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Sample records for human atrial fibrosis

  1. Slow conduction in the border zones of patchy fibrosis stabilises the drivers for atrial fibrillation: Insights from multi-scale human atrial modelling

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    Ross Morgan

    2016-10-01

    Full Text Available Introduction. The genesis of atrial fibrillation (AF and success of AF ablation therapy have been strongly linked with atrial fibrosis. Increasing evidence suggests that patient-specific distributions of fibrosis may determine the locations of electrical drivers (rotors sustaining AF, but the underlying mechanisms are incompletely understood. This study aims to elucidate a missing mechanistic link between patient-specific fibrosis distributions and AF drivers. Methods. 3D atrial models integrated human atrial geometry, rule-based fibre orientation, region-specific electrophysiology and AF-induced ionic remodelling. A novel detailed model for an atrial fibroblast was developed, and effects of myocyte-fibroblast (M-F coupling were explored at single-cell, 1D tissue and 3D atria levels. Left atrial LGE MRI datasets from 3 chronic AF patients were segmented to provide the patient-specific distributions of fibrosis. The data was non-linearly registered and mapped to the 3D atria model. Six distinctive fibrosis levels (0 – healthy tissue, 5 – dense fibrosis were identified based on LGE MRI intensity and modelled as progressively increasing M-F coupling and decreasing atrial tissue coupling. Uniform 3D atrial model with diffuse (level 2 fibrosis was considered for comparison.Results. In single cells and tissue, the largest effect of atrial M-F coupling was on the myocyte resting membrane potential, leading to partial inactivation of sodium current and reduction of conduction velocity (CV. In the 3D atria, further to the M-F coupling, effects of fibrosis on tissue coupling greatly reduce atrial CV. AF was initiated by fast pacing in each 3D model with either uniform or patient-specific fibrosis. High variation in fibrosis distributions between the models resulted in varying complexity of AF, with several drivers emerging. In the diffuse fibrosis models, waves randomly meandered through the atria, whereas in each the patient-specific models, rotors

  2. Increased susceptibility to atrial fibrillation secondary to atrial fibrosis in transgenic goats expressing transforming growth factor - B1

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    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in people with significant morbidity and mortality. There is a strong association between atrial fibrosis and AF. Transforming growth factor B1 (TGF-B1) is an essential mediator of atrial fibrosis in animal models and human pat...

  3. Increased amount of atrial fibrosis in patients with atrial fibrillation secondary to mitral valve disease

    NARCIS (Netherlands)

    Geuzebroek, Guillaume S. C.; van Amersfoorth, Shirley C. M.; Hoogendijk, Mark G.; Kelder, Johannes C.; van Hemel, Norbert M.; de Bakker, Jacques M. T.; Coronel, Ruben

    2012-01-01

    Objective: Atrial fibrosis is related to atrial fibrillation but may differ in patients with mitral valve disease or lone atrial fibrillation. Therefore, we studied atrial fibrosis in patients with atrial fibrillation + mitral valve disease or with lone atrial fibrillation and compared it with

  4. Fibrosis and electrophysiological characteristics of the atrial appendage in patients with atrial fibrillation and structural heart disease

    NARCIS (Netherlands)

    Brakel, T.J. van; Krieken, T. van der; Westra, S.W.; Laak, J.A.W.M. van der; Smeets, J.L.R.M.; Swieten, H.A. van

    2013-01-01

    PURPOSE: This study was conducted to investigate the degree of fibrosis in atrial appendages of patients with and without atrial fibrillation (AF) undergoing cardiac surgery. In addition, we hypothesized that areas of atrial fibrosis can be identified by electrogram fractionation and low voltage for

  5. Role of atrial endothelial cells in the development of atrial fibrosis and fibrillation in response to pressure overload.

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    Kume, Osamu; Teshima, Yasushi; Abe, Ichitaro; Ikebe, Yuki; Oniki, Takahiro; Kondo, Hidekazu; Saito, Shotaro; Fukui, Akira; Yufu, Kunio; Miura, Masahiro; Shimada, Tatsuo; Takahashi, Naohiko

    Monocyte chemoattractant protein-1 (MCP-1)-mediated inflammatory mechanisms have been shown to play a crucial role in atrial fibrosis induced by pressure overload. In the present study, we investigated whether left atrial endothelial cells would quickly respond structurally and functionally to pressure overload to trigger atrial fibrosis and fibrillation. Six-week-old male Sprague-Dawley rats underwent suprarenal abdominal aortic constriction (AAC) or a sham operation. By day 3 after surgery, macrophages were observed to infiltrate into the endocardium. The expression of MCP-1 and E-selectin in atrial endothelium and the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and ED1 in left atrial tissue were enhanced. Atrial endothelial cells were irregularly hypertrophied with the disarrangement of lines of cells by scanning electron microscopy. Various-sized gap formations appeared along the border in atrial endothelial cells, and several macrophages were located just in the endothelial gap. Along with the development of heterogeneous interstitial fibrosis, interatrial conduction time was prolonged and the inducibility of atrial fibrillation by programmed extrastimuli was increased in the AAC rats compared to the sham-operated rats. Atrial endothelium responds rapidly to pressure overload by expressing adhesion molecules and MCP-1, which induce macrophage infiltration into the atrial tissues. These processes could be an initial step in the development of atrial remodeling for atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Development of a transgenic goat model wih cardiac-specific overexpression of transforming growth factor - {beta} 1 to study the relationship between atrial fibrosis and atrial fibrillation

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    Studies on patients, large animal models and transgenic mouse models have shown a strong association of atrial fibrosis with atrial fibrillation (AF). However, it is unclear whether there is a causal relationship between atrial fibrosis and AF or whether these events appear as a result of independen...

  7. Hyperleptinemia Exacerbates High-Fat Diet-Mediated Atrial Fibrosis and Fibrillation.

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    Fukui, Akira; Ikebe-Ebata, Yuki; Kondo, Hidekazu; Saito, Shotaro; Aoki, Kohei; Fukunaga, Naoya; Shinohara, Tetsuji; Masaki, Takayuki; Teshima, Yasushi; Takahashi, Naohiko

    2017-06-01

    Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF. Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD. After 8 weeks, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed and left atrial (LA) tissues were collected for histological analysis, hydroxyproline assay, and reverse transcription-polymerase chain reaction. HFD treatment increased body weight in both WT and Ob mice compared with NFD (both P atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity-related AF. © 2017 Wiley Periodicals, Inc.

  8. Relaxin suppresses atrial fibrillation in aged rats by reversing fibrosis and upregulating Na+ channels.

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    Henry, Brian L; Gabris, Beth; Li, Qiao; Martin, Brian; Giannini, Marianna; Parikh, Ashish; Patel, Divyang; Haney, Jamie; Schwartzman, David S; Shroff, Sanjeev G; Salama, Guy

    2016-04-01

    Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly patients and has been correlated with enhanced age-dependent atrial fibrosis. Reversal of atrial fibrosis has been proposed as therapeutic strategy to suppress AF. To test the ability of relaxin to reverse age-dependent atrial fibrosis and suppress AF. Aged F-344 rats (24 months old) were treated with subcutaneous infusion of vehicle or relaxin (0.4 mg/kg/day) for 2 weeks. Rat hearts were excised, perfused on a Langendorff apparatus, and stained with voltage and Ca(2+) indicator dyes. Optical mapping and programmed electrical stimulation was used to test arrhythmia vulnerability and changes in electrophysiological characteristics. Changes in protein expression and Na(+) current density (INa) were measured by tissue immunofluorescence and whole-cell patch clamp technique. In aged rats, sustained AF was readily induced with a premature pulse (n = 7/8) and relaxin treatment suppressed sustained AF by a premature impulse or burst pacing (n = 1/6) (P atrial action potential conduction velocity and decreased atrial fibrosis. Relaxin treatment increased Nav1.5 expression (n = 6; 36% ± 10%) and decreased total collagen and collagen I (n = 5-6; 55%-66% ± 15%) in aged atria (P atrial INa by 46% ± 4% (n = 12-13/group, P atrial conduction velocity by decreasing atrial fibrosis and increasing INa. These data provide compelling evidence that relaxin may serve as an effective therapy to manage AF in geriatric patients by reversing fibrosis and modulating cardiac ionic currents. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

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    Chen, Xiao-Qing; Zhang, Dao-Liang; Zhang, Ming-Jian; Guo, Meng; Zhan, Yang-Yang; Liu, Fang; Jiang, Wei-Feng; Zhou, Li; Zhao, Liang; Wang, Quan-Xing; Liu, Xu

    2015-01-01

    Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. - Highlights: • Compared with SR, AF showed higher TRIF expression in left atrial appendage. • TRIF siRNA reversed macrophage chemotaxis induced by AngII-treated fibroblast. • TRIF siRNA reversed chemokines expressions induced by AngII in fibroblast. • AngII-stimulated atrial fibroblast proliferation was enhanced by macrophage

  10. TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

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    Chen, Xiao-Qing; Zhang, Dao-Liang [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhang, Ming-Jian; Guo, Meng; Zhan, Yang-Yang; Liu, Fang [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-Feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhao, Liang, E-mail: zhaol_zg@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Wang, Quan-Xing, E-mail: wqxejd@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Liu, Xu, E-mail: liuxu_xk@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China)

    2015-08-14

    Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. - Highlights: • Compared with SR, AF showed higher TRIF expression in left atrial appendage. • TRIF siRNA reversed macrophage chemotaxis induced by AngII-treated fibroblast. • TRIF siRNA reversed chemokines expressions induced by AngII in fibroblast. • AngII-stimulated atrial fibroblast proliferation was enhanced by macrophage.

  11. Involvement of Smad3 pathway in atrial fibrosis induced by elevated hydrostatic pressure.

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    Wei, Wei; Rao, Fang; Liu, Fangzhou; Xue, Yumei; Deng, Chunyu; Wang, Zhaoyu; Zhu, Jiening; Yang, Hui; Li, Xin; Zhang, Mengzhen; Fu, Yongheng; Zhu, Wensi; Shan, Zhixin; Wu, Shulin

    2018-06-01

    Hypertension is a main risk factor for atrial fibrillation, but the direct effects of hydrostatic pressure on the atrial fibrosis are still unknown. The present study investigated whether hydrostatic pressure is responsible for atrial fibrosis, and addressed a potential role of the Smad pathway in this pathology. Biochemical assays were used to study regulation and expression of fibrotic factors in spontaneously hypertensive rats (SHRs) and Wistar rats, and in cardiac fibroblasts (CFs) cultured under standard (0 mmHg) and elevated (20, 40 mmHg) hydrostatic pressure. Levels of atrial fibrosis and protein expression of fibrotic factors Col-1A1/-3A1, TGF-β1, and MMP-2 in SHRs' left atrial tissues were higher than those in Wistar rats. Exposure to elevated pressure was associated with the proliferation of CFs. The protein expression of Col-1A1/-3A1, TGF-β1, and MMP-2 in CFs was also up-regulated in a pressure-dependent manner. The proliferation of CFs and increased expressions of fibrotic markers induced by elevated hydrostatic pressure could be reversed by the Smad3 inhibitor naringenin. The activation of Smad3 pathway was also stimulated by elevated hydrostatic pressure. These results demonstrate that CF secretory function and proliferation can be up-regulated by exposure to elevated pressure, and that Smad3 may modulate CF activation induced by high hydrostatic pressure. © 2017 Wiley Periodicals, Inc.

  12. Importance of Pulmonary Vein Preferential Fibrosis for Atrial Fibrillation Promotion in Hypertensive Rat Hearts.

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    Iwasaki, Yu-Ki; Yamashita, Takeshi; Sekiguchi, Akiko; Hayami, Noriyuki; Shimizu, Wataru

    2016-06-01

    Hypertension is one of the independent risk factors for atrial fibrillation (AF). Pulmonary veins (PVs) play an important role as the substrate for AF and triggers of AF. The purpose of this study was to determine the structural remodelling of the PVs and its effect on promoting AF in hypertensive (HT) rat hearts. Eighteen-week-old Dahl salt-sensitive HT rats and their controls were used for histological and immunohistological analyses, and electrophysiological studies were performed in Langendorff perfused hearts. Masson-trichrome staining revealed that hypertension significantly increased the fibrosis in the PVs, particularly in subendocardial and perivascular areas, compared with that in control rats, however, at this early stage of hypertension, left atrial fibrosis was not prominent. In the HT rat hearts with PVs, electrical stimulation significantly increased the number of repetitive atrial firing and atrial tachycardia inducibility, which significantly diminished after the excision of the PVs. An immunofluorescent analysis revealed that HT rats had PV specific endocardial smooth muscle actin (αSMA)-positive cells with remarkable proliferation of platelet-derived growth factor (PDGF)-C and vascular endothelial growth factor (VEGF), which was lacking in the left atrial structures of the control and the HT rats. Pretreatment with imatinib, a PDGF receptor activity blocker, in HT rats reduced the αSMA-positive cell proliferation and fibrosis in the PVs and also induced a significant reduction in VEGF expression. Also, the drug pretreatment effectively prevented repetitive atrial firing promotion without affecting the blood pressure. PV preferential fibrosis might play an important role in the arrhythmogenic substrate of AF in HT rat hearts. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  13. LEFT ATRIAL FIBROSIS IN PATIENTS WITH ATRIAL FIBRILLATION ACCORDING TO MAGNETIC RESONANCE IMAGING WITH LATE GADOLINIUM ENHANCEMENT

    Directory of Open Access Journals (Sweden)

    O. V. Stukalova

    2015-01-01

    Full Text Available Rationale: Atrial fibrillation (AF is the most common type of arrhythmia. Left atrial abnormalities in AF require further investigation.Aim: To evaluate characteristics of myocardial structure of the left atrium by magnetic resonance imaging (MRI with delayed contrast enhancement in patients with AF associated with essential hypertension (EH, in those without any cardiovascular disorders, and in patients with AF after cryoablation of the pulmonary artery orifice.Materials and methods: The study enrolled 53 patients with AF (mean age 56 years. Twenty eight of them had AF without any associated cardiovascular disorders (lone AF, or LAF group, 25 patients had AF related to EH (AF + EH group. Three patients had undergone anti-arrhythmic intervention. Cardiac MRI was performed in all patients with high resolution late gadolinium enhancement (LGE at 15–20 min after i.v. gadoversetamide (0.15 mmol/kg. For LGE MRI, we used a novel high resolution inversion recovery (inversion times 290–340 ms magnetic resonance pulse sequence with isotropic voxel (size 1.25 . 1.25 .2.5 mm and fat saturation. Left atrium walls were segmented semi-automatically on the LGE images. Left atrium fibrosis quantification was performed with the original software LGE Heart Analyzer, developed in Russian Cardiology Research and Production Complex (Moscow.Results: Left atrium fibrosis (mean, 9 [1.7; 18] % was found both in patients with AF + EH and with lone AF. There was a trend towards more significant left atrial fibrosis in the group of AF + EH, compared to that in the lone AF group (10.972 [6.98; 19.366] % vs 4.37 [0.893; 18.575] %, respectively, p = 0.1. The extent of left atrium fibrosis correlated with left atrium dilatation (r = 0.37, p < 0.001 and with the decreased ejection fraction (r = -0.4, р < 0.001. The patients who had undergone an antiarrhythmic intervention, demonstrated formation of intensive LGE zones in the ablation areas.Conclusion: Quantification of

  14. Transforming growth factor-β-mediated CD44/STAT3 signaling contributes to the development of atrial fibrosis and fibrillation.

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    Chang, Shang-Hung; Yeh, Yung-Hsin; Lee, Jia-Lin; Hsu, Yu-Juei; Kuo, Chi-Tai; Chen, Wei-Jan

    2017-09-04

    Atrial fibrillation (AF) is associated with atrial fibrosis. Inhibition of atrial fibrosis might be a plausible approach for AF prevention and therapy. This study is designed to evaluate the potential role of CD44, a membrane receptor known to regulate fibrosis, and its related signaling in the pathogenesis of atrial fibrosis and AF. Treatment of cultured rat atrial fibroblasts with transforming growth factor-β (TGF-β, a key mediator of atrial fibrosis) led to a higher expression of hyaluronan (HA), CD44, STAT3, and collagen (a principal marker of fibrosis) than that of ventricular fibroblasts. In vivo, TGF-β transgenic mice and AF patients exhibited a greater expression of HA, CD44, STAT3, and collagen in their atria than wild-type mice and sinus rhythm subjects, respectively. Treating TGF-β transgenic mice with an anti-CD44 blocking antibody resulted in a lower expression of STAT3 and collagen in their atria than those with control IgG antibody. Programmed stimulation triggered less AF episodes in TGF-β transgenic mice treated with anti-CD44 blocking antibody than in those with control IgG. Blocking CD44 signaling with anti-CD44 antibody and mutated CD44 plasmids attenuated TGF-β-induced STAT3 activation and collagen expression in cultured atrial fibroblasts. Deletion and mutational analysis of the collagen promoter along with chromatin immunoprecipitation demonstrated that STAT3 served as a vital transcription factor in collagen expression. TGF-β-mediated HA/CD44/STAT3 pathway plays a crucial role in the development of atrial fibrosis and AF. Blocking CD44-dependent signaling may be a feasible way for AF management.

  15. Triggered Firing and Atrial Fibrillation in Transgenic Mice With Selective Atrial Fibrosis Induced by Overexpression of TGF-β1

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    Choi, Eue-Keun; Chang, Po-Cheng; Lee, Young-Soo; Lin, Shien-Fong; Zhu, Wuqiang; Maruyama, Mitsunori; Fishbein, Michael C.; Chen, Zhenhui; der Lohe, Michael Rubart-von; Field, Loren J.; Chen, Peng-Sheng

    2013-01-01

    Background Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Cai) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor β1 (TGF-β1). Methods and Results MHC-TGFcys33ser Tx mice develop atrial fibrosis because of elevated levels of TGF-β1. We studied membrane potential and Cai transients of isolated superfused atria from Tx and wild-type (Wt) littermates. Short APD and persistently elevated Cai transients promoted spontaneous repetitive EADs, triggered activity and spontaneous AF after cessation of burst pacing in Tx but not Wt atria (39% vs. 0%, P=0.008). We were able to map optically 4 episodes of spontaneous AF re-initiation. All first and second beats of spontaneous AF originated from the right atrium (4/4, 100%), which is more severely fibrotic than the left atrium. Ryanodine and thapsigargin inhibited spontaneous re-initiation of AF in all 7 Tx atria tested. Western blotting showed no significant changes of calsequestrin or sarco/endoplasmic reticulum Ca2+-ATPase 2a. Conclusions Spontaneous AF may occur in the Tx atrium because of CTTF, characterized by APD shortening, prolonged Cai transient, EAD and triggered activity. Inhibition of Ca2+ release from the sarcoplasmic reticulum suppressed spontaneous AF. Our results indicate that CTTF is an important arrhythmogenic mechanism in TGF-β1 Tx atria. PMID:22447020

  16. Splenectomy exacerbates atrial inflammatory fibrosis and vulnerability to atrial fibrillation induced by pressure overload in rats: Possible role of spleen-derived interleukin-10.

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    Kondo, Hidekazu; Takahashi, Naohiko; Gotoh, Koro; Fukui, Akira; Saito, Shotaro; Aoki, Kohei; Kume, Osamu; Shinohara, Tetsuji; Teshima, Yasushi; Saikawa, Tetsunori

    2016-01-01

    The spleen is important for cardiac remodeling induced by myocardial infarction. However, the role of the spleen in inflammatory atrial fibrosis induced by pressure overload is unknown. The purpose of this study was to investigate whether splenectomy (SPX) attenuates or exacerbates pressure overload-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in rats. Male Sprague-Dawley rats (6 weeks old) were divided into Sham+Sham, Sham+SPX, abdominal aortic constriction (AAC)+Sham, and AAC+SPX groups, and were evaluated for inflammation, fibrosis, and AF on days 2, 4, 14, and 28. On day 4, an AAC-induced rise in interleukin-10 (IL-10) level was observed in the spleen, serum, and left atrium (LA), with SPX showing inhibitory effects in the latter 2 instances. In addition, AAC-induced M2 macrophage recruitment into the LA was decreased by SPX, as determined by immunofluorescence labeling (P <.05). On day 28, AAC-induced heterogeneous interstitial fibrosis of the LA was enhanced by SPX (P <.05). Electrophysiologic recordings revealed that the duration of AF and prolongation of interatrial conduction time induced by AAC were increased by SPX (P < .01 and P <.05, respectively). Furthermore, in the AAC+SPX group, the number of macrophages infiltrating into the LA on day 2 was marginal, but increased on day 28 relative to the AAC+Sham group. IL-10 administration attenuated the AAC-induced atrial remodeling that was aggravated by SPX. The study results suggest that SPX exacerbates AAC-induced inflammatory atrial fibrosis and increases vulnerability to AF after 4 weeks, likely because of depletion of spleen-derived IL-10. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  17. Possible role of rivaroxaban in attenuating pressure-overload-induced atrial fibrosis and fibrillation.

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    Kondo, Hidekazu; Abe, Ichitaro; Fukui, Akira; Saito, Shotaro; Miyoshi, Miho; Aoki, Kohei; Shinohara, Tetsuji; Teshima, Yasushi; Yufu, Kunio; Takahashi, Naohiko

    2018-03-01

    Coagulation factor Xa (FXa) promotes thrombus formation and exacerbates inflammation via activation of protease-activated receptor (PAR)-2. We tested the hypothesis of whether administration of direct oral anticoagulant, rivaroxaban, would attenuate transverse aortic constriction (TAC)-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in mice. Ten-week-old male CL57/B6 mice were divided into a sham-operation (CNT) group and TAC-surgery group. These two groups were then subdivided into vehicle (VEH) and rivaroxaban (RVX) treatment (30μg/g/day) groups. We assessed PAR-2 expression in response to TAC-related stimulation using rat cultured cells. TAC-induced left atrial thrombus formation was not observed in the TAC-RVX group. Cardiac PAR-2 upregulation was observed in both TAC groups. In the quantitative analysis of mRNA levels, cardiac PAR-2 upregulation was attenuated in the TAC-RVX group compared to TAC-VEH group. In histological evaluation, the TAC-VEH group showed cardiac inhomogeneous interstitial fibrosis and abundant infiltration of macrophages, which were attenuated by RVX administration. Electrophysiological examination revealed that AF duration in the TAC group was shortened by RVX administration. TAC-induced protein overexpression of monocyte chemoattractant protein-1, and mRNA overexpression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the left atrium was suppressed by RVX treatment. In cardiac fibroblasts, persistent intermittent stretch upregulated PAR-2, which was suppressed by RVX pre-incubation. These observations demonstrate that coagulation FXa inhibitor probably has a cardioprotective effect against pressure-overload-induced atrial remodeling. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  18. Relevance of Electrical Remodeling in Human Atrial Fibrillation Results of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial Mechanisms of Atrial Fibrillation Study

    NARCIS (Netherlands)

    Healey, Jeff S.; Israel, Carsten W.; Connolly, Stuart J.; Hohnloser, Stefan H.; Nair, Girish M.; Divakaramenon, Syamkumar; Capucci, Alessandro; Van Gelder, Isabelle C.; Lau, Chu-Pak; Gold, Michael R.; Carlson, Mark; Themeles, Ellison; Morillo, Carlos A.

    Background-In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear. Methods and Results-The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the

  19. Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1

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    Glukhov, Alexey V.; Kalyanasundaram, Anuradha; Lou, Qing; Hage, Lori T.; Hansen, Brian J.; Belevych, Andriy E.; Mohler, Peter J.; Knollmann, Björn C.; Periasamy, Muthu; Györke, Sandor; Fedorov, Vadim V.

    2015-01-01

    Aims Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. Methods and results In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca2+ cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2−/−) mice. Casq2−/− mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca2+ cycling, including abnormal Ca2+ release, periods of significantly elevated diastolic Ca2+ levels leading to pauses and unstable pacemaker rate. Importantly, Ca2+ cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca2+ transient upstrokes throughout the atrial pacemaker complex. Conclusions Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca2+ release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients. PMID:24216388

  20. Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation.

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    Carlos Sánchez

    Full Text Available Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR and chronic atrial fibrillation (cAF patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP recorded in 363 patients both under SR and cAF conditions.Human AP recordings in atrial trabeculae (n = 469 from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in G(K1, G(Kur and G(to, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in I(K1 and I(NaK underlies variability in APD90, variability in I(Kur, I(CaL and I(NaK modulates variability in APD50 and combined variability in Ito and I(Kur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by I(K1 and either I(NaK or I(NaCa depending on the model.Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP

  1. Correlation between myocardial fibrosis and the occurrence of atrial fibrillation in hypertrophic cardiomyopathy: A cardiac magnetic resonance imaging study

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    Pujadas, S., E-mail: sandrapujadas@gmail.co [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Vidal-Perez, R. [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Hidalgo, A. [Radiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Leta, R.; Carreras, F.; Barros, A. [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Bayes-Genis, A. [Cardiomyopathy and Cardiac Transplant Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Subirana, M.T. [Congenital Heart Disease Unit, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Pons-Llado, Guillem [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain)

    2010-08-15

    Cardiac magnetic resonance imaging (CMR) in hypertrophic cardiomyopathy (HCM) often shows delayed contrast enhancement (DE) representing regions of focal myocardial fibrosis. Atrial fibrillation (AF) is a commonly reported complication of HCM. We determined the relationship between the presence of left ventricular myocardial fibrosis (LVMF) detected by DE-CMR and the occurrence AF in a series of patients with HCM. 67 patients with HCM (47 males; mean age 50.1 {+-} 18.5 years) were studied by CMR measuring mass of LVMF, left ventricular mass, volume and function, and left atrial (LA) area. AF was present in 17 (25%) patients. LVMF was observed in 57% of patients. AF was significantly more frequent in patients who also showed LVMF, compared with the group without LVMF (42.1% vs. 3.4%, respectively; p < 0.0001). LA size was larger in patients showing DE (LA area: 37.4 {+-} 11.1 vs. 25.9 {+-} 6.8 cm{sup 2}; respectively, p = 0.0001). AF in HCM is related with myocardial fibrosis detected by DE-CMR and dilatation of the LA. This fact adds to the proven adverse prognostic value of myocardial fibrosis in HCM, thus, reinforcing the usefulness of this technique in the assessment of these patients.

  2. Correlation between myocardial fibrosis and the occurrence of atrial fibrillation in hypertrophic cardiomyopathy: A cardiac magnetic resonance imaging study

    International Nuclear Information System (INIS)

    Pujadas, S.; Vidal-Perez, R.; Hidalgo, A.; Leta, R.; Carreras, F.; Barros, A.; Bayes-Genis, A.; Subirana, M.T.; Pons-Llado, Guillem

    2010-01-01

    Cardiac magnetic resonance imaging (CMR) in hypertrophic cardiomyopathy (HCM) often shows delayed contrast enhancement (DE) representing regions of focal myocardial fibrosis. Atrial fibrillation (AF) is a commonly reported complication of HCM. We determined the relationship between the presence of left ventricular myocardial fibrosis (LVMF) detected by DE-CMR and the occurrence AF in a series of patients with HCM. 67 patients with HCM (47 males; mean age 50.1 ± 18.5 years) were studied by CMR measuring mass of LVMF, left ventricular mass, volume and function, and left atrial (LA) area. AF was present in 17 (25%) patients. LVMF was observed in 57% of patients. AF was significantly more frequent in patients who also showed LVMF, compared with the group without LVMF (42.1% vs. 3.4%, respectively; p 2 ; respectively, p = 0.0001). AF in HCM is related with myocardial fibrosis detected by DE-CMR and dilatation of the LA. This fact adds to the proven adverse prognostic value of myocardial fibrosis in HCM, thus, reinforcing the usefulness of this technique in the assessment of these patients.

  3. Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate

    Science.gov (United States)

    Goldberger, Jeffrey J.; Arora, Rishi; Green, David; Greenland, Philip; Lee, Daniel C.; Lloyd-Jones, Donald M.; Markl, Michael; Ng, Jason; Shah, Sanjiv J.

    2015-01-01

    Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. Current diagnostic approaches in patients with AF focus on identifying clinical predictors with evaluation of left atrial size by echocardiography serving as the sole measure specifically evaluating the atrium. Although the atrial substrate underlying AF is likely developing for years prior to the onset of AF, there is no current evaluation to identify the pre-clinical atrial myopathy. Atrial fibrosis is one component of the atrial substrate that has garnered recent attention based on newer MRI techniques that have been applied to visualize atrial fibrosis in humans with prognostic implications regarding success of treatment. Advanced ECG signal processing, echocardiographic techniques, and MRI imaging of fibrosis and flow provide up-to-date approaches to evaluate the atrial myopathy underlying AF. While thromboembolic risk is currently defined by clinical scores, their predictive value is mediocre. Evaluation of stasis via imaging and biomarkers associated with thrombogenesis may provide enhanced approaches to assess risk for stroke in patients with AF. Better delineation of the atrial myopathy that serves as the substrate for AF and thromboembolic complications might improve treatment outcomes. Furthermore, better delineation of the pathophysiologic mechanisms underlying the development of the atrial substrate for AF, particularly in its earlier stages, could help identify blood and imaging biomarkers that could be useful to assess risk for developing new onset AF and suggest specific pathways that could be targeted for prevention. PMID:26216085

  4. Automatic detection and classification of human epicardial atrial unipolar electrograms

    International Nuclear Information System (INIS)

    Dubé, B; Vinet, A; Xiong, F; Yin, Y; LeBlanc, A-R; Pagé, P

    2009-01-01

    This paper describes an unsupervised signal processing method applied to three-channel unipolar electrograms recorded from human atria. These were obtained by epicardial wires sutured on the right and left atria after coronary artery bypass surgery. Atrial (A) and ventricular (V) activations had to be detected and identified on each channel, and gathered across the channels when belonging to the same global event. The algorithm was developed and optimized on a training set of 19 recordings of 5 min. It was assessed on twenty-seven 2 h recordings taken just before the onset of a prolonged atrial fibrillation for a total of 1593697 activations that were validated and classified as normal atrial or ventricular activations (A, V) and premature atrial or ventricular activations (PAA, PVA). 99.93% of the activations were detected, and amongst these, 99.89% of the A and 99.75% of the V activations were correctly labelled. In the subset of the 39705 PAA, 99.83% were detected and 99.3% were correctly classified as A. The false positive rate was 0.37%. In conclusion, a reliable fully automatic detection and classification algorithm was developed that can detect and discriminate A and V activations from atrial recordings. It can provide the time series needed to develop a monitoring system aiming to identify dynamic predictors of forthcoming cardiac events such as postoperative atrial fibrillation

  5. Direct Proof of Endo-Epicardial Asynchrony of the Atrial Wall During Atrial Fibrillation in Humans.

    Science.gov (United States)

    de Groot, Natasja; van der Does, Lisette; Yaksh, Ameeta; Lanters, Eva; Teuwen, Christophe; Knops, Paul; van de Woestijne, Pieter; Bekkers, Jos; Kik, Charles; Bogers, Ad; Allessie, Maurits

    2016-05-01

    The presence of focal fibrillation waves during atrial fibrillation (AF) can, besides ectopic activity, also be explained by asynchronous activation of the atrial endo- and epicardial layer and transmurally propagating fibrillation waves. To provide direct proof of endo-epicardial asynchrony, we performed simultaneous high-resolution mapping of the right atrial endo- and epicardial wall during AF in humans. Intraoperative mapping of the endo- and epicardial right atrial wall was performed during (induced) AF in 10 patients with AF (paroxysmal: n=3; persistent: n=4; and longstanding persistent: n=3) and 4 patients without a history of AF. A clamp made of 2 rectangular 8×16 electrode arrays (interelectrode distance 2 mm) was inserted into the incision in the right atrial appendage. Recordings of 10 seconds of AF were analyzed to determine the incidence of asynchronous endo-epicardial activation times (≥15 ms) of opposite electrodes. Asynchronous endo-epicardial activation ranged between 0.9 and 55.9% without preference for either side. Focal waves appeared equally frequent at endocardium and epicardium (11% versus 13%; ITALIC! P=0.18). Using strict criteria for breakthrough (presence of an opposite wave within 4 mm and ≤14 ms before the origin of the focal wave), the majority (65%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. We provided the first evidence for asynchronous activation of the endo-epicardial wall during AF in humans. Endo-epicardial asynchrony may play a major role in the pathophysiology of AF and may offer an explanation why in some patients therapy fails. © 2016 American Heart Association, Inc.

  6. Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation.

    Science.gov (United States)

    Glasscock, Edward; Voigt, Niels; McCauley, Mark D; Sun, Qiang; Li, Na; Chiang, David Y; Zhou, Xiao-Bo; Molina, Cristina E; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G; Noebels, Jeffrey L; Dobrev, Dobromir; Wehrens, Xander H T

    2015-09-01

    Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility.

  7. In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis

    DEFF Research Database (Denmark)

    Colman, Michael A; Ni, Haibo; Liang, Bo

    2017-01-01

    and quantify the functional impact of these KCNA5 mutations on atrial electrical activity. A multi-scale model of the human atria was updated to incorporate detailed experimental data on IKur from both wild-type and mutants. The effects of the mutations on human atrial action potential and rate dependence were...... provides new insights into understanding the mechanisms by which mutant IKur contributes to atrial arrhythmias. In addition, as IKur is an atrial-specific channel and a number of IKur-selective blockers have been developed as anti-AF agents, this study also helps to understand some contradictory results...

  8. Systemic right ventricular fibrosis detected by cardiovascular magnetic resonance is associated with clinical outcome, mainly new-onset atrial arrhythmia, in patients after atrial redirection surgery for transposition of the great arteries.

    Science.gov (United States)

    Rydman, Riikka; Gatzoulis, Michael A; Ho, Siew Yen; Ernst, Sabine; Swan, Lorna; Li, Wei; Wong, Tom; Sheppard, Mary; McCarthy, Karen P; Roughton, Michael; Kilner, Philip J; Pennell, Dudley J; Babu-Narayan, Sonya V

    2015-05-01

    We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance predicts outcomes in patients with transposition of the great arteries post atrial redirection surgery. These patients have a systemic right ventricle (RV) and are at risk of arrhythmia, premature RV failure, and sudden death. Fifty-five patients (aged 27±7 years) underwent LGE cardiovascular magnetic resonance and were followed for a median 7.8 (interquartile range, 3.8-9.6) years in a prospective single-center cohort study. RV LGE was present in 31 (56%) patients. The prespecified composite clinical end point comprised new-onset sustained tachyarrhythmia (atrial/ventricular) or decompensated heart failure admission/transplantation/death. Univariate predictors of the composite end point (n=22 patients; 19 atrial/2 ventricular tachyarrhythmia, 1 death) included RV LGE presence and extent, RV volumes/mass/ejection fraction, right atrial area, peak Vo(2), and age at repair. In bivariate analysis, RV LGE presence was independently associated with the composite end point (hazard ratio, 4.95 [95% confidence interval, 1.60-15.28]; P=0.005), and only percent predicted peak Vo(2) remained significantly associated with cardiac events after controlling for RV LGE (hazard ratio, 0.80 [95% confidence interval, 0.68-0.95]; P=0.009/5%). In 8 of 9 patients with >1 event, atrial tachyarrhythmia, itself a known risk factor for mortality, occurred first. There was agreement between location and extent of RV LGE at in vivo cardiovascular magnetic resonance and histologically documented focal RV fibrosis in an explanted heart. There was RV LGE progression in a different case restudied for clinical indications. Systemic RV LGE is strongly associated with adverse clinical outcome especially arrhythmia in transposition of the great arteries, thus LGE cardiovascular magnetic resonance should be incorporated in risk stratification of these patients. © 2015 American Heart

  9. Identification and purification of human induced pluripotent stem cell-derived atrial-like cardiomyocytes based on sarcolipin expression.

    Directory of Open Access Journals (Sweden)

    Rebecca Josowitz

    Full Text Available The use of human stem cell-derived cardiomyocytes to study atrial biology and disease has been restricted by the lack of a reliable method for stem cell-derived atrial cell labeling and purification. The goal of this study was to generate an atrial-specific reporter construct to identify and purify human stem cell-derived atrial-like cardiomyocytes. We have created a bacterial artificial chromosome (BAC reporter construct in which fluorescence is driven by expression of the atrial-specific gene sarcolipin (SLN. When purified using flow cytometry, cells with high fluorescence specifically express atrial genes and display functional calcium handling and electrophysiological properties consistent with atrial cardiomyocytes. Our data indicate that SLN can be used as a marker to successfully monitor and isolate hiPSC-derived atrial-like cardiomyocytes. These purified cells may find many applications, including in the study of atrial-specific pathologies and chamber-specific lineage development.

  10. Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Elmas, Elif; Doesch, Christina; Fluechter, Stephan; Freundt, Miriam; Weiss, Christel; Lang, Siegfried; Kälsch, Thorsten; Haghi, Dariush; Papassotiriou, Jana; Kunde, Jan; Schoenberg, Stefan O; Borggrefe, Martin; Papavassiliu, Theano

    2011-04-01

    We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.

  11. Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution.

    Directory of Open Access Journals (Sweden)

    Andrea Baiocchini

    Full Text Available Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis. Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

  12. Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics – Insights from a 3D Model of the Human Atria

    Science.gov (United States)

    Adeniran, Ismail; MacIver, David H.; Garratt, Clifford J.; Ye, Jianqiao; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Aims Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. Methods and Results A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2–3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. Conclusions This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients. PMID:26606047

  13. Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics - Insights from a 3D Model of the Human Atria.

    Science.gov (United States)

    Adeniran, Ismail; MacIver, David H; Garratt, Clifford J; Ye, Jianqiao; Hancox, Jules C; Zhang, Henggui

    2015-01-01

    Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2-3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients.

  14. Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study.

    Science.gov (United States)

    Tiffany Win, Theingi; Ambale Venkatesh, Bharath; Volpe, Gustavo J; Mewton, Nathan; Rizzi, Patricia; Sharma, Ravi K; Strauss, David G; Lima, Joao A; Tereshchenko, Larisa G

    2015-01-01

    Abnormal P-terminal force in lead V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation, and death. Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrial (LA) function and electrocardiographic (ECG) measures of LA electrical activity. Patients without atrial fibrillation (n = 91; mean age 59.5 years; 61.5% men; 65.9% white) with structural heart disease (spatial QRS-T angle ≥105° and/or Selvester QRS score ≥5 on ECG) but LV ejection fraction >35% underwent clinical evaluation, cardiac magnetic resonance, and resting ECG. LA function indices were obtained by multimodality tissue tracking using 2- and 4-chamber long-axis images. T1 mapping and late gadolinium enhancement were used to assess diffuse LV fibrosis and presence of scar. P-prime in V1 amplitude (PPaV1) and duration (PPdV1), averaged P-wave-duration, PR interval, and P-wave axis were automatically measured using 12 SLTM algorithm. PTFV1 was calculated as a product of PPaV1 and PPdV1. In linear regression after adjustment for demographic characteristics, body mass index, maximum LA volume index, presence of scar, and LV mass index, each decile increase in LV interstitial fibrosis was associated with 0.76 mV*ms increase in negative abnormal PTFV1 (95% confidence interval [CI] -1.42 to -0.09; P = .025), 15.3 ms prolongation of PPdV1 (95% CI 6.9 to 23.8; P = .001) and 5.4 ms prolongation of averaged P-duration (95% CI 0.9-10.0; P = .020). LV fibrosis did not affect LA function. PPaV1 and PTFV1 were associated with an increase in LA volumes and decrease in LA emptying fraction and LA reservoir function. LV interstitial fibrosis is associated with abnormal PTFV1, prolonged PPdV1, and P-duration, but does not affect LA function. Copyright © 2015 Heart Rhythm Society. All rights reserved.

  15. Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

    Science.gov (United States)

    Hansen, Brian J; Zhao, Jichao; Csepe, Thomas A; Moore, Brandon T; Li, Ning; Jayne, Laura A; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A; Simonetti, Orlando P; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L; Weiss, Raul; Hummel, John D; Fedorov, Vadim V

    2015-09-14

    The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. Published on

  16. Personalized medicine for cystic fibrosis: establishing human model systems.

    Science.gov (United States)

    Mou, Hongmei; Brazauskas, Karissa; Rajagopal, Jayaraj

    2015-10-01

    With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification. © 2015 Wiley Periodicals, Inc.

  17. Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

    Science.gov (United States)

    Walters, Tomos E; Kalman, Jonathan M; Patel, Sheila K; Mearns, Megan; Velkoska, Elena; Burrell, Louise M

    2017-08-01

    Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  18. Radioimmunoassay and characterization of atrial natriuretic peptide in human plasma

    International Nuclear Information System (INIS)

    Yandle, T.G.; Espiner, E.A.; Nicholls, M.G.; Duff, H.

    1986-01-01

    A RIA for alpha-human atrial natriuretic peptide (alpha hANP) in plasma was developed and used to study the immunoreactive components secreted by the heart and circulating in peripheral venous plasma. The assay used [125I]diiodotyrosyl-alpha hANP, purified by high pressure liquid chromatography (HPLC), and a C-terminal-specific antiserum purchased from Peninsula Laboratories. Serial dilution curves of coronary sinus plasma samples were parallel with the standard curve, but significant nonparallelism was found in peripheral plasma samples of low immunoreactivity. When plasma was extracted using C-18 Sep-Pak cartridges, serial dilution curves from both coronary sinus and peripheral plasma samples were parallel to the standard curve. Although values for plasma samples assayed before and after extraction agreed closely (r = 0.99; n = 76), immunoreactive ANP in unextracted plasma was consistently greater (70-79 pmol/liter) than in extracts of plasma, suggesting non-specific interference by a component in plasma when assayed without extraction. Mean plasma immunoreactive ANP in 19 normal subjects consuming a normal salt intake was 14 +/- 1 (+/- SE) pmol/liter. In 5 normal men, increasing dietary sodium intake from 10 to 200 mmol sodium/day was associated with a 2-fold increment in ANP levels, and similar changes accompanied acute sodium loading using iv saline. Elevated values were found in patients with congestive heart failure (mean, 58 pmol/liter; range, 0-200; n = 9), chronic renal failure (mean, 118 pmol/liter; range, 30-290; n = 8), and primary aldosteronism (range, 32-90 pmol/liter; n = 3). HPLC and gel chromatographic analysis of the immunoreactive material found in coronary sinus plasma extracts showed that a large amount of the material eluted in the position of alpha hANP

  19. 3D virtual human atria: A computational platform for studying clinical atrial fibrillation.

    Science.gov (United States)

    Aslanidi, Oleg V; Colman, Michael A; Stott, Jonathan; Dobrzynski, Halina; Boyett, Mark R; Holden, Arun V; Zhang, Henggui

    2011-10-01

    Despite a vast amount of experimental and clinical data on the underlying ionic, cellular and tissue substrates, the mechanisms of common atrial arrhythmias (such as atrial fibrillation, AF) arising from the functional interactions at the whole atria level remain unclear. Computational modelling provides a quantitative framework for integrating such multi-scale data and understanding the arrhythmogenic behaviour that emerges from the collective spatio-temporal dynamics in all parts of the heart. In this study, we have developed a multi-scale hierarchy of biophysically detailed computational models for the human atria--the 3D virtual human atria. Primarily, diffusion tensor MRI reconstruction of the tissue geometry and fibre orientation in the human sinoatrial node (SAN) and surrounding atrial muscle was integrated into the 3D model of the whole atria dissected from the Visible Human dataset. The anatomical models were combined with the heterogeneous atrial action potential (AP) models, and used to simulate the AP conduction in the human atria under various conditions: SAN pacemaking and atrial activation in the normal rhythm, break-down of regular AP wave-fronts during rapid atrial pacing, and the genesis of multiple re-entrant wavelets characteristic of AF. Contributions of different properties of the tissue to mechanisms of the normal rhythm and arrhythmogenesis were investigated. Primarily, the simulations showed that tissue heterogeneity caused the break-down of the normal AP wave-fronts at rapid pacing rates, which initiated a pair of re-entrant spiral waves; and tissue anisotropy resulted in a further break-down of the spiral waves into multiple meandering wavelets characteristic of AF. The 3D virtual atria model itself was incorporated into the torso model to simulate the body surface ECG patterns in the normal and arrhythmic conditions. Therefore, a state-of-the-art computational platform has been developed, which can be used for studying multi

  20. Atrial distension, haemodilution, and acute control of renin release during water immersion in humans

    DEFF Research Database (Denmark)

    Gabrielsen, A; Pump, B; Bie, P

    2002-01-01

    immersion. During WI, central venous pressure (CVP) and left atrial diameter (LAD) increased (P ... is not the single pivotal stimulus for the acute suppression of renin release in response to intravascular volume expansion by water immersion in humans. Haemodilution constitutes a significant and conceivably the principal stimulus for the acute immersion-induced suppression of renin-angiotensin system activity....

  1. Targeting Interleukin-13 with Tralokinumab Attenuates Lung Fibrosis and Epithelial Damage in a Humanized SCID Idiopathic Pulmonary Fibrosis Model

    Science.gov (United States)

    Zhang, Huilan; Oak, Sameer R.; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R.; Lee, Joyce; Bell, Matt; Knight, Darryl A.; Martinez, Fernando J.; Sleeman, Matthew A.; Herzog, Erica L.; Hogaboam, Cory M.

    2014-01-01

    The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung. PMID:24325475

  2. Simulation of biatrial conduction via different pathways during sinus rhythm with a detailed human atrial model

    Institute of Scientific and Technical Information of China (English)

    Dong-dong DENG; Ying-lan GONG; Guo-fa SHOU; Pei-feng JIAO; Heng-gui ZHANG; Xue-song YE; Ling XIA

    2012-01-01

    In order to better understand biatrial conduction,investigate various conduction pathways,and compare the differences between isotropic and anisotropic conductions in human atria,we present a simulation study of biatrial conduction with known/assumed conduction pathways using a recently developed human atrial model.In addition to known pathways:(1) Bachmann's bundle (BB),(2) limbus of fossa ovalis (LFO),and (3) coronary sinus (CS),we also hypothesize that there exist two fast conduction bundles that connect the crista terminalis (CT),LFO,and CS.Our simulation demonstrates that use of these fast conduction bundles results in a conduction pattern consistent with experimental data.The comparison of isotropic and anisotropoic conductions in the BB case showed that the atrial working muscles had small effect on conduction time and conduction speed,although the conductivities assigned in anisotropic conduction were two to four times higher than the isotropic conduction.In conclusion,we suggest that the hypothesized intercaval bundles play a significant role in the biatrial conduction and that myofiber orientation has larger effects on the conduction system than the atrial working muscles.This study presents readers with new insights into human atrial conduction.

  3. Atrial Fibrillation associated chromosome 4q25 variants are not associated with PITX2c expression in human adult left atrial appendages.

    Directory of Open Access Journals (Sweden)

    Shamone R Gore-Panter

    Full Text Available Atrial Fibrillation (AF, the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS have identified that the single nucleotide polymorphisms (SNPs most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.

  4. Pharmacoeconomic review of recombinant human DNase in the management of cystic fibrosis

    NARCIS (Netherlands)

    Zijlstra, Gerrit; Boersma, Cornelis; Frijlink, Henderik W.; Postma, Maarten J.

    For the treatment of patients with cystic fibrosis, recombinant human deoxyribonuclease I is widely used. Deoxyribonuclease I has a positive effect on lung function and the number of hospitalizations. Deoxyribonuclease I is currently administered by nebulization, which is an inefficient

  5. Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.

    Directory of Open Access Journals (Sweden)

    Daniel M Lombardo

    2016-08-01

    Full Text Available Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF. A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP morphology, action potential duration (APD restitution and conduction velocity (CV restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy.

  6. Increased expression of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in human atria during atrial fibrillation.

    Science.gov (United States)

    De-An, Pei; Li, Li; Zhi-Yun, Xu; Jin-Yu, Huang; Zheng-Ming, Xu; Min, Wang; Qiang, Yao; Shi-Eng, Huang

    2010-01-01

    Atrialfibrillation (AF) is associated with the activation of the renin-angiotensin-aldosterone system in the atria. It is not clear whether the expression of a mineralocorticoid receptor (MR), or 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), conferring aldosterone specificity to the MR, in patients with AF is altered. Patients with AF may be associated with increased expression of MR and 11betaHSD2 in the atria. Atrial tissue samples of 25 patients with rheumatic heart valve disease undergoing a valve replacement operation were examined. A total of 13 patients had chronic persistent AF (>6 mo) and 12 patients had no history of AF. The MR and 11betaHSD2 expression were analyzed at the mRNA and protein level. The localization of MR and 11betaHSD2 in atrial tissue was performed using specific immunohistochemistry staining. The results of real-time quantitative polymerase chain reaction (PCR) showed that AF groups, in comparison with sinus rhythm, had a higher mRNA expression level of MR or 11betaHSD2 (all P atrial tissue were also significantly increased in patients with AF compared with patients with sinus rhythm (P atrial interstitial fibrosis in patients with AF. These findings may have an important impact on the treatment of AF with aldosterone antagonists. Copyright 2010 Wiley Periodicals, Inc.

  7. Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue.

    Science.gov (United States)

    Brocklehurst, Paul; Ni, Haibo; Zhang, Henggui; Ye, Jianqiao

    2017-01-01

    We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER) of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM). Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanical myofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of the mechano

  8. Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue.

    Directory of Open Access Journals (Sweden)

    Paul Brocklehurst

    Full Text Available We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM. Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanical myofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of

  9. Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

    Science.gov (United States)

    Rainer, Peter P; Primessnig, Uwe; Harenkamp, Sandra; Doleschal, Bernhard; Wallner, Markus; Fauler, Guenter; Stojakovic, Tatjana; Wachter, Rolf; Yates, Ameli; Groschner, Klaus; Trauner, Michael; Pieske, Burkert M; von Lewinski, Dirk

    2013-11-01

    High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, pursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

  10. Insights from human genetic studies of lung and organ fibrosis.

    Science.gov (United States)

    Garcia, Christine Kim

    2018-01-02

    Genetic investigations of fibrotic diseases, including those of late onset, often yield unanticipated insights into disease pathogenesis. This Review focuses on pathways underlying lung fibrosis that are generalizable to other organs. Herein, we discuss genetic variants subdivided into those that shorten telomeres, activate the DNA damage response, change resident protein expression or function, or affect organelle activity. Genetic studies provide a window into the downstream cascade of maladaptive responses and pathways that lead to tissue fibrosis. In addition, these studies reveal interactions between genetic variants, environmental factors, and age that influence the phenotypic spectrum of disease. The discovery of forces counterbalancing inherited risk alleles identifies potential therapeutic targets, thus providing hope for future prevention or reversal of fibrosis.

  11. Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

    Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na+ ...

  12. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

    Science.gov (United States)

    Shak, S; Capon, D J; Hellmiss, R; Marsters, S A; Baker, C L

    1990-12-01

    Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions.

  13. Persistent atrial fibrillation vs paroxysmal atrial fibrillation: differences in management.

    Science.gov (United States)

    Margulescu, Andrei D; Mont, Lluis

    2017-08-01

    Atrial fibrillation (AF) is the most common human arrhythmia. AF is a progressive disease, initially being nonsustained and induced by trigger activity, and progressing towards persistent AF through alteration of the atrial myocardial substrate. Treatment of AF aims to decrease the risk of stroke and improve the quality of life, by preventing recurrences (rhythm control) or controlling the heart rate during AF (rate control). In the last 20 years, catheter-based and, less frequently, surgical and hybrid ablation techniques have proven more successful compared with drug therapy in achieving rhythm control in patients with AF. However, the efficiency of ablation techniques varies greatly, being highest in paroxysmal and lowest in long-term persistent AF. Areas covered: In this review, we discuss the fundamental differences between paroxysmal and persistent AF and the potential impact of those differences on patient management, emphasizing the available therapeutic strategies to achieve rhythm control. Expert commentary: Treatment to prevent AF recurrences is suboptimal, particularly in patients with persistent AF. Emerging technologies, such as documentation of atrial fibrosis using magnetic resonance imaging and documentation of electrical substrate using advanced electrocardiographic imaging techniques are likely to provide valuable insights about patient-specific tailoring of treatments.

  14. Impaired atrial electromechanical function and atrial fibrillation promotion in alloxan-induced diabetic rabbits.

    Science.gov (United States)

    Fu, Huaying; Liu, Changle; Li, Jian; Zhou, Changyu; Cheng, Lijun; Liu, Tong; Li, Guangping

    2013-01-01

    Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms are still not clearly elucidated. The aim of this study was to evaluate the atrial electromechanical function, atrial electrophysiological changes and AF inducibility in alloxan-induced diabetic rabbits. In 8 alloxan-induced diabetic rabbits and 8 controls, we evaluated atrial electromechanical function by tissue Doppler imaging. Isolated Langendorff-perfused rabbit hearts were prepared to measure atrial refractory effective period (AERP) and its dispersion (AERPD), interatrial conduction time (IACT) and vulnerability to AF. Atrial interstitial fibrosis was evaluated by Sirius-Red staining. Compared with controls, left atrial lateral wall Pa'-start interval (Pastart) and right atrial wall Pastart were increased in diabetic rabbits. AERPD was increased and IACT was prolonged in diabetic rabbits. Inducibility of AF in diabetic group was significant higher than controls (6/8 vs. 1/8, p TEMA); left atrial lateral wall Papeak and TEMA, left atrial posterior wall TEMA, and IACT were correlated with atrial areas of fibrosis. Atrial electromechanical function is impaired in diabetic rabbits, and is associated with atrial fibrosis and interatrial electrical conduction delay.

  15. A new dynamic 3D virtual methodology for teaching the mechanics of atrial septation as seen in the human heart.

    Science.gov (United States)

    Schleich, Jean-Marc; Dillenseger, Jean-Louis; Houyel, Lucile; Almange, Claude; Anderson, Robert H

    2009-01-01

    Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and pediatric cardiology. This has permitted the preparation of three-dimensional (3D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning.

  16. The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Williamson, James D; Sadofsky, Laura R; Hart, Simon P

    2015-03-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology, for which there is no curative pharmacological therapy. Bleomycin, an anti-neoplastic agent that causes lung fibrosis in human patients has been used extensively in rodent models to mimic IPF. In this review, we compare the pathogenesis and histological features of human IPF and bleomycin-induced pulmonary fibrosis (BPF) induced in rodents by intratracheal delivery. We discuss the current understanding of IPF and BPF disease development, from the contribution of alveolar epithelial cells and inflammation to the role of fibroblasts and cytokines, and draw conclusions about what we have learned from the intratracheal bleomycin model of lung fibrosis.

  17. Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.

    Science.gov (United States)

    Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

    2013-09-01

    Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca(2+) handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate

  18. Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.

    Science.gov (United States)

    Meyer-Roxlau, Stefanie; Lämmle, Simon; Opitz, Annett; Künzel, Stephan; Joos, Julius P; Neef, Stefan; Sekeres, Karolina; Sossalla, Samuel; Schöndube, Friedrich; Alexiou, Konstantin; Maier, Lars S; Dobrev, Dobromir; Guan, Kaomei; Weber, Silvio; El-Armouche, Ali

    2017-07-01

    Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

  19. Chymase-dependent generation of angiotensin II from angiotensin-(1-12 in human atrial tissue.

    Directory of Open Access Journals (Sweden)

    Sarfaraz Ahmad

    Full Text Available Since angiotensin-(1-12 [Ang-(1-12] is a non-renin dependent alternate precursor for the generation of cardiac Ang peptides in rat tissue, we investigated the metabolism of Ang-(1-12 by plasma membranes (PM isolated from human atrial appendage tissue from nine patients undergoing cardiac surgery for primary control of atrial fibrillation (MAZE surgical procedure. PM was incubated with highly purified ¹²⁵I-Ang-(1-12 at 37°C for 1 h with or without renin-angiotensin system (RAS inhibitors [lisinopril for angiotensin converting enzyme (ACE, SCH39370 for neprilysin (NEP, MLN-4760 for ACE2 and chymostatin for chymase; 50 µM each]. ¹²⁵I-Ang peptide fractions were identified by HPLC coupled to an inline γ-detector. In the absence of all RAS inhibitor, ¹²⁵I-Ang-(1-12 was converted into Ang I (2±2%, Ang II (69±21%, Ang-(1-7 (5±2%, and Ang-(1-4 (2±1%. In the absence of all RAS inhibitor, only 22±10% of ¹²⁵I-Ang-(1-12 was unmetabolized, whereas, in the presence of the all RAS inhibitors, 98±7% of ¹²⁵I-Ang-(1-12 remained intact. The relative contribution of selective inhibition of ACE and chymase enzyme showed that ¹²⁵I-Ang-(1-12 was primarily converted into Ang II (65±18% by chymase while its hydrolysis into Ang II by ACE was significantly lower or undetectable. The activity of individual enzyme was calculated based on the amount of Ang II formation. These results showed very high chymase-mediated Ang II formation (28±3.1 fmol × min⁻¹ × mg⁻¹, n = 9 from ¹²⁵I-Ang-(1-12 and very low or undetectable Ang II formation by ACE (1.1±0.2 fmol×min⁻¹ × mg⁻¹. Paralleling these findings, these tissues showed significant content of chymase protein that by immunocytochemistry were primarily localized in atrial cardiac myocytes. In conclusion, we demonstrate for the first time in human cardiac tissue a dominant role of cardiac chymase in the formation of Ang II from Ang-(1-12.

  20. Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

    Science.gov (United States)

    Emelyanova, Larisa; Ashary, Zain; Cosic, Milanka; Negmadjanov, Ulugbek; Ross, Gracious; Rizvi, Farhan; Olet, Susan; Kress, David; Sra, Jasbir; Tajik, A Jamil; Holmuhamedov, Ekhson L; Shi, Yang; Jahangir, Arshad

    2016-07-01

    Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF. Copyright © 2016 the American Physiological Society.

  1. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Sandra C. [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States); Chau, Mary D.L.; Yang, Qing [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Gauthier, Marie-Soleil [Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02140 (United States); Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Dole, William P., E-mail: bill.dole@novartis.com [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States)

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  2. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    International Nuclear Information System (INIS)

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-01-01

    Highlights: → Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). → ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. → ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. → Exposure of human adipocytes to fatty acids and (TNFα) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and peroxisome proliferator

  3. The histology of human right atrial tissue in patients with high-risk Obstructive Sleep Apnea and underlying cardiovascular disease: A pilot study

    Directory of Open Access Journals (Sweden)

    Erik M. van Oosten

    2015-03-01

    Conclusions: In this pilot study there were no observable histological differences in human right atrial tissue from individuals at high- and low-risk for OSA. Further investigation would be required for more definitive results.

  4. A Novel Genomic Signature with Translational Significance for Human Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Tedrow, John; de Bernard, Simon; Birker-Robaczewska, Magdalena; Gibson, Kevin F.; Guardela, Brenda Juan; Hess, Patrick; Klenk, Axel; Lindell, Kathleen O.; Poirey, Sylvie; Renault, Bérengère; Rey, Markus; Weber, Edgar; Nayler, Oliver; Kaminski, Naftali

    2015-01-01

    The bleomycin-induced rodent lung fibrosis model is commonly used to study mechanisms of lung fibrosis and to test potential therapeutic interventions, despite the well recognized dissimilarities to human idiopathic pulmonary fibrosis (IPF). Therefore, in this study, we sought to identify genomic commonalities between the gene expression profiles from 100 IPF lungs and 108 control lungs that were obtained from the Lung Tissue Research Consortium, and rat lungs harvested at Days 3, 7, 14, 21, 28, 42, and 56 after bleomycin instillation. Surprisingly, the highest gene expression similarity between bleomycin-treated rat and IPF lungs was observed at Day 7. At this point of maximal rat–human commonality, we identified a novel set of 12 disease-relevant translational gene markers (C6, CTHRC1, CTSE, FHL2, GAL, GREM1, LCN2, MMP7, NELL1, PCSK1, PLA2G2A, and SLC2A5) that was able to separate almost all patients with IPF from control subjects in our cohort and in two additional IPF/control cohorts (GSE10667 and GSE24206). Furthermore, in combination with diffusing capacity of carbon monoxide measurements, four members of the translational gene marker set contributed to stratify patients with IPF according to disease severity. Significantly, pirfenidone attenuated the expression change of one (CTHRC1) translational gene marker in the bleomycin-induced lung fibrosis model, in transforming growth factor-β1–treated primary human lung fibroblasts and transforming growth factor-β1–treated human epithelial A549 cells. Our results suggest that a strategy focused on rodent model–human disease commonalities may identify genes that could be used to predict the pharmacological impact of therapeutic interventions, and thus facilitate the development of novel treatments for this devastating lung disease. PMID:25029475

  5. Low energy transvenous cardioversion of short duration atrial tachyarrhythmias in humans using a single lead system.

    Science.gov (United States)

    Heisel, A; Jung, J; Fries, R; Stopp, M; Sen, S; Schieffer, H; Ozbek, C

    1997-01-01

    The purpose of this study was to investigate the efficacy and safety of atrial cardioversion using an endocardial single lead system presently used for ventricular defibrillation. The study population consisted of 26 recipients of an ICD in combination with a conventional endocardial single lead system with the proximal spring electrode as anode in the SVC and the distal as cathode in the apex of the RV. Atrial tachyarrhythmias were induced by right atrial burst pacing. If the arrhythmia sustained > 1 minute, biphasic shocks synchronized with the R wave were delivered using the implanted device, beginning with an energy of 4 J. If 4 J failed to terminate the arrhythmia, energy was increased stepwise, if the first shock was successful, a step-down testing was performed after reinduction of atrial tachyarrhythmias. The mean atrial defibrillation threshold was 2.3 +/- 1.2 J (range, 0.5-5 J). A total of 154 shocks were delivered and no adverse effects were observed. The mean defibrillation threshold for atrial flutter was somewhat lower than that for AF (1.8 +/- 1 J vs 2.7 +/- 1.4 J, P = 0.08). There was no correlation between the atrial defibrillation threshold and a history of previously occurring atrial tachyarrhythmias, the kind of the underlying heart disease, a prescription of antiarrhythmic drugs, the dimension of the LA, the LVEF, or the ventricular DFT. Internal atrial cardioversion of short duration atrial tachyarrhythmias using a transvenous single lead system designed for ventricular defibrillation is feasible and safe at low energies, and may have important clinical applications.

  6. PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

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    Cristiane Valle TOVO

    2013-03-01

    Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations.

  7. Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

    Science.gov (United States)

    Mahavadi, Poornima; Sasikumar, Satish; Cushing, Leah; Hyland, Tessa; Rosser, Ann E.; Riccardi, Daniela; Lu, Jining; Kalin, Tanya V.; Kalinichenko, Vladimir V.; Guenther, Andreas; Ramirez, Maria I.; Pardo, Annie; Selman, Moisés; Warburton, David

    2013-01-01

    Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity. PMID:24375798

  8. A 2D Electromechanical Model of Human Atrial Tissue Using the Discrete Element Method

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    Paul Brocklehurst

    2015-01-01

    Full Text Available Cardiac tissue is a syncytium of coupled cells with pronounced intrinsic discrete nature. Previous models of cardiac electromechanics often ignore such discrete properties and treat cardiac tissue as a continuous medium, which has fundamental limitations. In the present study, we introduce a 2D electromechanical model for human atrial tissue based on the discrete element method (DEM. In the model, single-cell dynamics are governed by strongly coupling the electrophysiological model of Courtemanche et al. to the myofilament model of Rice et al. with two-way feedbacks. Each cell is treated as a viscoelastic body, which is physically represented by a clump of nine particles. Cell aggregations are arranged so that the anisotropic nature of cardiac tissue due to fibre orientations can be modelled. Each cell is electrically coupled to neighbouring cells, allowing excitation waves to propagate through the tissue. Cell-to-cell mechanical interactions are modelled using a linear contact bond model in DEM. By coupling cardiac electrophysiology with mechanics via the intracellular Ca2+ concentration, the DEM model successfully simulates the conduction of cardiac electrical waves and the tissue’s corresponding mechanical contractions. The developed DEM model is numerically stable and provides a powerful method for studying the electromechanical coupling problem in the heart.

  9. Atrial fibrillation: effects beyond the atrium?

    Science.gov (United States)

    Wijesurendra, Rohan S; Casadei, Barbara

    2015-03-01

    Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and an estimated two-fold increase in premature death. Efforts to increase our understanding of AF and its complications have focused on unravelling the mechanisms of electrical and structural remodelling of the atrial myocardium. Yet, it is increasingly recognized that AF is more than an atrial disease, being associated with systemic inflammation, endothelial dysfunction, and adverse effects on the structure and function of the left ventricular myocardium that may be prognostically important. Here, we review the molecular and in vivo evidence that underpins current knowledge regarding the effects of human or experimental AF on the ventricular myocardium. Potential mechanisms are explored including diffuse ventricular fibrosis, focal myocardial scarring, and impaired myocardial perfusion and perfusion reserve. The complex relationship between AF, systemic inflammation, as well as endothelial/microvascular dysfunction and the effects of AF on ventricular calcium handling and oxidative stress are also addressed. Finally, consideration is given to the clinical implications of these observations and concepts, with particular reference to rate vs. rhythm control. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  10. [Relations between FANS, PPI and atrial fibrillation].

    Science.gov (United States)

    Ricci, Fabrizio; De Caterina, Raffaele

    2013-05-01

    Recent evidence supports the existence of an association between the use of non-steroidal anti-inflammatory drugs and the risk of atrial fibrillation. Anti-inflammatory drugs are widely used for the treatment of systemic inflammatory disorders, and chronic inflammation is a well-known risk factor for the development of myocardial fibrosis. The latter accounts for atrial inhomogeneities of conduction, thus triggering and perpetuating atrial fibrillation. Atrial inflammatory remodeling may therefore be responsible for the higher incidence of atrial fibrillation among patients assuming steroidal and non-steroidal anti-inflammatory drugs because of an underlying inflammatory disorders. Alternative theories contemplate gastroesophageal reflux, which is extremely common during the use of non-steroidal anti-inflammatory drugs and may trigger atrial fibrillation, as mediating the above-mentioned association.

  11. Prevention of adenosine A2A receptor activation diminishes beat-to-beat alternation in human atrial myocytes.

    Science.gov (United States)

    Molina, Cristina E; Llach, Anna; Herraiz-Martínez, Adela; Tarifa, Carmen; Barriga, Montserrat; Wiegerinck, Rob F; Fernandes, Jacqueline; Cabello, Nuria; Vallmitjana, Alex; Benitéz, Raúl; Montiel, José; Cinca, Juan; Hove-Madsen, Leif

    2016-01-01

    Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p < 0.01 for beta-adrenergic receptors and from 1.4 ± 0.1 to 0.5 ± 0.1 Hz; p < 0.05 for A2ARs. The latter was linked to increased spontaneous calcium release and after-depolarizations. Moreover, A2AR activation increased the fraction of non-uniformly responding cells in HL-1 myocyte cultures from 19 ± 3 to 51 ± 9 %; p < 0.02, and electrical mapping in perfused porcine atria revealed that adenosine induced electrical alternans at longer cycle lengths, doubled the fraction of electrodes showing alternation, and increased the amplitude of alternations. Importantly, protein kinase A inhibition increased the highest frequency where uniform responses could be maintained from 0.84 ± 0.12 to 1.86 ± 0.11 Hz; p < 0.001 and prevention of A2AR-activation with exogenous adenosine deaminase selectively increased the threshold from 0.8 ± 0.1 to 1.2 ± 0.1 Hz; p = 0.001 in myocytes from patients with AF. In conclusion, A2AR-activation promotes beat-to-beat irregularities in the calcium transient in human atrial myocytes, and prevention of A2AR activation may be a novel means to maintain uniform beat-to-beat responses at higher beating frequencies in patients with atrial fibrillation.

  12. Human atrial natriuretic peptide treatment for acute heart failure: a systematic review of efficacy and mortality.

    Science.gov (United States)

    Kobayashi, Daiki; Yamaguchi, Norihiro; Takahashi, Osamu; Deshpande, Gautam A; Fukui, Tsuguya

    2012-01-01

    The objectives of this study were to assess the effect of human atrial natriuretic peptide (hANP) treatment on physiological parameters and mortality in acute heart failure. The MEDLINE (1966-2009), EMBASE (1980-2009), Cochrane Central Register of Controlled Trials (1991-2009), American College of Physicians Journal Club (1991), Ichushi (Japana Centra Revuo Medicina) (1983-2009), Cinni (NII Scholarly and Academic Information Navigator) (1959-2009), National Diet Library Online Public Access Catalog (1969-2009), Webcat Plus (Japanese National Institute of Informatics) (1986-2009), Medical Online (1947-2009), and JST China (1981-2009) databases were searched for studies that compared the efficacy of hANP and the mortality in patients with acute heart failure with placebo controls. Only randomized controlled trials (RCTs) were included in the study. Out of 347 articles, a total of 4 studies involving 220 patients with acute heart failure fulfilled the predefined inclusion criteria. There were significant differences in the hemodynamic parameters between the hANP and placebo groups, especially in the pulmonary capillary wedge pressure (PCWP) reduction (standard mean difference [SMD] 2.07; 95% confidence interval [CI], 0.34-3.81) and the cardiac index (SMD 1.79; 95% CI, 0.12-3.47). No statistically significant differences in mortality rates were found (relative risk 1.03; 95% CI, 0.27-3.92). In a limited number of studies, hANP appears to improve several hemodynamic parameters, including pulmonary capillary wedge pressure and cardiac index, but not mortality. Further high-quality studies are needed to corroborate these results. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  13. Clinical Benefit of Ablating Localized Sources for Human Atrial Fibrillation: The Indiana University FIRM Registry.

    Science.gov (United States)

    Miller, John M; Kalra, Vikas; Das, Mithilesh K; Jain, Rahul; Garlie, Jason B; Brewster, Jordan A; Dandamudi, Gopi

    2017-03-14

    Mounting evidence shows that localized sources maintain atrial fibrillation (AF). However, it is unclear in unselected "real-world" patients if sources drive persistent atrial fibrillation (PeAF), long-standing persistent atrial fibrillation (LPeAF), or paroxysmal atrial fibrillation (PAF); if right atrial sites are important; and what the long-term success of source ablation is. The aim of this study was to analyze the role of rotors and focal sources in a large academic registry of consecutive patients undergoing source mapping for AF. One hundred seventy consecutive patients (mean age 59 ± 12 years, 79% men) with PAF (37%), PeAF (31%), or LPeAF (32%). Of these, 73 (43%) had undergone at least 1 prior ablation attempt (mean 1.9 ± 0.8; range: 1 to 4). Focal impulse and rotor modulation (FIRM) with an endocardial basket catheter was used in all cases. FIRM analysis revealed sources in the right atrium in 85% of patients (1.8 ± 1.3) and in the left atrium in 90% of patients (2.0 ± 1.3). FIRM ablation terminated AF to sinus rhythm or atrial flutter or tachycardia in 59% (PAF), 37% (PeAF), and 19% (LPeAF) of patients, with 15 of 67 terminations due to right atrial ablation. On follow-up, freedom from AF after a single FIRM procedure for the entire series was 95% (PAF), 83% (PeAF), and 82% (LPeAF) at 1 year and freedom from all atrial arrhythmias was 77% (PAF), 75% (PeAF), and 57% (LPeAF). In the Indiana University FIRM registry, FIRM-guided ablation produced high single-procedure success, mostly in patients with nonparoxysmal AF. Data from mapping, acute terminations, and outcomes strongly support the mechanistic role of biatrial rotors and focal sources in maintaining AF in diverse populations. Randomized trials of FIRM-guided ablation and mechanistic studies to determine how rotors form, progress, and regress are needed. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi

    Science.gov (United States)

    Martens, Chelsea J.; Inglis, Sarah K.; Valentine, Vincent G.; Garrison, Jennifer; Conner, Gregory E.

    2011-01-01

    To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 μl·cm−2·h−1). However, CF bronchi produce mucus with twice the percent solids (∼8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 μl·cm−2·h−1. PMID:21622844

  15. Aerosolized recombinant human DNase I for the treatment of cystic fibrosis.

    Science.gov (United States)

    Shak, S

    1995-02-01

    Respiratory symptoms, recurrent infectious exacerbations, and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. Purulent secretions contain high concentrations of extracellular DNA, a viscous material released by leukocytes. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase or Pulmozyme), the human enzyme was cloned, sequenced, and expressed. In in vitro studies, rhDNase has been shown to reduce the viscoelasticity, reduce the adhesiveness, and improve the mucociliary transportability of cystic fibrosis sputum. In short-term phase 1 and phase 2 clinical trials, rhDNase has been shown to be safely tolerated and to improve the FEV1, FVC, and symptoms of dyspnea. A long-term placebo-controlled phase 3 study was performed in 968 adults and children (> or = 5 years) with cystic fibrosis to determine the effect of rhDNase on the risk of respiratory exacerbations requiring parenteral antibiotics and on the FEV1. Compared with placebo-treated patients, patients treated with rhDNase once daily or twice daily experienced a reduced risk of respiratory exacerbations by 28% (p = 0.04) and 37% (p = 0.01), respectively, and had a mean improvement in FEV1 of 5.8% (p < 0.01) and 5.6% (p < 0.01), respectively. Compared with placebo-treated patients, patients treated with rhDNase spent 2.7 fewer days receiving parenteral antibiotics (p = 0.04) and spent 1.3 fewer days in the hospital (p = 0.06) over the 6-month treatment period. Inhalation of rhDNase did not cause anaphylaxis but was associated with upper airway symptoms (ie, voice alteration, hoarseness, pharyngitis) that were generally mild and transient. In conclusion, aerosol administration of rhDNase was safely tolerated, reduced the risk of infectious exacerbations requiring parenteral antibiotics, and improved pulmonary function and patient well-being.

  16. Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis

    NARCIS (Netherlands)

    Westra, Inge M.; Mutsaers, Henricus A. M.; Luangmonkong, Theerut; Hadi, Mackenzie; Oosterhuis, Dorenda; de Jong, Koert P.; Groothuis, Geny M. M.; Olinga, Peter

    Liver fibrosis is the progressive accumulation of connective tissue ultimately resulting in loss of organ function. Currently, no effective antifibrotics are available due to a lack of reliable human models. Here we investigated the fibrotic process in human precision-cut liver slices (PCLS) and

  17. The β3 -adrenoceptor agonist mirabegron increases human atrial force through β1 -adrenoceptors: an indirect mechanism?

    Science.gov (United States)

    Mo, Weilan; Michel, Martin C; Lee, Xiang Wen; Kaumann, Alberto J; Molenaar, Peter

    2017-08-01

    Mirabegron has been classified as a β 3 -adrenoceptor agonist approved for overactive bladder syndrome. We investigated possible cardiac effects of mirabegron in the absence or presence of β-adrenoceptor subtype antagonists. In view of its phenylethanolamine structure, we investigated whether mirabegron has indirect sympathomimetic activity by using neuronal uptake blockers. Right atrial trabeculae, from non-failing hearts, were paced and contractile force measured at 37°C. Single concentrations of mirabegron were added in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), β 3 (L-748,337), β 1 (CGP 20712A), β 2 (ICI 118,551) -adrenoceptor antagonists, neuronal uptake inhibitors desipramine or phenoxybenzamine. Mirabegron significantly increased contractile force in human right atrium (1 μM, 7.6 ± 2.6%, n = 7; 10 μM, 10.2 ± 1.5%, n = 22 compared with (-)-isoprenaline P < 0.05). In the presence of IBMX, mirabegron (10 μM) caused a greater contraction. L-748,337 (100 nM) had no effect on the increase in contractile force caused by mirabegron (10 μM). In contrast, mirabegron (10 μM) reduced contractile force in the presence of CGP 20712A, which was not affected by L-748,337 (100 nM) or ICI 118,551 (50 nM). Mirabegron (10 μM) also reduced contractile force in the presence of desipramine or phenoxybenzamine. Mirabegron increases human atrial force through β 1 - but not β 3 -adrenoceptors. Desipramine and phenoxybenzamine block neuronal uptake and conceivably prevent mirabegron from releasing noradrenaline. A non-specific cardiodepressant effect is not mediated through β 3 (or β 2 )-adrenoceptors, consistent with lack of β 3 -adrenoceptor function on human atrial contractility. © 2017 The British Pharmacological Society.

  18. Effect of Pancreatic Hormones on pro-Atrial Natriuretic Peptide in Humans

    DEFF Research Database (Denmark)

    Zois, Nora E.; Terzic, Dijana; Faerch, Kristine

    2017-01-01

    Plasma concentrations of pro-Atrial natriuretic peptide, proANP, are decreased in obesity and diabetes. Decreased proANP concentrations have also been noted after meal intake, and recently, a glucose-mediated regulation of ANP gene expression was reported. Hence, we evaluated the effects of insul...

  19. Pulmonary vein and atrial wall pathology in human total anomalous pulmonary venous connection

    NARCIS (Netherlands)

    Douglas, Yvonne L.; Jongbloed, Monique R. M.; den Hartog, Wietske C. E.; Bartelings, Margot M.; Bogers, Ad J. J. C.; Ebels, Tjark; DeRuiter, Marco C.; Gittenberger-de Groot, Adriana C.

    2009-01-01

    Background: Normally, the inside of the left atrial (LA) body and pulmonary veins (PVs) is lined by vessel wall tissue covered by myocardium. In total anomalous pulmonary venous connection (TAPVC), no connection of the PVs with the LA body exists. These veins have an increased incidence of PV

  20. Dried Human Amniotic Membrane Does Not Alleviate Inflammation and Fibrosis in Experimental Strabismus Surgery

    Directory of Open Access Journals (Sweden)

    Bo Young Chun

    2013-01-01

    Full Text Available Purpose. The purpose of this study was to evaluate the efficacy of dried human amniotic membrane (AM in reducing the postoperative inflammatory response and scarring after strabismus surgery. Methods. The inflammatory response at the extraocular muscle reattachment site was analyzed after superior rectus (SR resection in 12 rabbits. Dried human AM (Ambiodry2 was applied between the resected SR muscle plane and Tenon’s capsule of the left eyes of rabbits. As a control, the right eyes of rabbits underwent SR resection only. The surgeon randomly ordered which eye gets operated first during the experiment. Two weeks later, enucleation was performed. Six sagittal sections were made for each eye at the insertion of the SR muscle. The grade of postoperative inflammation and the presence of fibrosis were evaluated in histological examinations. Results. There was no statistically significant difference in the intensity of inflammation and fibrous proliferation between the eyes treated with dried human AM after SR resection and those treated with SR resection only. Conclusions. The use of dried human AM was not effective in controlling the postoperative inflammation and scarring in rabbit eyes after extraocular muscle surgery. However, this may be due to the devitalized dry preparation of human AM (Ambiodry2, which may have lost the expected anti-inflammatory and anti-scarring properties, and further studies on humans may be necessary.

  1. Atrial Fibrillation

    DEFF Research Database (Denmark)

    Staerk, Laila; Sherer, Jason A; Ko, Darae

    2017-01-01

    The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending...... on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established...

  2. Atrial Fibrillation: Diagnosis

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Diagnosis Past Issues / Winter 2015 Table of Contents ... of your body's cells and organs. Read More "Atrial Fibrillation" Articles Atrial Fibrillation / Who Is at Risk for ...

  3. Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis.

    Science.gov (United States)

    Nagy, Béla; Nagy, Béla; Fila, Libor; Clarke, Luka A; Gönczy, Ferenc; Bede, Olga; Nagy, Dóra; Újhelyi, Rita; Szabó, Ágnes; Anghelyi, Andrea; Major, Miklós; Bene, Zsolt; Fejes, Zsolt; Antal-Szalmás, Péter; Bhattoa, Harjit Pal; Balla, György; Kappelmayer, János; Amaral, Margarida D; Macek, Milan; Balogh, István

    2016-09-01

    Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells. HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. Human neutrophil peptide-1 promotes alcohol-induced hepatic fibrosis and hepatocyte apoptosis.

    Directory of Open Access Journals (Sweden)

    Rie Ibusuki

    Full Text Available Neutrophil infiltration of the liver is a typical feature of alcoholic liver injury. Human neutrophil peptide (HNP-1 is an antimicrobial peptide secreted by neutrophils. The aim of this study was to determine if HNP-1 affects ethanol-induced liver injury and to examine the mechanism of liver injury induced by HNP-1.Transgenic (TG mice expressing HNP-1 under the control of a β-actin-based promoter were established. Ethanol was orally administered to HNP-1 TG or wild-type C57BL/6N (WT mice. SK-Hep1 hepatocellular carcinoma cells were used to investigate the effect of HNP-1 on hepatocytes in vitro.After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte apoptosis were significantly more severe in TG mice than in WT mice. Levels of CD14, TLR4, and IL-6 in liver tissues were higher in TG mice than in WT mice. Apoptosis was accompanied by higher protein levels of caspase-3, caspase-8, and cleaved PARP in liver tissue. In addition, phosphorylated ASK1, ASK1, phosphorylated JNK, JNK1, JNK2, Bax, Bak and Bim were all more abundant in TG mice than in WT mice. In contrast, the level of anti-apoptotic Bcl2 in the liver was significantly lower in TG mice than in WT mice. Analysis of microRNAs in liver tissue showed that miR-34a-5p expression was significantly higher in TG mice than in WT mice. Furthermore, in the presence of ethanol, HNP-1 increased the apoptosis with the decreased level of Bcl2 in a concentration-dependent manner in vitro.HNP-1 secreted by neutrophils may exacerbate alcohol-induced hepatic fibrosis and hepatocyte apoptosis with a decrease in Bcl2 expression and an increase in miR-34a-5p expression.

  5. ATRIAL FLUTTER*

    African Journals Online (AJOL)

    1971-01-02

    Jan 2, 1971 ... Athero- sclerotic cardiovascular disease was present in 23 patients, of whom 3 had ... primum defect, atrial flutter was precipitated by cardiac catheterization. ..... Heart J., 70, 505. UNDERSTANDING REACTIVE DEPRESSION*

  6. Atrial fibrillation

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    Mean blood pressures were 126.03± ... optimal. Keywords: Atrial fibrillation, thrombosis, CHADS2 Score, stroke risk, hypertensive heart disease, ... general population and the average age group ... Appendix 1) to stratify the stroke risk and we.

  7. Obesity, metabolic dysfunction and cardiac fibrosis: pathophysiologic pathways, molecular mechanisms and therapeutic opportunities

    Science.gov (United States)

    Cavalera, Michele; Wang, Junhong; Frangogiannis, Nikolaos G

    2014-01-01

    Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients. PMID:24880146

  8. Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.

    Directory of Open Access Journals (Sweden)

    Chandra L Shrestha

    Full Text Available Members of the Burkholderia cepacia complex are virulent, multi-drug resistant pathogens that survive and replicate intracellularly in patients with cystic fibrosis (CF. We have discovered that B. cenocepacia cannot be cleared from CF macrophages due to defective autophagy, causing continued systemic inflammation and infection. Defective autophagy in CF is mediated through constitutive reactive oxygen species (ROS activation of transglutaminase-2 (TG2, which causes the sequestration (accumulation of essential autophagy initiating proteins. Cysteamine is a TG2 inhibitor and proteostasis regulator with the potential to restore autophagy. Therefore, we sought to examine the impact of cysteamine on CF macrophage autophagy and bacterial killing. Human peripheral blood monocyte-derived macrophages (MDMs and alveolar macrophages were isolated from CF and non-CF donors. Macrophages were infected with clinical isolates of relevant CF pathogens. Cysteamine caused direct bacterial growth killing of live B. cenocepacia, B. multivorans, P. aeruginosa and MRSA in the absence of cells. Additionally, B. cenocepacia, B. multivorans, and P. aeruginosa invasion were significantly decreased in CF MDMs treated with cysteamine. Finally, cysteamine decreased TG2, p62, and beclin-1 accumulation in CF, leading to increased Burkholderia uptake into autophagosomes, increased macrophage CFTR expression, and decreased ROS and IL-1β production. Cysteamine has direct anti-bacterial growth killing and improves human CF macrophage autophagy resulting in increased macrophage-mediated bacterial clearance, decreased inflammation, and reduced constitutive ROS production. Thus, cysteamine may be an effective adjunct to antibiotic regimens in CF.

  9. Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.

    Science.gov (United States)

    Maria, Alexandre T J; Toupet, Karine; Maumus, Marie; Fonteneau, Guillaume; Le Quellec, Alain; Jorgensen, Christian; Guilpain, Philippe; Noël, Danièle

    2016-06-01

    Displaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC). HOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs. Xenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues. Using primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

    Directory of Open Access Journals (Sweden)

    Jussi T Koivumäki

    Full Text Available Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR. Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1 the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2 the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future

  11. Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis.

    Science.gov (United States)

    Simon, Franck; Bergeron, Daniele; Larochelle, Sébastien; Lopez-Vallé, Carlos A; Genest, Hervé; Armour, Alexis; Moulin, Véronique J

    2012-05-01

    Hypertrophic scars are a pathological process characterized by an excessive deposition of extracellular matrix components. Using a tissue-engineered reconstructed human skin (RHS) method, we previously reported that pathological keratinocytes induce formation of a fibrotic dermal matrix. We further investigated keratinocyte action using conditioned media. Results showed that conditioned media induce a similar action on dermal thickness similar to when an epidermis is present. Using a two-dimensional electrophoresis technique, we then compared conditioned media from normal or hypertrophic scar keratinocytes and determined that TIMP-1 was increased in conditioned media from hypertrophic scar keratinocytes. This differential profile was confirmed using ELISA, assaying TIMP-1 presence on media from monolayer cultured keratinocytes and from RHS. The dermal matrix of these RHS was recreated using mesenchymal cells from three different origins (skin, wound and hypertrophic scar). The effect of increased TIMP-1 levels on dermal fibrosis was also validated independently from the mesenchymal cell origin. Immunodetection of TIMP-1 showed that this protein was increased in the epidermis of hypertrophic scar biopsies. The findings of this study represent an important advance in understanding the role of keratinocytes as a direct potent modulator for matrix degradation and scar tissue remodeling, possibly through inactivation of MMPs. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

  12. Atrial Natriuretic Peptide Accelerates Human Endothelial Progenitor Cell-Stimulated Cutaneous Wound Healing and Angiogenesis.

    Science.gov (United States)

    Lee, Tae Wook; Kwon, Yang Woo; Park, Gyu Tae; Do, Eun Kyoung; Yoon, Jung Won; Kim, Seung-Chul; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Jae Ho

    2018-05-26

    Atrial natriuretic peptide (ANP) is a powerful vasodilating peptide secreted by cardiac muscle cells, and endothelial progenitor cells (EPCs) have been reported to stimulate cutaneous wound healing by mediating angiogenesis. To determine whether ANP can promote the EPC-mediated repair of injured tissues, we examined the effects of ANP on the angiogenic properties of EPCs and on cutaneous wound healing. In vitro, ANP treatment enhanced the migration, proliferation, and endothelial tube-forming abilities of EPCs. Furthermore, small interfering RNA-mediated silencing of natriuretic peptide receptor-1, which is a receptor for ANP, abrogated ANP-induced migration, tube formation, and proliferation of EPCs. In a murine cutaneous wound model, administration of either ANP or EPCs had no significant effect on cutaneous wound healing or angiogenesis in vivo, whereas the co-administration of ANP and EPCs synergistically potentiated wound healing and angiogenesis. In addition, ANP promoted the survival and incorporation of transplanted EPCs into newly formed blood vessels in wounds. These results suggest ANP accelerates EPC-mediated cutaneous wound healing by promoting the angiogenic properties and survival of transplanted EPCs. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

  13. Atrial remodeling and metabolic dysfunction in idiopathic isolated fibrotic atrial cardiomyopathy.

    Science.gov (United States)

    Cui, Chang; Jiang, Xiaohong; Ju, Weizhu; Wang, Jiaxian; Wang, Daowu; Sun, Zheng; Chen, Minglong

    2018-04-26

    Idiopathic isolated fibrotic atrial cardiomyopathy (IIF-ACM) is a novel subtype of cardiomyopathy characterized by atrial fibrosis that does not involve the ventricular myocardium and is associated with significant atrial tachyarrhythmia. The mechanisms underlying its pathogenesis are unknown. Atrium samples were obtained from 3 patients with IIF-ACM via surgical intervention. Control samples were consisted of 3 atrium biopsies from patients with congenital heart disease and normal sinus rhythm, matched for gender, age and basic clinical characteristics. Comparative histology, immunofluorescence staining, electron microscopy and proteomics analyses were carried out to explore the unique pathogenesis of IIF-ACM. IIF-ACM atria displayed disordered myofibrils, profound fibrosis and mitochondrial damages compared to the control atria. Proteomics profiling identified metabolic pathways as the most profound changes in IIF-ACM. Our study suggested that metabolic changes in the atrial myocardium caused mitochondrial oxidative stress and potential cell damage, which further led to atrial fibrosis and myofibril disorganization, the characteristic phenotype of IIF-ACM. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Content of alpha-linolenic acid in human atrial tissue correlates with plasma levels of alpha-linolenic acid

    DEFF Research Database (Denmark)

    Gu, Jiwei; Eschen, Rikke Bülow; Andreasen, Annette

    and ALA levels were compared by the Pearson correlation coefficient. Results: There was a statistical significant correlation (r=0.54, 95% confidence interval: 0.30-0.71) between levels of ALA in plasma phospholipids and atrial tissue. Conclusion: The content of ALA in plasma phospholipids is a short term...... indicator of intake of ALA and this correlated well with the content of ALA in atrial tissue. Atrial tissue is not readily available but this study shows that determination of plasma phospholipids may be useful to further investigate an antiarrhythmic effect of ALA on AF....

  15. Atrial fibrillation

    DEFF Research Database (Denmark)

    Olesen, Morten S; Nielsen, Morten W; Haunsø, Stig

    2014-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1-2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized...

  16. [Atrial fibrillation].

    Science.gov (United States)

    Spinar, J; Vítovec, J

    2003-09-01

    Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

  17. Genetic basis of atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Oscar Campuzano

    2016-12-01

    Full Text Available Atrial fibrillation is the most common sustained arrhythmia and remains as one of main challenges in current clinical practice. The disease may be induced secondary to other diseases such as hypertension, valvular heart disease, and heart failure, conferring an increased risk of stroke and sudden death. Epidemiological studies have provided evidence that genetic factors play an important role and up to 30% of clinically diagnosed patients may have a family history of atrial fibrillation. To date, several rare variants have been identified in a wide range of genes associated with ionic channels, calcium handling protein, fibrosis, conduction and inflammation. Important advances in clinical, genetic and molecular basis have been performed over the last decade, improving diagnosis and treatment. However, the genetics of atrial fibrillation is complex and pathophysiological data remains still unraveling. A better understanding of the genetic basis will induce accurate risk stratification and personalized clinical treatment. In this review, we have focused on current genetics basis of atrial fibrillation.

  18. Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

    Science.gov (United States)

    Kumar, Akash; Dougherty, Max; Findlay, Gregory M; Geisheker, Madeleine; Klein, Jason; Lazar, John; Machkovech, Heather; Resnick, Jesse; Resnick, Rebecca; Salter, Alexander I; Talebi-Liasi, Faezeh; Arakawa, Christopher; Baudin, Jacob; Bogaard, Andrew; Salesky, Rebecca; Zhou, Qian; Smith, Kelly; Clark, John I; Shendure, Jay; Horwitz, Marshall S

    2014-01-01

    Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF). Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP), as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP), rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD) adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

  19. Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

    Directory of Open Access Journals (Sweden)

    Akash Kumar

    Full Text Available Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF. Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP, as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP, rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

  20. Atrial Fibrillation: Treatment

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Treatment Past Issues / Winter 2015 Table of Contents Treatment for atrial fibrillation depends on how often you have symptoms, how ...

  1. A sensitive radioimmunoassay of atrial natriuretic peptide in human plasma, using a tracer with an immobilized glycouril agent

    International Nuclear Information System (INIS)

    Rosmalen, F.M.A.; Tan, A.C.I.T.L.; Benraad, T.J.

    1987-01-01

    A highly specific and sensitive radioimmunoassay (RIA) for alpha-human atrial natriuretic peptide (hANP[1-28]) in plasma was developed. The assay used a [ 125 I]monoiodotyrosyl-hANP[1-28] tracer, prepared with an immobilized glycouril agent (Protag) and purified by high pressure liquid chromatography (HPLC), and a highly specific antiserum raised against hANP[1-28], coupled to keyhole limpet haemocyanin, in sheep. Plasma was extracted using C-18 Seppak cartridges. A good parallelism was found after dilution prior to extraction of plasma of patients with congestive heart failure (CHF) or of plasma of healthy subjects. Recovery of hANP[1-28] added to plasma was 96%. The limit of detection was 0.8 pg/tube, intra- and inter-assay variation were 9 and 12%, respectively. Mean plasma ANP values in 25 normal persons with a normal salt intake was 26.0 ± 15.5 (± SD) pg/ml. Plasma levels of 18 subjects (7 normals, 11 CHF) were measured using four different antisera after the extraction step. High correlations were found between the values obtained with these four antisera. (Auth.)

  2. Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing.

    Directory of Open Access Journals (Sweden)

    Dennis H Lau

    Full Text Available BACKGROUND: Both ageing and hypertension are known risk factors for atrial fibrillation (AF although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR. METHODS: SHR were studied at 12 and 15 months of age (n = 8 per group together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY. Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP, atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. RESULTS: COMPARED TO WKY CONTROLS, THE SHR DEMONSTRATED: Higher systolic blood pressure (p<0.0001, bi-atrial enlargement (p<0.05, bi-ventricular hypertrophy (p<0.05, lower atrial ERP (p = 0.008, increased atrial conduction heterogeneity (p = 0.001 and increased atrial interstitial fibrosis (p = 0.006 & CD68-positive macrophages infiltration (p<0.0001. These changes resulted in higher atrial arrhythmia inducibility (p = 0.01 and longer induced AF episodes (p = 0.02 in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01 and atrial conduction heterogeneity (p<0.01 without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. CONCLUSIONS: Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria.

  3. Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy.

    Science.gov (United States)

    Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V; Iser, David; Sasadeusz, Joe; Lewin, Sharon R

    2016-01-01

    Background.  Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods.  We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results.  The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%-20.4%) over a median of 31 months. Conclusions.  The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression.

  4. PROGRESSION OF LIVER FIBROSIS IN MONOINFECTED PATIENTS BY HEPATITIS C VIRUS AND COINFECTED BY HCV AND HUMAN IMMUNODEFICIENCY VIRUS

    Directory of Open Access Journals (Sweden)

    Cristiane Valle TOVO

    2013-03-01

    Full Text Available Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations. Contexto A progressão da fibrose hepática em pacientes coinfectados pelos vírus da hepatite C (VHC e da imunodeficiência humana (VHC/HIV tem sido mais estudada na última década. Estudos realizados antes da terapia antiretroviral de alta potência (HAART sugerem que o HIV pode mudar a história natural da infecção pelo VHC, levando a uma progressão mais rápida da fibrose hepática. Objetivo Avaliar e comparar a progressão de fibrose em duas populações de pacientes (coinfectados VHC/HIV e monoinfectados VHC. Métodos Foram avaliados retrospectivamente 70 pacientes monoinfectados VHC e 26 coinfectados VHC/HIV nunca tratados para o VHC e que haviam realizado duas biopsias hepáticas seriadas. Não houve diferença na progressão de fibrose entre os dois grupos. Conclusão A evolução do grau de fibrose não foi pior nos pacientes coinfectados. A ausência de imunodepressão e o menor intervalo de tempo entre as biopsias no grupo de coinfectados são poss

  5. CO, Pb++ and SO2 effects on L-type calcium channel and action potential in human atrial myocytes. In silico study

    Directory of Open Access Journals (Sweden)

    Diana C. Pachajoa

    2017-09-01

    Full Text Available Exposure to air pollutants like carbon monoxide (CO, lead (Pb++ and sulfur dioxide (SO2 promotes the occurrence of cardiovascular diseases. Experimental studies have shown that CO, Pb++ and SO2 block L-type calcium channels, reducing the calcium current (ICaL and the action potential duration (APD, which favors the initiation of atrial arrhythmias. The goal is to study the effects of CO, Pb++ and SO2 at different concentrations on ICaL and action potential using computational simulation. For this purpose, models of the effects of the air pollutants on the atrial L-type calcium channel were developed and were incorporated into a mathematical model of a human atrial cell. The results suggest that CO, Pb++ and SO2 block the ICaL current in a fraction that increases along with the concentration, generating an APD shortening. These results are consistent with experimental studies. The combined effect of the three air pollutants produced an APD shortening, which is considered to be a pro-arrhythmic effect.

  6. Introduction to Pulmonary Fibrosis

    Science.gov (United States)

    ... page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a disease where there is scarring ... of pulmonary fibrosis. Learn more How Is Pulmonary Fibrosis Diagnosed? Pulmonary fibrosis can be difficult to diagnose, so it ...

  7. Preparation of mono-radioiodinated tracers for study of the in vivo metabolism of atrial natriuretic peptide in humans

    International Nuclear Information System (INIS)

    Clerico, A.; Marastoni, M.; Del Chicca, M.G.; Giannessi, D.; Del Ry, S.; Andreassi, M.G.; Sabatino, L.; Iascone, M.R.; Biagini, A.; Donato, L.

    1995-01-01

    The authors evaluate the optimum chemical conditions for labelling atrial natriuretic peptide (ANP) and its metabolites and for preparing highly purified radiotracers which can be used for in vivo kinetic studies of ANP in humans. Synthetic α h 1-28 ANP and some hormone metabolites were iodinated with Na 125 I or Na 131 I by means of the lactoperoxidase (ANP) or the chloramine-T (ANP metabolites) technique. The biological activity of labelled ANP was tested by means of a binding study using mouse cardiac membranes. A high-performance liquid chromatography (HPLC) procedure was used to purify the labelled hormone and the principal labelled metabolites in venous plasma samples collected up to 50 min after the injection of 125 I-labelled ANP from nine healthy men. The main ANP kinetic parameters were derived from the disappearance curves of the [ 125 I]ANP, which were satisfactorily fitted by a bi-exponential function in all subjects. The main advantages of this tracer technique are high accuracy, allowing the identification of the metabolites produced in vivo under steady-state conditions after injection of the precursor (labelled hormone) high sensitivity, allowing the detection of minimal quantities of metabolites high specificity, allowing the detection of possible in vitro artefactual generation of cleavage products of ANP using an internal labelled standard. Utilizing this tracer method, it was possible to estimate the principal parameters of ANP kinetics and also to plot the appearance curves of the labelled metabolites produced in vivo after the injection of the labelled precursor. (orig.). With 5 figs

  8. A COUP-TFII Human Embryonic Stem Cell Reporter Line to Identify and Select Atrial Cardiomyocytes

    NARCIS (Netherlands)

    Schwach, Verena; Verkerk, Arie O.; Mol, Mervyn; Monshouwer-Kloots, Jantine J.; Devalla, Harsha D.; Orlova, Valeria V.; Anastassiadis, Konstantinos; Mummery, Christine L.; Davis, Richard P.; Passier, Robert

    2017-01-01

    Reporter cell lines have already proven valuable in identifying, tracking, and purifying cardiac subtypes and progenitors during differentiation of human pluripotent stem cells (hPSCs). We previously showed that chick ovalbumin upstream promoter transcription factor II (COUP-TFII) is highly enriched

  9. Distribution and function of sodium channel subtypes in human atrial myocardium

    NARCIS (Netherlands)

    Kaufmann, Susann G.; Westenbroek, Ruth E.; Maass, Alexander H.; Lange, Volkmar; Renner, Andre; Wischmeyer, Erhard; Bonz, Andreas; Muck, Jenny; Ertl, Georg; Catterall, William A.; Scheuer, Todd; Maier, Sebastian K. G.

    Voltage-gated sodium channels composed of a pore-forming alpha subunit and auxiliary beta subunits are responsible for the upstroke of the action potential in cardiac muscle. However, their localization and expression patterns in human myocardium have not yet been clearly defined. We used

  10. Exacerbating effects of human parvovirus B19 NS1 on liver fibrosis in NZB/W F1 mice.

    Directory of Open Access Journals (Sweden)

    Tsai-Ching Hsu

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19 is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-β/Smad fibrotic signaling by increasing the expressions of TGF-β, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and α-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling.

  11. Exacerbating Effects of Human Parvovirus B19 NS1 on Liver Fibrosis in NZB/W F1 Mice

    Science.gov (United States)

    Hsu, Tsai-Ching; Tsai, Chun-Chou; Chiu, Chun-Ching; Hsu, Jeng-Dong; Tzang, Bor-Show

    2013-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19) is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-β/Smad fibrotic signaling by increasing the expressions of TGF-β, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and α-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling. PMID:23840852

  12. Stability of rotors and focal sources for human atrial fibrillation: focal impulse and rotor mapping (FIRM) of AF sources and fibrillatory conduction.

    Science.gov (United States)

    Swarup, Vijay; Baykaner, Tina; Rostamian, Armand; Daubert, James P; Hummel, John; Krummen, David E; Trikha, Rishi; Miller, John M; Tomassoni, Gery F; Narayan, Sanjiv M

    2014-12-01

    Several groups report electrical rotors or focal sources that sustain atrial fibrillation (AF) after it has been triggered. However, it is difficult to separate stable from unstable activity in prior studies that examined only seconds of AF. We applied phase-based focal impulse and rotor mapping (FIRM) to study the dynamics of rotors/sources in human AF over prolonged periods of time. We prospectively mapped AF in 260 patients (169 persistent, 61 ± 12 years) at 6 centers in the FIRM registry, using baskets with 64 contact electrodes per atrium. AF was phase mapped (RhythmView, Topera, Menlo Park, CA, USA). AF propagation movies were interpreted by each operator to assess the source stability/dynamics over tens of minutes before ablation. Sources were identified in 258 of 260 of patients (99%), for 2.8 ± 1.4 sources/patient (1.8 ± 1.1 in left, 1.1 ± 0.8 in right atria). While AF sources precessed in stable regions, emanating activity including spiral waves varied from collision/fusion (fibrillatory conduction). Each source lay in stable atrial regions for 4,196 ± 6,360 cycles, with no differences between paroxysmal versus persistent AF (4,290 ± 5,847 vs. 4,150 ± 6,604; P = 0.78), or right versus left atrial sources (P = 0.26). Rotors and focal sources for human AF mapped by FIRM over prolonged time periods precess ("wobble") but remain within stable regions for thousands of cycles. Conversely, emanating activity such as spiral waves disorganize and collide with the fibrillatory milieu, explaining difficulties in using activation mapping or signal processing analyses at fixed electrodes to detect AF rotors. These results provide a rationale for targeted ablation at AF sources rather than fibrillatory spiral waves. © 2014 Wiley Periodicals, Inc.

  13. Connective matrix organization in human pulmonary fibrosis. Collagen polymorphism analysis in fibrotic deposits by immunohistological methods.

    Science.gov (United States)

    Takiya, C; Peyrol, S; Cordier, J F; Grimaud, J A

    1983-01-01

    In the interstitium of the alveolar septa in the peripheral parts of the lung, four molecular types of collagen (I, III, IV and V) each with different morphological appearances, can be identified. The structural integrity of collagens accounts for the physiological efficiency of the lung. Fibrous thickening of alveolar septa is an invariable result of various diseases affecting the interstitium of the lung. The light and electron microscopic findings, and the immunological typing of collagens in six cases of fibrotic alveolar disease, are described. In the alveolar septa, two different compartments (the alveolo-capillary junction and the supportive axis) were affected by fibrosis: the alveolo-capillary junction was widened by the addition of interstitial collagens to basement membranes. In the axis, the increase of interstitial (types I and III) collagen gave rise to different patterns of connective matrix organization, graded as Loose or Dense depending on quantitative alterations of the type I/III ratio. The mode of organization of the fibrotic lung connective matrix, which depends on the quality of deposits in the matrix, may be correlated with the evolution of interstitial pulmonary fibrosis, in terms of its stability, remodelling ability and reversibility.

  14. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling

    NARCIS (Netherlands)

    Kern, Georg; Mair, Sabine M; Noppert, Susie-Jane; Jennings, Paul; Schramek, Herbert; Rudnicki, Michael; Mueller, Gerhard A; Mayer, Gert; Koppelstaetter, Christian

    2014-01-01

    Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the

  15. Digoxin for atrial fibrillation and atrial flutter

    DEFF Research Database (Denmark)

    Sethi, Naqash J; Nielsen, Emil E; Safi, Sanam

    2018-01-01

    BACKGROUND: During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless...... of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo......, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm...

  16. Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway.

    Science.gov (United States)

    Alves, Michele Joana; Figuerêdo, Raquel Galvão; Azevedo, Flavia Figueiredo; Cavallaro, Diego Alexandre; Neto, Nelson Inácio Pinto; Lima, Joanna Darck Carola; Matos-Neto, Emidio; Radloff, Katrin; Riccardi, Daniela Mendes; Camargo, Rodolfo Gonzalez; De Alcântara, Paulo Sérgio Martins; Otoch, José Pinhata; Junior, Miguel Luiz Batista; Seelaender, Marília

    2017-03-14

    Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFβ) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFβ in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFβ pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFβ isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFβ1 and TGFβ3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas

  17. Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

    Science.gov (United States)

    Fan, Jinqi; Zou, Lili; Cui, Kun; Woo, Kamsang; Du, Huaan; Chen, Shaojie; Ling, Zhiyu; Zhang, Quanjun; Zhang, Bo; Lan, Xianbin; Su, Li; Zrenner, Bernhard; Yin, Yuehui

    2015-01-01

    The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF.

  18. Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Børresen-Dale, Anne-Lise; Alsner, Jan

    2008-01-01

    BACKGROUND AND PURPOSE: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last...... years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients. MATERIALS AND METHODS: Fibroblast cell lines from 31 individuals......-treated fibroblasts. Transcriptional differences in basal and radiation-induced gene expression profiles were investigated using 15K cDNA microarrays, and results analyzed by both SAM and PAM. RESULTS: Sixty differentially expressed genes were identified by applying SAM on 10 patients with the highest risk of RIF...

  19. Coffee consumption prevents fibrosis in a rat model that mimics secondary biliary cirrhosis in humans.

    Science.gov (United States)

    Arauz, Jonathan; Zarco, Natanael; Hernández-Aquino, Erika; Galicia-Moreno, Marina; Favari, Liliana; Segovia, José; Muriel, Pablo

    2017-04-01

    Investigations demonstrated that oxidative stress plays an important role in injury promotion in cholestatic liver disease. We hypothesized that coffee attenuates cholestasis-induced hepatic necrosis and fibrosis via its antioxidant, anti-inflammatory, and antifibrotic properties. The major aim of this study was to evaluate the hepatoprotective properties of coffee and caffeine in a model of chronic bile duct ligation (BDL) in male Wistar rats. Liver injury was induced by 28-day BDL, and conventional coffee, decaffeinated coffee, or caffeine was administered daily. After treatment, the hepatic oxidative status was estimated by measuring lipid peroxidation, the reduced to oxidized glutathione ratio, and glutathione peroxidase. Fibrosis was assessed by measuring the liver hydroxyproline content. The transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, collagen 1, and interleukin-10 proteins and mRNAs were measured by Western blot and polymerase chain reaction, respectively. Conventional coffee suppressed most of the changes produced by BDL; however, caffeine showed better antifibrotic effects. Coffee demonstrated antioxidant properties by restoring the redox equilibrium, and it also prevented the elevation of liver enzymes as well as hepatic glycogen depletion. Interestingly, coffee and caffeine administration prevented collagen increases. Western blot assays showed decreased expression levels of transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, and collagen 1 in the coffee- and caffeine-treated BDL groups. Similarly, coffee decreased the mRNA levels of these proteins. We conclude that coffee prevents liver cirrhosis induced by BDL by attenuating the oxidant processes, blocking hepatic stellate cell activation, and downregulating the main profibrotic molecules involved in extracellular matrix deposition. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Galectin-3 as a marker of interstitial atrial remodelling involved in atrial fibrillation

    OpenAIRE

    Diana Hernández-Romero; Juan Antonio Vílchez; Álvaro Lahoz; Ana I. Romero-Aniorte; Eva Jover; Arcadio García-Alberola; Rubén Jara-Rubio; Carlos M. Martínez; Mariano Valdés; Francisco Marín

    2017-01-01

    Remodelling in the atria could appear as a result of hypertension, diabetes or ischaemic heart disease. Galectin-3 (Gal-3) is a mediator of profibrotic pathways and a potential biomarker of cardiac remodelling. We prospectively recruited consecutive patients undergoing elective cardiac surgery. Preoperative Gal-3 levels were determined from serum samples, and the presence of fibrosis was assessed from atrial appendage tissue samples obtained during cardiac surgery. We included 100 patients wi...

  1. Atrial fibrillation or flutter

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000184.htm Atrial fibrillation or flutter To use the sharing features on this page, please enable JavaScript. Atrial fibrillation or flutter is a common type of abnormal ...

  2. Atrial fibrillation - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000237.htm Atrial fibrillation - discharge To use the sharing features on this ... have been in the hospital because you have atrial fibrillation . This condition occurs when your heart beats faster ...

  3. Atrial Fibrillation - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Atrial Fibrillation - Multiple Languages To use the sharing features on ...

  4. Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation.

    Science.gov (United States)

    Masè, Michela; Grasso, Margherita; Avogaro, Laura; D'Amato, Elvira; Tessarolo, Francesco; Graffigna, Angelo; Denti, Michela Alessandra; Ravelli, Flavia

    2017-01-24

    MicroRNAs (miRNAs) are emerging as key regulators of complex biological processes in several cardiovascular diseases, including atrial fibrillation (AF). Reverse transcription-quantitative polymerase chain reaction is a powerful technique to quantitatively assess miRNA expression profile, but reliable results depend on proper data normalization by suitable reference genes. Despite the increasing number of studies assessing miRNAs in cardiac disease, no consensus on the best reference genes has been reached. This work aims to assess reference genes stability in human cardiac tissue with a focus on AF investigation. We evaluated the stability of five reference genes (U6, SNORD48, SNORD44, miR-16, and 5S) in atrial tissue samples from eighteen cardiac-surgery patients in sinus rhythm and AF. Stability was quantified by combining BestKeeper, delta-C q , GeNorm, and NormFinder statistical tools. All methods assessed SNORD48 as the best and U6 as the worst reference gene. Applications of different normalization strategies significantly impacted miRNA expression profiles in the study population. Our results point out the necessity of a consensus on data normalization in AF studies to avoid the emergence of divergent biological conclusions.

  5. Atrial Fibrillation: Complications

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Complications Past Issues / Winter 2015 Table of Contents ... has two major complications—stroke and heart failure. Atrial Fibrillation and Stroke Click to enlarge image This illustration ...

  6. Atrial Na,K-ATPase increase and potassium dysregulation accentuate the risk of postoperative atrial fibrillation

    DEFF Research Database (Denmark)

    Tran, Cao Thach; Schmidt, Thomas Andersen; Christensen, John Brochorst

    2009-01-01

    BACKGROUND: Postoperative atrial fibrillation is a common complication to cardiac surgery. Na,K-ATPase is of major importance for the resting membrane potential and action potential. The purpose of the present study was to evaluate the importance of Na,K-ATPase concentrations in human atrial...... biopsies and plasma potassium concentrations for the development of atrial fibrillation. METHODS: Atrial myocardial biopsies were obtained from 67 patients undergoing open chest cardiac surgery. Na,K-ATPase was quantified using vanadate-facilitated 3H-ouabain binding. Plasma potassium concentration....../g wet weight (n = 33), p = 0.03]. Also with multivariable analysis, 3H-ouabain-binding site concentration was significantly associated with the development of atrial fibrillation. High increase in plasma potassium concentration during the perioperative period and surgery was associated...

  7. Association of Atrial Fibrillation with Morphological and Electrophysiological Changes of the Atrial Myocardium.

    Science.gov (United States)

    Matějková, Adéla; Šteiner, Ivo

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. For long time it was considered as pure functional disorder, but in recent years, there were identified atrial locations, which are involved in the initiation and maintenance of this arrhythmia. These structural changes, so called remodelation, start at electric level and later they affect contractility and morphology. In this study we attempted to find a possible relation between morphological (scarring, amyloidosis, left atrial (LA) enlargement) and electrophysiological (ECG features) changes in patients with AF. We examined grossly and histologically 100 hearts of necropsy patients - 54 with a history of AF and 46 without AF. Premortem ECGs were evaluated. The patients with AF had significantly heavier heart, larger LA, more severely scarred myocardium of the LA and atrial septum, and more severe amyloidosis in both atria. Severity of amyloidosis was higher in LAs vs. right atria (RAs). Distribution of both fibrosis and amyloidosis was irregular. The most affected area was in the LA anterior wall. Patients with a history of AF and with most severe amyloidosis have more often abnormally long P waves. Finding of long P wave may contribute to diagnosis of a hitherto undisclosed atrial fibrillation.

  8. Calmodulin and calmodulin-binding proteins in cystic fibrosis and normal human fibroblasts

    International Nuclear Information System (INIS)

    Tallant, E.A.; Wallace, R.W.

    1986-01-01

    The authors have investigated the possibility that a lesion in a calmodulin (CaM)-dependent regulatory mechanism may be involved in cystic fibrosis (CF). The level of CaM, CaM-binding proteins (CaM-BP) and a CaM-dependent phosphatase (CaM-Ptase) have been compared in cultured fibroblasts from CF patients versus age- and sex-matched control subjects. The CaM concentration, measured by radioimmunoassay, ranged from 0.20 to 0.76 μg/mg protein (n=8); there was no significant difference in the average CaM concentration from CF patients vs controls. Using Western blotting techniques with 125 I-CaM, they detected at least ten distinct CaM-BPs in fibroblasts with molecular weights ranging from 230K to 37K; the only consistent difference between control and CF cell lines was in a 46.5K CaM-BP, which was depressed in all three CF samples. The 46.5 K CaM-BP was found only in the particulate fraction. A 59K CaM-BP was identified as a CaM-Ptase by its crossreactivity with an antibody against a brain CaM-Ptase. There was no significant difference in CaM-Ptase activity or in the amount of the phosphatase as determined by radioimmunoassay in CF vs. normal samples (n=8). Thus, the level of CaM as well as its various enzymes and proteins do not appear to be altered in CF fibroblasts except for a CaM-BP of 46.5K, the identity of which is currently being investigated

  9. In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis.

    Science.gov (United States)

    Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

    2017-12-14

    To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. A CCl 4 -induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo . Functionally, the transplantation of hUC-MSCs to CCl 4 -treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl 4 -induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

  10. Atrial fibrillation.

    Science.gov (United States)

    Bang, Casper N

    2013-10-01

    Atrial fibrillation (AF) is a common complication after myocardial infarction (MI) and new-onset AF has been demonstrated to be associated with adverse outcome and a large excess risk of death in both MI and aortic stenosis (AS) patients. Prevention of new-onset AF is therefore a potential therapeutic target in AS and MI patients. Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent AF. Accordingly, statins are recommended as a class IIa recommendation for prevention of new-onset AF after coronary artery bypass grafting (CABG). However, this preventive effect has not been investigated on new-onset AF in asymptomatic patients with AS or a large scale first-time MI patient sample and data in patients not undergoing invasive cardiac interventions are limited. This PhD thesis was conducted at the Heart Centre, Rigshospitalet, Denmark, with the aim to investigate the three aforementioned questions and to add to the existing evidence of AF prevention with statins. This was done using three different settings: 1) a randomized patients sample of 1,873 from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, 2) a register patient sample of 97,499 with first-time MI, and 3) all published studies until beginning of June 2011 examining statin treatment on new-onset and recurrent AF in patients not undergoing cardiac surgery. This thesis revealed that statins did not lower the incidence or the time to new-onset AF in patients with asymptomatic AS. However, statin treatment showed an independently preventive effect on new-onset AF, including type-dependent effect and a trend to dosage-dependent effect. In addition, this thesis showed that good compliance to statin treatment was important to prevent new-onset AF. Finally, the meta-analysis in this PhD thesis showed a preventive effect in the observational studies although this effect was absent in the randomized controlled trials. Based on this PhD thesis

  11. Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

    Science.gov (United States)

    Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme V M; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna Mae

    2015-11-01

    Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (Pportal hypertension severity. © 2015 Authors; published by Portland Press Limited.

  12. Pulmonary Fibrosis Foundation

    Science.gov (United States)

    ... submissions. MORE We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources to provide ... its battle against the deadly lung disease, pulmonary fibrosis (PF). PULMONARY FIBROSIS WALK SURPASSES PARTICIPATION AND FUNDRAISING GOALS Nearly ...

  13. Pathogenic Mechanisms of Atrial Fibrillation in Obesity

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2016-01-01

    Full Text Available Atrial fibrillation (AF is one of the most common arrhythmias. It reduces quality of life and its duration due to thromboembolic complications. Obesity contributes to the structural and electrical remodeling of atrial myocardium. This leads to occurrence of ectopic foci in the mouths of the pulmonary veins and the disruption of normal electrical conduction in the atria. Systemic inflammation, myocardial fibrosis, cardiomyocyte overload by Na+ and Ca2+ ions, accumulation in the cells of unoxidized metabolic products, imbalance of the autonomic regulation are considered as the main mechanisms of arrhythmogenic substrate formation. Hypertension, insulin resistance, and obstructive sleep apnea, associated with obesity, increase the risk of development and progression of the arrhythmia. Study of pathogenetic mechanisms of AF in obesity is necessary to develop new strategies for its prevention and the creation of more effective methods of treatment of these patients.

  14. In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

    OpenAIRE

    Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

    2017-01-01

    AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was ...

  15. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    Energy Technology Data Exchange (ETDEWEB)

    Lasalvia, Maria [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Castellani, Stefano [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); D’Antonio, Palma [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Perna, Giuseppe [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Carbone, Annalucia [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); Colia, Anna Laura; Maffione, Angela Bruna [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Capozzi, Vito [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Conese, Massimo, E-mail: massimo.conese@unifg.it [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy)

    2016-10-15

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in

  16. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    International Nuclear Information System (INIS)

    Lasalvia, Maria; Castellani, Stefano; D’Antonio, Palma; Perna, Giuseppe; Carbone, Annalucia; Colia, Anna Laura; Maffione, Angela Bruna; Capozzi, Vito; Conese, Massimo

    2016-01-01

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in the

  17. 17β-Estradiol-induced interaction of estrogen receptor α and human atrial essential myosin light chain modulates cardiac contractile function.

    Science.gov (United States)

    Duft, Karolin; Schanz, Miriam; Pham, Hang; Abdelwahab, Ahmed; Schriever, Cindy; Kararigas, Georgios; Dworatzek, Elke; Davidson, Mercy M; Regitz-Zagrosek, Vera; Morano, Ingo; Mahmoodzadeh, Shokoufeh

    2017-01-01

    Chronic increased workload of the human heart causes ventricular hypertrophy, re-expression of the atrial essential myosin light chain (hALC-1), and improved contractile function. Although hALC-1 is an important positive inotropic regulator of the human heart, little is known about its regulation. Therefore, we investigated the role of the sex hormone 17β-estradiol (E2) on hALC-1 gene expression, the underlying molecular mechanisms, and the impact of this regulatory process on cardiac contractile function. We showed that E2 attenuated hALC-1 expression in human atrial tissues of both sexes and in human ventricular AC16 cells. E2 induced the nuclear translocation of estrogen receptor alpha (ERα) and hALC-1 in AC16 cells, where they cooperatively regulate the transcriptional activity of hALC-1 gene promoter. E2-activated ERα required the estrogen response element (ERE) motif within the hALC-1 gene promoter to reduce its transcriptional activity (vehicle: 15.55 ± 4.80 vs. E2: 6.51 ± 3.69; ~2 fold). This inhibitory effect was potentiated in the presence of hALC-1 (vehicle: 11.13 ± 3.66 vs. E2: 2.18 ± 1.10; ~5 fold), and thus, hALC-1 acts as a co-repressor of ERα-mediated transcription. Yeast two-hybrid screening of a human heart cDNA library revealed that ERα interacts physically with hALC-1 in the presence of E2. This interaction was confirmed by Co-Immunoprecipitation and immunofluorescence in human atrium. As a further novel effect, we showed that chronic E2-treatment of adult mouse cardiomyocytes overexpressing hALC-1 resulted in reduced cell-shortening amplitude and twitching kinetics of these cells independent of Ca 2+ activation levels. Together, our data showed that the expression of hALC-1 gene is, at least partly, regulated by E2/ERα, while hALC-1 acts as a co-repressor. The inotropic effect of hALC-1 overexpression in cardiomyocytes can be significantly repressed by E2.

  18. Surgery for atrial fibrillation.

    Science.gov (United States)

    Viganò, M; Graffigna, A; Ressia, L; Minzioni, G; Pagani, F; Aiello, M; Gazzoli, F

    1996-01-01

    The mechanisms of atrial fibrillation arc multiple reentry circuits spinning around the atrial surface, and these baffle any attempt to direct surgical interruption. The purpose of this article is to report the surgical experience in the treatment of isolated and concomitant atrial fibrillation at the Cardiac Surgical Institute of the University of Pavia. In cases of atrial fibrillation secondary to mitral/valve disease, surgical isolation of the left atrium at the time of mitral valve surgery can prevent atrial fibrillation from involving the right atrium, which can exert its diastolic pump function on the right ventricle. Left atrial isolation was performed on 205 patients at the time of mitral valve surgery. Atrial partitioning ("maze operation") creates straight and blind atrial alleys so that non-recentry circuits can take place. Five patients underwent this procedure. In eight-cases of atrial fibrillation secondary to atrial septal defect, the adult patients with atrial septal defect and chronic or paroxysmal atrial fibrillation underwent surgical isolation of the right atrium associated which surgical correction of the defect, in order to let sinus rhythm govern the left atrium and the ventricles. "Lone" atrial fibrillation occurs in hearts with no detectable organic disease. Bi-atrial isolation with creation of an atrial septal internodal "corridor" was performed on 14 patients. In cases of atrial fibrillation secondary to mitral valve disease, left atrial isolation was performed on 205 patients at the time of mitral valve surgery with an overall sinus rhythm recovery of 44%. In the same period, sinus rhythm was recovered and persisted in only 19% of 252 patients who underwent mitral valve replacement along (P < 0.001). Sinus rhythm was less likely to recover in patients with right atriomegaly requiring tricuspid valve annuloplasty: 59% vs 84% (P < 0.001). Restoration of the right atrial function raised the cardiac index from 2.25 +/- 0.55 1/min per m2

  19. Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-ß mediated fibrosis

    LENUS (Irish Health Repository)

    Watson, Chris J

    2012-07-07

    AbstractBackgroundMechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts’ response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.Methods and resultsThe effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.ConclusionWe postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.

  20. EMMPRIN expression is involved in the development of interstitial fibrosis and tubular atrophy in human kidney allografts.

    Science.gov (United States)

    Kemmner, Stephan; Schulte, Christian; von Weyhern, Claus Hann; Schmidt, Roland; Baumann, Marcus; Heemann, Uwe; Renders, Lutz; Schmaderer, Christoph

    2016-03-01

    Matrix metalloproteinases (MMP) are involved in the development of interstitial fibrosis and tubular atrophy (IF/TA) in renal disease. The synthesis of MMP is activated by the extracellular matrix metalloproteinases inducer protein (EMMPRIN). To analyze the role of EMMPRIN in IF/TA, we retrospectively detected EMMPRIN expression in specimens of human renal allografts with various levels of IF/TA. Immunohistochemistry was performed to detect EMMPRIN expression. In a retrospective analysis, a total cohort of 50 specimens were divided according to BANFF-classification into four subgroups (0-3): no, mild (≤ 25%), moderate (26-50%), or severe (>50%) IF/TA. Among other parameters, renal function was analyzed and compared to EMMPRIN expression. In 24 of 38 biopsies, we detected positive EMMPRIN staining. All nephrectomy (n = 12) samples were negative for EMMPRIN. Positive staining in the biopsy samples was detectable on the basolateral side of tubular epithelial cells. EMMPRIN staining was negatively correlated with IF/TA (p EMMPRIN expression in IF/TA groups 0 and 3 (p = 0.021) and groups 1 and 3 (p = 0.004). Furthermore, we found significant correlations between EMMPRIN staining and renal function. Our data suggest that EMMPRIN is involved in the pathophysiology of IF/TA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Organized Atrial Tachycardias after Atrial Fibrillation Ablation

    Science.gov (United States)

    Castrejón-Castrejón, Sergio; Ortega, Marta; Pérez-Silva, Armando; Doiny, David; Estrada, Alejandro; Filgueiras, David; López-Sendón, José L.; Merino, José L.

    2011-01-01

    The efficacy of catheter-based ablation techniques to treat atrial fibrillation is limited not only by recurrences of this arrhythmia but also, and not less importantly, by new-onset organized atrial tachycardias. The incidence of such tachycardias depends on the type and duration of the baseline atrial fibrillation and specially on the ablation technique which was used during the index procedure. It has been repeatedly reported that the more extensive the left atrial surface ablated, the higher the incidence of organized atrial tachycardias. The exact origin of the pathologic substrate of these trachycardias is not fully understood and may result from the interaction between preexistent regions with abnormal electrical properties and the new ones resultant from radiofrequency delivery. From a clinical point of view these atrial tachycardias tend to remit after a variable time but in some cases are responsible for significant symptoms. A precise knowledge of the most frequent types of these arrhythmias, of their mechanisms and components is necessary for a thorough electrophysiologic characterization if a new ablation procedure is required. PMID:21941669

  2. Right atrial isolation associated with atrial septal closure in patients with atrial septal defect and chronic atrial fibrillation.

    Science.gov (United States)

    Minzioni, G; Graffigna, A; Pagani, F; Vigano, M

    1993-12-01

    To restore sinus rhythm in the remaining heart chambers of six adult patients with atrial septal defect and chronic or paroxysmal atrial fibrillation, electrical, right atrial isolation associated with surgical correction of the defect was performed. All but one patient was free from atrial fibrillation without medication 2-25 months after operation. The isolated right atrial appendages showed intrinsic rhythmical activity in five patients and no electrical activity in one. Right atrial isolation is a safe and effective procedure that abolishes atrial fibrillation in patients with arrhythmia after surgical correction of atrial septal defect.

  3. Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Henning W Zimmermann

    Full Text Available BACKGROUND: Monocyte-derived macrophages critically perpetuate inflammatory responses after liver injury as a prerequisite for organ fibrosis. Experimental murine models identified an essential role for the CCR2-dependent infiltration of classical Gr1/Ly6C(+ monocytes in hepatic fibrosis. Moreover, the monocyte-related chemokine receptors CCR1 and CCR5 were recently recognized as important fibrosis modulators in mice. In humans, monocytes consist of classical CD14(+CD16(- and non-classical CD14(+CD16(+ cells. We aimed at investigating the relevance of monocyte subpopulations for human liver fibrosis, and hypothesized that 'non-classical' monocytes critically exert inflammatory as well as profibrogenic functions in patients during liver disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed circulating monocyte subsets from freshly drawn blood samples of 226 patients with chronic liver disease (CLD and 184 healthy controls by FACS analysis. Circulating monocytes were significantly expanded in CLD-patients compared to controls with a marked increase of the non-classical CD14(+CD16(+ subset that showed an activated phenotype in patients and correlated with proinflammatory cytokines and clinical progression. Correspondingly, CD14(+CD16(+ macrophages massively accumulated in fibrotic/cirrhotic livers, as evidenced by immunofluorescence and FACS. Ligands of monocyte-related chemokine receptors CCR2, CCR1 and CCR5 were expressed at higher levels in fibrotic and cirrhotic livers, while CCL3 and CCL4 were also systemically elevated in CLD-patients. Isolated monocyte/macrophage subpopulations were functionally characterized regarding cytokine/chemokine expression and interactions with primary human hepatic stellate cells (HSC in vitro. CD14(+CD16(+ monocytes released abundant proinflammatory cytokines. Furthermore, CD14(+CD16(+, but not CD14(+CD16(- monocytes could directly activate collagen-producing HSC. CONCLUSIONS/SIGNIFICANCE: Our data

  4. Effect of renin-angiotensin -aldosterone system blockers on myocardial remodeling processes and risk for atrial fibrillation in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2014-07-01

    Full Text Available The given review considers the mechanisms underlying the development and maintenance of atrial fibrillations (AF. It is noted that the processes of atrial fibrosis, ion channel remodeling, inflammation, apoptosis, impaired intercellular interactions, and myocardiocyte hypertrophy may give rise to atrial structural and functional changes in AF. The efficacy of angiotensinonverting enzyme inhibitors and angiotensin receptor antagonists is justified in patients with left ventricular systolic dysfunction.

  5. A survey of detergents for the purification of stable, active human cystic fibrosis transmembrane conductance regulator (CFTR).

    Science.gov (United States)

    Hildebrandt, Ellen; Zhang, Qinghai; Cant, Natasha; Ding, Haitao; Dai, Qun; Peng, Lingling; Fu, Yu; DeLucas, Lawrence J; Ford, Robert; Kappes, John C; Urbatsch, Ina L

    2014-11-01

    Structural knowledge of the cystic fibrosis transmembrane conductance regulator (CFTR) requires developing methods to purify and stabilize this aggregation-prone membrane protein above 1mg/ml. Starting with green fluorescent protein- and epitope-tagged human CFTR produced in mammalian cells known to properly fold and process CFTR, we devised a rapid tandem affinity purification scheme to minimize CFTR exposure to detergent in order to preserve its ATPase function. We compared a panel of detergents, including widely used detergents (maltosides, neopentyl glycols (MNG), C12E8, lysolipids, Chaps) and innovative detergents (branched alkylmaltosides, facial amphiphiles) for CFTR purification, function, monodispersity and stability. ATPase activity after reconstitution into proteoliposomes was 2-3 times higher when CFTR was purified using facial amphiphiles. ATPase activity was also demonstrated in purified CFTR samples without detergent removal using a novel lipid supplementation assay. By electron microscopy, negatively stained CFTR samples were monodisperse at low concentration, and size exclusion chromatography showed a predominance of monomer even after CFTR concentration above 1mg/ml. Rates of CFTR aggregation quantified in an electrophoretic mobility shift assay showed that detergents which best preserved reconstituted ATPase activity also supported the greatest stability, with CFTR monomer half-lives of 6-9days in MNG or Chaps, and 12-17days in facial amphiphile. Cryoelectron microscopy of concentrated CFTR in MNG or facial amphiphile confirmed mostly monomeric protein, producing low resolution reconstructions in conformity with similar proteins. These protocols can be used to generate samples of pure, functional, stable CFTR at concentrations amenable to biophysical characterization. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Atrial Fibrillation and Hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Jayaprasad N

    2005-10-01

    Full Text Available Atrial fibrillation occurs in 10 – 15% of patients with hyperthyroidism. Low serum thyrotropin concentration is an independent risk factor for atrial fibrillation. Thyroid hormone contributes to arrythmogenic activity by altering the electrophysiological characteristics of atrial myocytes by shortening the action potential duration, enhancing automaticity and triggered activity in the pulmonary vein cardio myocytes. Hyperthyroidism results in excess mortality from increased incidence of circulatory diseases and dysrhythmias. Incidence of cerebral embolism is more in hyperthyroid patients with atrial fibrillation, especially in the elderly and anti-coagulation is indicated in them. Treatment of hyperthyroidism results in conversion to sinus rhythm in up to two-third of patients. Beta-blockers reduce left ventricular hypertrophy and atrial and ventricular arrhythmias in patients with hyperthyroidism. Treatment of sub clinical hyperthyroidism is controversial. Optimizing dose of thyroxine treatment in those with replacement therapy and beta-blockers is useful in exogenous subclinical hyperthyroidism.

  7. Pulmonary fibrosis

    International Nuclear Information System (INIS)

    Yamakido, Michio; Okuzaki, Takeshi

    1992-01-01

    When the chest is exposed to x radiation and Co-60 gamma radiation, radiation damage may occur in the lungs 2 to 10 weeks after irradiation. This condition is generally referred to as radiation pneumonitis, with the incidence ranging from 5.4% to 91.8% in the literature. Then radiation pneumonitis may develop into pulmonary fibrosis associated with roentgenologically diffuse linear and ring-like shadows and strong contraction 6 months to one year after irradiation. Until recently, little attention has been paid to pulmonary pneumonitis as a delayed effect of A-bomb radiation. The recent study using the population of 9,253 A-bomb survivors have suggested that the prevalence of pulmonary fibrosis tended to be high in heavily exposed A-bomb survivors. Two other studies using the cohort of 16,956 and 42,728 A-bomb survivors, respectively, have shown that the prevalence of roentgenologically proven pulmonary fibrosis was higher in men than women (1.82% vs 0.41%), was increased with aging and had a higher tendency in heavily exposed A-bomb survivors. (N.K.)

  8. Role of the MAPKs/TGF-β1/TRAF6 signaling pathway in postoperative atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Daoliang Zhang

    Full Text Available To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD and its role in atrial fibrillation (AF after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis.A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF, respectively. Western blot was also used to measure the protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1. Serum angiotensin II (Ang II levels were assayed using enzyme-linked immunosorbent assay (ELISA.Eighteen patients developed AF, whereas 39 remained in sinus rhythm (SR. The severity of atrial fibrosis was significantly higher in patients who developed AF versus those who remained in SR; the mRNA and protein expression of TGF-β1, TRAF6 and CTGF were significantly higher in patients with AF. The protein expression of phosphorylated MAPKs and TAK1 was significantly increased in patients who developed AF compared with the patients who remained in SR. Serum Ang II levels were significantly higher in patients who developed AF versus those who remained in SR.The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis in patients with RHD, which results in the occurrence of AF after cardiac surgery.

  9. Protein S is protective in pulmonary fibrosis.

    Science.gov (United States)

    Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

    2016-08-01

    Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar

  10. Familial Pulmonary Fibrosis

    Science.gov (United States)

    ... Education & Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... more members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

  11. Pattern-Recognition Receptor Signaling Regulator mRNA Expression in Humans and Mice, and in Transient Inflammation or Progressive Fibrosis

    Science.gov (United States)

    Günthner, Roman; Kumar, Vankayala Ramaiah Santhosh; Lorenz, Georg; Anders, Hans-Joachim; Lech, Maciej

    2013-01-01

    The cell type-, organ-, and species-specific expression of the pattern-recognition receptors (PRRs) are well described but little is known about the respective expression profiles of their negative regulators. We therefore determined the mRNA expression levels of A20, CYLD, DUBA, ST2, CD180, SIGIRR, TANK, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, SHP1, SHP2, TOLLIP, IRF4, SIKE, NLRX1, ERBIN, CENTB1, and Clec4a2 in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. Additionally, we characterized their expression profiles in mononuclear blood cells upon bacterial endotoxin, which showed a consistent induction of A20, SOCS3, IRAK-M, and Clec4a2 in human and murine cells. Furthermore, we studied the expression pattern in transient kidney ischemia-reperfusion injury versus post-ischemic atrophy and fibrosis in mice. A20, CD180, ST2, SOCS1, SOCS3, SHIP, IRAK-M, DOK1, DOK2, IRF4, CENTB1, and Clec4a2 were all induced, albeit at different times of injury and repair. Progressive fibrosis was associated with a persistent induction of these factors. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to PRR-mediated innate immunity, which seems to be involved in tissue injury, tissue regeneration and in progressive tissue scarring. PMID:24009023

  12. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    Science.gov (United States)

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  13. Antiarrhythmic properties of atrial pacing.

    Science.gov (United States)

    Kliś, Magdalena; Sławuta, Agnieszka; Gajek, Jacek

    2017-01-01

    Bradycardia, atrial stretch and dilatation, autonomic nervous system disorders, and the presence of triggers such as atrial premature contractions, are factors which predispose a person to paroxysmal AF. Atrial pacing not only eliminates bradycardia but also prevents atrial premature contractions and dispersion of refractoriness, which are a substrate for atrial fibrillation. As the prolonged duration of atrial activation during pacing, especially from locations changing the physiological pattern of this activation (right atrium lateral wall, right atrium appendage), negatively influences both a mechanical and an electrical function of the atria, the atrial pacing site affects an atrial arrhythmogenesis. A conventional atrial lead location in the right atrium appendage causes non-physiological activation propagation, resulting in a prolongation of the activation time of both atria. This location is optimal according to a passive fixation of the atrial lead but the available contemporary active fixation leads could potentially be located in any area of the atrium. There is growing evidence of the benefit of pacing, imitating the physiological propagation of impulses within the atria. It seems that the Bachmann's bundle pacing is the best pacing site within the atria, not only positively influencing the atrial mechanical function but also best fulfilling the so-called atrial resynchronization function, in particular in patients with interatrial conduction delay. It can be effectively achieved using only one atrial electrode, and the slight shortening of atrioventricular conduction provides an additional benefit of this atrial pacing site.

  14. What Is Atrial Fibrillation?

    Science.gov (United States)

    ANSWERS by heart Cardiovascular Conditions What Is Atrial Fibrillation? Your heart has a natural pacemaker, called the “sinus node,” that makes electrical signals. These signals cause the heart to contract and pump ...

  15. Atrial therapies reduce atrial arrhythmia burden in defibrillator patients.

    Science.gov (United States)

    Friedman, P A; Dijkman, B; Warman, E N; Xia, H A; Mehra, R; Stanton, M S; Hammill, S C

    2001-08-28

    Approximately 25% of patients who receive an implantable cardioverter-defibrillator (ICD) to treat ventricular tachyarrhythmias have documented atrial tachyarrhythmias before implantation. This study assessed the ability of device-based prevention and termination therapies to reduce the burden of spontaneous atrial tachyarrhythmias. Patients with a standard indication for the implantation of an ICD and 2 episodes of atrial tachyarrhythmias in the preceding year received a dual-chamber ICD (Medtronic 7250 Jewel AF) that uses pacing and shock therapies for prevention and/or termination of atrial tachyarrhythmias. In a multicenter trial, patients were randomized to 3-month periods with atrial therapies "on" or "off" and subsequently crossed over. Analysis was performed on the 52 of 269 patients who had episodes of atrial tachyarrhythmia and had >/=30 days of follow-up with atrial therapies on and off. The atrial therapies resulted in a reduction of atrial tachyarrhythmia burden from a mean of 58.5 to 7.8 h/mo. A paired analysis (Wilcoxon signed-rank test) showed that the median difference in burden (1.1 h/mo) was highly significant (P=0.007). When the subgroup of 41 patients treated only with atrial pacing therapies was analyzed, the reduction in burden persisted (P=0.01). In this study, patients with a standard ICD indication and atrial tachyarrhythmias had a significant reduction in atrial tachyarrhythmia burden with use of atrial pacing and shock therapies.

  16. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  17. High incidence of echocardiographic abnormalities of the interatrial septum in patients undergoing ablation for atrial fibrillation.

    Science.gov (United States)

    Schernthaner, Christiana; Danmayr, Franz; Daburger, Apollonia; Eichinger, Jörg; Hammerer, Matthias; Strohmer, Bernhard

    2013-04-01

    Atrial fibrosis or fatty deposition is known to increase the propensity for the development of atrial fibrillation (AF). Apart from the pulmonic veins, the interatrial septum (IAS) might play a role in the maintenance of AF. In contrast to left atrial anatomy and adjacent veins, the IAS cannot be visualized in detail with computed tomography. Thus, preprocedural transesophageal echocardiography (TEE) may provide important morphologic information beyond exclusion from atrial thrombi. The study comprised 108 consecutive patients (mean age 60 ± 11 years; 98 men). AF was paroxysmal in 91 (84%) and persistent in 17 (16%) patients. We investigated the morphological characteristics of the IAS by TEE in patients who underwent radiofrequency ablation of AF. The IAS was structurally abnormal in 46 (43%) patients, showing the following echocardiograhic findings: atrial septal hypermobility or aneurysm (n = 27) associated with a patent foramen ovale (PFO) (n = 11) or with a small atrial septal defect (ASD) (n = 2), a septal flap associated with a PFO or an ASD (n = 8), and an abnormally thickened IAS (n = 12). A thrombus in the left atrial appendage was discovered in only 2 (2%) patients. A structurally abnormal IAS was diagnosed in nearly half of the patients undergoing ablation therapy for AF. The information obtained by TEE is mandatory to exclude left atrial thrombi prior the ablation procedure. Moreover, detailed knowledge of morphologic characteristics of the IAS facilitates an optimized and safe performance of the transseptal puncture using long sheaths with large diameters. © 2012, Wiley Periodicals, Inc.

  18. Transforming growth factor. beta. sub 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Broekelmann, T.J.; Limper, A.H.; McDonald, J.A. (Washington Univ., St. Louis, MO (United States)); Colby, T.V. (Mayo Clinic, Rochester, MN (United States))

    1991-08-01

    Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, the authors demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, they now demonstrate the presence of transforming growth factor {beta}{sub 1} (TGF-{beta}{sub 1}), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-{beta}{sub 1} may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-{beta}{sub 1} is the alveolar macrophage, and they demonstrate the expression of abundant TGF-{beta}{sub 1} mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis.

  19. Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways

    Science.gov (United States)

    Zhang, Changyi; Zhou, Guichi; Chen, Yezeng; Liu, Sizheng; Chen, Fen; Xie, Lichun; Wang, Wei; Zhang, Yonggang; Wang, Tianyou; Lai, Xiulan; Ma, Lian

    2018-01-01

    Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord-derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin-induced rat model of DCM. Male Lewis rats (aged 8-weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1×106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle-injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF-α, extracellular-signal regulated kinase 1/2 (ERK1/2) and TGF-β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF-α and the TGF-β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM. PMID:29115435

  20. The β3 Adrenergic Receptor Agonist BRL37344 Exacerbates Atrial Structural Remodeling Through iNOS Uncoupling in Canine Models of Atrial Fibrillation.

    Science.gov (United States)

    Wang, Xiaobing; Wang, Ruifeng; Liu, Guangzhong; Dong, Jingmei; Zhao, Guanqi; Tian, Jingpu; Sun, Jiayu; Jia, Xiuyue; Wei, Lin; Wang, Yuping; Li, Weimin

    2016-01-01

    The role of the β3-adrenergic receptor (β3-AR) agonist BRL37344 in atrial fibrillation (AF) structural remodeling and the underlying mechanisms as a therapeutic target were investigated. Four groups of dogs were evaluated: sham, pacing, β3-AR agonist BRL37344 (β3-AGO), and β3-AR antagonist L748337 (β3-ANT) groups. Dogs in the pacing, β3-AGO and β3-ANT groups were subjected to rapid atrial pacing for four weeks. Atrial structure and function, AF inducibility and duration, atrial myocyte apoptosis and interstitial fibrosis were assessed. Atrial superoxide anions were evaluated by fluorescence microscopy and colorimetric assays. Cardiac nitrate+nitrite levels were used to assess nitric oxide (NO) production. Protein and mRNA expression of β3-AR, neuronal NO synthase (nNOS), inducible NO synthase (iNOS), endothelial NO synthase (eNOS) and guanosine triphosphate cyclohydrolase-1 (GCH-1) as well as tetrahydrobiopterin (BH4) levels were measured. β3-AR was up-regulated in AF. Stimulation of β3-AR significantly increased atrial myocyte apoptosis, fibrosis and atrial dilatation, resulting in increased AF induction and prolonged duration. These effects were attenuated by β3-ANT. Moreover, β3-AGO reduced BH4 and NO production and increased superoxide production, which was inhibited by the specific iNOS inhibitor, 1400w β3-AGO also increased iNOS but decreased eNOS and had no effect on nNOS expression in AF. β3-AR stimulation resulted in atrial structural remodeling by increasing iNOS uncoupling and related oxidative stress. β3-AR up-regulation and iNOS uncoupling might be underlying AF therapeutic targets. © 2016 The Author(s) Published by S. Karger AG, Basel.

  1. Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal fibrosis by releasing from G2/M cell cycle arrest.

    Science.gov (United States)

    Chen, Wenxia; Yan, Yongbin; Song, Chundong; Ding, Ying; Du, Tao

    2017-12-14

    Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI); however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated. Tubular cell proliferation and apoptosis were identified by Ki67 or terminal-deoxynucleotidyl transferase-mediated nick end labeling immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin staining were used for assessing renal fibrosis. The mRNA or protein expression in the kidney was measured by quantitative reverse transcription-PCR or Western blot, respectively. The total collagen concentration was also determined. In vitro , NRK-52E cells that treated with MVs under hypoxia injury and with HGF or U0126 administration were used, and cell cycle analysis was performed. The effects of hWJMSC-MVs on enhancing the proliferation and mitigating the apoptosis of renal cells, abrogating IRI-induced fibrosis, improving renal function, decreasing collagen deposition, and altering the expression levels of epithelial-mesenchymal transition and cell cycle-related proteins in IRI rats were found. In vitro experiment showed that hWJMSC-MVs could induce G2/M cell cycle arrest and decrease the expression of collagen deposition-related proteins in NRK-52E cells after 24 or 48 h. However, U0126 treatment reversed these effects. In conclusion, MVs derived from hWJMSCs ameliorate IR-induced renal fibrosis by inducing G2/M cell cycle arrest via Erk1/2 signaling. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  2. Effect of renal sympathetic denervation on atrial substrate remodeling in ambulatory canines with prolonged atrial pacing.

    Directory of Open Access Journals (Sweden)

    Xule Wang

    Full Text Available We have previously demonstrated that catheter-based renal sympathetic denervation (RSD could suppress atrial fibrillation (AF in canines with short-time rapid right atrial pacing (RAP. However, the role of renal denervation on atrial remodeling is unclear. The aim of the present study was to explore the long-term effect of RSD on the atrial remodeling during prolonged RAP. Twenty mongrel dogs were implanted with a high-frequency cardiac pacemaker with a transvenous lead inserted into the right atrial appendage. The dogs were divided into three groups: a sham-operated group (n = 6, the chronic RAP (CRAP group (n = 7, and the CRAP+RSD group (n = 7. In the CRAP+RSD group, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recovery. RAP was maintained for 5 weeks in CRAP group and CRAP+RSD group. The plasma levels of Angiotensin II and aldosterone were significantly increased in CRAP group compared with sham-operated group, but the increasing trend was inhibited in CRAP+RSD group compared with CRAP group (P<0.05. Similarly, RSD suppressed the increasing trend that prolonged RAP produced in the left atrial levels of ANP, TNF-α and IL-6. Compared with the sham-operated group, the CRAP group had significantly increased levels of caspase-3, bax and Cx40 whereas the level of Bcl-2 decreased (P<0.05. RSD markedly reduced the upregulation of caspase-3, bax and Cx40 and the downregulation of Bcl-2 expression compared with the CRAP group (P<0.05. Picric acid-sirius red staining study suggested that RSD could markedly alleviate the lesion degree of cardic fibrosis induced by CRAP (P<0.05. Immunohistochemistry results showed that the densities of TH- and GAP43- positive nerves were significantly elevated in the CRAP group compared with the sham-operated group, while RSD operation signicantly inhibited the these changes produced by CRAP. These findings suggest that renal denervation could suppress the atrial remodeling after

  3. Atrial remodelling in atrial fibrillation: CaMKII as a nodal proarrhythmic signal

    Science.gov (United States)

    Mesubi, Olurotimi O.; Anderson, Mark E.

    2016-01-01

    CaMKII is a serine–threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflammation, and metabolism. Furthermore, CaMKII inhibition appears to protect against AF in animal models and correct proarrhythmic, defective intracellular Ca2+ homeostasis in fibrillating human atrial cells. This review considers current concepts and evidence from animal and human studies on the role of CaMKII in AF. PMID:26762270

  4. Multimodality Cardiac Imaging for the Assessment of Left Atrial Function and the Association With Atrial Arrhythmias

    DEFF Research Database (Denmark)

    Olsen, Flemming Javier; Bertelsen, Litten; de Knegt, Martina Chantal

    2016-01-01

    Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the c......Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function...... atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered...... an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing...

  5. MicroRNA regulatory networks reflective of polyhexamethylene guanidine phosphate-induced fibrosis in A549 human alveolar adenocarcinoma cells.

    Science.gov (United States)

    Shin, Da Young; Jeong, Mi Ho; Bang, In Jae; Kim, Ha Ryong; Chung, Kyu Hyuck

    2018-05-01

    Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis. Fibrosis, induced by recurrent epithelial damage, is significantly affected by epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of miRNAs and their target genes. A549 cells were treated with 0.75 μg/mL PHMG-phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted. The putative mRNA targets of the miRNAs were identified and subjected to Gene Ontology analysis. After exposure to PHMG-phosphate for 24 and 48 h, 46 and 33 miRNAs, respectively, showed a significant change in expression over 1.5-fold compared with the control. The integrated analysis of miRNA and mRNA microarray results revealed the putative targets that were prominently enriched were associated with the epithelial-mesenchymal transition (EMT), cell cycle changes, and apoptosis. The dose-dependent induction of EMT by PHMG-phosphate exposure was confirmed by western blot. We identified 13 putative EMT-related targets that may play a role in PHMG-phosphate-induced fibrosis according to the Comparative Toxicogenomic Database. Our findings contribute to the comprehension of the fibrogenic mechanism of PHMG-phosphate and will aid further study on PHMG-phosphate-induced toxicity. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Risk Factors for Atrial Fibrillation

    NARCIS (Netherlands)

    B.P. Krijthe (Bouwe)

    2013-01-01

    textabstractAtrial fibrillation is a common cardiac arrhythmia that is characterized by rapid disorganized atrial electrical activity resulting in absence of atrial contractions. It is diagnosed on the basis of typical findings on an electrocardiogram (ECG). The characteristic ECG findings are

  7. Left atrial appendage occlusion

    Directory of Open Access Journals (Sweden)

    Ahmad Mirdamadi

    2013-01-01

    Full Text Available Left atrial appendage (LAA occlusion is a treatment strategy to prevent blood clot formation in atrial appendage. Although, LAA occlusion usually was done by catheter-based techniques, especially percutaneous trans-luminal mitral commissurotomy (PTMC, it can be done during closed and open mitral valve commissurotomy (CMVC, OMVC and mitral valve replacement (MVR too. Nowadays, PTMC is performed as an optimal management of severe mitral stenosis (MS and many patients currently are treated by PTMC instead of previous surgical methods. One of the most important contraindications of PTMC is presence of clot in LAA. So, each patient who suffers of severe MS is evaluated by Trans-Esophageal Echocardiogram to rule out thrombus in LAA before PTMC. At open heart surgery, replacement of the mitral valve was performed for 49-year-old woman. Also, left atrial appendage occlusion was done during surgery. Immediately after surgery, echocardiography demonstrates an echo imitated the presence of a thrombus in left atrial appendage area, although there was not any evidence of thrombus in pre-pump TEE. We can conclude from this case report that when we suspect of thrombus of left atrial, we should obtain exact history of previous surgery of mitral valve to avoid misdiagnosis clotted LAA, instead of obliterated LAA. Consequently, it can prevent additional evaluations and treatments such as oral anticoagulation and exclusion or postponing surgeries including PTMC.

  8. Animal experimental research of the endothelialization of home-made atrial septal defect occluder device

    International Nuclear Information System (INIS)

    Chen Mingwu; Zhou Aiqing; Li Feng; Gao Wei; Yu Zhiqing; Tang Ning; Zhang Lan

    2003-01-01

    Objective: To evaluate the endothelialization of Chinese nitinol atrial septal defect occluder device. Methods: Atrial septal defect with controllable size was created by the Brockenborough needle and Rashkind balloon atrial septostomy, the occluder devices were implanted in six piglets (mean weight 7.5 kg). Two pigs were killed each time after 1 month, 3 months and 6 months after the device implantation and then the explanted devices were examined by scanning electron microscope (SEM). Results: The devices were found covering with collagen fibrosis together with diffuse endothelial cells spreading over the primer 1 month after implantation. The implants were covered mostly by neointima 3 months after implantation and completely covered by confluent endothelial cells 6 months after the implantation. Endothelial cells were not found on the smooth marker band at 3 months, however, did exist by 6 months. Conclusions: Home-made atrial septal defect occluder devices were mostly endothelialised 3 months after the implantation and did completely at 6 months

  9. Recurrent atrial myxoma.

    Science.gov (United States)

    Macarie, C; Stoica, E; Chioncel, O; Carp, A; Gherghiceanu, D; Stiru, O; Zarma, L; Herlea, V

    2004-01-01

    We have chosen this case of sporadic atrial myxoma for our presentation because it had a particular evolution, with recurrence at 8 years after surgical excision (echocardiography was performed every year) and a particular diagnostic means - at echocardiographic follow-up, the patient being asymptomatic. This presentation, together with a review of literature included in the article, emphasizes the importance of a careful postoperative follow-up of the patients and the existence of some particular aspects of the evolution and symptomatology of recurrent atrial myxoma.

  10. Thyrotoxic atrial fibrillation.

    Science.gov (United States)

    Parmar, Malvinder S

    2005-01-04

    Atrial fibrillation is the most common cardiac complication of hyperthyroidism and occurs in 15% of patients with hyperthyroidism. It is associated with a higher risk of thromboembolism that often involves the central nervous system. Oral anticoagulation is important in the majority of these patients to prevent thromboembolic complications. These patients require adjustment in the dose of various rate-controlling agents because of increased clearance associated with hyperthyroidism and a decrease in warfarin dosage because of increased clearance of vitamin K-dependent clotting factors. The management of thyrotoxic atrial fibrillation is summarized in this clinical review.

  11. Atrial natriuretic peptide in patients with heart failure and chronic atrial fibrillation : Role of duration of at atrial fibrillation

    NARCIS (Netherlands)

    Van Den Berg, MP; Crijns, HJGM; Van Veldhuisen, DJ; Van Gelder, IC; De Kam, PJ; Lie, KI

    The purpose of this study was to analyze the determinants of atrial natriuretic peptide level in patients with congestive heart failure and atrial fibrillation. In particular, the duration of atrial fibrillation was analyzed because atrial fibrillation per se might have a specific effect on atrial

  12. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

    Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

  13. LEFT ATRIAL FUNCTION: MODERN ASSESSMENT METHODS AND CLINICAL SIGNIFICANCE

    Directory of Open Access Journals (Sweden)

    E. N. Pavlyukova

    2017-01-01

    Full Text Available Assessment of the left atrial (LA function is important aspect of comprehensive cardiovascular system estimation. Many cardiac diseases make an impact to LA work either by direct affect on myocardium or hemodynamic condition changing. It is considered, LA and left ventricle diastolic pressure is interrelated, thus without mitral valve disease LA expanding is a sign of LV filling pressure augmentation. Examination of LA size and function by analysis of atrial reservoir, conduit, and booster pump can predict cardiovascular outcomes in patients with cardiomyopathy, ischemic heart disease and valvular heart disease. The last two decades gave new technologies to accurate and comprehensive LA mechanics estimation, in the first place related to tissue Doppler imaging. Atrial strain and strain rate obtained using two-dimensional speckle-tracking echocardiography have proved to be feasible and reproducible techniques to evaluate LA mechanics.In physiological settings, LA is a highly expandable chamber with relatively low pressures. However in the presence of acute and chronic injury, LA wall stretches. LA stretching is a hallmark of structure changing with myocardial fibrosis and has influence on LA strain and strain rate. LA strain estimation could be useful in the prediction of sinus rhythm restoration and maintenance after cardioversion and catheter ablation. Low values of global longitudinal LA strain indicate irreversible LA remodeling and are related to the atrial fibrillation progression from paroxysmal to permanent forms. The most interesting in these circumstances is the potential contribution of echocardiography to thromboembolic risk stratification in atrial fibrillation and invasive procedures such as atrial ablation. Therefore, at present, the main task is to understand the ways of clinical application of data  obtained during the LA study.

  14. Impact of the [delta]F508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Hal A.; Zhao, Xun; Wang, Chi; Sauder, J. Michael; Rooney, Isabelle; Noland, Brian W.; Lorimer, Don; Kearins, Margaret C.; Conners, Kris; Condon, Brad; Maloney, Peter C.; Guggino, William B.; Hunt, John F.; Emtage, Spencer (SG); (Columbia); (JHU)

    2010-07-19

    Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR), commonly the deletion of residue Phe-508 (DeltaF508) in the first nucleotide-binding domain (NBD1), which results in a severe reduction in the population of functional channels at the epithelial cell surface. Previous studies employing incomplete NBD1 domains have attributed this to aberrant folding of DeltaF508 NBD1. We report structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation. Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR. These results raise the possibility that the primary effect of DeltaF508 is a disruption of proper interdomain interactions at this site in CFTR rather than interference with the folding of NBD1. Interestingly, increases in the stability of NBD1 constructs are observed upon introduction of second-site mutations that suppress the trafficking defect caused by the DeltaF508 mutation, suggesting that these suppressors might function indirectly by improving the folding efficiency of NBD1 in the context of the full-length protein. The human NBD1 structures also solidify the understanding of CFTR regulation by showing that its two protein segments that can be phosphorylated both adopt multiple conformations that modulate access to the ATPase active site and functional interdomain interfaces.

  15. Modulation of atrial fibrillation

    NARCIS (Netherlands)

    Geuzebroek, G.S.C.

    2013-01-01

    In this thesis we investigate the results of various surgical procedures for atrial fibrillation which have been performed in the last 2 decades in the Sint Antonius Hospital, Nieuwegein, The Netherlands. In the 1990s the classical Maze III procedure was the main surgical technique for

  16. Screening for Atrial Fibrillation

    DEFF Research Database (Denmark)

    Freedman, Ben; Camm, John; Calkins, Hugh

    2017-01-01

    Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed...

  17. Comparison of vectorial ion transport in primary murine airway and human sinonasal air-liquid interface cultures, models for studies of cystic fibrosis, and other airway diseases.

    Science.gov (United States)

    Zhang, Shaoyan; Fortenberry, James A; Cohen, Noam A; Sorscher, Eric J; Woodworth, Bradford A

    2009-01-01

    The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium. Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport. The change in forskolin-stimulated current (delta-I(SC), expressed as micro-A/cm(2)) in murine septal (n = 19; 16.84 +/- 2.09) and human sinonasal (n = 18; 12.15 +/- 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 +/- 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated I(SC) was inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 microM). No forskolin-stimulated I(SC) was shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal I(SC) was largely inhibited by amiloride (12.03 +/- 0.66), whereas human sinonasal cultures had a very limited response (0.70 +/- 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 +/- 1.28; human sinonasal, 11.12 +/- 1.58; murine trachea, 4.85 +/- 0.49; p < 0.0001). Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.

  18. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

    Directory of Open Access Journals (Sweden)

    Georg Kern

    Full Text Available Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506 induced TGF-β-like effects, manifested by increased expression of NAD(PH-oxidase 4 (Nox4, transgelin, tropomyosin 1, and procollagen α1(V mRNA after three days. The macrolide mTOR inhibitor rapamycin had similar effects, while cyclosporine A did not induce fibrose-related genes. Concentration dependence curves were sigmoid, where mRNA expression was induced already at low nanomolar levels of tacrolimus, and reached saturation at 100-300 nM. The effects were independent of extracellular TGF-β as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-β receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-β receptor. The myofibroblast marker α-smooth muscle actin was neither induced by tacrolimus nor by TGF-β1, indicating an incomplete activation of TK-173 fibroblasts under culture conditions. Tacrolimus- and TGF-β1-induced Nox4 protein upregulation was confirmed by Western blotting, and was accompanied by a rise in intracellular H2O2 concentration. Si-RNA mediated knock-down of Nox4 expression prevented up-regulation of procollagen α1(V mRNA in tacrolimus-treated cells, but induced procollagen α1(V expression in control cells. Nox4 knock-down had no significant effect on the other genes tested. TGF-β is a key molecule in fibrosis, and the constant activation of aberrant receptor signaling by tacrolimus might contribute to the long-term development of interstitial kidney fibrosis in immunosuppressed patients. Nox4 levels possibly play a regulatory role in these processes.

  19. Absence of rotational activity detected using 2-dimensional phase mapping in the corresponding 3-dimensional phase maps in human persistent atrial fibrillation.

    Science.gov (United States)

    Pathik, Bhupesh; Kalman, Jonathan M; Walters, Tomos; Kuklik, Pawel; Zhao, Jichao; Madry, Andrew; Sanders, Prashanthan; Kistler, Peter M; Lee, Geoffrey

    2018-02-01

    Current phase mapping systems for atrial fibrillation create 2-dimensional (2D) maps. This process may affect the accurate detection of rotors. We developed a 3-dimensional (3D) phase mapping technique that uses the 3D locations of basket electrodes to project phase onto patient-specific left atrial 3D surface anatomy. We sought to determine whether rotors detected in 2D phase maps were present at the corresponding time segments and anatomical locations in 3D phase maps. One-minute left atrial atrial fibrillation recordings were obtained in 14 patients using the basket catheter and analyzed off-line. Using the same phase values, 2D and 3D phase maps were created. Analysis involved determining the dominant propagation patterns in 2D phase maps and evaluating the presence of rotors detected in 2D phase maps in the corresponding 3D phase maps. Using 2D phase mapping, the dominant propagation pattern was single wavefront (36.6%) followed by focal activation (34.0%), disorganized activity (23.7%), rotors (3.3%), and multiple wavefronts (2.4%). Ten transient rotors were observed in 9 of 14 patients (64%). The mean rotor duration was 1.1 ± 0.7 seconds. None of the 10 rotors observed in 2D phase maps were seen at the corresponding time segments and anatomical locations in 3D phase maps; 4 of 10 corresponded with single wavefronts in 3D phase maps, 2 of 10 with 2 simultaneous wavefronts, 1 of 10 with disorganized activity, and in 3 of 10 there was no coverage by the basket catheter at the corresponding 3D anatomical location. Rotors detected in 2D phase maps were not observed in the corresponding 3D phase maps. These findings may have implications for current systems that use 2D phase mapping. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  20. Acute termination of human atrial fibrillation by identification and catheter ablation of localized rotors and sources: first multicenter experience of focal impulse and rotor modulation (FIRM) ablation.

    Science.gov (United States)

    Shivkumar, Kalyanam; Ellenbogen, Kenneth A; Hummel, John D; Miller, John M; Steinberg, Jonathan S

    2012-12-01

    Catheter ablation of atrial fibrillation (AF) currently relies on eliminating triggers, and no reliable method exists to map the arrhythmia itself to identify ablation targets. The aim of this multicenter study was to define the use of Focal Impulse and Rotor Modulation (FIRM) for identifying ablation targets. We prospectively enrolled the first (n = 14, 11 males) consecutive patients undergoing FIRM-guided ablation for persistent (n = 11) and paroxysmal AF at 5 centers. A 64-pole basket catheter was used for panoramic right and left atrial mapping during AF. AF electrograms were analyzed using a novel system to identify sustained rotors (spiral waves), or focal beats (centrifugal activation to surrounding atrium). Ablation was performed first at identified sources. The primary endpoints were acute AF termination or organization (>10% cycle length prolongation). Conventional ablation was performed only after FIRM-guided ablation. Twelve out of 14 cases were mapped. AF sources were demonstrated in all patients (average of 1.9 ± 0.8 per patient). Sources were left atrial in 18 cases, and right atrial in 5 cases, and 21/23 were rotors. FIRM-guided ablation achieved the acute endpoint in all patients, consisting of AF termination in n = 8 (4.9 ± 3.9 minutes at the primary source), and organization in n = 4. Total FIRM time for all patients was 12.3 ± 8.6 minutes. FIRM-guided ablation revealed localized AF rotors/focal sources in patients with paroxysmal, persistent and longstanding persistent AF. Brief targeted FIRM-guided ablation at a priori identified sites terminated or substantially organized AF in all cases prior to any other ablation. © 2012 Wiley Periodicals, Inc.

  1. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    Cystic fibrosis is an autosomal recessive genetic disease. Among Caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among Caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

  2. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    Cystic fibrosis is a autosomal recessive genetic disease. Among caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

  3. Cystic Fibrosis (CF): Chloride Sweat Test

    Science.gov (United States)

    ... on this topic for: Parents Kids Teens Cystic Fibrosis Cystic Fibrosis and Nutrition Cystic Fibrosis (CF) Respiratory Screen: Sputum Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition View more Partner Message ...

  4. Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung.

    Science.gov (United States)

    Tagalakis, Aristides D; Munye, Mustafa M; Ivanova, Rositsa; Chen, Hanpeng; Smith, Claire M; Aldossary, Ahmad M; Rosa, Luca Z; Moulding, Dale; Barnes, Josephine L; Kafetzis, Konstantinos N; Jones, Stuart A; Baines, Deborah L; Moss, Guy W J; O'Callaghan, Christopher; McAnulty, Robin J; Hart, Stephen L

    2018-05-10

    Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air-liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (V t ), short circuit current (I sc ), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced V t , the amiloride-sensitive I sc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo. © 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.

  5. Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung Fibroblasts.

    Science.gov (United States)

    Newman, Donna R; Sills, W Shane; Hanrahan, Katherine; Ziegler, Amanda; Tidd, Kathleen McGinnis; Cook, Elizabeth; Sannes, Philip L

    2016-02-01

    The wingless (Wnt) family of signaling ligands contributes significantly to lung development and is highly expressed in patients with usual interstitial pneumonia (UIP). We sought to define the cellular distribution of Wnt5A in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF) and the signaling ligands that control its expression in human lung fibroblasts and IPF myofibroblasts. Tissue sections from 40 patients diagnosed with IPF or UIP were probed for the immunolocalization of Wnt5A. Further, isolated lung fibroblasts from normal or IPF human lungs, adenovirally transduced for the overexpression or silencing of Wnt7B or treated with TGF-β1 or its inhibitor, were analyzed for Wnt5A protein expression. Wnt5A was expressed in IPF lungs by airway and alveolar epithelium, smooth muscle cells, endothelium, and myofibroblasts of fibroblastic foci and throughout the interstitium. Forced overexpression of Wnt7B with or without TGF-β1 treatment significantly increased Wnt5A protein expression in normal human smooth muscle cells and fibroblasts but not in IPF myofibroblasts where Wnt5A was already highly expressed. The results demonstrate a wide distribution of Wnt5A expression in cells of the IPF lung and reveal that it is significantly increased by Wnt7B and TGF-β1, which, in combination, could represent key signaling pathways that modulate the pathogenesis of IPF. © 2016 The Histochemical Society.

  6. Genetics Home Reference: familial atrial fibrillation

    Science.gov (United States)

    ... Twitter Home Health Conditions Familial atrial fibrillation Familial atrial fibrillation Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Familial atrial fibrillation is an inherited abnormality of the heart's normal ...

  7. [Echocardiographic diagnosis of atrial thrombosis].

    Science.gov (United States)

    Pinto Tortolero, R; Vargas Barrón, J; Rodas, M A; Díaz de la Vega, V; Horwitz, S

    1982-01-01

    Seventy patients with rheumatic mitral disease were studied by M-Mode and 2D echocardiography in order to detect left atrial thrombosis before surgery. Thrombosis were suspected by the observation of abnormal echoes in the left atrium. During surgery 17 (24%) patients had atrial thrombosis. It had been suspected by echocardiography in 12 (sensitivity 70%). In 53 patients thrombosis were not found during surgery; in 46 the echo had been also negative (specificity 86%). There was a false positive detection of thrombosis by echo in 7 patients (14%) and false negativity in 5 (30%). Patients with atrial thrombosis had atrial fibrilation in 91% of cases; and the most frequent valvular disease was mitral stenosis. There was not a direct relationship among existence of left atrial thrombosis and the anteroposterior diameter of the left atrium as measured by echo. We conclude that echocardiography has good specificity to rule out atrial thrombosis and moderate sensitivity to detect it in rheumatic mitral disease.

  8. HYPERTHYROIDISM AND ATRIAL FIBRILLATION

    Directory of Open Access Journals (Sweden)

    I. M. Marusenko

    2017-01-01

    Full Text Available Review on a problem of the development of atrial fibrillation in patients with thyrotoxicosis is presented. Thyrotoxicosis is one of the most frequent endocrine diseases, conceding only to a diabetes mellitus. The most frequent reasons of hyperthyroidism are Graves’ disease and functional thyroid autonomy. The authors give an analysis of data on the cardiac effects of thyrotoxicosis, features of heart remodeling under the influence of thyroid hyperfunction, prevalence of atrial fibrillation in thyrotoxicosis, depending on age, as well as the possibility of restoring sinus rhythm in the combination of these diseases. Particular attention is paid to the effect on the heart of subclinical thyrotoxicosis, which is defined as a dysfunction of the thyroid gland, characterized by low serum concentration of thyrotropin, normal values of free thyroxine and free triiodothyronine. Subclinical hyperthyroidism is also capable of causing heart remodeling and diastolic dysfunction.Prevalence of thyrotoxicosis in elderly people is higher in areas of iodine deficiency; it is relevant for our country due to the large territory of iodine deficiency. In elderly patients, the cardiac effects of thyrotoxicosis prevail in the clinical picture, that makes it difficult to diagnose endocrine disorders, and correction of thyrotoxicosis is critically important for the successful control of the heart rhythm. The article also discusses the problem of thyrotoxic cardiomyopathy, caused by the toxic effect of excess thyroid hormones: features of this heart disorder, factors affecting its formation, clinical significance and contribution to the development of rhythm disturbances. The greatest significance is the development of atrial fibrillation as a result of thyrotox-icosis in older patients who already have various cardiovascular diseases.Atrial fibrillation is the most frequent heart rhythm disorder in thyrotoxicosis. The main cause of arrhythmia in hyperthyroidism is the

  9. Microsatellite polymorphism in the heme oxygenase-1 gene promoter and the risk of atrial fibrillation in Taiwanese.

    Directory of Open Access Journals (Sweden)

    Lung-An Hsu

    Full Text Available Atrial fibrillation (AF is associated with increased oxidative stress. Emerging evidence suggests that heme oxygenase-1 (HO-1 is a potent antioxidant system against various oxidative stress-related diseases. The human HO-1 promoter has a GT-repeat length polymorphism that can determine the level of gene transcription.The aim of this study is to assess the role of the GT-repeat polymorphism in the promoter region of the HO-1 gene in Chinese-Taiwanese patients with AF.This study enrolled 200 AF patients and 240 controls, comparable for age and gender. In each subject, the length of GT-repeat polymorphism in the HO-1 promoter region was examined by polymerase chain reactions. The frequencies of long GT-repeat alleles (≧32 were significantly higher in AF patients than in controls. Multivariate analysis showed that the presence of long allele was significantly and independently associated with AF (odds ratio: 1.91, 95% CI 1.07-3.72; P = 0.028. Right atrial tissues from patients with chronic AF were investigated with immunoconfocal microscopy. Patients homozygous for shorter GT-repeat alleles exhibited greater HO-1 expression in their atria than those homozygous for longer alleles, which was reflected by less oxidative stress, myofibril degradation, and fibrosis in the atria of patients with shorter GT-repeat. In vitro, transient transfection assay in HL-1 atrial myocytes showed that the responsiveness of HO-1 transcriptional activity to tachypacing was inversely correlated with the length of the GT-repeats.Our results suggest that the HO-1 microsatellite polymorphism may contribute to the genetic background of AF in Chinese-Taiwanese patients.

  10. An anthocyanin rich strawberry extract induces apoptosis and ROS while decreases glycolysis and fibrosis in human uterine leiomyoma cells.

    Science.gov (United States)

    Islam, Md Soriful; Giampieri, Francesca; Janjusevic, Milijana; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Mazzoni, Luca; Greco, Stefania; Giannubilo, Stefano Raffaele; Ciavattini, Andrea; Mezzetti, Bruno; Capocasa, Franco; Castellucci, Mario; Battino, Maurizio; Ciarmela, Pasquapina

    2017-04-04

    Uterine leiomyomas are highly prevalent benign tumors in reproductive aged women. Unfortunately, medical treatments are still limited and no preventive therapies have been developed. In the present study, we investigated the therapeutic effects of strawberry extract on uterine leiomyoma cells. Leiomyoma and myometrial cells were treated with strawberry (cultivar Alba) extract (250 μg/ml) for 48 h to measure apoptosis, reactive oxygen species (ROS), oxidative phosphorylation (OCR, oxygen consumption rate) and glycolysis (ECAR, extracellular acidification rate) as well as fibrosis associated gene and/or protein expression. In leiomyoma cells, strawberry increased the percentage of apoptotic and dead cells. Strawberry significantly increased ROS concentration in leiomyoma cells, while decreased it in myometrial cells. After strawberry treatment, leiomyoma cells showed a significant decreased rate of ECAR, while OCR was unchanged in both myometrial and leiomyoma cells. Strawberry significantly decreased collagen1A1, fibronectin and versican mRNA expression in leiomyoma cells. The reduced protein expression of fibronectin was observed by strawberry extract in leiomyoma cells as well. Furthermore, strawberry was able to reduce activin A induced fibronectin, collagen1A1, and versican as well as activin A and PAI-1 mRNA expression in leiomyoma cells. This study suggests that strawberry can be developed as therapeutic and/or preventive agent for uterine leiomyomas.

  11. Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.

    Science.gov (United States)

    Wang, Huan; Wang, Hong-Fei; Wang, Chen; Chen, Yu-Fang; Ma, Rong; Xiang, Ji-Zhou; Du, Xin-Ling; Tang, Qiang

    2016-10-15

    In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300μM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30μM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30μM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Atrial fibrillation in the elderly

    Science.gov (United States)

    Franken, Roberto A.; Rosa, Ronaldo F.; Santos, Silvio CM

    2012-01-01

    This review discusses atrial fibrillation according to the guidelines of Brazilian Society of Cardiac Arrhythmias and the Brazilian Cardiogeriatrics Guidelines. We stress the thromboembolic burden of atrial fibrillation and discuss how to prevent it as well as the best way to conduct cases of atrial fibrillatios in the elderly, reverting the arrhythmia to sinus rhythm, or the option of heart rate control. The new methods to treat atrial fibrillation, such as radiofrequency ablation, new oral direct thrombin inhibitors and Xa factor inhibitors, as well as new antiarrhythmic drugs, are depicted. PMID:22916053

  13. Toll-Like Receptor and Accessory Molecule mRNA Expression in Humans and Mice as Well as in Murine Autoimmunity, Transient Inflammation, and Progressive Fibrosis

    Science.gov (United States)

    Ramaiah, Santhosh Kumar Vankayala; Günthner, Roman; Lech, Maciej; Anders, Hans-Joachim

    2013-01-01

    The cell type-, organ-, and species-specific expression of the Toll-like receptors (TLRs) are well described, but little is known about the respective expression profiles of their accessory molecules. We therefore determined the mRNA expression levels of LBP, MD2, CD36, CD14, granulin, HMGB1, LL37, GRP94, UNC93b1, TRIL, PRAT4A, AP3B1, AEP and the respective TLRs in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. In addition, the expression profiles in transient tissue inflammation upon renal ischemia-reperfusion injury, in spleens and kidneys from mice with lupus-like systemic autoimmunity, and in progressive tissue fibrosis upon unilateral ureteral obstruction were studied. Several TLR co-factors were specifically regulated during the different phases of these disease entities, suggesting a functional involvement in the disease process. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to TLR-mediated innate immunity, which seems to be involved in the tissue injury phase, in the phase of tissue regeneration, and in progressive tissue remodelling. PMID:23803655

  14. Right atrial lipoma

    Directory of Open Access Journals (Sweden)

    Pêgo-Fernandes Paulo M.

    2003-01-01

    Full Text Available Benign cardiac tumors are rare, and lipomas are among those less frequently found. We report the case of a 48-year-old male complaining of high blood pressure and epistaxis in the last 2 months, with a diagnosis of right atrial lipoma established on echocardiography, magnetic resonance imaging, and anatomicopathological examination. The tumor was successfully removed, and up to 42 months after surgical excision, no evidence of tumor relapse was observed.

  15. RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Hoban PR

    2006-06-01

    Full Text Available Abstract Background Idiopathic Pulmonary Fibrosis (IPF is a debilitating disease characterized by exaggerated extracellular matrix deposition and aggressive lung structural remodeling. Disease pathogenesis is driven by fibroblastic foci formation, consequent on growth factor overexpression and myofibroblast proliferation. We have previously shown that both CTGF overexpression and myofibroblast formation in IPF cell lines are dependent on RhoA signaling. As RhoA-mediated regulation is also involved in cell cycle progression, we hypothesise that this pathway is key to lung fibroblast turnover through modulation of cyclin D1 kinetic expression. Methods Cyclin D1 expression was compared in primary IPF patient-derived fibroblasts and equivalent normal control cells. Quantitative real time PCR was employed to examine relative expression levels of cyclin D1 mRNA; protein expression was confirmed by western blotting. Effects of Rho signaling were investigated using transient transfection of constitutively active and dominant negative RhoA constructs as well as pharmacological inhibitors. Cellular proliferation of lung fibroblasts was determined by BrdU incorporation ELISA. To further explore RhoA regulation of cyclin D1 in lung fibroblasts and associated cell cycle progression, an established Rho inhibitor, Simvastatin, was incorporated in our studies. Results Cyclin D1 expression was upregulated in IPF compared to normal lung fibroblasts under exponential growth conditions (p Conclusion These findings report for the first time that cyclin D1 expression is deregulated in IPF through a RhoA dependent mechanism that influences lung fibroblast proliferation. This potentially unravels new molecular targets for future anti-IPF strategies; accordingly, Simvastatin inhibition of Rho-mediated cyclin D1 expression in IPF fibroblasts merits further exploitation.

  16. Occlusion of left atrial appendage in patients with atrial fibrillation

    Directory of Open Access Journals (Sweden)

    О. Н. Ганеева

    2015-10-01

    Full Text Available The article reviews a new method of prophylaxis of thromboembolitic complications, specifically occlusion of left atrial appendage, in patients with atrial fibrillation. Indications and contraindications for the procedure, as well as a step-by-step process of the intervention itself are described. Special emphasis is placed on the up-to-date evidence and the review of clinical trials.

  17. Abnormal atrial activation in young patients with lone atrial fibrillation

    DEFF Research Database (Denmark)

    Holmqvist, Fredrik; Olesen, Morten S; Tveit, Arnljot

    2011-01-01

    Patients with a history of atrial fibrillation (AF) have previously been shown to have altered atrial conduction, as seen non-invasively using signal-averaged P-wave analysis. However, little is known about the P-wave morphology in patients in the early phases of AF with structurally normal hearts....

  18. Effects of Prolonged Spaceflight on Atrial Size, Atrial Electrophysiology, and Risk of Atrial Fibrillation.

    Science.gov (United States)

    Khine, Htet W; Steding-Ehrenborg, Katarina; Hastings, Jeffrey L; Kowal, Jamie; Daniels, James D; Page, Richard L; Goldberger, Jeffery J; Ng, Jason; Adams-Huet, Beverley; Bungo, Michael W; Levine, Benjamin D

    2018-05-01

    The prevalence of atrial fibrillation (AF) in active astronauts is ≈5%, similar to the general population but at a younger age. Risk factors for AF include left atrial enlargement, increased number of premature atrial complexes, and certain parameters on signal-averaged electrocardiography, such as P-wave duration, root mean square voltage for the terminal 20 ms of the signal-averaged P wave, and P-wave amplitude. We aimed to evaluate changes in atrial structure, supraventricular beats, and atrial electrophysiology to determine whether spaceflight could increase the risk of AF. Thirteen astronauts underwent cardiac magnetic resonance imaging to assess atrial structure and function before and after 6 months in space and high-resolution Holter monitoring for multiple 48-hour time periods before flight, during flight, and on landing day. Left atrial volume transiently increased after 6 months in space (12±18 mL; P =0.03) without changing atrial function. Right atrial size remained unchanged. No changes in supraventricular beats were noted. One astronaut had a large increase in supraventricular ectopic beats but none developed AF. Filtered P-wave duration did not change over time, but root mean square voltage for the terminal 20 ms decreased on all fight days except landing day. No changes in P-wave amplitude were seen in leads II or V 1 except landing day for lead V 1 . Six months of spaceflight may be sufficient to cause transient changes in left atrial structure and atrial electrophysiology that increase the risk of AF. However, there was no definite evidence of increased supraventricular arrhythmias and no identified episodes of AF. © 2018 American Heart Association, Inc.

  19. Inhibition of the SphK1/S1P signaling pathway by melatonin in mice with liver fibrosis and human hepatic stellate cells.

    Science.gov (United States)

    González-Fernández, Bárbara; Sánchez, Diana I; Crespo, Irene; San-Miguel, Beatriz; Álvarez, Marcelino; Tuñón, María J; González-Gallego, Javier

    2017-03-01

    The sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) system is involved in different pathological processes, including fibrogenesis. Melatonin abrogates activation of hepatic stellate cells (HSCs) and attenuates different profibrogenic pathways in animal models of fibrosis, but it is unknown if protection associates with its inhibitory effect on the SphK1/S1P axis. Mice in treatment groups received carbon tetrachloride (CCl 4 ) 5 μL g -1 body wt i.p. twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg kg -1  day -1 i.p, beginning 2 weeks after the start of CCl 4 administration. At both 4 and 6 weeks following CCl 4 treatment, liver mRNA levels, protein concentration and immunohistochemical labelling for SphK1 increased significantly. S1P production, and expression of S1P receptor (S1PR)1, S1PR3 and acid sphingomyelinase (ASMase) were significantly elevated. However, there was a decreased expression of S1PR2 and S1P lyase (S1PL). Melatonin attenuated liver fibrosis, as shown by a significant inhibition of the expression of α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β and collagen (Col) Ι. Furthermore, melatonin inhibited S1P production, lowered expression of SphK1, S1PR1, SP1R3, and ASMase, and increased expression of S1PL. Melatonin induced a reversal of activated human HSCs cell line LX2, as evidenced by a reduction in α-SMA, TGF-β, and Col I expression. Melatonin-treated cells also exhibited an inhibition of the SphK1/S1P axis. Antifibrogenic effect of SphK1 inhibition was confirmed by treatment of LX2 cells with PF543. Abrogation of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in liver fibrogenesis. © 2016 BioFactors, 43(2):272-282, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  20. Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure

    Directory of Open Access Journals (Sweden)

    Kyoung-Im Cho

    2014-08-01

    Full Text Available Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF, and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI-induced heart failure (HF rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group and underwent echocardiography, AF induction studies and left atrial (LA fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX, sarcoplasmic reticulum calcium ATPase (SERCA, endothelial nitric oxide synthase (eNOS and induced nitric oxide synthase (iNOS were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham, which were significantly reduced by simvastatin (p < 0.05 vs. MI. The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.

  1. Nitrated fatty acids suppress angiotensin II-mediated fibrotic remodelling and atrial fibrillation

    Czech Academy of Sciences Publication Activity Database

    Rudolph, T.K.; Ravekes, T.; Klinke, A.; Friedrichs, K.; Mollenhauer, M.; Pekarová, Michaela; Ambrožová, Gabriela; Martíšková, Hana; Kaur, J.J.; Matthes, B.; Schwoerer, A.; Woodcock, S.R.; Kubala, Lukáš; Freeman, B.A.; Baldus, S.; Rudolph, V.

    2016-01-01

    Roč. 109, č. 1 (2016), s. 174-184 ISSN 0008-6363 R&D Projects: GA ČR(CZ) GP13-40824P; GA MŠk(CZ) EE2.3.30.0030 Grant - others:GAAV(CZ) M200041208 Institutional support: RVO:68081707 Keywords : Atrial fibrillation * Fibrosis * Nitro-fatty acids Subject RIV: BO - Biophysics Impact factor: 5.878, year: 2016

  2. Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers.

    Science.gov (United States)

    Ravens, Ursula; Odening, Katja E

    2017-08-01

    Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K + ) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two pore domain K + (K2P) channels TWIK-1, TASK-1 and TASK-3 that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Here, we briefly review the characteristics of these K + channels and their roles in atrial fibrillation. The antiarrhythmic potential of drugs targeting the described channels is discussed as well as their putative value in treatment of atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. [Atrial fibrillation in elderly].

    Science.gov (United States)

    Arquizan, Caroline

    2012-11-01

    Atrial fibrilation (AF) is frequent and a strong risk factor for ischemic stroke in elderly. Ischemic stroke in patients with AF are more severe. Vitamine K antagonist therapy is highly effective for stroke prevention but is associated with hemorrhagic risk. The new oral anticoagulants (direct thrombin inhibitor [dabigatran], and direct factor Xa inhibitors [rivaroxaban and apixaban]) have all shown non inferiority or superiority, with better safety, considering the risk of intracranial haemorrhage. On this basis, it is justified to give them in priority in the vast majority of patients with AF, the choice of the drug and the dose is individual.

  4. Relaxin and atrial natriuretic peptide pathways participate in the anti-fibrotic effect of a melon concentrate in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Julie Carillon

    2016-04-01

    Full Text Available Background: In spontaneously hypertensive rats (SHR, a model of human essential hypertension, oxidative stress is involved in the development of cardiac hypertrophy and fibrosis associated with hypertension. Dietary supplementation with agents exhibiting antioxidant properties could have a beneficial effect in remodeling of the heart. We previously demonstrated a potent anti-hypertrophic effect of a specific melon (Cucumis melo L. concentrate with antioxidant properties in spontaneously hypertensive rats. Relaxin and atrial natriuretic peptide (ANP were reported to reduce collagen deposition and fibrosis progression in various experimental models. Objective: The aim of the present investigation was to test the hypothesis that, beside reduction in oxidative stress, the melon concentrate may act through relaxin, its receptor (relaxin/insulin-like family peptide receptor 1, RXFP1, and ANP in SHR. Design and results: The melon concentrate, given orally during 4 days, reduced cardiomyocyte size (by 25% and totally reversed cardiac collagen content (Sirius red staining in SHR but not in their normotensive controls. Treatment with the melon concentrate lowered cardiac nitrotyrosine-stained area (by 45% and increased by 17–19% the cardiac expression (Western blot of superoxide dismutase (SOD and glutathione peroxidase. In addition, plasma relaxin concentration was normalized while cardiac relaxin (Western blot was lowered in treated SHR. Cardiac relaxin receptor level determined by immunohistochemical analysis increased only in treated SHR. Similarly, the melon concentrate reversed the reduction of plasma ANP concentration and lowered its cardiac expression. Conclusions: The present results demonstrate that reversal of cardiac fibrosis by the melon concentrate involves antioxidant defenses, as well as relaxin and ANP pathways restoration. It is suggested that dietary SOD supplementation could be a useful additional strategy against cardiac hypertrophy

  5. Neonatal cystic fibrosis screening test

    Science.gov (United States)

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  6. Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

    Science.gov (United States)

    Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

    1999-04-01

    Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

  7. Personalized management of atrial fibrillation

    DEFF Research Database (Denmark)

    Kirchhof, Paulus; Breithardt, Günter; Aliot, Etienne

    2013-01-01

    The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability......, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage...

  8. Imaging pulmonary fibrosis

    International Nuclear Information System (INIS)

    Brauner, M.W.; Rety, F.; Naccache, J.M.; Girard, F.; Valeyre, D.F.

    2001-01-01

    Localized fibrosis of the lung is usually scar tissue while diffuse pulmonary fibrosis is more often a sign of active disease. Chronic infiltrative lung disease may be classified into four categories: idiopathic pneumonitis, collagen diseases, granulomatosis (sarcoidosis), and caused by known diseases (pneumoconiosis, hypersensitivity pneumonitis, drug-induced lung disease, radiation). (authors)

  9. Angiogenesis in liver fibrosis

    NARCIS (Netherlands)

    Adlia, Amirah

    2017-01-01

    Angiogenesis emerges in parallel with liver fibrosis, but it is still unclear whether angiogenesis is a defense mechanism of the body in response to fibrosis, or whether it aggravates the fibrotic condition. In this thesis, Amirah Adlia applied different approaches to elucidate the role of

  10. Fibrosis and Cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R.; Erler, Janine T.

    2016-01-01

    The relation between fibrosis and cancer has long been debated, specifically whether desmoplasia precedes, accompanies, or succeeds tumourigenesis, progression, and metastasis. Recent reports have published opposing data, adding to the perplexity. However, what is emerging is that it is likely th...... the specific properties of the extracellular matrix (ECM) that determine the paradoxical nature of cancer-associated fibrosis....

  11. Diagnosis of cystic fibrosis

    NARCIS (Netherlands)

    H.J. Veeze

    1995-01-01

    textabstractApplying the sweat-test as the first choice of test when a diagnosis of cystic fibrosis is suspected is still common practice and advisable. Since the cloning of the CFTR gene more than 400 different cystic fibrosis (CF) mutations have already been identified. The use of CF mutation

  12. Atrial and ventricular function after cardioversion of atrial fibrillation.

    Science.gov (United States)

    Xiong, C.; Sonnhag, C.; Nylander, E.; Wranne, B.

    1995-01-01

    OBJECTIVE--Previous studies on atrial recovery after cardioversion of atrial fibrillation have not taken into account new knowledge about the pathophysiology of transmitral and transtricuspid flow velocity patterns. It is possible to shed further light on this problem if atrioventricular inflow velocity, venous filling pattern, and atrioventricular annulus motion are recorded and interpreted together. DESIGN--Prospective examinations of mitral and tricuspid transvalvar flow velocities, superior caval and pulmonary venous filling, and mitral and tricuspid annulus motion were recorded using Doppler echocardiography. Examinations were performed before and 24 hours, 1 month, and 20 months after cardioversion. SETTING--Tertiary referral centre for cardiac disease with facilities for invasive and non-invasive investigation. PATIENTS--16 patients undergoing cardioversion of atrial fibrillation in whom sinus rhythm had persisted for 24 hours or more. RESULTS--Before conversion there was no identifiable A wave in transvalvar flow recordings. The total motion of the tricuspid and mitral annulus was subnormal and there was no identifiable atrial component. Venous flow patterns in general showed a low systolic velocity. After conversion, A waves and atrial components were seen in all patients and increased significantly (P atrial components, an increased systolic component of venous inflow, an increased A wave velocity, and a decreased E/A ratio of the transvalvar velocity curves. The ventricular component of annulus motion was unchanged. Changes in general occurred earlier on the right side than the left. CONCLUSIONS--This study indicates that, in addition to the previously known electromechanical dissociation of atrial recovery that exists after cardioversion of atrial fibrillation, there may also be a transient deterioration of ventricular function modulating the transvalvar inflow velocity recordings. Function on the right side generally becomes normal earlier than on the

  13. Increased alveolar soluble Annexin V promotes lung inflammation and fibrosis

    OpenAIRE

    Buckley, S.; Shi, W.; Xu, W.; Frey, M.R.; Moats, R.; Pardo, A.; Selman, M.; Warburton, D.

    2015-01-01

    The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesized that alveolar soluble Annexin V contributes to lung fibrosis, based on the observation that human IPF BALF containing high Annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when Annexin V was depleted from the BALF.

  14. Atrial fibrillation and hyperthyroidism: A literature review.

    Science.gov (United States)

    Reddy, Vivek; Taha, Wael; Kundumadam, Shanker; Khan, Mazhar

    Atrial fibrillation is the most common arrhythmia worldwide with increasing frequency noted with age. Hyperthyroidism is a well-known cause of atrial fibrillation with a 16%-60% prevalence of atrial fibrillation in patients with known hyperthyroidism Ross et al. (2016). While hyperthyroidism as a causative factor of atrial fibrillation is well established, this literature review aims to answer several questions on this topic including: 1. The relationship of atrial fibrillation to hyperthyroidism 2. Atrial fibrillation as a predictor of hyperthyroidism 3. The pathophysiology of thyrotoxic atrial fibrillation 4. Subclinical hyperthyroidism and the relationship with atrial fibrillation 5. Cardioversion and Catheter ablation of hyperthyroid patients with atrial fibrillation 6. Thrombotic risk of hyperthyroid patients with atrial fibrillation 7. Management of Thyrotoxic Atrial fibrillation 8. Pharmacological rhythm control in patients with hyperthyroidism and atrial fibrillation 9. Treatment of Hyperthyroidism to prevent atrial fibrillation 10. Clinical Implications of Hyperthyroidism and Atrial Fibrillation. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  15. Evalutating Inward Rectifier Current Inhibiton for Treatment of Atrial Fibrillation

    NARCIS (Netherlands)

    Ji, Yuan

    2017-01-01

    Atrial Fibrillation (AF) is one of the most common forms of cardiac arrhythmia and affects a large percentage of the human population, especially in the elderly. Currently, more than 6 million Europeans suffer from AF, and due to ageing this number will at least double in the next 50 years.

  16. Comparative study of atrial fibrillation and AV conduction in mammals

    NARCIS (Netherlands)

    Meijler, F.L.; Tweel, I. van der

    1987-01-01

    Atrial fibrillation is one ofthe most common cardiac arrhythmias in humans. It a1so occurs quite frequent1y in dogs and horses. Comparative study of this arrhythmia may contribute to better understanding of the pathophysiologica1 mechanisms involved. In this study, we present a quantitative

  17. Role of the Atrioventricular Node in Atrial Fibrillation

    NARCIS (Netherlands)

    Meijler, F.L.; Wittkampf, F.H.M.

    1997-01-01

    Atrial fibrillation (AF) is probably the most cornmon cardiac arrhythmia in humans, particularly in the elderly (1-3). The irregularity and inequality of the he art beat first described by Hering in 1903 were, and continue to be, the landmark of the clinical diagnosis of AF (4,5). Sir Thomas

  18. MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?

    Science.gov (United States)

    Mölleken, Christian; Poschmann, Gereon; Bonella, Francesco; Costabel, Ulrich; Sitek, Barbara; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Marcussen, Niels; Helmer, Michael; Nielsen, Ole; Hansen, Søren; Schlosser, Anders; Holmskov, Uffe; Sorensen, Grith Lykke

    2016-03-29

    Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis. 91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model. Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis. MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.

  19. South African adolescents with cystic fibrosis: a qualitative ...

    African Journals Online (AJOL)

    South African adolescents with cystic fibrosis: a qualitative exploration of their ... years) who had the defining characteristics of CF and were living in Gauteng province. ... The fundamental human need to be understood and to understand was ...

  20. Noninvasive imaging of experimental lung fibrosis.

    Science.gov (United States)

    Zhou, Yong; Chen, Huaping; Ambalavanan, Namasivayam; Liu, Gang; Antony, Veena B; Ding, Qiang; Nath, Hrudaya; Eary, Janet F; Thannickal, Victor J

    2015-07-01

    Small animal models of lung fibrosis are essential for unraveling the molecular mechanisms underlying human fibrotic lung diseases; additionally, they are useful for preclinical testing of candidate antifibrotic agents. The current end-point measures of experimental lung fibrosis involve labor-intensive histological and biochemical analyses. These measures fail to account for dynamic changes in the disease process in individual animals and are limited by the need for large numbers of animals for longitudinal studies. The emergence of noninvasive imaging technologies provides exciting opportunities to image lung fibrosis in live animals as often as needed and to longitudinally track the efficacy of novel antifibrotic compounds. Data obtained by noninvasive imaging provide complementary information to histological and biochemical measurements. In addition, the use of noninvasive imaging in animal studies reduces animal usage, thus satisfying animal welfare concerns. In this article, we review these new imaging modalities with the potential for evaluation of lung fibrosis in small animal models. Such techniques include micro-computed tomography (micro-CT), magnetic resonance imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and multimodal imaging systems including PET/CT and SPECT/CT. It is anticipated that noninvasive imaging will be increasingly used in animal models of fibrosis to gain insights into disease pathogenesis and as preclinical tools to assess drug efficacy.

  1. Cryoballoon Ablation for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Jason G. Andrade, MD

    2012-03-01

    Full Text Available Focal point-by-point radiofrequency catheter ablation has shown considerable success in the treatment of paroxysmal atrial fibrillation. However, it is not without limitations. Recent clinical and preclinical studies have demonstrated that cryothermal ablation using a balloon catheter (Artic Front©, Medtronic CryoCath LP provides an effective alternative strategy to treating atrial fibrillation. The objective of this article is to review efficacy and safety data surrounding cryoballoon ablation for paroxysmal and persistent atrial fibrillation. In addition, a practical step-by-step approach to cryoballoon ablation is presented, while highlighting relevant literature regarding: 1 the rationale for adjunctive imaging, 2 selection of an appropriate cryoballoon size, 3 predictors of efficacy, 4 advanced trouble-shooting techniques, and 5 strategies to reduce procedural complications, such as phrenic nerve palsy.

  2. Early adaptive developments of Pseudomonas aeruginosa after the transition from life in the environment to persistent colonization in the airways of human cystic fibrosis hosts

    DEFF Research Database (Denmark)

    Rau, Martin Holm; Hansen, Susse Kirkelund; Johansen, H. K.

    2010-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen ubiquitous to the natural environment but with the capability of moving to the host environment. Long-term infection of the airways of cystic fibrosis patients is associated with extensive genetic adaptation of P. aeruginosa, and we have studied...... cases of the initial stages of infection in order to characterize the early adaptive processes in the colonizing bacteria. A combination of global gene expression analysis and phenotypic characterization of longitudinal isolates from cystic fibrosis patients revealed well-known characteristics...... such as conversion to a mucoid phenotype by mucA mutation and increased antibiotic resistance by nfxB mutation. Additionally, upregulation of the atu operon leading to enhanced growth on leucine provides a possible example of metabolic optimization. A detailed investigation of the mucoid phenotype uncovered profound...

  3. Atrial fibrillation and delayed gastric emptying.

    Directory of Open Access Journals (Sweden)

    Isadora C Botwinick

    Full Text Available BACKGROUND: Atrial fibrillation and delayed gastric emptying (DGE are common after pancreaticoduodenectomy. Our aim was to investigate a potential relationship between atrial fibrillation and DGE, which we defined as failure to tolerate a regular diet by the 7(th postoperative day. METHODS: We performed a retrospective chart review of 249 patients who underwent pancreaticoduodenectomy at our institution between 2000 and 2009. Data was analyzed with Fisher exact test for categorical variables and Mann-Whitney U or unpaired T-test for continuous variables. RESULTS: Approximately 5% of the 249 patients included in the analysis experienced at least one episode of postoperative atrial fibrillation. Median age of patients with atrial fibrillation was 74 years, compared with 66 years in patients without atrial fibrillation (p = 0.0005. Patients with atrial fibrillation were more likely to have a history of atrial fibrillation (p = 0.03. 92% of the patients with atrial fibrillation suffered from DGE, compared to 46% of patients without atrial fibrillation (p = 0.0007. This association held true when controlling for age. CONCLUSION: Patients with postoperative atrial fibrillation are more likely to experience delayed gastric emptying. Interventions to manage delayed gastric function might be prudent in patients at high risk for postoperative atrial fibrillation.

  4. Vernakalant selectively prolongs atrial refractoriness with no effect on ventricular refractoriness or defibrillation threshold in pigs.

    Science.gov (United States)

    Bechard, Jeff; Gibson, John Ken; Killingsworth, Cheryl R; Wheeler, Jeffery J; Schneidkraut, Marlowe J; Huang, Jian; Ideker, Raymond E; McAfee, Donald A

    2011-03-01

    Vernakalant is a novel antiarrhythmic agent that has demonstrated clinical efficacy for the treatment of atrial fibrillation. Vernakalant blocks, to various degrees, cardiac sodium and potassium channels with a pattern that suggests atrial selectivity. We hypothesized, therefore, that vernakalant would affect atrial more than ventricular effective refractory period (ERP) and have little or no effect on ventricular defibrillation threshold (DFT). Atrial and ventricular ERP and ventricular DFT were determined before and after treatment with vernakalant or vehicle in 23 anesthetized male mixed-breed pigs. Vernakalant was infused at a rate designed to achieve stable plasma levels similar to those in human clinical trials. Atrial and ventricular ERP were determined by endocardial extrastimuli delivered to the right atria or right ventricle. Defibrillation was achieved using external biphasic shocks delivered through adhesive defibrillation patches placed on the thorax after 10 seconds of electrically induced ventricular fibrillation. The DFT was estimated using the Dixon "up-and-down" method. Vernakalant significantly increased atrial ERP compared with vehicle controls (34 ± 8 versus 9 ± 7 msec, respectively) without significantly affecting ventricular ERP or DFT. This is consistent with atrial selective actions and supports the conclusion that vernakalant does not alter the efficacy of electrical defibrillation.

  5. Idiopathic pulmonary fibrosis: evolving concepts.

    Science.gov (United States)

    Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

    2014-08-01

    Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. Post-operative atrial fibrillation: a maze of mechanisms

    Science.gov (United States)

    Maesen, Bart; Nijs, Jan; Maessen, Jos; Allessie, Maurits; Schotten, Ulrich

    2012-01-01

    Post-operative atrial fibrillation (POAF) is one of the most frequent complications of cardiac surgery and an important predictor of patient morbidity as well as of prolonged hospitalization. It significantly increases costs for hospitalization. Insights into the pathophysiological factors causing POAF have been provided by both experimental and clinical investigations and show that POAF is ‘multi-factorial’. Facilitating factors in the mechanism of the arrhythmia can be classified as acute factors caused by the surgical intervention and chronic factors related to structural heart disease and ageing of the heart. Furthermore, some proarrhythmic mechanisms specifically occur in the setting of POAF. For example, inflammation and beta-adrenergic activation have been shown to play a prominent role in POAF, while these mechanisms are less important in non-surgical AF. More recently, it has been shown that atrial fibrosis and the presence of an electrophysiological substrate capable of maintaining AF also promote the arrhythmia, indicating that POAF has some proarrhythmic mechanisms in common with other forms of AF. The clinical setting of POAF offers numerous opportunities to study its mechanisms. During cardiac surgery, biopsies can be taken and detailed electrophysiological measurements can be performed. Furthermore, the specific time course of POAF, with the delayed onset and the transient character of the arrhythmia, also provides important insight into its mechanisms. This review discusses the mechanistic interaction between predisposing factors and the electrophysiological mechanisms resulting in POAF and their therapeutic implications. PMID:21821851

  7. State of the Art Review: Atrial Fibrillation in Athletes.

    Science.gov (United States)

    Flannery, M Darragh; Kalman, Jonathan M; Sanders, Prashanthan; La Gerche, André

    2017-09-01

    Exercise has substantial health benefits with pleomorphic vascular, metabolic, psychological and anti-neoplastic actions resulting in improved quality of life and longevity. Despite these many benefits, numerous studies have shown that endurance athletes are more likely to develop atrial fibrillation (AF) than non-athletes. The type, intensity and amount of sport appears to influence the risk of developing AF. Several endurance sport activities have been shown to increase the risk of developing AF but an excess in AF has not been shown in non-endurance sports. Furthermore, lifetime hours of participation appear to increase the risk of developing AF. Intriguingly, women appear relatively protected and an association between endurance sport and AF has not been clearly demonstrated amongst female endurance athletes. The mechanisms by which endurance sport promotes the development of AF are unclear. There are, however, a number of pathophysiological mechanisms which are known to increase the risk of AF in non-athletes which have correlates in athletes. These include structural remodelling of the left atrium, elevated left atrial pressure, inflammation, myocardial fibrosis, vagal tone, sinus bradycardia and genetic predisposition. In this article, we explore how some of these mechanisms may contribute to the development of AF in endurance athletes. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  8. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter; Skov, Lone; Rossen, Kristian

    2006-01-01

    Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases...... of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75...... d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P

  9. Syndecans in heart fibrosis.

    Science.gov (United States)

    Lunde, Ida G; Herum, Kate M; Carlson, Cathrine C; Christensen, Geir

    2016-09-01

    Heart disease is a deadly syndrome affecting millions worldwide. It reflects an unmet clinical need, and the disease mechanisms are poorly understood. Cardiac fibrosis is central to heart disease. The four-membered family of transmembrane proteoglycans, syndecan-1 to -4, is believed to regulate fibrosis. We review the current literature concerning syndecans in cardiac fibrosis. Syndecan expression is up-regulated in response to pro-inflammatory stimuli in various forms of heart disease with fibrosis. Mice lacking syndecan-1 and -4 show reduced activation of pro-fibrotic signaling and increased cardiac rupture upon infarction indicating an important role for these molecules. Whereas the short cytoplasmic tail of syndecans regulates signaling, their extracellular part, substituted with heparan sulfate glycosaminoglycan chains, binds a plethora of extracellular matrix (ECM) molecules involved in fibrosis, e.g., collagens, growth factors, cytokines, and immune cell adhesion proteins. Full-length syndecans induce pro-fibrotic signaling, increasing the expression of collagens, myofibroblast differentiation factors, ECM enzymes, growth factors, and immune cell adhesion molecules, thereby also increasing cardiac stiffness and preventing cardiac rupture. Upon pro-inflammatory stimuli, syndecan ectodomains are enzymatically released from heart cells (syndecan shedding). Shed ectodomains affect the expression of ECM molecules, promoting ECM degradation and cardiac rupture upon myocardial infarction. Blood levels of shed syndecan-1 and -4 ectodomains are associated with hospitalization, mortality, and heart remodeling in patients with heart failure. Improved understanding of syndecans and their modifying enzymes in cardiac fibrosis might contribute to the development of compounds with therapeutic potential, and enzymatically shed syndecan ectodomains might constitute a future prognostic tool for heart diseases with fibrosis. Graphical Abstract Graphical abstract summarizing

  10. Endomyocardial fibrosis in infancy

    Directory of Open Access Journals (Sweden)

    Jatene Marcelo Biscegli

    2003-01-01

    Full Text Available The patient was a 4-month-old infant, who underwent persistent ductus arteriosus interruption with titanium clips at the age of 13 days and, since the age of 2 months, had crises of hypoxia and hypertonicity. After clinical investigation, the presence of pulmonary hypertension was confirmed and left ventricular inflow tract obstruction was suspected. The patient underwent surgical treatment at the age of 4 months, during which right and left ventricular endocardial fibrosis was identified. The fibrosis was resected, but the infant had an unfavorable clinical evolution with significant diastolic restriction and died on the sixth postoperative day. Anatomicopathological and surgical findings suggested endomyocardial fibrosis, although that pathology is very rare at the patient's age.

  11. Stroke prevention in atrial fibrillation

    DEFF Research Database (Denmark)

    Fanaroff, Alexander C; Steffel, Jan; Alexander, John H

    2018-01-01

    of anticoagulation for atrial fibrillation (AF). Observational studies employing RWD are useful for describing how oral anticoagulants are used in clinical practice, but generally cannot be used to make claims regarding comparative treatment effects. Questions regarding treatment effect generally are best answered...

  12. Heart-specific overexpression of (pro)renin receptor induces atrial fibrillation in mice.

    Science.gov (United States)

    Lian, Hong; Wang, Xiaojian; Wang, Juan; Liu, Ning; Zhang, Li; Lu, Yingdong; Yang, Yanmin; Zhang, Lianfeng

    2015-04-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, causing substantial cardiovascular morbidity and mortality. The renin-angiotensin system (RAS) has been shown to be involved in the pathophysiology of AF. The (pro)renin receptor [(p)RR] is the last identified member of RAS. However, the role of (p)RR in AF is still unknown. Circulating levels of (p)RR were determined using an immunosorbent assay in 22 patients with AF (paroxysmal or persistent) and 22 healthy individuals. The plasma levels of (p)RR increased 3.6-fold in AF patients (Patrial flutter since 2 months, then spontaneously converted to atrial fibrillation by 10 months. The atria of the transgenic mice demonstrated significant dilation and fibrosis, and exhibited a high incidence of sudden death. Additionally, the genes of SERCA and HCN4, which are involved in the electrophysiology of AF, were significantly down-regulated and up-regulated respectively in transgenic mice atria. The phosphorylation of Erk1/2 significantly increased in the atria of the transgenic mice, and the activated Erk1/2 was found predominantly in cardiac fibroblasts, suggesting that the transgenic (p)RR gene may induce atrial fibrillation by activation of Erk1/2 in the cardiac fibroblasts of the atria. (p)RR promotes atrial structural and electrical remodeling in vivo, which indicates that (p)RR plays an important role in the pathological development of AF. Copyright © 2015. Published by Elsevier Ireland Ltd.

  13. Characteristics of PR interval as predictor for atrial fibrillation: association with biomarkers and outcomes.

    Science.gov (United States)

    Schumacher, Katja; Dagres, Nikolaos; Hindricks, Gerhard; Husser, Daniela; Bollmann, Andreas; Kornej, Jelena

    2017-10-01

    The PR interval may be considered as a simple and easily obtainable predictor for adverse events, including atrial fibrillation (AF), pacemaker implantation, and mortality. Interestingly, both high and low extremes of the PR duration are associated with AF risk. However, the results regarding PR prolongation as a risk factor for AF are inconsistent. Some studies have analyzed the impact of P duration (as a part of the PR interval) and demonstrated that the P-duration contributes to the length of PR interval and adverse outcomes. The PR prolongation could be considered as a marker for cardiovascular degenerative aging caused by myocardial fibrosis and vascular inflammation. Furthermore, due to PR prolongation chronically raised intra-atrial pressure and consequential neuro-hormonal activation predispose systemic vascular endothelial dysfunction and explain the associations with adverse vascular events. In this review, we discuss the association between biomarkers with PR interval in AF.

  14. Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression.

    Science.gov (United States)

    Law, Becker M P; Wilkinson, Ray; Wang, Xiangju; Kildey, Katrina; Lindner, Mae; Rist, Melissa J; Beagley, Kenneth; Healy, Helen; Kassianos, Andrew J

    2017-07-01

    Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3 - CD56 + ) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry. At a subset level, both the CD56 dim NK cell subset and particularly the CD56 bright NK cell subset were elevated in fibrotic kidney tissue. However, only CD56 bright NK cells significantly correlated with the loss of kidney function. Expression of the tissue-retention and -activation molecule CD69 on CD56 bright NK cells was significantly increased in fibrotic biopsy specimens compared with non-fibrotic kidney tissue, indicative of a pathogenic phenotype. Further flow cytometric phenotyping revealed selective co-expression of activating receptor CD335 (NKp46) and differentiation marker CD117 (c-kit) on CD56 bright NK cells. Multi-color immunofluorescent staining of fibrotic kidney tissue localized the accumulation of NK cells within the tubulointerstitium, with CD56 bright NK cells (NKp46 + CD117 + ) identified as the source of pro-inflammatory cytokine interferon-γ within the NK cell compartment. Thus, activated interferon-γ-producing CD56 bright NK cells are positioned to play a key role in the fibrotic process and progression to chronic kidney disease. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  15. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Khurram, Misbah; Skov, Lone; Rossen, Kristian

    2007-01-01

    Nephrogenic systemic fibrosis (NSF) is a fibrotic disease seen in renal failure patients that may lead to severe physical disability. It has been demonstrated in recent studies that NSF can be caused by some gadolinium-containing MRI contrast agents. In this report we present one of a total of 26...

  16. Effects of postshock atrial pacing on atrial defibrillation outcome in the isolated sheep heart

    NARCIS (Netherlands)

    Skanes, A. C.; Gray, R. A.; Zuur, C. L.; Jalife, J.

    1998-01-01

    BACKGROUND: Failed atrial defibrillation shocks are associated with organization of postshock activity and a substantial postshock electrical quiescence. We investigated the ability of a train of pacing stimuli to capture or locally entrain atrial myocardium during the quiescent period after

  17. Management of atrial fibrillation in the setting of heart failure

    NARCIS (Netherlands)

    Crijns, HJGM; VandenBerg, MP; VanGelder, IC; VanVeldhuisen, DJ

    Heart failure is often complicated by atrial fibrillation. Once atrial fibrillation has started it further enhances heart failure due to uncontrolled rate with shortened filling time and provocation of tachycardiomyopathy. Absent atrial kick and irregularity of the ventricular rhythm also

  18. Angiotensin II increases CTGF expression via MAPKs/TGF-{beta}1/TRAF6 pathway in atrial fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Jun [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Liu, Xu, E-mail: xkliuxu@yahoo.cn [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Wang, Quan-xing, E-mail: shmywqx@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Tan, Hong-wei [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Guo, Meng [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China)

    2012-10-01

    The activation of transforming growth factor-{beta}1(TGF-{beta}1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGF{beta}1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGF{beta}-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-{beta}1/non-Smad signaling pathways. In the present study, we explored the role of TGF-{beta}1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1 {mu}M) provoked the activation of P38 mitogen activated protein kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1 {mu}M) also promoted TGF{beta}1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGF{beta}1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGF{beta}1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis. -- Highlights: Black-Right-Pointing-Pointer MAPKs/TGF{beta}1/TRAF6 participates in AngII-induced CTGF expression in atrial fibroblasts. Black-Right-Pointing-Pointer TGF{beta}1/TRAF6 participates in AngII-induced atrial fibroblasts proliferation. Black-Right-Pointing-Pointer TRAF6 may represent a new target for reversing Ang II-induced atrial fibrosis.

  19. Risk of atrial fibrillation in diabetes mellitus

    DEFF Research Database (Denmark)

    Pallisgaard, Jannik L; Schjerning, Anne-Marie; Lindhardt, Tommi B

    2016-01-01

    AIM: Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients...... with diabetes compared to the background population in Denmark. METHODS AND RESULTS: Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes...... and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background...

  20. Surgical treatment for ectopic atrial tachycardia.

    Science.gov (United States)

    Graffigna, A; Vigano, M; Pagani, F; Salerno, G

    1992-08-01

    Atrial tachycardia is an infrequent but potentially dangerous arrhythmia which often determines cardiac enlargement. Surgical ablation of the arrhythmia is effective and safe, provided a careful atrial mapping is performed and the surgical technique is tailored to the individual focus location. Eight patients underwent surgical ablation of ectopic atrial tachycardia between 1977 and 1990. Different techniques were adopted for each patient according to the anatomical location of the focus and possibly associated arrhythmias. Whenever possible, a closed heart procedure was chosen. In 1 patient a double focal origin was found and treated by separate procedures. In 1 patient with ostium secundum atrial septal defect and atrial flutter, surgical isolation of the right appendage and the ectopic focus was performed. In all patients ectopic atrial tachycardia was ablated with maintenance of the sinoatrial and atrioventricular nodal function as well as internodal conduction. In follow-up up to December 1991, no recurrency was recorded.

  1. Atrial septal stenting - How I do it?

    Directory of Open Access Journals (Sweden)

    Kothandam Sivakumar

    2015-01-01

    Full Text Available A wide atrial communication is important to maintain hemodynamics in certain forms of congenital and acquired heart defects. In comparison to balloon septostomy or blade septostomy, atrial septal stenting provides a controlled, predictable, and long-lasting atrial communication. It often needs a prior Brockenbrough needle septal puncture to obtain a stable stent position. A stent deployed across a previously dilated and stretched oval foramen or tunnel form of oval foramen carries higher risk of embolization. This review provides technical tips to achieve a safe atrial septal stenting. Even though this is a "How to do it article," an initial discussion about the indications for atrial septal stenting is vital as the resultant size of the atrial septal communication should be tailored for each indication.

  2. Digoxin versus placebo, no intervention, or other medical interventions for atrial fibrillation and atrial flutter

    DEFF Research Database (Denmark)

    Sethi, Naqash; Safi, Sanam; Feinberg, Joshua

    2017-01-01

    BACKGROUND: Atrial fibrillation is the most common arrhythmia of the heart with a prevalence of approximately 2% in the western world. Atrial flutter, another arrhythmia, occurs less often with an incidence of approximately 200,000 new patients per year in the USA. Patients with atrial fibrillati...

  3. [Morphological and electrophysiological changes of the heart atria in necropsy patients with atrial fibrillation - a pilot study].

    Science.gov (United States)

    Matějková, Adéla; Steiner, Ivo

    2014-01-01

    Atrial fibrillation (AF), the most common supraventricular tachycardia, has a morphological base, so called remodelation of atrial myocardium, with its abnormal conduction pattern as a consequence. The remodelation regards electrical, contractile, and structural properties. In this pilot study we attempted to find relations between the myocardial morphological (scarring, amyloidosis, left atrial enlargement) and electrophysiological (ECG characteristics of the P-wave) changes in patients with AF. We examined 40 hearts of necropsy patients - 20 with a history of AF and 20 with no history of AF. Grossly, the heart weight and the size of the left atrium (LA) were evaluated. Histologically, 7 standard sites from the atria were examined. In each specimen, the degree of myocardial scarring and of deposition of isolated atrial amyloid (IAA) were assessed. We failed to show any significant difference in the P-wave pattern between patients with and without AF. Morphologically, however, there were several differences - the patients with AF had significantly heavier hearts, larger left atria, more severely scarred myocardium of the LA and the atrial septum, and more severe deposition of IAA in both atria in comparison to the control group of patients with sinus rhythm. The left atrial distribution of both fibrosis and amyloidosis was irregular. In patients with AF the former was most pronounced in the LA ceiling while the latter in the LA anterior wall. The entire series showed more marked amyloidosis in the left than in the right atrium. An interesting finding was the universal absence of IAA in the sinoatrial node. The knowledge of distribution of atrial myocardial structural changes could be utilized by pathologists in taking specimens for histology and also by cardiologists in targeting the radiofrequency ablation therapy.

  4. [Panic disorder and atrial fibrillation].

    Science.gov (United States)

    Olazabal Eizaguirre, N; Chavez, R; González-Torres, M A; Gaviria, M

    2013-10-01

    This paper studies the relationship between atrial fibrillation and panic disorder. There are often doubts on the differential diagnosis in emergency services and general medical settings. Panic disorder prevalence rates have been found to be high in patients suffering from atrial fibrillation. Various studies have observed that patients diagnosed with anxiety disorders frequently have higher cardiovascular disease rates compared to the general population. Usually, patients suffering from panic disorder exhibit somatic complaints suggesting coronary disease, such as chest pain or palpitations. The aim is to make the correct diagnosis and treatment for these different illnesses, and to decrease the costs due to misdiagnosis. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  5. Atrial fibrillation after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Nair Suresh

    2010-01-01

    Full Text Available Once considered as nothing more than a nuisance after cardiac surgery, the importance of postoperative atrial fibrillation (POAF has been realized in the last decade, primarily because of the morbidity associated with the condition. Numerous causative factors have been described without any single factor being singled out as the cause of this complication. POAF has been associated with stroke, renal failure and congestive heart failure, although it is difficult to state whether POAF is directly responsible for these complications. Guidelines have been formulated for prevention of POAF. However, very few cardiothoracic centers follow any form of protocol to prevent POAF. Routine use of prophylaxis would subject all patients to the side effects of anti-arrhythmic drugs, while only a minority of the patients do actually develop this problem postoperatively. Withdrawal of beta blockers in the postoperative period has been implicated as one of the major causes of POAF. Amiodarone, calcium channel blockers and a variety of other pharmacological agents have been used for the prevention of POAF. Atrial pacing is a non-pharmacological measure which has gained popularity in the prevention of POAF. There is considerable controversy regarding whether rate control is superior to rhythm control in the treatment of established atrial fibrillation (AF. Amiodarone plays a central role in both rate control and rhythm control in postoperative AF. Newer drugs like dronedarone and ranazoline are likely to come into the market in the coming years.

  6. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter

    2008-01-01

    PURPOSE OF REVIEW: The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. RECENT FINDINGS: Epidemiological and histochemical studies demonstrated....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...... that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases...

  7. Spatial Relationship of Focal Impulses, Rotors and Low Voltage Zones in Patients With Persistent Atrial Fibrillation.

    Science.gov (United States)

    Schade, Anja; Nentwich, Karin; Costello-Boerrigter, Lisa C; Halbfass, Philipp; Mueller, Patrick; Roos, Markus; Barth, Sebastian; Krug, Joachim; Szoelloesi, Geza-Atilla; Lapp, Harald; Deneke, Thomas

    2016-05-01

    Focal impulses (FI) and rotors are sources associated with the initiation and maintenance of atrial fibrillation (AF). Their ablation results in a lower recurrence rate. The aim of this study was to characterize for the first time the spatial relationship between such sources and atrial low voltage zones (LVZ) representing fibrosis. Twenty-five consecutive patients undergoing their first ablation for persistent AF were included. Voltage mapping of both atria was done during AF. Endocardial mapping of FI and rotors (sources) was performed using a basket catheter and displayed using RhythmView(TM) (Topera Inc.) before ablation. Spatial relationship of LVZ and sources was analyzed. LVZs covered 13 ± 12% of right atrial (RA) endocardial surface and 33 ± 25% of left atrial (LA) endocardial surface. The median number of sources was 1 [1-3] in RA and 3 [1-4] in LA. Of LA sources, 18 (30%) were definitely not associated with LVZs or pulmonary vein (PV) antra. Of RA sources, 32 (84%) were remote from LVZ. During ablation of such sources substantial cycle length (CL) prolongation or AF conversion occurred in 11/23 patients (48%). Altogether, 8/11 (73%) of these pertinent sources were located remotely from LVZ and PV antra. There is a wide discrepancy in distribution of LVZ areas and sites of identified rotors. Site and incidence of FIRM sources appear to be unpredictable with atrial substrate mapping. Further prospective, randomized studies are necessary to elucidate the impact of additional ablation of such sources in patients with persistent or longstanding persistent AF. © 2016 Wiley Periodicals, Inc.

  8. EG-VEGF, BV8, and their receptor expression in human bronchi and their modification in cystic fibrosis: Impact of CFTR mutation (delF508).

    Science.gov (United States)

    Chauvet, Sylvain; Traboulsi, Wael; Thevenon, Laura; Kouadri, Amal; Feige, Jean-Jacques; Camara, Boubou; Alfaidy, Nadia; Benharouga, Mohamed

    2015-08-01

    Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca(2+) and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion. Copyright © 2015 the American Physiological Society.

  9. Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Luciana Santos Cardoso

    2013-01-01

    Full Text Available The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4+CD28+ T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4+ T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8+ T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8+ T cells, CD4+CD25high T cells, and CD4+CTLA-4+ T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4+CD25low cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

  10. Total plasma proANP increases with atrial dilatation in horses

    DEFF Research Database (Denmark)

    Van Der Vekens, N; Hunter, I; Timm, A

    2015-01-01

    ANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample...... stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration...... was significantly (Phorses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; Phorses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation...

  11. Experimental models of liver fibrosis.

    Science.gov (United States)

    Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

  12. Radiation pneumonitis and fibrosis

    International Nuclear Information System (INIS)

    Shopova, V.; Salovsky, P.; Dancheva, V.

    2001-01-01

    The likelihood of toxic pulmonary lesions development as the result of radiation therapy for pulmonary carcinoma and breast cancer is discussed. Two possible forms of radiation induced changes are described, namely: classical radiation pneumonitis (RP) terminating with lung fibrosis circumscribed in the radiation zone, and sporadic RP giving rise to bilateral lymphatic alveolitis and manifestations outside the irradiation field. Attention is called to the fact that chemotherapy augments the risk of toxic lung damage occurrence. A number of markers for early RP diagnosis, including lactate dehydrogenase activity, KL-6, procollagen III, transforming growth factor β, C-reactive protein and partial oxygen pressure are listed. Therapeutic possibilities in coping with RP and pulmonary fibrosis are assayed. Apart from the standard therapeutic approach using corticosteroids and azatioprin, ideas are set forth concerning the application of some antioxidants, angiotensin converting enzyme inhibitors and γ-interferon. It is pointed out that radiation pneumonitis and pulmonary fibrosis treatment has an essential practical bearing on life expectancy and quality of life in a great number of cancer patients. (author)

  13. Radiotherapy of breast fibrosis

    International Nuclear Information System (INIS)

    Heibel, J.H.

    1979-01-01

    In a retrospective study radiotherapy of breast fibrosis in hormone-treated men with histologically confirmed prostate carcinoma was examined. 10 patients had received hormones even before irradiation, 113 obtained hormone administration only after irradiation. The objective size of the glandular body and the overall size of the breast were measured with a special method developed by the author. 46 patients indicated complaints. With hypertrophic mamma and hypertrophic mamilla in 67 examined patients, 127 different symptoms resulted in total. Four patients of the group who had obtained hormones before irradiation, suffered from subjective symptoms. It resulted that radiotherapy of breast fibrosis carried out during hormone treatment is no gynecomastia prophylaxis, that already existent mamma hypertrophies are irreversible, but that existent sensations were notably reduced within 6 months after irradiation therapy. These results indicate the necessity of a radiotherapy of the mamma fibrosis before the hormone treatment is begun. Particularly in cases of higher operative risks, also the possibility of preferring radiotherapy to mastectomy should be fully utilized, in view of adequate or even better therapeutic results. (orig./MG) [de

  14. Changes in plasma atrial natriuretic factor in patients with idiopathic atrial fibrillation

    International Nuclear Information System (INIS)

    Du Tongxin; Xia Xiaojie; Qu Wei; Wang Shukui; Sun Junjiang

    2002-01-01

    To observe the changes in plasma atrial natriuretic factor (AFN) in patients with idiopathic atrial fibrillation and investigate its mechanism, plasma ANF, platelet count and hematocrit were detected in 21 cases with transient idiopathic atrial fibrillation (group A, A1 representing attack, while A2 termination), 28 with persistent idiopathic atrial fibrillation (group B), 27 suffered from rheumatic heart disease with mitral stenosis and persistent atrial fibrillation (group C), 32 with transient supraventricular tachycardia (group D) and 20 normal controls (group E). It was found that the level of ANF was significantly higher in patients with attacking transient idiopathic atrial fibrillation than that in group A2, D and E (P 0.05), while there was significant difference in hematocrit in group A1 compared with group A2, D, E (P < 0.01). It suggested that ANF and hematocrit play an important role in the attack of idiopathic atrial fibrillation

  15. Adeno-associated virus for cystic fibrosis gene therapy

    Directory of Open Access Journals (Sweden)

    S.V. Martini

    2011-11-01

    Full Text Available Gene therapy is an alternative treatment for genetic lung disease, especially monogenic disorders such as cystic fibrosis. Cystic fibrosis is a severe autosomal recessive disease affecting one in 2500 live births in the white population, caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR. The disease is classically characterized by pancreatic enzyme insufficiency, an increased concentration of chloride in sweat, and varying severity of chronic obstructive lung disease. Currently, the greatest challenge for gene therapy is finding an ideal vector to deliver the transgene (CFTR to the affected organ (lung. Adeno-associated virus is the most promising viral vector system for the treatment of respiratory disease because it has natural tropism for airway epithelial cells and does not cause any human disease. This review focuses on the basic properties of adeno-associated virus and its use as a vector for cystic fibrosis gene therapy.

  16. Serum markers of liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne Skovgård; Bay-Jensen, Anne-Christine; Tougas, Gervais

    2010-01-01

    -epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo......, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis....

  17. Calcium signalling silencing in atrial fibrillation.

    Science.gov (United States)

    Greiser, Maura

    2017-06-15

    Subcellular calcium signalling silencing is a novel and distinct cellular and molecular adaptive response to rapid cardiac activation. Calcium signalling silencing develops during short-term sustained rapid atrial activation as seen clinically during paroxysmal atrial fibrillation (AF). It is the first 'anti-arrhythmic' adaptive response in the setting of AF and appears to counteract the maladaptive changes that lead to intracellular Ca 2+ signalling instability and Ca 2+ -based arrhythmogenicity. Calcium signalling silencing results in a failed propagation of the [Ca 2+ ] i signal to the myocyte centre both in patients with AF and in a rabbit model. This adaptive mechanism leads to a substantial reduction in the expression levels of calcium release channels (ryanodine receptors, RyR2) in the sarcoplasmic reticulum, and the frequency of Ca 2+ sparks and arrhythmogenic Ca 2+ waves remains low. Less Ca 2+ release per [Ca 2+ ] i transient, increased fast Ca 2+ buffering strength, shortened action potentials and reduced L-type Ca 2+ current contribute to a substantial reduction of intracellular [Na + ]. These features of Ca 2+ signalling silencing are distinct and in contrast to the changes attributed to Ca 2+ -based arrhythmogenicity. Some features of Ca 2+ signalling silencing prevail in human AF suggesting that the Ca 2+ signalling 'phenotype' in AF is a sum of Ca 2+ stabilizing (Ca 2+ signalling silencing) and Ca 2+ destabilizing (arrhythmogenic unstable Ca 2+ signalling) factors. Calcium signalling silencing is a part of the mechanisms that contribute to the natural progression of AF and may limit the role of Ca 2+ -based arrhythmogenicity after the onset of AF. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  18. [Typical atrial flutter: Diagnosis and therapy].

    Science.gov (United States)

    Thomas, Dierk; Eckardt, Lars; Estner, Heidi L; Kuniss, Malte; Meyer, Christian; Neuberger, Hans-Ruprecht; Sommer, Philipp; Steven, Daniel; Voss, Frederik; Bonnemeier, Hendrik

    2016-03-01

    Typical, cavotricuspid-dependent atrial flutter is the most common atrial macroreentry tachycardia. The incidence of atrial flutter (typical and atypical forms) is age-dependent with 5/100,000 in patients less than 50 years and approximately 600/100,000 in subjects > 80 years of age. Concomitant heart failure or pulmonary disease further increases the risk of typical atrial flutter.Patients with atrial flutter may present with symptoms of palpitations, reduced exercise capacity, chest pain, or dyspnea. The risk of thromboembolism is probably similar to atrial fibrillation; therefore, the same antithrombotic prophylaxis is required in atrial flutter patients. Acutely symptomatic cases may be subjected to cardioversion or pharmacologic rate control to relieve symptoms. Catheter ablation of the cavotricuspid isthmus represents the primary choice in long-term therapy, associated with high procedural success (> 97 %) and low complication rates (0.5 %).This article represents the third part of a manuscript series designed to improve professional education in the field of cardiac electrophysiology. Mechanistic and clinical characteristics as well as management of isthmus-dependent atrial flutter are described in detail. Electrophysiological findings and catheter ablation of the arrhythmia are highlighted.

  19. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    African Journals Online (AJOL)

    ANP) are present in the four regions of the atrial-auricular complex (two atria and two auricles). ANP-immunoreactivity was detected in all granules from the four regions. Ultrastructurally, atrial myocytes show the presence of very electron dense ...

  20. Radiofrequency catheter oblation in atrial flutter

    International Nuclear Information System (INIS)

    Yan Ji; Wang Heping; Xu Jian; Liu Fuyuan; Fan Xizhen; An Chunsheng; Han Xiaoping; Ding Xiaomei; Wang Jiasheng; Gu Tongyuan

    2002-01-01

    Objective: To evaluate the radiofrequency catheter ablation for type I atrial flutter through application of Holo catheter labelling with anatomic imaging localization to ablate the isthmus of IVCTA during complete double-way block. Methods: Eleven cases with type I atrial flutter undergone Holo catheter labelling technique and consecution with conduction time change of coronary venous sinus orifice with-right atrial lower lateral wall pace excitation, were performed with radiofrequency catheter ablation for the isthmus outcoming with complete double-way conduction block. Results: All together 11 cases with 4 of atrial flutter and 7 of sinus rhythm were undergone radiofrequency catheter ablation resulting with double-way conduction block of the isthmus accompanied by prolongation of right atrial conduction time 56.0 ± 2.3 ms and 53.0 ± 4.6 ms respectively. The right atrial excitation appeared to be in clockwise and counter-clockwise of single direction. No recurrence occurred during 3-34 months follow up with only one showing atrial fibrillation. Conclusions: The application of Holo catheter labelling technique with anatomic imaging localization to achieve the double-way conduction block by radiofrequency catheter ablation of TVC-TA isthmus, is a reliable method for treating atrial flutter

  1. Artificial atrial fibrillation in the dog. An artifact?

    NARCIS (Netherlands)

    Strackee, J.; Hoelen, A.J.; Zimmerman, A.N.E.; Meijler, F.L.

    R-R interval sequences during artificial atrial fibrillation in dogs were studied in the same way as in patients in a previous study and compared with results obtained in dogs with spontaneous atrial fibrillation. Artificial atrial fibrillation was effected by right atrial stimulation in three

  2. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

    Science.gov (United States)

    Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

    2016-09-01

    CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

  3. Left Atrial 4D Blood Flow Dynamics and Hemostasis following Electrical Cardioversion of Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Merih Cibis

    2017-12-01

    Full Text Available Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored.Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2–3 h (Time-1 and 4 weeks (Time-2 following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed.Results: From Time-1 to Time-2: Heart rate decreased (61 ± 7 vs. 56 ± 8 bpm, p = 0.01; Maximum change in left atrial volume increased (8 ± 4 vs. 22 ± 15%, p = 0.009; The duration of stasis (68 ± 11 vs. 57 ± 8%, p = 0.002 and the volume of stasis (14 ± 9 vs. 9 ± 7%, p = 0.04 decreased; Thrombin-antithrombin complex (TAT decreased (5.2 ± 3.3 vs. 3.3 ± 2.2 μg/L, p = 0.008. A significant correlation was found between TAT and the volume of stasis (r2 = 0.69, p < 0.001 at Time-1 and between TAT and the duration of stasis (r2 = 0.34, p = 0.04 at Time-2.Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation

  4. Left Atrial 4D Blood Flow Dynamics and Hemostasis following Electrical Cardioversion of Atrial Fibrillation

    Science.gov (United States)

    Cibis, Merih; Lindahl, Tomas L.; Ebbers, Tino; Karlsson, Lars O.; Carlhäll, Carl-Johan

    2017-01-01

    Background: Electrical cardioversion in patients with atrial fibrillation is followed by a transiently impaired atrial mechanical function, termed atrial stunning. During atrial stunning, a retained risk of left atrial thrombus formation exists, which may be attributed to abnormal left atrial blood flow patterns. 4D Flow cardiovascular magnetic resonance (CMR) enables blood flow assessment from the entire three-dimensional atrial volume throughout the cardiac cycle. We sought to investigate left atrial 4D blood flow patterns and hemostasis during left atrial stunning and after left atrial mechanical function was restored. Methods: 4D Flow and morphological CMR data as well as blood samples were collected in fourteen patients at two time-points: 2–3 h (Time-1) and 4 weeks (Time-2) following cardioversion. The volume of blood stasis and duration of blood stasis were calculated. In addition, hemostasis markers were analyzed. Results: From Time-1 to Time-2: Heart rate decreased (61 ± 7 vs. 56 ± 8 bpm, p = 0.01); Maximum change in left atrial volume increased (8 ± 4 vs. 22 ± 15%, p = 0.009); The duration of stasis (68 ± 11 vs. 57 ± 8%, p = 0.002) and the volume of stasis (14 ± 9 vs. 9 ± 7%, p = 0.04) decreased; Thrombin-antithrombin complex (TAT) decreased (5.2 ± 3.3 vs. 3.3 ± 2.2 μg/L, p = 0.008). A significant correlation was found between TAT and the volume of stasis (r2 = 0.69, p < 0.001) at Time-1 and between TAT and the duration of stasis (r2 = 0.34, p = 0.04) at Time-2. Conclusion: In this longitudinal study, left atrial multidimensional blood flow was altered and blood stasis was elevated during left atrial stunning compared to the restored left atrial mechanical function. The coagulability of blood was also elevated during atrial stunning. The association between blood stasis and hypercoagulability proposes that assessment of left atrial 4D flow can add to the pathophysiological understanding of thrombus formation during atrial fibrillation related

  5. Relaxin reduces susceptibility to post-infarct atrial fibrillation in mice due to anti-fibrotic and anti-inflammatory properties

    DEFF Research Database (Denmark)

    Beiert, Thomas; Tiyerili, Vedat; Knappe, Vincent

    2017-01-01

    Background Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial...... infarction (MI). Methods Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps. Results RLX treatment significantly attenuated the increase in AF......-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant...

  6. Isthmus Dependent Atrial Flutter Cycle Length Correlates with Right Atrial Cross-Sectional Area

    Directory of Open Access Journals (Sweden)

    Kousik Krishnan

    2009-05-01

    Full Text Available Background: Right atrial flutter cycle length can prolong in the presence of antiarrhythmic drug therapy. We hypothesized that the cycle length of right atrial isthmus dependent flutter would correlate with right atrial cross-sectional area measurements. Methods: 60 patients who underwent ablation for electrophysiologically proven isthmus dependent right atrial flutter, who were not on Class I or Class III antiarrhythmic drugs and had recent 2-dimensional echocardiographic data comprised the study group. Right atrial length and width were measured in the apical four chamber view. Cross-sectional area was estimated by multiplying the length and width. 35 patients had an atrial flutter rate ≥250 bpm (Normal Flutter Group and 25 patients had an atrial flutter rate < 250 bpm (Slow Flutter Group. Results: Mean atrial flutter rate was 283 bpm in the normal flutter group and 227 bpm in the slow flutter group. Mean atrial flutter cycle length was 213 ms in the Normal Flutter Group and 265 ms in the Slow Flutter Group (p<0.0001. Mean right atrial cross sectional area was 1845 mm2 in the Normal Flutter group and 2378 mm2 in the Slow Flutter Group, (p< 0.0001. Using linear regression, CSA was a significant predictor of cycle length (β =0.014 p = 0.0045. For every 1 mm2 increase in cross-sectional area, cycle length is 0.014 ms longer.Conclusion: In the absence of antiarrhythmic medications, right atrial cross sectional area enlargement correlates with atrial flutter cycle length. These findings provide further evidence that historical rate-related definitions of typical isthmus dependent right atrial are not mechanistically valid.

  7. [Left versus bi-atrial radiofrequency ablation in the treatment of atrial fibrillation].

    Science.gov (United States)

    Wang, Jian-Gang; Meng, Xu; Li, Hui

    2008-11-25

    To evaluate the effectiveness of radiofrequency modified maze operation for the treatment of atrial fibrillation (AF) and compare the results of the left versus bi-atrial procedures. 305 patients of organic heart disease combined with AF, 117 males and 188 females, aged (53 +/- 10), that underwent cardiac valve operation (n = 293) and/or coronary artery bypass graft surgery (n = 14), received concomitant atrial fibrillation, bi-atrial (n = 160) or left atrial (n = 145) with a mean duration of (36 +/- 43) months. Follow-up was conducted for (28 +/- 5) (3 - 42) months. Thirteen patients (4.3%) died postoperatively: 7 died of multisystem and organ failure, 3 of low cardiac output, 1 of rupture of left ventricle, 1 of arrhythmia, and 1 of sudden death. During the follow-up, 1 patient died of heart failure, 1 of encephalorrhagia and 1 of unknown reason in the bi-atrial group. At the end of the procedure 223 patients (73.1%) had sinus rhythm, with a sinus rhythm rate of 66.9% (107/160) in the bi-atrial group, significant lower than that in the left atrial group (80.0%, 116/145, P bi-atrial group was 80.0%, not significantly different from that of the left atrial group (81.9%, P > 0.05). The Kaplan-Meier survival analysis showed there was no significant difference in the AF rhythm rate between these 2 groups (P = 0.33). Logistic regression analysis showed that the left atrial diameter of >/= 80 mm was an independent predictor of AF recurrence. Both the left and bi-atrial procedures are successful in terms of restoring sinus rhythm. Left atrial ablation in severe cases and where the incision of right atrium is not needed is a reasonable choice.

  8. Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

    Science.gov (United States)

    Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

    2018-01-01

    Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

  9. Cetirizine-Induced atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Altuğ Osken

    2016-01-01

    Full Text Available Atrial fibrillation (AF is the most common observed arrhythmia in clinical practice. In the literature, AF events associated with drug induction are available. Cetirizine is a second-generation histamine antagonist used in the treatment of allergies, angioedema, and urticaria. We wish to present an atypical case who took cetirizine medication for relieving symptoms of upper tract respiratory system infection, experienced rapid ventricular response AF and treated successfully. To best of our knowledge, this is the first case of cetirizine-induced AF.

  10. Imaging from cystic fibrosis

    International Nuclear Information System (INIS)

    Schmidt, H.; Posselt, H.G.

    2008-01-01

    Cystic fibrosis (CF) is the most frequent metabolic disorder with autosomal recessive inheritance in the Caucasian population. The gene defect is located on the long arm of chromosome 7. In Germany today, the actual median survival is 37 years. The genetic defect caused by chloride anion disturbances affects multiple body systems but the morbidity and mortality is due to lung disease. The secretion of highly viscous mucus promotes viral and bacterial pulmonary infections leading to airway obstruction and consecutive destruction of the lung parenchyma. This article will review and discuss both the clinical aspects of the disease and the diagnostic methods, referring in particular to new imaging strategies. (orig.)

  11. Role of histone deacetylases(HDACs) in progression and reversal of liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xing; Wu, Xiao-Qin; Xu, Tao; Li, Xiao-Feng; Yang, Yang; Li, Wan-Xia; Huang, Cheng; Meng, Xiao-Ming; Li, Jun, E-mail: lijun@ahmu.edu.cn

    2016-09-01

    Liver fibrosis refers to a reversible wound healing process response to chronic liver injuries. Activation of hepatic stellate cells (HSCs) is closely correlated with the development of liver fibrosis. Histone deacetylases(HDACs) determine the acetylation levels of core histones to modulate expression of genes. To demonstrate the link between HDACs and liver fibrosis, CCl4-induced mouse liver fibrosis model and its spontaneous reversal model were established. Results of the current study demonstrated that deregulation of liver HDACs may involved in the development of liver fibrosis. Among 11 HDACs tested in our study (Class I, II, and IV HDACs), expression of HDAC2 was maximally increased in CCl4-induced fibrotic livers but decreased after spontaneous recovery. Moreover, expression of HDAC2 was elevated in human liver fibrotic tissues. In this regard, the potential role of HDAC2 in liver fibrosis was further evaluated. Our results showed that administration of HSC-T6 cells with transforming growth factor-beta1 (TGF-β1) resulted in an increase of HDAC2 protein expression in dose- and time-dependent manners. Moreover, HDAC2 deficiency inhibited HSC-T6 cell proliferation and activation induced by TGF-β1. More importantly, the present study showed HDAC2 may regulate HSCs activation by suppressing expression of Smad7, which is a negative modulator in HSCs activation and liver fibrosis. Collectively, these observations revealed that HDAC2 may play a pivotal role in HSCs activation and liver fibrosis while deregulation of HDACs may serve as a novel mechanism underlying liver fibrosis. - Highlights: • This is the first report to systematically examine expressions of HDACs during liver fibrosis and fibrosis reversal. • Aberrant expression of HDAC2 contributes to the development of liver fibrosis. • Provided important foundation for further liver fibrosis conversion studies.

  12. Atrial fibrillation and survival in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Justin Timothy A

    2004-11-01

    Full Text Available Abstract Background Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. Patients and methods A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. Results A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test. However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. Conclusion The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.

  13. Idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

    2017-02-23

    Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Nephrogenic systemic fibrosis

    International Nuclear Information System (INIS)

    Samtleben, W.

    2007-01-01

    A scleromyxedema-like disease was recognized in 1997. In 2000 this disorder was first published and termed nephrogenic fibrosing dermopathy because all patients had advanced renal failure. In 2006 it was discovered that the patients had a history of a preceding contrast-enhanced magnetic resonance imaging (MRI). All patients had acute or chronic severe renal insufficiency with a glomerular filtration rate (GFR) 2 . So far a total of about 215 patients with this new skin disorder have been reported to international registries. The skin thickening has a typical histology and begins in the peripheral extremities and progresses proximally, including also the abdominal wall and the head in some patients. NSF involves not only the skin, but also the muscles and other organs (e.g., lungs, heart, eyes) in some patients. Therefore the term nephrogenic systemic fibrosis (NSF) was introduced. Skin fibrosis and sclerosis are usually progressive with disabling contractures of involved joints (knees, hands, feet). NSF may be lethal in up to 28% of patients. Spontaneous remissions are rare. No generally accepted treatment is available. So far, the pathogenesis is not well understood. One hypothesis supposes a role of gadolinium liberated from the contrast agents. As patients with acute or chronic advanced renal failure (GFR 2 ) including those with hepatorenal dysfunctions are at high risk to develop NSF after exposure to gadolinium-based contrast agents, contrast-enhanced MRI should be avoided in this group and alternative diagnostic procedures should be used whenever possible. (orig.) [de

  15. Left Atrial Mechanical Function and Global Strain in Hypertrophic Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Kyung-Jin Kim

    Full Text Available Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM. Although left atrial (LA remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction.Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men. The LA diameter, volume, and mechanical function, including global strain (ε, were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE were evaluated with cardiac magnetic resonance imaging.HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε.HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis by LGE-magnetic resonance

  16. Box Isolation of Fibrotic Areas (BIFA): A Patient-Tailored Substrate Modification Approach for Ablation of Atrial Fibrillation.

    Science.gov (United States)

    Kottkamp, Hans; Berg, Jan; Bender, Roderich; Rieger, Andreas; Schreiber, Doreen

    2016-01-01

    Catheter ablation strategies beyond pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF) are less well defined. Increasing clinical data indicate that atrial fibrosis is a critical common left atrial (LA) substrate in AF patients (pts). We applied a new substrate modification concept according to the individual fibrotic substrate as estimated from electroanatomic voltage mapping (EAVM) in 41 pts undergoing catheter ablation of AF. First, EAVM during sinus rhythm was done in redo cases of 10 pts with paroxysmal AF despite durable PVI. Confluent low-voltage areas (LVA) were found in all pts and were targeted with circumferential isolation, so-called box isolation of fibrotic areas (BIFA). This strategy led to stable sinus rhythm in 9/10 pts and was transferred prospectively to first procedures of 31 pts with nonparoxysmal AF. In 13 pts (42%), no LVA (atrial tachycardia was achieved in 72.2% of pts and in 83.3% of pts with 1.17 procedures/patient. In approximately 40% of pts with nonparoxysmal AF, no substantial LVA were identified, and PVI alone showed high success rate. In pts with paroxysmal AF despite durable PVI and in approximately 60% of pts with nonparoxysmal AF, individually localized LVA were identified and could be targeted successfully with the BIFA strategy. © 2015 Wiley Periodicals, Inc.

  17. The circadian variation of premature atrial contractions

    DEFF Research Database (Denmark)

    Larsen, Bjørn Strøier; Kumarathurai, Preman; Nielsen, Olav W

    2016-01-01

    AIMS: The aim of the study was to assess a possible circadian variation of premature atrial contractions (PACs) in a community-based population and to determine if the daily variation could be used to assess a more vulnerable period of PACs in predicting later incidence of atrial fibrillation (AF...... variation in heart rate. After adjusting for relevant risk factors, the risk of AF was equal in all time intervals throughout the day. CONCLUSION: Premature atrial contractions showed a circadian variation in subjects with frequent PACs. No specific time interval of the day was more predictive of AF than...

  18. Cystic fibrosis: a mucosal immunodeficiency syndrome

    Science.gov (United States)

    Cohen, Taylor Sitarik; Prince, Alice

    2013-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes—airway inflammation and spontaneous infection—may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance. PMID:22481418

  19. Thoracic periaortal fibrosis and Ormond's disease

    International Nuclear Information System (INIS)

    Kacl, G.M.; Bino, M.; Salomon, F.; Risti, B.; Marincek, B.

    1995-01-01

    Two cases of thoracic periaortal fibrosis as a manifestation of retroperitoneal fibrosis (Ormond's disease) are shown on CT and MRI. Thoracic periaortal fibrosis can result in an inflammatory aneurysmo with chronic dissection. Manifestation of thoracic periaortal fibrosis may typically occur intermittently over decades. (orig.) [de

  20. Dynamic approximate entropy electroanatomic maps detect rotors in a simulated atrial fibrillation model.

    Science.gov (United States)

    Ugarte, Juan P; Orozco-Duque, Andrés; Tobón, Catalina; Kremen, Vaclav; Novak, Daniel; Saiz, Javier; Oesterlein, Tobias; Schmitt, Clauss; Luik, Armin; Bustamante, John

    2014-01-01

    There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping.

  1. Dynamic Approximate Entropy Electroanatomic Maps Detect Rotors in a Simulated Atrial Fibrillation Model

    Science.gov (United States)

    Ugarte, Juan P.; Orozco-Duque, Andrés; Tobón, Catalina; Kremen, Vaclav; Novak, Daniel; Saiz, Javier; Oesterlein, Tobias; Schmitt, Clauss; Luik, Armin; Bustamante, John

    2014-01-01

    There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping. PMID:25489858

  2. A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis.

    Science.gov (United States)

    Calès, Paul; Boursier, Jérôme; Oberti, Frédéric; Moal, Valérie; Fouchard Hubert, Isabelle; Bertrais, Sandrine; Hunault, Gilles; Rousselet, Marie Christine

    2018-04-01

    Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeter V2G ) with those of a test targeted for cirrhosis (CirrhoMeter V2G ). In the derivation CHC population, we first compared Multi-FibroMeter V2G to FibroMeter V2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeter V2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeter V2G and FibroMeter V2G were the following: cirrhosis AUROC, 0.906 versus 0.878 ( P fibrosis AUROC, 0.833 versus 0.832 ( P = 0.366). Multi-FibroMeter V2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates

  3. Increasing Prevalence of Atrial Fibrillation and Permanent Atrial Arrhythmias in Congenital Heart Disease.

    Science.gov (United States)

    Labombarda, Fabien; Hamilton, Robert; Shohoudi, Azadeh; Aboulhosn, Jamil; Broberg, Craig S; Chaix, Marie A; Cohen, Scott; Cook, Stephen; Dore, Annie; Fernandes, Susan M; Fournier, Anne; Kay, Joseph; Macle, Laurent; Mondésert, Blandine; Mongeon, François-Pierre; Opotowsky, Alexander R; Proietti, Anna; Rivard, Lena; Ting, Jennifer; Thibault, Bernard; Zaidi, Ali; Khairy, Paul

    2017-08-15

    Atrial arrhythmias are the most common complication encountered in the growing and aging population with congenital heart disease. This study sought to assess the types and patterns of atrial arrhythmias, associated factors, and age-related trends. A multicenter cohort study enrolled 482 patients with congenital heart disease and atrial arrhythmias, age 32.0 ± 18.0 years, 45.2% female, from 12 North American centers. Qualifying arrhythmias were classified by a blinded adjudicating committee. The most common presenting arrhythmia was intra-atrial re-entrant tachycardia (IART) (61.6%), followed by atrial fibrillation (28.8%), and focal atrial tachycardia (9.5%). The proportion of arrhythmias due to IART increased with congenital heart disease complexity from 47.2% to 62.1% to 67.0% in patients with simple, moderate, and complex defects, respectively (p = 0.0013). Atrial fibrillation increased with age to surpass IART as the most common arrhythmia in those ≥50 years of age (51.2% vs. 44.2%; p congenital heart disease, with a predominantly paroxysmal pattern. However, atrial fibrillation increases in prevalence and atrial arrhythmias progressively become permanent as the population ages. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Towards Low Energy Atrial Defibrillation

    Directory of Open Access Journals (Sweden)

    Philip Walsh

    2015-09-01

    Full Text Available A wireless powered implantable atrial defibrillator consisting of a battery driven hand-held radio frequency (RF power transmitter (ex vivo and a passive (battery free implantable power receiver (in vivo that enables measurement of the intracardiac impedance (ICI during internal atrial defibrillation is reported. The architecture is designed to operate in two modes: Cardiac sense mode (power-up, measure the impedance of the cardiac substrate and communicate data to the ex vivo power transmitter and cardiac shock mode (delivery of a synchronised very low tilt rectilinear electrical shock waveform. An initial prototype was implemented and tested. In low-power (sense mode, >5 W was delivered across a 2.5 cm air-skin gap to facilitate measurement of the impedance of the cardiac substrate. In high-power (shock mode, >180 W (delivered as a 12 ms monophasic very-low-tilt-rectilinear (M-VLTR or as a 12 ms biphasic very-low-tilt-rectilinear (B-VLTR chronosymmetric (6ms/6ms amplitude asymmetric (negative phase at 50% magnitude shock was reliably and repeatedly delivered across the same interface; with >47% DC-to-DC (direct current to direct current power transfer efficiency at a switching frequency of 185 kHz achieved. In an initial trial of the RF architecture developed, 30 patients with AF were randomised to therapy with an RF generated M-VLTR or B-VLTR shock using a step-up voltage protocol (50–300 V. Mean energy for successful cardioversion was 8.51 J ± 3.16 J. Subsequent analysis revealed that all patients who cardioverted exhibited a significant decrease in ICI between the first and third shocks (5.00 Ω (SD(σ = 1.62 Ω, p < 0.01 while spectral analysis across frequency also revealed a significant variation in the impedance-amplitude-spectrum-area (IAMSA within the same patient group (|∆(IAMSAS1-IAMSAS3[1 Hz − 20 kHz] = 20.82 Ω-Hz (SD(σ = 10.77 Ω-Hz, p < 0.01; both trends being absent in all patients that failed to cardiovert

  5. Gastrointestinal Manifestations of Cystic Fibrosis

    Science.gov (United States)

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  6. Radiation Fibrosis of the Vocal Fold: From Man to Mouse

    Science.gov (United States)

    Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

    2013-01-01

    Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis. PMID:23242839

  7. Atrial Fibrillation During an Exploration Class Mission

    Science.gov (United States)

    Lipsett, Mark; Hamilton, Douglas; Lemery, Jay; Polk, James

    2011-01-01

    This slide presentation reviews a possible scenario of an astronaut having Atrial Fibrillation during a Mars Mission. In the case review the presentation asks several questions about the alternatives for treatment, medications and the ramifications of the decisions.

  8. Assessment of right atrial function analysis

    International Nuclear Information System (INIS)

    Shohgase, Takashi; Miyamoto, Atsushi; Kanamori, Katsushi; Kobayashi, Takeshi; Yasuda, Hisakazu

    1988-01-01

    To assess the potential utility of right atrial function analysis in cardiac disease, reservoir function, pump function, and right atrial peak emptying rate (RAPER) were compared in 10 normal subjects, 32 patients with coronary artery disease, and 4 patients with primary pulmonary hypertension. Right atrial volume curves were obtained using cardiac radionuclide method with Kr-81m. In normal subjects, reservoir function index was 0.41+-0.05; pump function index was 0.25+-0.05. Both types of patients has decreased reservoir funcion and increased pump function. Pump function tended to decrease with an increase of right ventricular end-diastolic pressure. RAPER correlated well with right ventricular peak filling rate, probably reflecting right ventricular diastolic function. Analysis of right atrial function seemed to be of value in evaluating factors regulating right ventricular contraction and diastolic function, and cardiac output. (Namekawa, K)

  9. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    African Journals Online (AJOL)

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... morphometry and function. Eliane Florencio ... granules is greatest in the right atrium followed by the left atrium and left auricle and right auricle, in this order. ... family: Atrial natriuretic peptide (ANP), Urodilatin, Brain natriuretic ...

  10. Nephrogenic systemic fibrosis.

    LENUS (Irish Health Repository)

    Kennedy, C

    2010-11-05

    Nephroaenic systemic fibrosis (NSF) is a potentiallv fatal dermatiological condition found exclusively in patients with advanced renal I failure. There is minimal literature regarding the epidemiology and outcomes of patients with NSF in Ireland. A retrospective chart review was performed for all patients with NSF in Ireland. Ireland\\'s experience with the disease was examined in light of international reports. There have been three cases of NSF in Ireland; an area which serves 1915 dialysis patients--giving a point prevalence among Irish end-stage kidney disease patients of 0.002. There was a large variation in disease severity between the three patients. All three patients had significant exposure to gadolinium chelate. Caution with gadolinium administration must be exercised in patients with advanced renal failure.

  11. Profile of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mona M. El-Falaki

    2014-09-01

    Full Text Available It was generally believed that Cystic fibrosis (CF is rare among Arabs; however, the few studies available from Egypt and other Arabic countries suggested the presence of many undiagnosed patients. The aim of the present study was to determine the frequency of CF patients out of the referred cases in a single referral hospital in Egypt. A total of 100 patients clinically suspected of having CF were recruited from the CF clinic of the Allergy and Pulmonology Unit, Children’s Hospital, Cairo University, Egypt, throughout a 2 year period. Sweat chloride testing was done for all patients using the Wescor macroduct system for collection of sweat. Quantitative analysis for chloride was then done by the thiocyanate colorimetric method. Patients positive for sweat chloride (⩾60 mmol/L were tested for the ΔF508 mutation using primer specific PCR for cystic fibrosis transmembrane conductance regulator (CFTR gene. Thirty-six patients (36% had a positive sweat chloride test. The main clinical presentations in patients were chronic cough in 32 (88.9%, failure to thrive in 27 (75%, steatorrhea in 24 (66.7%, and hepatobiliary involvement in 5 (13.9%. Positive consanguinity was reported in 50% of CF patients. Thirty-two patients were screened for ΔF508 mutation. Positive ΔF508 mutation was detected in 22 (68.8% patients, 8 (25% were homozygous, 14 (43.8% were heterozygous, and 10 (31.3% tested were negative. CF was diagnosed in more than third of patients suspected of having the disease on clinical grounds. This high frequency of CF among referred patients indicates that a high index of suspicion and an increasing availability of diagnostic tests lead to the identification of a higher number of affected individuals.

  12. Radiotherapy and pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Sone, S; Miyata, Y; Tachiiri, H [Osaka Univ. (Japan). Faculty of Medicine

    1975-04-01

    Clinical findings of radiation pneumonitis and pulmonary fibrosis were outlined, and the relationship between occurence of these disorders and radiotherapy, clinical findings and X-ray picture were studied. Standard radiation dose as cell lethal response of carcinoma of the lung were 4,500 to 5,500 rad in 4 to 5.5 weeks in undifferentiated carcinoma, 6,000 to 7,000 rad in 6 to 7 weeks in squamous cell carcinoma, 7,000 to 9,000 rad in 7 to 9 weeks in adenocarcinoma, 4,500 to 5,000 rad in 4 to 5 weeks in the large sized cancer of the esophagus, 6,500 to 7,000 rad in 5 to 7 weeks in the small sized cancer of the esophagus, and irradiation of these amount of dose caused hazards in pulmonary function. Pathological and clinical findings of pulmonary hazards within 6 month period after irradiation, factors causing them and changes in X-ray pictures before and after irradiation were observed and discussed in clinical cases: the case of breast cancer in which 3,000 R/6 times/18 days of 5.5 MeV Liniac electron was irradiated to the chest wall, and the case of pulmonary cancer in which 5,000 rad/25 times/34 days of 6 MeV Liniac X-ray was irradiated in opposite 2 ports radiation beam treatment. The former revealed alveolar lesion and interlobular pleuritis at 4 month later, and remarkable lesion of pulmonary fibrosis was followed at 9 month after radiotherapy. The later developed radiation pneumonitis 1 month after radiotherapy, of which lesion extended to the upper part by 3 months later, and cancer recurred 6.5 month later.

  13. Psychosomatic correlations in atrial fibrillations

    Directory of Open Access Journals (Sweden)

    Vladimir Ernstovich Medvedev

    2011-01-01

    Full Text Available Patients with atrial fibrillations (AF and comorbid mental disorders were examined. Two patient groups differing in the structure of psychosomatic ratios were identified. Group 1 comprised patients with AF and signs of reactivity lability that manifested itself as psychopathological reactions to the primary manifestations of AF; Group 2 included those who had developed mental disorders mainly in end-stage cardiovascular disease (predominantly a permanent form of AF in the presence of such events as chronic heart failure (CHF. The results of the study suggest that the patients with AF have frequently anxiety and hypochondriacal disorders, which agrees with the data available in the literature. In addition, end-stage AF is marked by depressive syndromes caused by the severe course of cardiovascular diseases resulting in CHF.

  14. Relaxin reduces susceptibility to post-infarct atrial fibrillation in mice due to anti-fibrotic and anti-inflammatory properties.

    Science.gov (United States)

    Beiert, Thomas; Tiyerili, Vedat; Knappe, Vincent; Effelsberg, Verena; Linhart, Markus; Stöckigt, Florian; Klein, Sabine; Schierwagen, Robert; Trebicka, Jonel; Nickenig, Georg; Schrickel, Jan W; Andrié, René P

    2017-08-26

    Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps. RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups. Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Inhibition of small-conductance Ca2+-activated K+ channels terminates and protects against atrial fibrillation

    DEFF Research Database (Denmark)

    Diness, Jonas Goldin; Sørensen, Ulrik S; Nissen, Jakob Dahl

    2010-01-01

    Recently, evidence has emerged that small-conductance Ca(2+)-activated K(+) (SK) channels are predominantly expressed in the atria in a number of species including human. In rat, guinea pig, and rabbit ex vivo and in vivo models of atrial fibrillation (AF), we used 3 different SK channel inhibito...

  16. Gene therapy in cystic fibrosis.

    Science.gov (United States)

    Flotte, T R; Laube, B L

    2001-09-01

    Theoretically, cystic fibrosis transmembrane conductance regulator (CFTR) gene replacement during the neonatal period can decrease morbidity and mortality from cystic fibrosis (CF). In vivo gene transfers have been accomplished in CF patients. Choice of vector, mode of delivery to airways, translocation of genetic information, and sufficient expression level of the normalized CFTR gene are issues that currently are being addressed in the field. The advantages and limitations of viral vectors are a function of the parent virus. Viral vectors used in this setting include adenovirus (Ad) and adeno-associated virus (AAV). Initial studies with Ad vectors resulted in a vector that was efficient for gene transfer with dose-limiting inflammatory effects due to the large amount of viral protein delivered. The next generation of Ad vectors, with more viral coding sequence deletions, has a longer duration of activity and elicits a lesser degree of cell-mediated immunity in mice. A more recent generation of Ad vectors has no viral genes remaining. Despite these changes, the problem of humoral immunity remains with Ad vectors. A variety of strategies such as vector systems requiring single, or widely spaced, administrations, pharmacologic immunosuppression at administration, creation of a stealth vector, modification of immunogenic epitopes, or tolerance induction are being considered to circumvent humoral immunity. AAV vectors have been studied in animal and human models. They do not appear to induce inflammatory changes over a wide range of doses. The level of CFTR messenger RNA expression is difficult to ascertain with AAV vectors since the small size of the vector relative to the CFTR gene leaves no space for vector-specific sequences on which to base assays to distinguish endogenous from vector-expressed messenger RNA. In general, AAV vectors appear to be safe and have superior duration profiles. Cationic liposomes are lipid-DNA complexes. These vectors generally have been

  17. Red Wine, Resveratrol and Atrial Fibrillation

    Science.gov (United States)

    Garavaglia, Juliano; Marcadenti, Aline

    2017-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF. PMID:29084143

  18. Red Wine, Resveratrol and Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Laura Siga Stephan

    2017-10-01

    Full Text Available Atrial fibrillation (AF is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF.

  19. Red Wine, Resveratrol and Atrial Fibrillation.

    Science.gov (United States)

    Stephan, Laura Siga; Almeida, Eduardo Dytz; Markoski, Melissa Medeiros; Garavaglia, Juliano; Marcadenti, Aline

    2017-10-30

    Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF.

  20. RR-Interval variance of electrocardiogram for atrial fibrillation detection

    Science.gov (United States)

    Nuryani, N.; Solikhah, M.; Nugoho, A. S.; Afdala, A.; Anzihory, E.

    2016-11-01

    Atrial fibrillation is a serious heart problem originated from the upper chamber of the heart. The common indication of atrial fibrillation is irregularity of R peak-to-R-peak time interval, which is shortly called RR interval. The irregularity could be represented using variance or spread of RR interval. This article presents a system to detect atrial fibrillation using variances. Using clinical data of patients with atrial fibrillation attack, it is shown that the variance of electrocardiographic RR interval are higher during atrial fibrillation, compared to the normal one. Utilizing a simple detection technique and variances of RR intervals, we find a good performance of atrial fibrillation detection.

  1. Clinical Meaning of Ascites in Patients with Endomyocardial Fibrosis

    Directory of Open Access Journals (Sweden)

    Barretto Antonio Carlos Pereira

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate the clinical meaning of ascites and the main features of patients with ascites and endomyocardial fibrosis. METHODS: We studied 166 patients with endomyocardial fibrosis (mean age 37 years, 114 women treated over the last 20 years. Ventriculography findings, surgery or necropsy confirmed the diagnosis in all patients. Most patients belonged to New York Heart Association Functional Class III/IV (134, 83.7%. Eighty-one (50.6% had biventricular, 28 (17.5% had right ventricular, and 51 (31.8% had left ventricular involvement. During follow-up, 56 patients died. RESULTS: Ascites was present in 67 (41.8% patients, and right ventricular involvement was present in 59 (88%. In the comparison between patients with or without ascites, those with ascites had higher mortality (49.2% and 24.7%, respectively. Patients with ascites had a higher incidence of edema (95% vs. 43%, hepatomegaly (5.8cm vs. 4.1cm, mean right atrium pressure (19.3 vs. 12mmHg, and final right ventricle diastolic pressure (18.7 vs. 12.9mmHg. Also, patients with ascites had a longer history of illness (5.1 and 3.9 years, respectively and had atrial fibrillation more frequently (44.7% vs. 30.1%. CONCLUSION: Ascites was observed in less than 50% of cases of endomyocardial fibrosis and was associated with greater involvement of the right ventricle and with a longer duration of the disease, thus being a characteristic of a worse prognosis.

  2. Atorvastatin can ameliorate left atrial stunning induced by radiofrequency ablation for atrial fibrillation.

    Science.gov (United States)

    Xie, Ruiqin; Yang, Yingtao; Cui, Wei; Yin, Hongning; Zheng, Hongmei; Zhang, Jidong; You, Ling

    2017-09-01

    The objective of this study was to study the functional changes of the left atrium after radiofrequency ablation treatment for atrial fibrillation and the therapeutic effect of atorvastatin. Fifty-eight patients undergoing radiofrequency ablation for atrial fibrillation were randomly divided into non-atorvastatin group and atorvastatin group. Patients in the atorvastatin group were treated with atorvastatin 20 mg p.o. per night in addition to the conventional treatment of atrial fibrillation; patients in the non-atorvastatin group received conventional treatment of atrial fibrillation only. Echocardiography was performed before radiofrequency ablation operation and 1 week, 2 weeks, 3 weeks, and 4 weeks after operation. Two-dimensional ultrasound speckle tracking imaging system was used to measure the structural indexes of the left atrium. Results indicated that there was no significant change for indexes representing the structural status of the left atrium within a month after radiofrequency ablation (P > 0.05); however, there were significant changes for indexes representing the functional status of the left atrium. There were also significant changes in indexes reflecting left atrial strain status: the S and SRs of atorvastatin group were higher than those of non-atorvastatin group (P atorvastatin could improve left atrial function and shorten the duration of atrial stunning after radiofrequency ablation of atrial fibrillation.

  3. Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs

    NARCIS (Netherlands)

    Shiroshita-Takeshita, A; Brundel, BJJM; Lavoie, J; Nattel, S

    2006-01-01

    Background: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and calcineurin-inhibitory drugs on promotion of atrial fibrillation by

  4. Incisional left atrial isolation for ablation of atrial fibrillation in mitral valve surgery.

    Science.gov (United States)

    Graffigna, Angelo; Branzoli, Stefano; Sinelli, Stefano; Vigano, Mario

    2009-01-01

    The renewed interest in surgical techniques for atrial fibrillation (AF) limited to the left atrium has risen the importance of the original technique of left atrial isolation by means of surgical incision. Transmurality of lesions and cost containment are strong elements to be appreciated in this technique.

  5. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    Because cardiovascular disease remains a serious problem in modern human society, the aim of this study was to establish the rat model animal and to compare the heart dysfunction and fibrosis with SD and LE rats when treated with myocardial ischemia and reperfusion operation. A 20-minute thoracotomy was performed ...

  6. Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial fibrillation investigators

    DEFF Research Database (Denmark)

    van Walraven, Carl; Hart, Robert G; Connolly, Stuart

    2009-01-01

    contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure......BACKGROUND AND PURPOSE: Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age...... on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation. METHODS: This is an analysis of the Atrial Fibrillation Investigators database, which...

  7. Microbial ecology and adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Yang, Lei; Jelsbak, Lars; Molin, Søren

    2011-01-01

    Chronic infections in the respiratory tracts of cystic fibrosis (CF) patients are important to investigate, both from medical and from fundamental ecological points of view. Cystic fibrosis respiratory tracts can be described as natural environments harbouring persisting microbial communities...... constitute the selective forces that drive the evolution of the microbes after they migrate from the outer environment to human airways. Pseudomonas aeruginosa adapts to the new environment through genetic changes and exhibits a special lifestyle in chronic CF airways. Understanding the persistent...... colonization of microbial pathogens in CF patients in the context of ecology and evolution will expand our knowledge of the pathogenesis of chronic infections and improve therapeutic strategies....

  8. Cystic fibrosis genetics: from molecular understanding to clinical application

    Science.gov (United States)

    Cutting, Garry R.

    2015-01-01

    The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethalautosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the d iscove1y of the disease-causing gene. PMID:25404111

  9. Anterior uveitis and congenital fibrosis of the extraocular muscles in a patient with Noonan syndrome

    Directory of Open Access Journals (Sweden)

    Elgohary Mostafa

    2005-01-01

    Full Text Available We describe a patient with Noonan syndrome who presented with Human Leukocyte Antigen B27-associated recurrent acute anterior uveitis and manifestations of congenital fibrosis of the extraocular muscles, which has not been reported before.

  10. Applying non-linear dynamics to atrial appendage flow data to understand and characterize atrial arrhythmia

    International Nuclear Information System (INIS)

    Chandra, S.; Grimm, R.A.; Katz, R.; Thomas, J.D.

    1996-01-01

    The aim of this study was to better understand and characterize left atrial appendage flow in atrial fibrillation. Atrial fibrillation and flutter are the most common cardiac arrhythmias affecting 15% of the older population. The pulsed Doppler velocity profile data was recorded from the left atrial appendage of patients using transesophageal echocardiography. The data was analyzed using Fourier analysis and nonlinear dynamical tools. Fourier analysis showed that appendage mechanical frequency (f f ) for patients in sinus rhythm was always lower (around1 Hz) than that in atrial fibrillation (5-8 Hz). Among patients with atrial fibrillation spectral power below f f was significantly different suggesting variability within this group of patients. Results that suggested the presence of nonlinear dynamics were: a) the existence of two arbitrary peak frequencies f 1 , f 2 , and other peak frequencies as linear combinations thereof (mf 1 ±nf 2 ), and b) the similarity between the spectrum of patient data and that obtained using the Lorenz equation. Nonlinear analysis tools, including Phase plots and differential radial plots, were also generated from the velocity data using a delay of 10. In the phase plots, some patients displayed a torus-like structure, while others had a more random-like pattern. In the differential radial plots, the first set of patients (with torus-like phase plots) showed fewer values crossing an arbitrary threshold of 10 than did the second set (8 vs. 27 in one typical example). The outcome of cardioversion was different for these two set of patients. Fourier analysis helped to: differentiate between sinus rhythm and atrial fibrillation, understand the characteristics of the wide range of atrial fibrillation patients, and provide hints that atrial fibrillation could be a nonlinear process. Nonlinear dynamical tools helped to further characterize and sub-classify atrial fibrillation

  11. Idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Noble Paul W

    2008-03-01

    Full Text Available Abstract Idiopathic pulmonary fibrosis (IPF is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000 than in women (13.2/100,000. The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock. IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP. The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis, forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational exposures. IPF is typically progressive and leads to significant

  12. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

    Directory of Open Access Journals (Sweden)

    Claudio M. Mastroianni

    2014-05-01

    Full Text Available Chronic hepatitis C virus (HCV infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV. Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

  13. Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Minrui Liang

    2013-01-01

    Full Text Available Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL- 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM- induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis.

  14. A new model of progressive pulmonary fibrosis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. (Univ. of California, Davis (United States))

    1993-08-01

    Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

  15. Areca nut and its role in oral submucous fibrosis.

    Science.gov (United States)

    Prabhu, Rachana V; Prabhu, Vishnudas; Chatra, Laxmikanth; Shenai, Prashant; Suvarna, Nithin; Dandekeri, Savita

    2014-12-01

    Areca nut, commonly called as betel nut or supari, is a fruit of areca catechu palm tree, which is native of South Asia and Pacific Islands. The seed or endosperm is consumed fresh, boiled or after sun drying or curing. Chewing areca nut is thought to have central nervous system stimulating effect and along with this it is known to have salivary stimulating and digestive properties. According to the traditional Ayurvedic medicine, chewing areca nut and betel leaf is a good remedy against halitosis. It is also used for its deworming property. Along with these beneficial effects of areca nut one of its most harmful effects on the human body in general and oral cavity in particular is the development of potentially malignant disorder called Oral Submucous Fibrosis. The present paper discusses in detail the effects of the components of areca nut on pathogenesis of Oral Submucous Fibrosis. Key words:Areca nut, oral submucous fibrosis, potentially malignant disorder, supari.

  16. Understanding the Process of Fibrosis in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Yacine Kharraz

    2014-01-01

    Full Text Available Fibrosis is the aberrant deposition of extracellular matrix (ECM components during tissue healing leading to loss of its architecture and function. Fibrotic diseases are often associated with chronic pathologies and occur in a large variety of vital organs and tissues, including skeletal muscle. In human muscle, fibrosis is most readily associated with the severe muscle wasting disorder Duchenne muscular dystrophy (DMD, caused by loss of dystrophin gene function. In DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells and the functions of the muscle stem cells (satellite cells become impeded and fibrogenic cells hyperproliferate and are overactivated, leading to the substitution of skeletal muscle with nonfunctional fibrotic tissue. Here, we review new developments in our understanding of the mechanisms leading to fibrosis in DMD and several recent advances towards reverting it, as potential treatments to attenuate disease progression.

  17. Breakdown in Breathing: The Complexities of Cystic Fibrosis

    Science.gov (United States)

    ... Healthier Lungs in Kids Wise Choices Living with Cystic Fibrosis In between checkups, practice good self-care and ... Links What Is Cystic Fibrosis? Learning About Cystic Fibrosis NIH Cystic Fibrosis Fact Sheet Genetic and Rare Diseases Information ...

  18. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    BACKGROUND: Refractoriness of cardiac cells limits maximum frequency of electrical activity and protects the heart from tonic contractions. Short refractory periods support major arrhythmogenic substrates and augmentation of refractoriness is therefore seen as a main mechanism of antiarrhythmic...... drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...

  19. Atrial tachyarrhythmia in adult congenital heart disease

    Science.gov (United States)

    Karbassi, Arsha; Nair, Krishnakumar; Harris, Louise; Wald, Rachel M; Roche, S Lucy

    2017-01-01

    The adult congenital heart disease (ACHD) population continues to grow and most cardiologists, emergency room physicians and family doctors will intermittently come into contact with these patients. Oftentimes this may be in the setting of a presentation with atrial tachyarrhythmia; one of the commonest late complications of ACHD and problem with potentially serious implications. Providing appropriate initial care and ongoing management of atrial tachyarrhythmia in ACHD patients requires a degree of specialist knowledge and an awareness of certain key issues. In ACHD, atrial tachyarrhythmia is usually related to the abnormal anatomy of the underlying heart defect and often occurs as a result of surgical scar or a consequence of residual hemodynamic or electrical disturbances. Arrhythmias significantly increase mortality and morbidity in ACHD and are the most frequent reason for ACHD hospitalization. Intra-atrial reentrant tachycardia and atrial fibrillation are the most prevalent type of arrhythmia in this patient group. In hemodynamically unstable patients, urgent cardioversion is required. Acute management of the stable patient includes anticoagulation, rate control, and electrical or pharmacological cardioversion. In ACHD, rhythm control is the preferred management strategy and can often be achieved. However, in the long-term, medication side-effects can prove problematic. Electrophysiology studies and catheter ablation are important treatments modalities and in certain cases, surgical or percutaneous treatment of the underlying cardiac defect has a role. ACHD patients, especially those with complex CHD, are at increased risk of thromboembolic events and anticoagulation is usually required. Female ACHD patients of child bearing age may wish to pursue pregnancies. The risk of atrial arrhythmias is increased during pregnancy and management of atrial tachyarrhythmia during pregnancy needs specific consideration. PMID:28706585

  20. Spectral of electrocardiographic RR intervals to indicate atrial fibrillation

    Science.gov (United States)

    Nuryani, Nuryani; Satrio Nugroho, Anto

    2017-11-01

    Atrial fibrillation is a serious heart diseases, which is associated on the risk of death, and thus an early detection of atrial fibrillation is necessary. We have investigated spectral pattern of electrocardiogram in relation to atrial fibrillation. The utilized feature of electrocardiogram is RR interval. RR interval is the time interval between a two-consecutive R peaks. A series of RR intervals in a time segment is converted to a signal with a frequency domain. The frequency components are investigated to find the components which significantly associate to atrial fibrillation. A segment is defined as atrial fibrillation or normal segments by considering a defined number of atrial fibrillation RR in the segment. Using clinical data of 23 patients with atrial fibrillation, we find that the frequency components could be used to indicate atrial fibrillation.

  1. Risk of atrial fibrillation and stroke in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Lindhardsen, Jesper; Ahlehoff, Ole; Gislason, Gunnar Hilmar

    2012-01-01

    To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke.......To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke....

  2. Treatment Guidelines of Atrial Fibrillation (AFib or AF)

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Treatment Guidelines of Atrial Fibrillation (AFib or AF) Updated:Jun 28,2017 What are the treatment guidelines for atrial fibrillation? Medical guidelines are written by ...

  3. Impact of stepwise ablation on the biatrial substrate in patients with persistent atrial fibrillation and heart failure.

    Science.gov (United States)

    Jones, David G; Haldar, Shouvik K; Jarman, Julian W E; Johar, Sofian; Hussain, Wajid; Markides, Vias; Wong, Tom

    2013-08-01

    Ablation of persistent atrial fibrillation can be challenging, often involving not only pulmonary vein isolation (PVI) but also additional linear lesions and ablation of complex fractionated electrograms (CFE). We examined the impact of stepwise ablation on a human model of advanced atrial substrate of persistent atrial fibrillation in heart failure. In 30 patients with persistent atrial fibrillation and left ventricular ejection fraction ≤35%, high-density CFE maps were recorded biatrially at baseline, in the left atrium (LA) after PVI and linear lesions (roof and mitral isthmus), and biatrially after LA CFE ablation. Surface area of CFE (mean cycle length ≤120 ms) remote to PVI and linear lesions, defined as CFE area, was reduced after PVI (18.3±12.03 to 10.2±7.1 cm(2); Patrial CFE area was reduced by LA ablation, from 25.9±14.1 to 12.9±11.8 cm(2) (Patrial CFE area. Reduction of CFE area at sites remote from ablation would suggest either regression of the advanced atrial substrate or that these CFE were functional phenomena. Nevertheless, in an advanced atrial fibrillation substrate, linear lesions after PVI diminished the target area for CFE ablation, and complete lesions resulted in a favorable clinical outcome.

  4. Rising rates of hospital admissions for atrial fibrillation

    DEFF Research Database (Denmark)

    Friberg, Jens; Buch, Nina Pernille Gardshodn; Scharling, Henrik

    2003-01-01

    Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study).......Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study)....

  5. Giant right atrial myxoma: characterization with cardiac magnetic resonance imaging.

    LENUS (Irish Health Repository)

    Ridge, Carole A

    2012-02-01

    A 53-year-old woman presented to the emergency department with a 2-week history of dyspnoea and chest pain. Computed tomography pulmonary angiography was performed to exclude acute pulmonary embolism (PE). This demonstrated a large right atrial mass and no evidence of PE. Transthoracic echocardiography followed by cardiac magnetic resonance imaging confirmed a mobile right atrial mass. Surgical resection was then performed confirming a giant right atrial myxoma. We describe the typical clinical, radiologic, and pathologic features of right atrial myxoma.

  6. Electrical remodeling and atrial dilation during atrial tachycardia are influenced by ventricular rate : Role of developing tachycardiomyopathy

    NARCIS (Netherlands)

    Schoonderwoerd, BA; Van Gelder, IC; Van Veldhuisen, DJ; Tieleman, RG; Grandjean, JG; Bel, KJ; Allessie, MA; Crijns, HJGM

    2001-01-01

    Atrial Remodeling in Tachycardiomyopathy. Introduction: Atrial fibrillation (AF) and congestive heart failure (CHF) are two clinical entities that often coincide. Our aim was to establish the influence of concomitant high ventricular rate and consequent development of CHF on electrical remodeling

  7. Ventricular myocarditis coincides with atrial myocarditis in patients

    NARCIS (Netherlands)

    Begieneman, Mark P. V.; Emmens, Reindert W.; Rijvers, Liza; Kubat, Bela; Paulus, Walter J.; Vonk, Alexander B. A.; Rozendaal, Lawrence; Biesbroek, P. Stefan; Wouters, Diana; Zeerleder, Sacha; van Ham, Marieke; Heymans, Stephane; van Rossum, Albert C.; Niessen, Hans W. M.; Krijnen, Paul A. J.

    2016-01-01

    Atrial fibrillation (AF) is a common complication in myocarditis. Atrial inflammation has been suggested to play an important role in the pathophysiology of AF. However, little is known about the occurrence of atrial inflammation in myocarditis patients. Here, we analyzed inflammatory cell numbers

  8. Atrial electromechanical delay in patients undergoing heart transplantation

    Directory of Open Access Journals (Sweden)

    Mustafa Bulut, MD

    2017-04-01

    Conclusion: Inter-AEMD and intra-AEMD were prolonged in patients who underwent heart transplantation as compared to a control population. This may explain the increased atrial fibrillation and other atrial arrhythmia incidences associated with the biatrial anastomosis heart transplantation technique and may contribute to the treatment of atrial fibrillation in this special patient group.

  9. Therapy of experimental NASH and fibrosis with galectin inhibitors.

    Directory of Open Access Journals (Sweden)

    Peter G Traber

    GR-MD-02. The results, in combination with previous experiments in toxin-induced fibrosis, suggest that these galectin-targeting drugs may have potential in human NASH with fibrosis.

  10. A Therapeutic Challenge: Management of Atrial Thrombus

    Directory of Open Access Journals (Sweden)

    Serkan Burc Deser

    2016-09-01

    Full Text Available Introduction: Primary cause of atrial thrombi include atrial fibrillation, foreign bodies inside the atrium such as catheters and pacemaker leads, emboli of deep venous thrombus and primary or metastatic tumors of the heart. We review the clinical features, epidemiology, diagnosis and treatment of nine intriguing cases with atrial thrombus. Methods: This is a retrospective study of nine patients (seven female (78%, two male (33% who were diagnosed with atrial thrombi (average age of 50 ± 12 years and were treated at the Ondokuz Mayis University, Department of Cardiovascular Surgery from February 2014 to January 2015. Among them, six patients had atrial fibrillation (one male, five female, seven patients were suffering from dispne and orthopnoea, five patients were suffering from leg swelling, seven patients had a history of hypertension and three patients had a history of mitral valve replacement surgery. Results: All patients underwent surgery except one. Four patients recovered uneventfully and discharged with oral anticoagulation (warfarin therapy (adjusted to maintain an international normalized ratio of INR between two and three times. Five of nine patients (55% died after surgery. Conclusion: The response to the thrombolytic therapy is poor, mostly ineffective and unsafe so it is often recommended as a bridge to surgery. In patients diagnosed with mechanical mitral valve thrombosis, medical therapy has the possibility of end organ emboli and also fail to resolve the organised thrombus on the stuck valve. On the other hand surgery does not always give satisfactory results. J Clin Exp Invest 2016; 7(4: 278-282

  11. Atrial antitachycardia pacing and atrial remodeling: A substudy of the international, randomized MINERVA trial.

    Science.gov (United States)

    Boriani, Giuseppe; Tukkie, Raymond; Biffi, Mauro; Mont, Lluis; Ricci, Renato; Pürerfellner, Helmut; Botto, Giovanni Luca; Manolis, Antonis S; Landolina, Maurizio; Gulizia, Michele; Hudnall, J Harrison; Mangoni, Lorenza; Grammatico, Andrea; Padeletti, Luigi

    2017-10-01

    Atrial tachycardia (AT) and atrial fibrillation (AF) are common in pacemaker patients and are associated with bad prognoses. The purpose of this study was to evaluate atrial antitachycardia pacing impact on AT/AF-induced atrial remodeling, measured by early recurrence of AT/AF (ERAF) and by change in left atrial diameter (LAD), and to evaluate the impact of AT/AF duration on ERAF incidence. Pacemaker patients were randomized to dual-chamber pacing (Control DDDR: 385 patients), managed ventricular pacing (MVP: 398 patients), or atrial antitachycardia pacing plus MVP (DDDRP+MVP: 383 patients). LAD change, estimated by echocardiography, was considered significant if the relative difference between baseline and 24-month measurements was >10%. At median follow-up of 34 months, ERAF incidence was significantly lower in the DDDRP+MVP arm for all AT/AF durations, in particular, ERAF followed AT/AF longer than 3 hours in 53% cases in Control DDDR, in 51% cases in MVP, and in 39% cases in DDDRP+MVP (P MVP, and 70% in DDDRP+MVP (P MVP, DDDRP+MVP reduces ERAF and favors LAD reduction, suggesting that atrial antitachycardia pacing may reverse electrical and mechanical remodeling. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  12. Inactivated Orf virus (Parapoxvirus ovis) elicits antifibrotic activity in models of liver fibrosis.

    Science.gov (United States)

    Nowatzky, Janina; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Limmer, Andreas; Knolle, Percy; Weber, Olaf

    2013-05-01

    Inactivated Orf virus (ORFV, Parapoxvirus ovis) demonstrates strong antiviral activity in animal models including a human hepatitis B virus (HBV)-transgenic mouse. In addition, expression of interferon (IFN)-γ and interleukin-10 (IL-10) was induced after administration of inactivated ORFV in these mice. IFN-γ and IL-10 are known to elicit antifibrotic activity. We therefore aimed to study antifibrotic activity of inactivated ORFV in models of liver fibrosis. We characterized ORFV-induced hepatic cytokine expression in rats. We then studied ORFV in two models of liver fibrosis in rats, pig serum-induced liver fibrosis and carbon tetrachloride (CCL4 )-induced liver fibrosis. ORFV induced hepatic expression of IFN-γ and IL-10 in rats. ORFV mediated antifibrotic activity when administrated concomitantly with the fibrosis-inducing agents in both models of liver fibrosis. Importantly, when CCL4 -induced liver fibrosis was already established, ORFV application still showed significant antifibrotic activity. In addition, we were able to demonstrate a direct antifibrotic effect of ORFV on stellate cells. These results establish a potential novel antifibrotic therapeutic approach that not only prevents but also resolves established liver fibrosis. Further studies are required to unravel the details of the mechanisms involved. © 2012 The Japan Society of Hepatology.

  13. Left atrial size and function as predictors of new-onset of atrial fibrillation in patients with asymptomatic aortic stenosis

    DEFF Research Database (Denmark)

    Bang, Casper Niels Furbo; Dalsgaard, Morten; Greve, Anders

    2013-01-01

    Left atrial (LA) size and function change with chronically increased left ventricular (LV) filling pressures. It remains unclear whether these variations in LA parameters can predict new-onset atrial fibrillation (AF) in asymptomatic patients with aortic stenosis (AS).......Left atrial (LA) size and function change with chronically increased left ventricular (LV) filling pressures. It remains unclear whether these variations in LA parameters can predict new-onset atrial fibrillation (AF) in asymptomatic patients with aortic stenosis (AS)....

  14. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    Science.gov (United States)

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: pharmacodynamic evaluation and comparison with isogenic normal-phenotype and revertant strains.

    Science.gov (United States)

    Nguyen, Hoang Anh; Denis, Olivier; Vergison, Anne; Theunis, Anne; Tulkens, Paul M; Struelens, Marc J; Van Bambeke, Françoise

    2009-04-01

    Small-colony variant (SCV) strains of Staphylococcus aureus show reduced antibiotic susceptibility and intracellular persistence, potentially explaining therapeutic failures. The activities of oxacillin, fusidic acid, clindamycin, gentamicin, rifampin, vancomycin, linezolid, quinupristin-dalfopristin, daptomycin, tigecycline, moxifloxacin, telavancin, and oritavancin have been examined in THP-1 macrophages infected by a stable thymidine-dependent SCV strain in comparison with normal-phenotype and revertant isogenic strains isolated from the same cystic fibrosis patient. The SCV strain grew slowly extracellularly and intracellularly (1- and 0.2-log CFU increase in 24 h, respectively). In confocal and electron microscopy, SCV and the normal-phenotype bacteria remain confined in acid vacuoles. All antibiotics tested, except tigecycline, caused a net reduction in bacterial counts that was both time and concentration dependent. At an extracellular concentration corresponding to the maximum concentration in human serum (total drug), oritavancin caused a 2-log CFU reduction at 24 h; rifampin, moxifloxacin, and quinupristin-dalfopristin caused a similar reduction at 72 h; and all other antibiotics had only a static effect at 24 h and a 1-log CFU reduction at 72 h. In concentration dependence experiments, response to oritavancin was bimodal (two successive plateaus of -0.4 and -3.1 log CFU); tigecycline, moxifloxacin, and rifampin showed maximal effects of -1.1 to -1.7 log CFU; and the other antibiotics produced results of -0.6 log CFU or less. Addition of thymidine restored intracellular growth of the SCV strain but did not modify the activity of antibiotics (except quinupristin-dalfopristin). All drugs (except tigecycline and oritavancin) showed higher intracellular activity against normal or revertant phenotypes than against SCV strains. The data may help rationalizing the design of further studies with intracellular SCV strains.

  16. Pulmonary vein isolation in the treatment of atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Kumar S

    2016-05-01

    Full Text Available Saurabh Kumar, Gregory F Michaud Cardiac Arrhythmia Service, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA Abstract: Atrial fibrillation (AF is the commonest arrhythmia in humans and is associated with marked reduction in quality of life and an elevated thromboembolic risk. Paroxysmal, persistent, and permanent forms of AF have been recognized. Whilst antiarrhythmic drugs are considered as first-line therapy, the role of catheter ablation is increasing due to its superior efficacy in terms of quality of life and reduction in AF burden. The central paradigm for catheter ablation of AF is that triggers for AF are located near and within the pulmonary veins (PVs, and electrical isolation of the PVs from the left atrium forms the cornerstone of most catheter ablation strategies. Whilst paroxysmal form is generally trigger dependent, persistent and permanent forms are associated with variable interaction between triggers and "substrate" comprised of atrial and PV electrical and structural remodeling. Nevertheless, isolation of the PVs still forms a critical component of catheter ablation strategies, regardless of AF type. Procedural efficacy, however, is limited by PV conduction recovery. This is likely due to deficiencies in ablation tools or limitations of intraprocedural assessment of lesion efficacy. Careful attention to surrogates of tissue heating, such as impedance decrease and electrogram morphology changes, along with advances in catheter technology like contact force catheters may improve rates of durable PV isolation and single-procedural success. This review discusses the mechanism of paroxysmal AF with particular focus on the role of the PVs in AF initiation and PV isolation in the management of AF. Keywords: contact force, lesion transmurality, radiofrequency catheter ablation, paroxysmal atrial fibrillation, electrophysiology, AF

  17. Fibrosis imaging : Current concepts and future directions

    NARCIS (Netherlands)

    Baues, Maike; Dasgupta, Anshuman; Ehling, Josef; Prakash, Jai; Boor, Peter; Tacke, Frank; Kiessling, Fabian; Lammers, Twan

    2017-01-01

    Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis

  18. Pathological assessment of liver fibrosis regression

    Directory of Open Access Journals (Sweden)

    WANG Bingqiong

    2017-03-01

    Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

  19. Computed tomography of cystic pancreatic fibrosis

    International Nuclear Information System (INIS)

    Brachlow, M.; Zaunbauer, W.; Haertel, M.

    1984-01-01

    The computer tomographic appearances of atrophic and lipomatous degeneration of the pancreas in cystic pancreatic fibrosis are described. CT exploration of the pancreas in recommended, particularly in differential diagnostic aspects of cystic fibrosis. (orig.) [de

  20. Atrial Model Development and Prototype Simulations: CRADA Final Report on Tasks 3 and 4

    Energy Technology Data Exchange (ETDEWEB)

    O' Hara, T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zhang, X. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Villongco, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Lightstone, F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Richards, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-10-28

    The goal of this CRADA was to develop essential tools needed to simulate human atrial electrophysiology in 3-dimensions using an anatomical image-based anatomy and physiologically detailed human cellular model. The atria were modeled as anisotropic, representing the preferentially longitudinal electrical coupling between myocytes. Across the entire anatomy, cellular electrophysiology was heterogeneous, with left and right atrial myocytes defined differently. Left and right cell types for the “control” case of sinus rhythm (SR) was compared with remodeled electrophysiology and calcium cycling characteristics of chronic atrial fibrillation (cAF). The effects of Isoproterenol (ISO), a beta-adrenergic agonist that represents the functional consequences of PKA phosphorylation of various ion channels and transporters, was also simulated in SR and cAF to represent atrial activity under physical or emotional stress. Results and findings from Tasks 3 & 4 are described. Tasks 3 and 4 are, respectively: Input parameters prepared for a Cardioid simulation; Report including recommendations for additional scenario development and post-processing analytic strategy.

  1. Nephrogenic systemic fibrosis

    Directory of Open Access Journals (Sweden)

    Bhushan Madke

    2011-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF is a relatively new fibrosing disorder which has caught the attention of various specialities in the past decade. NSF is an extremely disabling and often painful condition, affecting up to 13% of the individuals with chronic kidney disease. The administration of a gadolinium chelate contrast agent has been reported to induce the development of NSF, particularly in patients who have acute or chronic renal disease with a glomerular filtration rate (GFR lower than 30-mL/min/1.73 m 2 and in those with acute renal insufficiency. Mass spectroscopy studies have demonstrated particles of gadolinium in the lesional tissue. The exact pathogenesis of this curious sclerosing condition is unknown. The role of the aberrant targeting of ′circulating fibrocytes′ to the peripheral tissues and viscera has been hypothesized. NSF has distinct clinicopathological features in the setting of renal failure and needs to be looked upon as a new entity on the block. The condition is characterized by irregular indurated plaques, with amoeba-like projections and islands of sparing, chiefly on the trunk and extremities. Flexion contractures of fingers, knees, and elbow joints are known to occur in advanced cases of NSF. The course is frequently associated with painful episodes and loss of ambulation. Histopathology shows haphazard arrangement of thickened bundles of collagen, varying amount of mucin, and increased population of fibroblast-like cells in the dermis. Immunohistochemistry shows increased deposition of type-I procollagen and CD 34+ cells having fibroblastic activity. The condition is refractory to treatment with corticosteroids and immunosuppressive agents. Various modalities of therapy such as UVA1 phototherapy, imatinib mesylate, photodynamic therapy, plasmapheresis, extracorporeal photochemotherapy, and high-dose intravenous immunoglobulin have shown a moderate degree of improvement in skin thickness scores. A prudent

  2. Pulmonary Vein, Dorsal Atrial Wall and Atrial Septum Abnormalities in Podoplanin Knockout Mice With Disturbed Posterior Heart Field Contribution

    NARCIS (Netherlands)

    Douglas, Yvonne L.; Mahtab, Edris A. F.; Jongbloed, Monique R. M.; Uhrin, Pavel; Zaujec, Jan; Binder, Bernd R.; Schalij, Martin J.; Poelmann, Robert E.; Deruiter, Marco C.; Gittenberger-De Groot, Adriana C.

    The developing sinus venosus myocardium, derived from the posterior heart field, contributes to the atrial septum, the posterior atrial wall, the sino-atrial node, and myocardium lining the pulmonary and cardinal veins, all expressing podoplanin, a coelomic and myocardial marker. . We compared

  3. Cystic fibrosis in adults

    Directory of Open Access Journals (Sweden)

    C. Damas

    2007-05-01

    Full Text Available The authors reviewed adult cystic fibrosis patients followed in the Pulmonology Unit from 1994-2004 (n = 8, five female and three male, aged 20-34 years old (median = 27 years. Patients were diagnosed at 18 months - 31 years old by sweat testing (positive in six patients and genotyping (four patients homozygous for ΔF508 mutation.Respiratory involvement was characterised by sinusitis and bronchiectasis. Pulmonary involvement was accompanied by functional abnormalities and gas exchange impairment in the majority of the patients. Bronchial tree was colonised permanently in five patients: Pseudomonas aeruginosa in four and Staphilococcus aureus in four (three patients affected by both agents simultaneously.The main causes of exacerbation were respiratory infections and haemoptysis.Non-respiratory involvement was variable. Four patients had digestive involvement (one with hepatic cirrhosis, one had renal failure and only one had a sperm count to document infertility. Four patients had osteopaenia.Treatment included chest physiotherapy, bronchodilators, dornase alfa, mucolytics, digestive enzymes, vitamins, antibiotics and oxygen therapy.At review, one had left follow-up, one had died, one was awaiting lung transplant and the others evidenced no difference in clinical characteristics.In this group of patients the severity of the pulmonary disease was not related to a late diagnosis. It can be explained by the diversity of cystic fibrosis presentation in adults Resumo: Os autores efectuaram uma revisão de doentes adultos com fibrose quística (FQ, seguidos na consulta de Pneumologia no período de 1994-2004 (n = 8: cinco mulheres e três homens, com idades compreendidas entre 20 e 34 anos (mediana  =  27 anos, cuja idade de diagnóstico variou entre os 18 meses e os 31 anos.O diagnóstico foi obtido por prova de suor (positiva em seis doentes e estudo genético (homozigotia para a mutação ΔF508 em

  4. Left Atrial Linear Ablation of Paroxysmal Atrial Fibrillation Guided by Three-dimensional Electroanatomical System

    DEFF Research Database (Denmark)

    Zhang, Dai-Fu; Li, Ying; Qi, Wei-Gang

    2005-01-01

    Objective To investigate the safety and efficacy of Left atrial linear ablation of paroxysmal atrial fibrillation guided by three-dimensional electroanatomical system. Methods 29 patients with paroxysmal atrial fibrillation in this study. A nonfluoroscopic mapping system was used to generate a 3D...... electroanatomic LA mapping, and all pulmonary vein ostia were marked under the help of pulmonary veins angiography on the 3D map. Radiofrequency (RF) energy was delivered to create continuous linear lesions encircling the pulmonary veins, it was delivered with a target temperature of 43¿, a maximal power limit...

  5. Alcohol consumption and risk of atrial fibrillation

    DEFF Research Database (Denmark)

    Tolstrup, Janne Schurmann; Wium-Andersen, Marie Kim; Ørsted, David Dynnes

    2016-01-01

    BACKGROUND: The aim of this study was to test the hypothesis that alcohol consumption, both observational (self-reported) and estimated by genetic instruments, is associated with a risk of atrial fibrillation and to determine whether people with high cardiovascular risk are more sensitive towards...... alcohol than people with low risk. METHODS: We used data for a total of 88,782 men and women from the Copenhagen City Heart Study 1991-1994 and 2001-2003 and the Copenhagen General Population Study 2003-2010. Information on incident cases of atrial fibrillation was obtained from a validated nationwide...... register. As a measure of alcohol exposure, both self-reported consumption and genetic variations in alcohol metabolizing genes (ADH1B/ADH1C) were used as instrumental variables. The endpoint was admission to hospital for atrial fibrillation as recorded in a validated hospital register. RESULTS: A total...

  6. The atrial fibrillation ablation pilot study

    DEFF Research Database (Denmark)

    Arbelo, Elena; Brugada, Josep; Hindricks, Gerhard

    2014-01-01

    AIMS: The Atrial Fibrillation Ablation Pilot Study is a prospective registry designed to describe the clinical epidemiology of patients undergoing an atrial fibrillation (AFib) ablation, and the diagnostic/therapeutic processes applied across Europe. The aims of the 1-year follow-up were to analyse...... was achieved in 40.7% of patients (43.7% in paroxysmal AF; 30.2% in persistent AF; 36.7% in long-lasting persistent AF). A second ablation was required in 18% of the cases and 43.4% were under antiarrhythmic treatment. Thirty-three patients (2.5%) suffered an adverse event, 272 (21%) experienced a left atrial...... tachycardia, and 4 patients died (1 haemorrhagic stroke, 1 ventricular fibrillation in a patient with ischaemic heart disease, 1 cancer, and 1 of unknown cause). CONCLUSION: The AFib Ablation Pilot Study provided crucial information on the epidemiology, management, and outcomes of catheter ablation of AFib...

  7. Antihypertensive treatment and risk of atrial fibrillation

    DEFF Research Database (Denmark)

    Marott, Sarah C W; Nielsen, Sune F; Benn, Marianne

    2014-01-01

    AIMS: To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish...... population from 1995 through 2010. METHODS AND RESULTS: Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on β-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals...... on ARB monotherapy were matched 1:1 with individuals on β-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus...

  8. Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF, VEGF and PDGF signaling.

    Directory of Open Access Journals (Sweden)

    Ikuo Nakamura

    Full Text Available Brivanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR and fibroblast growth factor receptor (FGFR tyrosine kinases, which are both involved in mechanisms of liver fibrosis. We hypothesized that inhibition of VEGFR and FGFR by brivanib would inhibit liver fibrosis. We therefore examined the effect of brivanib on liver fibrosis in three mouse models of fibrosis.In vivo, we induced liver fibrosis by bile duct ligation (BDL, chronic carbon tetrachloride (CCl4, and chronic thioacetamide (TAA administration. Liver fibrosis was examined by immunohistochemistry and Western immunoblotting. In vitro, we used LX-2 human hepatic stellate cells (HSCs to assess the effect of brivanib on stellate cell proliferation and activation.After in vivo induction with BDL, CCl4, and TAA, mice treated with brivanib showed reduced liver fibrosis and decreased expression of collagen Iα1 and α-smooth muscle actin in the liver. In vitro, brivanib decreased proliferation of HSCs induced by platelet-derived growth factor (PDGF, VEGF, and FGF. Brivanib also decreased stellate cell viability and inhibited PDGFBB-induced phosphorylation of its cognate receptor.Brivanib reduces liver fibrosis in three different animal models and decreases human hepatic stellate cell activation. Brivanib may represent a novel therapeutic approach to treatment of liver fibrosis and prevention of liver cancer.

  9. Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation

    Science.gov (United States)

    Robinson, Erik; Kaushal, Sunjay; Alaboson, Justice; Sharma, Sudhish; Belagodu, Amogh; Watkins, Claire; Walker, Brandon; Webster, Gregory; McCarthy, Patrick; Ho, Dean

    2016-02-01

    Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 +/- 6.8 s vs. 187.6 +/- 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 +/- 1.2 s vs. 103.2 +/- 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to

  10. Exercise-based cardiac rehabilitation for adults with atrial fibrillation

    DEFF Research Database (Denmark)

    Risom, Signe Stelling; Zwisler, Ann-Dorthe; Johansen, Pernille Palm

    2017-01-01

    BACKGROUND: Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria....... OBJECTIVES: To assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF. SEARCH METHODS: We searched the following electronic databases; CENTRAL...... the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes....

  11. The coagulation factor Xa/protease activated receptor-2 axis in the progression of liver fibrosis : a multifaceted paradigm

    NARCIS (Netherlands)

    Borensztajn, Keren; von der Thusen, Jan H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2010-01-01

    Introduction Activation of the coagulation cascade during liver fibrosis: a puzzling paradox Protease-activated receptors: the link between coagulation cascade activation and liver fibrosis Expression and distribution of human PAR-2 in normal and pathological liver tissue FXa signalling on PAR-2

  12. Patients with atrial fibrillation and permanent pacemaker

    DEFF Research Database (Denmark)

    Dalgaard, Frederik; Ruwald, Martin H; Lindhardt, Tommi Bo

    2018-01-01

    BACKGROUND: The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM). METHODS: Through Danish......,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p

  13. Atrial fibrillation and risk of stroke

    DEFF Research Database (Denmark)

    Christiansen, Christine Benn; Gerds, Thomas A.; Olesen, Jonas Bjerring

    2016-01-01

    AIM: Although the relation between stroke risk factors and stroke in patients with atrial fibrillation (AF) has been extensively examined, only few studies have explored the association of AF and the risk of ischaemic stroke/systemic thromboembolism/transient ischaemic attack (stroke.......5-10.6), and 15.4% (14.5-16.4), respectively. CONCLUSIONS: Stroke/TE/TIA risk was particularly increased when prior stroke/TE/TIA was present. Atrial fibrillation is associated with an increase in risk of stroke/TE/TIA in the absence of other risk factors but only a moderate increase in risk when other risk...

  14. Integrating new approaches to atrial fibrillation management

    DEFF Research Database (Denmark)

    Kotecha, Dipak; Breithardt, Günter; Camm, A John

    2018-01-01

    There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse...... of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new...

  15. Initiation of anticoagulation in atrial fibrillation

    DEFF Research Database (Denmark)

    Gundlund, A.; Staerk, L.; Fosbøl, E. L.

    2017-01-01

    Background: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). Methods: Using Danish nationwide registry data, we...... compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28–1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67–0.77). Conclusions: Atrial fibrillation patients who were initiated...

  16. Cryoballoon Catheter Ablation in Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Cevher Ozcan

    2011-01-01

    Full Text Available Pulmonary vein isolation with catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation refractory or intolerant to antiarrhythmic medications. The cryoballoon catheter was recently approved for this procedure. In this paper, the basics of cryothermal energy ablation are reviewed including its ability of creating homogenous lesion formation, minimal destruction to surrounding vasculature, preserved tissue integrity, and lower risk of thrombus formation. Also summarized here are the publications describing the clinical experience with the cryoballoon catheter ablation in both paroxysmal and persistent atrial fibrillation, its safety and efficacy, and discussions on the technical aspect of the cryoballoon ablation procedure.

  17. Atrial fibrillation and the 4P medicine.

    Science.gov (United States)

    Censi, Federica; Cianfrocca, Cinzia; Purificato, Ivana

    2013-01-01

    Although the paradigm of the 4P medicine - Predictive, Personalized, Preemptive, and Participatory - has been suggested several years ago, its application to atrial fibrillation is still far away. Given the increasing prevalence and incidence of this pathology it is the time to promote preventive strategies, by identifying the risk factors associated to life style and by incentivizing innovative diagnostic technologies. The promotion of the correct life style and of the use of diagnostic devices based on innovative and reliable technologies, represent a first step towards the full realization of the revolution of 4P medicine in atrial fibrillation.

  18. Atrial fibrillation and the 4P medicine

    Directory of Open Access Journals (Sweden)

    Federica Censi

    2013-09-01

    Full Text Available Although the paradigm of the 4P medicine - Predictive, Personalized, Preemptive, and Participatory - has been suggested several years ago, its application to atrial fibrillation is still far away. Given the increasing prevalence and incidence of this pathology it is the time to promote preventive strategies, by identifying the risk factors associated to life style and by incentivizing innovative diagnostic technologies. The promotion of the correct life style and of the use of diagnostic devices based on innovative and reliable technologies, represent a first step towards the full realization of the revolution of 4P medicine in atrial fibrillation.

  19. Posibilities of cardiac pacemaker use in paroxsysmal atrial fibrilation

    Directory of Open Access Journals (Sweden)

    Borut Kamenik

    2005-12-01

    Full Text Available Background: Prevention of atrial fibrillation is a big therapeutic challenge because of all known negative consequences of this the most frequent cardiac arrhythmia. Numerous of clinical studies showed bad control or ineffectiveness of antiarhythmic drugs. Nonfarmakological therapies like surgical treatment, radiofrequency ablation and atrial pacing are being tested. Effectiveness of atrial pacing in prevention of paroxysmal artial fibrillation has been documented in numerous prospective studies and is effective for a long time interval, but only for patients with bradicardic underlying cardiac rhythm. In Normocardic rhythm or normal AV conduction the effective Atrial fibrillation prevention was not proven. The mechanism of action is based on premature atrial complex suppression, reduction of dispersion of refractoriness after short-long cycles and reduction of interatrial conduction delay. The atrial stimulation site or multi-site atrial pacing could be effective in AF prevention when interatrial conduction delay is present; otherwise the difference is not significant.Conclusions: In bradicardic patient who has frequent paroxysms of atrial fibrillation, regardless if bradycardia is due to ineffective antiarrhythmic drug treathement, implantation of DDDR pacemaker with atrial prevention algorhythm is indicated. If the P-wave duration is >120 milliseconds multi-site atrial pacing or septal atrial pacing should be considered. Pacemaker diagnostic tools could be used for adequate start of anticoagulant therapy and control of effectiveness of anthyarhythmic drug therapy.

  20. Embolic Risk in Atrial Fibrillation that Arises from Hyperthyroidism

    Science.gov (United States)

    Traube, Elie; Coplan, Neil L.

    2011-01-01

    Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial thromboembolism associated with hyperthyroidism, including cases of young adults without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: national organizations provide conflicting recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism. PMID:21720457

  1. New risk factors for atrial fibrillation : causes of 'not-so-lone atrial fibrillation'

    NARCIS (Netherlands)

    Schoonderwoerd, Bas A.; Smit, Marcelle D.; Pen, Lucas; Van Gelder, Isabelle C.

    Atrial fibrillation (AF) is a prevalent arrhythmia in patients with cardiovascular disease. The classical risk factors for developing AF include hypertension, valvular disease, (ischaemic) cardiomyopathy, diabetes mellitus, and thyroid disease. In some patients with AF, no underlying

  2. Left atrial size in patients with cryptogenic stroke as a predictor of occurrence of atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Antonio Cruz Culebras

    2017-04-01

    Full Text Available Objective: To determine whether the left atrial size can predict the development of atrial fibrillation (AF in patients with embolic stroke of undetermined source (ESUS. Methods: Patients with ischemic stroke were included prospectively (January 2015-July 2015 when ESUS was suspected. Clinical and cardiac imaging data were recorded. Patients with cardiac failure were excluded. Results: a total of 55 patients were included. Medium age was 71 years. The proportion of patients who developed AF during the follow-up (1 year was 23, 63%. 10 % of patients did not have any vascular risk factor. Basal ECG was normal in 98% of cases. The left atrial size volume was 36, 08 ml in patients who developed AF and 27, 14 ml in patients who did not. Conclusions: In patients with ESUS, left atrial size dimensions do not predict the occurrence of AF.

  3. Left atrial low-voltage areas predict atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

    Science.gov (United States)

    Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Matsuda, Yasuhiro; Okuno, Shota; Ohashi, Takuya; Tsuji, Aki; Mano, Toshiaki

    2018-04-15

    Association between the presence of left atrial low-voltage areas and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been shown mainly in persistent AF patients. We sought to compare the AF recurrence rate in paroxysmal AF patients with and without left atrial low-voltage areas. This prospective observational study included 147 consecutive patients undergoing initial ablation for paroxysmal AF. Voltage mapping was performed after PVI during sinus rhythm, and low-voltage areas were defined as regions where bipolar peak-to-peak voltage was low-voltage areas after PVI were observed in 22 (15%) patients. Patients with low-voltage areas were significantly older (72±6 vs. 66±10, plow-voltage areas than without (36% vs. 6%, pLow-voltage areas were independently associated with AF recurrence even after adjustment for the other related factors (Hazard ratio, 5.89; 95% confidence interval, 2.16 to 16.0, p=0.001). The presence of left atrial low-voltage areas after PVI predicts AF recurrence in patients with paroxysmal AF as well as in patients with persistent AF. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Impact of Voltage Mapping to Guide Whether to Perform Ablation of the Posterior Wall in Patients With Persistent Atrial Fibrillation.

    Science.gov (United States)

    Cutler, Michael J; Johnson, Jeremy; Abozguia, Khalid; Rowan, Shane; Lewis, William; Costantini, Otto; Natale, Andrea; Ziv, Ohad

    2016-01-01

    Fibrosis as a substrate for atrial fibrillation (AF) has been shown in numerous preclinical models. Voltage mapping enables in vivo assessment of scar in the left atrium (LA), which can be targeted with catheter ablation. We hypothesized that using the presence or absence of low voltage to guide ablation beyond pulmonary vein antral isolation (PVAI) will improve atrial arrhythmia (AF/AT)-free survival in persistent AF. Single-center retrospective analysis of 2 AF ablation strategies: (1) standard ablation (SA) versus (2) voltage-guided ablation (VGA). PVAI was performed in both groups. With SA, additional lesions beyond PVAI were performed at the discretion of the operator. With VGA, additional lesions to isolate the LA posterior wall were performed if voltage mapping of this region in sinus rhythm showed scar (LA voltage atrial size. Posterior wall ablation was performed in 57% of patient with SA compared to 42% with VGA. VGA ablation increased 1-year AF-/AT-free survival in patients when compared to SA (80% vs. 57%; P = 0.005). In a multivariate analysis, VGA was the only independent predictor of AF-/AT-free survival (hazard ratio of 0.30; P = 0.002). The presence of LA posterior wall scar may be an important ablation target in persistent AF. A prospective randomized trial is needed to confirm these data. © 2015 Wiley Periodicals, Inc.

  5. Investigation of hepatic fibrosis with synchrotron X-ray diffraction enhanced imaging

    International Nuclear Information System (INIS)

    Li Hui; Beijing Univ., Health Science Center, Beijing; Wang Xueyan; Zhao Tao; Hu Chunhong; Lu Weiyuan; Luo Shuqian; Wang Tailing; Wang Baoen; Zhao Xinyan; Zhu Peiping; Huang Wanxia; Yuan Qingxi; Wang Junyue

    2008-01-01

    In this paper, imaging investigation of hepatic fibrosis in rats induced by human albumin with hard X-ray diffraction enhanced imaging (DEI) is reported. The experiments were performed at 4W1A beamline of Beijing Synchrotron Radiation Facility (BSRF). The results show that great differences can be observed in DEI images between the normal and diseased rats in different stages of liver fibrosis. The difference can also be revealed by the profile curve and texture measurements on regions of interest. The results show that DEI may be a potential way for diagnosis of hepatic fibrosis. (authors)

  6. Remodelling of cellular excitation (reaction) and intercellular coupling (diffusion) by chronic atrial fibrillation represented by a reaction-diffusion system

    Science.gov (United States)

    Zhang, Henggui; Garratt, Clifford J.; Kharche, Sanjay; Holden, Arun V.

    2009-06-01

    Human atrial tissue is an excitable system, in which myocytes are excitable elements, and cell-to-cell electrotonic interactions are via diffusive interactions of cell membrane potentials. We developed a family of excitable system models for human atrium at cellular, tissue and anatomical levels for both normal and chronic atrial fibrillation (AF) conditions. The effects of AF-induced remodelling of cell membrane ionic channels (reaction kinetics) and intercellular gap junctional coupling (diffusion) on atrial excitability, conduction of excitation waves and dynamics of re-entrant excitation waves are quantified. Both ionic channel and gap junctional coupling remodelling have rate dependent effects on atrial propagation. Membrane channel conductance remodelling allows the propagation of activity at higher rates than those sustained in normal tissue or in tissue with gap junctional remodelling alone. Membrane channel conductance remodelling is essential for the propagation of activity at rates higher than 300/min as seen in AF. Spatially heterogeneous gap junction coupling remodelling increased the risk of conduction block, an essential factor for the genesis of re-entry. In 2D and 3D anatomical models, the dynamical behaviours of re-entrant excitation waves are also altered by membrane channel modelling. This study provides insights to understand the pro-arrhythmic effects of AF-induced reaction and diffusion remodelling in atrial tissue.

  7. Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2015-07-01

    Full Text Available Background/Aims: Angiotensin II receptor blockers (ARBs have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF. Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Methods: Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT antibody. Western blot was used to analysis the protein expression of neurturin. Results: Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Conclusion: Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway.

  8. Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway.

    Science.gov (United States)

    Liu, Lei; Geng, Jianqiang; Zhao, Hongwei; Yun, Fengxiang; Wang, Xiaoyu; Yan, Sen; Ding, Xue; Li, Wenpeng; Wang, Dingyu; Li, Jianqiang; Pan, Zhenwei; Gong, Yongtai; Tan, Xiangyang; Li, Yue

    2015-01-01

    Angiotensin II receptor blockers (ARBs) have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF). Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II) and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT) antibody. Western blot was used to analysis the protein expression of neurturin. Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway. © 2015 S. Karger AG, Basel.

  9. Left atrial appendage occlusion for stroke prevention in atrial fibrillation in Europe

    DEFF Research Database (Denmark)

    Lip, Gregory Y.H.; Dagres, Nikolaos; Proclemer, Alessandro

    2013-01-01

    The purpose of this EP wire survey was to assess clinical practice in relation to the use of left atrial appendage occlusion (LAAO) devices for stroke prevention in atrial fibrillation (AF) among members of the European Heart Rhythm Association research network. The average number of performed LA...... are most often performed by interventional cardiologists. Experience varied widely, and this was reflected in the wide range of thromboembolic and procedural (tamponade, bleeding) complications reported by the respondents to this EP wire survey....

  10. Left Atrial Decompression by Percutaneous Left Atrial Venting Cannula Insertion during Venoarterial Extracorporeal Membrane Oxygenation Support

    Directory of Open Access Journals (Sweden)

    Ha Eun Kim

    2016-06-01

    Full Text Available Patients with venoarterial extracorporeal membrane oxygenation (ECMO frequently suffer from pulmonary edema due to left ventricular dysfunction that accompanies left heart dilatation, which is caused by left atrial hypertension. The problem can be resolved by left atrium (LA decompression. We performed a successful percutaneous LA decompression with an atrial septostomy and placement of an LA venting cannula in a 38-month-old child treated with venoarterial ECMO for acute myocarditis.

  11. Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy.

    Science.gov (United States)

    Sticherling, Christian; Müller, Dirk; Schaer, Beat A; Krüger, Silke; Kolb, Christof

    2018-03-27

    Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF. Seventeen patients (16 males, mean age 73 ± 6 years, mean EF 25 ± 5%) with permanent AF and an indication for CRT-defibrillator placement were implanted with a designated CRT-D system comprising a single pass defibrillator lead with a atrial floating bipole. They were followed-up for 103 ± 22 days using remote monitoring for AEGM transmission. All patients had at last one AEGM suitable for atrial rhythm diagnosis and of 100 AEGM 99% were suitable for visual atrial rhythm assessment. Four patients were discharged in sinus rhythm and one reverted to AF during follow-up. Atrial electrograms retrieved from a single-pass defibrillator lead with a floating atrial bipole can be reliably used for atrial rhythm diagnosis in CRT recipients with permanent AF. Hence, a single pass ventricular defibrillator lead with a floating bipole can be considered in this population. Copyright © 2018 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

  12. Learning about Cystic Fibrosis

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  13. ANTIARRHYTMIC EFFICACY OF SOTALOL IN PATIENTS WITH TACHY-BRADY SYNDROME HAVING ATRIAL PACEMAKER WITH DIFFERENT ATRIAL ELECTRODE POSITION

    Directory of Open Access Journals (Sweden)

    T. N. Novikova

    2009-01-01

    Full Text Available Aim. To evaluate efficacy of the combined therapy (sotalol and constant electric cardiostimulation in AAI regimen at two atrial electrode position: in low back part of interatrial septum (IAS and in right atrial auricle (RAA.Material and methods. 20 patients with tachy-brady syndrome were examined. They were randomized in 2 groups depending on atrial electrode position. Sotalol (160 mg daily was prescribed to all patients in a month after implantation of constant atrial pacemaker (CAP. A number of atrial fibrillation paroxysms (AFP was evaluated initially, in a month after CAP implantation and in a month after start of sotalol therapy.Results. Significant AFP reduction was observed in IAS stimulation, unlike RAA stimulation. Sotalol addition had essential significance in the termination or reduction of AFP. Sotalol effect did not depend on atrial electrode position.Conclusion. Sotalol usage together with constant electric cardiostimulation significantly reduces AFP irrespectively of atrial electrode position. 

  14. Nephrogenic Systemic Fibrosis in Denmark

    DEFF Research Database (Denmark)

    Elmholdt, Tina Rask; Olesen, Anne; J�rgensen, Bettina

    2013-01-01

    Nephrogenic systemic fibrosis is a debilitating and painful disorder with an increased stimulation of the connective tissue in the skin and systemic tissues. The disease is associated with exposure to gadolinium-based contrast agent used in magnetic resonance imaging in patients with renal...

  15. Radiation pericarditis and myocardial fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Westerhof, P W; van der Putte, S C.J.

    1976-06-01

    The case of a 45-yr-old man with constrictive pericarditis due to radiation for Hodgkin's disease is described. After pericardiectomy the clinical condition did not improve. At necropsy an extensive fibrosis of the myocardium especially located in the anterior part of the heart was found. The clinical consequences of this finding with respect to surgical treatment are briefly discussed.

  16. Hepatic fibrosis: Concept to treatment.

    Science.gov (United States)

    Trautwein, Christian; Friedman, Scott L; Schuppan, Detlef; Pinzani, Massimo

    2015-04-01

    Understanding the molecular mechanisms underlying liver fibrogenesis is fundamentally relevant to developing new treatments that are independent of the underlying etiology. The increasing success of antiviral treatments in blocking or reversing the fibrogenic progression of chronic liver disease has unearthed vital information about the natural history of fibrosis regression, and has established important principles and targets for antifibrotic drugs. Although antifibrotic activity has been demonstrated for many compounds in vitro and in animal models, none has been thoroughly validated in the clinic or commercialized as a therapy for fibrosis. In addition, it is likely that combination therapies that affect two or more key pathogenic targets and/or pathways will be needed. To accelerate the preclinical development of these combination therapies, reliable single target validation is necessary, followed by the rational selection and systematic testing of combination approaches. Improved noninvasive tools for the assessment of fibrosis content, fibrogenesis and fibrolysis must accompany in vivo validation in experimental fibrosis models, and especially in clinical trials. The rapidly changing landscape of clinical trial design for liver disease is recognized by regulatory agencies in the United States (FDA) and Western Europe (EMA), who are working together with the broad range of stakeholders to standardize approaches to testing antifibrotic drugs in cohorts of patients with chronic liver diseases. Copyright © 2015. Published by Elsevier B.V.

  17. [Genetic counseling in cystic fibrosis].

    Science.gov (United States)

    Julia, S; Bieth, E

    2000-08-01

    Genetic counseling is an important part of health care in patients with cystic fibrosis or respiratory diseases associated with the CFTR (cystic fibrosis transmembrane conductance regulator) gene, including certain types of allergic bronchopulmonary aspergilloses or bronchial diseases (diffuse bronchiectasia). The basic goal is to provide patients with information on the transmission of cystic fibrosis and to asses the risk of recurrence. This risk is determined from molecular biology analyses examining the CFTR gene. Genotyping is the only means of screening for the heterozygous state, frequent in the French population (about 1/30). Because of the large number of mutated alleles not covered entirely by the genetic tests, there remains a question of probability expressed as a residual risk of a heterozygous state. A prenatal genotype diagnosis should be proposed to heterozygous couples who have a 25% risk of having a diseased child. Technically, this is almost always possible and the results are highly reliable. Nevertheless, there remains the risks related to sample taking and the ethical issue about which the patients must be informed. Management of these at risk couples who desire a child must be based on a multidisciplinary approach, particularly important when one of the parents has overt cystic fibrosis.

  18. MR enhancement of epidural fibrosis by Gd-DTPA: Biodistribution and mechanism

    International Nuclear Information System (INIS)

    Ross, J.S.; Delamater, R.; Van Dyke, C.W.; Masaryk, T.J.; Hueftle, M.G.; Bohlman, H.; Modic, M.T.

    1987-01-01

    Epidural lumbar fibrosis was induced in eight beagle dogs at the L-6 level. Vascular injection with india ink showed abundant vessels in the scar. This agreed with light microscopy in eight patients with epidural fibrosis, which enhanced with Gd-DTPA from a clinical trial. Electron microscopy of epidural scar in humans and dogs demonstrated a continuous endothelium with scattered tight junctions. Biodistirbution was determined in four dogs with rapid MR scanning following intravenous (IV) bolus of 0.1 mmol/kg of Gd-DTPA and radioassay of tissue samples following Gd-153-DTPA IV injection. Maximum percent enhancement (70% humans, 100% dogs) occurred at 3-6 minutes in epidural fibrosis with a slow decline in enhancement over the next hour. These findings suggest that Gd-DTPA enhancement of epidural fibrosis is via an extracellular distribution within vascularized scar tissue

  19. Spontaneous conversion of first onset atrial fibrillation

    DEFF Research Database (Denmark)

    Lindberg, Søren Østergaard; Hansen, Sidsel; Nielsen, Tonny

    2011-01-01

    Background  We studied all patients admitted to hospital with first onset atrial fibrillation (AF) to determine the probability of spontaneous conversion to sinus rhythm and to identify factors predictive of such a conversion. Methods and Results  We retrospectively reviewed charts of 438...

  20. Genetic aspects of lone atrial fibrillation

    DEFF Research Database (Denmark)

    Andreasen, Laura; Nielsen, Jonas B; Olesen, Morten S

    2015-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia. A subgroup of patients presents with AF without traditional risk factors and is diagnosed before the age of 60 years. Such patients are commonly referred as having "lone AF" and comprise 10-20% of all cases. A number of studies have...

  1. Atrial fibrillation in the Middle East

    DEFF Research Database (Denmark)

    Al-Shamkhani, Warkaa; Ayetey, Harold; Lip, Gregory Y H

    2018-01-01

    INTRODUCTION: Atrial fibrillation (AF) is the commonest persistent cardiac arrhythmia with an estimated incidence rate of between 1.5-2% and an important cause of strokes. Few epidemiological studies and clinical trials on the management of AF have been conducted outside Europe and North America...

  2. An "account" of digitalis and atrial fibrillation

    NARCIS (Netherlands)

    Meijler, F.L.

    This review deals with the mechanisms by which digitalis exerts its "opium-Iike" action on the ventricular rate in patients with atrial fibrillation. To understand the effect of digitalis on ventricular rate and rhythm, it is essential to learn more about the basic electrophysiologic

  3. Multimodal Examination of Atrial Fibrillation Substrate: Correlation of Left Atrial Bipolar Voltage Using Multi-Electrode Fast Automated Mapping, Point-by-Point Mapping, and Magnetic Resonance Image Intensity Ratio.

    Science.gov (United States)

    Zghaib, Tarek; Keramati, Ali; Chrispin, Jonathan; Huang, Dong; Balouch, Muhammad A; Ciuffo, Luisa; Berger, Ronald D; Marine, Joseph E; Ashikaga, Hiroshi; Calkins, Hugh; Nazarian, Saman; Spragg, David D

    2018-01-01

    Bipolar voltage mapping, as part of atrial fibrillation (AF) ablation, is traditionally performed in a point-by-point (PBP) approach using single-tip ablation catheters. Alternative techniques for fibrosis-delineation include fast-anatomical mapping (FAM) with multi-electrode circular catheters, and late gadolinium-enhanced magnetic-resonance imaging (LGE-MRI). The correlation between PBP, FAM, and LGE-MRI fibrosis assessment is unknown. In this study, we examined AF substrate using different modalities (PBP, FAM, and LGE-MRI mapping) in patients presenting for an AF ablation. LGE-MRI was performed pre-ablation in 26 patients (73% males, age 63±8years). Local image-intensity ratio (IIR) was used to normalize myocardial intensities. PBP- and FAM-voltage maps were acquired, in sinus rhythm, prior to ablation and co-registered to LGE-MRI. Mean bipolar voltage for all 19,087 FAM voltage points was 0.88±1.27mV and average IIR was 1.08±0.18. In an adjusted mixed-effects model, each unit increase in local IIR was associated with 57% decrease in bipolar voltage (p0.74 corresponded to bipolar voltage voltage was significantly associated with log-PBP bipolar voltage (ß=0.36, pvoltages, FAM-mapping distribution was shifted to the left compared to PBP-mapping; at intermediate voltages, FAM and PBP voltages were overlapping; and at high voltages, FAM exceeded PBP-voltages. LGE-MRI, FAM and PBP-mapping show good correlation in delineating electro-anatomical AF substrate. Each approach has fundamental technical characteristics, the awareness of which allows proper assessment of atrial fibrosis.

  4. Adverse outcome pathway development from protein alkylation to liver fibrosis.

    Science.gov (United States)

    Horvat, Tomislav; Landesmann, Brigitte; Lostia, Alfonso; Vinken, Mathieu; Munn, Sharon; Whelan, Maurice

    2017-04-01

    In modern toxicology, substantial efforts are undertaken to develop alternative solutions for in vivo toxicity testing. The adverse outcome pathway (AOP) concept could facilitate knowledge-based safety assessment of chemicals that does not rely exclusively on in vivo toxicity testing. The construction of an AOP is based on understanding toxicological processes at different levels of biological organisation. Here, we present the developed AOP for liver fibrosis and demonstrate a linkage between hepatic injury caused by chemical protein alkylation and the formation of liver fibrosis, supported by coherent and consistent scientific data. This long-term process, in which inflammation, tissue destruction, and repair occur simultaneously, results from the complex interplay between various hepatic cell types, receptors, and signalling pathways. Due to the complexity of the process, an adequate liver fibrosis cell model for in vitro evaluation of a chemical's fibrogenic potential is not yet available. Liver fibrosis poses an important human health issue that is also relevant for regulatory purposes. An AOP described with enough mechanistic detail might support chemical risk assessment by indicating early markers for downstream events and thus facilitating the development of an in vitro testing strategy. With this work, we demonstrate how the AOP framework can support the assembly and coherent display of distributed mechanistic information from the literature to support the use of alternative approaches for prediction of toxicity. This AOP was developed according to the guidance document on developing and assessing AOPs and its supplement, the users' handbook, issued by the Organisation for Economic Co-operation and Development.

  5. An American Thoracic Society Official Research Statement: Future Directions in Lung Fibrosis Research.

    Science.gov (United States)

    White, Eric S; Borok, Zea; Brown, Kevin K; Eickelberg, Oliver; Guenther, Andreas; Jenkins, R Gisli; Kolb, Martin; Martinez, Fernando J; Roman, Jesse; Sime, Patricia

    2016-04-01

    Pulmonary fibrosis encompasses a group of lung-scarring disorders that occur owing to known or unknown insults and accounts for significant morbidity and mortality. Despite intense investigation spanning decades, much remains to be learned about the natural history, pathophysiology, and biologic mechanisms of disease. To identify the most pressing research needs in the lung fibrosis community and to provide a roadmap of priorities to investigators, funding agencies, patient advocacy groups, and other interested stakeholders. An ad hoc international working group of the American Thoracic Society with experience in clinical, translational, and bench-based research in fibrotic lung diseases was convened. The group used an iterative consensus process to identify successes and challenges in pulmonary fibrosis research. The group identified five main priority areas in which substantial resources should be invested to advance our understanding and to develop novel therapies for patients with pulmonary fibrosis. These priorities include develop newer models of human lung fibrosis, engage current and new stakeholders to provide sustained funding for the initiatives, create a global infrastructure for storing patient-derived materials, establish collaborative preclinical and clinical research networks in fibrotic lung disease, and create a global lung fibrosis initiative that unites these multifaceted efforts into a single virtual umbrella structure. Despite recent advances in the treatment of some forms of lung fibrosis, many gaps in knowledge about natural history, pathophysiology, and treatment remain. Investment in the research priorities enumerated above will help address these shortcomings and enhance patient care worldwide.

  6. Assessment of the dynamics of atrial signals and local atrial period series during atrial fibrillation: effects of isoproterenol administration

    Directory of Open Access Journals (Sweden)

    Mantica Massimo

    2004-10-01

    Full Text Available Abstract Background The autonomic nervous system (ANS plays an important role in the genesis and maintenance of atrial fibrillation (AF, but quantification of its electrophysiologic effects is extremely complex and difficult. Aim of the study was to evaluate the capability of linear and non-linear indexes to capture the fine changing dynamics of atrial signals and local atrial period (LAP series during adrenergic activation induced by isoproterenol (a sympathomimetic drug infusion. Methods Nine patients with paroxysmal or persistent AF (aged 60 ± 6 underwent electrophysiological study in which isoproterenol was administered to patients. Atrial electrograms were acquired during i sinus rhythm (SR; ii sinus rhythm during isoproterenol (SRISO administration; iii atrial fibrillation (AF and iv atrial fibrillation during isoproterenol (AFISO administration. The level of organization between two electrograms was assessed by the synchronization index (S, whereas the degree of recurrence of a pattern in a signal was defined by the regularity index (R. In addition, the level of predictability (LP and regularity of LAP series were computed. Results LAP series analysis shows a reduction of both LP and R index during isoproterenol infusion in SR and AF (RSR = 0.75 ± 0.07 RSRISO = 0.69 ± 0.10, p AF = 0.31 ± 0.08 RAFISO = 0.26 ± 0.09, p SR = 99.99 ± 0.001 LPSRISO = 99.97 ± 0.03, p AF = 69.46 ± 21.55 LPAFISO = 55 ± 24.75; p SR = 0.49 ± 0.08 RSRISO = 0.46 ± 0.09 p AF = 0.29 ± 0.09 RAFISO = 0.28 ± 0.08 n.s.. Conclusions The proposed parameters succeeded in discriminating the subtle changes due to isoproterenol infusion during both the rhythms especially when considering LAP series analysis. The reduced value of analyzed parameters after isoproterenol administration could reflect an important pro-arrhythmic influence of adrenergic activation on favoring maintenance of AF.

  7. Hyperplasia of elastic tissue in hepatic schistosomal fibrosis

    Directory of Open Access Journals (Sweden)

    Zilton A. Andrade

    1991-12-01

    Full Text Available Elastic tissue hyperplasia, revealed by means of histological, immunocytochemical and ultrastructural methods, appeared as a prominent change in surgical liver biopsies taken from 61 patients with schistosomal periportal and septal fibrosis. Such hyperplasia was absent in ecperimental murine schistosomiasis, including mice with "pipe-stem" fibrosis. Displaced connective tissue cells in periportal areas, such as smooth muscle cells, more frequently observed in human material, could be the site of excessive elastin synthesis, and could explain the differences observed in human and experimental materials. Elastic tissue, sometimes represented by its microfibrillar components, also appeared to be more condensed in areas of matrix (collagen degradation, suggesting a participation of this tissue in the remodelling of the extracellular matrix. By its rectratile properties elastic tissue hyperplasia in hepatic schistosomiasis can cause vascular narrowing and thus play a role in the pathogenesis of portal hypeertension.

  8. [Effect of benazepril on atrial cytoskeleton remodeling in the canine atrial fibrillation models].

    Science.gov (United States)

    Liu, Li; Qu, Xiu-Fen; Yu, Yang; Bai, Bing; Huang, Yong-Lin

    2009-10-20

    To investigate the effect of benazepril on atrial cytoskeleton remodeling in atrial fibrillation (AF) canines induced by chronic rapid atrial pacing (RAP). Twenty canines were randomly divided into 3 groups: (1) Sham-operated group without RAP; (2) AF group: AF established by RAP at 600 beats per minute for 6 weeks; (3) Benazepril group: benazepril was dosed from 1 week pre-pacing to 6 weeks post-pacing. The diameter of atrial cardiomyocyte was measured, collagen volume fraction (CVF) analyzed by Masson staining and the expression and distribution of desmin were assayed by immunohistochemistry. RT-PCR method was used to semi-quantify the mRNA expression of beta-tubulin and desmin. The diameter of atrial cardiomyocyte increased in AF group [LA:(27.9 +/- 3.8) microm; RA: (26.8 +/- 3.2) microm] and benazepril group[LA: (25.1 +/- 3.4) microm; RA: (25.2 +/- 3.5) microm] than sham-operated group [LA: (19.6 +/- 2.9) microm; RA: (18.7 +/- 2.6) microm] (P benazepril group than AF group [LA: (11.3 +/- 0.8)% vs (16.9 +/- 1.1)%, RA: (10.9 +/- 0.8)% vs (15.7 +/- 2.3)%, P benazepril group than AF group (P benazepril group than AF group (LA:0.8 +/- 0.4 vs 1.0 +/- 0.3, 0.7 +/- 0.3 vs 0.9 +/- 0.4; RA:0.7 +/- 0.3 vs 1.0 +/- 0.6, 0.7 +/- 0.3 vs 1.1 +/- 0.3, P Benazepril can favorably improve atrial cytoskeleton remodeling in the canine atrial fibrillation model.

  9. Sensitivity of reentrant driver localization to electrophysiological parameter variability in image-based computational models of persistent atrial fibrillation sustained by a fibrotic substrate

    Science.gov (United States)

    Deng, Dongdong; Murphy, Michael J.; Hakim, Joe B.; Franceschi, William H.; Zahid, Sohail; Pashakhanloo, Farhad; Trayanova, Natalia A.; Boyle, Patrick M.

    2017-09-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, causing morbidity and mortality in millions worldwide. The atria of patients with persistent AF (PsAF) are characterized by the presence of extensive and distributed atrial fibrosis, which facilitates the formation of persistent reentrant drivers (RDs, i.e., spiral waves), which promote fibrillatory activity. Targeted catheter ablation of RD-harboring tissues has shown promise as a clinical treatment for PsAF, but the outcomes remain sub-par. Personalized computational modeling has been proposed as a means of non-invasively predicting optimal ablation targets in individual PsAF patients, but it remains unclear how RD localization dynamics are influenced by inter-patient variability in the spatial distribution of atrial fibrosis, action potential duration (APD), and conduction velocity (CV). Here, we conduct simulations in computational models of fibrotic atria derived from the clinical imaging of PsAF patients to characterize the sensitivity of RD locations to these three factors. We show that RDs consistently anchor to boundaries between fibrotic and non-fibrotic tissues, as delineated by late gadolinium-enhanced magnetic resonance imaging, but those changes in APD/CV can enhance or attenuate the likelihood that an RD will anchor to a specific site. These findings show that the level of uncertainty present in patient-specific atrial models reconstructed without any invasive measurements (i.e., incorporating each individual's unique distribution of fibrotic tissue from medical imaging alongside an average representation of AF-remodeled electrophysiology) is sufficiently high that a personalized ablation strategy based on targeting simulation-predicted RD trajectories alone may not produce the desired result.

  10. Vernakalant hydrochloride for the rapid conversion of atrial fibrillation after cardiac surgery

    DEFF Research Database (Denmark)

    Kowey, Peter R; Dorian, Paul; Mitchell, L Brent

    2009-01-01

    Postoperative atrial arrhythmias are common and are associated with considerable morbidity. This study was designed to evaluate the efficacy and safety of vernakalant for the conversion of atrial fibrillation (AF) or atrial flutter (AFL) after cardiac surgery....

  11. Environmental Mycobiome Modifiers of Inflammation and Fibrosis in Systemic Sclerosis

    Science.gov (United States)

    2016-09-01

    shown that PBMCs and macrophages from SSc patients (monocytes isolated from peripheral blood of SSc patients that are differentiated in autologous...systemic sclerosis, pulmonary fibrosis and pulmonary arterial hypertension ” Scleroderma Research Foundation Annual Workshop, San Francisco, CA 2/16...Cruz), and patient sera for 1 h at room temperature. Secondary antibodies (anti-goat-Cy3, anti-mouse-Cy2, and anti-human-Cy5) were purchased from

  12. Early recurrences of atrial fibrillation after electrical cardioversion : A result of fibrillation-induced electrical remodeling of the atria?

    NARCIS (Netherlands)

    Tieleman, RG; Van Gelder, IC; Crijns, HJGM; De Kam, PJ; Van den Berg, MP; Haaksma, J; Van der Woude, HJ; Allessie, MA

    Objectives, We sought to investigate whether, in humans, the timing and incidence of a relapse of atrial fibrillation (AF) during the first month after cardioversion indicates the presence of electrical remodeling and whether this could be influenced by prevention of intracellular calcium overload

  13. [Atrial fibrillation as consequence and cause of structural changes of atria].

    Science.gov (United States)

    Aparina, O P; Chikhireva, L N; Stukalova, O V; Mironova, N A; Kashtanova, S Iu; Ternovoĭ, S K; Golitsyn, S P

    2014-01-01

    Changes of atrial structure and function are the contributors of atrial fibrillation clinical course, complications and treatment effectiveness. Effects of inflammation and mechanical stretch on atrial structural remodeling leading to atrial fibrillation are reviewed in the article. Contemporary invasive and non-invasive methods of evaluation (including late gadolinium enhancement magnetic resonance imaging) of patients with atrial structural remodeling in atrial fibrillation are also described.

  14. Genetic variation in the two-pore domain potassium channel, TASK-1, may contribute to an atrial substrate for arrhythmogenesis

    DEFF Research Database (Denmark)

    Liang, Bo; Soka, Magdalena; Christensen, Alex Horby

    2013-01-01

    The two-pore domain potassium channel, K2P3.1 (TASK-1) modulates background conductance in isolated human atrial cardiomyocytes and has been proposed as a potential drug target for atrial fibrillation (AF). TASK-1 knockout mice have a predominantly ventricular phenotype however, and effects of TASK......-1 inactivation on atrial structure and function have yet to be demonstrated in vivo. The extent to which genetic variation in KCNK3, that encodes TASK-1, might be a determinant of susceptibility to AF is also unknown. To address these questions, we first evaluated the effects of transient knockdown...... of the zebrafish kcnk3a and kcnk3b genes and cardiac phenotypes were evaluated using videomicroscopy. Combined kcnk3a and kcnk3b knockdown in 72 hour post fertilization embryos resulted in lower heart rate (p

  15. Role of spiral wave pinning in inhomogeneous active media in the termination of atrial fibrillation by electrical cardioversion.

    Science.gov (United States)

    Kuklik, Pawel; Wong, Christopher X; Brooks, Anthony G; Zebrowski, Jan Jacek; Sanders, Prashanthan

    2010-03-01

    Atrial fibrillation is the most common type of arrhythmia to affect humans. One of the treatment modalities for atrial fibrillation is an electrical cardioversion. Electrical cardioversion can result in one of three outcomes: an immediate termination of arrhythmic activity, a delayed termination or unsuccessful termination. The mechanism of delayed termination is unknown. Here we present a model of an atrial fibrillation as a coexistence of several spiral waves pinned to the inhomogeneities in active media. We show that in inhomogeneous system delayed termination can be explained as the unpinning of a spiral wave from inhomogeneities and its termination after collision with the edge of the system. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  16. Atrial infarction is a unique and often unrecognized clinical entity

    Directory of Open Access Journals (Sweden)

    Rosana G. G. Mendes

    1999-03-01

    Full Text Available A patient with heart failure and acute atrial fibrillation received the final diagnosis of atrial infarction associated with ventricular infarction based on clinical findings of ischemia in association with atrial fibrillation and heart failure (mechanisms probably involved: contractile dysfunction and loss of atrial contribution. Although a transesophageal echocardiography, which could refine the diagnosis of anatomic abnormalities, was not performed, all evidence led to the diagnosis of atrial involvement. Electrocardiographic findings were consistent with Liu's major criterion 3. Therapy with digitalis, quinidine and angiotensin-converting enzyme inhibitors was chosen, as the patient had acute pulmonary edema. The use of beta-blockers and verapamil was restricted. No other complications, such as thrombo-embolism or atrial rupture, were noted.

  17. Cardiorespiratory interactions in patients with atrial flutter.

    Science.gov (United States)

    Masè, Michela; Disertori, Marcello; Ravelli, Flavia

    2009-01-01

    Respiratory sinus arrhythmia (RSA) is generally known as the autonomically mediated modulation of the sinus node pacemaker frequency in synchrony with respiration. Cardiorespiratory interactions have been largely investigated during sinus rhythm, whereas little is known about interactions during reentrant arrhythmias. In this study, cardiorespiratory interactions at the atrial and ventricular level were investigated during atrial flutter (AFL), a supraventricular arrhythmia based on a reentry, by using cross-spectral analysis and computer modeling. The coherence and phase between respiration and atrial (gamma(AA)(2), phi(AA)) and ventricular (gamma(RR)(2), phi(RR)) interval series were estimated in 20 patients with typical AFL (68.0 +/- 8.8 yr) and some degree of atrioventricular (AV) conduction block. In all patients, atrial intervals displayed oscillations strongly coupled and in phase with respiration (gamma(AA)(2)= 0.97 +/- 0.05, phi(AA) = 0.71 +/- 0.31 rad), corresponding to a paradoxical lengthening of intervals during inspiration. The modulation pattern was frequency independent, with in-phase oscillations and short time delays (0.40 +/- 0.15 s) for respiratory frequencies in the range 0.1-0.4 Hz. Ventricular patterns were affected by AV conduction type. In patients with fixed AV conduction, ventricular intervals displayed oscillations strongly coupled (gamma(RR)(2)= 0.97 +/- 0.03) and in phase with respiration (phi(RR) = 1.08 +/- 0.80 rad). Differently, in patients with variable AV conduction, respiratory oscillations were secondary to Wencheback rhythmicity, resulting in a decreased level of coupling (gamma(RR)(2)= 0.50 +/- 0.21). Simulations with a simplified model of AV conduction showed ventricular patterns to originate from the combination of a respiratory modulated atrial input with the functional properties of the AV node. The paradoxical frequency-independent modulation pattern of atrial interval, the short time delays, and the complexity of

  18. Nephrogenic systemic fibrosis: epidemiology update

    DEFF Research Database (Denmark)

    Marckmann, P.

    2008-01-01

    Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. Recent findings Epidemiological and histochemical studies demonstrated....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...... that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases...

  19. Epidemiology of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Ley B

    2013-11-01

    Full Text Available Brett Ley, Harold R Collard Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, USA Abstract: Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause that occurs in adults and has a poor prognosis. Its epidemiology has been difficult to study because of its rarity and evolution in diagnostic and coding practices. Though uncommon, it is likely underappreciated both in terms of its occurrence (ie, incidence, prevalence and public health impact (ie, health care costs and resource utilization. Incidence and mortality appear to be on the rise, and prevalence is expected to increase with the aging population. Potential risk factors include occupational and environmental exposures, tobacco smoking, gastroesophageal reflux, and genetic factors. An accurate understanding of its epidemiology is important, especially as novel therapies are emerging. Keywords: idiopathic pulmonary fibrosis, epidemiology, incidence, prevalence, mortality, risk factors

  20. MRI in mucoviscidosis (cystic fibrosis)

    International Nuclear Information System (INIS)

    Eichinger, M.; Puderbach, M.; Kauczor, H.-U.; Heussel, C.-P.

    2006-01-01

    Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients. The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure. Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function. (orig.) [de

  1. [Historical compilation of cystic fibrosis].

    Science.gov (United States)

    Navarro, Salvador

    2016-01-01

    Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  2. Fibrosis endomiocárdica

    Directory of Open Access Journals (Sweden)

    María Juliana Rodríguez-González

    2017-07-01

    Una de las formas más comunes de miocardiopatía restrictiva es la fibrosis endomiocárdica la cual es endémica en algunas zonas tropicales especialmente en África (países de bajos ingresos, pero en nuestro medio hay pocos reportes de aparición. Su etiología es desconocida, aunque existen diversos mecanismos que han sido involucrados en su fisiopatología. Su diagnóstico se basa en estudios imagenológicos (ecocardiograma transtorácico y resonancia magnética nuclear cardíaca. El pronóstico es muy pobre, y usualmente se diagnostica en etapas muy avanzadas de la enfermedad. Se describe el caso de una paciente femenina, adulta media, que debutó con cardiopatía restrictiva, cuyo diagnóstico final fue fibrosis endomiocárdica.

  3. Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.

    Directory of Open Access Journals (Sweden)

    Kurt J Williams

    Full Text Available Gammaherpesviruses (γHV are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF, a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg was significantly increased compared to control horses (26 µg/mg (p < 0.5, as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4% (mean ± SEM; p < 0.001. Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.

  4. Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.

    Science.gov (United States)

    Williams, Kurt J; Robinson, N Edward; Lim, Ailam; Brandenberger, Christina; Maes, Roger; Behan, Ashley; Bolin, Steven R

    2013-01-01

    Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.

  5. Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on Cystic Fibrosis

    NARCIS (Netherlands)

    Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ

    These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external

  6. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

    Bensel, Tobias; Stotz, Martin; Borneff-Lipp, Marianne

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated...... and 25 stable CF patients via spectrophotometry and gaschromatography. Lung function was assessed via spirometry. Seven patients with chronic obstructive pulmonary disease (COPD) and three patients with acute lung inflammation served as control groups. Neutrophil and bacterial lactate production...

  7. Anorexia nervosa in cystic fibrosis.

    Science.gov (United States)

    Linkson, Lynette; Macedo, Patricia; Perrin, Felicity M R; Elston, Caroline M

    2018-03-01

    This article explores the challenges associated with diagnosing and managing eating disorders such as anorexia nervosa amongst adolescents and adults with cystic fibrosis. It reviews the known risk factors, generic verses disease specific eating disorder risk screening tools and considers the ethical dilemmas associated with critically low body mass indices. A case review is included to illustrate the complexities of managing both conditions in the context of declining respiratory function. Copyright © 2017. Published by Elsevier Ltd.

  8. Idiopathic pulmonary fibrosis: treatment update.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2011-11-01

    Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Despite multiple recent clinical trials, there is no strong evidence supporting a survival advantage for any agent in the management of patients with IPF. The limited effectiveness of current treatment regimes has led to a search for novel therapies including antifibrotic strategies. This article reviews the evidence supporting the treatments currently used in the management of IPF.

  9. Cardiac ion channels and mechanisms for protection against atrial fibrillation

    DEFF Research Database (Denmark)

    Grunnet, Morten; Bentzen, Bo Hjorth; Sørensen, Ulrik S

    2011-01-01

    Atrial fibrillation (AF) is recognised as the most common sustained cardiac arrhythmia in clinical practice. Ongoing drug development is aiming at obtaining atrial specific effects in order to prevent pro-arrhythmic, devastating ventricular effects. In principle, this is possible due to a differe...... to the recent discovery that Ca(2+)-activated small conductance K(+) channels (SK channels) are important for the repolarisation of atrial action potentials. Finally, an overview of current pharmacological treatment of AF is included....

  10. Extreme variation in the atrial septation of caecilians (Amphibia: Gymnophiona)

    Science.gov (United States)

    de Bakker, Desiderius M; Wilkinson, Mark; Jensen, Bjarke

    2015-01-01

    Caecilians (order Gymnophiona) are elongate, limbless, snake-like amphibians that are the sister-group (closest relatives) of all other recent amphibians (frogs and salamanders). Little is known of their cardiovascular anatomy and physiology, but one nearly century old study suggests that Hypogeophis (family Indotyphlidae), commonly relied upon as a representative caecilian species, has atrial septation in the frontal plane and more than one septum. In contrast, in other vertebrates there generally is one atrial septum in the sagittal plane. We studied the adult heart of Idiocranium (also Indotyphlidae) using immunohistochemistry and confirm that the interatrial septum is close to the frontal plane. Additionally, a parallel right atrial septum divides three-fourths of the right atrial cavity of this species. Idiocranium embryos in the Hill collection reveal that atrial septation initiates in the sagittal plane as in other tetrapods. Late developmental stages, however, see a left-ward shift of visceral organs and a concordant rotation of the atria that reorients the atrial septa towards the frontal plane. The gross anatomies of species from six other caecilian families reveal that (i) the right atrial septum developed early in caecilian evolution (only absent in Rhinatrematidae) and that (ii) rotation of the atria evolved later and its degree varies between families. In most vertebrates a prominent atrial trabeculation associates with the sinuatrial valve, the so-called septum spurium, and the right atrial septum seems homologous to this trabeculation but much more developed. The right atrial septum does not appear to be a consequence of body elongation because it is absent in some caecilians and in snakes. The interatrial septum of caecilians shares multiple characters with the atrial septum of lungfishes, salamanders and the embryonic septum primum of amniotes. In conclusion, atrial septation in caecilians is based on evolutionarily conserved structures but

  11. Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains

    NARCIS (Netherlands)

    Varga, J.J.; Barbier, Mariette; Mulet, Xavier; Bielecki, Piotr; Bartell, J.A.; Owings, J.P.; Martinez-Ramos, Inmaculada; Hittle, L.E.; Davis, M.R.; Damron, F.H.; Liechti, G.W.; Puchałka, Jacek; Martins dos Santos, Vitor; Ernst, R.K.; Papin, J.A.; Albertí, Sebastian; Oliver, Antonio; Goldberg, J.B.

    2015-01-01

    Background: Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify

  12. Pathogenic mechanism in lung fibrosis

    International Nuclear Information System (INIS)

    Witschi, H.; Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Dalbey, W.E.

    1979-01-01

    The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O 2 or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O 2 or x rays was synergistic. If exposure to O 2 or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed

  13. Oral submucous fibrosis: an update

    Directory of Open Access Journals (Sweden)

    Wollina U

    2015-04-01

    Full Text Available Uwe Wollina,1 Shyam B Verma,2 Fareedi Mukram Ali,3 Kishor Patil4 1Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany; 2Nirvana Skin Clinic, Vadodara, Gujarat, India; 3Departments of Oral and Maxillofacial Surgery, SMBT Dental College, Sangamner, Maharashtra, India; 4Departments of Oral Pathology and Microbiology, SMBT Dental College, Sangamner, Maharashtra, India Abstract: Oral submucous fibrosis (OSF is a premalignant condition caused by betel chewing. It is very common in Southeast Asia but has started to spread to Europe and North America. OSF can lead to squamous cell carcinoma, a risk that is further increased by concomitant tobacco consumption. OSF is a diagnosis based on clinical symptoms and confirmation by histopathology. Hypovascularity leading to blanching of the oral mucosa, staining of teeth and gingiva, and trismus are major symptoms. Major constituents of betel quid are arecoline from betel nuts and copper, which are responsible for fibroblast dysfunction and fibrosis. A variety of extracellular and intracellular signaling pathways might be involved. Treatment of OSF is difficult, as not many large, randomized controlled trials have been conducted. The principal actions of drug therapy include antifibrotic, anti-inflammatory, and antioxygen radical mechanisms. Potential new drugs are on the horizon. Surgery may be necessary in advanced cases of trismus. Prevention is most important, as no healing can be achieved with available treatments. Keywords: betel nut, betel quid, oral disease, squamous cell carcinoma, tobacco, fibrosis

  14. Cystic Fibrosis-Related Diabetes

    Directory of Open Access Journals (Sweden)

    Kayani Kayani

    2018-02-01

    Full Text Available Cystic fibrosis (CF is the most common autosomal recessive disorder in Caucasian populations. Individuals with CF have seen significant increases in life expectancy in the last 60 years. As a result, previously rare complications are now coming to light. The most common of these is cystic fibrosis-related diabetes (CFRD, which affects 40–50% of CF adults. CFRD significantly impacts the pulmonary function and longevity of CF patients, yet a lack of consensus on the best methods to diagnose and treat CFRD remains. We begin by reviewing our understanding of the pathogenesis of CFRD, as emerging evidence shows the cystic fibrosis transmembrane conductance regulator (CFTR also has important roles in the release of insulin and glucagon and in the protection of β cells from oxidative stress. We then discuss how current recommended methods of CFRD diagnosis are not appropriate, as continuous glucose monitoring becomes more effective, practical, and cost-effective. Finally, we evaluate emerging treatments which have narrowed the mortality gap within the CF patient group. In the future, pharmacological potentiators and correctors directly targeting CFTR show huge promise for both CFRD and the wider CF patient groups.

  15. Chronic pulmonary interstitial fibrosis in a blue-fronted Amazon parrot (Amazona aestiva aestiva).

    Science.gov (United States)

    Amann, Olga; Kik, Marja J L; Passon-Vastenburg, Maartje H A C; Westerhof, Ineke; Lumeij, Johannes T; Schoemaker, Nico J

    2007-03-01

    A 30-yr-old blue-fronted Amazon parrot (Amazon aestiva aestiva) was presented to the clinic with a history of sneezing more often during the last 2 mo. Physical examination revealed only a mild nasal discharge. Complete hematologic and plasma biochemical examination showed no abnormalities. Computerized tomography (CT) of the complete bird showed generalized lung alterations consistent with lung fibrosis. Two lung biopsies were taken. The results of the histologic examination of the biopsies confirmed the tentative CT diagnosis of pulmonary interstitial fibrosis. To our knowledge this is the first reported case of chronic pulmonary interstitial fibrosis diagnosed by means of a lung biopsy in an avian species. The histologic characteristics are discussed and compared with those of human idiopathic pulmonary fibrosis.

  16. Hemodynamic forces regulate developmental patterning of atrial conduction.

    Directory of Open Access Journals (Sweden)

    Michael C Bressan

    Full Text Available Anomalous action potential conduction through the atrial chambers of the heart can lead to severe cardiac arrhythmia. To date, however, little is known regarding the mechanisms that pattern proper atrial conduction during development. Here we demonstrate that atrial muscle functionally diversifies into at least two heterogeneous subtypes, thin-walled myocardium and rapidly conducting muscle bundles, during a developmental window just following cardiac looping. During this process, atrial muscle bundles become enriched for the fast conduction markers Cx40 and Nav1.5, similar to the precursors of the fast conduction Purkinje fiber network located within the trabeculae of the ventricles. In contrast to the ventricular trabeculae, however, atrial muscle bundles display an increased proliferation rate when compared to the surrounding myocardium. Interestingly, mechanical loading of the embryonic atrial muscle resulted in an induction of Cx40, Nav1.5 and the cell cycle marker Cyclin D1, while decreasing atrial pressure via in vivo ligation of the vitelline blood vessels results in decreased atrial conduction velocity. Taken together, these data establish a novel model for atrial conduction patterning, whereby hemodynamic stretch coordinately induces proliferation and fast conduction marker expression, which in turn promotes the formation of large diameter muscle bundles to serve as preferential routes of conduction.

  17. Entropy measurements in paroxysmal and persistent atrial fibrillation

    International Nuclear Information System (INIS)

    Cervigón, R; Moreno, J; Pérez-Villacastín, J; Reilly, R B; Millet, J; Castells, F

    2010-01-01

    Recent studies on atrial fibrillation (AF) have identified different activation patterns in paroxysmal and persistent AF. In this study, bipolar intra-atrial registers from 28 patients (14 paroxysmal AF and 14 persistent AF) were analyzed in order to find out regional differences in the organization in both types of arrhythmias. The organization of atrial electrical activity was assessed in terms of nonlinear parameters, such as entropy measurements. Results showed differences between the atrial chambers with a higher disorganization in the left atrium in paroxysmal AF patients and a more homogenous behavior along the atria in persistent AF patients

  18. Microencapsulation of Lefty-secreting engineered cells for pulmonary fibrosis therapy in mice.

    Science.gov (United States)

    Ma, Hongge; Qiao, Shupei; Wang, Zeli; Geng, Shuai; Zhao, Yufang; Hou, Xiaolu; Tian, Weiming; Chen, Xiongbiao; Yao, Lifen

    2017-05-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated GFP gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses. Copyright © 2017 the American Physiological Society.

  19. [Atrial fibrillation concomitant with valvular heart disease].

    Science.gov (United States)

    Ishii, Yosuke

    2013-01-01

    Patients with valvular heart disease frequently have atrial fibrillation(AF) due to elevated pressure and dilatation of the left and right atria and pulmonary veins. Guidelines for valvular heart disease and AF recommend that surgical treatment for the valvular heart disease should be performed concomitantly with AF surgery. The Full-Maze procedure has evolved into the gold standard of treatment for medically refractory AF. In addition to the pulmonary vein isolation, the right and left atrial incisions of the Full-Maze procedure are designed to block potential macroreentrant pathways. According to the mechanisms of AF with valvular heart disease, the Full-Maze procedure is more effective for the patients than the pulmonary vein isolation alone.

  20. Otorhinolaryngologic manifestations of cystic fibrosis: literature review

    Directory of Open Access Journals (Sweden)

    Carvalho, Carolina Pimenta

    2008-12-01

    Full Text Available Introduction: Cystic Fibrosis is the most common recessive autosomic genetic disease among Caucasians. It's caused by mutations in the gene that decodes regulatory protein for transmembrane conductance, resulting in defective transport of chlorine. Objective: Review the literature about Cystic Fibrosis, with emphasis on otorhinolaryngologic manifestations. Method: The online Pub Med databases were researched and we applied the following search terms Fibrosis Cystic and Sinusitis, and Mucoviscidosis and Sinusitis. Conclusions: Although it is not the main cause of death, the otorhinolaryngologic manifestations of the Cystic Fibrosis bring important morbidity to these patients.

  1. Endurance Sport Practice and Atrial Fibrillation

    OpenAIRE

    Calvo, Naiara; Mont, Lluis

    2010-01-01

    Atrial fibrillation (AF) is the most common cardiac rhythm disorder in clinical practice, with an estimated prevalence of 0.4% to 1% in the general population, increasing with age to 8% in those older than 80 years. The recognized risk factors for developing AF include age, hypertension, structural heart disease, diabetes mellitus, and hyperthyroidism. However, the etiology remains unclear in a significant number of patients younger than age 60 in whom no cardiovascular disease or any other k...

  2. Red Wine, Resveratrol and Atrial Fibrillation

    OpenAIRE

    Stephan, Laura Siga; Almeida, Eduardo Dytz; Markoski, Melissa Medeiros; Garavaglia, Juliano; Marcadenti, Aline

    2017-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as a...

  3. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Henrique Horta Veloso

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  4. Acute atrial fibrillation during dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Veloso Henrique Horta

    2003-01-01

    Full Text Available Dengue fever is a viral infection transmitted by the mosquito, Aedes aegypti. Cardiac rhythm disorders, such as atrioventricular blocks and ventricular ectopic beats, appear during infection and are attributed to viral myocarditis. However, supraventricular arrhythmias have not been reported. We present a case of acute atrial fibrillation, with a rapid ventricular rate, successfully treated with intravenous amiodarone, in a 62-year-old man with dengue hemorrhagic fever, who had no structural heart disease.

  5. Association Between Left Atrial Compression And Atrial Fibrillation: A Case Presentation And A Short Review Of Literature.

    Science.gov (United States)

    Ahmed, Niloy; Carlos, Morales-Mangual; Moshe, Gunsburg; Yitzhak, Rosen

    2016-01-01

    This case report describes a patient who developed palpitations and chest pain and was found to be in atrial fibrillation, which was likely due to the presence of an extra-cardiac mass. This was compressing the left atrium. The mass was related to small cell carcinoma, which decreased significantly in size after chemotherapy. Resolution of the atrial fibrillation correlated temporally with reduction in the size of the mass and alleviation of the left atrial compression.

  6. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease.

    Directory of Open Access Journals (Sweden)

    Peter G Traber

    Full Text Available Galectin-3 protein is critical to the development of liver fibrosis because galectin-3 null mice have attenuated fibrosis after liver injury. Therefore, we examined the ability of novel complex carbohydrate galectin inhibitors to treat toxin-induced fibrosis and cirrhosis. Fibrosis was induced in rats by intraperitoneal injections with thioacetamide (TAA and groups were treated with vehicle, GR-MD-02 (galactoarabino-rhamnogalaturonan or GM-CT-01 (galactomannan. In initial experiments, 4 weeks of treatment with GR-MD-02 following completion of 8 weeks of TAA significantly reduced collagen content by almost 50% based on Sirius red staining. Rats were then exposed to more intense and longer TAA treatment, which included either GR-MD-02 or GM-CT-01 during weeks 8 through 11. TAA rats treated with vehicle developed extensive fibrosis and pathological stage 6 Ishak fibrosis, or cirrhosis. Treatment with either GR-MD-02 (90 mg/kg ip or GM-CT-01 (180 mg/kg ip given once weekly during weeks 8-11 led to marked reduction in fibrosis with reduction in portal and septal galectin-3 positive macrophages and reduction in portal pressure. Vehicle-treated animals had cirrhosis whereas in the treated animals the fibrosis stage was significantly reduced, with evidence of resolved or resolving cirrhosis and reduced portal inflammation and ballooning. In this model of toxin-induced liver fibrosis, treatment with two galectin protein inhibitors with different chemical compositions significantly reduced fibrosis, reversed cirrhosis, reduced galectin-3 expressing portal and septal macrophages, and reduced portal pressure. These findings suggest a potential role of these drugs in human liver fibrosis and cirrhosis.

  7. Atrial Fibrillation in Eight New World Camelids.

    Science.gov (United States)

    Bozorgmanesh, R; Magdesian, K G; Estell, K E; Stern, J A; Swain, E A; Griffiths, L G

    2016-01-01

    There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). Describe clinical signs and outcome of AF in NWC. Eight New World Camelids admitted with AF. A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  8. Atrial fibrillation pearls and perils of management.

    Science.gov (United States)

    Kudenchuk, P J

    1996-01-01

    Atrial fibrillation, a common arrhythmia, is responsible for considerable cardiovascular morbidity. Its management demands more than antiarrhythmic therapy alone, but must address the causes and consequences of the arrhythmia. Although remediable causes are infrequently found, a thorough search for associated heart disease or its risk factors results in better-informed patient management. Controlling the ventricular response and protecting from thromboembolic complications are important initial goals of therapy and may include the administration of aspirin in younger, low-risk patients. Older patients and those with risk factors for systemic embolism are not adequately protected from stroke complications by aspirin therapy alone. It remains controversial whether all high-risk patients should receive warfarin and at what intensity. Whether and how sinus rhythm should be restored and maintained poses the greatest therapeutic controversy for atrial fibrillation. The mortal risk of antiarrhythmic therapy is substantially greater in patients with evidence of heart failure. In such persons, the risks and benefits of maintaining normal sinus rhythm with antiarrhythmic medications should be weighted carefully. A definitive cure for atrial fibrillation remains elusive, but promising surgical and catheter ablation therapies are being developed. PMID:8686300

  9. The mechanisms of atrial fibrillation in hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Bielecka-Dabrowa Agata

    2009-04-01

    Full Text Available Abstract Atrial fibrillation (AF is a complex condition with several possible contributing factors. The rapid and irregular heartbeat produced by AF increases the risk of blood clot formation inside the heart. These clots may eventually become dislodged, causing embolism, stroke and other disorders. AF occurs in up to 15% of patients with hyperthyroidism compared to 4% of people in the general population and is more common in men and in patients with triiodothyronine (T3 toxicosis. The incidence of AF increases with advancing age. Also, subclinical hyperthyroidism is a risk factor associated with a 3-fold increase in development of AF. Thyrotoxicosis exerts marked influences on electrical impulse generation (chronotropic effect and conduction (dromotropic effect. Several potential mechanisms could be invoked for the effect of thyroid hormones on AF risk, including elevation of left atrial pressure secondary to increased left ventricular mass and impaired ventricular relaxation, ischemia resulting from increased resting heart rate, and increased atrial eopic activity. Reentry has been postulated as one of the main mechanisms leading to AF. AF is more likely if effective refractory periods are short and conduction is slow. Hyperthyroidism is associated with shortening of action potential duration which may also contribute to AF.

  10. Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm.

    Directory of Open Access Journals (Sweden)

    Natalia Smorodinova

    Full Text Available Atrial fibrillation (AF is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients.The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR.We examined 46 subjects (19 with AF, and 27 in SR undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry.The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample.An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence.

  11. Cadmium stimulates myofibroblast differentiation and mouse lung fibrosis

    International Nuclear Information System (INIS)

    Hu, Xin; Fernandes, Jolyn; Jones, Dean P.; Go, Young-Mi

    2017-01-01

    Highlights: • Low-dose Cd stimulates differentiation of human lung fibroblast to myofibroblast. • Cd-stimulated fibrosis signaling involves activation of SMAD transcription factor. • Low-dose Cd intake in mice activates myofibroblast differentiation. - Abstract: Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain inCompletely defined. In the current study, we tested whether Cd activates fibrotic signaling in human fetal lung fibroblasts (HFLF) at micromolar and submicromolar Cd concentrations that do not cause cell death. Exposure of HFLF to low-dose Cd (≤1.0 μM) caused an increase in stress fibers and increased protein levels of myofibroblast differentiation markers, including α-smooth muscle actin (α-SMA) and extra-domain-A-containing fibronectin (ED-A-FN). Assay of transcription factor (TF) activity using a 45-TF array showed that Cd increased activity of 12 TF, including SMAD2/3/4 (mothers against decapentaplegic homolog) signaling differentiation and fibrosis. Results were confirmed by real-time PCR and supported by increased expression of target genes of SMAD2/3/4. Immunocytochemistry of lungs of mice exposed to low-dose Cd (0.3 and 1.0 mg/L in drinking water) showed increased α-SMA protein level with lung Cd accumulation similar to lung Cd in non-smoking humans. Together, the results show that relatively low Cd exposures stimulate pulmonary fibrotic signaling and myofibroblast differentiation by activating SMAD2/3/4-dependent signaling. The results

  12. A functional polymorphism C-509T in TGFβ-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.

    Directory of Open Access Journals (Sweden)

    Hailong Cao

    Full Text Available Transforming growth factor-β1 (TGF-β1 is an important mediator of atrial fibrosis and atrial fibrillation (AF. But the involved genetic mechanism is unknown. Herein, the TGF-β1 C-509 T polymorphism (rs1800469 was genotyped in a case-control study of 840 patients and 845 controls in Chinese population to explore the association between the polymorphism and susceptibility and prognosis of lone AF. As a result, the CT and/or TT genotypes had an increased lone AF risk [adjusted odds ratio (OR = 1.50 for CT, OR = 3.72 for TT, and OR = 2.15 for CT/TT], compared with the TGF-β1CC genotype. Moreover, patients carrying CT/TT genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying CC genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial TGF-β1 expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CT and TT genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -509 T allele than that of the -509 C allele. In conclusion, the TGF-β1 C-509 T polymorphism is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of TGF-β1 in AF.

  13. Recurrence of pulmonary vein conduction and atrial fibrillation after pulmonary vein isolation for atrial fibrillation

    DEFF Research Database (Denmark)

    Nilsson, Brian; Chen, Xu; Pehrson, Steen

    2006-01-01

    BACKGROUND: Both segmental ostial and circumferential extraostial pulmonary vein (PV) isolation have been proven effective in the treatment of atrial fibrillation (AF). However, the recurrence of AF and PV conduction after the 2 ablation strategies has never been compared in a randomized study...... isolation. Extraostial PV isolation was performed by encircling the paired left and right PVs, respectively, guided by an electroanatomic mapping system. RESULTS: A total of 84% of the patients had recurrent AF after the first PV isolation procedure, showing 72% with AF and 12% with organized left atrial...

  14. The Sociology and Entrenchment. A Cystic Fibrosis Test for Everyone?

    DEFF Research Database (Denmark)

    Koch, Lene; Stemerding, Dirk

    1994-01-01

    Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology......Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology...

  15. Staging of fibrosis in experimental non-alcoholic steatohepatitis by quantitative molecular imaging in rat models

    International Nuclear Information System (INIS)

    Schnabl, Bernd; Farshchi-Heydari, Salman; Loomba, Rohit; Mattrey, Robert F.; Hoh, Carl K.; Sirlin, Claude B.; Brenner, David A.; Behling, Cynthia A.; Vera, David R.

    2016-01-01

    Objectives: The aim of this study was to test the ability of hepatocyte-specific functional imaging to stage fibrosis in experimental rat models of liver fibrosis and progressive NASH. Using ROC analysis we tested the ability of a functional imaging metric to discriminate early (F1) from moderate (F2) fibrosis in the absence and presence of non-alcoholic steatohepatitis, which has not been achieved by any modality other than biopsy. Methods: Galactosyl Human Serum Albumin (GSA) was radiolabeled with the positron-emitter, 68 Ga, and injected (i.v., 45–95 μCi, 1.5 pmol/g TBW) into 44 healthy, 19 DEN-, and 22 CDAA-treated male rats. Quantification of liver function was achieved by calculating T90, defined as the time for the liver to accumulate 90 percent of the [ 68 Ga]GSA plateau value. All livers were excised immediately after imaging and prepared for a “blinded” histologic examination, which included fibrosis and fat content scores. Two sets of fibrosis scores were recorded for all of animals. The dominant fibrosis stage was recorded as the “Dominant Pattern” score and the “Maximum Pattern” score was assigned if a smaller distinct region with a higher fibrosis score was observed. Results: Animals with Dominant Pattern F0–F1 liver fibrosis (D − = 39) demonstrated significantly (P < 0.0001) faster accumulation of [ 68 Ga]GSA (2.40 ± 0.52 min) than those with moderate to advanced Dominant Pattern fibrosis F2 and F4 (D + = 26) (3.48 ± 1.01 min). ROC analysis (F0–F1 vs F2–F4) produced an area under the binormal curve (AUC) of 0.867 ± 0.045. Twenty-seven of the 65 rats had small regions with higher fibrosis scores. Six of these Maximum Pattern scores reclassified the animals from D − to D + . ROC analysis of F0–F1 versus F2–F4 rats without liver fat produced AUCs of 0.881 ± 0.053 for the Dominant Pattern Score and 0.944 ± 0.035 for the Maximum Pattern Score. Conclusions: PET Functional Imaging of [ 68 Ga]GSA accurately discriminates

  16. Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model.

    Science.gov (United States)

    van Koppen, Arianne; Verschuren, Lars; van den Hoek, Anita M; Verheij, Joanne; Morrison, Martine C; Li, Kelvin; Nagabukuro, Hiroshi; Costessi, Adalberto; Caspers, Martien P M; van den Broek, Tim J; Sagartz, John; Kluft, Cornelis; Beysen, Carine; Emson, Claire; van Gool, Alain J; Goldschmeding, Roel; Stoop, Reinout; Bobeldijk-Pastorova, Ivana; Turner, Scott M; Hanauer, Guido; Hanemaaijer, Roeland

    2018-01-01

    The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets. High-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involved in the development of NASH were identified, including lipid metabolism, inflammation, oxidative stress, and fibrosis. A data-integrative approach enabled identification of the active fibrotic process preceding histopathologic detection using a novel molecular fibrosis signature. Human studies were used to identify overlap of genes and processes and to perform a network biology-based prioritization to rank top candidate markers representing the early manifestation of fibrosis. An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (pre)clinical experimental time frames.

  17. Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease.

    Science.gov (United States)

    Morinaga, Jun; Kadomatsu, Tsuyoshi; Miyata, Keishi; Endo, Motoyoshi; Terada, Kazutoyo; Tian, Zhe; Sugizaki, Taichi; Tanigawa, Hiroki; Zhao, Jiabin; Zhu, Shunshun; Sato, Michio; Araki, Kimi; Iyama, Ken-ichi; Tomita, Kengo; Mukoyama, Masashi; Tomita, Kimio; Kitamura, Kenichiro; Oike, Yuichi

    2016-02-01

    Renal fibrosis is a common pathological consequence of chronic kidney disease (CKD) with tissue fibrosis closely associated with chronic inflammation in numerous pathologies. However, molecular mechanisms underlying that association, particularly in the kidney, remain unclear. Here, we determine whether there is a molecular link between chronic inflammation and tissue fibrosis in CKD progression. Histological analysis of human kidneys indicated abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Numerous ANGPTL2-positive renal tubule epithelial cells colocalized with cells positive for transforming growth factor (TGF)-β1, a critical mediator of tissue fibrosis. Analysis of M1 collecting duct cells in culture showed that TGF-β1 increases ANGPTL2 expression by attenuating its repression through microRNA-221. Conversely, ANGPTL2 increased TGF-β1 expression through α5β1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF-β1 signal amplification in kidney. Thus, ANGPTL2 and TGF-β1 positively regulate each other as renal fibrosis progresses. Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies potential therapeutic targets for CKD treatment. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction

    Directory of Open Access Journals (Sweden)

    Juan M. Povedano

    2015-07-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a degenerative disease of the lungs with an average survival post-diagnosis of 2–3 years. New therapeutic targets and treatments are necessary. Mutations in components of the telomere-maintenance enzyme telomerase or in proteins important for telomere protection are found in both familial and sporadic IPF cases. However, the lack of mouse models that faithfully recapitulate the human disease has hampered new advances. Here, we generate two independent mouse models that develop IPF owing to either critically short telomeres (telomerase-deficient mice or severe telomere dysfunction in the absence of telomere shortening (mice with Trf1 deletion in type II alveolar cells. We show that both mouse models develop pulmonary fibrosis through induction of telomere damage, thus providing proof of principle of the causal role of DNA damage stemming from dysfunctional telomeres in IPF development and identifying telomeres as promising targets for new treatments.

  19. Histopathologic analysis of atrial tissue in patients with atrial fibrillation: comparison between patients with atrial septal defect and patients with mitral valvular heart disease.

    Science.gov (United States)

    Kwak, Jae Gun; Seo, Jeong-Wook; Oh, Sam Se; Lee, Sang Yun; Ham, Eui Keun; Kim, Woong-Han; Kim, Soo-Jin; Bae, Eun Jung; Lim, Cheoung; Lee, Chang-Ha; Lee, Cheul

    2014-01-01

    Atrial fibrillation (AF) in adult patients with atrial septal defect (ASD) accompanies an enlarged right atrium (RA) with a less enlarged left atrium (LA), which is the opposite situation in patients with AF and mitral valvular disease. This study was to compare the histopathological change in the atrium of patients with AF of two different etiologies: ASD and mitral disease. Twenty-four patients were enrolled. Group 1 included patients with ASD (8), Group 2 included patients with ASD with AF (6), and Group 3 included patients with mitral disease with AF (10). Preoperative atrial volumes were measured. Atrial tissues were obtained during surgical procedures and stained with periodic acid-Schiff, smooth muscle actin, Sirius red, and Masson's trichrome to detect histopathologic changes compatible with AF. The severity of histopathological changes was represented with "positivity" and "strong positivity" after analyzing digitalized images of the staining. We investigated the relationship between the degree of atrial dilatation and severity of histopathological changes according to the groups and tissues. Group 2 and Group 3 patients showed a tendency toward an enlarged RA volume and enlarged LA volume, respectively, compared with each others. However, in the histopathologic analysis, "positivity" and "strong positivity" showed no significant positive correlations with the degree of atrial volume in special staining. A similar degree of histopathologic changes was observed in both atria in patients with AF (Group 2 and 3) regardless of the degree of dilatation of atrial volume and disease entities. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  20. Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

    Science.gov (United States)

    Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

    2016-01-01

    Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

  1. Bacteriocin-mediated competition in cystic fibrosis lung infections

    DEFF Research Database (Denmark)

    Ghoul, Melanie; West, Stuart A.; Johansen, Helle Krogh

    2015-01-01

    Bacteriocins are toxins produced by bacteria to kill competitors of the same species. Theory and laboratory experiments suggest that bacteriocin production and immunity play a key role in the competitive dynamics of bacterial strains. The extent to which this is the case in natural populations......, especially human pathogens, remains to be tested. We examined the role of bacteriocins in competition using Pseudomonas aeruginosa strains infecting lungs of humans with cystic fibrosis (CF). We assessed the ability of different strains to kill each other using phenotypic assays, and sequenced their genomes...

  2. Outcome in cystic fibrosis liver disease.

    LENUS (Irish Health Repository)

    Rowland, Marion

    2011-01-01

    Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.

  3. Laparoscopic cholecystectomy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    McGrath, D S

    2012-02-03

    Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic Fibrosis centre at the Cork University Hospital, were investigated for upper abdominal pain and found to have gallstones at ultrasonography. Laparoscopic cholecystectomy was performed successfully and, without complication, in both patients.

  4. Genetics Home Reference: idiopathic pulmonary fibrosis

    Science.gov (United States)

    ... these health problems has idiopathic pulmonary fibrosis . Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms. In people with idiopathic pulmonary fibrosis , scarring of the lungs increases over time until the lungs can no longer ...

  5. Imaging pulmonary fibrosis; Imagerie des fibroses pulmonaires

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, M.W.; Rety, F.; Naccache, J.M.; Girard, F.; Valeyre, D.F. [Hopital Avicenne, 93 - Bobigny (France). Service de radiologie et de pneumologie

    2001-02-01

    Localized fibrosis of the lung is usually scar tissue while diffuse pulmonary fibrosis is more often a sign of active disease. Chronic infiltrative lung disease may be classified into four categories: idiopathic pneumonitis, collagen diseases, granulomatosis (sarcoidosis), and caused by known diseases (pneumoconiosis, hypersensitivity pneumonitis, drug-induced lung disease, radiation). (authors)

  6. Self-management education for cystic fibrosis.

    LENUS (Irish Health Repository)

    Savage, Eileen

    2011-01-01

    Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted.

  7. Unusual Presentation Of Idiopathic Retroperitoneal Fibrosis: Case ...

    African Journals Online (AJOL)

    Idiopathic retroperitoneal fibrosis (IRF) is an uncommon entity described as progressive proliferation of connective tissues leading to a fibrous plaque-like lesions that encases the aorta and inferior vena cava inferior to the level of the renal arteries. Mass forming retroperitoneal fibrosis is rare. We present a rare case of a ...

  8. Pulmonary complications of cystic fibrosis

    International Nuclear Information System (INIS)

    Ng, M.Y.; Flight, W.; Smith, E.

    2014-01-01

    The life expectancy of patients with cystic fibrosis (CF) has steadily increased over recent decades with a corresponding increase in the frequency of complications of the disease. Radiologists are increasingly involved with managing and identifying the pulmonary complications of CF. This article reviews the common manifestations of CF lung disease as well as updating radiologists with a number of less well-known complications of the condition. Early and accurate detection of the pulmonary effects of CF are increasingly important to prevent irreversible lung damage and give patients the greatest possibility of benefiting from the new therapies becoming available, which correct the underlying defect causing CF

  9. Liver manifestations of cystic fibrosis

    International Nuclear Information System (INIS)

    Akata, Deniz; Akhan, Okan

    2007-01-01

    Chronic liver disease is one of the major complications of cystic fibrosis (CF). Significant liver disease is seen in 13-25% of children with CF. Improved life expectancy and prolonged follow-up have favored better characterization of the hepatic manifestations of CF and allowed direct observation of an increasing number of liver-related events. Liver disease typically develops in the first decade of life, with the incidence dropping rapidly after the age of 10 years. The wide spectrum of liver disease ranging from asymptomatic gallbladder abnormalities to biliary cirrhosis will be reviewed in this article

  10. Endocrine Disorders in Cystic Fibrosis.

    Science.gov (United States)

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Atrial Fibrillation in Embolic Stroke: Anticoagulant Therapy at UNTH ...

    African Journals Online (AJOL)

    Objective: The decision to commence anticoagulation in a patient with embolic stroke and atrial fibrillation (AF) is often a difficult one for many clinicians. The result can have significant impact on the patient. This study was therefore undertaken to review the use of anticoagulation in embolic stroke in the setting of atrial ...

  12. Dronedarone in high-risk permanent atrial fibrillation

    DEFF Research Database (Denmark)

    Connolly, Stuart J; Camm, A John; Halperin, Jonathan L

    2011-01-01

    Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events...... in high-risk permanent atrial fibrillation....

  13. The safety of flecainide treatment of atrial fibrillation

    DEFF Research Database (Denmark)

    Almroth, H; Andersson, Torben Bech; Fengsrud, E

    2011-01-01

    To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events.......To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events....

  14. Visualization of atrial myocardium with thallium-201: case report

    International Nuclear Information System (INIS)

    Cowley, M.J.; Coghlan, H.C.; Logic, J.R.

    1977-01-01

    An adult patient evaluated for cyanotic congenital heart disease was found to have pulmonary atresia with intact ventricular septum, hypoplastic right ventricle, and right atrial enlargement. Thallium-201 myocardial imaging before surgical correction showed thallium activity in the right atrium. Following the establishment of a conduit from the right atrium to pulmonary artery, the right-atrial thallium uptake was even more prominent

  15. Dabigatran versus warfarin in patients with atrial fibrillation

    NARCIS (Netherlands)

    Connolly, Stuart J.; Ezekowitz, Michael D.; Yusuf, Salim; Eikelboom, John; Oldgren, Jonas; Parekh, Amit; Pogue, Janice; Reilly, Paul A.; Themeles, Ellison; Varrone, Jeanne; Wang, Susan; Alings, Marco; Xavier, Denis; Zhu, Jun; Diaz, Rafael; Lewis, Basil S.; Darius, Harald; Diener, Hans-Christoph; Joyner, Campbell D.; Wallentin, Lars; Connolly, S. J.; Ezekowitz, M. D.; Yusuf, S.; Eikelboom, J.; Oldgren, J.; Parekh, A.; Reilly, P. A.; Themeles, E.; Varrone, J.; Wang, S.; Palmcrantz-Graf, E.; Haehl, M.; Wallentin, L.; Alings, A. M. W.; Amerena, J. V.; Avezum, A.; Baumgartner, I.; Brugada, J.; Budaj, A.; Caicedo, V.; Ceremuzynski, L.; Chen, J. H.; Commerford, P. J.; Dans, A. L.; Darius, H.; Di Pasquale, G.; Diaz, R.; Erol, C.; Ferreira, J.; Flaker, G. C.; Flather, M. D.; Franzosi, M. G.; Gamboa, R.; Golitsyn, S. P.; Gonzalez Hermosillo, J. A.; Halon, D.; Heidbuchel, H.; Hohnloser, S. H.; Hori, M.; Huber, K.; Jansky, P.; Kamensky, G.; Keltai, M.; Kim, S.; Lau, C. P.; Le Heuzey, J. Y. F.; Lewis, B. S.; Liu, L. S.; Nanas, J.; Razali, O.; Pais, P. S.; Parkhomenko, A. N.; Pedersen, K. E.; Piegas, L. S.; Raev, D.; Simmers, T. A.; Smith, P. J.; Talajic, M.; Tan, R. S.; Tanomsup, S.; Toivonen, L.; Vinereanu, D.; Xavier, D.; Zhu, J.; Diener, H. C.; Joyner, C. D.; Diehl, A.; Ford, G.; Robinson, M.; Silva, J.; Sleight, P.; Wyse, D. G.; Collier, J.; de Mets, D.; Hirsh, J.; Lesaffre, E.; Ryden, L.; Sandercock, P.; Anastasiou-Nana, M. I.; Andersen, G.; Annex, B. H.; Atra, M.; Bornstein, N. M.; Boysen, G.; Brouwers, P. J. A. M.; Buerke, M.; Burrell, L. M.; Chan, Y. K.; Chen, W. H.; Cheung, R. T. F.; Divakaramenon, S.; Donnan, G. A.; Duray, G. Z.; Dvorakova, H.; Fiedler, J.; Gardinale, E.; Gates, P. C.; Goshev, E. G.; Goto, S.; Gross, B.; Guimaraes, H. P.; Gulkevych, O.; Haberl, R. L.; Hankey, G.; Hartikainen, J.; Healey, J.; Iliesiu, A. M.; Irkin, O.; Jaxa-Chamiec, T.; Jolly, S.; Kaste, K. A. M.; Kies, B.; Kostov, K. D.; Kristensen, K. S.; Labovitz, A. J.; Lassila, R. P. T.; Lee, K. L. F.; Lutay, Y. M.; Magloire, P.; Mak, K. H.; Meijer, A.; Mihov, L.; Morillo, C. A.; Morillo, L. E.; Nair, G. M.; Norrving, B.; Ntalianis, A.; Ntsekhe, M.; Olah, L.; Pasco, P. M. D.; Peeters, A.; Perovic, V.; Petrov, I.; Pizzolato, G.; Rafti, F.; Rey, N. R.; Ribas, S.; Rokoss, M.; Sarembock, I. J.; Sheth, T.; Shuaib, A.; Sitkei, E.; Sorokin, E.; Srámek, M.; Strozynska, E.; Tanne, D.; Thijs, V. N. S.; Tomek, A.; Turazza, F.; Vanhooren, G.; Vizel, S. A.; Vos, J.; Wahlgren, N.; Weachter, R.; Zaborska, B.; Zaborski, J.; Zimlichman, R.; Cong, J.; Fendt, K.; Muldoon, S.; Bajkor, S.; Grinvalds, A.; Malvaso, M.; Pogue, J.; Simek, K.; Yang, S.; Alzogaray, M. F.; Bono, J. O.; Caccavo, A.; Cartasegna, L.; Casali, W. P.; Cuello, J. L.; Cuneo, C. A.; Elizari, M. V.; Fernandez, A. A.; Ferrari, A. E.; Gabito, A. J.; Goicoechea, R. F.; Gorosito, V. M.; Hirschson, A.; Hominal, M. A.; Hrabar, A. D.; Liberman, A.; Mackinnon, I. J.; Manzano, R. D.; Muratore, C. A.; Nemi, S. A.; Rodriguez, M. A.; Sanchez, A. S.; Secchi, J.; Vogel, D. R.; Colquhoun, D. M.; Crimmins, D. S.; Dart, A. M.; Davis, S. M.; Hand, P. J.; Kubler, P. A.; Lehman, R. G.; McBain, G.; Morrison, H. C.; New, G.; Singh, B. B.; Spence, C. Z.; Waites, J. H.; Auer, J.; Doweik, L.; Freihoff, F.; Gaul, G.; Gazo, F.; Geiger, H.; Giacomini, G.; Huber, G. W.; Jukic, I.; Lamm, G.; Niessner, H.; Podczeck, A.; Schuh, J.; Siostrzonek, P.; Steger, C.; Vogel, B.; Watzak, R.; Weber, H. S.; Weihs, W.; Blankoff, I.; Boland, J. L.; Brike, C.; Carlier, M.; Cools, F.; de Meester, A.; de Raedt, H. J.; de Wolf, L.; Dhooghe, G. M.; Dilling-Boer, D.; Elshot, S. R.; Fasseaux, S.; Goethals, M.; Goethals, P.; Gurne, O.; Hellemans, S.; Ivan, B.; Jottrand, M.; Kersschot, I.; Lecoq, E.; Marcovitch, O.; Melon, D.; Miljoen, H.; Missault, L.; Pierard, L. A.; Provenier, F.; Rousseau, M. F.; Stockman, D.; Tran-Ngoc, E.; van Mieghem, W.; Vandekerckhove, Y.; Vandervoort, P.; Verrostte, J.; Vijgen, J.; Armaganijan, D.; Braga, C.; Braga, J. C. F.; Cipullo, R.; Cunha, C. L. P.; de Paola, A.; Delmonaco, M. I.; Guimaraes, F. V.; Herek, L.; Kerr Saraiva, J. F.; Maia, L. N.; Lorga, A. M.; Lorga-Filho, A. M.; Marino, R. L.; Melo, C. S.; Mouco, O. M.; Pereira, V. C.; Precoma, D. B.; Rabelo, W.; Rassi, S.; Rossi, P. R.; Rossi Neto, J. M.; Silva, F. M.; Vidotti, M. H.; Zimmermann, S. L.; Anev, E. D.; Balabanov, T. A.; Baldjiev, E. S.; Bogusheva, E. S.; Chaneva, M. A.; Filibev, I. G.; Gotcheva, N. N.; Goudev, A. R.; Gruev, I. T.; Guenova, D. T.; Kamenova, Z. A.; Manov, E. I.; Panov, I. A.; Parvanova, Z. I.; Pehlivanova, M. B.; Penchev, P. T.; Penkov, N. Y.; Radoslavov, A. L.; Ramshev, K. N.; Runev, N. M.; Sindzhielieva, M. N.; Spirova, D. A.; Tsanova, V. M.; Tzekova, M. L.; Yaramov, G. K.; Aggarwal, R.; Bakbak, A. I.; Bayly, K.; Berlingieri, J. C.; Blackburn, K.; Bobbie, C.; Booth, A. W.; Borts, D.; Bose, S.; Boucher, P.; Brown, K.; Burstein, J. M.; Butt, J. C.; Carlson, B. D.; Chetty, R.; Chiasson, J. D.; Constance, C.; Costi, P.; Coutu, B.; Deneufbourg, I.; Dion, D.; Dorian, P.; Douketis, J. D.; Farukh, S.; Filipchuk, N. G.; Fox, B. A.; Fox, H. I.; Gailey, C. B.; Gauthier, M.; Glanz, A.; Green, M. S.; Habot, J.; Hink, H.; Kearon, C.; Kouz, S.; Lai, C.; Lai, K.; Lalani, A. V.; Lam, A. S.; Lapointe, L. A.; Leather, R. A.; Ma, P. T. S.; MacKay, E.; Mangat, I.; Mansour, S.; Melton, E.; Mitchell, L. B.; Morris, A. L.; Nisker, W. A.; O'Donnell, M. J.; O'Hara, G.; Omichinski, L. M.; Pandey, A. S.; Parkash, R.; Pesant, Y.; Pilon, C.; Pistawka, K. J.; Powell, C. N.; Price, J. B.; Prieur, S.; Rebane, T. M.; Ricci, A. J.; Roberge, J.; Roy, M.; Sapp, J. L.; Savard, D.; Schulman, S.; Sehl, M. J.; Sestier, F.; Shandera, R.; Shu, D.; Sterns, L. D.; St-Hilaire, R.; Syan, G. S.; Talbot, P.; Teitelbaum, I.; Tytus, R. H.; Winkler, L.; Zadra, R.; Zidel, B. S.; Bai, X. J.; Gao, W.; Gao, X.; Guan, D. M.; He, Z. S.; Hua, Q.; Li, H.; Li, L.; Li, W. M.; Lu, G. P.; Lv, S.; Meng, K.; Niu, H. Y.; Qi, D. G.; Qi, S. Y.; Qian, F.; Sun, N. L.; Wang, H. Y.; Wang, N. F.; Yang, Y. M.; Zeng, H.; Zhang, F.; Zhang, F. R.; Zhang, L.; Bohorquez, R.; Rosas, J. F.; Saent, L.; Vacca, M.; Velasco, V. M.; Belohlavek, J.; Cernohous, M.; Choura, M.; Dedek, V.; Filipensky, B.; Hemzsky, L.; Karel, I.; Kopeckova, I.; Kovarova, K.; Labrova, R.; Madr, T.; Poklopova, Z.; Rucka, D.; Simon, J.; Skalicka, H.; Smidova, M.; Spinar, J.; Dodt, K. K.; Egstrup, K.; Friberg, J.; Haar, D.; Husted, S.; Jensen, G. V.; Joensen, A. M.; Klarlund, K. K.; Lind Rasmussen, S.; Melchior, T. M.; Olsen, M. E.; Poulsen, M. K.; Ralfkiaer, N.; Rasmussen, L. H.; Skagen, K.; Airaksinen, K. E.; Huikuri, H. V.; Hussi, E. J.; Kettunen, P.; Mänttäri, M.; Melin, J. H.; Mikkelsson, J.; Peuhkurinen, K.; Virtanen, V. K.; Ylitalo, A.; Agraou, B.; Boucher, L.; Bouvier, J. M.; Boye, A.; Boye, B.; Decoulx, E. M.; Defaye, P.; Delay, M.; Desrues, H.; Gacem, K.; Igigabel, P.; Jacon, P.; Leparree, S.; Magnani, C.; Martelet, M.; Movallem, J.; Olive, T.; Poulard, J. E.; Tiam, B.; Appel, K. F.; Appel, S.; Bansemir, L.; Borggrefe, M.; Brachmann, J.; Bulut-Streich, N.; Busch, K.; Dempfle, C. E. H.; Desaga, M.; Desaga, V.; Dormann, A.; Fechner, I.; Genth-Zotz, S.; Haberbosch, W. G.; Harenberg, J.; Haverkamp, W. L.; Henzgen, R.; Heuer, H.; Horacek, T.; Huttner, H. B.; Janssens, U.; Jantke, H. J.; Klauss, V.; Koudonas, D.; Kreuzer, J.; Kuckuck, H.; Maselli, A.; Müegge, A.; Munzel, T. F.; Nitsche, K.; Nledegjen, A.; Parwani, A.; Pluemer-Schmidt, M.; Pollock, B. W.; Salbach, B. I.; Salbach, P. B.; Schaufele, T.; Schoels, W.; Schwab, S.; Siegmund, U.; Veltkamp, R.; Von Hodenberg, E.; Weber, R.; Zechmeister, M.; Anastasopoulous, A. A.; Foulidis, V. O.; Kaldara, E.; Karamitsos, K.; Karantzis, J.; Kirpizidis, H.; Kokkinakis, C.; Krommydas, A.; Lappas, C.; Lappas, G. I.; Manolis, A.; Manolis, A. S.; Orfanidis, Z.; Papamichalis, M.; Peltekis, L.; Savvas, S.; Skoumpourdis, E. A.; Stakos, D. A.; Styliadis, I.; Triposkiadis, F.; Tsounis, D.; Tziakas, D. N.; Zafiridis, T.; Zarifis, J. H.; Chan, G. C. P.; Chan, W. K.; Chan, W. S.; Lau, C. L.; Tse, H. F.; Tsui, P. T.; Yu, C. M.; Yue, C. S.; Fugedi, K.; Garai, B.; Jánosi, A.; Kadar, A.; Karpati, P.; Keltai, K.; Kosa, I.; Kovacs, I.; Laszlo, Z.; Mezei, L.; Rapi, J.; Regos, L. I.; Szakal, I.; Szigyarto, I.; Toth, K.; Zsa'ry, A.; Agarwal, D. K.; Aggarwal, R. K.; Arulvenkatesh, R.; Bharani, A.; Bhuvaneswaran, J. S.; Byrapaneni, R. B.; Chandwani, P.; Chopra, S.; Desai, N.; Deshpande, V.; Golla, N. P.; Gupta, J. B.; Haridas, K. K.; Hiremath, J.; Jain, A. S.; Jain, M.; Jhala, D. A.; Joseph, J.; Kaila, M.; Kannaiyan, A.; Kumar, S.; Kuruvila, P.; Mahorkar, V. K.; Metha, A.; Naik, A. M.; Narayanan, S.; Panwar, R. B.; Reddy, C.; Sawhney, J. P. S.; Shah, S. M.; Sharma, S.; Shetty, G. S.; Sinha, N.; Sontakke, N. N.; Srinivas, A.; Trivedi, M. 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H.; Wolff, R.; Yarnitsky, D.; Zeltser, D.; Argiolas, G.; Arteni, F.; Barbiero, M.; Bazzucco, R.; Bernardi, D.; Bianconi, L.; Bicego, D.; Brandini, R.; Bresciani, B.; Busoni, F.; Carbonieri, E.; Carini, M.; Catalano, A.; Cavallini, C.; D'Angelo, G.; de Caterina, R.; Di Niro, M.; Filigheddu, F.; Fraticelli, A.; Marconi, R.; Mennuni, M.; Moretti, L.; Mos, L.; Pancaldi, L. G.; Pirelli, S.; Renda, G.; Santini, M.; Tavarozzi, I.; Terrosu, P.; Uneddu, F.; Viccione, M.; Zanini, R.; Zingarini, G.; Aoyagi, T.; Eguma, H.; Fujii, K.; Fukuchi, M.; Fukunami, M.; Furukawa, Y.; Furuya, J.; Haneda, K.; Hara, S.; Hiroe, M.; Iesaka, Y.; Iijima, T.; Ishibashi, Y.; Iwade, K.; Kajiya, T.; Kakinoki, S.; Kamakura, S.; Katayama, Y.; Kihara, Y.; Kimura, K.; Kobayashi, S.; Kono, K.; Koretsune, Y.; Marui, N.; Matsuyama, T.; Meno, H.; Miyamoto, N.; Morikawa, S.; Myojin, K.; Nakamura, T.; Nishi, Y.; Ogawa, T.; Onaka, H.; Sakakibara, T.; Sakurai, S.; Sasaki, Y.; Sato, H.; Sugii, M.; Sumii, K.; Suzuki, S.; Takagi, M.; Takenaka, T.; Takeuchi, K.; Tanaka, S.; Tanouchi, J.; Ueda, K.; Ueyama, Y.; Ujihira, T.; Usui, M.; Yagi, M.; Yamada, T.; Yamamoto, H.; Yokochi, M.; Zen, E.; Abd Ghaphar, A. K.; Ang, C. K.; Chee, K. H.; Fong, A. F. Y.; Ismail, O.; Jeyaindran, S.; Kaur, S.; Lee, T. C.; Sandhu, R. S.; Shah, R. 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L.; Wilkinson, P. R.; Wilmott, R.; Wrigley, M. J.; Abadier, R.; Abbud, Z. A.; Adams, K. V.; Adler, S. W.; Agarwal, S.; Ahmed, A. M.; Ahmed, I. S.; Aiuto, M. A.; Albrittun, T. D.; Aliyar, P.; Allan, J. J.; Allen, D. P.; Allen, S. L.; Altschuller, A.; Amin, M.; Anand, I. S.; Antolick, A. B.; Arora, R.; Arouni, A. J.; Arslanian, C. L.; Asinger, R. W.; Aycock, G. R.; Bariciano, R. J.; Baron, S. B.; Barr, M. A.; Bartkowiak, A. J.; Baruch, L.; Basignani, C.; Bass, M. L.; Bean, B.; Bedwell, N. W.; Belber, A. D.; Belew, K.; Bell, Y. C.; Bellinger, R. L.; Bennett, W. T.; Bensimhon, D. R.; Benton, R.; Benton, R. E.; Ben-Yehuda, O.; Bertolet, B. D.; Betkowski, A. S.; Bilazarian, S. D.; Bissette, J. K.; Bobade, M. B.; Bolster, D. E.; Bomba, J.; Book, D. M.; Boscia, J. A.; Bouchard, A.; Bowman, L. M.; Bradley, A. J.; Brandt, H. D.; Bricker, C. R.; Brobyn, T. L.; Brock, R. I.; Broderick, T. M.; Broedlin, K.; Brown, A. M.; Browne, K. F.; Burke, S. W.; Burton, M. E.; Buser, G. A.; Capasso, M. K.; Caplan, W. E.; Cappelli, J.; Cardona, C.; Cardona, F.; Carlson, T.; Carr, K. W.; Casey, T.; Cashion, W. R.; Cass, D. T.; Chandrashekar, Y. S.; Changlani, M.; Chapla, P. G.; Chappell, J. H.; Chen, C.; Chen, Y.; Cho, N. R.; Cieszkowski, J. H.; Clark, D. M.; Clayton, R.; Clogston, C. W.; Cockrell, D. J.; Cohen, A. I.; Cohen, T. J.; Cole, J. F.; Conway, G.; Cook, V. R.; Cornish, A. L.; Cossu, S. F.; Costello, D. L.; Courtade, D. J.; Covelli, H. C.; Crenshaw, B. S.; Crews, L. A.; Crossley, G. H.; Culp, S. C.; Curtis, B. M.; Darrow, K.; de Raad, R. E.; DeGregorio, M.; DelNegro, A. A.; Denny, D. M.; Desai, V. S.; Deumite, N. J.; Dewey, L.; Dharawat, R. N.; Dobbs, B.; Donahue, S. M.; Downey, B.; Downing, J.; Drehobl, M. A.; Drewes, W. A.; Drucker, M. N.; Duff, R.; Duggal, M.; Dunlap, S. H.; Dunning, D. W.; DuThinh, V.; Dykstra, G. T.; East, C.; Eblaghie, M. C.; Edelstein, J.; Edmiston, W. A.; Eisen, H. J.; Eisenberg, S. J.; Ellis, J. R.; Ellison, H. 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L.; Guarnieri, T.; Gupta, A.; Gupta, J.; Hack, T. C.; Hall, B.; Hallak, O.; Halpern, S. W.; Hamburg, C.; Hamroff, G. S.; Han, J.; Handel, F.; Hankins, S. R.; Hanovich, G. D.; Hanrahan, J. A.; Haque, I. U.; Hargrove, J. L.; Harnick, P. E.; Harris, J. L.; Hartley, P. A.; Haskel, E. J.; Hatch, D.; Haught, W. H.; Hearne, S.; Hearne, S. E.; Hemphill, J. A.; Henderson, D. A.; Henes, C. H.; Hengerer-Yates, T.; Hermany, P. R.; Herzog, W. R.; Hickey, K.; Hilton, T. C.; Hockstad, E. S.; Hodnett, P.; Hoffmeister, R.; Holland, J.; Hollenweger, L.; Honan, M. B.; Hoopes, D. A.; Hordes, A. R.; Hotchkiss, D. A.; Howard, M. A.; Howard, V. N.; Hulyalkar, A. R.; Hurst, P.; Hutchison, L. C.; Ingram, J.; Isakov, T.; Ison, R. K.; Israel, C. N.; Jackson, B. K.; Jackson, K. N.; Jacobson, A. K.; Jain, S.; Jarmukli, N. F.; Joffe, I.; Johnson, L. E.; Johnson, S. A.; Johnson, S. L.; Jones, A. A.; Joyce, D. B.; Judson, P. L.; Juk, S. S.; Kaatz, S.; Kaddaha, R. M.; Kaplan, K. J.; Karunaratne, H. B.; Kennett, J. D.; Kenton, D. M.; Kettunen, J. A.; Khan, M. A.; Khant, R. N.; Kirkwood, M. D.; Knight, B. P.; Knight, P. O.; Knutson, T. J.; Kobayashi, J. F.; Kogan, A.; Kogan, A. D.; Koren, M. J.; Kosinski, E. J.; Kosolcharoen, P.; Kostis, J. B.; Kramer, J. H.; Kramer, S. D.; Kron, J.; Kuchenrither, C. R.; Kulback, S. J.; Kumar, A.; Kushner, D.; Kutscher, A.; Lai, C. K.; Lam, J. B.; Landau, C.; Landzberg, J. S.; Lang, D. T.; Lang, J. M.; Lanzarotti, C. J.; Lascewski, D. L.; Lau, T. K.; Lee, J. K.; Lee, S.; Leimbach, W. N.; LePine, A. M.; Lesser, M. F.; Leuchak, S. H.; Levy, R. M.; Lewis, W. R.; Lincoln, T. L.; Lingerfelt, W. M.; Liston, M.; Liu, Z. G.; Lloret, R. L.; Lohrbauer, L.; Longoria, D. C.; Lott, B. M.; Louder, D. R.; Loukinen, K. L.; Lovell, J.; Lue, S.; Mackall, J. A.; Maletz, L.; Marlow, L.; Martin, R. C.; Matsumura, M.; McCartney, M. J.; McDuffie, D.; McGough, M. F.; McGrew, F. A.; McGuinn, Wm P.; McMillen, M. D.; McNeff, J.; McPherson, C. A.; Meengs, M. E.; Meengs, W. L.; Meholick, A. W.; Meisner, J. S.; Melucci, M. B.; Mercando, A.; Merlino, J. D.; Meymandi, S. K.; Miele, M. B.; Miller, R. H.; Miller, S. H.; Minor, S. T.; Mitchell, M. R.; Modi, M.; Mody, F. V.; Moeller, C. L.; Moloney, J. F.; Moran, J. E.; Morcos, N. C.; Morgan, A.; Mukherjee, S. K.; Mullinax, K.; Murphy, A. L.; Mustin, A. J.; Myers, G. I.; Naccarelli, G. V.; Nadar, V. K.; Nallasivan, M.; Navas, J. P.; Niazi, I. K.; Nsah, E. N.; Nunamaker, J. L.; Ochalek, T. B.; O'dea, D. J.; Ogilvie, P. D.; Olliff, B.; Omalley, A. K.; O'Neill, P. G.; Onufer, J. R.; Orchard, R. C.; Orihuela, L. A.; Ortiz, E. C.; O'Sullivan, M. T.; Padanilam, B. J.; Pandey, P.; Patel, D. V.; Patel, R. J.; Patel, V. B.; Patlola, R. R.; Pennock, G. D.; Perlman, R.; Peters, P. H.; Petrillo, A. V.; Pezzella, S.; Phillips, D.; Pierre-Louis, J. R.; Pilcher, G.; Pillai, C.; Pollock, S. G.; Pond, M. S.; Porterfield, J. K.; Presant, L.; Pressler, J.; Pribble, A. H.; Promisloff, S. D.; Pudi, K. K.; Putnam, D. L.; Quartner, J.; Quinn, J. C.; Quinnell, C. M.; Raad, G. L.; Rasmussen, L. A.; Ray, C.; Reiffel, J. A.; Reynertson, S.; Richardson, J. W.; Riley, C. P.; Rippy, J. S.; Rittelmeyer, J. T.; Roberts, D. M.; Robertson, R.; Robinson, V. J. B.; Rocco, T. A.; Rosenbaum, D.; Roth, E. M.; Rottman, J. N.; Rough, R. R.; Rubenstein, J. J.; Sakkal, A. M.; Saleem, T.; Salerno, D. M.; Samendinger, M. L.; Sandeno, S.; Santilli, T. M.; Santucci, P.; Sattar, P.; Saxman, K. A.; Schaefer, S.; Schmidt, J.; Schneider, R. M.; Schocken, D. D.; Schrader, M. K.; Schramm, B. A.; Schultz, R. W.; Schussheim, A. E.; Schwarz, E. F.; Seamon, M. C.; Sestero, J. D.; Shah, M. P.; Shah, R.; Shalaby, A.; Shanes, J. G.; Sheftel, G. L.; Sheikh, K. H.; Shein, A. B.; Shemonsky, N. K.; Shepler, A.; Sheridan, E.; Shipwash, T. M.; Shopnick, R. I.; Short, W. G.; Shoukfeh, M. F.; Sibia, R. S.; Siler, T. M.; Silva, J. A.; Simons, G. R.; Simpson, A. G.; Simpson, H. R.; Simpson, V. J.; Singh, B. N.; Singh, N.; Singh, V. N.; Sitz, C. J.; Skatrud, L.; Sklar, J.; Slotwiner, D. J.; Smith, P. F.; Smith, P. N.; Smith, R. H.; Smith, J. E.; Sodowick, B. C.; Solomon, A. J.; Soltero, E. A.; Sonel, A. F.; Sperling, R.; Spiller, C.; Spink, B. Z.; Sprinkle, L. W.; Spyropoulos, A. C.; Stamos, T. D.; Steljes, A. D.; Stillabower, M. E.; Stover, T.; Strain, J. E.; Strickland, T. L.; Suresh, D. P.; Takata, T. S.; Taylor, J. S.; Taylor, M.; Teague, S. M.; Teixeia, J. M.; Telfer, E. A.; Terry, P. S.; Terry, R. W.; Thai, H. M.; Thalin, M.; Thomas, V. N.; Thompson, C. A.; Thompson, M. A.; Thornton, J. W.; Tidman, R. E.; Toler, B. S.; Traina, M. I.; Trippi, J. A.; Ujiiye, D. L.; Usedom, J. E.; van de Graaff, E.; van de Wall, L. R.; Vaughn, J. W.; Ver Steeg, D.; Vicari, R. M.; Vijay, N.; Vitale, C. B.; Vlastaris, A. G.; Voda, J.; Vora, K. N.; Voyles, W. F.; Vranian, R. B.; Vrooman, P. S.; Waack, P.; Waldo, A. L.; Walker, J. L.; Wallace, M. A.; Walsh, E. A.; Walsh, R. L.; Walton, A.; Washam, M.; Wehner, P. S.; Wei, J. Y.; Weiner, S.; Weiss, R. J.; Wells, D. M.; Wera-Archakul, W.; Wertheimer, J. H.; West, S. A.; Whitaker, J. H.; White, M. L.; White, R. H.; Whitehill, J. N.; Wiegman, P. J.; Wiesel, J.; Williams, J.; Williams, L. E.; Williams, M. L.; Williamson, V. K.; Wilson, V. E.; Wilson, W. W.; Woodfield, S. L.; Wulff, C. W.; Yates, S. W.; Yousuf, K. A.; Zakhary, B. G.; Zambrano, R.; Zimetbaum, P.; Zoble, R.; Zopo, A. R.; Zwerner, P. L.

    2009-01-01

    BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial

  16. EFFECT OF EXERCISE ON CYCLE LENGTH IN ATRIAL-FLUTTER

    NARCIS (Netherlands)

    VANDENBERG, MP; CRIJNS, HJGM; SZABO, BM; BROUWER, J; LIE, KI

    Objective-To examine the effect of exercise on cycle length in atrial flutter. Patients-15 patients with chronic atrial flutter. Seven patients were taking digoxin and six verapamil; two were not taking medication. Methods-All patients underwent bicycle ergometry. Flutter cycle length was measured

  17. Atrial fibrillation and bleeding complication - risk factors and risk marker

    NARCIS (Netherlands)

    Breithardt, G.; Ravens, U.; Kirchhof, P.; van Gelder, I. C.

    2012-01-01

    The development of atrial fibrillation (AF) is closely linked to risk factors like hypertension and heart failure, diabetes mellitus, myocardial infarction and valvular heart disease. These factors partly overlap with those which determine the progression of atrial fibrillation and the incidence of

  18. Percutaneous left atrial appendage closure for stroke prevention

    DEFF Research Database (Denmark)

    De Backer, Ole; Loupis, Anastasia M; Ihlemann, Nikolaj

    2014-01-01

    INTRODUCTION: In atrial fibrillation (AF) patients with an increased stroke risk, oral anticoagulation (OAC) is the standard treatment for stroke prevention. However, this therapy carries a high risk of major bleeding. Percutaneous closure of the left atrial appendage (LAA) is suggested as an alt...

  19. Right atrial myxoma at Muhimbili National Hospital: a case report ...

    African Journals Online (AJOL)

    lower cava hypertension and was in NYHA class IV. The 2-D echocardiography revealed a right atrial tumor encroaching the tricuspid valve, chest radiography showed gross cardiomegally and right lower lung collapse. A clinical diagnosis of right atrial tumour was reached. The patient was scheduled to undergo open heart ...

  20. Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum

    Directory of Open Access Journals (Sweden)

    Yan-Rong Yu

    2016-04-01

    Full Text Available In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4+ Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor β1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response. Keywords: Schistosomiasis, Schistosoma japonicum, Granuloma, Fibrosis, Taurine

  1. Identification of Novel Fibrosis Modifiers by In Vivo siRNA Silencing

    Directory of Open Access Journals (Sweden)

    Elisabeth H. Vollmann

    2017-06-01

    Full Text Available Fibrotic diseases contribute to 45% of deaths in the industrialized world, and therefore a better understanding of the pathophysiological mechanisms underlying tissue fibrosis is sorely needed. We aimed to identify novel modifiers of tissue fibrosis expressed by myofibroblasts and their progenitors in their disease microenvironment through RNA silencing in vivo. We leveraged novel biology, targeting genes upregulated during liver and kidney fibrosis in this cell lineage, and employed small interfering RNA (siRNA-formulated lipid nanoparticles technology to silence these genes in carbon-tetrachloride-induced liver fibrosis in mice. We identified five genes, Egr2, Atp1a2, Fkbp10, Fstl1, and Has2, which modified fibrogenesis based on their silencing, resulting in reduced Col1a1 mRNA levels and collagen accumulation in the liver. These genes fell into different groups based on the effects of their silencing on a transcriptional mini-array and histological outcomes. Silencing of Egr2 had the broadest effects in vivo and also reduced fibrogenic gene expression in a human fibroblast cell line. Prior to our study, Egr2, Atp1a2, and Fkbp10 had not been functionally validated in fibrosis in vivo. Thus, our results provide a major advance over the existing knowledge of fibrogenic pathways. Our study is the first example of a targeted siRNA assay to identify novel fibrosis modifiers in vivo.

  2. Identifying and quantifying the stromal fibrosis in muscularis propria of colorectal carcinoma by multiphoton microscopy

    Science.gov (United States)

    Chen, Sijia; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2014-10-01

    The examination of stromal fibrosis within colorectal cancer is overlooked, not only because the routine pathological examinations seem to focus more on tumour staging and precise surgical margins, but also because of the lack of efficient diagnostic methods. Multiphoton microscopy (MPM) can be used to study the muscularis stroma of normal and colorectal carcinoma tissue at the molecular level. In this work, we attempt to show the feasibility of MPM for discerning the microstructure of the normal human rectal muscle layer and fibrosis colorectal carcinoma tissue practicably. Three types of muscularis propria stromal fibrosis beneath the colorectal cancer infiltration were first observed through the MPM imaging system by providing intercellular microstructural details in fresh, unstained tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen, which may further characterize the severity of fibrosis. By comparing with the pathology analysis, these results show that the MPM has potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidence, which may guide subsequent therapy procedures for patients into good prognosis.

  3. Left Atrial Sphericity Index Predicts Early Recurrence of Atrial Fibrillation After Direct-Current Cardioversion

    DEFF Research Database (Denmark)

    Osmanagic, Armin; Möller, Sören; Osmanagic, Azra

    2016-01-01

    BACKGROUND: Attempts to achieve rhythm control using direct-current cardioversion (DCC) are common in those with persistent atrial fibrillation (AF). Although often successful, AF recurs within 1 month in as many as 57% of patients. The aim of this study was to assess whether a baseline left atri...

  4. Does Myocardial Infarction Beget Atrial Fibrillation and Atrial Fibrillation Beget Myocardial Infarction?

    NARCIS (Netherlands)

    Vermond, Rob A.; Van Gelder, Isabelle C.; Crijns, Harry J.; Rienstra, Michiel

    2015-01-01

    Atrial fibrillation (AF) affects millions of people worldwide.(1) It is already known several decades that AF is not a benign condition, and it's associated with a 5-fold increased risk of stroke, 3-fold increased risk of heart failure, and doubling of risk of dementia and death.(2-4) Myocardial

  5. Family history of atrial fibrillation is associated with earlier-onset and more symptomatic atrial fibrillation

    DEFF Research Database (Denmark)

    Gundlund, Anna; Fosbøl, Emil Loldrup; Kim, Sunghee

    2016-01-01

    BACKGROUND: We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. METHODS: Using the ORBIT-AF, we compared symptoms and disease...

  6. [Recurrent right atrial thrombus in a patient with atrial fibrillation and heart failure].

    Science.gov (United States)

    Elikowski, Waldemar; Wróblewski, Dariusz; Małek-Elikowska, Małgorzata; Mazurek, Andrzej; Foremska-Iciek, Joanna; Łazowski, Stanisław

    2015-11-01

    Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness. © 2015 MEDPRESS.

  7. Percutaneous left atrial appendage occlusion for stroke prevention in atrial fibrillation

    DEFF Research Database (Denmark)

    De Backer, O; Arnous, S; Ihlemann, N

    2014-01-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. One of its most devastating complications is the development of thromboembolism leading to fatal or disabling stroke. Oral anticoagulation (OAC, warfarin) is the standard treatment for strok...

  8. Atrial fibrillation and vascular disease-a bad combination

    DEFF Research Database (Denmark)

    Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

    2012-01-01

    This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...... pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic...

  9. Ventricular rhythm in atrial fibrillation under anaesthetic infusion with propofol

    International Nuclear Information System (INIS)

    Cervigón, R; Moreno, J; Pérez-Villacastín, J; Reilly, R B; Castells, F

    2009-01-01

    Changes in patients' autonomic tone and specific pharmacologic interventions may modify the ventricular response (actual heart rate) during atrial fibrillation (AF). Hypnotic agents such as propofol may modify autonomic balance as they promote a sedative state. It has been shown that propofol slightly slows atrial fibrillatory activity, but the net global effect on the ventricular response remains unknown. We aimed to evaluate in patients in AF the effect of a propofol bolus on the ventricular rate and regularity at ECG. We analysed the possible relation with local atrial fibrillatory activities, as ratios between atrial and ventricular rates (AVRs), analysing atrial activity from intracardiac electrograms at the free wall of the right and left atria and at the interatrial septum. We compared data at the baseline and after complete hypnosis. Propofol was associated with a more homogeneous ventricular response and lower AVR values at the interatrial septum

  10. Atrial Arrhythmias in Astronauts. Summary of a NASA Summit

    Science.gov (United States)

    Barr, Yael; Watkins, Sharmila; Polk, J. D.

    2011-01-01

    This slide presentation reviews the findings of a panel of heart experts brought together to study if atrial arrhythmias more prevalent in astronauts, and potential risk factors that may predispose astronauts to atrial arrhythmias. The objective of the panel was to solicit expert opinion on screening, diagnosis, and treatment options, identify gaps in knowledge, and propose relevant research initiatives. While Atrial Arrhythmias occur in approximately the same percents in astronauts as in the general population, they seem to occur at younger ages in astronauts. Several reasons for this predisposition were given: gender, hypertension, endurance training, and triggering events. Potential Space Flight-Related Risk factors that may play a role in precipitating lone atrial fibrillation were reviewed. There appears to be no evidence that any variable of the space flight environment increases the likelihood of developing atrial arrhythmias during space flight.

  11. Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Robin Lemmens

    2011-01-01

    Full Text Available Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease.

  12. Importância da anatomia da circulação coronária atrial na operação de Cox para controle da fibrilação atrial The importance of atrial coronary circulation on Cox surgery for control atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Marcelo B. JATENE

    1999-01-01

    Full Text Available Com o advento de novas técnicas cirúrgicas para o tratamento das arritmias cardíacas, em especial da fibrilação atrial, como a cirurgia de Cox, o conhecimento das características e do trajeto das artérias coronárias atriais assumiu grande importância. O objetivo deste trabalho é o estudo desta circulação e a definição dos padrões de irrigação atrial. Para tanto, utilizamos 30 corações a fresco de indivíduos sem cardiopatia prévia, cujas artérias coronárias e ramos foram visibilizados através de injeção de resina vinílica corada com tinta laca preta, seguida de cuidadosa dissecção. Após avaliação macroscópica das peças, não foram encontrados padrões de irrigação uniforme dos átrios. Porém, a artéria do nó sinoatrial (ANSA, quando analisada isoladamente, revelou não apenas padrões de origem, como também padrões de trajeto. Foram descritos 7 padrões de origem e trajeto da ANSA, considerando-se pontos de referências da estrutura anatômica dos átrios. Os padrões descritos, diferente dos encontrados por outros autores, são de fácil interpretação e de aplicabilidade direta em técnicas cirúrgicas que abordam os átrios.Since the appearance of new surgical techniques such as Cox surgery employed for the treatment of cardiac arrhythmia, especially for atrial fibrillation, the knowledge of coronary artery characteristics and courses has been of increasing importance. The aim of this study was the analysis of this circulation and definition of atrial irrigation patterns. Hence, the coronary arteries of 30 normal human hearts were injected with colored resin and carefully dissected. After macroscopic evaluation of the hearts, no atrial irrigation patterns were found. However, when only the sinus atrial node was analyzed, it showed origin patterns as well as course patterns. Seven origin and route patterns of this artery are described, considering the anatomical structure of the atria as reference

  13. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

    Full Text Available We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis.Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines.Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood.Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  14. T2 relaxation time is related to liver fibrosis severity

    Science.gov (United States)

    Siqueira, Luiz; Uppal, Ritika; Alford, Jamu; Fuchs, Bryan C.; Yamada, Suguru; Tanabe, Kenneth; Chung, Raymond T.; Lauwers, Gregory; Chew, Michael L.; Boland, Giles W.; Sahani, Duhyant V.; Vangel, Mark; Hahn, Peter F.; Caravan, Peter

    2016-01-01

    echo T2 weighted data. Statistical comparison was performed using ANOVA. Results (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1–2) 66.7±1.9 ms (n=30); moderate (Ishak 3–4) 71.6±1.7 ms (n=26); severe (Ishak 5–6) 72.4±1.4 ms (n=61); with relatively low standard error (~2.9 ms). There was a statistically significant difference between degrees of mild (Ishak fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA Pliver (e.g., 20–100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). Conclusions The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis. PMID:27190762

  15. Atrial Fibrillation: When the heart is not in rhythm | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: When the heart is not in rhythm Past ... show, Deal With It . Photo: TBS/Deal Understanding Atrial Fibrillation Atrial fibrillation (AFib) is the most common type ...

  16. Anomalous muscle bundle in the right atrium; Implication to trans atrial device closure

    Directory of Open Access Journals (Sweden)

    Saji Philip

    2017-09-01

    Full Text Available Intracavitary muscle bands or aberrant bands have been well described in all four chambers of the heart but rarely seen thick muscular band crossing right atrium. We report a case of devisable secundum atrial septal defect with an intra-atrial anomalous muscular band, crossing right atrial wall to the rim of the secundum atrial septal defect warranting surgical closure.

  17. Pulmonary artery-to-left atrial fistula discovered after the closure of atrial septal defect: A rare clinical scenario

    Directory of Open Access Journals (Sweden)

    Akshay Chauhan

    2018-01-01

    Full Text Available A case of the right pulmonary artery-to- left atrial fistula with atrial septal defect (ASD is presented. The fistula was detected after the patient developed desaturation following surgical closure of the ASD. It was managed with a transcatheter (trans-RPA route closure of the fistula using a 12-mm Amplatzer ventricular septal defect closure device.

  18. Does Left Atrial Volume and Pulmonary Venous Anatomy Predict the Outcome of Catheter Ablation of Atrial Fibrillation ?

    NARCIS (Netherlands)

    Hof, Irene; Chilukuri, Karuna; Arbab-Zadeh, Armin; Scherr, Daniel; Dalal, Darshan; Nazarian, Saman; Henrikson, Charles; Spragg, David; Berger, Ronald; Marine, Joseph; Calkins, Hugh

    Introduction: Preprocedural factors may be helpful in selecting patients with atrial fibrillation (AF) for treatment with catheter ablation and in making an assumption regarding their prognosis. The aims of this study were to investigate whether left atrial (LA) volume and pulmonary venous (PV)

  19. Assessment of non-invasive time and frequency atrial fibrillation organization markers with unipolar atrial electrograms

    International Nuclear Information System (INIS)

    Alcaraz, Raúl; Hornero, Fernando; Rieta, José J

    2011-01-01

    The standard electrocardiogram (ECG) is the most common non-invasive way to study atrial fibrillation (AF). In this respect, previous works have shown that the surface lead V 1 reflects mainly the dominant atrial frequency (DAF) of the right atrium (RA), which has been widely used to study AF. In a similar way, AF organization and fibrillatory (f) wave amplitude are two recently proposed non-invasive AF markers. These markers need to be validated with invasive recordings in order to assess their capability to reliably reflect the internal fibrillatory activity dynamics. In this work, these two non-invasive metrics have been compared with similar measures recorded from two unipolar atrial electrograms (AEGs). For both ECG and AEG signals, AF organization has been computed by applying a nonlinear regularity index, such as sample entropy (SampEn), to the atrial activity (AA) and to its fundamental waveform, defined as the main atrial wave (MAW). The surface and epicardial f wave amplitude has been estimated through their mean power. Results obtained for 38 patients showed statistically significant correlations between the values measured from surface and invasive recordings, thus corroborating the usefulness of the aforesaid markers in the non-invasive study of AF. Precisely, for AF organization computed from the MAW, the correlation coefficients between surface and both AEGs were R = 0.926 (p < 0.001) and R = 0.932 (p < 0.001). For f wave amplitude, slightly lower significant relationships were noticed, the correlation coefficients being R = 0.765 (p < 0.001) and R = 0.842 (p < 0.001). These outcomes together with interesting linear relationships found among the parameters suggest that AF regularity estimated via SampEn and f wave amplitude can non-invasively characterize the epicardial activity related to AF

  20. Interatrial septum pacing decreases atrial dyssynchrony on strain rate imaging compared with right atrial appendage pacing.

    Science.gov (United States)

    Yasuoka, Yoshinori; Abe, Haruhiko; Umekawa, Seiko; Katsuki, Keiko; Tanaka, Norio; Araki, Ryo; Imanaka, Takahiro; Matsutera, Ryo; Morisawa, Daisuke; Kitada, Hirokazu; Hattori, Susumu; Noda, Yoshiki; Adachi, Hidenori; Sasaki, Tatsuya; Miyatake, Kunio

    2011-03-01

    Interatrial septum pacing (IAS-P) decreases atrial conduction delay compared with right atrial appendage pacing (RAA-P). We evaluate the atrial contraction with strain rate of tissue Doppler imaging (TDI) during sinus activation or with IAS-P or RAA-P. Fifty-two patients with permanent pacemaker for sinus node disease were enrolled in the study. Twenty-three subjects were with IAS-P and 29 with RAA-P. The time from end-diastole to peak end-diastolic strain rate was measured and corrected with RR interval on electrocardiogram. It was defined as the time from end-diastole to peak end-diastolic strain rate (TSRc), and the balance between maximum and minimum TSRc at three sites (ΔTSRc) was compared during sinus activation and with pacing rhythm in each group. There were no significant differences observed in general characteristics and standard echocardiographic parameters except the duration of pacing P wave between the two groups. The duration was significantly shorter in the IAS-P group compared with the RAA-P group (95 ± 34 vs 138 ± 41; P = 0.001). TSRc was significantly different between sinus activation and pacing rhythm (36.3 ± 35.7 vs 61.6 ± 36.3; P = 0.003) in the RAA-P group, whereas no significant differences were observed in the IAS-P group (25.4 ± 12.1 vs 27.7 ± 14.7; NS). During the follow-up (mean 2.4 ± 0.7 years), the incidence of paroxysmal atrial fibrillation (AF) conversion to permanent AF was not significantly different between the two groups. IAS-P decreased the contraction delay on atrial TDI compared to RAA-P; however, it did not contribute to the reduction of AF incidence in the present study. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

  1. Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

    Science.gov (United States)

    Ravens, Ursula

    2017-11-01

    In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K + ) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two-pore domain K + (K2P) channels (tandem of P domains, weak inward-rectifying K + channels (TWIK-1), TWIK-related acid-sensitive K + channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

  2. [Left atrial electric isolation in the treatment of atrial fibrillation secondary to rheumatic valvular disease].

    Science.gov (United States)

    Graffigna, A; Pagani, F; Minzioni, G; Salerno, J; Viganò, M

    1992-08-01

    Surgical isolation of the left atrium was performed for the treatment of chronic atrial fibrillation secondary to valvular disease in 100 patients who underwent valve surgery. From May 1989 to September 1991, 62 patients underwent mitral valve surgery (Group I), 19 underwent mitral valve surgery and DeVega tricuspid annuloplasty (Group II), 15 underwent mitral and aortic surgery (Group III), and 4 patients underwent mitral and aortic surgery and DeVega tricuspid annuloplasty (Group IV). Left atrial isolation was performed prolonging the usual left paraseptal atriotomy towards the left fibrous trigone anteriorly, and the postero-medial commissure posteriorly. The incision was conducted a few millimeters apart from the mitral valve annulus, and cryolesion were placed at the edges to ensure complete electrophysiological isolation of the left atrium. Operative mortality accounted for 3 cases (3%). In 79 patients (81.4%) sinus rhythm recovered and persisted until discharge from the hospital. No differences were found between the groups (Group I: 80.7%; Group II: 68.5%; Group III 86.7%, Group IV 75% - p = N.S.). Three cases of late mortality (3.1%) were registered. long-term results showed persistence of SR in 71% of Group I, 61.2% of Group II, 85.8% of Group III, and 100% of Group IV. The unique risk factor for late recurrency of atrial fibrillation was found to be a duration of preoperative AF longer than 6 months. Due to the high success rate in recovering the sinus rhythm, we suggest left atrial isolation in patients with chronic atrial fibrillation undergoing valvular surgery.

  3. Postinjection Muscle Fibrosis from Lupron

    Directory of Open Access Journals (Sweden)

    Erica Everest

    2015-01-01

    Full Text Available We describe the case of a 6.5-year-old girl with central precocious puberty (CPP, which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate Depot-Ped (3 months intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection.

  4. Drug-induced Pulmonary Fibrosis

    International Nuclear Information System (INIS)

    Daba, Mohammad H.; Al-Arifi, Mohammad N; Gubar, Othman A.; El-Tahir, Kamal E.

    2004-01-01

    Pulmonary fibrosis is characterized by the accumulation of excessive connective tissue in the lungs. Its causes include chronic administration of some drugs for example bleomycin, cyclophosphamide, amiodarone, procainamide, penicillamine, gold and nitrofurantoin; exposure to certain environmental factors such as gases, asbestos and silica and bacterial or fungal infections. Some systemic diseases also predispose to the disease for example rheumatoid arthritis and systemic lupus erythematosus. The disease is associated with release of oxygen radicals and some mediators such as tumor necrosis factor-alpha TNF-alpha, transforming growth factor-beta Tbgf-beta, PDGF, If-I, Et-I and interleukins 1, 4, 8 and 13. The symptoms of the disease include dyspne a, non-productive cough, fever and damage to the lung cells. It is diagnosed with the aid of chest radiography, high resolution computed tomographic scanning and the result of pulmonary function tests. Drug-induced pulmonary fibrosis may involve release of free oxygen radicals and various cytokines for example Il-I beta and TNF-alpha via activation of nuclear transcription factor Nf-beta as in the case of bleomycin and mitomycin or via release of TGF-beta as in case of tamoxifen or via inhibition of macrophages and lymphocytes phospholipases as in the case of amiodarone with the resultant accumulation of phospholipids and reduction of the immune system. (author)

  5. Combined percutaneous balloon mitral valvuloplasty and left atrial appendage occlusion device implantation for rheumatic mitral stenosis and atrial fibrillation

    International Nuclear Information System (INIS)

    Murdoch, Dale; McAulay, Laura; Walters, Darren L.

    2014-01-01

    Rheumatic heart disease is a common cause of cardiovascular morbidity and mortality worldwide, mostly in developing countries. Mitral stenosis and atrial fibrillation often coexist, related to both structural and inflammatory changes of the mitral valve and left atrium. Both predispose to left atrial thrombus formation, commonly involving the left atrial appendage. Thromboembolism can occur, with devastating consequences. We report the case of a 62 year old woman with rheumatic heart disease resulting in mitral stenosis and atrial fibrillation. Previous treatment with warfarin resulted in life-threatening gastrointestinal bleeding and she refused further anticoagulant therapy. A combined procedure was performed, including percutaneous balloon mitral valvuloplasty and left atrial appendage occlusion device implantation with the Atritech® Watchman® device. No thromboembolic or bleeding complications were encountered at one year follow-up. Long-term follow-up in a cohort of patients will be required to evaluate the safety and efficacy of this strategy

  6. Combined percutaneous balloon mitral valvuloplasty and left atrial appendage occlusion device implantation for rheumatic mitral stenosis and atrial fibrillation

    Energy Technology Data Exchange (ETDEWEB)

    Murdoch, Dale, E-mail: dale_murdoch@health.qld.gov.au [The Prince Charles Hospital, Brisbane (Australia); The University of Queensland, Brisbane (Australia); McAulay, Laura [The Prince Charles Hospital, Brisbane (Australia); Walters, Darren L. [The Prince Charles Hospital, Brisbane (Australia); The University of Queensland, Brisbane (Australia)

    2014-11-15

    Rheumatic heart disease is a common cause of cardiovascular morbidity and mortality worldwide, mostly in developing countries. Mitral stenosis and atrial fibrillation often coexist, related to both structural and inflammatory changes of the mitral valve and left atrium. Both predispose to left atrial thrombus formation, commonly involving the left atrial appendage. Thromboembolism can occur, with devastating consequences. We report the case of a 62 year old woman with rheumatic heart disease resulting in mitral stenosis and atrial fibrillation. Previous treatment with warfarin resulted in life-threatening gastrointestinal bleeding and she refused further anticoagulant therapy. A combined procedure was performed, including percutaneous balloon mitral valvuloplasty and left atrial appendage occlusion device implantation with the Atritech® Watchman® device. No thromboembolic or bleeding complications were encountered at one year follow-up. Long-term follow-up in a cohort of patients will be required to evaluate the safety and efficacy of this strategy.

  7. Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63-Integrin β1 Interaction.

    Science.gov (United States)

    Takawale, Abhijit; Zhang, Pu; Patel, Vaibhav B; Wang, Xiuhua; Oudit, Gavin; Kassiri, Zamaneh

    2017-06-01

    Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway. We examined the function of TIMP1 in myocardial fibrosis using Timp1 -deficient mice and 2 in vivo models of myocardial fibrosis (angiotensin II infusion and cardiac pressure overload), in vitro analysis of adult cardiac fibroblasts, and fibrotic myocardium from patients with dilated cardiomyopathy (DCM). Timp1 deficiency significantly reduced myocardial fibrosis in both in vivo models of cardiomyopathy. We identified a novel mechanism for TIMP1 action whereby, independent from its matrix metalloproteinase-inhibitory function, it mediates an association between CD63 (cell surface receptor for TIMP1) and integrin β1 on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and β-catenin, leading to de novo collagen synthesis. This mechanism was consistently observed in vivo, in cultured cardiac fibroblasts, and in human fibrotic myocardium. In addition, after long-term pressure overload, Timp1 deficiency persistently reduced myocardial fibrosis and ameliorated diastolic dysfunction. This study defines a novel matrix metalloproteinase-independent function of TIMP1 in promoting myocardial fibrosis. As such targeting TIMP1 could prove to be a valuable approach in developing antifibrosis therapies. © 2017 American Heart Association, Inc.

  8. NASA's First Atrial Fibrillation Case - Deke Slayton

    Science.gov (United States)

    Tarver, William J.

    2010-01-01

    Concerns about heart dysrhythmia have been present since the earliest days of the US manned space program. While information about an astronaut's health is general kept private, one of the original seven American astronaut's health status was played out in a very public forum. Donald "Deke" Slayton was removed from the second manned space flight when it was discovered he had idiopathic atrial fibrillation. Referencing the original medical documents, details of how this was discovered and managed from the medical perspective will be reviewed. This is NASA's first heart dysrhythmia case in an astronaut and it proves quite interesting when placed in historic perspective.

  9. Current approaches in atrial fibrillation treatment

    Directory of Open Access Journals (Sweden)

    Cenk Sarı

    2014-09-01

    Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia encountered in clinical practice. Its incidence increases with age. AF is classified into subtypes according to the duration and/or able to provide sinus rhytym. İnitially, patients should be evaluated for rhythm or rate control for appropriate treatment. Second stage of strategy aimed to investigate the feasibility of anticoagulation therapy. Recently, due to the progress made in treatment with rhythm control and anticoagulation therapy, either American or European guidelines have been renovated. These developments have taken place in the newly published guide. In this article, the current change in the management of AF is discussed.

  10. The polyuria of paroxysmal atrial tachycardia

    Science.gov (United States)

    Kinney, M. J.; Stein, R. M.; Discala, V. A.

    1974-01-01

    Two patients with paroxysmal atrial fibrillation and an associated polyuria were studied to delineate the mechanism of the increase in urine flow. A striking saluresis was noted in both patients. The increased sodium excretion was probably due to decreased sodium reabsorption, perhaps at proximal tubular nephron sites. This inhibition of sodium reabsorption could explain both the saluresis and some part or all of the polyuria. Re-evaluation of earlier case reports reveals patterns of concomitant salt and water excretion consistent with this mechanism. The saluresis cannot be explained by the previously favored hypothesis of antidiuretic hormone inhibition.

  11. Echocardiographic study of left atrial myxoma

    Directory of Open Access Journals (Sweden)

    Dalal J

    1979-01-01

    Full Text Available Four cases of left atrial myxoma were diagnosed pre-operatively by echocardiography. All cases showed characteristic echocardio-graphic features of variegated shadows behind the mitral valve in diastole and within the left atrium in systole. In two cases the my-xomas were surgically removed and confirmed on histology. In one case the post-operative echocardiogram showed complete dis-appearance of the abnormal shadows. Echocardiography is the most reliable method today for the diagnosis of a myxoma.

  12. Exhaled nitric oxide in paediatric asthma and cystic fibrosis.

    Science.gov (United States)

    Lundberg, J O; Nordvall, S L; Weitzberg, E; Kollberg, H; Alving, K

    1996-01-01

    Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases. PMID:8984919

  13. Atrial conduction times and left atrial mechanical functions and their relation with diastolic function in prediabetic patients.

    Science.gov (United States)

    Gudul, Naile Eris; Karabag, Turgut; Sayin, Muhammet Rasit; Bayraktaroglu, Taner; Aydin, Mustafa

    2017-03-01

    The aim of this study was to investigate atrial conduction times and left atrial mechanical functions, the noninvasive predictors of atrial fibrillation, in prediabetic patients with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Study included 59 patients (23 males, 36 females; mean age 52.5 ± 10.6 years) diagnosed with IFG or IGT by the American Diabetes Association criteria, and 43 healthy adults (22 males, 21 females; mean age 48.5 ± 12.1 years). Conventional and tissue Doppler echocardiography were performed. The electromechanical delay parameters were measured from the onset of the P wave on the surface electrocardiogram to the onset of the atrial systolic wave on tissue Doppler imaging from septum, lateral, and right ventricular annuli. The left atrial volumes were calculated by the disk method. Left atrial mechanical functions were calculated. The mitral E/A and E'/A' ratios measured from the lateral and septal annuli were significantly lower in the prediabetics compared to the controls. The interatrial and left atrial electromechanical delay were significantly longer in prediabetic group compared to the controls. Left atrial active emptying volume (LAAEV) and fraction (LAAEF) were significantly higher in the prediabetics than the controls. LAAEV and LAAEF were significantly correlated with E/A, lateral and septal E'/A'. In the prediabetic patients, the atrial conduction times and P wave dispersion on surface electrocardiographic were longer before the development of overt diabetes. In addition, the left atrial mechanical functions were impaired secondary to a deterioration in the diastolic functions in the prediabetic patients.

  14. Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

    Science.gov (United States)

    Marchlinski, F; Callans, D; Gottlieb, C; Rodriguez, E; Coyne, R; Kleinman, D

    1998-08-01

    Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the

  15. Long-term follow-up of patients with paroxysmal atrial fibrillation and severe left atrial scarring: comparison between pulmonary vein antrum isolation only or pulmonary vein isolation combined with either scar homogenization or trigger ablation.

    Science.gov (United States)

    Mohanty, Sanghamitra; Mohanty, Prasant; Di Biase, Luigi; Trivedi, Chintan; Morris, Eli Hamilton; Gianni, Carola; Santangeli, Pasquale; Bai, Rong; Sanchez, Javier E; Hranitzky, Patrick; Gallinghouse, G Joseph; Al-Ahmad, Amin; Horton, Rodney P; Hongo, Richard; Beheiry, Salwa; Elayi, Claude S; Lakkireddy, Dhanunjaya; Madhu Reddy, Yaruva; Viles Gonzalez, Juan F; Burkhardt, J David; Natale, Andrea

    2017-11-01

    Left atrial (LA) scarring, a consequence of cardiac fibrosis is a powerful predictor of procedure-outcome in atrial fibrillation (AF) patients undergoing catheter ablation. We sought to compare the long-term outcome in patients with paroxysmal AF (PAF) and severe LA scarring identified by 3D mapping, undergoing pulmonary vein isolation (PVAI) only or PVAI and the entire scar areas (scar homogenization) or PVAI+ ablation of the non-PV triggers. Totally, 177 consecutive patients with PAF and severe LA scarring were included. Patients underwent PVAI only (n = 45, Group 1), PVAI+ scar homogenization (n = 66, Group 2) or PVAI+ ablation of non-PV triggers (n = 66, Group 3) based on operator's choice. Baseline characteristics were similar across the groups. After first procedure, all patients were followed-up for a minimum of 2 years. The success rate at the end of the follow-up was 18% (8 pts), 21% (14 pts), and 61% (40 pts) in Groups 1, 2, and 3, respectively. Cumulative probability of AF-free survival was significantly higher in Group 3 (overall log-rank P homogenization. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

  16. Right and Left Ventricular Volumes in Atrial Septal Defect Studied by Radiocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Ivancevic, D. [Radioisotope Department, Internal Clinic, Rebro, Zagreb, Yugoslavia (Croatia); Vernejoul, P. de; Kellershohn, C. [CEA, Service Hospitalier Frederic Joliot, Departement de Biologie, Orsay (France)

    1971-02-15

    Radiocardiography with radioiodinated ({sup 131}I) human serum albumin and barium ({sup 137m}Ba) solution injected into the right subclavian vein has been performed in a group of 43 patients with atrial septal defect and left-to-right shunt. Data on the output and ejection index of each ventricle are essential for the estimation of the diastolic and residual volumes of the right and left ventricle. The systemic flow was therefore calculated according to Veall's formula and the pulmonary flow and the shunt How were determined using the method of de Vernejoul and co-workers. The formulas for the calculation of ventricular volumes were modified. The results show that many cases of atrial septal defect have an enlarged right ventricle whereas the left ventricle remains normal or is diminished. These changes correlate well with the amount of the shunt flow. In both ventricles the ventricular volumes show a good correlation with the stroke volumes. For the regulation of the pulmonary blood volume the right ventricle seems to be more important than the left ventricle. The operative closure of atrial septal defect (in 14 patients) has normalized the size of ventricular volumes. (author)

  17. Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in