cardiac Intensive Care Unit between January 2011 and September 2016 treated with eCPR were enrolled in the study. 112 CA patients received eCPR. 82 (73.2%) died in hospital, 25 BD (22.3%) and 57 for other causes (50.9%). At the time of first neurological evaluation after rewarming, variables related to evolution to BD were a lower GCS (3 [3-3] vs. 8 [3-11], pdonation in BD patients was 56%, with 39 donated organs: 23 kidneys, 12 livers, and 4 lungs. 89.74% of the transplanted organs reached an early good functional recovery. In refractory CA patients treated with eCPR, the prevalence of BD is high. This population has a high potential for considering organ donation. Donated organs have a good outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. [Current provision of cardiac rehabilitation intervention in the Lombardy Region, Italy: a benchmark study].

    Science.gov (United States)

    Ambrosetti, Marco; Porazzi, Emanuele; Diaco, Tommaso; Febo, Oreste; Tramarin, Roberto; Malinverni, Claudio; Zaniboni, Daniela; Passera, Martina; Marchetti, Paolo

    2010-11-01

    Benchmarking is a process of comparison between the performance characteristics of separate, often competing organizations, intended to enable each participant to improve its own performance in the marketplace. Benchmarking could be translated to the health system from the management field, in order to improve quality and health outcomes. This benchmarking study focused on structural and process aspects regarding the current delivery of cardiac rehabilitation (CR) interventions in the Lombardy Region. Data for analysis were derived from the ISYDE-2008 (Italian Survey on Cardiac Rehabilitation) project of the Italian Association for Cardiovascular Prevention, Rehabilitation, and Epidemiology. Thirty-eight CR units accepted to provide open information about types of supply of CR interventions, organization, location, number of active beds, personnel, duty services, expectancy days before admission, and complexity of patient populations. As a major finding, in-hospital programs actually represent the largest part of CR interventions delivered in the Lombardy Region, generally in well-defined cardiovascular departments, and patients are mostly referred in the short period after a major cardiovascular event. This model could help healthcare organizations to understand where they have strengths and weaknesses depending upon changes in supply, demand and market conditions.

  4. [Incidence of urinary tract infections after cardiac surgery: comparative study accordind to catheterization device].

    Science.gov (United States)

    Hidalgo Fabrellas, I; Rebollo Pavón, M; Planas Canals, M; Barbero Cabezas, M

    2015-01-01

    Urinary tract infections (UTI) associated with urethral catheterization are the second cause of nosocomial infections in Intensive care units. We confirm a UTI when we get a result of 100,000 CFU/ml with at least one microorganism in a urine culture. Compare and determine the incidence of UTI in cardiac surgery postpoperative patients according to the catheterization device. A prospective, randomized analytical observational study of patients in the immediate cardiac surgery postoperative period. One group was probed with catheter Foley and one was inserted the catheter BIPFoley-Bactiguard® (CBF). The CBF is coated with noble metals (silver, gold and palladium) and biocompatible antimicrobial properties, covering the entire surface of the device and prevents the formation of biofilm, microbial adherence and colonization. 116 cases, 59.5% (69 cases) were negative for UTI and 40.5% (47 cases) were positive. Out of the positive UTI results, 25% were carriers of catheter Foley and 15.5% of CBF. Most common etiologic microorganisms: Escherichia coli 29.8% Klebsiella pneumonia 29.8%, Klebsiella oxytoca 9%. With the data we have observed that patients catheterized BIPfoley-Bactiguard® are infected to a lesser extent than Foley carriers. Copyright © 2013 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

  5. Cardiac rehabilitation

    Science.gov (United States)

    ... rehab; Heart failure - cardiac rehab References Anderson L, Taylor RS. Cardiac rehabilitation for people with heart disease: ... of Medicine, Division of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed ...

  6. Psychiatric disorders and cardiac anxiety in exercising and sedentary coronary artery disease patients: a case-control study

    Directory of Open Access Journals (Sweden)

    A. Sardinha

    2012-12-01

    Full Text Available Regular physical exercise has been shown to favorably influence mood and anxiety; however, there are few studies regarding psychiatric aspects of physically active patients with coronary artery disease (CAD. The objective of the present study was to compare the prevalence of psychiatric disorders and cardiac anxiety in sedentary and exercising CAD patients. A total sample of 119 CAD patients (74 men were enrolled in a case-control study. The subjects were interviewed to identify psychiatric disorders and responded to the Cardiac Anxiety Questionnaire. In the exercise group (N = 60, there was a lower prevalence (45 vs 81%; P < 0.001 of at least one psychiatric diagnosis, as well as multiple comorbidities, when compared to the sedentary group (N = 59. Considering the Cardiac Anxiety Questionnaire, sedentary patients presented higher scores compared to exercisers (mean ± SEM = 55.8 ± 1.9 vs 37.3 ± 1.6; P < 0.001. In a regression model, to be attending a medically supervised exercise program presented a relevant potential for a 35% reduction in cardiac anxiety. CAD patients regularly attending an exercise program presented less current psychiatric diagnoses and multiple mental-related comorbidities and lower scores of cardiac anxiety. These salutary mental effects add to the already known health benefits of exercise for CAD patients.

  7. Characterization of the hypothermic effect of the synthetic cannabinoid HU-210 in the rat. Relation to the adrenergic system and endogenous pyrogens.

    Science.gov (United States)

    Ovadia, H; Wohlman, A; Mechoulam, R; Weidenfeld, J

    1995-02-01

    In the present study we have characterized the hypothermic effect of the psychoactive cannabinoid HU-210, by investigating its interaction with the endogenous pyrogens, IL-1 and PGE2. We also studied the involvement of the adrenergic system in mediation of this hypothermic effect. Injection of HU-210 directly into the preoptic area caused a dose dependent reduction of rectal temperature from 37 to 32.1 degrees C. Injection of the non-psychoactive analog, HU-211 which does not bind to brain cannabinoid receptor, did not affect body temperature. Injection of the adrenergic agonists, CGP-12177 and clonidine (beta, and alpha adrenergic agonists, respectively) abrogated the hypothermia induced by HU-210. Injection of the adrenergic antagonists, prazosin (alpha 1) and propranolol (beta) enhanced the hypothermic effect of HU-210. Intracerebral administration of IL-1 or PGE2 to rats pretreated with HU-210 caused a transient inhibition of the hypothermia. The ex vivo rate of basal or bacterial endotoxin-induced synthesis of PGE2 by different brain regions, including the preoptic area was not affected by HU-210 administration. These results suggest that the synthetic cannabinoid HU-210 acts in the preoptic area, probably via the brain cannabinoid receptor to induce hypothermia. The hypothermic effect can be antagonized by adrenergic agonists and enhanced by adrenergic antagonists. HU-210 does not interfere with the pyrogenic effect of IL-1 or PGE2.

  8. Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function.

    Science.gov (United States)

    Wang, Xinrui; Fitts, Robert H

    2017-08-01

    Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the β-adrenergic

  9. Study on the effect of hypoxia on apoptosis of cultured newly born rat cardiac myocytes

    International Nuclear Information System (INIS)

    Su Weidong; Li Huiqiang; Yao Zhi

    2005-01-01

    Objective: To investigate the possible hypoxia-mediated cellular apoptosis after ischemic cardiac injury via a model of cultured newly born rat cardiac myocytes. Methods: Cardiac myocytes cultures from newly born rats (1-3d) were examined for apoptosis with HE stain and flow cytometry after cultured 96h and again examined after exposure to hypoxic environment for 16h. Results: Apoptotic changes were evident in the hypoxic culture cells. The HE stain revealed cellular shrinkage, nuclear chromosomal condensation with cytoplasmic eosinophilia. Also, distinct apoptosis peak was observed in the flow cytometry. Conclusion: This experiment proved that hypoxic model of cardiac myocyte culture showed definite apoptosis of the cells. (authors)

  10. Heart shaking transitions - A phenomenological-hermeneutic study of patients´ experiences in cardiac rehabilitation

    DEFF Research Database (Denmark)

    Simonÿ, Charlotte; Dreyer, Pia; Pedersen, Birthe D.

    enrolled in the cardiac rehabilitation programme. The data underwent interpretation consisting of three phases: naïve reading, structural analysis and comprehensive interpretation. Results. The preliminary findings are that the patients go through a Heart Shaking Journey in Cardiac Rehabilitation. Three......-patient cardiac rehabilitation during 1-2 months is offered after the acute treatment. Knowledge of the patients’ experiences of cardiac problems when receiving the current standards of treatment is needed in order to develop sufficient care. Hence the aim was to investigate how patients with new onset unstable...

  11. Effects of superior cervical ganglionectomy on alpha 2 adrenergic receptors in dog cerebral arteries

    International Nuclear Information System (INIS)

    Fujiwara, M.; Tsukahara, T.; Taniguchi, T.; Usui, H.

    1986-01-01

    Norepinephrine (NE)- and clonidine-induced contractions of dog cerebral arteries were attenuated by yohimbine but not affected by prazosin. There was no detectable 3 H-prazosin binding site in the cerebral arteries. On the other hand, 3 H-yohimbine binding studies revealed the presence of two binding sites with high and low affinities in the cerebral arteries. After superior cervical ganglionectomy, NE- and clonidine-induced contractions of the denervated cerebral arteries were not altered compared with the control arteries. The binding study revealed that there was low affinity 3 H-yohimbine binding sites, whereas high affinity sites were not detectable. These results suggest that there are two different NE binding sites in alpha 2 adrenergic receptors, and that the high affinity sites are presynaptically located and low affinity sites are postsynaptic. It is also suggested that NE-induced contractions are mediated by postsynaptic low affinity sites of alpha 2 adrenergic receptors in the dog cerebral arteries

  12. Monovalent cation and amiloride analog modulation of adrenergic ligand binding to the unglycosylated alpha 2B-adrenergic receptor subtype

    International Nuclear Information System (INIS)

    Wilson, A.L.; Seibert, K.; Brandon, S.; Cragoe, E.J. Jr.; Limbird, L.E.

    1991-01-01

    The unglycosylated alpha 2B subtype of the alpha 2-adrenergic receptor found in NG-108-15 cells possesses allosteric regulation of adrenergic ligand binding by monovalent cations and 5-amino-substituted amiloride analogs. These findings demonstrate that allosteric modulation of adrenergic ligand binding is not a property unique to the alpha 2A subtype. The observation that amiloride analogs as well as monovalent cations can modulate adrenergic ligand binding to the nonglycosylated alpha 2B subtype indicates that charge shielding due to carbohydrate moieties does not play a role in this allosteric modulation but, rather, these regulatory effects result from interactions of cations and amiloride analogs with the protein moiety of the receptor. Furthermore, the observation that both alpha 2A and alpha 2B receptor subtypes are modulated by amiloride analogs suggests that structural domains that are conserved between the two are likely to be involved in this allosteric modulation

  13. Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.

    Directory of Open Access Journals (Sweden)

    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies to the alpha(1-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A-adrenergic receptor and maintained them for one year. Alpha(1A-adrenergic antibodies (alpha(1A-AR-AB were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min. Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A-AR-AB could contribute to cardiovascular endorgan damage.

  14. Impact of exercise rehabilitation on cardiac neuronal function in heart failure. An iodine-123 metaiodobenzylguanidine scintigraphy study

    Energy Technology Data Exchange (ETDEWEB)

    Agostini, D.; Bouvard, G. [Service de Medecine Nucleaire, CHU Cote de Nacre, Caen (France); Lecluse, E.; Grollier, G.; Potier, J.C. [Service de Cardiologie, CHU Cote de Nacre, Caen (France); Belin, A. [Service de Readaptation Cardiaque, CHU Cote de Nacre, Caen (France); Babatasi, G. [Service de Chirurgie Cardio-Thoracique, CHU Cote de Nacre, Caen (France); Amar, M.H. [Centre Francois Baclesse, Caen (France). Service de Recherche Clinique

    1998-03-01

    Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiobodenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable chronic heart failure of NYHA class II-III and an initial resting radionuclide left ventricular ejection fraction (LVEF) <50% were enrolled in the study. Patients underwent progressive, supervised endurance training (treadmill test, Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a cardiac rehabilitation referral centre in order to measure exercise parameters. Planar {sup 123}I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801{+-}428 vs 1229{+-}245 kpm.min{sup -1}, P=0.001), exercise duration (504{+-}190 vs 649{+-}125 s, P=0.02), and myocardial MIBG uptake (135%{+-}19% vs 156%{+-}25%, P=0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%{+-}9% vs 21%{+-}10%, p=NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. (orig.)

  15. Exercise training normalizes renal blood flow responses to acute hypoxia in experimental heart failure: role of the α1-adrenergic receptor.

    Science.gov (United States)

    Pügge, Carolin; Mediratta, Jai; Marcus, Noah J; Schultz, Harold D; Schiller, Alicia M; Zucker, Irving H

    2016-02-01

    Recent data suggest that exercise training (ExT) is beneficial in chronic heart failure (CHF) because it improves autonomic and peripheral vascular function. In this study, we hypothesized that ExT in the CHF state ameliorates the renal vasoconstrictor responses to hypoxia and that this beneficial effect is mediated by changes in α1-adrenergic receptor activation. CHF was induced in rabbits. Renal blood flow (RBF) and renal vascular conductance (RVC) responses to 6 min of 5% isocapnic hypoxia were assessed in the conscious state in sedentary (SED) and ExT rabbits with CHF with and without α1-adrenergic blockade. α1-adrenergic receptor expression in the kidney cortex was also evaluated. A significant decline in baseline RBF and RVC and an exaggerated renal vasoconstriction during acute hypoxia occurred in CHF-SED rabbits compared with the prepaced state (P renal denervation (DnX) blocked the hypoxia-induced renal vasoconstriction in CHF-SED rabbits. α1-adrenergic protein in the renal cortex of animals with CHF was increased in SED animals and normalized after ExT. These data provide evidence that the acute decline in RBF during hypoxia is caused entirely by the renal nerves but is only partially mediated by α1-adrenergic receptors. Nonetheless, α1-adrenergic receptors play an important role in the beneficial effects of ExT in the kidney. Copyright © 2016 the American Physiological Society.

  16. Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis

    Science.gov (United States)

    Prosper, Boris W.; Marathe, Swanand; Husain, Basma F. A.; Kernie, Steven G.; Bartlett, Perry F.; Vaidya, Vidita A.

    2014-01-01

    Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis. PMID:24922313

  17. THE STUDY OF CARDIAC ABNORMALITY IN GERIATRIC POPULATION OF RURAL CENTRAL INDIA

    Directory of Open Access Journals (Sweden)

    Aman Chaturvedi

    2017-09-01

    Full Text Available BACKGROUND Health care of elderly in the society has emerged as an increasingly important issue in the recent years. As the elderly proportion of our population expands, maintaining health and wellness of the aged will continue to be an important research priority in the near future. This study was undertaken to determine cardiac abnormalities in geriatric population by echocardiography in rural central India. The aim of this study is to map the spectrum of cardiac abnormality in geriatric population of rural central India. MATERIALS AND METHODS The study was carried out on subjects from September 2014 – August 2016. All geriatric subjects i.e. above the age of 60 years who were admitted in medicine ward or who attended medicine OPD were considered for the study. All the preliminary biodata was collected, history taking and physical examination were done, ECG was recorded and finally 2D echo was performed in MMode, 2D echo, Doppler (CW and PW and TDI. All observations were recorded on a standard proforma sheet, statistical analysis was performed and results and conclusions drawn. RESULTS In present study, there was higher prevalence of major diseases. On M-Mode echocardiography, left atrial enlargement, LV hypertrophy/dilatation was found in significant number of subjects. On 2D echo, Myocardial Scarring/Thinning, valvular Degeneration was found significantly higher in elderly males, mitral and aortic calcification was found most frequently with prevalence higher in males. On Doppler echocardiography, diastolic dysfunction was common in elderly with very few subjects having normal diastolic function, most of the subjects having grade II diastolic dysfunction. Aortic, mitral and tricuspid regurgitation was common in elderly, and stenotic lesions of aortic and mitral valve were common. CONCLUSION We recommend that echocardiography should become an investigative norm in the elderly, this will aid in early detection of cardiovascular abnormalities

  18. β-Adrenergic regulation of a novel isoform of NCX: sequence and expression of shark heart NCX in human kidney cells

    Science.gov (United States)

    Janowski, Einsley; Day, Regina; Kraev, Alexander; Roder, John C.; Cleemann, Lars; Morad, Martin

    2009-01-01

    The function, regulation, and molecular structure of the cardiac Na+/Ca2+ exchangers (NCXs) vary significantly among vertebrates. We previously reported that β-adrenergic suppression of amphibian cardiac NCX1.1 is associated with specific molecular motifs. Here we investigated the bimodal, cAMP-dependent regulation of spiny dogfish shark (Squalus acanthias) cardiac NCX, exploring the effects of molecular structure, host cell environment, and ionic milieu. The shark cardiac NCX sequence (GenBank accession no. DQ 068478) revealed two novel proline/alanine-rich amino acid insertions. Wild-type and mutant shark NCXs were cloned and expressed in mammalian cells (HEK-293 and FlpIn-293), where their activities were measured as Ni2+-sensitive Ca2+ fluxes (fluo 4) and membrane (Na+/Ca2+ exchange) currents evoked by changes in extracellular Na+ concentration and/or membrane potential. Regardless of Ca2+ buffering, β-adrenergic stimulation of cloned wild-type shark NCX consistently produced bimodal regulation (defined as differential regulation of Ca2+-efflux and -influx pathways), with suppression of the Ca2+-influx mode and either no change or enhancement of the Ca2+-efflux mode, closely resembling results from parallel experiments with native shark cardiomyocytes. In contrast, mutant shark NCX, with deletion of the novel region 2 insertion, produced equal suppression of the inward and outward currents and Ca2+ fluxes, thereby abolishing the bimodal nature of the regulation. Control experiments with nontransfected and dog cardiac NCX-expressing cells showed no cAMP regulation. We conclude that bimodal β-adrenergic regulation is retained in cloned shark NCX and is dependent on the shark's unique molecular motifs. PMID:19395557

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  20. LRRC10 is required to maintain cardiac function in response to pressure overload.

    Science.gov (United States)

    Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

    2016-01-15

    We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. Copyright © 2016 the American Physiological Society.

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

    Science.gov (United States)

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

    2017-09-21

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

  2. Study of High Sensitive-CRP and Cardiac Marker Enzymes in Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Srikrishna R,

    2015-04-01

    Full Text Available Background: Inflammation has been proposed as a contributor to different stages in the pathogenesis of Coronary Heart Disease (CHD. High sensitive C-Reactive Protein (hs-CRP, an acute-phase plasma protein synthesized by the liver, is the most extensively studied systemic marker of inflammation. Elevated hsCRP concentrations early in Acute Coronary Syndrome (ACS, prior to the tissue necrosis, may be a surrogate marker for cardiovascular co-morbidities. The cardiac marker enzymes Creatine Kinase myocardial bound (CK-MB, Aspartate Aminotransferase (AST and lactate dehydrogenase (LDH have been known to be increased in coronary artery diseases. Objective: The aim of the study was to measure hs-CRP levels and other cardiac marker enzymes in ACS patients and to compare the levels of hs-CRP with other cardiac marker enzymes between ST Elevation Myocardial Infarction (STEMI and Non-ST Elevation Myocardial Infarction (NSTEMI patients. Material and Methods: The study group consisted of 207 consecutive patients admitted to Sri Siddhartha Medical College Hospital within the first 6 hours from the onset of chest pain. Patients were diagnosed as Unstable Angina (UA, (n=84; STEMI (n=63 and NSTEMI (n=60. ACS patients were compared with 211 healthy age and sex matched controls. Hs-CRP, CK-MB, AST and LDH levels were measured by standard methods in both groups at baseline and forcases at 36-48 hours i.e. Peak levels. Results: ACS patients had significantly (p<0.05 higher levels of hs-CRP, CKMB, AST and LDH in comparison to controls at baseline. Hs-CRP, CK-MB, AST and LDH levels were significantly higher in STEMI patients compared to NSTEMI patients (p<0.05 at baseline. There was a significant difference regarding peak hs-CRP levels between the two groups, as STEMI patients had significantly higher peak hs-CRP levels compared to NSTEMI patients (p<0.05. Conclusion: STEMI patients have significantly higher peak hsCRP levels compared to NSTEMI patients. These data

  3. Prevalence and characteristics of impaired glucose metabolism in patients referred to comprehensive cardiac rehabilitation: the DANSUK study

    DEFF Research Database (Denmark)

    Boas Soja, Anne Merete; Zwisler, Ann-Dorthe Olsen; Melchior, Thomas

    2006-01-01

    and mortality. We studied the prevalence of impaired glucose metabolism (T2DM, IGT and impaired fasting glucose; IFG) in patients referred to cardiac rehabilitation, and further studied whether we could identify groups in which an oral glucose tolerance test (OGTT) need not be performed. METHODS: As part...... of a cardiac rehabilitation trial, 201 patients participated. Patients without a diagnosis of T2DM (N=159) underwent an OGTT 3 months after inclusion. RESULTS: Forty-two patients (21%) had known T2DM at enrolment. Based on the OGTT, 26 patients (13%) had unrecognized T2DM, 36 (18%) had IGT and 19 (9%) were...... predictive value of 39%. CONCLUSION: More than 60% of the patients (123/201) referred to cardiac rehabilitation had impaired glucose metabolism and 18% of the screened patients (29/159) would be misclassified if an OGTT was omitted. IFG and IGT did not identify the same patients or the same cardiovascular...

  4. Historical Overview of the Effect of -Adrenergic Agonists on Beef Cattle Production

    Directory of Open Access Journals (Sweden)

    Bradley J. Johnson

    2014-05-01

    Full Text Available Postnatal muscle hypertrophy of beef cattle is the result of enhanced myofibrillar protein synthesis and reduced protein turnover. Skeletal muscle hypertrophy has been studied in cattle fed β-adrenergic agonists (β-AA, which are receptor-mediated enhancers of protein synthesis and inhibitors of protein degradation. Feeding β-AA to beef cattle increases longissimus muscle cross-sectional area 6% to 40% compared to non-treated cattle. The β-AA have been reported to improve live animal performance, including average daily gain, feed efficiency, hot carcass weight, and dressing percentage. Treatment with β-AA increased mRNA concentration of the β2 or β1-adrenergic receptor and myosin heavy chain IIX in bovine skeletal muscle tissue. This review will examine the effects of skeletal muscle and adipose development with β-AA, and will interpret how the use of β-AA affects performance, body composition, and growth in beef cattle.

  5. Design and synthesis of aryloxypropanolamine as β3-adrenergic receptor antagonist in cancer and lipolysis.

    Science.gov (United States)

    Jin, Jiyu; Miao, Chunxiao; Wang, Zhilong; Zhang, Wanli; Zhang, Xiongwen; Xie, Xin; Lu, Wei

    2018-04-25

    β-adrenergic receptors (β-ARs) are broadly distributed in various tissues and regulate a panel of important physiological functions and disease states including cancer. Above all, β 3 -adrenergic receptor (β 3 -AR) plays a significant role in regulating lipolysis and thermogenesis in adipose tissue. In this study, we designed and synthesized a series of novel L-748,337 derivatives as selective human β 3 -AR antagonists. Among all the tested L-748,337 analogs, compound 23d was found to display 23-fold more potent β 3 -AR antagonist activity (EC 50  = 0.5117 nM) than L-748,337 (EC 50  = 11.91 nM). In vivo, compound 23d could alleviate weight loss and inhibit tumor growth in C26 tumor cachexia animal model. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. Alpha-Amylase Activity in Blood Increases after Pharmacological, But Not Psychological, Activation of the Adrenergic System.

    Directory of Open Access Journals (Sweden)

    Urs M Nater

    Full Text Available Alpha-amylase in both blood and saliva has been used as a diagnostic parameter. While studies examining alpha-amylase activity in saliva have shown that it is sensitive to physiological and psychological challenge of the adrenergic system, no challenge studies have attempted to elucidate the role of the adrenergic system in alpha-amylase activity in blood. We set out to examine the impact of psychological and pharmacological challenge on alpha-amylase in blood in two separate studies.In study 1, healthy subjects were examined in a placebo-controlled, double-blind paradigm using yohimbine, an alpha2-adrenergic antagonist. In study 2, subjects were examined in a standardized rest-controlled psychosocial stress protocol. Alpha-amylase activity in blood was repeatedly measured in both studies.Results of study 1 showed that alpha-amylase in blood is subject to stronger increases after injection of yohimbine compared to placebo. In study 2, results showed that there was no significant effect of psychological stress compared to rest.Alpha-amylase in blood increases after pharmacological activation of the adrenergic pathways suggesting that sympathetic receptors are responsible for these changes. Psychological stress, however, does not seem to have an impact on alpha-amylase in blood. Our findings provide insight into the mechanisms underlying activity changes in alpha-amylase in blood in healthy individuals.

  7. Exercise capacity in diabetes mellitus is predicted by activity status and cardiac size rather than cardiac function: a case control study.

    Science.gov (United States)

    Roberts, Timothy J; Burns, Andrew T; MacIsaac, Richard J; MacIsaac, Andrew I; Prior, David L; La Gerche, André

    2018-03-23

    The reasons for reduced exercise capacity in diabetes mellitus (DM) remains incompletely understood, although diastolic dysfunction and diabetic cardiomyopathy are often favored explanations. However, there is a paucity of literature detailing cardiac function and reserve during incremental exercise to evaluate its significance and contribution. We sought to determine associations between comprehensive measures of cardiac function during exercise and maximal oxygen consumption ([Formula: see text]peak), with the hypothesis that the reduction in exercise capacity and cardiac function would be associated with co-morbidities and sedentary behavior rather than diabetes itself. This case-control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and 10 healthy controls age/sex-matched to each diabetes subtype] performing cardiopulmonary exercise testing and bicycle ergometer echocardiography studies. Measures of biventricular function were assessed during incremental exercise to maximal intensity. T2DM subjects were middle-aged (52 ± 11 years) with a mean T2DM diagnosis of 12 ± 7 years and modest glycemic control (HbA 1c 57 ± 12 mmol/mol). T1DM participants were younger (35 ± 8 years), with a 19 ± 10 year history of T1DM and suboptimal glycemic control (HbA 1c 65 ± 16 mmol/mol). Participants with T2DM were heavier than their controls (body mass index 29.3 ± 3.4 kg/m 2 vs. 24.7 ± 2.9, P = 0.001), performed less exercise (10 ± 12 vs. 28 ± 30 MET hours/week, P = 0.031) and had lower exercise capacity ([Formula: see text]peak = 26 ± 6 vs. 38 ± 8 ml/min/kg, P accounting for age, sex and body surface area in a multivariate analysis, significant positive predictors of [Formula: see text]peak were cardiac size (LV end-diastolic volume, LVEDV) and estimated MET-hours, while T2DM was a negative predictor. These combined factors accounted for 80% of the variance in [Formula: see text

  8. Oral Contraceptives Attenuate Cardiac Autonomic Responses to Musical Auditory Stimulation: Pilot Study.

    Science.gov (United States)

    Milan, Réveni Carmem; Plassa, Bruna Oliveira; Guida, Heraldo Lorena; de Abreu, Luiz Carlos; Gomes, Rayana L; Garner, David M; Valenti, Vitor E

    2015-01-01

    The literature presents contradictory results regarding the effects of contraceptives on cardiac autonomic regulation. The research team aimed to evaluate the effects of musical auditory stimulation on cardiac autonomic regulation in women who use oral contraceptives. The research team designed a transversal observational pilot study. The setting was the Centro de Estudos do Sistema Nervoso Autônomo (CESNA) in the Departamento de Fonoaudiologia at the Universidade Estadual Paulista (UNESP) in Marília, SP, Brazil. Participants were 22 healthy nonathletic and nonsedentary females, all nonsmokers and aged between 18 and 27 y. Participants were divided into 2 groups: (1) 12 women who were not taking oral contraceptives, the control group; and (2) 10 women who were taking oral contraceptives, the oral contraceptive group. In the first stage, a rest control, the women sat with their earphones turned off for 20 min. After that period, the participants were exposed to 20 min of classical baroque music (ie, "Canon in D Major," Johann Pachelbel), at 63-84 dB. Measurements of the equivalent sound levels were conducted in a soundproof room, and the intervals between consecutive heartbeats (R-R intervals) were recorded, with a sampling rate of 1000 Hz. For calculation of the linear indices, the research team used software to perform an analysis of heart rate variability (HRV). Linear indices of HRV were analyzed in the time domain: (1) the standard deviation of normal-to-normal R-R intervals (SDNN), (2) the root-mean square of differences between adjacent normal R-R intervals in a time interval (RMSSD), and (3) the percentage of adjacent R-R intervals with a difference of duration greater than 50 ms (pNN50). The study also analyzed the frequency domain-low frequency (LF), high frequency (HF), and LF/HF ratio. For the control group, the musical auditory stimulation reduced (1) the SDNN from 52.2 ± 10 ms to 48.4 ± 16 ms (P = .0034); (2) the RMSSD from 45.8 ± 22 ms to 41.2

  9. Population-based studies of antithyroid drugs and sudden cardiac death

    NARCIS (Netherlands)

    C. van Noord (Charlotte); M.C.J.M. Sturkenboom (Miriam); S.M.J.M. Straus (Sabine); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); B.H.Ch. Stricker (Bruno)

    2009-01-01

    textabstractWHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Thyroid hormone free T4 is associated with QTc-interval prolongation, which is a risk factor for sudden cardiac death. • The association between hyperthyroidism and ventricular arrhythmias or sudden cardiac death has been reported in several

  10. Pilot Study: Estimation of Stroke Volume and Cardiac Output from Pulse Wave Velocity.

    Directory of Open Access Journals (Sweden)

    Yurie Obata

    Full Text Available Transesophageal echocardiography (TEE is increasingly replacing thermodilution pulmonary artery catheters to assess hemodynamics in patients at high risk for cardiovascular morbidity. However, one of the drawbacks of TEE compared to pulmonary artery catheters is the inability to measure real time stroke volume (SV and cardiac output (CO continuously. The aim of the present proof of concept study was to validate a novel method of SV estimation, based on pulse wave velocity (PWV in patients undergoing cardiac surgery.This is a retrospective observational study. We measured pulse transit time by superimposing the radial arterial waveform onto the continuous wave Doppler waveform of the left ventricular outflow tract, and calculated SV (SVPWV using the transformed Bramwell-Hill equation. The SV measured by TEE (SVTEE was used as a reference.A total of 190 paired SV were measured from 28 patients. A strong correlation was observed between SVPWV and SVTEE with the coefficient of determination (R2 of 0.71. A mean difference between the two (bias was 3.70 ml with the limits of agreement ranging from -20.33 to 27.73 ml and a percentage error of 27.4% based on a Bland-Altman analysis. The concordance rate of two methods was 85.0% based on a four-quadrant plot. The angular concordance rate was 85.9% with radial limits of agreement (the radial sector that contained 95% of the data points of ± 41.5 degrees based on a polar plot.PWV based SV estimation yields reasonable agreement with SV measured by TEE. Further studies are required to assess its utility in different clinical situations.

  11. Myocardial ischaemia and the cardiac nervous system.

    Science.gov (United States)

    Armour, J A

    1999-01-01

    The intrinsic cardiac nervous system has been classically considered to contain only parasympathetic efferent postganglionic neurones which receive inputs from medullary parasympathetic efferent preganglionic neurones. In such a view, intrinsic cardiac ganglia act as simple relay stations of parasympathetic efferent neuronal input to the heart, the major autonomic control of the heart purported to reside solely in the brainstem and spinal cord. Data collected over the past two decades indicate that processing occurs within the mammalian intrinsic cardiac nervous system which involves afferent neurones, local circuit neurones (interconnecting neurones) as well as both sympathetic and parasympathetic efferent postganglionic neurones. As such, intrinsic cardiac ganglionic interactions represent the organ component of the hierarchy of intrathoracic nested feedback control loops which provide rapid and appropriate reflex coordination of efferent autonomic neuronal outflow to the heart. In such a concept, the intrinsic cardiac nervous system acts as a distributive processor, integrating parasympathetic and sympathetic efferent centrifugal information to the heart in addition to centripetal information arising from cardiac sensory neurites. A number of neurochemicals have been shown to influence the interneuronal interactions which occur within the intrathoracic cardiac nervous system. For instance, pharmacological interventions that modify beta-adrenergic or angiotensin II receptors affect cardiomyocyte function not only directly, but indirectly by influencing the capacity of intrathoracic neurones to regulate cardiomyocytes. Thus, current pharmacological management of heart disease may influence cardiomyocyte function directly as well as indirectly secondary to modifying the cardiac nervous system. This review presents a brief summary of developing concepts about the role of the cardiac nervous system in regulating the normal heart. In addition, it provides some

  12. Cardiac MRI in addition to MR angiography: a longitudinal study in vascular risk patients; Kardiale MRT als Ergaenzung zur MR-Angiografie: Eine longitudinale Studie bei vaskulaeren Risikopatienten

    Energy Technology Data Exchange (ETDEWEB)

    Seeger, A.; Grimm, F.; Fenchel, M.; Kramer, U.; Doering, J.S.; Klumpp, B.; Claussen, C.D.; Miller, S. [Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany); Scheule, A. [Abt. fuer Herz-, Thorax- und Gefaesschirurgie, Eberhard-Karls-Univ. Tuebingen (Germany); May, A.E. [Abt. fuer Kardiologie, Eberhard-Karls-Univ. Tuebingen (Germany)

    2008-05-15

    Purpose: the aim of the study was to assess the feasibility and additional diagnostic information of cardiac MRI as a supplement to state-of-the-art MR angiography (MRA) in the case of vascular risk patients. Therefore, the prevalence of delayed myocardial enhancement (DE) was determined in patients suffering from peripheral artery disease (PAD) and a clinical follow-up was evaluated after 2 years. Materials and method: 87 consecutive patients (ages 66 {+-} 10 years, 67 males) with symptomatic peripheral arterial occlusive disease (n = 68) or abdominal aortic aneurysm (n = 19) were examined using delayed cardiac enhancement (DE) within the clinical indication of MRA at a 1.5T system. A follow-up examination was carried out two years later (24 months {+-} 4 months) with regards to cardiac events (cardiac death, myocardial infarction or acute coronary syndrome, heart insufficiency, coronary revascularization). Results: in total, 40/87 patients had myocardial infarctions shown in MRI (46%). In 25 patients (29%), the myocardial infarction was already known, while in 15 patients (17%) an occult progressing infarction was diagnosed (38% of the myocardial infarcts). Follow-up data was able to be obtained after 2 years for 82 patients. 15 patients had a major cardiac event during the follow-up period, and 10 (67%) of them already showed DE in the MRI. In the group with occult progressing infarctions, cardiac events occurred in 40% (6/15 patients, cardiac death n = 1, ischemia n = 4, heart insufficiency n = 1, bypass n = 1), in patients with known infarction in 17% (4/23 patients, cardiac death n = 1, ischemia n = 3, bypass n = 2) and in 11% of patients without myocardial scars (5/44 patients, cardiac death n = 1, ischemia n = 2, heart insufficiency n = 2). (orig.)

  13. Performance of the European System for Cardiac Operative Risk Evaluation II: a meta-analysis of 22 studies involving 145,592 cardiac surgery procedures.

    Science.gov (United States)

    Guida, Pietro; Mastro, Florinda; Scrascia, Giuseppe; Whitlock, Richard; Paparella, Domenico

    2014-12-01

    A systematic review of the European System for Cardiac Operative Risk Evaluation (euroSCORE) II performance for prediction of operative mortality after cardiac surgery has not been performed. We conducted a meta-analysis of studies based on the predictive accuracy of the euroSCORE II. We searched the Embase and PubMed databases for all English-only articles reporting performance characteristics of the euroSCORE II. The area under the receiver operating characteristic curve, the observed/expected mortality ratio, and observed-expected mortality difference with their 95% confidence intervals were analyzed. Twenty-two articles were selected, including 145,592 procedures. Operative mortality occurred in 4293 (2.95%), whereas the expected events according to euroSCORE II were 4802 (3.30%). Meta-analysis of these studies provided an area under the receiver operating characteristic curve of 0.792 (95% confidence interval, 0.773-0.811), an estimated observed/expected ratio of 1.019 (95% confidence interval, 0.899-1.139), and observed-expected difference of 0.125 (95% confidence interval, -0.269 to 0.519). Statistical heterogeneity was detected among retrospective studies including less recent procedures. Subgroups analysis confirmed the robustness of combined estimates for isolated valve procedures and those combined with revascularization surgery. A significant overestimation of the euroSCORE II with an observed/expected ratio of 0.829 (95% confidence interval, 0.677-0.982) was observed in isolated coronary artery bypass grafting and a slight underestimation of predictions in high-risk patients (observed/expected ratio 1.253 and observed-expected difference 1.859). Despite the heterogeneity, the results from this meta-analysis show a good overall performance of the euroSCORE II in terms of discrimination and accuracy of model predictions for operative mortality. Validation of the euroSCORE II in prospective populations needs to be further studied for a continuous

  14. Use of implantable cardioverter defibrillators after out-of-hospital cardiac arrest: a prospective follow-up study

    Science.gov (United States)

    Parkash, Ratika; Tang, Anthony; Wells, George; Blackburn, Josée; Stiell, Ian; Simpson, Christopher; Dorian, Paul; Yee, Raymond; Cameron, Doug; Connolly, Stuart; Birnie, David; Nichol, Graham

    2004-01-01

    Background Survivors of out-of-hospital cardiac arrest are at high risk of recurrent arrests, many of which could be prevented with implantable cardioverter defibrillators (ICDs). We sought to determine the ICD insertion rate among survivors of out-of-hospital cardiac arrest and to determine factors associated with ICD implantation. Methods The Ontario Prehospital Advanced Life Support (OPALS) study is a prospective, multiphase, before–after study assessing the effectiveness of prehospital interventions for people experiencing cardiac arrest, trauma or respiratory arrest in 19 Ontario communities. We linked OPALS data describing survivors of cardiac arrest with data from all defibrillator implantation centres in Ontario. Results From January 1997 to April 2002, 454 patients in the OPALS study survived to hospital discharge after experiencing an out-of-hospital cardiac arrest. The mean age was 65 (standard deviation 14) years, 122 (26.9%) were women, 398 (87.7%) had a witnessed arrest, 372 (81.9%) had an initial rhythm of ventricular tachycardia or ventricular fibrillation (VT/VF), and 76 (16.7%) had asystole or another arrhythmia. The median cerebral performance category at discharge (range 1–5, 1 = normal) was 1. Only 58 (12.8%) of the 454 patients received an ICD. Patients with an initial rhythm of VT/VF were more likely than those with an initial rhythm of asystole or another rhythm to undergo device insertion (adjusted odds ratio [OR] 9.63, 95% confidence interval [CI] 1.31–71.50). Similarly, patients with a normal cerebral performance score were more likely than those with abnormal scores to undergo ICD insertion (adjusted OR 12.52, 95% CI 1.74–92.12). Interpretation A minority of patients who survived cardiac arrest underwent ICD insertion. It is unclear whether this low usage rate reflects referral bias, selection bias by electrophysiologists, supply constraint or patient preference. PMID:15505267

  15. Dynamic studies of cardiac valvular disease using a new fast multiphase MR imaging technique

    International Nuclear Information System (INIS)

    Pettigrew, R.; Churchwell, A.; Parks, W.J.; Dannels, W.; Smith, H. III; Baron, M.G.

    1986-01-01

    To determine the potential utility of fast multiphase (FM) imaging for the assessment of cardiac valvular disease, ten healthy volunteers and 18 patients were studied. The FM technique employed gradient echoes with TE -- 15 msec and small exitation angles with TR -- 50 msec. Cine display of the electrocardiographically gated FM images allowed clear visualization of regurgitant blood flow in each of 15 patients with tricuspid or mitral insufficiency. Magnetic field distortions in two patients with Bjork-Shiley aortic prostheses and regurgitation prevented definitive visualization of the flow patterns. An equivocal flow pattern was seen in one case of mitral stenosis. Thus, FM imaging may have significant utility as an adjunctive procedure for the assessment of atrioventricular valve insufficiently, without requiring a contrast agent. Difficulties may exist with some prosthetic valves

  16. Phosphorus nuclear magnetic resonance studies on normoxic and ischemic cardiac tissue.

    Science.gov (United States)

    Gadian, D G; Hoult, D I; Radda, G K; Seeley, P J; Chance, B; Barlow, C

    1976-12-01

    The intact heart of a young rat was excised rapidly and cooled to 0 degree C; its energy-rich compounds were examined by 31P Fourier Transform nuclear magnetic resonance. The heart showed the characteristic spectrum of sugar phosphates, inorganic phosphate, phosphocreatine, and magniesium phates, inorganic phosphate, phosphocreatine, and magnesium ATP, characteristics of the energizing state of the nonbeating tissue. Warming to 30 degrees C imposes an energy load upon the heart consistent with short-term resumption of beating, concomitant intracellular acidosis, and decomposition of all detectable energy-rich compounds. The intracellular acidity causes a shift from pH 7.0 to 6.0. The effects of possible interferences with this pH measurement are considered. The method appears to have wide usefulness in cardiac infarct models for detecting the fraction of the total volume occupied by the infarct and for studying the effect of various proposed therapies upon this infarcted volume.

  17. Radionuclide techniques in studies of cardiac performance and circulatory changes during antihypertensive treatment

    International Nuclear Information System (INIS)

    Falch, D.K.

    A non-invasive radionuclide technique to determine variables in the systematic and pulmonary circulation useful in out- patient studies is described. Indium 113m chloride was chosen as the tracer, and iodine 125 iothalamate may be used for simultaneous determination of the glomerular filtration rate. The counting geometry is discussed at some length. The errors of the method and its reproducability seem to be acceptable. The method was tested on two groups of healthy subjects, one of which was composed of well-trained athletes, and two groups of patients, one with chronic cardiac insufficiency, the other with primary hypertension. Tables are presented giving hemodynamic data for these groups. It is concluded that the technique gives some useful data, but that further refinement and supplementation is necessary to obtain a guidance in drug therapy. (JIW)

  18. Prevalence of extra-cardiac findings on studies of noninvasive coronary angiography multidetector computed tomography 64 rows

    International Nuclear Information System (INIS)

    Carrascosa, Patricia M.; Capunay, Carlos M.; Deviggiano, A.; Melendez, F.; Carrascosa, Jorge M.; Garcia, M.

    2007-01-01

    The aim of this paper is to show the importance of evaluating in a full form images obtained from a studio of noninvasive coronary angiography by multidetector computed tomography (AC-TCMD). 90 users of AC-TCMD were evaluated retrospectively conducted between October 2006 and April 2007 with a multidetector tomography of 64-rows(Phillips Medical Systems) . The images were reprocessed with a maximum field of vision and determined the presence of extra-cardiac findings, which were classified according to their impact on the management and treatment of patient at 3 degrees: low, medium and high grade. The studies were assessed jointly by a cardiologist and a radiologist qualified for cardiac and corporal evaluation. Extra-cardiac findings were identified in 58 patients. There were 38 patients with findings of low grade, 31 medium grade and 1 high grade. It was recommended to 16 patients its monitoring by images on reasonable period of time [es

  19. Adverse events in cardiac surgery, a mixed methods retrospective study in an Italian teaching hospital.

    Science.gov (United States)

    Bellandi, Tommaso; Tartaglia, Riccardo; Forni, Silvia; D'Arienzo, Sara; Tulli, Giorgio

    2017-08-01

    Adverse events (AEs) are a major concern in surgery, but the evidence in cardiac surgery is limited, especially on the contributory factors. According to the data of the National Outcomes Program, a unit was selected to conduct a mixed methods investigation into the incidence, type, and cause of AE, given its mortality rate that was double the national average on coronary artery bypass grafting, valve reparation, and replacement. A retrospective investigation on the performance of a cardiac surgery, combining the routinely collected data on process and outcome measures with a 2-stage structured review of 280 medical records performed by 3 expert clinicians, with the support of a methodologist. At least one risk had been verified in 137 of 280 cases (48.9%, 95% CI, 43.1-54.8). The total number of AE was 42, with an incidence of 15% (95% CI, 10.8-20.2) and a preventability of 80.9% (95% CI, 69.1-92.8). In 11.9% of AE, the consequence is death, disability in 40.5%, and extended hospital stay in 69% of the cases. Adverse events are associated with problems in care management at the ward (89/137, 64.9%, 95% CI, 56.9-72.9), followed by surgical complications (46/137, 33.6%, 95% CI, 25.7-41.5) and infection/sepsis (32/137, 23.4%, 95% CI, 16.3-30.4). An active error was made by the health care workers in 31 of 42 cases with AE, either during the decision making or during the execution of an action. A total of 36 AEs were due to deficiencies attributed to organizational factors and 31 were linked to poor teamwork. The mixed methods approach demonstrated how a deep understanding of AE and poor performance may emerge thanks to the combination of routinely available data and experts' evaluations. The main limitation of this study is its focus on the cardiac surgery rather than on the entire process of care. The evaluation could have been integrated with on-site observations and the analysis of reported incidents. © 2017 John Wiley & Sons, Ltd.

  20. Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

    Science.gov (United States)

    Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.

    2014-09-01

    The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric β2-adrenoreceptors and the activity of two factors which are involved in β2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric β2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

  1. Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: Comparison between two model systems.

    Science.gov (United States)

    Backman, L J; Andersson, G; Fong, G; Alfredson, H; Scott, A; Danielson, P

    2013-12-01

    The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α2A AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α2A AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research. © 2013 The Authors. Scand J Med Sci Sports published by John Wiley & Sons Ltd.

  2. Norepinephrine signaling through β-adrenergic receptors is critical for expression of cocaine-induced anxiety

    Science.gov (United States)

    Schank, Jesse R.; Liles, L. Cameron; Weinshenker, David

    2008-01-01

    Background Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine’s rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. Methods In this study we evaluated the performance of dopamine β-hydroxylase knockout (Dbh −/−) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. Results We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/−) mice, as measured by a decrease in open arm exploration. Dbh −/− mice had normal baseline performance in the EPM, but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/− mice following administration of disulfiram, a DBH inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the β-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/− and wild-type C57BL6/J mice, while the α1 antagonist prazosin and the α2 antagonist yohimbine had no effect. Conclusions These results indicate that noradrenergic signaling via β-adrenergic receptors is required for cocaine-induced anxiety in mice. PMID:18083142

  3. Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.

    Science.gov (United States)

    Schank, Jesse R; Liles, L Cameron; Weinshenker, David

    2008-06-01

    Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.

  4. Zebrafish heart as a model to study the integrative autonomic control of pacemaker function

    Science.gov (United States)

    Stoyek, Matthew R.; Quinn, T. Alexander; Croll, Roger P.

    2016-01-01

    The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons. PMID:27342878

  5. Perspectives on barriers and facilitators to self-care in Lebanese cardiac patients: A qualitative descriptive study.

    Science.gov (United States)

    Dumit, Nuhad Yazbik; Noureddine, Samar Nayef; Magilvy, Joan Kathy

    2016-08-01

    Cardiovascular disease is the leading cause of mortality worldwide. Cardiac self-care practices are essential for managing cardiac illness and improving quality of life. However, these practices may be affected by factors that may hinder or facilitate self-care especially in countries that experience political and economic instabilities. The purpose of this study was to explore self-care practices among Lebanese cardiac patients. Another aim was to reveal factors that might influence these self-care practices. This is a qualitative descriptive study. Participants were recruited from a referral medical center in Beirut, Lebanon and interviews took place in their homes. Purposive sample of 15 adult participants, seven females and eight males, diagnosed with coronary artery disease at least a year ago and not in critical condition recruited from the cardiology clinics of the medical center. Data were collected through semi-structured audio-recorded interviews that took place in their places of residents. Three themes emerged from the data: I. The behaviors of cardiac patients demonstrated selected self-care practices; II. Patients identified barriers to self-care reflective of the Lebanese political and socio-economic situation; and, III. Patients described facilitators to self-care consistent with the Lebanese socio-cultural values and norms. The most common self-care practices included taking medications and eating properly. Participants emphasized avoiding stress and being upset as a self-protective measure for cardiac health. Health care costs, family responsibilities, psychological factors and the country's political situation impeded self-care practices whereas family support facilitated them. Lebanese patients reported select self-care practices in dealing with their cardiac illness. Barriers and facilitators to their self-care behaviors reflected the Lebanese context and culture. Thus health care providers must assess their patients' practices within their

  6. Mammalian β1- and β2-adrenergic receptors: immunological and structural comparison

    International Nuclear Information System (INIS)

    Moxham, C.P.; George, S.T.; Graziano, M.P.; Brandwein, H.J.; Malbon, C.C.

    1986-01-01

    β 1 - and β 2 -adrenergic receptors, pharmacologically distinct proteins, have been reported to be structurally dissimilar. In the present study three techniques were employed to compare the nature of mammalian β 1 - and β 2 -adrenergic receptors. Antibodies against each of the receptor subtypes were raised separately. Polyclonal antisera against β 1 -receptors of rat fat cells were raised in mice, and antisera against β 2 -receptors of guinea pig lung were raised in rabbits. Receptors purified from rat fat cells (β 1 -), S49 mouse lymphoma cells (β 2 -), and rat liver (β 2 -) were probed with these antisera. Each anti-receptor antisera demonstrated the ability to immunoprecipitate purified receptors of both β 1 - and β 2 -subtypes. The mobility of β-receptors subjected to polyacrylamide gel electrophoresis was probed using antireceptor antibodies and nitrocellulose blots of the gels. Fat cell β 1 -adrenergic receptors display M/sub r/ = 67,000 under reducing conditions and M/sub r/ = 54,000 under nonreducing conditions, as previously reported. Both β 1 - and β 2 -receptors displayed this same shift in electrophoretic mobility observed in the presence as compared to the absence of disulfide bridge-reducing agents, as detected both by autoradiography of the radiolabeled receptors and by immunoblotting of native receptors. Finally, isoelectric focusing of purified radioiodinated β 1 - and β 2 -adrenergic receptors revealed identical isoelectric points. These data are the first to provide analyses of immunological, structural, and biochemical features of β 1 - and β 2 -subtypes in tandem and underscore the structural similarities that exist between these pharmacologically distinct receptors

  7. Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum

    International Nuclear Information System (INIS)

    Lepor, H.; Rigaud, G.; Shapiro, E.; Baumann, M.; Kodner, I.J.; Fleshman, J.W.

    1990-01-01

    The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments

  8. alpha-adrenergic Blockade Unmasks a Greater Compensatory Vasodilation in Hypoperfused Contracting Muscle

    Directory of Open Access Journals (Sweden)

    Darren P. Casey

    2012-07-01

    Full Text Available We previously demonstrated that acute hypoperfusion in exercising human muscle causes an immediate increase in vascular resistance that is followed by a partial restoration (less than 100% recovery of flow. In the current study we examined the contribution of alpha-adrenergic vasoconstriction in the initial changes in vascular resistance at the onset of hypoperfusion as well as in the recovery of flow over time. Nine healthy male subjects (29 ± 2 performed rhythmic forearm exercise (20% of maximum during hypoperfusion evoked by intra-arterial balloon inflation. Each trial included; baseline, exercise prior to inflation, exercise with inflation, and exercise after deflation (3 min each. Forearm blood flow (FBF; ultrasound, local (brachial artery, and systemic arterial pressure (MAP; Finometer were measured. The trial was repeated during phentolamine infusion (alpha-adrenergic receptor blockade. Forearm vascular conductance (FVC; ml min-1 100 mmHg-1 and resistance (mmHg ml min-1 was calculated from BF (ml min-1 and local MAP (mmHg. Recovery of FBF and FVC (steady state inflation plus exercise value – nadir/ [steady state exercise (control value-nadir] with phentolamine was enhanced compared with the respective control (no drug trial (FBF = 97 ± 5% vs. 81 ± 6%, P < 0.05; FVC = 126 ± 9% vs. 91 ± 5%, P < 0.01. However, the absolute (0.05 ± 0.01 vs. 0.06 ± 0.01 mmHg ml min-1; P = 0.17 and relative (35 ± 5% vs. 31 ± 2%; P = 0.41 increase in vascular resistance at the onset of balloon inflation was not different between the alpha-adrenergic receptor inhibition and control (no drug trials. Therefore, our data indicate that alpha-adrenergic mediated vasoconstriction restricts compensatory vasodilation during forearm exercise with hypoperfusion, but is not responsible for the initial increase in vascular resistance at the onset of hypoperfusion.

  9. Revisiting acute normovolemic hemodilution and blood transfusion during pediatric cardiac surgery: a prospective observational study.

    Science.gov (United States)

    Sebastian, Roby; Ratliff, Todd; Winch, Peter D; Tumin, Dmitry; Gomez, Daniel; Tobias, Joseph; Galantowicz, Mark; Naguib, Aymen N

    2017-01-01

    The majority of allogeneic transfusions occur in the perioperative setting, especially during cardiac surgery. In addition to the economic implications, there is emerging evidence that blood transfusion may increase both morbidity and mortality. Acute normovolemic hemodilution (ANH) may limit the need for blood products. The primary objective of this study was to determine if the method of blood collection (syringe or bag) during the ANH process impacted the platelet count and function. The secondary objectives included the need for perioperative blood transfusions during the procedure and in the intensive care unit. In addition, we assessed these outcomes' associations with ANH parameters including the method of collection, time of storage, and volume removed. Data were collected prospectively from 50 patients undergoing cardiac surgery on cardiopulmonary bypass over a 6-month period. Platelet count and function were measured for the ANH blood immediately after collection and again prior to transfusing to the patient at the end of cardiopulmonary bypass. Other data collected included ANH volume, length of storage, and the quantity of all blood products given throughout the perioperative period. No change in platelet count or function was noted regardless of the length of time or collection method for the ANH blood. Twenty-three patients received blood or blood products in the operating room or the intensive care unit, while 27 patients received no blood transfusion during their entire hospitalization. Higher ANH volume (ml·kg -1 ) and longer storage time were associated with a greater need for intraoperative transfusions. Acute normovolemic hemodilution protects the platelets from the untoward effects of cardiopulmonary bypass and offers an important autologous blood product that improves hemostasis at the conclusion of surgery. Platelet count and function are preserved regardless of the method of collection or the length of storage. The volume of ANH removed

  10. Hemodynamic challenge to early mobilization after cardiac surgery: A pilot study

    Directory of Open Access Journals (Sweden)

    Tiziano Cassina

    2016-01-01

    Full Text Available Background: Active mobilization is a key component in fast-track surgical strategies. Following major surgery, clinicians are often reluctant to mobilize patients arguing that circulatory homeostasis would be impaired as a result of myocardial stunning, fluid shift, and autonomic dysfunction. Aims: We examined the feasibility and safety of a mobilization protocol 12-24 h after elective cardiac surgery. Setting and Design: This observational study was performed in a tertiary nonacademic cardiovascular Intensive Care Unit. Materials and Methods: Over a 6-month period, we prospectively evaluated the hemodynamic response to a two-staged mobilization procedure in 53 consecutive patients. Before, during, and after the mobilization, hemodynamics parameters were recorded, including the central venous oxygen saturation (ScvO 2 , lactate concentrations, mean arterial pressure (MAP, heart rate (HR, right atrial pressure (RAP, and arterial oxygen saturation (SpO 2 . Any adverse events were documented. Results: All patients successfully completed the mobilization procedure. Compared with the supine position, mobilization induced significant increases in arterial lactate (34.6% [31.6%, 47.6%], P = 0.0022 along with reduction in RAP (−33% [−21%, −45%], P 10% and nine of them (17% required treatment. Hypotensive patients experienced a greater decrease in ScvO 2 (−18 ± 5% vs. −9 ± 4%, P = 0.004 with similar changes in RAP and HR. All hemodynamic parameters, but arterial lactate, recovered baseline values after resuming the horizontal position. Conclusions: Early mobilization after cardiac surgery appears to be a safe procedure as far as it is performed under close hemodynamic and clinical monitoring in an intensive care setting.

  11. Effect of socioeconomic deprivation on waiting time for cardiac surgery: retrospective cohort study

    Science.gov (United States)

    Pell, Jill P; Pell, Alastair C H; Norrie, John; Ford, Ian; Cobbe, Stuart M

    2000-01-01

    Objective To determine whether the priority given to patients referred for cardiac surgery is associated with socioeconomic status. Design Retrospective study with multivariate logistic regression analysis of the association between deprivation and classification of urgency with allowance for age, sex, and type of operation. Multivariate linear regression analysis was used to determine association between deprivation and waiting time within each category of urgency, with allowance for age, sex, and type of operation. Setting NHS waiting lists in Scotland. Participants 26 642 patients waiting for cardiac surgery, 1 January 1986 to 31 December 1997. Main outcome measures Deprivation as measured by Carstairs deprivation category. Time spent on NHS waiting list. Results Patients who were most deprived tended to be younger and were more likely to be female. Patients in deprivation categories 6 and 7 (most deprived) waited about three weeks longer for surgery than those in category 1 (mean difference 24 days, 95% confidence interval 15 to 32). Deprived patients had an odds ratio of 0.5 (0.46 to 0.61) for having their operations classified as urgent compared with the least deprived, after allowance for age, sex, and type of operation. When urgent and routine cases were considered separately, there was no significant difference in waiting times between the most and least deprived categories. Conclusions Socioeconomically deprived patients are thought to be more likely to develop coronary heart disease but are less likely to be investigated and offered surgery once it has developed. Such patients may be further disadvantaged by having to wait longer for surgery because of being given lower priority. PMID:10617517

  12. Altered secretion and processing of epidermal growth factor in adrenergic-induced growth of the rat submandibular gland

    DEFF Research Database (Denmark)

    Thulesen, Jesper; Bor, Mustafa Vakur; Thulesen, Stina

    2002-01-01

    The granular convoluted tubule (GCT) cells of the submandibular glands represent a major production site for epidermal growth factor (EGF). This study investigates EGF production in the submandibular glands in relation to beta-adrenergic stimulation. Rats were treated with isoproterenol (beta...

  13. Food restriction modulates β-adrenergic-sensitive adenylate cyclase in rat liver during aging

    International Nuclear Information System (INIS)

    Katz, M.S.

    1988-01-01

    Adenylate cyclase activities were studied in rat liver during postmaturational aging of male Fischer 344 rats fed ad libitum or restricted to 60% of the ad libitum intake. Catecholamine-stimulated adenylate cyclase activity increased by 200-300% between 6 and 24-27 mo of age in ad libitum-fed rats, whereas in food-restricted rats catecholamine response increased by only 58-84% between 6 and 30 mo. In ad libitum-fed rats, glucagon-stimulated enzyme activity also increased by 40% between 6 and 12 mo and in restricted rats a similar age-related increase was delayed until 18 mo. β-Adrenergic receptor density increased by 50% between 6 and 24 mo in livers from ad libitum-fed but not food-restricted rats and showed a highly significant correlation with maximal isoproterenol-stimulated adenylate cyclase activity over the postmaturational life span. Age-related increases in unstimulated (basal) adenylate cyclase activity and nonreceptor-mediated enzyme activation were retarded by food restriction. The results demonstrate that food restriction diminishes a marked age-related increase in β-adrenergic-sensitive adenylate cyclase activity of rat liver. Alterations of adrenergic-responsive adenylate cyclase with age and the modulatory effects of food restriction appear to be mediated by changes in both receptor and nonreceptor components of adenylate cyclase

  14. Dietary sodium restriction and β2-adrenergic receptor polymorphism modulate cardiovascular function in humans

    Science.gov (United States)

    Eisenach, John H; Schroeder, Darrell R; Pike, Tasha L; Johnson, Christopher P; Schrage, William G; Snyder, Eric M; Johnson, Bruce D; Garovic, Vesna D; Turner, Stephen T; Joyner, Michael J

    2006-01-01

    Dietary Na+ intake influences β2-adrenergic receptor (β2AR) responsiveness. While receiving a normal Na+ diet (150 mmol day−1), subjects homozygous for glycine at amino acid 16 (Gly16) have greater forearm β2AR-mediated vasodilatation than subjects homozygous for arginine (Arg16), an effect that is mediated by endothelial NO. We tested the hypothesis that dietary Na+ restriction eliminates genotype differences in forearm and systemic β2AR-mediated dilatation in these groups. We measured heart rate, mean arterial pressure and cardiac output (CO, acetylene breathing) responses to administration of intravenous terbutaline (TRB) before and after 5 days of low dietary Na+ intake (10 mmol day−1) in healthy Gly16 (n = 17; age, 31 ± 7 year) and Arg16 homozygotes (n = 15; age, 29 ± 8 year). After the low-Na+ diet, a catheter was placed in the brachial artery to measure forearm blood flow (FBF, plethysmography) responses to administration of isoprenaline (isoproterenol) before and after NO inhibition with NG-mono-methyl-l-arginine (l-NMMA). In the Gly16 group, the low-Na+ diet decreased baseline CO from 6.4 ± 1.4 to 5.5 ± 1.2 l min−1 (P = 0.003, paired t test), tended to decrease stroke volume from 97.0 ± 20.6 to 86.9 ± 21.7 ml (P = 0.06) and increased peripheral resistance from 1106 ± 246 to 1246 ± 222 dynes s cm−5 (P = 0.02); significant effects of the low-Na+ diet were not observed in Arg16 subjects. In a repeated measures ANOVA, the responses of all cardiovascular measures to systemic administration of TRB were not influenced by genotype or diet. Additionally, the FBF response to incremenetal doses of isoprenaline did not differ between genotype groups before or after administration of l-NMMA. We conclude that dietary Na+ restriction blunted the increased forearm NO-mediated β2AR responsiveness in Gly16 homozygotes observed in a previous study after normal dietary Na+ intake, while baseline CO decreased and peripheral resistance increased in this

  15. Exploration of the psychological impact and adaptation to cardiac events in South Asians in the UK: a qualitative study.

    Science.gov (United States)

    Bhattacharyya, Mimi; Stevenson, Fiona; Walters, Kate

    2016-07-08

    There is little research on how different ethnic groups adapt after an acute cardiac event. This qualitative study explores between-ethnicity and within-ethnicity variation in adaptation, and the psychological impact of an acute cardiac event among UK South Asian and white British people. We purposively sampled people by ethnic group from general practices in London who had a new myocardial infarction, angina or acute arrhythmia in the preceding 18 months. We conducted 28 semistructured interviews for exploring the psychological symptoms, experiences and adaptations following a cardiac event among South Asians (Indian and Bangladeshi) in comparison to white British people. Data were analysed using a thematic 'framework' approach. Findings showed heterogeneity in experiences of the cardiac event and its subsequent psychological and physical impact. Adaptation to the event related predominantly to life circumstances, personal attitudes and employment status. Anxiety and low mood symptoms were common sequelae, especially in the Bangladeshi group. Indian men tended to normalise symptoms and the cardiac event, and reported less negative mood symptoms than other groups. Fear of physical exertion, particularly heavy lifting, persisted across the groups. Some people across all ethnic groups indicated the need for more psychological therapy postcardiac event. Socioeconomic circumstances, age and prior work status appeared to be more important in relation to adaptation after a cardiac event than ethnic status. Heterogeneity in views and experiences related to the socioeconomic background, age and work status of the participants along with some cultural influences. Rehabilitation programmes should be flexibly tailored for individuals in particular and where relevant, specific support should be provided for returning to work. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Exploration of the psychological impact and adaptation to cardiac events in South Asians in the UK: a qualitative study

    Science.gov (United States)

    Bhattacharyya, Mimi; Stevenson, Fiona; Walters, Kate

    2016-01-01

    Objective There is little research on how different ethnic groups adapt after an acute cardiac event. This qualitative study explores between-ethnicity and within-ethnicity variation in adaptation, and the psychological impact of an acute cardiac event among UK South Asian and white British people. Setting We purposively sampled people by ethnic group from general practices in London who had a new myocardial infarction, angina or acute arrhythmia in the preceding 18 months. Participants We conducted 28 semistructured interviews for exploring the psychological symptoms, experiences and adaptations following a cardiac event among South Asians (Indian and Bangladeshi) in comparison to white British people. Data were analysed using a thematic ‘framework’ approach. Results Findings showed heterogeneity in experiences of the cardiac event and its subsequent psychological and physical impact. Adaptation to the event related predominantly to life circumstances, personal attitudes and employment status. Anxiety and low mood symptoms were common sequelae, especially in the Bangladeshi group. Indian men tended to normalise symptoms and the cardiac event, and reported less negative mood symptoms than other groups. Fear of physical exertion, particularly heavy lifting, persisted across the groups. Some people across all ethnic groups indicated the need for more psychological therapy postcardiac event. Socioeconomic circumstances, age and prior work status appeared to be more important in relation to adaptation after a cardiac event than ethnic status. Conclusions Heterogeneity in views and experiences related to the socioeconomic background, age and work status of the participants along with some cultural influences. Rehabilitation programmes should be flexibly tailored for individuals in particular and where relevant, specific support should be provided for returning to work. PMID:27401355

  17. Impaired modulation of postjunctional α1 - but not α2 -adrenergic vasoconstriction in contracting forearm muscle of postmenopausal women.

    Science.gov (United States)

    Kruse, Nicholas T; Hughes, William E; Ueda, Kenichi; Hanada, Satoshi; Feider, Andrew J; Iwamoto, Erika; Bock, Joshua M; Casey, Darren P

    2018-04-30

    Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in skeletal muscle of ageing males, brought on by altered postjunctional α 1 - and α 2 -adrenergic receptor sensitivity. The extent to which postjunctional α-adrenergic vasoconstriction occurs in the forearms at rest and during exercise in postmenopausal women remains unknown. The novel findings indicate that contraction-mediated blunting of α 1 - (via intra-arterial infusion of phenylephrine) but not α 2 -adrenergic (via intra-arterial infusion of dexmedetomidine) vasoconstriction was attenuated in postmenopausal women compared to young women. Additional important findings revealed that postjunctional α-adrenergic vasoconstrictor responsiveness at rest does not appear to be affected by age in women. Collectively, these results contribute to our understanding of local neurovascular control at rest and during exercise with age in women. Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α-adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24 ± 1 years) and eight PMW (65 ± 1 years) completed a series of randomized experimental trials: (1) at rest, (2) under high flow (adenosine infusion) conditions and (3) during 6 min of forearm exercise at relative (20% of maximum) and absolute (7 kg) intensities. Phenylephrine (α 1 -agonist) or dexmedetomidine (α 2 -agonist) was administered during the last 3 min of each trial to elicit α-adrenergic vasoconstriction. Forearm vascular conductance (FVC) was calculated from blood flow and blood pressure. Vasoconstrictor responsiveness was identified as the change in FVC (%) during α-adrenergic

  18. Semi-automatic detection and correction of body organ motion, particularly cardiac