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 ...

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

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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

Effect of sodium channel blocker, pilsicainide hydrochloride, on net inward current of atrial myocytes in thyroid hormone toxicosis rats.

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Yamakawa, Munesada; Sunagawa, Masanori; Shimabukuro, Michio; Higa, Namio; Takasu, Nobuyuki; Kosugi, Tadayoshi

2005-07-01

To investigate effect of pilsicainide hydrochloride (pilsicainide) on electrocardiogram (ECG) signals and action potentials (APs) of atrial myocytes, levo-thyroxine (T4, 500 microg/kg body weight) was daily injected into peritoneal cavity of Sprague-Dawley rats for 14 days. T4-treatment significantly shortened RR interval, P wave, and QRS complex durations on ECG. Although pilsicainide did not affect the heart rate, P wave and corrected QT interval (QTc) was increased in T4-treated rats. AP recordings revealed that AP durations at 20%, 50%, and 90% repolarization were significantly shortened and maximal rate of rise (Max dV/dt) was significantly increased in T4-treated rat atrial cells. Pilsicainide significantly decreased AP amplitude (APA) and Max dV/dt in both control and T4-treated rat atrial cells. Concentration-inhibition study demonstrated that pilsicainide significantly inhibited net inward current of T4-treated rats at lower concentration (IC50 of 29.2 microg/mL) than that of control rats (133 microg/mL). In conclusion, pilsicainide could decrease the conduction velocity in T4-treated rat atrium by decreasing the Max dV/dt and net inward current, which could be a possible treatment of thyrotoxicosis-induced arrhythmia.

Quantitative analysis of the Ca2+‐dependent regulation of delayed rectifier K+ current I Ks in rabbit ventricular myocytes

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Bartos, Daniel C.; Morotti, Stefano; Ginsburg, Kenneth S.; Grandi, Eleonora

2017-01-01

Key points [Ca2+]i enhanced rabbit ventricular slowly activating delayed rectifier K+ current (I Ks) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol.Rabbit ventricular rapidly activating delayed rectifier K+ current (I Kr) amplitude and voltage dependence were unaffected by high [Ca2+]i.When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca2+ transient or when [Ca2+]i was buffered to 500 nm. Abstract The slowly activating delayed rectifier K+ current (I Ks) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca2+ ([Ca2+]i) and β‐adrenergic receptor (β‐AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca2+]i dependence of I Ks in steady‐state conditions and with dynamically changing membrane potential and [Ca2+]i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole‐cell patch clamp. With intracellular pipette solutions that controlled free [Ca2+]i, we found that raising [Ca2+]i from 100 to 600 nm produced similar increases in I Ks as did β‐AR activation, and the effects appeared additive. Both β‐AR activation and high [Ca2+]i increased maximally activated tail I Ks, negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well‐established mathematical model of the rabbit myocyte. In both AP‐clamp experiments and simulations, I Ks recorded during a normal physiological Ca2+ transient was similar to I Ks measured with [Ca2+]i clamped at 500–600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca2+]i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca2+]i, in the submembrane or junctional cleft

Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.

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Nisbet, Ashley M; Camelliti, Patrizia; Walker, Nicola L; Burton, Francis L; Cobbe, Stuart M; Kohl, Peter; Smith, Godfrey L

2016-05-01

Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result: time to earliest activation of the LV was increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction protein (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte-non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genetically Encoded Biosensors Reveal PKA Hyperphosphorylation on the Myofilaments in Rabbit Heart Failure.

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Barbagallo, Federica; Xu, Bing; Reddy, Gopireddy R; West, Toni; Wang, Qingtong; Fu, Qin; Li, Minghui; Shi, Qian; Ginsburg, Kenneth S; Ferrier, William; Isidori, Andrea M; Naro, Fabio; Patel, Hemal H; Bossuyt, Julie; Bers, Donald; Xiang, Yang K

2016-09-30

In heart failure, myofilament proteins display abnormal phosphorylation, which contributes to contractile dysfunction. The mechanisms underlying the dysregulation of protein phosphorylation on myofilaments is not clear. This study aims to understand the mechanisms underlying altered phosphorylation of myofilament proteins in heart failure. We generate a novel genetically encoded protein kinase A (PKA) biosensor anchored onto the myofilaments in rabbit cardiac myocytes to examine PKA activity at the myofilaments in responses to adrenergic stimulation. We show that PKA activity is shifted from the sarcolemma to the myofilaments in hypertrophic failing rabbit myocytes. In particular, the increased PKA activity on the myofilaments is because of an enhanced β2 adrenergic receptor signal selectively directed to the myofilaments together with a reduced phosphodiesterase activity associated with the myofibrils. Mechanistically, the enhanced PKA activity on the myofilaments is associated with downregulation of caveolin-3 in the hypertrophic failing rabbit myocytes. Reintroduction of caveolin-3 in the failing myocytes is able to normalize the distribution of β2 adrenergic receptor signal by preventing PKA signal access to the myofilaments and to restore contractile response to adrenergic stimulation. In hypertrophic rabbit myocytes, selectively enhanced β2 adrenergic receptor signaling toward the myofilaments contributes to elevated PKA activity and PKA phosphorylation of myofilament proteins. Reintroduction of caveolin-3 is able to confine β2 adrenergic receptor signaling and restore myocyte contractility in response to β adrenergic stimulation. © 2016 American Heart Association, Inc.

Ca(2+ release events in cardiac myocytes up close: insights from fast confocal imaging.

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Vyacheslav M Shkryl

Full Text Available The spatio-temporal properties of Ca(2+ transients during excitation-contraction coupling and elementary Ca(2+ release events (Ca(2+ sparks were studied in atrial and ventricular myocytes with ultra-fast confocal microscopy using a Zeiss LSM 5 LIVE system that allows sampling rates of up to 60 kHz. Ca(2+ sparks which originated from subsarcolemmal junctional sarcoplasmic reticulum (j-SR release sites in atrial myocytes were anisotropic and elongated in the longitudinal direction of the cell. Ca(2+ sparks in atrial cells originating from non-junctional SR and in ventricular myocytes were symmetrical. Ca(2+ spark recording in line scan mode at 40,000 lines/s uncovered step-like increases of [Ca(2+]i. 2-D imaging of Ca(2+ transients revealed an asynchronous activation of release sites and allowed the sequential recording of Ca(2+ entry through surface membrane Ca(2+ channels and subsequent activation of Ca(2+-induced Ca(2+ release. With a latency of 2.5 ms after application of an electrical stimulus, Ca(2+ entry could be detected that was followed by SR Ca(2+ release after an additional 3 ms delay. Maximum Ca(2+ release was observed 4 ms after the beginning of release. The timing of Ca(2+ entry and release was confirmed by simultaneous [Ca(2+]i and membrane current measurements using the whole cell voltage-clamp technique. In atrial cells activation of discrete individual release sites of the j-SR led to spatially restricted Ca(2+ release events that fused into a peripheral ring of elevated [Ca(2+]i that subsequently propagated in a wave-like fashion towards the center of the cell. In ventricular myocytes asynchronous Ca(2+ release signals from discrete sites with no preferential subcellular location preceded the whole-cell Ca(2+ transient. In summary, ultra-fast confocal imaging allows investigation of Ca(2+ signals with a time resolution similar to patch clamp technique, however in a less invasive fashion.

Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

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Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

2013-11-01

Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

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Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

2015-01-01

Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

Atrial SERCA2a Overexpression Has No Affect on Cardiac Alternans but Promotes Arrhythmogenic SR Ca2+ Triggers.

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Nassal, Michelle M J; Wan, Xiaoping; Laurita, Kenneth R; Cutler, Michael J

2015-01-01

Atrial fibrillation (AF) is the most common arrhythmia in humans, yet; treatment has remained sub-optimal due to poor understanding of the underlying mechanisms. Cardiac alternans precede AF episodes, suggesting an important arrhythmia substrate. Recently, we demonstrated ventricular SERCA2a overexpression suppresses cardiac alternans and arrhythmias. Therefore, we hypothesized that atrial SERCA2a overexpression will decrease cardiac alternans and arrhythmias. Adult rat isolated atrial myocytes where divided into three treatment groups 1) Control, 2) SERCA2a overexpression (Ad.SERCA2a) and 3) SERCA2a inhibition (Thapsigargin, 1μm). Intracellular Ca2+ was measured using Indo-1AM and Ca2+ alternans (Ca-ALT) was induced with a standard ramp pacing protocol. As predicted, SR Ca2+ reuptake was enhanced with SERCA2a overexpression (poverexpression or inhibition when compared to controls (p = 0.73). In contrast, SERCA2a overexpression resulted in increased premature SR Ca2+ (SCR) release compared to control myocytes (28% and 0%, p overexpression in atrial myocytes can increase SCR, which may be arrhythmogenic.

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

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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.

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

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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.

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

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Yang, Baode; Li, Chenxing [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Sun, Junyi [Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi' an Jiaotong University, Xi' an (China); Department of Periodontology, College of Stomatology, Xi' an Jiaotong University, Xi' an (China); Wang, Xinghui; Liu, Xinling [Basic Medical Experiment Teaching Center, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Yang, Chun [Department of Cardiology, The First Affiliated Hospital, Xi' an Jiaotong University, Xi' an (China); Chen, Lina; Zhou, Jun [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University, Ministry of Education of China, Xi' an (China); Hu, Hao, E-mail: huhao@mail.xjtu.edu.cn [Department of Pharmacology, Health Science Center, Xi' an Jiaotong University, Xi' an (China); Key Laboratory of Environment and Genes Related to Diseases, Xi' an Jiaotong University, Ministry of Education of China, Xi' an (China)

2017-05-01

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I{sub Kv1.5}) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I{sub hERG}). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I{sub Kir2.1}). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I{sub Kv1.5} and I{sub hERG}, which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.

Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation

International Nuclear Information System (INIS)

Yang, Baode; Li, Chenxing; Sun, Junyi; Wang, Xinghui; Liu, Xinling; Yang, Chun; Chen, Lina; Zhou, Jun; Hu, Hao

2017-01-01

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5–50.0 mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I Kv1.5 ) were markedly inhibited by 12.5–50.0 mM ethanol in a concentration-dependent manner. Ethanol with 50.0 mM could inhibit rapid delayed rectifier potassium currents (I hERG ). Ethanol under 6.25–50.0 mM did not affect on inward rectifier potassium currents (I Kir2.1 ). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I Kv1.5 and I hERG , which contributed to preventing the development and duration of AF. - Highlights: • Moderate ethanol prevented the development of AF in animal models. • Moderate ethanol prolonged APD in guinea pig atrial myocytes. • Moderate ethanol inhibited Kv1.5 currents.

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.

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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.

Reduced density and altered regulation of rat atrial L-type Ca2+ current in heart failure.

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Bond, Richard C; Bryant, Simon M; Watson, Judy J; Hancox, Jules C; Orchard, Clive H; James, Andrew F

2017-03-01

Constitutive regulation by PKA has recently been shown to contribute to L-type Ca 2+ current ( I CaL ) at the ventricular t-tubule in heart failure. Conversely, reduction in constitutive regulation by PKA has been proposed to underlie the downregulation of atrial I CaL in heart failure. The hypothesis that downregulation of atrial I CaL in heart failure involves reduced channel phosphorylation was examined. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N =10) or equivalent sham-operation (Sham, N =12). Left atrial myocytes were isolated ~18 wk postsurgery and whole cell currents recorded (holding potential=-80 mV). I CaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted. CAL cell capacitances were ~1.67-fold greater than Sham ( P ≤ 0.0001). Maximal I CaL conductance ( G max ) was downregulated more than 2-fold in CAL vs. Sham myocytes ( P 50% more effectively in CAL than in Sham so that differences in I CaL density were abolished. Differences between CAL and Sham G max were not abolished by calyculin A (100 nmol/l), suggesting that increased protein dephosphorylation did not account for I CaL downregulation. Treatment with either H-89 (10 μmol/l) or AIP (5 μmol/l) had no effect on basal currents in Sham or CAL myocytes, indicating that, in contrast to ventricular myocytes, neither PKA nor CaMKII regulated basal I CaL Expression of the L-type α 1C -subunit, protein phosphatases 1 and 2A, and inhibitor-1 proteins was unchanged. In conclusion, reduction in PKA-dependent regulation did not contribute to downregulation of atrial I CaL in heart failure. NEW & NOTEWORTHY Whole cell recording of L-type Ca 2+ currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit

Impaired Na⁺-dependent regulation of acetylcholine-activated inward-rectifier K⁺ current modulates action potential rate dependence in patients with chronic atrial fibrillation.

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Voigt, Niels; Heijman, Jordi; Trausch, Anne; Mintert-Jancke, Elisa; Pott, Lutz; Ravens, Ursula; Dobrev, Dobromir

2013-08-01

Shortened action-potential duration (APD) and blunted APD rate adaptation are hallmarks of chronic atrial fibrillation (cAF). Basal and muscarinic (M)-receptor-activated inward-rectifier K(+) currents (IK1 and IK,ACh, respectively) contribute to regulation of human atrial APD and are subject to cAF-dependent remodeling. Intracellular Na(+) ([Na(+)]i) enhances IK,ACh in experimental models but the effect of [Na(+)]i-dependent regulation of inward-rectifier K(+) currents on APD in human atrial myocytes is currently unknown. Here, we report a [Na(+)]i-dependent inhibition of outward IK1 in atrial myocytes from sinus rhythm (SR) or cAF patients. In contrast, IK,ACh activated by carbachol, a non-selective M-receptor agonist, increased with elevation of [Na(+)]i in SR. This [Na(+)]i-dependent IK,ACh regulation was absent in cAF. Including [Na(+)]i dependence of IK1 and IK,ACh in a recent computational model of the human atrial myocyte revealed that [Na(+)]i accumulation at fast rates inhibits IK1 and blunts physiological APD rate dependence in both groups. [Na(+)]i-dependent IK,ACh augmentation at fast rates increased APD rate dependence in SR, but not in cAF. These results identify impaired Na(+)-sensitivity of IK,ACh as one potential mechanism contributing to the blunted APD rate dependence in patients with cAF. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes". Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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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.

Calcium signalling silencing in atrial fibrillation.

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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.

Direct toxic effects of aqueous extract of cigarette smoke on cardiac myocytes at clinically relevant concentrations

International Nuclear Information System (INIS)

Yamada, Shigeyuki; Zhang Xiuquan; Kadono, Toshie; Matsuoka, Nobuhiro; Rollins, Douglas; Badger, Troy; Rodesch, Christopher K.; Barry, William H.

2009-01-01

Aims: Our goal was to determine if clinically relevant concentrations of aqueous extract of cigarette smoke (CSE) have direct deleterious effects on ventricular myocytes during simulated ischemia, and to investigate the mechanisms involved. Methods: CSE was prepared with a smoking chamber. Ischemia was simulated by metabolic inhibition (MI) with cyanide (CN) and 0 glucose. Adult rabbit and mouse ventricular myocyte [Ca 2+ ] i was measured by flow cytometry using fluo-3. Mitochondrial [Ca 2+ ] was measured with confocal microscopy, and Rhod-2 fluorescence. The mitochondrial permeability transition (MPT) was detected by TMRM fluorescence and myocyte contracture. Myocyte oxidative stress was quantified by dichlorofluorescein (DCF) fluorescence with confocal microscopy. Results: CSE 0.1% increased myocyte contracture caused by MI. The nicotine concentration (HPLC) in 0.1% CSE was 15 ng/ml, similar to that in humans after smoking cigarettes. CSE 0.1% increased mitochondrial Ca 2+ uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca 2+ ] i in paced myocytes exposed to 2.0 mM CN, 0 glucose (P-MI). These effects were inhibited by the superoxide scavenger Tiron. The effect of CSE on [Ca 2+ ] i during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca 2+ ] i during simulated ischemia, and increases myocyte susceptibility to the MPT. These effects appear to be mediated at least in part by oxidative radicals in CSE, and likely contribute to the effects of cigarette smoke to increase myocardial infarct size, and to decrease angina threshold

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

Post-translational processing and secretion of atrial natriuretic factor

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Shields, P.P.

1988-01-01

The post-translational processing and regulated secretion of atrial natriuretic factor (ANF) were studied in primary cultures of rat cardiac myocytes. Cultures were established from neonatal rat atria or ventricles, and were maintained for 7-14 days in complete serum free medium. The cultures contained high and constant levels of ANF-(1-126), the known storage form of the hormone in vivo. The cultures also secreted ANF-(1-126), instead of the known circulating form of the hormone, ANF-(99-126). However, the inclusion of the glucocorticoids dexamethasone or hydrocortisone in the culture medium increased the levels of ir-ANF contained and secreted by the cultures, and caused both atrial and ventricular cultures to secrete principally ANF-(99-126) instead of ANF-(1-126). The secreted peptide was shown to be authentic ANF-(99-126) by chromatographic, amino acid composition and radiosequence analysis, thus confirming that the cultures were accurately processing ANF to the in vivo circulating form in the presence of glucocorticoids. Glucocorticoids also caused an increase in size and clustering of atrial myocytes as determined by immunocytochemical analysis, but the morphological effects could be dissociated from the stimulation of ANF-(99-126) secretion by manipulating the timing of glucocorticoid exposure. The location of ANF-(99-126) formation was investigated using biosynthetically labeled 35 S-Cys-ANF-(1-126) in conjunction with actively processing cultures

Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway

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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.

Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway.

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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.

[The contribution of inflammatory process in pathogenesis and natural history of atrial fibrillation].

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Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

2005-02-01

The inflammatory process plays important role in pathogenesis of some cardiovascular diseases. Atrial fibrillation is atrial arrhythmia with rapid, asynchronous activation of atrial myocytes. The inflammatory process can be responsible for atrial electrical and anatomical remodeling and therefore shifts towards arrhythmia persistence. The presence of systemic inflammation may be assessed by means of C-reactive protein (CRP) measurement. Maximal concentration of CRP coincidences with the peak of paroxysmal atrial fibrillation occurrence in patients after cardiac surgery. In patients with sinus rhythm the concentration of CRP is a risk factor for this arrhythmia in long-term follow-up. In patients with atrial fibrillation mean CRP concentration is 2-fold higher comparing to control group. CRP concentration is higher in patients with chronic than paroxysmal form of this arrhythmia. High CRP level predicts worse results of direct current cardioversion and more frequent paroxysms of atrial fibrillation during follow-up. Besides of, the patients with echocardiographic signs of thromboembolic risk have higher CRP levels than control subjects. There is no data about the influence of anti-inflammatory therapy on atrial fibrillation or its recurrences.

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway.

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Liu, Guang-Zhong; Hou, Ting-Ting; Yuan, Yue; Hang, Peng-Zhou; Zhao, Jing-Jing; Sun, Li; Zhao, Guan-Qi; Zhao, Jing; Dong, Jing-Mei; Wang, Xiao-Bing; Shi, Hang; Liu, Yong-Wu; Zhou, Jing-Hua; Dong, Zeng-Xiang; Liu, Yang; Zhan, Cheng-Chuang; Li, Yue; Li, Wei-Min

2016-03-01

Atrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action. The expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min(-1) for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed. The PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF. Fenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF. © 2016 The British Pharmacological Society.

Characterization of the adenosine receptor in cultured embryonic chick atrial myocytes: Coupling to modulation of contractility and adenylate cyclase activity and identification by direct radioligand binding

International Nuclear Information System (INIS)

Liang, B.T.

1989-01-01

Adenosine receptors in a spontaneously contracting atrial myocyte culture from 14-day chick embryos were characterized by radioligand binding studies and by examining the involvement of G-protein in coupling these receptors to a high-affinity state and to the adenylate cyclase and the myocyte contractility. Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3-diproylxanthine ([3H]CPX) was rapid, reversible and saturable and was to a homogeneous population of sites with a Kd value of 2.1 +/- 0.2 nM and an apparent maximum binding of 26.2 +/- 3 fmol/mg of protein (n = 10, +/- S.E.). Guanyl-5-yl-(beta, gamma-imido)diphosphate had no effect on either the Kd or the maximum binding and CPX reversed the N6-R-phenyl-2-propyladenosine-induced inhibition of adenylate cyclase activity and contractility, indicating that [3H] CPX is an antagonist radioligand. Competition curves for [3H] CPX binding by a series of reference adenosine agonists were consistent with labeling of an A1 adenosine receptor and were better fit by a two-site model than by a one-site model. ADP-ribosylation of the G-protein by the endogenous NAD+ in the presence of pertussis toxin shifted the competition curves from bi to monophasic with Ki values similar to those of the KL observed in the absence of prior pertussis intoxication. The adenosine agonists were capable of inhibiting both the adenylate cyclase activity and myocyte contractility in either the absence or the presence of isoproterenol. The A1 adenosine receptor-selective antagonist CPX reversed these agonist effects. The order of ability of the reference adenosine receptor agonists in causing these inhibitory effects was similar to the order of potency of the same agonists in inhibiting the specific [3H]CPX binding (N6-R-phenyl-2-propyladenosine greater than N6-S-phenyl-2-propyladenosine or N-ethyladenosine-5'-uronic acid)

Nuclear triiodothyronine receptors in rabbit heart

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Banerjee, S.K.; Ulrich, J.M.; Kaldor, G.J.

1986-01-01

Nuclear triiodothyronine receptors from rat liver have been characterized in detail by several investigators. However, little work has been done in this area using heart tissue. In this study they examined and characterized the triiodothyronine binding in rabbit hearts. Nuclei have been prepared from ventricular muscle cells of normal and thyrotoxic rabbits as well as from atrial muscle cells of normal rabbit. Hearts were perfused with a minimum essential medium containing collagenase and bovine serum albumin. Myocardial cells were isolated and then disrupted by sonication and washing with a Triton X-100 buffer solution. A discontinuous sucrose density gradient was then used to isolate the mycoardial nuclei. Radiolabelled triiodothyronine (T 3 ) binding to nuclei was examined using conditions described by established procedures. Scatchard analysis of the binding data yields maximum binding capacity (B/sub max/) of 0.17 +/- 0.2 pmol/mg DNA and apparent dissociation constant (K/sub d/) of 400 +/- 50 pM for normal heart T 3 -receptors. The apparent capacity for T 3 binding is approximately 40% greater in myocardial nuclei prepared from hearts of hyperthyroid rabbits. The binding capacity of atrial muscle nuclei is about fourfold lower than ventricular cell nuclei. The results suggest that binding capacity for T 3 -receptor in the atrium is considerably lower than that found in the ventricle

Removal of atrial natriuretic factor by perfused rabbit lungs in situ

International Nuclear Information System (INIS)

Turrin, M.; Maack, T.; Gillis, C.N.

1986-01-01

Because atrial natriuretic factor (ANF) can be released from the right atrium into pulmonary blood, the authors studied the possibility of uptake of the peptide by rabbit lung, perfused in situ, at 20 ml/min with Krebs-albumin medium. Single pass removal (multiple indicator dilution with 14 C-dextran as reference) of trace amounts (40 pmoles) of 125 I-ANF was 66 +/- 4% (n=12). This was reduced to 8 +/- 4% by co-injection of 10 μM ANF but was unchanged by co-injection of CPAP (340 nM), an inhibitor of angiotensin-converting enzyme (ACE). When 125 I-ANF was re-circulated through lung, uptake reached maximum at 14 min (64 +/- 5%; n=7). Efflux of 125 I-ANF from preloaded lungs was monoexponential with t/sub 1/2/ = 17.7 min. Recovery of 125 I-ANF uptake after block by unlabelled ANF was studied. For this purpose, lungs were loaded with 0.1 μM unlabelled ANF by recirculating for 20 minutes, after which medium was changed to Krebs-albumin and removal of bolus injections of 125 I-ANF was measured every 5 min. Removal of 125 I-ANF, initially 0%, returned to control levels after 20 min. Thus, 125 I-ANF is removed from the pulmonary circulation by a saturable and reversible process which probably does not involve binding to the ACE present on endothelial cells

Effect of PPAR γ activators on hypertrophic cardiac myocytes in vitro

International Nuclear Information System (INIS)

Wu Shimin; Zhou Xin; Ye Ping; Wang Qiong; Gao Yue; Liu Yongxue

2004-01-01

Objective: To investigate the effects of peroxisome proliferator-activated receptor γ (PPAR γ) activators pioglitazone and 15-deoxy-Δ 12,14 prostaglandin J 2 (15d-PGJ 2 ) on hypertrophic cardiac myocytes (MC) of neonatal rats in vitro. Methods; With the stimulation of angiotensin II(Ang II), a model of hypertrophy of MC was established. With the method of reverse transcription-polymerase chain reaction (RT-PCR), mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was amplified; with the aid of NIH Image J software the surface area of MC was analyzed and with 3 H-leucine incorporation, the synthesizing rate of protein in MC was measured. Results: Increases in surface area of MC, mRNA expression of ANP and BNP and 3 H-leucine incorporation in MC were observed in the model of cardiac hypertrophy. Pioglitazone and 15d-PGJ 2 , two kinds of PPAR γ activators, inhibited the above changes in a dose-dependent manner. Conclusion: It is suggested that PPAR γ activators inhibit hypertrophy of cardiac myocytes and PPAR γ-dependent pathway be involved in the inhibitory course

A MicroRNA-Transcription Factor Blueprint for Early Atrial Arrhythmogenic Remodeling

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Mario Torrado

2015-01-01

Full Text Available Spontaneous self-terminating atrial fibrillation (AF is one of the most common heart rhythm disorders, yet the regulatory molecular mechanisms underlying this syndrome are rather unclear. MicroRNA (miRNA transcriptome and expression of candidate transcription factors (TFs with potential roles in arrhythmogenesis, such as Pitx2, Tbx5, and myocardin (Myocd, were analyzed by microarray, qRT-PCR, and Western blotting in left atrial (LA samples from pigs with transitory AF established by right atrial tachypacing. Induced ectopic tachyarrhythmia caused rapid and substantial miRNA remodeling associated with a marked downregulation of Pitx2, Tbx5, and Myocd expression in atrial myocardium. The downregulation of Pitx2, Tbx5, and Myocd was inversely correlated with upregulation of the corresponding targeting miRNAs (miR-21, miR-10a/10b, and miR-1, resp. in the LA of paced animals. Through in vitro transient transfections of HL-1 atrial myocytes, we further showed that upregulation of miR-21 did result in downregulation of Pitx2 in cardiomyocyte background. The results suggest that immediate-early miRNA remodeling coupled with deregulation of TF expression underlies the onset of AF.

A MicroRNA-Transcription Factor Blueprint for Early Atrial Arrhythmogenic Remodeling

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Torrado, Mario; Franco, Diego; Lozano-Velasco, Estefanía; Hernández-Torres, Francisco; Calviño, Ramón; Aldama, Guillermo; Centeno, Alberto; Castro-Beiras, Alfonso; Mikhailov, Alexander

2015-01-01

Spontaneous self-terminating atrial fibrillation (AF) is one of the most common heart rhythm disorders, yet the regulatory molecular mechanisms underlying this syndrome are rather unclear. MicroRNA (miRNA) transcriptome and expression of candidate transcription factors (TFs) with potential roles in arrhythmogenesis, such as Pitx2, Tbx5, and myocardin (Myocd), were analyzed by microarray, qRT-PCR, and Western blotting in left atrial (LA) samples from pigs with transitory AF established by right atrial tachypacing. Induced ectopic tachyarrhythmia caused rapid and substantial miRNA remodeling associated with a marked downregulation of Pitx2, Tbx5, and Myocd expression in atrial myocardium. The downregulation of Pitx2, Tbx5, and Myocd was inversely correlated with upregulation of the corresponding targeting miRNAs (miR-21, miR-10a/10b, and miR-1, resp.) in the LA of paced animals. Through in vitro transient transfections of HL-1 atrial myocytes, we further showed that upregulation of miR-21 did result in downregulation of Pitx2 in cardiomyocyte background. The results suggest that immediate-early miRNA remodeling coupled with deregulation of TF expression underlies the onset of AF. PMID:26221584

Towards modeling of cardiac micro-structure with catheter-based confocal microscopy: a novel approach for dye delivery and tissue characterization.

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Lasher, Richard A; Hitchcock, Robert W; Sachse, Frank B

2009-08-01

This work presents a methodology for modeling of cardiac tissue micro-structure. The approach is based on catheter-based confocal imaging systems, which are emerging as tools for diagnosis in various clinical disciplines. A limitation of these systems is that a fluorescent marker must be available in sufficient concentration in the imaged region. We introduce a novel method for the local delivery of fluorescent markers to cardiac tissue based on a hydro-gel carrier brought into contact with the tissue surface. The method was tested with living rabbit cardiac tissue and applied to acquire three-dimensional image stacks with a standard inverted confocal microscope and two-dimensional images with a catheter-based confocal microscope. We processed these image stacks to obtain spatial models and quantitative data on tissue microstructure. Volumes of atrial and ventricular myocytes were 4901 +/- 1713 and 10 299 +/-3598 mum (3) (mean+/-sd), respectively. Atrial and ventricular myocyte volume fractions were 72.4 +/-4.7% and 79.7 +/- 2.9% (mean +/-sd), respectively. Atrial and ventricular myocyte density was 165 571 +/- 55 836 and 86 957 +/- 32 280 cells/mm (3) (mean+/-sd), respectively. These statistical data and spatial descriptions of tissue microstructure provide important input for modeling studies of cardiac tissue function. We propose that the described methodology can also be used to characterize diseased tissue and allows for personalized modeling of cardiac tissue.

Removal of atrial natriuretic factor by perfused rabbit lungs in situ

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Turrin, M.; Maack, T.; Gillis, C.N.

1986-03-05

Because atrial natriuretic factor (ANF) can be released from the right atrium into pulmonary blood, the authors studied the possibility of uptake of the peptide by rabbit lung, perfused in situ, at 20 ml/min with Krebs-albumin medium. Single pass removal (multiple indicator dilution with /sup 14/C-dextran as reference) of trace amounts (40 pmoles) of /sup 125/I-ANF was 66 +/- 4% (n=12). This was reduced to 8 +/- 4% by co-injection of 10 ..mu..M ANF but was unchanged by co-injection of CPAP (340 nM), an inhibitor of angiotensin-converting enzyme (ACE). When /sup 125/I-ANF was re-circulated through lung, uptake reached maximum at 14 min (64 +/- 5%; n=7). Efflux of /sup 125/I-ANF from preloaded lungs was monoexponential with t/sub 1/2/ = 17.7 min. Recovery of /sup 125/I-ANF uptake after block by unlabelled ANF was studied. For this purpose, lungs were loaded with 0.1 ..mu..M unlabelled ANF by recirculating for 20 minutes, after which medium was changed to Krebs-albumin and removal of bolus injections of /sup 125/I-ANF was measured every 5 min. Removal of /sup 125/I-ANF, initially 0%, returned to control levels after 20 min. Thus, /sup 125/I-ANF is removed from the pulmonary circulation by a saturable and reversible process which probably does not involve binding to the ACE present on endothelial cells.

Gene Expression Networks in the Murine Pulmonary Myocardium Provide Insight into the Pathobiology of Atrial Fibrillation

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Jordan K. Boutilier

2017-09-01

Full Text Available The pulmonary myocardium is a muscular coat surrounding the pulmonary and caval veins. Although its definitive physiological function is unknown, it may have a pathological role as the source of ectopic beats initiating atrial fibrillation. How the pulmonary myocardium gains pacemaker function is not clearly defined, although recent evidence indicates that changed transcriptional gene expression networks are at fault. The gene expression profile of this distinct cell type in situ was examined to investigate underlying molecular events that might contribute to atrial fibrillation. Via systems genetics, a whole-lung transcriptome data set from the BXD recombinant inbred mouse resource was analyzed, uncovering a pulmonary cardiomyocyte gene network of 24 transcripts, coordinately regulated by chromosome 1 and 2 loci. Promoter enrichment analysis and interrogation of publicly available ChIP-seq data suggested that transcription of this gene network may be regulated by the concerted activity of NKX2-5, serum response factor, myocyte enhancer factor 2, and also, at a post-transcriptional level, by RNA binding protein motif 20. Gene ontology terms indicate that this gene network overlaps with molecular markers of the stressed heart. Therefore, we propose that perturbed regulation of this gene network might lead to altered calcium handling, myocyte growth, and contractile force contributing to the aberrant electrophysiological properties observed in atrial fibrillation. We reveal novel molecular interactions and pathways representing possible therapeutic targets for atrial fibrillation. In addition, we highlight the utility of recombinant inbred mouse resources in detecting and characterizing gene expression networks of relatively small populations of cells that have a pathological significance.

Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and left ventricular remodeling after myocardial infarction in rabbits.

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Li, Bao; Tian, Jing; Sun, Yi; Xu, Tao-Rui; Chi, Rui-Fang; Zhang, Xiao-Li; Hu, Xin-Ling; Zhang, Yue-An; Qin, Fu-Zhong; Zhang, Wei-Fang

2015-05-01

Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase activity and endoplasmic reticulum (ER) stress are increased after myocardial infarction (MI). In this study, we proposed to test whether activation of the NADPH oxidase in the remote non-infarcted myocardium mediates ER stress and left ventricular (LV) remodeling after MI. Rabbits with MI or sham operation were randomly assigned to orally receive an NADPH oxidase inhibitor apocynin or placebo for 30 days. The agents were administered beginning at 1 week after surgery. MI rabbits exhibited decreases in LV fractional shortening, LV ejection fraction and the first derivative of the LV pressure rise, which were abolished by apocynin treatment. NADPH oxidase Nox2 protein and mRNA expressions were increased in the remote non-infarcted myocardium after MI. Immunolabeling further revealed that Nox2 was increased in cardiac myocytes in the remote myocardium. The apocynin treatment prevented increases in the Nox2 expression, NADPH oxidase activity, oxidative stress, myocyte apoptosis and GRP78, CHOP and cleaved caspase 12 protein expression in the remote myocardium. The apocynin treatment also attenuated increases in myocyte diameter and cardiac fibrosis. In cultured H9C2 cardiomyocytes exposed to angiotensin II, an important stimulus for post-MI remodeling, Nox2 knockdown with siRNA significantly inhibited angiotensin II-induced NADPH oxidase activation, reactive oxygen species and GRP78 and CHOP protein expression. We conclude that NADPH oxidase inhibition attenuates increased ER stress in the remote non-infarcted myocardium and LV remodeling late after MI in rabbits. These findings suggest that the activation of NADPH oxidase in the remote non-infarcted myocardium mediates increased ER stress, contributing to myocyte apoptosis and LV remodeling after MI. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

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Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

2013-01-01

Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

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

ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

International Nuclear Information System (INIS)

Icli, Basak; Bharti, Ajit; Pentassuglia, Laura; Peng, Xuyang; Sawyer, Douglas B.

2012-01-01

Highlights: ► ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. ► Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. ► Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or γ-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

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

Science.gov (United States)

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

Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00075467 modulates atrial electrical remodeling by sponging miR-328 to regulate CACNA1C.

Science.gov (United States)

Li, Zhan; Wang, Ximin; Wang, Weizong; Du, Juanjuan; Wei, Jinqiu; Zhang, Yong; Wang, Jiangrong; Hou, Yinglong

2017-07-01

Electrical remodeling has been reported to play a major role in the initiation and maintenance of atrial fibrillation (AF). Long non-coding RNAs (lncRNAs) have been increasingly recognized as contributors to the pathology of heart diseases. However, the roles and mechanisms of lncRNAs in electrical remodeling during AF remain unknown. In this study, the lncRNA expression profiles of right atria were investigated in AF and non-AF rabbit models by using RNA sequencing technique and validated using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 99,843 putative new lncRNAs were identified, in which 1220 differentially expressed transcripts exhibited >2-fold change. Bioinformatics analysis was conducted to predict the functions and interactions of the aberrantly expressed genes. On the basis of a series of filtering pipelines, one lncRNA, TCONS_00075467, was selected to explore its effects and mechanisms on electrical remodeling. The atrial effective refractory period was shortened in vivo and the L-type calcium current and action potential duration were decreased in vitro by silencing of TCONS_00075467 with lentiviruses. Besides, the expression of miRNA-328 was negatively correlated with TCONS_00075467. We further demonstrated that TCONS_00075467 could sponge miRNA-328 in vitro and in vivo to regulate the downstream protein coding gene CACNA1C. In addition, miRNA-328 could partly reverse the effects of TCONS_00075467 on electrical remodeling. In summary, dysregulated lncRNAs may play important roles in modulating electrical remodeling during AF. Our study may facilitate the mechanism studies of lncRNAs in AF pathogenesis and provide potential therapeutic targets for AF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral Transmucosal Detomidine Gel in New Zealand White Rabbits (Oryctolagus cuniculus).

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Williams, Morika D; Long, C Tyler; Durrant, Jessica R; McKeon, Gabriel P; Shive, Heather R; Griffith, Emily H; Messenger, Kristen M; Fish, Richard E

2017-07-01

Handling and restraining rabbits for routine procedures may be impossible without prior sedation, result in unnecessary stress or injury to the rabbit or handler, and increase experimental variability. Parenteral administration of sedatives can cause stress also, as well as localized pain and tissue damage, especially in fractious animals. Detomidine hydrochloride, an α2-adrenergic receptor agonist, is commercially available in an oral transmucosal (OTM) gel formulation that is FDA-approved for sedation and restraint in horses. This study investigated the efficacy and safety of detomidine gel as an alternative to injectable sedation in rabbits. Eight adult male New Zealand White rabbits each received 0.6, 1.2, or 1.8 mg/kg OTM detomidine gel. Physiologic parameters and sedation scores (SS) were assessed at 10-min intervals from before administration until 100 min afterward. Histopathology of cardiac tissue was scored through 12 d after dosing. Gel administration increased the SS in all rabbits, but none of the animals developed clinically effective sedation (SS of 10 or greater, based on 5 reflex responses on a 3- or 4-point scale). The SS did not differ among dosage groups, and the time-dose interaction was not statistically significant. Heart rate decreased rapidly in all rabbits, with no difference among dosage groups, and there was no effect of time or dosage on peripheral capillary oxygen saturation. Minimal to mild degenerative changes were seen in the myocardium of all treated rabbits, but myocyte necrosis, inflammation, fibrosis, and mural thrombi-reported previously in rabbits that had received parenteral detomidine-did not occur. OTM detomidine gel was safely and easily administered to rabbits, but the duration and level of sedation were unpredictable. The use of OTM detomidine as a sole agent to facilitate handling and restraint of rabbits does not offer advantages over existing parenteral regimens.

A New Class III Antiarrhythmic Drug Niferidil Prolongs Action Potentials in Guinea Pig Atrial Myocardium via Inhibition of Rapid Delayed Rectifier.

Science.gov (United States)

Abramochkin, Denis V; Kuzmin, Vladislav S; Rosenshtraukh, Leonid V

2017-12-01

A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium. APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K + currents in isolated myocytes. In multicellular atrial preparations, 10 -8  M niferidil effectively prolonged APs by 15.2 ± 2.8% at 90% repolarization level. However, even the highest tested concentrations, 10 -6  M and 10 -5  M failed to prolong APs more than 32.5% of control duration. The estimated concentration of niferedil for half-maximal AP prolongation was 1.13 × 10 -8  M. Among the potassium currents responsible for AP repolarization phase, I K1 was found to be almost insensitive to niferidil. However, another inward rectifier, I KACh , was effectively suppressed by micromolar concentrations of niferidil with IC 50  = 9.2 × 10 -6  M. I KATP was much less sensitive to the drug with IC 50  = 2.26 × 10 -4  M. The slow component of delayed rectifier, I Ks , also demonstrated low sensitivity to niferidil-the highest used concentration, 10 -4  M, decreased peak I Ks density to 46.2 ± 5.5% of control. Unlike I Ks , the rapid component of delayed rectifier, I Kr , appeared to be extremely sensitive to niferidil. The IC 50 was 1.26 × 10 -9  M. I Kr measured in ventricular myocytes was found to be less sensitive to niferidil with IC 50  = 3.82 × 10 -8  M. Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I Kr .

Effect of ethanol at clinically relevant concentrations on atrial inward rectifier potassium current sensitive to acetylcholine.

Science.gov (United States)

Bébarová, Markéta; Matejovič, Peter; Pásek, Michal; Hořáková, Zuzana; Hošek, Jan; Šimurdová, Milena; Šimurda, Jiří

2016-10-01

Alcohol intoxication tends to induce arrhythmias, most often the atrial fibrillation. To elucidate arrhythmogenic mechanisms related to alcohol consumption, the effect of ethanol on main components of the ionic membrane current is investigated step by step. Considering limited knowledge, we aimed to examine the effect of clinically relevant concentrations of ethanol (0.8-80 mM) on acetylcholine-sensitive inward rectifier potassium current I K(Ach). Experiments were performed by the whole-cell patch clamp technique at 23 ± 1 °C on isolated rat and guinea-pig atrial myocytes, and on expressed human Kir3.1/3.4 channels. Ethanol induced changes of I K(Ach) in the whole range of concentrations applied; the effect was not voltage dependent. The constitutively active component of I K(Ach) was significantly increased by ethanol with the maximum effect (an increase by ∼100 %) between 8 and 20 mM. The changes were comparable in rat and guinea-pig atrial myocytes and also in expressed human Kir3.1/3.4 channels (i.e., structural correlate of I K(Ach)). In the case of the acetylcholine-induced component of I K(Ach), a dual ethanol effect was apparent with a striking heterogeneity of changes in individual cells. The effect correlated with the current magnitude in control: the current was increased by eth-anol in the cells showing small current in control and vice versa. The average effect peaked at 20 mM ethanol (an increase of the current by ∼20 %). Observed changes of action potential duration agreed well with the voltage clamp data. Ethanol significantly affected both components of I K(Ach) even in concentrations corresponding to light alcohol consumption.

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.

Myomaker mediates fusion of fast myocytes in zebrafish embryos

Energy Technology Data Exchange (ETDEWEB)

Landemaine, Aurélie; Rescan, Pierre-Yves; Gabillard, Jean-Charles, E-mail: Jean-charles.gabillard@rennes.inra.fr

2014-09-05

Highlights: • Myomaker is transiently expressed in fast myocytes during embryonic myogenesis. • Myomaker is essential for fast myocyte fusion in zebrafish. • The function of myomaker is conserved among Teleostomi. - Abstract: Myomaker (also called Tmem8c), a new membrane activator of myocyte fusion was recently discovered in mice. Using whole mount in situ hybridization on zebrafish embryos at different stages of embryonic development, we show that myomaker is transiently expressed in fast myocytes forming the bulk of zebrafish myotome. Zebrafish embryos injected with morpholino targeted against myomaker were alive after yolk resorption and appeared morphologically normal, but they were unable to swim, even under effect of a tactile stimulation. Confocal observations showed a marked phenotype characterized by the persistence of mononucleated muscle cells in the fast myotome at developmental stages where these cells normally fuse to form multinucleated myotubes. This indicates that myomaker is essential for myocyte fusion in zebrafish. Thus, there is an evolutionary conservation of myomaker expression and function among Teleostomi.

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum

Science.gov (United States)

Saburkina, Inga; Gukauskiene, Ligita; Rysevaite, Kristina; Brack, Kieran E; Pauza, Audrys G; Pauziene, Neringa; Pauza, Dainius H

2014-01-01

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure-distended whole hearts and whole-mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517–2788; aged) vs. 2118 ± 108 (range 1513–2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well-developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans. PMID:24527844

Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

Science.gov (United States)

Lambertenghi-Deliliers, G; Zanon, P L; Pozzoli, E F; Bellini, O; Praga, C

1978-02-28

The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

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...

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

Science.gov (United States)

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

2016-12-14

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

Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

Science.gov (United States)

Wilkinson, M; Giles, A; Armour, J A; Cardinal, R

1996-01-01

To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

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.

Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-alpha.

Science.gov (United States)

Petkova-Kirova, Polina S; Gursoy, Erdal; Mehdi, Haider; McTiernan, Charles F; London, Barry; Salama, Guy

2006-05-01

Mice that overexpress the inflammatory cytokine tumor necrosis factor-alpha in the heart (TNF mice) develop heart failure characterized by atrial and ventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias, and increased mortality (males > females). Abnormalities in Ca2+ handling, prolonged action potential duration (APD), calcium alternans, and reentrant atrial and ventricular arrhythmias were previously observed with the use of optical mapping of perfused hearts from TNF mice. We therefore tested whether altered voltage-gated outward K+ and/or inward Ca2+ currents contribute to the altered action potential characteristics and the increased vulnerability to arrhythmias. Whole cell voltage-clamp recordings of K+ currents from left ventricular myocytes of TNF mice revealed an approximately 50% decrease in the rapidly activating, rapidly inactivating transient outward K+ current Ito and in the rapidly activating, slowly inactivating delayed rectifier current IK,slow1, an approximately 25% decrease in the rapidly activating, slowly inactivating delayed rectifier current IK,slow2, and no significant change in the steady-state current Iss compared with controls. Peak amplitudes and inactivation kinetics of the L-type Ca2+ current ICa,L were not altered. Western blot analyses revealed a reduction in the proteins underlying Kv4.2, Kv4.3, and Kv1.5. Thus decreased K+ channel expression is largely responsible for the prolonged APD in the TNF mice and may, along with abnormalities in Ca2+ handling, contribute to arrhythmias.

Matrix elasticity regulates the optimal cardiac myocyte shape for contractility

Science.gov (United States)

McCain, Megan L.; Yuan, Hongyan; Pasqualini, Francesco S.; Campbell, Patrick H.

2014-01-01

Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease. PMID:24682394

Design-based stereological estimation of the total number of cardiac myocytes in histological sections

DEFF Research Database (Denmark)

Brüel, Annemarie; Nyengaard, Jens Randel

2005-01-01

in LM sections using design-based stereology. MATERIALS AND METHODS: From formalin-fixed left rat ventricles (LV) isotropic uniformly random sections were cut. The total number of myocyte nuclei per LV was estimated using the optical disector. Two-microm-thick serial paraffin sections were stained......BACKGROUND: Counting the total number of cardiac myocytes has not previously been possible in ordinary histological sections using light microscopy (LM) due to difficulties in defining the myocyte borders properly. AIM: To describe a method by which the total number of cardiac myocytes is estimated...... with antibodies against cadherin and type IV collagen to visualise the intercalated discs and the myocyte membranes, respectively. Using the physical disector in "local vertical windows" of the serial sections, the average number of nuclei per myocyte was estimated.RESULTS: The total number of myocyte nuclei...

Amphiphile-induced heart muscle-cell (myocyte) injury: effects of intracellular fatty acid overload.

Science.gov (United States)

Janero, D R; Burghardt, C; Feldman, D

1988-10-01

Lipid amphiphile toxicity may be an important contributor to myocardial injury, especially during ischemia/reperfusion. In order to investigate directly the potential biochemical and metabolic effects of amphiphile overload on the functioning heart muscle cell (myocyte), a novel model of nonesterified fatty acid (NEFA)-induced myocyte damage has been defined. The model uses intact, beating neonatal rat myocytes in primary monolayer culture as a study object and 5-(tetradecyloxy)-2-furoic acid (TOFA) as a nonmetabolizable fatty acid. Myocytes incubated with TOFA accumulated it as NEFA, and the consequent NEFA amphiphile overload elicited a variety of cellular defects (including decreased beating rate, depletion of high-energy stores and glycogen pools, and breakdown of myocyte membrane phospholipid) and culminated in cell death. The amphiphile-induced cellular pathology could be reversed by removing TOFA from the culture medium, which resulted in intracellular TOFA "wash-out." Although the development and severity of amphiphile-induced myocyte injury could be correlated with both the intracellular TOFA/NEFA content (i.e., the level of TOFA to which the cells were exposed) and the duration of this exposure, removal of amphiphile overload did not inevitably lead to myocyte recovery. TOFA had adverse effects on myocyte mitochondrial function in situ (decoupling of oxidative phosphorylation, impairing respiratory control) and on myocyte oxidative catabolism (transiently increasing fatty acid beta oxidation, citric acid cycle flux, and glucose oxidation). The amphiphile-induced bioenergetic abnormalities appeared to constitute a state of "metabolic anoxia" underlying the progression of myocyte injury to cell death. This anoxic state could be ameliorated to some extent, but not prevented, by carbohydrate catabolism.

Jamb and jamc are essential for vertebrate myocyte fusion.

Directory of Open Access Journals (Sweden)

Gareth T Powell

2011-12-01

Full Text Available Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both jamb and jamc are dynamically co-expressed in developing muscles and encode receptors that physically interact. Heritable mutations in either gene prevent myocyte fusion in vivo, resulting in an overabundance of mononuclear, but otherwise overtly normal, functional fast-twitch muscle fibres. Transplantation experiments show that the Jamb and Jamc receptors must interact between neighbouring cells (in trans for fusion to occur. We also show that jamc is ectopically expressed in prdm1a mutant slow muscle precursors, which inappropriately fuse with other myocytes, suggesting that control of myocyte fusion through regulation of jamc expression has important implications for the growth and patterning of muscles. Our discovery of a receptor-ligand pair critical for fusion in vivo has important implications for understanding the molecular mechanisms responsible for myocyte fusion and its regulation in vertebrate myogenesis.

Mechanical analysis of single myocyte contraction in a 3-D elastic matrix.

Directory of Open Access Journals (Sweden)

John Shaw

Full Text Available Cardiac myocytes experience mechanical stress during each heartbeat. Excessive mechanical stresses under pathological conditions cause functional and structural remodeling that lead to heart diseases, yet the precise mechanisms are still incompletely understood. To study the cellular and molecular level mechanotransduction mechanisms, we developed a new 'cell-in-gel' experimental system to exert multiaxial (3-D stresses on a single myocyte during active contraction.Isolated myocytes are embedded in an elastic hydrogel to simulate the mechanical environment in myocardium (afterload. When electrically stimulated, the in-gel myocyte contracts while the matrix resists shortening and broadening of the cell, exerting normal and shear stresses on the cell. Here we provide a mechanical analysis, based on the Eshelby inclusion problem, of the 3-D strain and stress inside and outside the single myocyte during contraction in an elastic matrix.(1 The fractional shortening of the myocyte depends on the cell's geometric dimensions and the relative stiffness of the cell to the gel. A slender or softer cell has less fractional shortening. A myocyte of typical dimensions embedded in a gel of similar elastic stiffness can contract only 20% of its load-free value. (2 The longitudinal stress inside the cell is about 15 times the transverse stress level. (3 The traction on the cell surface is highly non-uniform, with a maximum near its ends, showing 'hot spots' at the location of intercalated disks. (4 The mechanical energy expenditure of the myocyte increases with the matrix stiffness in a monotonic and nonlinear manner.Our mechanical analyses provide analytic solutions that readily lend themselves to parametric studies. The resulting 3-D mapping of the strain and stress states serve to analyze and interpret ongoing cell-in-gel experiments, and the mathematical model provides an essential tool to decipher and quantify mechanotransduction mechanisms in cardiac

Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes

International Nuclear Information System (INIS)

Hallaq, H.; Leaf, A.; Sellmayer, A.; Smith, T.W.

1990-01-01

Isolated neonatal cardiac myocytes have been utilized as a model for the study of cardiac arrhythmogenic factors. The myocytes respond to the toxic effects of a potent cardiac glycoside, ouabain at 0.1 mM, by an increase in their spontaneous beating rate and a reduction in amplitude of contractions resulting within minutes in a lethal state of contracture. Incubating the isolated myocytes for 3 endash 5 days in culture medium enriched with 5 μM arachidonic acid had no effect on the development of lethal contracture after subsequent exposure to 0.1 mM ouabain. By contrast, incubating the myocytes for 3 endash 5 days with 5 μM eicosapentaenoic acid completely prevented the toxic effects of ouabain at 0.1 mM. No differences in bumetanide-inhibitable 86 Rb flux were observed between the three preparations. However, measurements with fura-2 of cytosolic free calcium levels indicated that control and arachidonic acid-enriched myocytes developed toxic cytosolic calcium concentrations of 845 ± 29 and 757 ± 64 nM, respectively, on exposure to 0.1 mM ouabain, whereas in eicosapentaenoic acid-enriched myocytes, physiologic calcium levels were preserved. Incubating the myocytes with eicosapentaenoic acid for 3 endash 5 days resulted in a small reduction of arachidonic acid and a small but significant increase of eicosapentaenoic acid in membrane phospolipids of the myocytes

SMOOTH MYOCYTES AND COLLAGENOUS FIBERS OF THE URINARY BLADDER OF RATS IN DIABETES MELLITUS

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Nadiya Tokaruk

2015-12-01

Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine   Key words: diabetes mellitus; smooth myocytes; collagenous fibers.   Introduction. Diabetes mellitus (DM causes diabetic cystopathy, which is associated with detrusor dysfunction and the content of collagenous fibers. The results of the performed studies are ambiguous and often contradictory, requiring objective data which could be obtained on the basis of the simultaneous determination of relative areas of smooth myocytes and collagenous fibers and their ultrastructural study. Objective: To determine the peculiarities of the structural and metric organization of smooth myocytes and collagenous fibers of the urinary bladder (UB of rats during different stages of DM. Materials and methods. DM was modeled by streptozotocin in Wistar rats. Relative areas of the studied structures were defined on digital images of histological sections of UB stained by Mason using the original automatic way. Smooth myocytes were studied ultrastructurally. Results. During the 14th-28th day of DM development the percent of collagenous fibers area decreases and the percentage of smooth myocytes area of UB wall increases. The expanding of intercellular spaces and the development of vacuolar degeneration of myocytes are observed. During the 42nd-56th days the percentage of collagenous fibers area increases and the percentage of the area of smooth myocytes decreases. Ultrastructurally subsiding of vacuolar dystrophy, short-term baloon dystrophy, the appearance of dark myocytes, moderate karyorrhexis were observed. During the 70th day of the experiment the percentage of collagenous fibers and smooth myocytes areas does not change significantly, most dark myocytes are involutive, there are local fibrosis and myocyte sequestration areas. Conclusions. Ultrastructural changes are characterized by a pronounced polymorphism and have a chronological relationship. Author’s worked out original method of determination of the

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

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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.

De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges

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Veronique Hamel

2017-01-01

Full Text Available The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts, from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells, and from human embryonic stem cells (hESCs. Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.

BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.

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Feldman, Arthur M; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D; Tilley, Douglas G; Gao, Erhe; Hoffman, Nicholas E; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y

2016-03-01

Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na(+)-K(+)-ATPase and L-type Ca(2+) channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca(2+) channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca(2+)]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca(2+) current (ICa) and sarcoplasmic reticulum (SR) Ca(2+) content but not Na(+)/Ca(2+) exchange current (INaCa) or SR Ca(2+) uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyryl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca(2+) entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca(2+) channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. Copyright © 2016 Elsevier Ltd. All rights

BAG3 regulates contractility and Ca2+ homeostasis in adult mouse ventricular myocytes

Science.gov (United States)

Feldman, Arthur M.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue-Qian; Myers, Valerie D.; Tilley, Douglas G.; Gao, Erhe; Hoffman, Nicholas E.; Tomar, Dhanendra; Madesh, Muniswamy; Rabinowitz, Joseph; Koch, Walter J.; Su, Feifei; Khalili, Kamel; Cheung, Joseph Y.

2016-01-01

Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid anti-apoptotic protein that is constitutively expressed in the heart. BAG3 mutations, including mutations leading to loss of protein, are associated with familial cardiomyopathy. Furthermore, BAG3 levels have been found to be reduced in end-stage non-familial failing myocardium. In contrast to neonatal myocytes in which BAG3 is found in the cytoplasm and involved in protein quality control and apoptosis, in adult mouse left ventricular (LV) myocytes BAG3 co-localized with Na+-K+-ATPase and L-type Ca2+ channels in the sarcolemma and t-tubules. BAG3 co-immunoprecipitated with β1-adrenergic receptor, L-type Ca2+ channels and phospholemman. To simulate decreased BAG3 protein levels observed in human heart failure, we targeted BAG3 by shRNA (shBAG3) in adult LV myocytes. Reducing BAG3 by 55% resulted in reduced contraction and [Ca2+]i transient amplitudes in LV myocytes stimulated with isoproterenol. L-type Ca2+ current (ICa) and sarcoplasmic reticulum (SR) Ca2+ content but not Na+/Ca2+ exchange current (INaCa) or SR Ca2+ uptake were reduced in isoproterenol-treated shBAG3 myocytes. Forskolin or dibutyrl cAMP restored ICa amplitude in shBAG3 myocytes to that observed in WT myocytes, consistent with BAG3 having effects upstream and at the level of the receptor. Resting membrane potential and action potential amplitude were unaffected but APD50 and APD90 were prolonged in shBAG3 myocytes. Protein levels of Ca2+ entry molecules and other important excitation-contraction proteins were unchanged in myocytes with lower BAG3. Our findings that BAG3 is localized at the sarcolemma and t-tubules while modulating myocyte contraction and action potential duration through specific interaction with the β1-adrenergic receptor and L-type Ca2+ channel provide novel insight into the role of BAG3 in cardiomyopathies and increased arrhythmia risks in heart failure. PMID:26796036

Atrial therapies reduce atrial arrhythmia burden in defibrillator patients.

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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.

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

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

2014-01-01

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

Hypoxic-induced stress protein expression in rat cardiac myocytes

International Nuclear Information System (INIS)

Howard, G.; Geoghegan, T.E.

1986-01-01

Mammalian stress proteins can be induced in cells and tissues exposed to a variety of conditions including hyperthermia and diminished O 2 supply. The authors have previously shown that the expression of three stress proteins (71, 85, and 95 kDa) was induced in cardiac tissue from mice exposed to hypoxic conditions. The expression of mRNAs coding for the 85 and 95 kDa proteins increase with time of exposure to hypoxia, while the mRNA coding for the 71 kDa protein is transiently induced. The authors extended these studies to investigate the expression of stress proteins in isolated rat cardiac myocytes. Freshly prepared myocytes were exposed to control, hypoxic, anoxic, or heat-shock environments for up to 16 h. The proteins were then labeled for 6 hours with [ 35 S]methionine. Analysis of the solubilized proteins by SDS-PAGE and autoradiography showed that there was a 6-fold increase in synthesis of the 85 kDa protein upon exposure to hypoxia but not heat-shock conditions. The 71 kDa protein was present at high levels in both control and treated myocyte protein preparations, and presumably had been induced during the isolation procedure. Total RNA isolated from intact rat heart and isolated myocytes was compared by cell-free translation analysis and showed induction of RNAs coding for several stress proteins in the myocyte preparation. The induced proteins at 85 and 95 kDa have molecular weights similar to reported cell stress and/or glucose-regulated proteins

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...

Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

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Yuan Hung Lo

2013-01-01

Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes.

Science.gov (United States)

Feng, Li; Gong, Jing; Jin, Zhen-yi; Li, Ning; Sun, Li-ping; Wu, Yi-ling; Pu, Jie-lin

2009-07-05

Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). SSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change. The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

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.

Atrioventricular node functional remodeling induced by atrial fibrillation.

Science.gov (United States)

Zhang, Youhua; Mazgalev, Todor N

2012-09-01

The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF. To determine whether AVN undergoes functional remodeling during AF. AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls. Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P AVN effective refractory period and a slower ventricular rate during AF compared with the controls. Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

Science.gov (United States)

Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

2017-09-01

The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation

Science.gov (United States)

Tsai, Chia-Ti; Hsieh, Chia-Shan; Chang, Sheng-Nan; Chuang, Eric Y.; Ueng, Kwo-Chang; Tsai, Chin-Feng; Lin, Tsung-Hsien; Wu, Cho-Kai; Lee, Jen-Kuang; Lin, Lian-Yu; Wang, Yi-Chih; Yu, Chih-Chieh; Lai, Ling-Ping; Tseng, Chuen-Den; Hwang, Juey-Jen; Chiang, Fu-Tien; Lin, Jiunn-Lee

2016-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10−24). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway. PMID:26831368

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.

Compromised redox homeostasis, altered nitroso-redox balance, and therapeutic possibilities in atrial fibrillation.

Science.gov (United States)

Simon, Jillian N; Ziberna, Klemen; Casadei, Barbara

2016-04-01

Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso-redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed; yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review, we summarize how redox second-messenger systems are regulated and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets that may serve as superior therapeutic options for the treatment of AF. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

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

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

Characterization of human septic sera induced gene expression modulation in human myocytes

Science.gov (United States)

Hussein, Shaimaa; Michael, Paul; Brabant, Danielle; Omri, Abdelwahab; Narain, Ravin; Passi, Kalpdrum; Ramana, Chilakamarti V.; Parrillo, Joseph E.; Kumar, Anand; Parissenti, Amadeo; Kumar, Aseem

2009-01-01

To gain a better understanding of the gene expression changes that occurs during sepsis, we have performed a cDNA microarray study utilizing a tissue culture model that mimics human sepsis. This study utilized an in vitro model of cultured human fetal cardiac myocytes treated with 10% sera from septic patients or 10% sera from healthy volunteers. A 1700 cDNA expression microarray was used to compare the transcription profile from human cardiac myocytes treated with septic sera vs normal sera. Septic sera treatment of myocytes resulted in the down-regulation of 178 genes and the up-regulation of 4 genes. Our data indicate that septic sera induced cell cycle, metabolic, transcription factor and apoptotic gene expression changes in human myocytes. Identification and characterization of gene expression changes that occur during sepsis may lead to the development of novel therapeutics and diagnostics. PMID:19684886

Effect of high-voltage impulse current on the structure and function of rabbit heart

Directory of Open Access Journals (Sweden)

Xin-ping XU

2011-06-01

Full Text Available Objective To explore the effect of high-voltage impulse current(HVIC on the structure and function of rabbit heart.Methods Sixty healthy male rabbits were involved in present study and divided into 6 groups randomly(n=10.The rabbits were then shocked using a high-voltage pulse generator with current intensity of 0,50,100,150,250 and 500mA(pulse width 100μs,duration 5s respectively.The heart rate and electrocardiogram(ECG of rabbits were detected before and 0,1,3,7,14 and 28 days after the electric shock.Moreover,the myocardial tissue of rabbits was obtained immediately and 28 days after shock to observe the pathological changes.Results Immediately after electric shock of 50 to 500mA,the heart rate of rabbit increased by different degree,and the ECG showed arrhythmia,myocardial ischemia,atrial fibrillation and atrioventricular block,and the changes recovered gradually one day later.The pathological observation showed cell swelling,separation of myofibril and sarcoplasmic condensation of Purkinje fibers immediately after electric shock of 50 to 500mA,and the changes recovered 28 days after shock.The cardiac injuries aggravated with the increasing of current intensity,especially when it exceeded 150mA,and the recovery time prolonged.Conclusion High-voltage impulse current may induce recoverable injuries on heart structure and function,and the damage effect shows a correlation with the current intensity.

Atrial Fibrillation: Diagnosis

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... 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 ...

Nuclear thyroid hormone receptors in rabbit heart: reduced triiodothyronine binding in atrium compared with ventricle

International Nuclear Information System (INIS)

Banerjee, S.K.; Ulrich, J.M.; Kaldor, G.J.

1988-01-01

Radiolabeled triiodothyronine (T3) binding to isolated nuclei was measured to compare the binding characteristics of the nuclear receptors in rabbit ventricular and atrial muscle cells. Scatchard analysis of the binding data yielded a maximum binding capacity of 170 +/- 20 fmol per mg DNA and apparent dissociation constant of 525 +/- 100 pM for ventricular nuclei. The binding capacity and the dissociation constant for the atrial muscle cell nuclei were 55 +/- 10 fmol per mg DNA and 500 +/- 75 pM, respectively. The results suggest that the binding capacity for T3 receptor in the atrium is considerably lower than that found in the ventricle. The reduced binding capacity of the T3 receptor in the atrium might reflect differences in the nuclear T3 receptors between ventricle and atrium

Signaling Pathways in Cardiac Myocyte Apoptosis

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Xia, Peng; Liu, Yuening

2016-01-01

Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation. PMID:28101515

Isomyosin expression patterns in tubular stages of chicken heart development: a 3-D immunohistochemical analysis

NARCIS (Netherlands)

de Jong, F.; Geerts, W. J.; Lamers, W. H.; Los, J. A.; Moorman, A. F.

1987-01-01

The 3-D distribution of atrial and ventricular isomyosins is analysed in tubular chicken hearts (stage 12+ to 17 (H/H)) using antibodies specific for adult chicken atrial and ventricular myosin heavy chains, respectively. At stage 12+ (H/H) all myocytes express the atrial isomyosin; furthermore, all

Surgery for atrial fibrillation.

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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

IGF-1 protects cardiac myocytes from hyperosmotic stress-induced apoptosis via CREB

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Maldonado, Carola; Cea, Paola; Adasme, Tatiana; Collao, Andres; Diaz-Araya, Guillermo; Chiong, Mario; Lavandero, Sergio

2005-01-01

Hyperosmotic stress stimulates a rapid and pronounced apoptosis in cardiac myocytes which is attenuated by insulin-like growth factor-1 (IGF-1). Because in these cells IGF-1 induces intracellular Ca 2+ increase, we assessed whether the cyclic AMP response element-binding protein (CREB) is activated by IGF-1 through Ca 2+ -dependent signalling pathways. In cultured cardiac myocytes, IGF-1 induced phosphorylation (6.5 ± 1.0-fold at 5 min), nuclear translocation (30 min post-stimulus) and DNA binding activity of CREB. IGF-1-induced CREB phosphorylation was mediated by MEK1/ERK, PI3-K, p38-MAPK, as well as Ca 2+ /calmodulin kinase and calcineurin. Exposure of cardiac myocytes to hyperosmotic stress (sorbitol 600 mOsm) decreased IGF-1-induced CREB activation Moreover, overexpression of a dominant negative CREB abolished the anti-apoptotic effects of IGF-1. Our results suggest that IGF-1 activates CREB through a complex signalling pathway, and this transcription factor plays an important role in the anti-apoptotic action of IGF-1 in cultured cardiac myocytes

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

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Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

2018-01-01

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

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

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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.

Slow [Na+]i dynamics impacts arrhythmogenesis and spiral wave reentry in cardiac myocyte ionic model.

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Krogh-Madsen, Trine; Christini, David J

2017-09-01

Accumulation of intracellular Na + is gaining recognition as an important regulator of cardiac myocyte electrophysiology. The intracellular Na + concentration can be an important determinant of the cardiac action potential duration, can modulate the tissue-level conduction of excitation waves, and can alter vulnerability to arrhythmias. Mathematical models of cardiac electrophysiology often incorporate a dynamic intracellular Na + concentration, which changes much more slowly than the remaining variables. We investigated the dependence of several arrhythmogenesis-related factors on [Na + ] i in a mathematical model of the human atrial action potential. In cell simulations, we found that [Na + ] i accumulation stabilizes the action potential duration to variations in several conductances and that the slow dynamics of [Na + ] i impacts bifurcations to pro-arrhythmic afterdepolarizations, causing intermittency between different rhythms. In long-lasting tissue simulations of spiral wave reentry, [Na + ] i becomes spatially heterogeneous with a decreased area around the spiral wave rotation center. This heterogeneous region forms a functional anchor, resulting in diminished meandering of the spiral wave. Our findings suggest that slow, physiological, rate-dependent variations in [Na + ] i may play complex roles in cellular and tissue-level cardiac dynamics.

Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

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Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

2011-07-01

Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Atrial Fibrillation: Treatment

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... 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 ...

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

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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.

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

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

Image Processing Techniques for Assessing Contractility in Isolated Adult Cardiac Myocytes

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Carlos Bazan

2009-01-01

The physiologic application of the methodology is evaluated by assessing overall contraction in enzymatically dissociated adult rat cardiocytes. Our results demonstrate the effectiveness of the proposed approach in characterizing the true, two-dimensional, “shortening” in the contraction process of adult cardiocytes. We compare the performance of the proposed method to that of a popular edge detection system in the literature. The proposed method not only provides a more comprehensive assessment of the myocyte contraction process but also can potentially eliminate historical concerns and sources of errors caused by myocyte rotation or translation during contraction. Furthermore, the versatility of the image processing techniques makes the method suitable for determining myocyte shortening in cells that usually bend or move during contraction. The proposed method can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease modeling, transgeneity, or other common applications to mammalian cardiocytes.

Atrial Fibrillation: Complications

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... 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 ...

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

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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.

Attenuated response of L-type calcium current to nitric oxide in atrial fibrillation.

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Rozmaritsa, Nadiia; Christ, Torsten; Van Wagoner, David R; Haase, Hannelore; Stasch, Johannes-Peter; Matschke, Klaus; Ravens, Ursula

2014-03-01

Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF). Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.

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

Atrial and ventricular function after cardioversion of atrial fibrillation.

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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

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

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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

Dynamic Changes in Sarcoplasmic Reticulum Structure in Ventricular Myocytes

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Amanda L. Vega

2011-01-01

sarcoplasmic reticulum (SR and the sarcolemma where Ca2+ release is activated. Here, we tested the hypothesis that the SR is a structurally inert organelle in ventricular myocytes. Our data suggest that rather than being static, the SR undergoes frequent dynamic structural changes. SR boutons expressing functional ryanodine receptors moved throughout the cell, approaching or moving away from the sarcolemma of ventricular myocytes. These changes in SR structure occurred in the absence of changes in [Ca2+] during EC coupling. Microtubules and the molecular motors dynein and kinesin 1(Kif5b were important regulators of SR motility. These findings support a model in which the SR is a motile organelle capable of molecular motor protein-driven structural changes.

Numerical Analysis of the Effect of T-tubule Location on Calcium Transient in Ventricular Myocytes

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George, Uduak Z.; Wang, Jun; Yu, Zeyun

2013-01-01

Intracellular calcium (Ca2+) signaling in cardiac myocytes is vital for proper functioning of the heart. Understanding the intracellular Ca2+ dynamics would give an insight into the functions of normal and diseased hearts. In the current study, spatiotemporal Ca2+ dynamics is investigated in ventricular myocytes by considering Ca2+ release and re-uptake via sarcolemma and transverse tubules (T-tubules), Ca2+ diffusion and buffering in the cytosol, and the blockade of Ca2+ activities associated with the sarcoplasmic reticulum. This study is carried out using a three dimensional (3D) geometric model of a branch of T-tubule extracted from the electron microscopy (EM) images of a partial ventricular myocyte. Mathematical modeling is done by using a system of partial differential equations involving Ca2+ , buffers, and membrane channels. Numerical simulation results suggest that a lack of T-tubule structure at the vicinity of the cell surface could increase the peak time of Ca2+ concentration in myocytes. The results also show that T-tubules and mobile buffers play an important role in the regulation of Ca2+ transient in ventricular myocytes. PMID:24212025

Antiarrhythmic properties of atrial pacing.

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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.

Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy.

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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.

The ER stress-mediated mitochondrial apoptotic pathway and MAPKs modulate tachypacing-induced apoptosis in HL-1 atrial myocytes.

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Jiaojiao Shi

Full Text Available Cell apoptosis is a contributing factor in the initiation, progression and relapse of atrial fibrillation (AF, a life-threatening illness accompanied with stroke and heart failure. However, the regulatory cascade of apoptosis is intricate and remains unidentified, especially in the setting of AF. The aim of this study was to explore the roles of endoplasmic reticulum (ER stress, mitochondrial apoptotic pathway (MAP, mitogen-activated protein kinases (MAPKs, and their cross-talking in tachypacing-induced apoptosis.HL-1 cells were cultured in the presence of tachypacing for 24 h to simulate atrial tachycardia remodeling. Results showed that tachypacing reduced cell viability measured by the cell counting kit-8, dissipated mitochondrial membrane potential detected by JC-1 staining and resulted in approximately 50% apoptosis examined by Hoechst staining and annexin V/propidium iodide staining. In addition, the proteins involved in ER stress, MAP and MAPKs were universally up-regulated or activated via phosphorylation, as confirmed by western blotting; and reversely silencing of ER stress, caspase-3 (the ultimate executor of MAP and MAPKs with specific inhibitors prior to pacing partially alleviated apoptosis. An inhibitor of ER stress was applied to further investigate the responses of mitochondria and MAPKs to ER stress, and results indicated that suppression of ER stress comprehensively but incompletely attenuated the activation of MAP and MAPKs aroused by tachypacing, with the exception of ERK1/2, one branch of MAPKs.Our study suggested tachypacing-induced apoptosis is regulated by ER stress-mediated MAP and MAPKs. Thus, the above three components are all promising anti-apoptotic targets in AF patients and ER stress appears to play a dominant role due to its comprehensive effects.

A Parsimonious Model of the Rabbit Action Potential Elucidates the Minimal Physiological Requirements for Alternans and Spiral Wave Breakup.

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Gray, Richard A; Pathmanathan, Pras

2016-10-01

Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates). Here we develop a simple "parsimonious" rabbit AP model that is mathematically identifiable (i.e., not over parameterized) by combining a novel Hodgkin-Huxley formulation of INa with a phenomenological model of repolarization similar to the voltage dependent, time-independent rectifying outward potassium current (IK). The model was calibrated using the following experimental data sets measured from the same species (rabbit) under physiological conditions: dynamic current-voltage (I-V) relationships during the AP upstroke; rapid recovery of AP excitability during the relative refractory period; and steady-state INa inactivation via voltage clamp. Simulations reproduced several important "emergent" phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocytes, reentrant spiral waves as observed on the surface of the rabbit heart, and spiral wave breakup. Model variants were studied which elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics of INa inactivation and the non-linear rectification of IK.The simplicity of the model, and the fact that its parameters have physiological meaning, make it ideal for engendering generalizable mechanistic

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

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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.

Validation of an in vitro contractility assay using canine ventricular myocytes

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Harmer, A.R., E-mail: alex.harmer@astrazeneca.com; Abi-Gerges, N.; Morton, M.J.; Pullen, G.F.; Valentin, J.P.; Pollard, C.E.

2012-04-15

Measurement of cardiac contractility is a logical part of pre-clinical safety assessment in a drug discovery project, particularly if a risk has been identified or is suspected based on the primary- or non-target pharmacology. However, there are limited validated assays available that can be used to screen several compounds in order to identify and eliminate inotropic liability from a chemical series. We have therefore sought to develop an in vitro model with sufficient throughput for this purpose. Dog ventricular myocytes were isolated using a collagenase perfusion technique and placed in a perfused recording chamber on the stage of a microscope at ∼ 36 °C. Myocytes were stimulated to contract at a pacing frequency of 1 Hz and a digital, cell geometry measurement system (IonOptix™) was used to measure sarcomere shortening in single myocytes. After perfusion with vehicle (0.1% DMSO), concentration–effect curves were constructed for each compound in 4–30 myocytes taken from 1 or 2 dog hearts. The validation test-set was 22 negative and 8 positive inotropes, and 21 inactive compounds, as defined by their effect in dog, cynolomolgous monkey or humans. By comparing the outcome of the assay to the known in vivo contractility effects, the assay sensitivity was 81%, specificity was 75%, and accuracy was 78%. With a throughput of 6–8 compounds/week from 1 cell isolation, this assay may be of value to drug discovery projects to screen for direct contractility effects and, if a hazard is identified, help identify inactive compounds. -- Highlights: ► Cardiac contractility is an important physiological function of the heart. ► Assessment of contractility is a logical part of pre-clinical drug safety testing. ► There are limited validated assays that predict effects of compounds on contractility. ► Using dog myocytes, we have developed an in vitro cardiac contractility assay. ► The assay predicted the in vivo contractility with a good level of accuracy.

Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes

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Higashi Richard M

2008-10-01

Full Text Available Abstract Background The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30 and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis. Results The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells. Conclusion The specific 13C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells

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

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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

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

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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

Atrial Fibrillation

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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...

Characterization of human septic sera induced gene expression modulation in human myocytes

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Hussein, Shaimaa; Michael, Paul; Brabant, Danielle; Omri, Abdelwahab; Narain, Ravin; Passi, Kalpdrum; Ramana, Chilakamarti V.; Parrillo, Joseph E.; Kumar, Anand; Parissenti, Amadeo; Kumar, Aseem

2009-01-01

To gain a better understanding of the gene expression changes that occurs during sepsis, we have performed a cDNA microarray study utilizing a tissue culture model that mimics human sepsis. This study utilized an in vitro model of cultured human fetal cardiac myocytes treated with 10% sera from septic patients or 10% sera from healthy volunteers. A 1700 cDNA expression microarray was used to compare the transcription profile from human cardiac myocytes treated with septic sera vs normal sera....

Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling.

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Das, Anindita; Xi, Lei; Kukreja, Rakesh C

2005-04-01

We investigated the effect of sildenafil in protection against necrosis or apoptosis in cardiomyocytes. Adult mouse ventricular myocytes were treated with sildenafil (1 or 10 microM) for 1 h before 40 min of simulated ischemia (SI). Necrosis was determined by trypan blue exclusion and lactate dehydrogenase release following SI alone or plus 1 or 18 h of reoxygenation (RO). Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and mitochondrial membrane potential measured using a fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1). Sildenafil reduced necrosis as indicated by decrease in trypan blue-positive myocytes and leakage of lactate dehydrogenase compared with untreated cells after either SI or SI-RO. The number of terminal deoxynucleotidyl transferase-mediated nick end labeling-positive myocytes or loss of JC-1 fluorescence following SI and 18 h of RO was attenuated in the sildenafil-treated group with concomitant inhibition of caspase 3 activity. An early increase in Bcl-2 to Bax ratio with sildenafil treatment was also observed in myocytes after SI-RO. The increase of Bcl-2 expression by sildenafil was inhibited by nitric-oxide synthase (NOS) inhibitor, L-nitro-amino-methyl-ester. The drug also enhanced mRNA and protein content of inducible NOS (iNOS) and endothelial NOS (eNOS) in the myocytes. Sildenafil-induced protection against necrosis and apoptosis was absent in the myocytes derived from iNOS knock-out mice and was attenuated in eNOS knock-out myocytes. The up-regulation of Bcl-2 expression by sildenafil was also absent in iNOS-deficient myocytes. Reverse transcription-PCR, Western blots, and immunohistochemical assay confirmed the expression of phosphodiesterase-5 in mouse cardiomyocytes. These data provide strong evidence for a direct protective effect of sildenafil against necrosis and apoptosis through NO signaling pathway. The results may have possible

TNF-α- Mediated-p38-Dependent Signaling Pathway Contributes to Myocyte Apoptosis in Rats Subjected to Surgical Trauma

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Huaxing Wu

2015-03-01

Full Text Available Background: The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma. Methods: Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580. Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively. Results: Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580. Conclusion: Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.

Study on the effect of hypoxia on apoptosis of cultured newly born rat cardiac myocytes

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Su Weidong; Li Huiqiang; Yao Zhi

2005-01-01

Objective: To investigate the possible hypoxia-mediated cellular apoptosis after ischemic cardiac injury via a model of cultured newly born rat cardiac myocytes. Methods: Cardiac myocytes cultures from newly born rats (1-3d) were examined for apoptosis with HE stain and flow cytometry after cultured 96h and again examined after exposure to hypoxic environment for 16h. Results: Apoptotic changes were evident in the hypoxic culture cells. The HE stain revealed cellular shrinkage, nuclear chromosomal condensation with cytoplasmic eosinophilia. Also, distinct apoptosis peak was observed in the flow cytometry. Conclusion: This experiment proved that hypoxic model of cardiac myocyte culture showed definite apoptosis of the cells. (authors)

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

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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.

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

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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

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

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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.

Atrial fibrillation and hyperthyroidism: A literature review.

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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.

Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.

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Ali, Ramez M; Al Kury, Lina T; Yang, Keun-Hang Susan; Qureshi, Anwar; Rajesh, Mohanraj; Galadari, Sehamuddin; Shuba, Yaroslav M; Howarth, Frank Christopher; Oz, Murat

2015-04-01

Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1μM) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca(2+) transients. However, the amplitudes of caffeine-evoked Ca(2+) transients and the rate of recovery of electrically evoked Ca(2+) transients following caffeine application were not altered. CBD (1μM) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1μM in a voltage-independent manner. Radioligand studies indicated that the specific binding of [(3)H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca(2+) channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacological Treatment for Atrial Fibrillation

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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.

Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres.

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Hanft, Laurin M; McDonald, Kerry S

2010-08-01

According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length

Stochastic Alternating Dynamics for Synchronous EAD-Like Beating Rhythms in Cultured Cardiac Myocytes

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ZHANG Ning; ZHANG Hui-Min; LIU Zhi-Qiang; DING Xue-Li; YANG Ming-Hao; GU Hua-Guang; REN Wei

2009-01-01

Dissolved cardiac myocytes can couple together and generate synchronous beatings in culture. We observed a synchronized early after-depolarization(EAD)-like rhythm in cultured cardiac myocytes and reproduced the experimental observation in a network mathematical model whose dynamics are close to a Hopf bifurcation. The mechanism for this EAD-like rhythm is attributed to noised-induced stochastic alternatings between the focus and the limit cycle. These results provide novel understandings for pathological heart rhythms like the early immature beatings.

Role of Non-Myocyte Gap Junctions and Connexin Hemichannels in Cardiovascular Health and Disease: Novel Therapeutic Targets?

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Johnson, Robert D; Camelliti, Patrizia

2018-03-15

The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes. Connexins are expressed in both cardiomyocytes and non-myocytes, including cardiac fibroblasts, endothelial cells, and macrophages. Non-myocytes are the largest population of cells in the heart, and therefore it is important to consider what roles connexins, hemichannels, and gap junctions play in these cell types. The aim of this review is to provide insight into connexin-based signalling in non-myocytes during health and disease, and highlight how targeting these proteins could lead to the development of novel therapies. We conclude that connexins in non-myocytes contribute to arrhythmias and adverse ventricular remodelling following myocardial infarction, and are associated with the initiation and development of atherosclerosis. Therefore, therapeutic interventions targeting these connexins represent an exciting new research avenue with great potential.

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

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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.

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.

Heuristic problems in defining the three-dimensional arrangement of the ventricular myocytes.

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Anderson, Robert H; Ho, Siew Yen; Sanchez-Quintana, Damian; Redmann, Klaus; Lunkenheimer, Paul P

2006-06-01

There is lack of consensus concerning the three-dimensional arrangement of the myocytes within the ventricular muscle masses. Bioengineers are seeking to model the structure of the heart. Although the success of such models depends on the accuracy of the anatomic evidence, most of them have been based on concepts that are far from anatomical reality, which ignore many significant previous accounts of anatomy presented over the past 400 years. During the 19th century, Pettigrew emphasized that the heart was built on the basis of a modified blood vessel rather than in the form of skeletal muscles. This fact was reemphasized by Lev and Simkins as well as Grant in the 20th century, but the caveats listed by these authors have been ignored by proponents of two current concepts, which state either that the myocardium is arranged in the form of a "unique myocardial band," or that the walls of the ventricles are sequestrated in uniform fashion by laminar sheets of fibrous tissue extending from epicardium to endocardium. These two concepts are themselves incompatible and are further at variance with the majority of anatomic studies, which have emphasized the regional heterogeneity to be found in the three-dimensional packing of the myocytes within a supporting matrix of fibrous tissue. We reemphasize the significance of this three-dimensional muscular mesh, showing how the presence of intruding aggregates of myocytes extending in oblique transmural fashion also contends against the notion that all myocytes are orientated with their long axes parallel to the epicardial and enodcardial surfaces.

Atrial fibrillation - discharge

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... 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 ...

Calcium release-dependent inactivation precedes formation of the tubular system in developing rat cardiac myocytes.

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Macková, Katarina; Zahradníková, Alexandra; Hoťka, Matej; Hoffmannová, Barbora; Zahradník, Ivan; Zahradníková, Alexandra

2017-12-01

Developing cardiac myocytes undergo substantial structural and functional changes transforming the mechanism of excitation-contraction coupling from the embryonic form, based on calcium influx through sarcolemmal DHPR calcium channels, to the adult form, relying on local calcium release through RYR calcium channels of sarcoplasmic reticulum stimulated by calcium influx. We characterized day-by-day the postnatal development of the structure of sarcolemma, using techniques of confocal fluorescence microscopy, and the development of the calcium current, measured by the whole-cell patch-clamp in isolated rat ventricular myocytes. We characterized the appearance and expansion of the t-tubule system and compared it with the appearance and progress of the calcium current inactivation induced by the release of calcium ions from sarcoplasmic reticulum as structural and functional measures of direct DHPR-RYR interaction. The release-dependent inactivation of calcium current preceded the development of the t-tubular system by several days, indicating formation of the first DHPR-RYR couplons at the surface sarcolemma and their later spreading close to contractile myofibrils with the growing t-tubules. Large variability of both of the measured parameters among individual myocytes indicates uneven maturation of myocytes within the growing myocardium.

Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

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Song, Yejia; Belardinelli, Luiz

2017-12-14

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

Trichostatin A (TSA) improves the development of rabbit-rabbit intraspecies cloned embryos, but not rabbit-human interspecies cloned embryos.

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Shi, Li-Hong; Miao, Yi-Liang; Ouyang, Ying-Chun; Huang, Jun-Cheng; Lei, Zi-Li; Yang, Ji-Wen; Han, Zhi-Ming; Song, Xiang-Fen; Sun, Qing-Yuan; Chen, Da-Yuan

2008-03-01

The interspecies somatic cell nuclear transfer (iSCNT) technique for therapeutic cloning gives great promise for treatment of many human diseases. However, the incomplete nuclear reprogramming and the low blastocyst rate of iSCNT are still big problems. Herein, we observed the effect of TSA on the development of rabbit-rabbit intraspecies and rabbit-human interspecies cloned embryos. After treatment with TSA for 6 hr during activation, we found that the blastocyst rate of rabbit-rabbit cloned embryos was more than two times higher than that of untreated embryos; however, the blastocyst rate of TSA-treated rabbit-human interspecies cloned embryos decreased. We also found evident time-dependent histone deacetylation-reacetylation changes in rabbit-rabbit cloned embryos, but not in rabbit-human cloned embryos from fusion to 6 hr after activation. Our results suggest that TSA-treatment does not improve blastocyst development of rabbit-human iSCNT embryos and that abnormal histone deacetylation-reacetylation changes in iSCNT embryos may account for their poor blastocyst development. (c) 2008 Wiley-Liss, Inc.

Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

NARCIS (Netherlands)

Burt, S.A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H.M.

2016-01-01

Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

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....

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

Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

NARCIS (Netherlands)

Burt, Sara A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; Poel, van der Wim H.M.

2016-01-01

Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs

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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

Ultrasonic destruction of albumin microbubbles enhances gene transfection and expression in cardiac myocytes.

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Wang, Guo-zhong; Liu, Jing-hua; Lü, Shu-zheng; Lü, Yun; Guo, Cheng-jun; Zhao, Dong-hui; Fang, Dong-ping; He, Dong-fang; Zhou, Yuan; Ge, Chang-jiang

2011-05-01

It has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial. This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes. The β-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed. The ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95 ± 2.41) U/g or (29.28 ± 3.65) U/g vs. (0.84 ± 0.21) U/g, P ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced β-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35 ± 11.21) U/g protein vs. (14.13 ± 2.58) U/g protein, P < 0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63 ± 7.65) U/g vs. (14.13 ± 2.58) U/g, P < 0.05). Ultrasonic destruction of microbubbles might be a promising method for the delivery of non-viral DNA into

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

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Philip Gemmell

Full Text Available Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+, inward rectifying K(+, L-type Ca(2+, and Na(+/K(+ pump currents in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al. at multiple cycle lengths (400, 600, 1,000 ms was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

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Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

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

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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.

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

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.

[Echocardiographic diagnosis of atrial thrombosis].

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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.

[Left atrial function and left atrial appendage flow velocity in hypertrophic cardiomyopathy: comparison of patients with and without paroxysmal atrial fibrillation].

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Akasaka, K; Kawashima, E; Shiokoshi, T; Ishii, Y; Hasebe, N; Kikuchi, K

1998-07-01

The involvement of left atrial (LA) appendage flow velocity in reduced left atrial function was investigated in 24 patients with hypertrophic cardiomyopathy, who retained sinus rhythm at the examination. Patients were divided into 11 with a history of paroxysmal atrial fibrillation [PAf(+)] and 13 without such history [PAf(-)]. Transthoracic echocardiography was performed to evaluate LA fractional shortening (LA%FS) and mean velocity of circumferential LA fiber shortening (LAmVcf), as contractile functions of the left atrium at the phase of active atrial contraction. Transesophageal echocardiographic Doppler examination was performed in all patients to measure the LA appendage velocity. In all patients, significant positive correlations were observed between the LA appendage velocity and LA%FS (r = 0.50, p fibrillation were significantly lower than in those without (0.84 +/- 0.15 vs 1.28 +/- 0.37 circ/sec, 44 +/- 12 vs 65 +/- 20 cm/sec, both p fibrillation. These results indicate that there is a close relationship between LA appendage velocity and LA contractile function in patients with hypertrophic cardiomyopathy with paroxysmal atrial fibrilation, and these patients have potential risk of cerebral infarction.

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...

Atrial fibrillation in the elderly

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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

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...

[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.

[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.

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

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.

Genetically engineered cardiac pacemaker: Stem cells transfected with HCN2 gene and myocytes-A model

Energy Technology Data Exchange (ETDEWEB)

Kanani, S. [Institut Genomique Fonctionelle, 141 Rue de la Cardonille, 34396 Montpellier (France); Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Pumir, A. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France); Laboratoire J.A. Dieudonne, CNRS and Universite de Nice, Parc Valrose, 06108 Nice (France)], E-mail: alain.pumir@unice.fr; Krinsky, V. [Institut Non Lineaire de Nice, CNRS and Universite de Nice, 1361 route des Lucioles, 06560 Valbonne (France)

2008-01-07

One of the successfully tested methods to design genetically engineered cardiac pacemaker cells consists in transfecting a human mesenchymal stem cell (hMSC) with a HCN2 gene and connecting it to a myocyte. We develop and study a mathematical model, describing a myocyte connected to a hMSC transfected with a HCN2 gene. The cardiac action potential is described both with the simple Beeler-Reuter model, as well as with the elaborate dynamic Luo-Rudy model. The HCN2 channel is described by fitting electrophysiological records, in the spirit of Hodgkin-Huxley. The model shows that oscillations can occur in a pair myocyte-stem cell, that was not observed in the experiments yet. The model predicted that: (1) HCN pacemaker channels can induce oscillations only if the number of expressed I{sub K1} channels is low enough. At too high an expression level of I{sub K1} channels, oscillations cannot be induced, no matter how many pacemaker channels are expressed. (2) At low expression levels of I{sub K1} channels, a large domain of values in the parameter space (n, N) exists, where oscillations should be observed. We denote N the number of expressed pacemaker channels in the stem cell, and n the number of gap junction channels coupling the stem cell and the myocyte. (3) The expression levels of I{sub K1} channels observed in ventricular myocytes, both in the Beeler-Reuter and in the dynamic Luo-Rudy models are too high to allow to observe oscillations. With expression levels below {approx}1/4 of the original value, oscillations can be observed. The main consequence of this work is that in order to obtain oscillations in an experiment with a myocyte-stem cell pair, increasing the values of n, N is unlikely to be helpful, unless the expression level of I{sub K1} has been reduced enough. The model also allows us to explore levels of gene expression not yet achieved in experiments, and could be useful to plan new experiments, aimed at improving the robustness of the oscillations.

Atrial fibrillation or flutter

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... 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 ...

Atrial conduction times and left atrial mechanical functions and their relation with diastolic function in prediabetic patients.

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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.

Genetics Home Reference: familial atrial fibrillation

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... 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 ...

[Atrial fibrillation].

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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.

Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a role for thyroid hormone?

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Havekes, Bas; Sauerwein, Hans P

2010-11-01

To review original research studies and reviews that present data on adipocyte-myocyte crosstalk in the development of skeletal muscle insulin resistance with a specific focus on thyroid hormone. Adipose tissue communicates with skeletal muscle not only through free fatty acids but also through secretion of various products called adipokines. Adipokines came out as governors of insulin sensitivity and are deregulated in obesity. In addition to well known leptin, adiponectin, interleukin-6 and tumor necrosis factor-alpha, newer adipokines like retinol-binding protein 4 have been associated with insulin resistance. There is mounting evidence that not only adipose tissue but also skeletal muscle produces and secretes biologically active proteins or 'myokines' that facilitate metabolic crosstalk between organ systems. In recent years, increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Both hypothyroidism and hyperthyroidism affect insulin sensitivity in multiple ways that might overlap adipocyte-myocyte crosstalk. Recent studies have provided new insights in effects of processing of the parent hormone T4 to the active T3 at the level of the skeletal muscle. Adipocyte-myocyte crosstalk is an important modulator in the development of skeletal muscle insulin resistance. Thyroid disorders are very common and may have detrimental effects on skeletal muscle insulin resistance, potentially by interacting with adipocyte-myocyte crosstalk.

Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

Directory of Open Access Journals (Sweden)

Hester M Den Ruijter

2010-11-01

Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in rabbit kittens.

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Matthaei, Markus; Kerr, Peter J; Read, Andrew J; Hick, Paul; Haboury, Stephanie; Wright, John D; Strive, Tanja

2014-06-09

Only one strain (the Czech CAPM-v351) of rabbit haemorrhagic disease virus (RHDV) has been released in Australia and New Zealand to control pest populations of the European rabbit O. cuniculus. Antigenic variants of RHDV known as RHDVa strains are reportedly replacing RHDV strains in other parts of the world, and Australia is currently investigating the usefulness of RHDVa to complement rabbit biocontrol efforts in Australia and New Zealand. RHDV efficiently kills adult rabbits but not rabbit kittens, which are more resistant to RHD the younger they are and which may carry the virus without signs of disease for prolonged periods. These different infection patterns in young rabbits may significantly influence RHDV epidemiology in the field and hence attempts to control rabbit numbers. We quantified RHDV replication and shedding in 4-5 week old rabbits using quantitative real time PCR to assess their potential to shape RHDV epidemiology by shedding and transmitting virus. We further compared RHDV-v351 with an antigenic variant strain of RHDVa in kittens that is currently being considered as a potential RHDV strain for future release to improve rabbit biocontrol in Australia. Kittens were susceptible to infection with virus doses as low as 10 ID50. Virus growth, shedding and transmission after RHDVa infection was found to be comparable or non-significantly lower compared to RHDV. Virus replication and shedding was observed in all kittens infected, but was low in comparison to adult rabbits. Both viruses were shed and transmitted to bystander rabbits. While blood titres indicated that 4-5 week old kittens mostly clear the infection even in the absence of maternal antibodies, virus titres in liver, spleen and mesenteric lymph node were still high on day 5 post infection. Rabbit kittens are susceptible to infection with very low doses of RHDV, and can transmit virus before they seroconvert. They may therefore play an important role in RHDV field epidemiology, in

Accumulation of 125I-factor XI in atheroma of rabbit with hereditary hyperlipidemia (WHHL-rabbit)

International Nuclear Information System (INIS)

Komiyama, Y.; Masuda, M.; Murakami, T.; Nishikado, H.; Egawa, H.; Nishimura, T.; Morii, S.; Murata, K.

1989-01-01

We have studied the turnover and accumulation of rabbit factor XI (F.XI) in atherosclerotic lesion in Watanabe-hereditable hyperlipidemic rabbit (WHHL rabbit) to reveal the participation of blood coagulation in atherosclerotic lesion. Rabbit F.XI was iodinated and administered intravenously to WHHL rabbits and Japanese white rabbits. The turnover of 125 I-rabbit F.XI was significantly faster in WHHL rabbits (T1/2 = 2.84 +/- 0.44 days) than in normal rabbits (T1/2 = 4.44 +/- 0.42 days). The thoracic aorta of WHHL rabbit was strongly labelled with 125 I-rabbit F.XI, in sections obtained after 5 days by en-face autoradiography, whereas no radioactivity was detected in normal aorta. By an immunohistochemical study of WHHL rabbit aorta, we confirmed that many F.XI- and fibrin-related compounds existed in the atheroma, whereas albumin did not in these area. These results suggest that the activation of F.XI proceeds on the atherosclerotic lesions of WHHL rabbits

Atrial Fibrillation - Multiple Languages

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... 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 ...

Allergy to Rabbits. 1

International Nuclear Information System (INIS)

Price, J.A.; Longbottom, J.L.

1986-01-01

Investigations have been carried out into the presence of antibody light chains in rabbit allergenic extracts and the interference in RAST and crossed-radioimmunoelectrophoresis (XRIE) caused by antibodies directed against them. A ''non-specific'' uptake of radioactivity in XRIE has been demonstrated to be caused by direct cross-linking of the 125 I rabbit anti-human IgE by the sheep antibodies in the immunoprecipitate of rabbit light chains. Preincubation with normal rabbit serum blocked this direct uptake of the labelled antibody and enabled specific IgE uptake on the light chains to be demonstrated for rabbit allergic sera. Verification of the allergenicity of the light chains was obtained from a specific light chain RAST. Elution from a Sephacryl S-200 gel filtration column indicated a MW of approx. 50Kd and confirmation of the components as light chain dimers, not Fab fragments, was obtained by allotyping for loci present on heavy chains and light chains in the Fab region. Light chains were detected in urine from rabbits of all ages and in an extract of dust collected in a rabbit housing area. No background staining was observed in XRIE using rabbit antisera, either with rabbit allergic sera with specific IgE or with a human serum containing specific IgG antibodies to rabbit IgG. This latter serum also showed no evidence of uptake on all immunoprecipitates in systems using rabbit antisera, and did not give false positive RAST results when the labelled rabbit anti-human IgE contained unlabelled rabbit IgG. Those sera with specific IgE to light chains showed no uptake in XRIE using rabbit antisera, indicating that the IgE was possibly specific for epitopes revealed by the dissociation on the whole IgG molecule. (author)

Left atrial low-voltage areas predict atrial fibrillation recurrence after catheter ablation in patients with paroxysmal atrial fibrillation.

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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.

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.

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.

Rabbit analgesia.

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Barter, Linda S

2011-01-01

With the increasing popularity of rabbits as household pets, the complexity of diagnostic and surgical procedures performed on rabbits is increasing, along with the frequency of routine surgical procedures. More practitioners are faced with the need to provide adequate analgesia for this species. Preemptive analgesia prior to planned surgical interventions may reduce nervous system changes in response to noxious input, as well as reduce postoperative pain levels and analgesic drug requirements. Concurrent administration of analgesic drugs to anesthetized rabbits undergoing painful procedures is warranted both pre- and intraoperatively as well as postoperatively. This article discusses the neuropharmacologic and pharmacologic aspects of pain in rabbits, and reviews current protocols for the use of analgesic drugs. Published by Elsevier Inc.

Modulation of contraction by intracellular Na+ via Na(+)-Ca2+ exchange in single shark (Squalus acanthias) ventricular myocytes.

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Näbauer, M; Morad, M

1992-01-01

1. The effect of direct alteration of intracellular Na+ concentration on contractile properties of whole-cell clamped shark ventricular myocytes was studied using an array of 256 photodiodes to monitor the length of the isolated myocytes. 2. In myocytes dialysed with Na(+)-free solution, the voltage dependence of Ca2+ current (ICa) and contraction were similar and bell shaped. Contractions activated at all voltages were completely suppressed by nifedipine (5 microM), and failed to show significant tonic components, suggesting dependence of the contraction on Ca2+ influx through the L-type Ca2+ channel. 3. In myocytes dialysed with 60 mM Na+, a ICa-dependent and a ICa-independent component of contraction could be identified. The Ca2+ current-dependent component was prominent in voltages between -30 to +10 mV. The ICa-independent contractions were maintained for the duration of depolarization, increased with increasing depolarization between +10 to +100 mV, and were insensitive to nifedipine. 4. In such myocytes, repolarization produced slowly decaying inward tail currents closely related to the time course of relaxation and the degree of shortening prior to repolarization. 5. With 60 mM Na+ in the pipette solution, positive clamp potentials activated decaying outward currents which correlated to the size of contraction. These outward currents appeared to be generated by the Na(+)-Ca(2+)-exchanger since they depended on the presence of intracellular Na+, and were neither suppressed by nifedipine nor by K+ channel blockers. 6. The results suggest that in shark (Squalus acanthias) ventricular myocytes, which lack functionally relevant Ca2+ release pools, both Ca2+ channel and the Na(+)-Ca2+ exchanger deliver sufficient Ca2+ to activate contraction, though the effectiveness of the latter mechanism was highly dependent on the [Na+]i. PMID:1338467

Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors.

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Patel, Hemal H; Head, Brian P; Petersen, Heidi N; Niesman, Ingrid R; Huang, Diane; Gross, Garrett J; Insel, Paul A; Roth, David M

2006-07-01

The role of caveolae, membrane microenvironments enriched in signaling molecules, in myocardial ischemia is poorly defined. In the current study, we used cardiac myocytes prepared from adult rats to test the hypothesis that opioid receptors (OR), which are capable of producing cardiac protection in vivo, promote cardiac protection in cardiac myocytes in a caveolae-dependent manner. We determined protein expression and localization of delta-OR (DOR) using coimmunohistochemistry, caveolar fractionation, and immunoprecipitations. DOR colocalized in fractions with caveolin-3 (Cav-3), a structural component of caveolae in muscle cells, and could be immunoprecipitated by a Cav-3 antibody. Immunohistochemistry confirmed plasma membrane colocalization of DOR with Cav-3. Cardiac myocytes were subjected to simulated ischemia (2 h) or an ischemic preconditioning (IPC) protocol (10 min ischemia, 30 min recovery, 2 h ischemia) in the presence and absence of methyl-beta-cyclodextrin (MbetaCD, 2 mM), which binds cholesterol and disrupts caveolae. We also assessed the cardiac protective effects of SNC-121 (SNC), a selective DOR agonist, on cardiac myocytes with or without MbetaCD and MbetaCD preloaded with cholesterol. Ischemia, simulated by mineral oil layering to inhibit gas exchange, promoted cardiac myocyte cell death (trypan blue staining), a response blunted by SNC (37 +/- 3 vs. 59 +/- 3% dead cells in the presence and absence of 1 muM SNC, respectively, P protective effects of IPC or SNC, resulting in cell death comparable to that of the ischemic group. By contrast, SNC-induced protection was not abrogated in cells incubated with cholesterol-saturated MbetaCD, which maintained caveolae structure and function. These findings suggest a key role for caveolae, perhaps through enrichment of signaling molecules, in contributing to protection of cardiac myocytes from ischemic damage.

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. 

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...

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

Directory of Open Access Journals (Sweden)

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

Surface atrial frequency analysis in patients with atrial fibrillation: a tool for evaluating the effects of intervention.

Science.gov (United States)

Raine, Dan; Langley, Philip; Murray, Alan; Dunuwille, Asunga; Bourke, John P

2004-09-01

The aims of this study were to evaluate (1) principal component analysis as a technique for extracting the atrial signal waveform from the standard 12-lead ECG and (2) its ability to distinguish changes in atrial fibrillation (AF) frequency parameters over time and in response to pharmacologic manipulation using drugs with different effects on atrial electrophysiology. Twenty patients with persistent AF were studied. Continuous 12-lead Holter ECGs were recorded for 60 minutes, first, in the drug-free state. Mean and variability of atrial waveform frequency were measured using an automated computer technique. This extracted the atrial signal by principal component analysis and identified the main frequency component using Fourier analysis. Patients were then allotted sequentially to receive 1 of 4 drugs intravenously (amiodarone, flecainide, sotalol, or metoprolol), and changes induced in mean and variability of atrial waveform frequency measured. Mean and variability of atrial waveform frequency did not differ within patients between the two 30-minute sections of the drug-free state. As hypothesized, significant changes in mean and variability of atrial waveform frequency were detected after manipulation with amiodarone (mean: 5.77 vs 4.86 Hz; variability: 0.55 vs 0.31 Hz), flecainide (mean: 5.33 vs 4.72 Hz; variability: 0.71 vs 0.31 Hz), and sotalol (mean: 5.94 vs 4.90 Hz; variability: 0.73 vs 0.40 Hz) but not with metoprolol (mean: 5.41 vs 5.17 Hz; variability: 0.81 vs 0.82 Hz). A technique for continuously analyzing atrial frequency characteristics of AF from the surface ECG has been developed and validated.

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.

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.

[Quantitative Measurements on the Blood Flow Fields of Left Atrial Appendage using Vector Flow Mapping in Patients with Nonvalvular Atrial Fibrillation].

Science.gov (United States)

Cai, Yu-Yan; Wei, Xin; Zhang, Xiao-Ling; Liu, Gu-Yue; Li, Xi; Tang, Hong

2018-01-01

To quantify the hemodynamic characteristics of patients with nonvalvular atrial fibrillation. Twenty patients with paroxysmal atrial fibrillation and 15 patients with persistent atrial fibrillation enrolled in this study,while 12 patients with sinus rhythms served as controls. The hemodynamic characteristics of the patients in left atrial appendage were measured by transesophageal echocardiography (TEE) and vector flow mapping (VFM) using indicators such as vectors,vortex and energy loss (EL). ① Significant differences appeared between the patients with atrial fibrillation and the controls in heart rate,size of left atrium,size of left atrial appendage (LAA),and velocities of LAA filling and emptying. ② Regular vectors in LAA in early systole and late diastole were found in the patients with paroxysmal atrial fibrillation and the controls; whereas,irregular vectors with direction alternating were visualized in the whole cardiac cycle in the patients with persistent atrial fibrillation. ③ Small vortexes were observed at the opening of the left atrial appendage in late diastole in the patients with paroxysmal atrial fibrillation and the controls. ④ Peak EL values occurred in early systole and late diastole in the patients with paroxysmal atrial fibrillation and the controls. But the patients with persistent atrial fibrillation had increased EL values over the whole cardiac cycle. VFM can visualize and quantify the hemodynamics of LAA in patients with different heart rhythms. It may provide a new method for assessing atrial fibrillation. CopyrightCopyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

Intracellular calcium modulation of voltage-gated sodium channels in ventricular myocytes

NARCIS (Netherlands)

Casini, Simona; Verkerk, Arie O.; van Borren, Marcel M. G. J.; van Ginneken, Antoni C. G.; Veldkamp, Marieke W.; de Bakker, Jacques M. T.; Tan, Hanno L.

2009-01-01

AIMS: Cardiac voltage-gated sodium channels control action potential (AP) upstroke and cell excitability. Intracellular calcium (Ca(i)(2+)) regulates AP properties by modulating various ion channels. Whether Ca(i)(2+) modulates sodium channels in ventricular myocytes, is unresolved. We studied

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

Stimulation of ICa by basal PKA activity is facilitated by caveolin-3 in cardiac ventricular myocytes.

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Bryant, Simon; Kimura, Tomomi E; Kong, Cherrie H T; Watson, Judy J; Chase, Anabelle; Suleiman, M Saadeh; James, Andrew F; Orchard, Clive H

2014-03-01

L-type Ca channels (LTCC), which play a key role in cardiac excitation-contraction coupling, are located predominantly at the transverse (t-) tubules in ventricular myocytes. Caveolae and the protein caveolin-3 (Cav-3) are also present at the t-tubules and have been implicated in localizing a number of signaling molecules, including protein kinase A (PKA) and β2-adrenoceptors. The present study investigated whether disruption of Cav-3 binding to its endogenous binding partners influenced LTCC activity. Ventricular myocytes were isolated from male Wistar rats and LTCC current (ICa) recorded using the whole-cell patch-clamp technique. Incubation of myocytes with a membrane-permeable peptide representing the scaffolding domain of Cav-3 (C3SD) reduced basal ICa amplitude in intact, but not detubulated, myocytes, and attenuated the stimulatory effects of the β2-adrenergic agonist zinterol on ICa. The PKA inhibitor H-89 also reduced basal ICa; however, the inhibitory effects of C3SD and H-89 on basal ICa amplitude were not summative. Under control conditions, myocytes stained with antibody against phosphorylated LTCC (pLTCC) displayed a striated pattern, presumably reflecting localization at the t-tubules. Both C3SD and H-89 reduced pLTCC staining at the z-lines but did not affect staining of total LTCC or Cav-3. These data are consistent with the idea that the effects of C3SD and H-89 share a common pathway, which involves PKA and is maximally inhibited by H-89, and suggest that Cav-3 plays an important role in mediating stimulation of ICa at the t-tubules via PKA-induced phosphorylation under basal conditions, and in response to β2-adrenoceptor stimulation. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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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.

[Relations between FANS, PPI and atrial fibrillation].

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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.

Atrial septal stenting - How I do it?

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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.

Raman probing of lipids, proteins, and mitochondria in skeletal myocytes: a case study on obesity

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Brazhe, Nadezda A.; Nikelshparg, Evelina I.; Prats, Clara

2017-01-01

We propose a novel approach to assess simultaneously lipid composition in lipid droplets, the redox state of cytochromes, and the relative amount of [Fe–S] clusters in the electron transport chain in the mitochondria of skeletal myocytes by means of near-infrared Raman spectroscopy. Mitochondria...... technique allows to estimate qualitatively the relative amount of cholesterol and unsaturated lipids, ordering of lipid phase in lipid droplets, changes in the redox state of c-type and b-type cytochromes, and the relative amount of [Fe–S] clusters in the mitochondria of intact myocytes. The proposed...

Atrial fibrillation and survival in colorectal cancer

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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.

Oclusão percutânea do apêndice atrial esquerdo com o Amplatzer Cardiac PlugTM na fibrilação atrial Percutaneous occlusion of left atrial appendage with the Amplatzer Cardiac PlugTM in atrial fibrillation

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Márcio José Montenegro

2012-02-01

Full Text Available Fundamento: A fibrilação atrial está associada a acidentes vasculares embólicos que frequentemente resultam em morte ou invalidez. Eficaz na redução desses eventos, a anticoagulação possui várias limitações e vem sendo amplamente subutilizada. Mais de 90% dos trombos identificados nos portadores de fibrilação atrial sem doença valvar se originam no apêndice atrial esquerdo, cuja oclusão é investigada como uma alternativa à anticoagulação. Objetivo: Determinar a viabilidade da oclusão percutânea do apêndice atrial esquerdo em pacientes com alto risco de eventos embólicos e limitações ao uso de anticoagulação. Métodos: Relatamos a experiência inicial com o Amplatzer Cardiac PlugTM (St. Jude Medical Inc., Saint Paul, Estados Unidos em pacientes com fibrilação atrial não valvar. Foram selecionados pacientes com alto risco de tromboembolia, sangramentos maiores e contraindicações ao uso ou grande labilidade na resposta ao anticoagulante. Os procedimentos foram realizados por via percutânea, sob anestesia geral e com ecocardiografia transesofágica. O desfecho primário foi a presença de complicações periprocedimento e o seguimento programado incluiu reavaliação clínica e ecocardiográfica em 30 dias e por contato telefônico após nove meses. Resultados: Nos cinco pacientes selecionados se conseguiu a oclusão do apêndice atrial esquerdo sem complicações periprocedimento. Não houve eventos clínicos no seguimento. Conclusão: Ensaios clínicos controlados são necessários antes que o fechamento percutâneo do apêndice atrial esquerdo constitua uma alternativa à anticoagulação na fibrilação atrial não associada a doença valvar. Mas o dispositivo se mostrou promissor em pacientes com alto risco de embolia e restrições ao uso de anticoagulantes.Background: Atrial fibrillation is associated with embolic strokes that often result in death or disability. Effective in reducing these events

Novel protective role of endogenous cardiac myocyte P2X4 receptors in heart failure.

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Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A; Liang, Bruce T

2014-05-01

Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N(5)-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. © 2014 American Heart Association, Inc.

Assessment of the dynamics of atrial signals and local atrial period series during atrial fibrillation: effects of isoproterenol administration

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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.

Effects of atrial fibrillation/atrial flutter on the short and medium-term prognosis of patients with acute myocardial infarction

International Nuclear Information System (INIS)

Cui Kejian; Gu Shuiming; Ding Yueyou; Zheng Hongchao; Zhang Yachen; Li Yigang

2008-01-01

Objective: To evaluate the influnce of atrial fibrillation(AF)/atrial flutter on the mortality and prognosis of patients with AMI. Methods: A total of 297 consecutive patients were studied from Jan. 2001 to Dec. 2005 and were categorized into 2 groups according to the presence or absence of AF/atrial flutter. The 30 d and 6 mo mortalities, Killip Grades, cardiogenic shock, arrhythmia and left ventricular ejectory functional (LVEF) 6 months after AMI with Doppler US between the 2 groups were compared. Results: The incidence of AF/atrial fluttler was 12.5% with older age, higher Killip Gorade, higher CPK peak, higher rates of previous myocardial infarction and multivascular involvement than those without AF/ atrial flutter. The short and medium-term mortalities in AF/atriat flutter group were both significantly higher than those of non-AF/atrial flutter group (P<0.05). Conclusions: The short and medium-term mortalities increase obviously in AMI complicated with AF/atrial flutter, probably related to the severity of atherosclerosis. (authors)

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

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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.

Effect of atrial preference pacing on reducing long-term burden of atrial fibrillation:a clinical study

International Nuclear Information System (INIS)

Xu Jianfeng; Chen Yueguang; Su Yangang; Zhang Dadong

2010-01-01

Objective: To evaluate the clinical effect of atrial preference pacing (APP) on the prevention of paroxysmal atrial fibrillation. Methods: Based on the type of implanted pacemaker, 46 patients with sick sinus syndrome and paroxysmal atrial fibrillation were divided into two groups. Dual-chamber pacemaker equipped with APP function was implanted in patients of group APP (n=21), while conventional dual-chamber pacemaker was implanted in patients of control group (n=25). The patients were followed up for six months, the maximum P wave duration (Pmax), the P wave dispersion (Pd), the structure of heart chambers, the data of automatic mode switch (AMS) and the total burden of atrial fibrillation were estimated,and the results were statistically analyzed and compared between two groups. Results: The basic clinical characteristics of two groups were comparable. After six months pacing, the difference in Pmax between two groups was of no significance (115.0 ± 10.1 ms vs 122.0 ± 11.0 ms, P > 0.05), while the increase of Pd in control group was more obvious than that in group APP (32.7 ± 4.2 ms vs 20.1 ± 5.3 ms, P 0.05), and also no remarkable difference in the left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) could be found (P > 0.05). Moreover, no significant difference existed between two groups (P > 0.05). After six months pacing,in group APP the frequencies of AMS decreased more sharply (145 ± 37 times vs 327 ± 13 times, P < 0.05), the duration of AMS shortened more apparently (73 ± 15 hours vs 139 ± 28 hours, P < 0.05) and the total burden of atrial fibrillation was alleviated more obviously (13 ± 5% vs 28 ± 6%, P < 0.05) when compared to those in control group. Conclusion: Atrial preference pacing can coordinate the anisotropy of double atrial depolarization, reduce the frequencies of long-term paroxysmal atrial fibrillation, shorten the duration of atrial fibrillation

Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

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Chen Li

Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

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Quan He

2014-01-01

Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

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

Rapid Estrogen Receptor-Mediated Mechanisms Determine the Sexually Dimorphic Sensitivity of Ventricular Myocytes to 17β-Estradiol and the Environmental Endocrine Disruptor Bisphenol A

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Belcher, Scott M.; Chen, Yamei; Yan, Sujuan

2012-01-01

Previously we showed that 17β-estradiol (E2) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca2+ handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E2 or BPA on Ca2+ handling in rodent ventricular myocytes. The concentration-response curve for the stimulatory effects of BPA and E2 on female myocyte was inverted-U shaped. Detectable effects for each compound were observed at 10−12 m, and the most efficacious concentrations for each were at 10−9 m. Sensitivity to E2 and BPA was not observed in male myocytes and was abolished in myocytes from ovariectomized females. Analysis using protein-conjugated E2 suggests that these rapid actions are induced by membrane-associated receptors. Analysis using selective ER agonists and antagonists and a genetic ERβ knockout mouse model showed that ERα and ERβ have opposing actions in myocytes and that the balance between ERβ and ERα signaling is the prime regulator of the sex-specific sensitivity toward estrogens. The response of female myocytes to E2 and BPA is dominated by the stimulatory ERβ-mediated signaling, and the absence of BPA and E2 responsiveness in males is due to a counterbalancing-suppressive action of ERα. We conclude that the sex-specific sensitivity of myocytes to estrogens and the rapid arrhythmogenic effects of BPA and estradiol in the female heart are regulated by the balance between ERα and ERβ signaling. PMID:22166976

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...

The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

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Beiru Zhang

2014-08-01

Full Text Available β-Amyloid (Aβ is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer’s disease (AD. Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed Aβ had an effect on cardiovascular cells. We represent as a major discovery that Aβ25–35 had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by Aβ25–35 was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that Aβ25–35 played a critical role in cardiac myocytes, suggesting that Alzheimer’s disease (AD had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies.

Left atrial appendage occlusion

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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.

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

Expression of androgen-binding protein (ABP) in human cardiac myocytes.

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Schock, H W; Herbert, Z; Sigusch, H; Figulla, H R; Jirikowski, G F; Lotze, U

2006-04-01

Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

Risk of atrial fibrillation in diabetes mellitus

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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...

Personalized management of atrial fibrillation

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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...

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

Science.gov (United States)

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...

Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes

DEFF Research Database (Denmark)

Väremo, Leif; Henriksen, Tora Ida; Scheele, Camilla

2017-01-01

BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize...... in sphingolipid metabolism was transcriptionally regulated. CONCLUSIONS: Our findings identify inherent characteristics in myocytes, as a memory of the in vivo phenotype, without the influence from a diabetic or obese extracellular environment, highlighting their importance in the development of T2D....... intrinsic properties of myocytes, associated independently with T2D or obesity. METHODS: We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor...

Effect of left ventricular diastolic dysfunction on left atrial appendage function and thrombotic potential in nonvalvular atrial fibrillation.

Science.gov (United States)

Demirçelik, Muhammed Bora; Çetin, Mustafa; Çiçekcioğlu, Hülya; Uçar, Özgül; Duran, Mustafa

2014-05-01

We aimed to investigate effects of left ventricular diastolic dysfunction on left atrial appendage functions, spontaneous echo contrast and thrombus formation in patients with nonvalvular atrial fibrillation. In 58 patients with chronic nonvalvular atrial fibrilation and preserved left ventricular systolic function, left atrial appendage functions, left atrial spontaneous echo contrast grading and left ventricular diastolic functions were evaluated using transthoracic and transoesophageal echocardiogram. Patients divided in two groups: Group D (n=30): Patients with diastolic dysfunction, Group N (n=28): Patients without diastolic dysfunction. Categorical variables in two groups were evaluated with Pearson's chi-square or Fisher's exact test. The significance of the lineer correlation between the degree of spontaneous echo contrast (SEC) and clinical measurements was evaluated with Spearman's correlation analysis. Peak pulmonary vein D velocity of the Group D was significantly higher than the Group N (p=0.006). However, left atrial appendage emptying velocity, left atrial appendage lateral wall velocity, peak pulmonary vein S, pulmonary vein S/D ratio were found to be significantly lower in Group D (p=0.028, patrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities respectively (r=-0.438, r=-0.328, r=-0.233, r=-0.447). Left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities were significantly lower in SEC 2-3-4 than SEC 1 (p=0.003, p=0.029, patrial fibrillation and preserved left ventricular ejection fraction, left atrial appendage functions are decreased in patients with left ventricular diastolic dysfunction. Left ventricular diastolic dysfunction may constitute a potential risk for formation of thrombus and stroke.

Optimal Population of Embryonic Stem Cells in "Hanging Drop" Culture for in-vitro Differentiation to Cardiac Myocytes

OpenAIRE

MIWA, Keiko; LEE, Jong-Kook; HIDAKA, Kyoko; SHI, Rong-qian; MORISAKI, Takayuki; KODAMA, Itsuo

2002-01-01

Pluripotent embryonic stem (ES) cells differentiate to cardiac myocytes in vitro by many other previous reports demonstrated "hanging-drop" method. In this study, the number of ES cells in each hanging-drop plays an important role in the cultivation of cardiac myocytes. We examined the optimal hanging-drop size to obtain embryonic stem cell-derived cardiac cells (ESCMs) in vitro using specific labeled mouse ES cells (hCGP7) which were stably transfected with the enhanced green fluorescent pro...

[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.

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

International Nuclear Information System (INIS)

Morton, M.J.; Armstrong, D.; Abi Gerges, N.; Bridgland-Taylor, M.; Pollard, C.E.; Bowes, J.; Valentin, J.-P.

2014-01-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

Energy Technology Data Exchange (ETDEWEB)

Morton, M.J., E-mail: michael.morton@astrazeneca.com [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Armstrong, D.; Abi Gerges, N. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Bridgland-Taylor, M. [Discovery Sciences, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom); Pollard, C.E.; Bowes, J.; Valentin, J.-P. [Drug Safety and Metabolism, AstraZeneca, Macclesfield, Cheshire SK10 4TG (United Kingdom)

2014-09-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.

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

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)....

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.

Hemodynamic forces regulate developmental patterning of atrial conduction.

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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.

Nicotine at clinically relevant concentrations affects atrial inward rectifier potassium current sensitive to acetylcholine.

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Bébarová, Markéta; Matejovič, Peter; Švecová, Olga; Kula, Roman; Šimurdová, Milena; Šimurda, Jiří

2017-05-01

Nicotine abuse is associated with variety of diseases including arrhythmias, most often atrial fibrillation (AF). Altered inward rectifier potassium currents including acetylcholine-sensitive current I K(Ach) are known to be related to AF pathogenesis. Since relevant data are missing, we aimed to investigate I K(Ach) changes at clinically relevant concentrations of nicotine. Experiments were performed by the whole cell patch clamp technique at 23 ± 1 °C on isolated rat atrial myocytes. Nicotine was applied at following concentrations: 4, 40 and 400 nM; ethanol at 20 mM (∼0.09%). Nicotine at 40 and 400 nM significantly activated constitutively active component of I K(Ach) with the maximum effect at 40 nM (an increase by ∼100%); similar effect was observed at -110 and -50 mV. Changes at 4 nM nicotine were negligible on average. Coapplication of 40 nM nicotine and 20 mM ethanol (which is also known to activate this current) did not show cumulative effect. In the case of acetylcholine-induced component of I K(Ach) , a dual effect of nicotine and its correlation with the current magnitude in control were apparent: the current was increased by nicotine in the cells showing small current in control and vice versa. The effect of 40 and 400 nM nicotine on acetylcholine-induced component of I K(Ach) was significantly different at -110 and -50 mV. We conclude that nicotine at clinically relevant concentrations significantly increased constitutively active component of I K(Ach) and showed a dual effect on its acetylcholine-induced component, similarly as ethanol. Synchronous application of nicotine and ethanol did not cause additive effect.

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.

GSK-3β/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy.

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Javier Duran

Full Text Available Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis. Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results

Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content

Science.gov (United States)

Vaughan, Roger A.; Gannon, Nicholas P.; Carriker, Colin R.

2015-01-01

Beetroot (甜菜 tián cài) juice consumption is of current interest for improving aerobic performance by acting as a vasodilator and possibly through alterations in skeletal muscle metabolism and physiology. This work explored the effects of a commercially available beetroot supplement on metabolism, gene expression, and mitochondrial content in cultured myocytes. C2C12 myocytes were treated with various concentrations of the beetroot supplement for various durations. Glycolytic metabolism and oxidative metabolism were quantified via measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured using quantitative reverse transcription–polymerase chain reaction, and mitochondrial content was assessed with flow cytometry and confocal microscopy. Cells treated with beetroot exhibited significantly increased oxidative metabolism, concurrently with elevated metabolic gene expression including peroxisome proliferator-activated receptor gamma coactivator-1 alpha, nuclear respiratory factor 1, mitochondrial transcription factor A, and glucose transporter 4, leading to increased mitochondrial biogenesis. Our data show that treatment with a beetroot supplement increases basal oxidative metabolism. Our observations are also among the first to demonstrate that beetroot extract is an inducer of metabolic gene expression and mitochondrial biogenesis. These observations support the need for further investigation into the therapeutic and pharmacological effects of nitrate-containing supplements for health and athletic benefits. PMID:26870674

Formulation and in vitro interaction of rhodamine-B loaded PLGA nanoparticles with cardiac myocytes.

Directory of Open Access Journals (Sweden)

Antranik Jonderian

2016-12-01

Full Text Available This study aims to characterize rhodamine B (Rh B loaded poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized nanoparticles were about 184 nm, 0.19, 40% and -21.7 mV respectively. In vitro release showed that 29% of the Rh B was released within the first 8 hours. Scanning electron microscopy (SEM measurements performed on the optimized nanoparticles showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on fetal cardiac myocytes after 24 and 48 hours of exposure with concentrations up to 200 µg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the first hours. Interestingly, our data show an increase in the nanoparticles’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes.

Posibilities of cardiac pacemaker use in paroxsysmal atrial fibrilation

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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.

α-Catenin localization and sarcomere self-organization on N-cadherin adhesive patterns are myocyte contractility driven.

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Anant Chopra

Full Text Available The N-cadherin (N-cad complex plays a crucial role in cardiac cell structure and function. Cadherins are adhesion proteins linking adjacent cardiac cells and, like integrin adhesions, are sensitive to force transmission. Forces through these adhesions are capable of eliciting structural and functional changes in myocytes. Compared to integrins, the mechanisms of force transduction through cadherins are less explored. α-catenin is a major component of the cadherin-catenin complex, thought to provide a link to the cell actin cytoskeleton. Using N-cad micropatterned substrates in an adhesion constrainment model, the results from this study show that α-catenin localizes to regions of highest internal stress in myocytes. This localization suggests that α-catenin acts as an adaptor protein associated with the cadherin mechanosensory apparatus, which is distinct from mechanosensing through integrins. Myosin inhibition in cells bound by integrins to fibronectin-coated patterns disrupts myofibiril organization, whereas on N-cad coated patterns, myosin inhibition leads to better organized myofibrils. This result indicates that the two adhesion systems provide independent mechanisms for regulating myocyte structural organization.

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.

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.

Genetic basis of atrial fibrillation

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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.

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

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.

Left atrial size in patients with cryptogenic stroke as a predictor of occurrence of atrial fibrillation

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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.

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.

C-reactive protein inhibits survivin expression via Akt/mTOR pathway downregulation by PTEN expression in cardiac myocytes.

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Beom Seob Lee

Full Text Available C-reactive protein (CRP is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We demonstrated that treatment of CRP resulted in a significant decrease of survivin protein expression in a concentration-dependent manner in cardiac myocytes. The upstream signaling proteins of survivin, such as Akt, mTOR and p70S6K, were also downregulated by CRP treatment. In addition, CRP increased the protein and mRNA levels of PTEN. The siRNA transfection or specific inhibitor treatment for PTEN restored the CRP-induced downregulation of Akt/mTOR/p70S6K pathway and survivin protein expression. Moreover, pretreatment with a specific p53 inhibitor decreased the CRP-induced PTEN expression. ERK-specific inhibitor also blocked the p53 phosphorylation and PTEN expression induced by CRP. Our study provides a novel insight into CRP-induced downregulation of survivin protein expression in cardiac myocytes through mechanisms that involved in downregulation of Akt/mTOR/p70S6K pathway by expression of PTEN.

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

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.

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....

Polygons and adhesion plaques and the disassembly and assembly of myofibrils in cardiac myocytes.

Science.gov (United States)

Lin, Z X; Holtzer, S; Schultheiss, T; Murray, J; Masaki, T; Fischman, D A; Holtzer, H

1989-06-01

Successive stages in the disassembly of myofibrils and the subsequent assembly of new myofibrils have been studied in cultures of dissociated chick cardiac myocytes. The myofibrils in trypsinized and dispersed myocytes are sequentially disassembled during the first 3 d of culture. They split longitudinally and then assemble into transitory polygons. Multiples of single sarcomeres, the cardiac polygons, are analogous to the transitory polygonal configurations assumed by stress fibers in spreading fibroblasts. They differ from their counterparts in fibroblasts in that they consist of muscle alpha-actinin vertices and muscle myosin heavy chain struts, rather than of the nonmuscle contractile protein isoforms of stress fiber polygons. EM sections reveal the vertices and struts in cardiac polygons to be typical Z and A bands. Most cardiac polygons are eliminated by day 5 of culture. Concurrent with the disassembly and elimination of the original myofibrils new myofibrils are rapidly assembled elsewhere in the same myocyte. Without exception both distal tips of each nascent myofibril terminate in adhesion plaques. The morphology and composition of the adhesion plaques capping each end of each myofibril are similar to those of the termini of stress fibers in fibroblasts. However, whereas the adhesion complexes involving stress fibers in fibroblasts consist of vinculin/nonmuscle alpha-actinin/beta- and gamma-actins, the analogous structures in myocytes involving myofibrils consist of vinculin/muscle alpha-actinin/alpha-actin. The addition of 1.7-2.0 microns sarcomeres to the distal tips of an elongating myofibril, irrespective of whether the myofibril consists of 1, 10, or several hundred tandem sarcomeres, occurs while the myofibril appears to remain linked to its respective adhesion plaques. The adhesion plaques in vitro are the equivalent of the in vivo intercalated discs, both in terms of their molecular composition and with respect to their functioning as initiating

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)....

Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

Science.gov (United States)

Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

2003-01-01

INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

Biomarkers of Atrial Cardiopathy and Atrial Fibrillation Detection on Mobile Outpatient Continuous Telemetry After Embolic Stroke of Undetermined Source.

Science.gov (United States)

Sebasigari, Denise; Merkler, Alexander; Guo, Yang; Gialdini, Gino; Kummer, Benjamin; Hemendinger, Morgan; Song, Christopher; Chu, Antony; Cutting, Shawna; Silver, Brian; Elkind, Mitchell S V; Kamel, Hooman; Furie, Karen L; Yaghi, Shadi

2017-06-01

Biomarkers of atrial dysfunction or "cardiopathy" are associated with embolic stroke risk. However, it is unclear if this risk is mediated by undiagnosed paroxysmal atrial fibrillation or flutter (AF). We aim to determine whether atrial cardiopathy biomarkers predict AF on continuous heart-rhythm monitoring after embolic stroke of undetermined source (ESUS). This was a single-center retrospective study including all patients with ESUS undergoing 30 days of ambulatory heart-rhythm monitoring to look for AF between January 1, 2013 and December 31, 2015. We reviewed medical records for clinical, radiographic, and cardiac variables. The primary outcome was a new diagnosis of AF detected during heart-rhythm monitoring. The primary predictors were atrial biomarkers: left atrial diameter on echocardiography, P-wave terminal force in electrocardiogram (ECG) lead V1, and P wave - R wave (PR) interval on ECG. A multiple logistic regression model was used to assess the relationship between atrial biomarkers and AF detection. Among 196 eligible patients, 23 (11.7%) were diagnosed with AF. In unadjusted analyses, patients with AF were older (72.4 years versus 61.4 years, P atrial diameter (39.2 mm versus 35.7 mm, P = .03). In a multivariable model, the only predictor of AF was age ≥ 60 years (odds ratio, 3.0; 95% CI, 1.06-8.5; P = .04). Atrial biomarkers were weakly associated with AF after ESUS. This suggests that previously reported associations between these markers and stroke may reflect independent cardiac pathways leading to stroke. Prospective studies are needed to investigate these mechanisms. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

Science.gov (United States)

Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

2015-01-01

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

Directory of Open Access Journals (Sweden)

Theodora Nikolaidou

Full Text Available Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ. Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT. Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.

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*

ABO blood groups: A risk factor for left atrial and left atrial appendage thrombogenic milieu in patients with non-valvular atrial fibrillation.

Science.gov (United States)

Fu, Yuan; Li, Kuibao; Yang, Xinchun

2017-08-01

Previous studies have identified ABO blood groups as predictors of thromboembolic diseases. In patients with atrial fibrillation (AF), however, potential association between ABO blood groups and the risk of left atrial (LA) and/or left atrial appendage (LAA) thrombogenic milieu (TM) has not been established. This is a retrospective case-control study that included 125 consecutive patients with non-valvular atrial fibrillation (NVAF) plus TM, as evidenced by transesophageal echocardiography (TEE) during a period from1 January 2010 to 31 December 2016. The controls were selected randomly from 1072 NVAF without TM at a 1:2 ratio. Potential association between ABO blood groups and TM was analyzed using multivariate logistic regression analysis. The risk of TM was higher in patients with blood group A (33.6% vs. 20.2% in non-A blood groups, P=0.005). After adjusting for age, sex, oral anticoagulant use, AF type and duration, and relevant functional measures (e.g., NT-pro BNP level, left atrium diameter, and left ventricular ejection fraction), blood group A remained associated with an increased risk of TM (OR=2.99, 95% CI 1.4-6.388, P=0.005). Blood group A is an independent risk factor for TM in NVAF patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Elevated NF-κB activation is conserved in human myocytes cultured from obese type 2 diabetic patients and attenuated by AMP-activated protein kinase

DEFF Research Database (Denmark)

Green, Charlotte Jane; Pedersen, Maria; Pedersen, Bente K

2011-01-01

To examine whether the inflammatory phenotype found in obese and diabetic individuals is preserved in isolated, cultured myocytes and to assess the effectiveness of pharmacological AMP-activated protein kinase (AMPK) activation upon the attenuation of inflammation in these myocytes....

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

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.

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)

[Virus-like inclusions in the myocytes of the skeletal muscle in lateral amyotrophic sclerosis].

Science.gov (United States)

Musaeva, L S; Sakharova, A V; Zavalishin, I A

2004-01-01

Microscopic examination of musculus gastrocnemius biopsies was made in four cases of sporadic lateral amyotrophic sclerosis (LAS). The validity of the clinical diagnosis was confirmed by detected neurotrophic atrophy of the muscular fibers typical for LAS. Electron microscopic study revealed virus-like inclusions 200-450 nm in size in sarcoplasm of myocytes of all the patients. The inclusions consist of lined cells of hexagonal shape at the distance of 37-41 nm from each other. The inclusions resemble enteroviruses but are not identical to them both by size and structure of their elements. There were also specific ultrastructural changes of myocytes corresponding to viral infection. The above virus-like inclusions should be considered as specific structures formed as a result of metabolic shifts caused by productive action on the cell of infective or unknown factor.

The Rabbit Stream Cipher

DEFF Research Database (Denmark)

Boesgaard, Martin; Vesterager, Mette; Zenner, Erik

2008-01-01

The stream cipher Rabbit was first presented at FSE 2003, and no attacks against it have been published until now. With a measured encryption/decryption speed of 3.7 clock cycles per byte on a Pentium III processor, Rabbit does also provide very high performance. This paper gives a concise...... description of the Rabbit design and some of the cryptanalytic results available....

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

[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.

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

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...

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

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.

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

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

Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes

DEFF Research Database (Denmark)

Stengl, Milan; Volders, Paul G A; Thomsen, Morten Bækgaard

2003-01-01

In guinea-pig ventricular myocytes, in which the deactivation of slowly activating delayed rectifier potassium current (IKs) is slow, IKs can be increased by rapid pacing as a result of incomplete deactivation and subsequent current accumulation. Whether accumulation of IKs occurs in dogs, in which...

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.

Stochastic Simulation of Cardiac Ventricular Myocyte Calcium Dynamics and Waves

OpenAIRE

Tuan, Hoang-Trong Minh; Williams, George S. B.; Chikando, Aristide C.; Sobie, Eric A.; Lederer, W. Jonathan; Jafri, M. Saleet

2011-01-01

A three dimensional model of calcium dynamics in the rat ventricular myocyte was developed to study the mechanism of calcium homeostasis and pathological calcium dynamics during calcium overload. The model contains 20,000 calcium release units (CRUs) each containing 49 ryanodine receptors. The model simulates calcium sparks with a realistic spontaneous calcium spark rate. It suggests that in addition to the calcium spark-based leak, there is an invisible calcium leak caused by the stochastic ...

RabbitMQ essentials

CERN Document Server

Dossot, David

2014-01-01

This book is a quick and concise introduction to RabbitMQ. Follow the unique case study of Clever Coney Media as they progressively discover how to fully utilize RabbitMQ, containing clever examples and detailed explanations.Whether you are someone who develops enterprise messaging products professionally or a hobbyist who is already familiar with open source Message Queuing software and you are looking for a new challenge, then this is the book for you. Although you should be familiar with Java, Ruby, and Python to get the most out of the examples, RabbitMQ Essentials will give you the push y

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.

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.

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)

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....

Serological Survey for RHD Antibodies in Rabbits from Two Types of Rabbit Breeding Farms.

Science.gov (United States)

Fitzner, A; Niedbalski, W

2016-09-01

Seroprevalence studies of RHDV antibodies in domestic rabbits were conducted between 2008-2014. A total of 12,169 sera from the provinces of central, southern and south-east Poland, including 7,570 samples collected from mixed-breed rabbits reared in smallholder farms and nearly 4,600 sera taken mainly from unvaccinated rabbits kept in industrial farms, were examined using ELISA tests. Additionally, cross-reactivity of selected tested and control archival sera using both classic RHDV and RHDVa antigens was determined by HI assay. The overall seroprevalence was 13.3%. In rabbits with unkown history of immunisation or RHD infection which came from small farms, RHDV antibodies were detected in 6.1% ranging between 1.0% to 17.2% of animals. In rabbits of the same group, but with a declared vaccination status, or confirmed exposure to an infectious virus, or coming from exposed females, the seroprevalence ranged from 83% to 100%. Among unvaccinated meat rabbits aged 71 to 90 days from industrial farms, low (1.85%, 4.17%, 11%), medium (34%, 54%) or high rates (98.7%) of seropositivity were detected. The seroconversion recorded in adult vaccinated females from industrial farms was 70% and 95%. Generally, the antibody levels examined by ELISAs and HI were comparable. However, a number of sera from the rabbits from small farms, as well as archival sera, showed clear differences. Several-fold differences in antibody titers, evidenced mainly in the postoutbreak sera, indictaed the contact of animals with RHDVa antigen. The overall results of the survey revealed a great proportion of seronegative rabbits potentially highly susceptible to RHD infection. In combination with the emergence of a novel pathogenic RHD virus type (RHDV2), it poses a severe risk of a next wave of fatal disease cases spreading in the native population of domestic rabbits, especially in farms with a traditional system of husbandry.

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

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

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.

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

Simple Additive Weighting to Diagnose Rabbit Disease

Science.gov (United States)

Ramadiani; Marissa, Dyna; Jundillah, Muhammad Labib; Azainil; Hatta, Heliza Rahmania

2018-02-01

Rabbit is one of the many pets maintained by the general public in Indonesia. Like other pet, rabbits are also susceptible to various diseases. Society in general does not understand correctly the type of rabbit disease and the way of treatment. To help care for sick rabbits it is necessary a decision support system recommendation diagnosis of rabbit disease. The purpose of this research is to make the application of rabbit disease diagnosis system so that can help user in taking care of rabbit. This application diagnoses the disease by tracing the symptoms and calculating the recommendation of the disease using Simple Additive Weighting method. This research produces a web-based decision support system that is used to help rabbit breeders and the general public.

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.

[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.

Left atrial function in heart failure with impaired and preserved ejection fraction.

Science.gov (United States)

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

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

Simple Additive Weighting to Diagnose Rabbit Disease

Directory of Open Access Journals (Sweden)

Ramadiani

2018-01-01

Full Text Available Rabbit is one of the many pets maintained by the general public in Indonesia. Like other pet, rabbits are also susceptible to various diseases. Society in general does not understand correctly the type of rabbit disease and the way of treatment. To help care for sick rabbits it is necessary a decision support system recommendation diagnosis of rabbit disease. The purpose of this research is to make the application of rabbit disease diagnosis system so that can help user in taking care of rabbit. This application diagnoses the disease by tracing the symptoms and calculating the recommendation of the disease using Simple Additive Weighting method. This research produces a web-based decision support system that is used to help rabbit breeders and the general public.

Norepinephrine-Induced Adrenergic Activation Strikingly Increased the Atrial Fibrillation Duration through β1- and α1-Adrenergic Receptor-Mediated Signaling in Mice.

Directory of Open Access Journals (Sweden)

Kenji Suita

Full Text Available Atrial fibrillation (AF is the most common arrhythmias among old people. It causes serious long-term health problems affecting the quality of life. It has been suggested that the autonomic nervous system is involved in the onset and maintenance of AF in human. However, investigation of its pathogenesis and potential treatment has been hampered by the lack of suitable AF models in experimental animals.Our aim was to establish a long-lasting AF model in mice. We also investigated the role of adrenergic receptor (AR subtypes, which may be involved in the onset and duration of AF.Trans-esophageal atrial burst pacing in mice could induce AF, as previously shown, but with only a short duration (29.0 ± 8.1 sec. We found that adrenergic activation by intraperitoneal norepinephrine (NE injection strikingly increased the AF duration. It increased the duration to more than 10 minutes, i.e., by more than 20-fold (656.2 ± 104.8 sec; P<0.001. In this model, a prior injection of a specific β1-AR blocker metoprolol and an α1-AR blocker prazosin both significantly attenuated NE-induced elongation of AF. To further explore the mechanisms underlying these receptors' effects on AF, we assessed the SR Ca(2+ leak, a major trigger of AF, and consequent spontaneous SR Ca(2+ release (SCR in atrial myocytes. Consistent with the results of our in-vivo experiments, both metoprolol and prazosin significantly inhibited the NE-induced SR Ca(2+ leak and SCR. These findings suggest that both β1-AR and α1-AR may play important roles in the development of AF.We have established a long-lasting AF model in mice induced by adrenergic activation, which will be valuable in future AF study using experimental animals, such as transgenic mice. We also revealed the important role of β1- and α1-AR-mediated signaling in the development of AF through in-vivo and in-vitro experiments.

Model of excitation-contraction coupling of rat neonatal ventricular myocytes.

Science.gov (United States)

Korhonen, Topi; Hänninen, Sandra L; Tavi, Pasi

2009-02-01

The neonatal rat ventricular myocyte culture is one of the most popular experimental cardiac cell models. To our knowledge, the excitation-contraction coupling (ECC) of these cells, i.e., the process linking the electrical activity to the cytosolic Ca2+ transient and contraction, has not been previously analyzed, nor has it been presented as a complete system in detail. Neonatal cardiomyocytes are in the postnatal developmental stage, and therefore, the features of their ECC differ vastly from those of adult ventricular myocytes. We present the first complete analysis of ECC in these cells by characterizing experimentally the action potential and calcium signaling and developing the first mathematical model of ECC in neonatal cardiomyocytes that we know of. We show that in comparison to adult cardiomyocytes, neonatal cardiomyocytes have long action potentials, heterogeneous cytosolic Ca2+ signals, weaker sarcoplasmic reticulum Ca2+ handling, and stronger sarcolemmal Ca2+ handling, with a significant contribution by the Na+/Ca2+ exchanger. The developed model reproduces faithfully the ECC of rat neonatal cardiomyocytes with a novel description of spatial cytosolic [Ca2+] signals. Simulations also demonstrate how an increase in the cell size (hypertrophy) affects the ECC in neonatal cardiomyocytes. This model of ECC in developing cardiomyocytes provides a platform for developing future models of cardiomyocytes at different developmental stages.

Effect of atrial systole on canine and porcine coronary blood flow.

Science.gov (United States)

Bellamy, R F

1981-09-01

A feature of phasic coronary flow patterns recorded in conscious chronically instrumented dogs is the atrial cove--a transient depression of arterial flow that occurs during atrial systole. The association between the hemodynamic effects of atrial systole and the atrial cove was studied in anesthetized dogs and pigs with complete heart block. Many atrial coves are available for study in these preparations because atrial activity continues unabated during the diastolic ventricular arrest that follows cessation of electrical pacing. The effect of atrial systole is to translate the pressure-flow relation found during diastole to a higher intercept pressure without change in slope. The increase in the intercept pressure equals the increase in intramyocardial pressure measured with microtransducers embedded in the left ventricular wall. The decrement in flow during the atrial cove is a direct function of the change in intramyocardial pressure and an inverse function of coronary vascular resistance. Each atrial systole is associated with a forward flow transient in the coronary veins, the peak of which occurs at the same instant as does the nadir of atrial flow. These data suggest that the coronary vessels are acting as collapsible tubes and that the waterfall model of the coronary circulation is applicable. The following sequence is proposed to account for the atrial cove. Atrial systole ejects a bolus of blood into the left ventricle increasing both ventricular cavity and intramyocardial pressures. The increase in intramyocardial pressure raises the back pressure opposing coronary flow, reducing the arterial perfusion pressure gradient and causing flow to fall.

The absence of 2,3-diphosphoglycerate from myocytes, hepatocytes and adipocytes.

Science.gov (United States)

Reddy, W J; Burns, A H

1976-04-23

Myocytes, hepatocytes and adipocytes were prepared from heart, liver and epididymal fat pad of the rat. No detectable level of 2,3-diphosphoglycerate was found. Evidence is also presented which indicates the absence from these cells of 2,3-diphosphoglycerate mutase and 2,3-diphosphoglycerate phosphatase. Previous findings by others of the presence of 2,3-diphosphoglycerate and 2,3-diphosphoglycerate mutase probably resulted from erythrocytes sequestered in the tissue.

Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits.

Science.gov (United States)

Bertó-Moran, Alejandro; Pacios, Isabel; Serrano, Emmanuel; Moreno, Sacramento; Rouco, Carlos

2013-01-01

The interaction among several parasites in European rabbits (Oryctolagus cuniculus) is crucial to host fitness and to the epidemiology of myxomatosis and rabbit hemorrhagic disease. These diseases have caused significant reductions in rabbit populations on the Iberian Peninsula. Most studies have focused on the epidemiology and pathogenesis of these viruses individually, and little is known about interactions between these viruses and other parasites. Taking advantage of an experimental restocking program in Spain, the effects of coccidian and nematode infections on the probability of having detectable antibody to myxoma and rabbit hemorrhagic disease viruses were tested in European wild rabbits. For 14 mo, we monitored rabbit abundance and parasite loads (coccidia and nematodes) in three reintroduced rabbit populations. While coccidian and nematode loads explained seasonal antibody prevalences to myxoma virus, the pattern was less clear for rabbit hemorrhagic disease. Contrary to expectations, prevalence of antibody to myxoma virus was inversely proportional to coccidian load, while nematode load seemed to play a minor role. These results have implications for viral disease epidemiology and for disease management intended to increase rabbit populations in areas where they are important for ecosystem conservation.

Left atrial accessory appendages, diverticula, and left-sided septal pouch in multi-slice computed tomography. Association with atrial fibrillation and cerebrovascular accidents.

Science.gov (United States)

Hołda, Mateusz K; Koziej, Mateusz; Wszołek, Karolina; Pawlik, Wiesław; Krawczyk-Ożóg, Agata; Sorysz, Danuta; Łoboda, Piotr; Kuźma, Katarzyna; Kuniewicz, Marcin; Lelakowski, Jacek; Dudek, Dariusz; Klimek-Piotrowska, Wiesława

2017-10-01

The aim of this study is to provide a morphometric description of the left-sided septal pouch (LSSP), left atrial accessory appendages, and diverticula using cardiac multi-slice computed tomography (MSCT) and to compare results between patient subgroups. Two hundred and ninety four patients (42.9% females) with a mean of 69.4±13.1years of age were investigated using MSCT. The presence of the LSSP, left atrial accessory appendages, and diverticula was evaluated. Multiple logistic regression analysis was performed to check whether the presence of additional left atrial structures is associated with increased risk of atrial fibrillation and cerebrovascular accidents. At least one additional left atrial structure was present in 51.7% of patients. A single LSSP, left atrial diverticulum, and accessory appendage were present in 35.7%, 16.0%, and 4.1% of patients, respectively. After adjusting for other risk factors via multiple logistic regression, patients with LSSP are more likely to have atrial fibrillation (OR=2.00, 95% CI=1.14-3.48, p=0.01). The presence of a LSSP was found to be associated with an increased risk of transient ischemic attack using multiple logistic regression analysis after adjustment for other risk factors (OR=3.88, 95% CI=1.10-13.69, p=0.03). In conclusion LSSPs, accessory appendages, and diverticula are highly prevalent anatomic structures within the left atrium, which could be easily identified by MSCT. The presence of LSSP is associated with increased risk for atrial fibrillation and transient ischemic attack. Copyright © 2017 Elsevier B.V. All rights reserved.

Skeletal Myocyte Types and Vascularity in the Black Sicilian Pig

OpenAIRE

S. Velotto; E. Varricchio; M. R. Di Prisco; T. Stasi; A. Crasto

2007-01-01

The objective of this study was to verify the presence of giant fibres in the Black Sicilian pig skeletal muscle and to evaluate the effect of sex on histochemical and morphometric characteristics of the myocytes (myofibres) as well as vascularity of the muscle. Twenty Black Sicilian pigs (10 males, 10 females) from a farm in Sicily (Italy) were slaughtered at two years of age. Muscle tissues were obtained from three muscles: psoas major, longissimus dorsi, and trapezius. Myofibres were stain...

Vernakalant hydrochloride for the treatment of atrial fibrillation.

Science.gov (United States)

Kozlowski, Dariusz; Budrejko, Szymon; Lip, Gregory Y H; Mikhailidis, Dimitri P; Rysz, Jacek; Raczak, Grzegorz; Banach, Maciej

2009-12-01

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Rhythm control strategy for AF is limited by drug toxicity and side effects, and recent trials have shown that this strategy is not superior to a rate control one. New antiarrhythmic drugs, free of undesired effects, would enhance rhythm control, with the possibility of sinus rhythm restoration and maintenance. A promising find in the search for new antiarrhythmic therapies is atrial-tissue specific ion channels. The findings that the ultrarapid delayed rectifier (I(Kur)) and the inwardly rectifying, acetylcholine-regulated current (I(K-Ach)) exist in atrial but not ventricular tissue increase the probability that atrioselective drugs without ventricular proarrhythmic toxicity can be developed for treatment of patients with AF. There are also other potential targets for atrial-selective therapy: transient outward current (I(to)), rapidly and slowly activating delayed rectifier currents (I(Kr) and I(Ks)), atrial sodium current (I(Na)) and atrially expressed connexins. New drugs under development with promising atrial-selectivity include: tertiapin, NIP-142, NIP-141, JTV-519, AVE0118, AVE1231, DPO-1, AZD7009 and many others. Among such new agents, vernakalant hydrochloride is currently in an advanced phase of development and has already been evaluated in clinical trials. In this overview, we describe the history and current state of developmental process of the drug, as well as its mechanism of action and influence on electrophysiological parameters. Vernakalant seems to be effective in terminating recent-onset AF, but is not efficacious in long-lasting AF and atrial flutter. The drug may be relatively free of proarrhythmic effects, and exerts a protective effect on ventricular tissue and ventricular repolarization. It is expected that the intravenous formulation will soon be approved for the pharmacological termination of recent-onset AF.

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.

Prostaglandin synthesis and catabolism in the gastric mucosa: studies in normal rabbits and rabbits immunized with prostaglandin E2

International Nuclear Information System (INIS)

Redfern, J.S.

1988-01-01

Antral and fundic mucosal homogenates obtained from prostaglandin E2-immunized rabbits converted 14C-arachidonic acid to prostaglandin E2, 6-keto prostaglandin F1 alpha, prostaglandin F2 alpha, and prostaglandin D2. Percentage conversion of 14C-arachidonic acid to these prostaglandin products was not significantly different in prostaglandin E2-immunized rabbits compared with control rabbits (thyroglobulin-immunized and unimmunized rabbits combined). Synthesis of 6-keto prostaglandin F1 alpha, prostaglandin E2 and 13,14-dihydro 15-keto prostaglandin E2 from endogenous arachidonic acid after vortex mixing fundic mucosal homogenates was similar in prostaglandin E2 immunized rabbits and control rabbits. Both in prostaglandin E2-immunized rabbits and controls, 3H-prostaglandin E2 was catabolized extensively by the fundic mucosa, whereas 3H-6-keto prostaglandin F1 alpha, 3H-prostaglandin F2 alpha, and 3H-prostaglandin D2 were not catabolized to any appreciable extent. The rate of catabolism of PGs was not significantly different in prostaglandin E2-immunized rabbits and control rabbits, with the exception of prostaglandin F2 alpha which was catabolized slightly more rapidly in prostaglandin E2-immunized rabbits. These results indicate that development of gastric ulcers in prostaglandin E2-immunized rabbits is not associated with an alteration in the capacity of the gastric mucosa to synthesize or catabolize prostaglandins

Dermatophytes in pet Guinea pigs and rabbits.

Science.gov (United States)

Kraemer, A; Mueller, R S; Werckenthin, C; Straubinger, R K; Hein, J

2012-05-25

The frequency of dermatophytes in pet Guinea pigs and rabbits. To determine the frequency and types of dermatophytes in pet Guinea pigs and rabbits. First, 2153 samples collected from pet Guinea pigs (n=1132) and rabbits (n=1021) with suspected dermatophytosis and submitted to three different laboratories for fungal culture were analysed. Subsequently, healthy Guinea pigs and rabbits, animals with skin lesions and with noncutaneous diseases were examined prospectively for dermatophytes. Trichophyton (T.) mentagrophytes was the most common fungal species isolated (91.6% and 72.3% of positive cultures from Guinea pigs (n=431) and rabbits (n=83), respectively). Animals with positive fungal culture did not show any gender predisposition, but affected animals were younger than those with negative fungal culture (PGuinea pigs and 0/140 healthy rabbits. In addition, fungal cultures of Guinea pigs with skin lesions (n=26) and other diseases (n=25) were positive in 7.7% and 8.0% respectively. Samples collected from 17 rabbits with skin lesions and 32 rabbits with noncutaneous disease were all negative in culture. T. mentagrophytes is the most common dermatophyte in pet Guinea pigs and rabbits, asymptomatic carriers are regularly seen in Guinea pigs, but not in rabbits. Copyright © 2011 Elsevier B.V. All rights reserved.

Evidence-Based Advances in Rabbit Medicine.

Science.gov (United States)

Summa, Noémie M; Brandão, João

2017-09-01

Rabbit medicine has been continuously evolving over time with increasing popularity and demand. Tremendous advances have been made in rabbit medicine over the past 5 years, including the use of imaging tools for otitis and dental disease management, the development of laboratory testing for encephalitozoonosis, or determination of prognosis in rabbits. Recent pharmacokinetic studies have been published, providing additional information on commonly used antibiotics and motility-enhancer drugs, as well as benzimidazole toxicosis. This article presents a review of evidence-based advances for liver lobe torsions, thymoma, and dental disease in rabbits and controversial and new future promising areas in rabbit medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Proteome- and transcriptome-driven reconstruction of the human myocyte metabolic network and its use for identification of markers for diabetes

DEFF Research Database (Denmark)

Väremo, Leif; Scheele, Camilla; Broholm, Christa

2015-01-01

-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism......Skeletal myocytes are metabolically active and susceptible to insulin resistance and are thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes, and their elucidation at the systems level requires genome-wide data and biological networks. Genome...

Long-term biatrial recordings in post-operative atrial fibrillation.

Science.gov (United States)

Masè, M; Graffigna, A; Sinelli, S; Pallaoro, G; Nollo, G; Ravelli, F

2010-01-01

Although atrial fibrillation (AF) is a common complication of cardiac surgery, its pathophysiology remains unclear. The study of post-operative AF demands for the recording of cardiac electrical activity in correspondence of AF onset and progression. Long-term recordings in post-surgery patients could provide this information, but, to date, have been limited to surface signals, which precludes a characterization of the arrhythmic triggers and substrate. In this study we demonstrate the feasibility of a continuous long-term recording of atrial electrical activities from the right and left atria in post-surgery patients. Local atrial epicardial electrograms are acquired by positioning temporary pacing wires in the right and left atria at the end of the intervention, while three day recordings are obtained by a digital holter recorder, adapted to epicardial signal features. The capability of the system to map local atrial activity and the possibility to obtain quantitative information on atrial rate and synchronization from the processed epicardial signals are proven in representative examples. The quantitative description of local atrial properties opens new perspective in the investigation of post-surgery AF.

Is there a difference between hare syphilis and rabbit syphilis? Cross infection experiments between rabbits and hares

NARCIS (Netherlands)

Lumeij, J.T.|info:eu-repo/dai/nl/073286826; Mikalová, L.; Smajs, D.

2013-01-01

Abstract Cross infection of rabbits and hares with Treponema paraluiscuniculi from rabbits and the related microorganism from hares, which was provisionally named "Treponema paraluisleporis", revealed that T. paraluiscuniculi affects rabbits clinically, but only causes seroconversion in hares

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...

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

Natriuretic peptides stimulate the cardiac sodium pump via NPR-C-coupled NOS activation

DEFF Research Database (Denmark)

William, M.; Hamilton, E.J.; Garcia, A.

2008-01-01

Natriuretic peptides (NPs) and their receptors (NPRs) are expressed in the heart, but their effects on myocyte function are poorly understood. Because NPRs are coupled to synthesis of cGMP, an activator of the sarcolemmal Na(+)-K(+) pump, we examined whether atrial natriuretic peptide (ANP) regul...

Decreased expression of natriuretic peptides associated with lipid accumulation in cardiac ventricle of obese mice

DEFF Research Database (Denmark)

Bartels, E.D.; Nielsen, J.M.; Bisgaard, L.S.

2010-01-01

% (P depression of ANP mRNA expression in cultured HL-1 atrial myocytes. The data suggest that obesity and altered cardiac lipid metabolism are associated with reduced production of ANP and BNP in the cardiac ventricles in the setting of normal as well as impaired cardiac function....

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....

Assistência de enfermagem a paciente com fibrilação atrial Asistencia de enfermería al paciente con fibrilación atrial Nursing assistance to patients with atrial fibrillation

Directory of Open Access Journals (Sweden)

Lutgarde Magda Suzanne Vanheusden

2006-04-01

Full Text Available Este estudo tem por objetivo apresentar uma revisão atualizada sobre as questões que envolvem a assistência à paciente que desenvolve fibrilação atrial. Essa revisão discute a condição complexa dessa taquiarritmia que influencia a mortalidade, morbidade, abordando o seu elevado custo para o sistema de saúde. A assistência e o importante papel da educação para a enfermagem nessa área estão sendo discutidos. Como a prevalência da fibrilação atrial aumenta com a idade e o Brasil tem uma população idosa cada vez mais crescente, a enfermagem enfrenta atualmente o desafio para cuidar dessa população que apresenta necessidades variadas.Este estudio tiene por objetivo presentar una revisión actualizada sobre las cuestiones que envuelven la asistencia al paciente que desarrolla fibrilación atrial. Esa revisión discute la condición compleja de esa taquiarritmia que influencia la morbidad, mortalidad, enfocando el costo que es muy grande para el sistema de salud. Se discute también la asistencia y el importante papel de la educación para la enfermería en esa área. Como la prevalencia de la fibrilación atrial aumenta con la edad y como el Brasil tiene una población de ancianos cada vez más creciente, la enfermería, actualmente, enfrenta el desafío para cuidar de esa población que presenta necesidades variadas.The objective of this study is to present an up to date revision about the assistance of the patient that develops atrial fibrilation. This revision raises the discussion on the complexity of atrial fibrillation that influences the mortality, morbidity, and the high cost for the health system. The assistance and the important paper of education of nursing on atrial fibrillation are here discussed. The population of Brazil is increasing in time and age consequently the prevalence of atrial fibrillation is also increasing. Thus, nursing faces the current challenge to take care of this specific population that presents

Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition.

Science.gov (United States)

Chia, Karin K M; Liu, Chia-Chi; Hamilton, Elisha J; Garcia, Alvaro; Fry, Natasha A; Hannam, William; Figtree, Gemma A; Rasmussen, Helge H

2015-08-15

Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na(+)-K(+) pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na(+)-K(+) pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na(+)-K(+) pump current (Ip). Coexposure to 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na(+)-K(+) pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47(phox) NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22(phox) subunit, and it decreased O2 (·-)-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47(phox) indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22(phox) and p47(phox) NADPH oxidase subunits and decrease β1-Na(+)-K(+) pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. Copyright © 2015 the American Physiological Society.

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...

Atrial anatomy and function postcardioversion: insights from transthoracic and transesophageal echocardiography.

Science.gov (United States)

Manning, W J; Silverman, D I

1996-01-01

Echocardiography provides a valuable tool for the evaluation and assessment of atrial function in patients with atrial fibrilation (AF). Atrial morphology after restoration of sinus rhythm is dynamic, with a decrease in atrial size if sinus rhythm is maintained and atrial growth among those with sustained AF. Restoration of electrocardiographic sinus rhythm is frequently accompanied by relatively depressed atrial mechanical function, with recovery that appears to be related to multiple factors, including the duration of AF before cardioversion and the mode of cardioversion. Such delay appears to confer ongoing risk for thrombus formation and thromboembolism in the days after cardioversion and argues strongly for the need to maintain therapeutic anticoagulation during the pericardioversion and postcardioversion period.

Newer Anticoagulants for Non-Valvular Atrial Fibrillation

Directory of Open Access Journals (Sweden)

Joseph M. Harburger

2012-05-01

Full Text Available Non-valvular atrial fibrillation is a recognized risk factor for stroke and systemic embolism. It has been clearly established that warfarin reduces the risk of stroke and systemic embolism in persons with atrial fibrillation and additional risk factors for stroke. The use of warfarin, however, requires frequent monitoring, and there is great variability in patient response to warfarin. Warfarin interacts with several medications and foods. In addition, warfarin use portends a significant risk of bleeding. For these reasons, warfarin is frequently not prescribed to persons for whom the drug would provide a clear benefit. Over the past decade, attempts have been made to develop drugs that are at least as safe and effective as warfarin for the treatment of atrial fibrillation that do not require monitoring nor have as many interactions. Initial studies of compounds in this regard ultimately failed due to safety concerns, but over the past two years two novel agents have been approved by the United States Food and Drug Association for anticoagulation in non-valvular atrial fibrillation, another drug is under review, and additional compounds are being studied. This article will review the use of warfarin and these new agents in the treatment of non-valvular atrial fibrillation.

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.

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

Detection and localization of rabbit hepatitis e virus and antigen in systemic tissues from experimentally intraperitoneally infected rabbits.

Directory of Open Access Journals (Sweden)

Jingjing Mao

Full Text Available Rabbit hepatitis E virus (HEV is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

Efeitos da estimulação temporária atrial direita na prevenção da fibrilação atrial no pós-operatório de revascularização do miocárdio com circulação extracorpórea Effect of temporary right atrial pacing in prevention of atrial fibrillation after coronary artery bypass graft surgery

Directory of Open Access Journals (Sweden)

Vicente Avila Neto

2007-09-01

Full Text Available OBJETIVO: Avaliar os efeitos da estimulação atrial direita temporária na prevenção da fibrilação atrial no pósoperatório de revascularização do miocárdio com circulação extracorpórea e identificar os fatores de risco para o aparecimento dessa arritmia. MÉTODO: Estudamos 160 pacientes que, ao término da cirurgia de revascularização miocárdica, submeteram-se ao implante de eletrodos epicárdicos na parede lateral do átrio direito e foram randomizados em grupos não-estimulado (NE e grupo com estímulo atrial direito (AD. O ritmo cardíaco foi monitorizado durante as 72 horas seguintes ao término da operação e as variáveis estudadas foram: a incidência de fibrilação atrial, os fatores de risco pré, intra e pós-operatórios para o seu aparecimento e eventos pósoperatórios. Resultados: Foram detectados 21 (13,1% episódios de fibrilação atrial, sendo 20 no grupo NE e um no grupo submetido à estimulação do átrio direito (AD. O risco relativo para o desenvolvimento de fibrilação atrial foi de 0,18 (IC 95%= 0,05-0,60 para o grupo AD quando comparado ao grupo NE. A regressão logística identificou que as variáveis idade mais jovem, uso de beta-bloqueador no pré-operatório e presença da estimulação atrial direita estiveram associadas a uma menor razão de chances (odds ratio para o surgimento de fibrilação atrial no pós-operatório. CONCLUSÕES: A estimulação atrial direita temporária reduziu a incidência de fibrilação atrial pós-operatória. A idade avançada e a não estimulação atrial foram fatores preditivos independentes para a ocorrência dessa arritmia.OBJECTIVE: To evaluated the effects of temporary atrial pacing to prevent the atrial fibrillation after coronary artery bypass graft surgery and the risk factors to the occurrence of this arrhytmia. METHODS: We have studied 160 patients who, at the end of coronary artery bypass graft surgery, were submitted to epicardial electrode

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 ...

Rabbit haemorrhagic disease: are Australian rabbits (Oryctolagus cuniculus) evolving resistance to infection with Czech CAPM 351 RHDV?

Science.gov (United States)

Elsworth, P G; Kovaliski, J; Cooke, B D

2012-11-01

Rabbit haemorrhagic disease is a major tool for the management of introduced, wild rabbits in Australia. However, new evidence suggests that rabbits may be developing resistance to the disease. Rabbits sourced from wild populations in central and southeastern Australia, and domestic rabbits for comparison, were experimentally challenged with a low 60 ID50 oral dose of commercially available Czech CAPM 351 virus - the original strain released in Australia. Levels of resistance to infection were generally higher than for unselected domestic rabbits and also differed (0-73% infection rates) between wild populations. Resistance was lower in populations from cooler, wetter regions and also low in arid regions with the highest resistance seen within zones of moderate rainfall. These findings suggest the external influences of non-pathogenic calicivirus in cooler, wetter areas and poor recruitment in arid populations may influence the development rate of resistance in Australia.

Plain chest PA evaluation of left atrial thrombosis in mitral valvular disease

International Nuclear Information System (INIS)

Choo, Yeon Myung; Park, Jae Hyung; Han, Man Chung

1984-01-01

Conventional posteroanterior chest radiographs of 73 patients with mitral valve disease who had had surgery were analyzed, and particular attention was directed to the absence of the convexity of the left lower mid cardiac border (left atrial segment) and to the relation with duration of illness, atrial fibrillation, pulmonary capillary wedge pressure (PCWP) as well as surgical findings. The results obtained are as follows: 1. The flatness or concavity of this segment, despite other evidence of left atrial enlargement, was observed in eleven (64.7%) of 17 patients who had left atrial thrombosis and in six (10.7%) of 56 patients who did not have thrombosis (false positive diagnosis). Six (35.5%) of the 17 patients who had left atrial thrombosis did not this findings on radiographs (false positive diagnosis). Six (35.3%) of the 17 patients who had left atrial thrombosis did not show this finding on radiographs (false positive diagnosis). Therefore, the accuracy in the diagnosis of thrombosis of left atrium wa 64.7% (eleven of seventeen) for patients who had thrombosis of left atrium. 2. The atrial fibrillation was observed in sixteen (94.1%)of 17 patients who had left atrial thrombosis. So, correlation between the presence of left atrial thrombosis and atrial fibrillation wa evident. But there was no correlation between the duration of illness of the PCWP of patients and the presence of left atrial thrombosis.

Plain chest PA evaluation of left atrial thrombosis in mitral valvular disease

Energy Technology Data Exchange (ETDEWEB)

Choo, Yeon Myung; Park, Jae Hyung; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1984-09-15

Conventional posteroanterior chest radiographs of 73 patients with mitral valve disease who had had surgery were analyzed, and particular attention was directed to the absence of the convexity of the left lower mid cardiac border (left atrial segment) and to the relation with duration of illness, atrial fibrillation, pulmonary capillary wedge pressure (PCWP) as well as surgical findings. The results obtained are as follows: 1. The flatness or concavity of this segment, despite other evidence of left atrial enlargement, was observed in eleven (64.7%) of 17 patients who had left atrial thrombosis and in six (10.7%) of 56 patients who did not have thrombosis (false positive diagnosis). Six (35.5%) of the 17 patients who had left atrial thrombosis did not this findings on radiographs (false positive diagnosis). Six (35.3%) of the 17 patients who had left atrial thrombosis did not show this finding on radiographs (false positive diagnosis). Therefore, the accuracy in the diagnosis of thrombosis of left atrium wa 64.7% (eleven of seventeen) for patients who had thrombosis of left atrium. 2. The atrial fibrillation was observed in sixteen (94.1%)of 17 patients who had left atrial thrombosis. So, correlation between the presence of left atrial thrombosis and atrial fibrillation wa evident. But there was no correlation between the duration of illness of the PCWP of patients and the presence of left atrial thrombosis.

Analysis of brain natriuretic peptide in 30 patients with atrial fibrillation

International Nuclear Information System (INIS)

Jin Qiang; Lu Jianghui; Li Weipeng; Yuan Yuan; Sun Weili

2009-01-01

To investigate the relationship between atrial fibrillation and brain natriuretic peptide (BNP), plasma levels of BNP in 30 patients with atrial fibrillation and 30 health controls were assayed and compared. The results showed that plasma levels of BNP in patients with atrial fibrillation were significantly higher than those of health controls (P<0.05). When the patients with atrial fibrillation were restored sinus rhythm, the concentration of BNP decreased significantly (P<0.05). BNP was a sensitive marker of cardiac dysfunction, and BNP was positively correlated with atrial fibrillation. (authors)

Meta-analysis identifies six new susceptibility loci for atrial fibrillation

NARCIS (Netherlands)

Ellinor, Patrick T; Lunetta, Kathryn L; Albert, Christine M; Glazer, Nicole L; Ritchie, Marylyn D; Smith, Albert V; Arking, Dan E; Müller-Nurasyid, Martina; Krijthe, Bouwe P; Lubitz, Steven A; Bis, Joshua C; Chung, Mina K; Dörr, Marcus; Ozaki, Kouichi; Roberts, Jason D; Smith, J Gustav; Pfeufer, Arne; Sinner, Moritz F; Lohman, Kurt; Ding, Jingzhong; Smith, Nicholas L; Smith, Jonathan D; Rienstra, Michiel; Rice, Kenneth M; Van Wagoner, David R; Magnani, Jared W; Wakili, Reza; Clauss, Sebastian; Rotter, Jerome I; Steinbeck, Gerhard; Launer, Lenore J; Davies, Robert W; Borkovich, Matthew; Harris, Tamara B; Lin, Honghuang; Völker, Uwe; Völzke, Henry; Milan, David J; Hofman, Albert; Boerwinkle, Eric; Chen, Lin Y; Soliman, Elsayed Z; Voight, Benjamin F; Li, Guo; Chakravarti, Aravinda; Kubo, Michiaki; Tedrow, Usha B; Rose, Lynda M; Ridker, Paul M; Conen, David; Tsunoda, Tatsuhiko; Furukawa, Tetsushi; Sotoodehnia, Nona; Xu, Siyan; Kamatani, Naoyuki; Levy, Daniel; Nakamura, Yusuke; Parvez, Babar; Mahida, Saagar; Furie, Karen L; Rosand, Jonathan; Muhammad, Raafia; Psaty, Bruce M; Meitinger, Thomas; Perz, Siegfried; Wichmann, H-Erich; Witteman, Jacqueline C M; Kao, W H Linda; Kathiresan, Sekar; Roden, Dan M; Uitterlinden, Andre G; Rivadeneira, Fernando; McKnight, Barbara; Sjögren, Marketa; Newman, Anne B; Liu, Yongmei; Gollob, Michael H; Melander, Olle; Tanaka, Toshihiro; Stricker, Bruno H Ch; Felix, Stephan B; Alonso, Alvaro; Darbar, Dawood; Barnard, John; Chasman, Daniel I; Heckbert, Susan R; Benjamin, Emelia J; Gudnason, Vilmundur; Kääb, Stefan

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation

A mathematical model for active contraction in healthy and failing myocytes and left ventricles.

Directory of Open Access Journals (Sweden)

Li Cai

Full Text Available Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV. The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model. We first studied the electro-mechanics coupling in a single myocyte in the healthy and diseased left ventricle, and then the single cell model was embedded in a dynamic LV model to investigate the compensation mechanism of LV pump function due to myocardial dysfunction caused by abnormality in cellular calcium dynamics. The multi-scale LV model was solved using an in-house developed hybrid immersed boundary method with finite element extension. The predictions of the healthy LV model agreed well with the clinical measurements and other studies, and likewise, the results in the failing states were also consistent with clinical observations. In particular, we found that a low level of intracellular Ca2+ transient in myocytes can result in LV pump function failure even with increased myocardial contractility, decreased systolic blood pressure, and increased diastolic filling pressure, even though they will increase LV stroke volume. Our work suggested that treatments targeted at increased contractility and lowering the systolic blood pressure alone are not sufficient in preventing LV pump dysfunction, restoring a balanced physiological Ca2+ handling mechanism is necessary.

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.

Increased sarcolemmal Na+/H+ exchange activity in hypertrophied myocytes from dogs with chronic atrioventricular block

NARCIS (Netherlands)

van Borren, Marcel M. G. J.; Vos, Marc A.; Houtman, Marien J. C.; Antoons, Gudrun; Ravesloot, Jan H.

2013-01-01

Dogs with compensated biventricular hypertrophy due to chronic atrioventricular block (cAVB), are more susceptible to develop drug-induced Torsade-de-Pointes arrhythmias and sudden cardiac death. It has been suggested that the increased Na+ influx in hypertrophied cAVB ventricular myocytes

Dual effect of ethanol on inward rectifier potassium current IK1 in rat ventricular myocytes

Czech Academy of Sciences Publication Activity Database

Bébarová, M.; Matejovič, P.; Pásek, Michal; Šimurdová, M.; Šimurda, J.

2014-01-01

Roč. 65, č. 4 (2014), s. 497-509 ISSN 0867-5910 Grant - others:GA MZd NT14301 Institutional support: RVO:61388998 Keywords : ethanol * rat ventricular myocyte * rat ventricular action potential model Subject RIV: BO - Biophysics Impact factor: 2.386, year: 2014

Atrial fibrillation detection and R-wave synchronization by Metrix implantable atrial defibrillator - Implications for long-term efficacy and safety

NARCIS (Netherlands)

Tse, HF; Lau, CP; Sra, JS; Crijns, HJGM; Edvardsson, N; Kacet, S; Wyse, DG

1999-01-01

Background-The long-term efficacy of atrial fibrillation (AF) detection and R-wave synchronization are critical safety requirements for the development of an implantable atrial defibrillator (LAD) for treatment of AF. Methods and Results The long-term efficacy of the Metrix IAD for AF detection and

Hyperthyroidism and atrial myxoma--an intriguing cardio-endocrine association.

Science.gov (United States)

Kumar, Gautam; Chow, John T; Klarich, Kyle W; Dean, Diana S

2007-12-01

A 65-year-old woman presented with dyspnea and bilateral leg edema for 1 week, worsening fatigue for 1 month, and a 7-lb weight loss over the last summer. She was clinically and biochemically hyperthyroid. Echocardiography revealed a left atrial myxoma measuring 6.2 x 3.3 cm protruding into the mitral orifice and left ventricle during diastole. She was treated for Graves' disease with Iodine-131. Six weeks later, her left atrial myxoma measuring 10.1 x 6.2 x 2.4 cm was resected. She became euthyroid before surgery and then biochemically hypothyroid 6 weeks after radioiodine treatment, for which she subsequently required thyroxine replacement. Atrial myxomas are the most common primary cardiac neoplasms. At least 5% to 10% can be attributed to Carney's complex. More than two-thirds of patients with Carney's complex develop one or more cardiac myxomas. Although atrial myxomas in Carney's complex are histologically indistinguishable from the sporadic form, their clinical presentation and course is distinct. This is the first case of newly diagnosed Graves' disease that has been reported in association with an atrial myxoma. The features discussed in this article help differentiate between syndromic and sporadic atrial myxomas.

Rabbit haemorrhagic disease: advantages of cELISA in assessing immunity in wild rabbits (Oryctolagus cuniculus).

Science.gov (United States)

Zheng, Tao; Parkes, John P

2011-12-15

Rabbit haemorrhagic disease (RHD) is an acute fatal disease of domestic and wild European rabbits (Oryctolagus cuniculus) caused by RHD virus (RHDV). Accurate assessment of immunity is of great importance for the conservation and control of wild rabbits. We evaluated a competitive ELISA (cELISA) against isotype ELISAs for assessing the protective immunity against the disease by challenging 50 wild-caught rabbits with a lethal dose of RHDV. Death or survival to the challenge was used as a criterion to determine the performance characteristics of the assay for the assessment of immunity in rabbits. At 1:10 dilution, a serum exhibiting ≥ 25% inhibition (1:10(25)) was regarded as the presence of RHDV-specific antibodies. Eleven of 16 (68.8%) rabbits with antibodies at 1:10(25) (<1:40) died of RHD. When the cut-off was moved from 25% to 50% inhibition (1:10(50)) at 1:10 serum dilution, the assay sensitivity, specificity and accuracy for the protective immunity were improved from 84%, 54.2% and 69.4% to 84%, 100% and 91.8%, respectively. We also demonstrated at the epitope amino acid sequence level why the presence of the RHDV-cross reactive benign rabbit calicivirus, which interfered with isotype ELISAs, had little impact on the specificity of the cELISA for the diagnosis of RHDV infection. The presence of RHDV-specific antibody at 1:10(50) by the cELISA is a reliable indicator for the protective immunity. In contrast to isotype ELISAs, the cELISA is a valuable specific tool for monitoring the herd immunity to RHD for the conservation and management of wild rabbits in the field. Copyright © 2011 Elsevier B.V. All rights reserved.

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...

High rabbit abundance proves detrimental to the population growth rate in European rabbit (Oryctolagus cuniculus L. extensive breeding enclosures

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L. Ruiz-Aizpurua

2014-09-01

Full Text Available The European rabbit (Oryctolagus cuniculus L. is a key prey species in Mediterranean ecosystems that has declined in its natural ranges as a result of diseases and loss of habitat. This situation has led to the production of wild rabbits in enclosures in which they can acclimate and breed. The efficiency of these enclosures as extensive breeding systems is defined by their population growth rate (PGR. The aim of this study is to analyse the effect of rabbit abundance on the PGR. This has been done by creating general linear models to explain autumn and spring PGR with the use of rabbit abundance estimates, enclosure size, aerial predation and previous PGR as possible explanatory variables. Rabbit abundance and enclosure size negatively affected the autumn PGR, while only rabbit abundance affected the spring PGR in the best-fit models. It is suggested that maintaining rabbit densities at fewer than 30 rabbits per hectare might help to optimise the efficiency inside enclosures.

Left Atrial Decompression by Percutaneous Left Atrial Venting Cannula Insertion during Venoarterial Extracorporeal Membrane Oxygenation Support

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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.

Insights into new-onset atrial fibrillation following open heart surgery and implications for type II atrial flutter.

Science.gov (United States)

Sadrpour, Shervin A; Srinivasan, Deepa; Bhimani, Ashish A; Lee, Seungyup; Ryu, Kyungmoo; Cakulev, Ivan; Khrestian, Celeen M; Markowitz, Alan H; Waldo, Albert L; Sahadevan, Jayakumar

2015-12-01

Postoperative atrial fibrillation (POAF), new-onset AF after open heart surgery (OHS), is thought to be related to pericarditis. Based on AF studies in the canine sterile pericarditis model, we hypothesized that POAF in patients after OHS may be associated with a rapid, regular rhythm in the left atrium (LA), suggestive of an LA driver maintaining AF. The aim of this study was to test the hypothesis that in patients with POAF, atrial electrograms (AEGs) recorded from at least one of the two carefully selected LA sites would manifest a rapid, regular rhythm with AEGs of short cycle length (CL) and constant morphology, but a selected right atrial (RA) site would manifest AEGs with irregular CLs and variable morphology. In 44 patients undergoing OHS, AEGs recorded from the epicardial surface of the RA, the LA portion of Bachmann's bundle, and the posterior LA during sustained AF were analysed for regularity of CL and morphology. Sustained AF occurred in 15 of 44 patients. Atrial electrograms were recorded in 11 of 15 patients; 8 of 11 had rapid, regular activation with constant morphology recorded from at least one LA site; no regular AEG sites were present in 3 of 11 patients. Atrial electrograms recorded during sustained POAF frequently demonstrated rapid, regular activation in at least one LA site, consistent with a driver maintaining AF. Published by Oxford University Press on behalf of the European Society of Cardiology 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Long-term effectiveness of surgical treatment of ectopic atrial tachycardia.

Science.gov (United States)

Prager, N A; Cox, J L; Lindsay, B D; Ferguson, T B; Osborn, J L; Cain, M E

1993-07-01

The purpose of this study was to determine the long-term clinical outcome of patients with ectopic atrial tachycardias treated surgically. Ectopic atrial tachycardia is an uncommon arrhythmia that can be symptomatic and is associated with the development of a cardiomyopathy. Management strategies are not well defined because of the paucity of data on the long-term effectiveness of pharmacologic and nonpharmacologic therapies. The long-term clinical impact of medical and surgical therapy was determined in 15 consecutive patients with ectopic atrial tachycardia. All 15 patients were initially treated with antiarrhythmic drugs (mean 5.7 +/- 2.2 drugs/patient). An effective drug regimen was identified in only 5 (33%) of the 15 patients; the remaining 10 patients were treated surgically. In each, individualized surgical procedures were guided by computer-assisted intraoperative mapping, with atrial plaques comprising up to 156 electrodes. Focal ablation was performed in four patients and atrial isolation procedures in six. The 10 patients treated surgically were followed up a mean of 4 +/- 3.2 years. Ectopic atrial tachycardia recurred in one patient. A permanent pacemaker was implanted in two patients, one of whom also required reoperation for constrictive pericarditis. There were no operative deaths. Ectopic atrial tachycardia recurred in three (60%) of the five patients discharged on antiarrhythmic drug therapy during a mean follow-up interval of 6.4 +/- 4.3 years. There was one nonarrhythmic death. Map-guided surgery demonstrated long-term efficacy in abolishing symptoms in 9 of the 10 patients with ectopic atrial tachycardia. Results demonstrate that surgery is effective for patients with ectopic atrial tachycardias who are not easily treated with antiarrhythmic drugs.

Pulmonary artery-to-left atrial fistula discovered after the closure of atrial septal defect: A rare clinical scenario

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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.

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

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

OpenAIRE

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

2008-01-01

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

Investigation of atrial vulnerability by analysis of the sinus node EG from atrial fibrillation models using a phase synchronization method.

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Chen, Ying; Wu, Zhong; Yang, Cuiwei; Shao, Jun; Wong, Kelvin Kian Loong; Abbott, Derek

2012-09-01

Atrial fibrillation (AF) can result in life-threatening arrhythmia, and a clinically convenient means for detecting vulnerability remains elusive. We investigated atrial vulnerability by analyzing the sinus electrogram (EG) from AF animal models using a phase synchronization method. Using acetylcholine (ACh)-induced acute canine AF models (n= 4), a total of 128 electrical leads were attached to the surface of the anterior and posterior atria, and the pulmonary veins to form an electrocardiological mapping system. ACh was injected at varying concentrations with ladder-type adjustments. Sinus EGs and induced AF EGs that pertain to specific ACh concentrations were recorded.We hypothesize that the atrial vulnerability may be correlated with the Shannon entropy (SE) of the phase difference matrix that is extracted from the sinus EG. Our research suggests that the combination of SE with the synchronization method enables the sinus node EG to be analyzed and used to estimate atrial vulnerability.

Aorto-right atrial fistula after ascending aortic replacement or aortic value replacement

International Nuclear Information System (INIS)

Zhi Aihua; Dai Ruping; Jiang Shiliang; Lu Bin

2012-01-01

Objective: To evaluate the CT features of aorto-right atrial fistula after aortic valve replacement (AVR) or ascending aortic replacement. Methods: Eighty-seven patients with aortic-right atrial fistula underwent CT after operation. The CT features were retrospectively analyzed. Fistula was measured according to maximum width of the shunt. Results: Aorto-right atrial fistula was detected in 87 patients after aortic valve replacement or ascending aortic replacement by CT scan. Among them, 25 patients were diagnosed as mild aorto-right atrial fistula, 47 patients as moderate, and 15 patients as severe. Thirty-seven patients underwent follow-up CT.Among them, 10 patients with mild to moderate aorto-right atrial fistula were considered to have complete regression, 8 patients with mild aorto-right atrial fistula considered to have incomplete regression, 14 patients with mild to moderate aorto-right atrial fistula considered to have stable condition, and 5 patients with moderate aorto-right atrial fistula considered to have progression at the 3-month follow-up. Conclusion: CT is a useful tool for defining aorto-right atrial fistula after AVR or ascending aortic replacement and for evaluating it in follow-up. (authors)

Three-dimensional atrial wall thickness maps to inform catheter ablation procedures for atrial fibrillation.

Science.gov (United States)

Bishop, Martin; Rajani, Ronak; Plank, Gernot; Gaddum, Nicholas; Carr-White, Gerry; Wright, Matt; O'Neill, Mark; Niederer, Steven

2016-03-01

Transmural lesion formation is critical to success in atrial fibrillation ablation and is dependent on left atrial wall thickness (LAWT). Pre- and peri-procedural planning may benefit from LAWT measurements. To calculate the LAWT, the Laplace equation was solved over a finite element mesh of the left atrium derived from the segmented computed tomographic angiography (CTA) dataset. Local LAWT was then calculated from the length of field lines derived from the Laplace solution that spanned the wall from the endocardium or epicardium. The method was validated on an atrium phantom and retrospectively applied to 10 patients who underwent routine coronary CTA for standard clinical indications at our institute. The Laplace wall thickness algorithm was validated on the left atrium phantom. Wall thickness measurements had errors of atrial wall thickness measurements were performed on 10 patients. Successful comprehensive LAWT maps were generated in all patients from the coronary CTA images. Mean LAWT measurements ranged from 0.6 to 1.0 mm and showed significant inter and intra patient variability. Left atrial wall thickness can be measured robustly and efficiently across the whole left atrium using a solution of the Laplace equation over a finite element mesh of the left atrium. Further studies are indicated to determine whether the integration of LAWT maps into pre-existing 3D anatomical mapping systems may provide important anatomical information for guiding radiofrequency ablation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

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.

Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

Science.gov (United States)

Sirish, Padmini; Li, Ning; Timofeyev, Valeriy; Zhang, Xiao-Dong; Wang, Lianguo; Yang, Jun; Lee, Kin Sing Stephen; Bettaieb, Ahmed; Ma, Sin Mei; Lee, Jeong Han; Su, Demetria; Lau, Victor C; Myers, Richard E; Lieu, Deborah K; López, Javier E; Young, J Nilas; Yamoah, Ebenezer N; Haj, Fawaz; Ripplinger, Crystal M; Hammock, Bruce D; Chiamvimonvat, Nipavan

2016-05-01

Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β. This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation. © 2016 American Heart Association, Inc.

Functional role of voltage gated Ca2+ channels in heart automaticity

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Pietro eMesirca

2015-02-01

Full Text Available Pacemaker activity of automatic cardiac myocytes controls the heartbeat in everyday life. Cardiac automaticity is under the control of several neurotransmitters and hormones and is constantly regulated by the autonomic nervous system to match the physiological needs of the organism. Several classes of ion channels and proteins involved in intracellular Ca2+ dynamics contribute to pacemaker activity. The functional role of voltage-gated calcium channels (VGCCs in heart automaticity and impulse conduction has been matter of debate for 30 years. However, growing evidence shows that VGCCs are important regulators of the pacemaker mechanisms and play also a major role in atrio-ventricular impulse conduction. Incidentally, studies performed in genetically modified mice lacking L-type Cav1.3 (Cav1.3-/- or T-type Cav3.1 (Cav3.1-/- channels show that genetic inactivation of these channels strongly impacts pacemaking. In cardiac pacemaker cells, VGCCs activate at negative voltages at the beginning of the diastolic depolarization and importantly contribute to this phase by supplying inward current. Loss-of-function of these channels also impairs atrio-ventricular conduction. Furthermore, inactivation of Cav1.3 channels promotes also atrial fibrillation and flutter in knockout mice suggesting that these channels can play a role in stabilizing atrial rhythm. Genomic analysis demonstrated that Cav1.3 and Cav3.1 channels are widely expressed in pacemaker tissue of mice, rabbits and humans. Importantly, human diseases of pacemaker activity such as congenital bradycardia and heart block have been attributed to loss-of-function of Cav1.3 and Cav3.1 channels. In this article, we will review the current knowledge on the role of VGCCs in the generation and regulation of heart rate and rhythm. We will discuss also how loss of Ca2+ entry through VGCCs could influence intracellular Ca2+ handling and promote atrial arrhythmias.

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...

Phos-tag-based analysis of myosin regulatory light chain phosphorylation in human uterine myocytes.

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Hector N Aguilar

Full Text Available The 'phosphate-binding tag' (phos-tag reagent enables separation of phospho-proteins during SDS-PAGE by impeding migration proportional to their phosphorylation stoichiometry. Western blotting can then be used to detect and quantify the bands corresponding to the phospho-states of a target protein. We present a method for quantification of data regarding phospho-states derived from phos-tag SDS-PAGE. The method incorporates corrections for lane-to-lane loading variability and for the effects of drug vehicles thus enabling the comparison of multiple treatments by using the untreated cellular set-point as a reference. This method is exemplified by quantifying the phosphorylation of myosin regulatory light chain (RLC in cultured human uterine myocytes.We have evaluated and validated the concept that, when using an antibody (Ab against the total-protein, the sum of all phosphorylation states in a single lane represents a 'closed system' since all possible phospho-states and phosphoisotypes are detected. Using this approach, we demonstrate that oxytocin (OT and calpeptin (Calp induce RLC kinase (MLCK- and rho-kinase (ROK-dependent enhancements in phosphorylation of RLC at T18 and S19. Treatment of myocytes with a phorbol ester (PMA induced phosphorylation of S1-RLC, which caused a mobility shift in the phos-tag matrices distinct from phosphorylation at S19.We have presented a method for analysis of phospho-state data that facilitates quantitative comparison to a reference control without the use of a traditional 'loading' or 'reference' standard. This analysis is useful for assessing effects of putative agonists and antagonists where all phospho-states are represented in control and experimental samples. We also demonstrated that phosphorylation of RLC at S1 is inducible in intact uterine myocytes, though the signal in the resting samples was not sufficiently abundant to allow quantification by the approach used here.

Atrialización de un caso de síndrome de aurícula paralítica Atrialization in one case of atrial palsy syndrome

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Alejandro Orjuela

Full Text Available El síndrome de aurícula paralítica es una entidad poco común y generalmente se presenta aislada o asociada a trastornos degenerativos musculares. Se ha propuesto un mecanismo de transmisión familiar por transmisión autosómica dominante. Su presentación es más frecuente en hombres jóvenes y puede manifestarse como evento cerebrovascular, falla cardiaca o fenómenos tromboembólicos. En este artículo se presenta el caso de un hombre joven con historia de síncope recurrente y quien había recibido, tiempo atrás, implante de marcapaso definitivo monocameral. Se descartaron enfermedades inflamatorias cardiacas, distrofias musculares y otras causas secundarias de su trastorno en la formación del impulso sinusal. Una vez la batería de su marcapaso se encontró cerca de su fin de vida y durante el cambio programado del generador, se realizó estudio electrofisiológico de la aurícula y no se encontró mayor actividad. Se implantó electrodo atrial y se realizó seguimiento ecocardiográfico de la función auricular, la cual mostró una discreta mejoría al cabo de seis meses post-implante, para retornar a los valores basales, razón por la que se apagó el canal atrial. Aunque algunos pacientes recuperan la función atrial posterior a la cardioversión por fibrilacion atrial, no se conoce el porcentaje de pacientes que lo hacen tras la estimulación atrial en una aurícula poco activa mecánica y eléctricamente. Esto hace útil la medición de la actividad atrial y la estimulación, antes de decidir sobre el implante de un electrodo en el atrio.Atrial palsy syndrome is an uncommon entity which generally occurs isolated or associated with degenerative muscular disorders. An autosomic dominant familiar transmission mechanism has been proposed. It appears more frequently in young males, and may be manifested as cerebro-vascular event, heart failure or thromboembolic phenomena. In this article, the case of a young man with history of

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

Science.gov (United States)

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...

Structural and functional characteristics of myocard in patients with different forms of atrial fibrillation

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L. I. Vasilyeva

2015-02-01

Full Text Available Aim. To study structural and functional characteristics of myocard in patients with different forms of atrial fibrillation. Atrial fibrillation is the most prevalent arrhythmia in clinical practice. Atrial fibrillation is a progressive disease: the duration of paroxysms increases over time and paroxysmal atrial fibrillation transforms to persistent, the last one becomes refractory to pharmacological and electrical cardioversion in time and transforms to permanent. So assessment of myocardial remodeling in patients with persistent and permanent atrial fibrillation is very actual. Methods and results. According to the aim of the study 133 patients with persistent atrial fibrillation and 100 patients with permanent atrial fibrillation were included into the study. Echocardiographic parameters of left and right atria function were studied. Conclusion. It was found that patients with persistent and permanent atrial fibrillation are characterized with both left and right atrias remodeling. Remodeling of the atrias is less pronounced in patients with permanent atrial fibrillation in comparison with persistent atrial fibrillation patients and arrhythmia recurrence.

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

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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.

Cerebral Pulsatility Index Is Elevated in Patients with Elevated Right Atrial Pressure.

Science.gov (United States)

Lahiri, Shouri; Schlick, Konrad H; Padrick, Matthew M; Rinsky, Brenda; Gonzalez, Nestor; Jones, Heather; Mayer, Stephan A; Lyden, Patrick D

2018-01-01

Extracerebral venous congestion can precipitate intracranial hypertension due to obstruction of cerebral blood outflow. Conditions that increase right atrial pressure, such as hypervolemia, are thought to increase resistance to jugular venous outflow and contribute to cerebro-venous congestion. Cerebral pulsatility index (CPI) is considered a surrogate marker of distal cerebrovascular resistance and is elevated with intracranial hypertension. Thus, we sought to test the hypothesis that elevated right atrial pressure is associated with increased CPI compared to normal right atrial pressure. We retrospectively reviewed 61 consecutive patients with subarachnoid hemorrhage. We calculated CPI from transcranial Doppler studies and correlated these with echocardiographic measures of right atrial pressure. CPIs were compared from patients with elevated and normal right atrial pressure. There was a significant difference between CPI obtained from all patients with elevated right atrial pressure compared to those with normal right atrial pressure (P right and left hemispheric CPI from patients with both elevated and normal right atrial pressure. Patients with elevated right atrial pressure had significantly higher CPI compared to patients with normal right atrial pressure. These findings suggest that cerebro-venous congestion due to impaired jugular venous outflow may increase distal cerebrovascular resistance as measured by CPI. Since elevated CPI is associated with poor outcome in numerous neurological conditions, future studies are needed to elucidate the significance of these results in other populations. Copyright © 2017 by the American Society of Neuroimaging.

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....

Left atrial isolation associated with mitral valve operations.

Science.gov (United States)

Graffigna, A; Pagani, F; Minzioni, G; Salerno, J; Viganò, M

1992-12-01

Surgical isolation of the left atrium was performed for the treatment of chronic atrial fibrillation secondary to valvular disease in 100 patients who underwent mitral valve operations. From May 1989 to September 1991, 62 patients underwent mitral valve operations (group I); 19, mitral valve operations and DeVega tricuspid annuloplasty (group II); 15, mitral and aortic operations (group III); and 4, mitral and aortic operations and DeVega tricuspid annuloplasty (group IV). Left atrial isolation was performed, prolonging the usual left paraseptal atriotomy toward the left fibrous trigone anteriorly and the posteromedial commissure posteriorly. The incision was conducted a few millimeters apart from the mitral valve annulus, and cryolesions were placed at the edges to ensure complete electrophysiological isolation of the left atrium. Operative mortality accounted for 3 patients (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 = not significant). Three late deaths (3.1%) were registered. Long-term results show persistence of sinus rhythm 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 recurrence of atrial fibrillation was found to be preoperative atrial fibrillation longer than 6 months. Due to the satisfactory success rate in recovering sinus rhythm, we suggest performing left atrial isolation in patients with chronic atrial fibrillation undergoing valvular operations.

Some factors affecting rabbit production under egyptian environment

International Nuclear Information System (INIS)

Nessim, M.Z.

1994-01-01

The present work was carried out in the rabbit of the department of animal production, faculty of agriculture, Zagazig University, Zagazig, Egypt, Blood biochemical analysis and hormonal assay were conducted in tracer bio climatology Unit., Department of radiobiology, nuclear research centre, Atomic Energy Authority, Cairo, Egypt. Eighty male New Zealand white (NZW) and 80 male californian (Cal) rabbits aged 5-6 weeks were used. The animals were housed in rabbit building, naturally ventilated. Rabbits cages were provided with automatic nipple drinkers and drinking and drinking water ad libitum.Rabbits were fed ad libitum on balanced growing pelted rabbit ration. 21 tabs.,13 figs.,158 refs

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...

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. 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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. S.; Ellsworth, S.; Elshahawy, M.; Emlein, G.; Entcheva, M.; Essandoh, L. K.; Estrada, A. Q.; Ewing, B.; Faillace, R. T.; Fanelli, A.; Farrell, P. W.; Farris, S. W.; Fattal, P. G.; Feigenblum, D. Y.; Feldman, G. J.; Fialkow, J. A.; Fiddler, K. M.; Fields, R. H.; Finkel, M. S.; Finn, C.; Fischell, T. A.; Fishbach, M.; Fishbein, G. J.; Fisher, M. M.; Fleischhauer, F. J.; Folk, T. G.; Folkerth, S. D.; Fortman, R. R.; Frais, M. A.; Friedman, D. C.; Fuchs, G.; Fuller, F.; Garibian, G.; Gee, F. H.; Gelernt, M. D.; Genovely, H. C.; Gerber, J. R.; Germano, J. J.; Giardina, J. J.; Gilbert, J. M.; Gillespie, E. L.; Gilman, E. M.; Gitler, B.; Givens, D. H.; Glover, R.; Gogia, H. S.; Gohn, D. C.; Goldberg, R. K.; Goldberger, J. J.; Goldscher, D. A.; Goldstein, M.; Goraya, T.; Gordon, D. F.; Gottlieb, D.; Grafner, H. L.; Graham, M.; Graves, M. W.; Graziano, M.; Greco, S. N.; Greenberg, M. L.; Greenspon, A. J.; Greer, G. S.; Griffin, D. D.; Grogan, E. W.; Groo, V. 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

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...

Light colour preference of growing rabbits

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Zsolt Szendrő

2010-01-01

Full Text Available The objective of the experiment was to evaluate the light colour preference of growing rabbits placed in a free-choice cage. The experiment was carried out on 128 Pannon White growing rabbits weaned at the age of 5 weeks and placed into blocks (2m2 of four cages. The rabbits could move freely among the four cages (0.5m2 each through swing doors. The cages differed only in the colour of the light applied (white, yellow, green or blue. The lighting schedule was 16L: 8D. From 6 until 10 weeks of age, infrared video recording was performed once a week (24 hours. The number of rabbits in each cage was counted every 15 minutes. Feed consumption was measured weekly. Between 6 and 10 weeks of age the rabbits significantly preferred white light (28.0%. The preference order was the following: yellow (26.3%, blue (23.4% and green (22.3% (P<0.001. No significant differences were recorded in the feed consumption among the cages. In conclusion, the cage preference of the rabbits was slightly affected by the light colour.

Correlation of right atrial appendage velocity with left atrial appendage velocity and brain natriuretic Peptide.

Science.gov (United States)

Kim, Bu-Kyung; Heo, Jung-Ho; Lee, Jae-Woo; Kim, Hyun-Soo; Choi, Byung-Joo; Cha, Tae-Joon

2012-03-01

Left atrial appendage (LAA) anatomy and function have been well characterized both in healthy and diseased people, whereas relatively little attention has been focused on the right atrial appendage (RAA). We sought to evaluate RAA flow velocity and to compare these parameters with LAA indices and with a study of biomarkers, such as brain natriuretic peptide, among patients with sinus rhythm (SR) and atrial fibrillation (AF). In a series of 79 consecutive patients referred for transesophageal echocardiography, 43 patients (23 with AF and 20 controls) were evaluated. AF was associated with a decrease in flow velocity for both LAA and RAA [LAA velocity-SR vs. AF: 61 ± 22 vs. 29 ± 18 m/sec (p vs. AF: 46 ± 20 vs. 19 ± 8 m/sec (p brain natriuretic peptide (BNP). AF was associated with decreased RAA and LAA flow velocities. RAA velocity was found to be positively correlated with LAA velocity and negatively correlated with BNP. The plasma BNP concentration may serve as a determinant of LAA and RAA functions.

Ebstein's anomaly as a cause of paroxysmal atrial fibrillation

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Damjanović Miodrag R.

2008-01-01

Full Text Available Background. Ebstein's anomaly is characterized by a displacement of the tricuspid valve toward apex, because of anomalous attachment of the tricuspid leaflets. There are type B of Wolff-Parkinson-White (WPW syndrome and paroxysmal arrhythmias in more than a half of all patients. Case report. We presented a female, 32-year old, with frequent paroxysms of atrial fibrillation. After conversion of rhythm an ECG showed WPW syndrome. Echocardiographic examination discovered normal size of the left cardiac chambers with paradoxical ventricular septal motion. The right ventricle was very small because of its atrialization. The origin of the tricuspid valve was 20 mm closer to apex of the right ventricle than the origin of the mitral valve. Electrophysiological examination showed a posterolateral right accesorial pathway. Atrial fibrillation was induced very easily in electrophysiological laboratory and a successful ablation of accessorial pathway was made. There were no WPW syndrome and paroxysms of atrial fibrillation after that. Conclusion. Ebstein's anomaly is one of the reasons of paroxysmal atrial fibrillation, especially in young persons with WPW syndrome.

Heart failure and atrial fibrillation: current concepts and controversies.

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Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

1997-01-01

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

Science.gov (United States)

Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

2017-08-01

Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

LEFT ATRIAL APPENDAGE CLOSURE AS AN ALTERNATIVE TO WARFARIN FOR STROKE PREVENTION IN ATRIAL FIBRILLATION: A PATIENT¬LEVEL META¬ANALYSIS

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2015-01-01

Full Text Available Holmes D.R. Jr, Doshi S.K., Kar S., et al. Left Atrial Appendage Closure as an Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation: A Patient­Level Meta­Analysis // J. Am. Coll. Cardiol. – 2015. – Vol. 65. – P. 2614–2623.

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...

77 FR 11121 - Scientific Information Request on Treatment of Atrial Fibrillation

Science.gov (United States)

2012-02-24

... Information Request on Treatment of Atrial Fibrillation AGENCY: Agency for Healthcare Research and Quality... Review of the Treatment of Atrial Fibrillation, which is currently being conducted by the Evidence-based... the treatment of atrial fibrillation. The EHC Program is dedicated to identifying as many studies as...

PR Interval Associated Genes, Atrial Remodeling and Rhythm Outcome of Catheter Ablation of Atrial Fibrillation—A Gene-Based Analysis of GWAS Data

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Daniela Husser

2017-12-01

Full Text Available Background: PR interval prolongation has recently been shown to associate with advanced left atrial remodeling and atrial fibrillation (AF recurrence after catheter ablation. While different genome-wide association studies (GWAS have implicated 13 loci to associate with the PR interval as an AF endophenotype their subsequent associations with AF remodeling and response to catheter ablation are unknown. Here, we perform a gene-based analysis of GWAS data to test the hypothesis that PR interval candidate genes also associate with left atrial remodeling and arrhythmia recurrence following AF catheter ablation.Methods and Results: Samples from 660 patients with paroxysmal (n = 370 or persistent AF (n = 290 undergoing AF catheter ablation were genotyped for ~1,000,000 SNPs. Gene-based association was investigated using VEGAS (versatile gene-based association study. Among the 13 candidate genes, SLC8A1, MEIS1, ITGA9, SCN5A, and SOX5 associated with the PR interval. Of those, ITGA9 and SOX5 were significantly associated with left atrial low voltage areas and left atrial diameter and subsequently with AF recurrence after radiofrequency catheter ablation.Conclusion: This study suggests contributions of ITGA9 and SOX5 to AF remodeling expressed as PR interval prolongation, low voltage areas and left atrial dilatation and subsequently to response to catheter ablation. Future and larger studies are necessary to replicate and apply these findings with the aim of designing AF pathophysiology-based multi-locus risk scores.

Endothelial actions of atrial and B-type natriuretic peptides.

Science.gov (United States)

Kuhn, Michaela

2012-05-01

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the

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

Science.gov (United States)

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.

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

Possible interaction between myxomatosis and calicivirosis related to rabbit haemorrhagic disease affecting the European rabbit.

Science.gov (United States)

Marchandeau, S; Bertagnoli, S; Peralta, B; Boucraut-Baralon, C; Letty, J; Reitz, F

2004-11-06

Serological data on myxoma virus, rabbit haemorrhagic disease (RHD) virus and RHD-like viruses in juvenile rabbits (Oryctolagus cuniculus) trapped in 1995, 1996 and 1997 in two areas of France were analysed. For each disease, the effects of bodyweight, year, month and seropositivity for the other disease were modelled by using logistic regressions. In one area, a model including RHD seropositivity was selected to explain the myxoma virus seropositivity. Models including myxoma virus seropositivity were selected to explain the RHD seropositivity in both areas, and the odds of a rabbit being seropositive to both viruses were 5.1 and 8.4 times higher than the odds of a rabbit being seronegative to myxoma virus and seropositive to RHD. The year and bodyweight had significant effects for myxomatosis in one area and for RHD in both areas.

Gene transfer, expression, and sarcomeric incorporation of a headless myosin molecule in cardiac myocytes: evidence for a reserve in myofilament motor function

Science.gov (United States)

Vandenboom, Rene; Herron, Todd; Favre, Elizabeth; Albayya, Faris P.

2011-01-01

The purpose of this study was to implement a living myocyte in vitro model system to test whether a motor domain-deleted headless myosin construct could be incorporated into the sarcomere and affect contractility. To this end we used gene transfer to express a “headless” myosin heavy chain (headless-MHC) in complement with the native full-length myosin motors in the cardiac sarcomere. An NH2-terminal Flag epitope was used for unique detection of the motor domain-deleted headless-MHC. Total MHC content (i.e., headless-MHC + endogenous MHC) remained constant, while expression of the headless-MHC in transduced myocytes increased from 24 to 72 h after gene transfer until values leveled off at 96 h after gene transfer, at which time the headless-MHC comprised ∼20% of total MHC. Moreover, immunofluorescence labeling and confocal imaging confirmed expression and demonstrated incorporation of the headless-MHC in the A band of the cardiac sarcomere. Functional measurements in intact myocytes showed that headless-MHC modestly reduced amplitude of dynamic twitch contractions compared with controls (P < 0.05). In chemically permeabilized myocytes, maximum steady-state isometric force and the tension-pCa relationship were unaltered by the headless-MHC. These data suggest that headless-MHC can express to 20% of total myosin and incorporate into the sarcomere yet have modest to no effects on dynamic and steady-state contractile function. This would indicate a degree of functional tolerance in the sarcomere for nonfunctional myosin molecules. PMID:21112946

S100A6 is a negative regulator of the induction of cardiac genes by trophic stimuli in cultured rat myocytes

International Nuclear Information System (INIS)

Tsoporis, J.N.; Marks, A.; Haddad, A.; O'Hanlon, D.; Jolly, S.; Parker, T.G.

2005-01-01

S100A6 (calcyclin), a member of the S100 family of EF-hand Ca 2+ binding proteins, has been implicated in the regulation of cell growth and proliferation. We have previously shown that S100B, another member of the S100 family, is induced postinfarction and limits the hypertrophic response of surviving cardiac myocytes. We presently report that S100A6 expression is also increased in the periinfarct zone of rat heart postinfarction and in cultured neonatal rat myocytes by treatment with several trophic agents, including platelet-derived growth factor (PDGF), the α 1 -adrenergic agonist phenylephrine (PE), and angiotensin II (AII). Cotransfection of S100A6 in cultured neonatal rat cardiac myocytes inhibits induction of the cardiac fetal gene promoters skeletal α-actin (skACT) and β-myosin heavy chain (β-MHC) by PDGF, PE, AII, and the prostaglandin F 2α (PGF 2α ), induction of the S100B promoter by PE, and induction of the α-MHC promoter by triiodothyronine (T3). By contrast, S100B cotransfection selectively inhibited only PE induction of skACT and β-MHC promoters. Fluorescence microscopy demonstrated overlapping intracellular distribution of S100B and S100A6 in transfected myocytes and in postinfarct myocardium but heterodimerization of the two proteins could not be detected by co-immunoprecipitation. We conclude that S100A6 may function as a global negative modulator of differentiated cardiac gene expression comparable to its putative role in cell cycle progression of dividing cells

Assessment of blood stasis in left-atrial appendage with electron-beam CT: filling delay in atrial fibrillation

International Nuclear Information System (INIS)

Nakanishi, Tadashi; Hamada, Seiki; Takamiya, Makoto; Kuribayashi, Sachio; Naito, Hiroaki

1994-01-01

The left-atrial appendage (LAA) is the most frequent site of thrombus formation. The most probable reason is its anatomical structure and blood stasis. We hypothesized that peak time delay should occur in the LAA with stagnant blood flow. We measured peak time delay in LAA against left atrium with the flow-mode study of electron-beam CT for 49 patients (including 23 patients with atrial fibrillation [AF]). Volume-mode scannings were also performed to detect intracardiac thrombi. Patients with atrial fibrillation showed a larger value than those with sinus rhythm. Some AF patients with no filling of contrast media into the LAA and/or thrombus showed a larger value than the others. The value obtained by the flow-mode study might have the potential by the flow-mode study might have the potential to assess blood stasis and to predict the jeopardized state in the LAA. (orig.)

Assessment of blood stasis in left-atrial appendage with electron-beam CT: filling delay in atrial fibrillation

Energy Technology Data Exchange (ETDEWEB)

Nakanishi, Tadashi [Dept. of Radiology, National Cardiovascular Center, Suita, Osaka (Japan); Hamada, Seiki [Dept. of Radiology, National Cardiovascular Center, Suita, Osaka (Japan); Takamiya, Makoto [Dept. of Radiology, National Cardiovascular Center, Suita, Osaka (Japan); Kuribayashi, Sachio [Dept. of Radiology, National Cardiovascular Center, Suita, Osaka (Japan); Naito, Hiroaki [Biomedical Research Center, Osaka Univ. School of Medicine, Suita (Japan)

1994-10-01

The left-atrial appendage (LAA) is the most frequent site of thrombus formation. The most probable reason is its anatomical structure and blood stasis. We hypothesized that peak time delay should occur in the LAA with stagnant blood flow. We measured peak time delay in LAA against left atrium with the flow-mode study of electron-beam CT for 49 patients (including 23 patients with atrial fibrillation [AF]). Volume-mode scannings were also performed to detect intracardiac thrombi. Patients with atrial fibrillation showed a larger value than those with sinus rhythm. Some AF patients with no filling of contrast media into the LAA and/or thrombus showed a larger value than the others. The value obtained by the flow-mode study might have the potential by the flow-mode study might have the potential to assess blood stasis and to predict the jeopardized state in the LAA. (orig.)

Noninvasive evaluation of reverse atrial remodeling after catheter ablation of atrial fibrillation by P wave dispersion.

Science.gov (United States)

Fujimoto, Yuhi; Yodogawa, Kenji; Takahashi, Kenta; Tsuboi, Ippei; Hayashi, Hiroshi; Uetake, Shunsuke; Iwasaki, Yu-Ki; Hayashi, Meiso; Miyauchi, Yasushi; Shimizu, Wataru

2017-11-01

Atrial fibrillation (AF) itself creates structural and electrophysiological changes such as atrial enlargement, shortening of refractory period and decrease in conduction velocity, called "atrial remodeling", promoting its persistence. Although the remodeling process is considered to be reversible, it has not been elucidated in detail. The aim of this study was to assess the feasibility of P wave dispersion in the assessment of reverse atrial remodeling following catheter ablation of AF. Consecutive 126 patients (88 males, age 63.0 ± 10.4 years) who underwent catheter ablation for paroxysmal AF were investigated. P wave dispersion was calculated from the 12 lead ECG before, 1 day, 1 month, 3 months and 6 months after the procedure. Left atrial diameter (LAD), left atrial volume index (LAVI), left ventricular ejection fraction (LVEF), transmitral flow velocity waveform (E/A), and tissue Doppler (E/e') on echocardiography, plasma B-type natriuretic peptide (BNP) concentrations, serum creatinine, and estimated glomerular filtration rate (eGFR) were also measured. Of all patients, 103 subjects remained free of AF for 1 year follow-up. In these patients, P wave dispersion was not changed 1 day and 1 month after the procedure. However, it was significantly decreased at 3 and 6 months (50.1 ± 14.8 to 45.4 ± 14.4 ms, p < 0.05, 45.2 ± 9.9 ms, p < 0.05, respectively). Plasma BNP concentrations, LAD and LAVI were decreased (81.1 ± 103.8 to 44.8 ± 38.3 pg/mL, p < 0.05, 38.2 ± 5.7 to 35.9 ± 5.6 mm, p < 0.05, 33.3 ± 14.2 to 29.3 ± 12.3 mL/m 2 , p < 0.05) at 6 months after the procedure. There were no significant changes in LVEF, E/A, E/e', serum creatinine, and eGFR during the follow up period. P wave dispersion was decreased at 3 and 6 months after catheter ablation in patients without recurrence of AF. P wave dispersion is useful for assessment of reverse remodeling after catheter ablation of AF.

Role of Echocardiography in the Management and Prognosis of Atrial Fibrillation

Science.gov (United States)

Silverman, David I; Ayirala, Srilatha R; Manning, Warren J

2012-01-01

Echocardiography plays a longstanding and vital role in the management of atrial fibrillation (AF). Advances in 2D imaging, Doppler echocardiography and strain imaging have all contributed to major progress in AF treatment. Echocardiographically measured left atrial (LA) volume is a powerful predictor of maintenance of sinus rhythm following cardioversion as well as risk of thrombus formation and thromboembolism. Doppler derived parameters of atrial mechanical function including atrial ejection force provide related prognostic information. Transesophageal echocardiocardiograpy (TEE) guided cardioversion of AF allows for rapid conversion to sinus rhythm without prolonged oral anticoagulation, and TEE serves as a useful tool during catheter ablation of AF and atrial flutter. Newer measures derived from speckle tracking offer great promise in further improving the care of patients with AF. PMID:28496715

Myocyte specific overexpression of myoglobin impairs angiogenesis after hind-limb ischemia.

Science.gov (United States)

Hazarika, Surovi; Angelo, Michael; Li, Yongjun; Aldrich, Amy J; Odronic, Shelley I; Yan, Zhen; Stamler, Jonathan S; Annex, Brian H

2008-12-01

In preclinical models of peripheral arterial disease the angiogenic response is typically robust, though it can be impaired in conditions such as hypercholesterolemia and diabetes where the endothelium is dysfunctional. Myoglobin (Mb) is expressed exclusively in striated muscle cells. We hypothesized that myocyte specific overexpression of myoglobin attenuates ischemia-induced angiogenesis even in the presence of normal endothelium. Mb overexpressing transgenic (MbTg, n=59) and wild-type (WT, n=56) C57Bl/6 mice underwent unilateral femoral artery ligation/excision. Perfusion recovery was monitored using Laser Doppler. Ischemia-induced changes in muscle were assessed by protein and immunohistochemistry assays. Nitrite/nitrate and protein-bound NO, and vasoreactivity was measured. Vasoreactivity was similar between MbTg and WT. In ischemic muscle, at d14 postligation, MbTg increased VEGF-A, and activated eNOS the same as WT mice but nitrate/nitrite were reduced whereas protein-bound NO was higher. MbTg had attenuated perfusion recovery at d21 (0.37+/-0.03 versus 0.47+/-0.02, P<0.05), d28 (0.40+/-0.03 versus 0.50+/-0.04, P<0.05), greater limb necrosis (65.2% versus 15%, P<0.001), a lower capillary density, and greater apoptosis versus WT. Increased Mb expression in myocytes attenuates angiogenesis after hind-limb ischemia by binding NO and reducing its bioavailability. Myoglobin can modulate the angiogenic response to ischemia even in the setting of normal endothelium.

Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle

NARCIS (Netherlands)

Le, C. T.; Hollaar, L.; van der Valk, E. J.; Franken, N. A.; van Ravels, F. J.; Wondergem, J.; van der Laarse, A.

1995-01-01

The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG),

Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes

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Trine Krogh-Madsen

2017-12-01

Full Text Available In silico cardiac myocyte models present powerful tools for drug safety testing and for predicting phenotypical consequences of ion channel mutations, but their accuracy is sometimes limited. For example, several models describing human ventricular electrophysiology perform poorly when simulating effects of long QT mutations. Model optimization represents one way of obtaining models with stronger predictive power. Using a recent human ventricular myocyte model, we demonstrate that model optimization to clinical long QT data, in conjunction with physiologically-based bounds on intracellular calcium and sodium concentrations, better constrains model parameters. To determine if the model optimized to congenital long QT data better predicts risk of drug-induced long QT arrhythmogenesis, in particular Torsades de Pointes risk, we tested the optimized model against a database of known arrhythmogenic and non-arrhythmogenic ion channel blockers. When doing so, the optimized model provided an improved risk assessment. In particular, we demonstrate an elimination of false-positive outcomes generated by the baseline model, in which simulations of non-torsadogenic drugs, in particular verapamil, predict action potential prolongation. Our results underscore the importance of currents beyond those directly impacted by a drug block in determining torsadogenic risk. Our study also highlights the need for rich data in cardiac myocyte model optimization and substantiates such optimization as a method to generate models with higher accuracy of predictions of drug-induced cardiotoxicity.

Inhibition of sarcoplasmic reticulum Ca(2+)-ATPase decreases atrioventricular node-paced heart rate in rabbits.

Science.gov (United States)

Cheng, Hongwei; Smith, Godfrey L; Orchard, Clive H; Hancox, Jules C; Burton, Francis L

2012-10-01

Recent data indicate that Ca(2+) cycling in isolated atrioventricular node (AVN) cells contributes to setting spontaneous rate. The aim of the present study was to extend this observation to the intact AVN in situ, by evaluating the effects of inhibiting sarcoplasmic reticulum Ca(2+) uptake with cyclopiazonic acid (CPA) on intact AVN spontaneous activity and its response to isoprenaline. A model of the AVN-paced heart was produced to investigate intact AVN automaticity, by surgical ablation of the sino-atrial node (SAN) in the rabbit Langendorff-perfused heart. Electrograms were recorded from a site close to the AVN (triangle of Koch), an atrial site above the AVN, the left atrium and right ventricle, enabling AVN pacing of the preparation to be confirmed. Before SAN ablation, the heart rate was 166.8 ± 5.4 beats min(-1). Ablation of the SAN was clearly indicated by a sudden and significant decrease of heart rate to 108.6 ± 9.6 beats min(-1) (P AVN rate to 187.8 ± 12.0 beats min(-1) after 1 min of application (P AVN rate to 81.6 ± 4.8 (n = 9) and 77.4 ± 6.0 beats min(-1) (n = 7), respectively [P AVN rate increase in response to isoprenaline from 78.8 ± 10.0 to 46.8 ± 6.8 and 26.7 ± 5.3%, respectively (P AVN rate and its response to isoprenaline indicate that Ca(2+) cycling is important to the intact AVN spontaneous activity and its acceleration during sympathetic stimulation.

A Therapeutic Challenge: Management of Atrial Thrombus

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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

Atrial natriuretic peptide and feeding activity patterns in rats

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Oliveira M.H.A.

1997-01-01

Full Text Available This review presents historical data about atrial natriuretic peptide (ANP from its discovery as an atrial natriuretic factor (ANF to its role as an atrial natriuretic hormone (ANH. As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways

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....

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

Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

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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.

Cost of illness of atrial fibrillation: a nationwide study of societal impact.

Science.gov (United States)

Johnsen, Søren Paaske; Dalby, Lene Worsaae; Täckström, Tomas; Olsen, Jens; Fraschke, Anina

2017-11-10

The prevalence of atrial fibrillation is increasing rapidly; however, to date, population-based data are lacking on the attributable cost of illness of atrial fibrillation from a societal perspective, including both direct and indirect costs. The study was an incidence-based cost-of-illness study based on national registries covering the entire population of Denmark. We identified all patients with a first-time hospital diagnosis of atrial fibrillation between 2001 and 2012. For every atrial fibrillation patient, we identified three age- and sex-matched controls from the general population. Both the total and the attributable costs of atrial fibrillation were estimated based on individual level information on hospital care (in- and out-patient contacts), primary sector care, use of prescription drugs and productivity loss. Average 3-year societal costs per patient attributable to atrial fibrillation were estimated to be €20,403-26,544 during the study period. The costs were highest during the first year after diagnosis of atrial fibrillation. Admission costs constituted the largest cost component, whereas primary sector costs and medicine costs only constituted minor components. The attributable costs were more than two-fold higher among patients experiencing a stroke. The total 3-year cost attributable to atrial fibrillation in Denmark was estimated to be €219-295 million. The societal costs attributable to atrial fibrillation are significant. Reducing the need for hospitalizations, in particular from stroke, is a key factor in controlling the costs.

A case of low success of blind vaccination campaigns against myxomatosis and rabbit haemorrhagic disease on survival of adult European wild rabbits.

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Rouco, Carlos; Moreno, Sacramento; Santoro, Simone

2016-10-01

Vaccination campaigns against myxomatosis and rabbit haemorrhagic disease (RHD) are commonly used in translocation programs conducted for the purpose of recovering wild European rabbit populations in Iberian Mediterranean ecosystems. In most cases rabbits are vaccinated 'blind' (i.e. without assessing their prior immunological status) for economic and logistic reasons. However, there is conflicting evidence on the effectiveness of such an approach. We tested whether blind vaccination against myxomatosis and rabbit haemorrhagic disease improved rabbit survival in a rabbit translocation program where wild rabbits were kept in semi-natural conditions in three enclosures. We conducted nine capture sessions over two years (2008-2010) and used the information collected to compare the survival of vaccinated (n=511) versus unvaccinated (n=161) adult wild rabbits using capture-mark-recapture analysis. Average monthly survival was no different for vaccinated versus unvaccinated individuals, both in the period between release and first capture (short-term) and after the first capture onward (long-term). Rabbit survival was lower in the short term than in the long term regardless of whether rabbits were vaccinated or not. Lower survival in the short-term could be due to the stress induced by the translocation process itself (e.g. handling stress). However, we did not find any overall effect of vaccination on survival which could be explained by two non-exclusive reasons. First, interference of the vaccine with the natural antibodies in the donor population. Due to donor populations have high density of rabbits with, likely, high prevalence of antibodies as a result of previous natural exposure to these diseases. Second, the lack of severe outbreaks during the study period. Based on our findings we argue that blind vaccination of adult rabbits in translocation programs may be often mostly ineffective and unnecessarily costly. In particular, since outbreaks are hard to predict

Characterization of Pasteurella multocida involved in rabbit infections

DEFF Research Database (Denmark)

Massacci, Francesca Romana; Magistrali, Chiara Francesca; Cucco, Lucilla

2018-01-01

In rabbit, P. multocida is considered a predominant pathogenic agent; despite this, few data on the molecular epidemiology are available so far. The aim of this work was to characterize P. multocida isolates from rabbit affected by various diseases in Italy. Comparison was made to reference strains...... belonged to the LPS genotypes 3 (22/39) or 6 (17/39). The clonal relationships of the Italian strains from rabbit had similarity to previously reported rabbit isolates that belonged to ST9, ST74, ST204 and ST206, however, they differed from other rabbit references strains that belonged to six other STs....... In particular, ST9 with capsular type F has been previously reported from diseased rabbit in Czech Republic and ST74 has been observed for older rabbit isolates. ST50 has probably been reported from Spain. ST9 and ST50 have previously also been reported from birds and pig, respectively, whereas ST74 has...

A new therapeutic strategy for electrical cardioversion of atrial fibrillation.

Science.gov (United States)

de Luca, I; Sorino, M; Del Salvatore, B; de Luca, L

2001-11-01

The conventional approach to cardioversion of atrial fibrillation includes a period of anticoagulation with oral anticoagulant therapy (OAT) extending from 3 weeks precardioversion to 4 weeks postcardioversion. The protocol of rapid anticoagulation (such as that of the ACUTE study) consists of a precardioversion transesophageal echocardiography (TEE) followed by OAT for 4 weeks. In the last few years low-molecular-weight heparins have established themselves as a safe and efficacious alternative to traditional antithrombotic therapies. The aim of this study was to demonstrate that the exclusion of thrombi by precardioversion TEE together with the exclusion of atrial stunning by a second TEE performed after 1 week, to date not suggested in the literature, could reduce to 7 days the period of pericardioversion anticoagulation. This therapy would be carried out using low-molecular-weight heparins with no need for biological monitoring and with the possibility of self-administration. We have studied 57 consecutive patients who had atrial fibrillation or flutter with a history of atrial fibrillation lasting > 48 hours. All patients received enoxaparin at a dosage of 100 IU antiXa/kg twice daily before undergoing multiplane TEE. Previous informed consent and ethical committee authorization had been obtained. Twenty-four hours following TEE, in the absence of thrombi and/or spontaneous moderate/severe echocontrast in the atrial chambers, the patients underwent electrical cardioversion and were discharged within 24 hours of sinus rhythm restoration. These patients were prescribed enoxaparin at the indicated dosage twice daily until TEE, performed in an outpatients setting 7 days following cardioversion. In the absence of thrombi and/or atrial and/or left atrial appendage stunning, OAT was terminated. Enoxaparin was associated with OAT for the following 3 weeks if any of the following signs of stunning were present: A wave inferior to the normal value for age at transmitral

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...

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 ...

Atrial flutter: from ECG to electroanatomical 3D mapping

Directory of Open Access Journals (Sweden)

Livio Dei Cas

2009-08-01

Full Text Available Atrial flutter is a common arrhythmia that may cause significant symptoms, including palpitations, dyspnea, chest pain and even syncope. Frequently it’s possible to diagnose atrial flutter with a 12-lead surface ECG, looking for distinctive waves in leads II, III, aVF, aVL, V1,V2. Puech and Waldo developed the first classification of atrial flutter in the 1970s. These authors divided the arrhythmia into type I and type II. Therefore, in 2001 the European Society of Cardiology and the North American Society of Pacing and Electrophysiology developed a new classification of atrial flutter, based not only on the ECG, but also on the electrophysiological mechanism. New developments in endocardial mapping, including the electroanatomical 3D mapping system, have greatly expanded our understanding of the mechanism of arrhythmias. More recently, Scheinman et al, provided an updated classification and nomenclature. The terms like common, uncommon, typical, reverse typical or atypical flutter are abandoned because they may generate confusion. The authors worked out a new terminology, which differentiates atrial flutter only on the basis of electrophysiological mechanism. (Heart International 2006; 3-4: 161-70

Crosstalk between monocytes and myometrial smooth muscle in culture generates synergistic pro-inflammatory cytokine production and enhances myocyte contraction, with effects opposed by progesterone.

Science.gov (United States)

Rajagopal, S P; Hutchinson, J L; Dorward, D A; Rossi, A G; Norman, J E

2015-08-01

Both term and preterm parturition are characterized by an influx of macrophages and neutrophils into the myometrium and cervix, with co-incident increased peripheral blood monocyte activation. Infection and inflammation are strongly implicated in the pathology of preterm labour (PTL), with progesterone considered a promising candidate for its prevention or treatment. In this study, we investigated the effect of monocytes on myometrial smooth muscle cell inflammatory cytokine production both alone and in response to LPS, a TLR4 agonist used to trigger PTL in vivo. We also investigated the effect of monocytes on myocyte contraction. Monocytes, isolated from peripheral blood samples from term pregnant women, were cultured alone, or co-cultured with PHM1-41 myometrial smooth muscle cells, for 24 h. In a third set of experiments, PHM1-41 myocytes were cultured for 24 h in isolation. Cytokine secretion was determined by ELISA or multiplex assays. Co-culture of monocytes and myocytes led to synergistic secretion of pro-inflammatory cytokines and chemokines including IL-6, IL-8 and MCP-1, with the secretion being further enhanced by LPS (100 ng/ml). The synergistic secretion of IL-6 and IL-8 from co-cultures was mediated in part by direct cell-cell contact, and by TNF. Conditioned media from co-cultures stimulated contraction of PHM1-41 myocytes, and the effect was inhibited by progesterone. Both progesterone and IL-10 inhibited LPS-stimulated IL-6 and IL-8 secretion from co-cultures, while progesterone also inhibited chemokine secretion. These data suggest that monocytes infiltrating the myometrium at labour participate in crosstalk that potentiates pro-inflammatory cytokine secretion, an effect that is enhanced by LPS, and can augment myocyte contraction. These effects are all partially inhibited by progesterone. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke

DEFF Research Database (Denmark)

Christensen, L M; Krieger, D W; Højberg, S

2014-01-01

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrilla......BACKGROUND AND PURPOSE: Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial...... lasting predominantly between 1 and 4 h. Four recurrent strokes were observed, three in patients with PAF; all three patients were on oral anticoagulation (OAC). CONCLUSIONS: One in five patients with CS had PAF, which occurred at low burden and long after stroke. Future studies should determine the role...

Atrial angioleiomyoma with myopericytoma-like features: a case report.

Science.gov (United States)

Nassereddine, Hussein; Cazes, Aurélie; Verdonk, Constance; Assous, Benjamin; Dautry, Raphael; Nataf, Patrick; Wassef, Michel; Deschamps, Lydia

A 66-year-old female patient was referred to our hospital for resection of a right atrial mass. Four months earlier, she had suffered an acute cerebrovascular accident due to occlusion of the sylvian segment of the right middle cerebral artery from atheromatous tight stenosis in the right internal carotid artery. Later, investigations with transthoracic and transesophageal echocardiography revealed a 3.4-cm right atrial mass that was resected surgically. Microscopic evaluation revealed a well-circumscribed nodular tumor, located within the interatrial septum, and corresponding to an angioleiomyoma (ALM). This tumor differs histologically from atrial myxoma. ALM is a ubiquitous benign tumor but has never been reported to occur in the atrium. ALM can mimic cardiac myxoma and should be considered in the differential diagnosis of atrial tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

Parasitic infections of wild rabbits and hares

Directory of Open Access Journals (Sweden)

Ilić Tamara

2014-01-01

Full Text Available The paper presents the most important parasitic infections of wild rabbits and hares, which harmful effect in this animal population is manifested as a gradual weakening of the immune system, reduction in fertility, weight loss and constant exhaustion. Order of Lagomorpha (hares or lagomorphs belongs to superorder of higher mammals which includes the family of rabbits (Leporidae which are represented in Europe as well as the family of whistleblowers (Ochotonidae which live only in North America and Northern regions of Asia. The most important representatives of Leporidae family are European hare (Lepus europeus and wild rabbit (Oryctolagus cuniculus. The most important endoparasitosis of hares and wild rabbits are: coccidiosis, encephalitozoonosis (nosemosis, toxoplasmosis, sarcocystosis, giardiasis, cryptosporidiosis, protostrongylosis, trichostrngylodosis, passalurosis, anoplocephalidosis, cysticercosis and fasciolosis. The most frequent ectoparasites of rabbits and wild hares are fleas, lice and ticks. Reduction in hare population, which is noticed in whole Europe including Serbia, is caused by changed living conditions, quantitatively and qualitatively insufficient nutrition, increased use of herbicides as well as various infectious diseases and the diseases of parasitic etiology. Since wild rabbits and hares pose a threat to health of domestic rabbits and people, knowledge of parasitic fauna of these wild animals is of extreme epizootiological and epidemiological importance.

Welfare aspects in rabbit rearing and transport

Directory of Open Access Journals (Sweden)

Claudio Cavani

2010-01-01

Full Text Available The review starts with the description of the rabbits’ (Oryctolagus cuniculus main habits and the current situation concerning the rabbit husbandry and management systems, as well as their effects on the welfare of these animals. As far as the intensive rabbit husbandry systems are concerned, the main problems are related to the time since rabbits have been domesticated and their adaptive capacity and coping styles as respects the farming environment and management systems. Both these aspects have implications in the present and future of rabbit rearing for different purposes. Examples are given on the effects of different housing and management systems on rabbit welfare, as well as examples of the ethological, physiological and productive indicators used to evaluate these effects. Transportation and, more generally, preslaughter phases including catching, fasting and lairage at the abattoir are considered major stressors for farmed rabbits and might have deleterious effects on health, well-being, performance, and finally, product quality. A general statement of the recent scientific studies considering the effects of pre-slaughter factors on physiological and productive measurements are reported. Finally, some indications in order to improve rabbit welfare, already present at the European level, are also outlined, together with the European Food Safety Authority opinions.

Rapid slowing of the atrial fibrillatory rate after administration of AZD7009 predicts conversion of atrial fibrillation

DEFF Research Database (Denmark)

Aunes, Maria; Egstrup, Kenneth; Frison, Lars

2014-01-01

to sinus rhythm (SR) and were matched to 35 non-converters. The mean AFR before conversion was 231 fibrillations per minute (fpm), having decreased by 41%; in non-converters, it was 296 fpm at the end of infusion, having decreased by 26%. The rate of decrease was greater in converters at 5 min, -88 vs. -66......BACKGROUND: Effects on the atrial fibrillatory rate (AFR) were studied during infusion with the combined potassium and sodium channel blocker AZD7009. METHODS AND RESULTS: Patients with persistent atrial fibrillation (AF) were randomized to AZD7009 or placebo. Thirty-five patients converted...... fpm (p=0.02), and at 10 min, -133 vs. -111 fpm (p=0.048). The AFR-SD and the exponential decay decreased. A small left atrial area was the only baseline predictor of conversion to SR. CONCLUSIONS: AZD7009 produced a significantly more rapid decrease of the AFR in converters than in non...

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 ...

Observation of the efficacy of radiofrequency catheter ablation on patients with different forms of atrial fibrillation.

Science.gov (United States)

Zhao, R-C; Han, W; Han, J; Yu, J; Guo, J; Fu, J-L; Li, Z; Zhao, R-Z

2016-10-01

To study the efficacy and safety of radiofrequency catheter ablation (RFCA) in patients with different forms of atrial fibrillation. By retrospective analysis, we summarize 720 cases, where patients diagnosed with atrial fibrillation in our hospital were treated with RFCA from February 2010 to October 2014. Among the cases, 425 were diagnosed with paroxysmal atrial fibrillation and 295 with non-paroxysmal atrial fibrillation (including persistent atrial fibrillation and permanent atrial fibrillation). All patients were followed up until June 2015 to compare and analyze the differences in operation success rates, complications and recurrence rates. 395 cases (92.9%) of paroxysmal atrial fibrillation and 253 cases (85.8%) with non-paroxysmal atrial fibrillation were subject to surgery and followed up. The age of onset, disease course, underlying diseases, left atrial diameter and combined anti-arrhythmics of patients with paroxysmal atrial fibrillation were lower than those of patients with non-paroxysmal atrial fibrillation, and the differences were statistically significant (p success rate of the first ablation was higher than that of non-paroxysmal atrial fibrillation. Procedure time, procedure method, complications and recurrence rate of patients with paroxysmal atrial fibrillation were lower than those of non-paroxysmal atrial fibrillation group, and the differences were statistically significant (p failure caused by atrial fibrillation in the two groups, the difference was not statistically significant (Apoplexy: p = 0.186; Heart failure: p = 0.170). The individual ablation success rate was higher for paroxysmal atrial fibrillation, and long-term follow-up showed that the occurrence of apoplexy and heart failure was not different from the non-paroxysmal atrial fibrillation group.

Blood Profile of Rabbits Infected with Eimeria magna

Directory of Open Access Journals (Sweden)

A Hana

2011-09-01

Full Text Available Abstract. The research aimed at determining the blood profile of local rabbits infected with different dose of Eimeria magna oocysts. This research used 45 male rabbits with the age of 4 month old, range from 1.5 to 1.8 kg, clinically healthy and free from coccidiosis. The rabbits were randomly divided into 3 groups, group I as control (K-0 was given 1.0 ml distilled water/rabbit orally, group II (K-10 was infected with single dose of 10x106 oocysts of E. magna/rabbit orally, and group III (K-20 was infected with single dose of 20x106 oocysts of E. magna/rabbit orally. After infection, rabbits were examined for clinical signs, body weight and temperature daily for five days. Blood samples were drawn from the vena marginalis to examine the number of erythrocytes, hemoglobine, packed cell volume (PCV, leukocytes and its deferent, total protein plasma (TPP and fibrinogen, activities of alkaline phosphatase (ALP, alanine amino transferase (ALT, and aspartat aminotransferase (AST. The data were statistically analyzed by two-way anova using factorial design. The results of this research showed that the infection of E. magna in rabbits caused fever and weight loss, accompanied by normochromic microcytic anemia (at doses of 10x106 oocysts, macrocytic normochromic (at doses of 20x106 oocysts, leukocytosis, lymphocytosis, hiperfibrinogenemia, and increased of ALP activity. There were correlations between clinical symptoms and blood profile of rabbits infected with E. magna for five days. The higher the dose and the longer the infection of E. magna in rabbits caused weight loss, increased body temperature, MCV (microcytic to macrocytic, leukocyte, fibrinogen and ALP activity. These findings were useful to have a better understanding of pathophysiology of E. magna infection in  rabbits. Key Words: Eimeria magna, oocyst, rabbit, blood profile A Hana et al/Animal Production 13(3:185-190 (2011

Left Atrial Appendage Closure in Atrial Fibrillation: A World without Anticoagulation?

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Tahmeed Contractor

2011-01-01

Full Text Available Atrial Fibrillation (AF is a common arrhythmia with an incidence that is as high as 10% in the elderly population. Given the large proportion of strokes caused by AF as well as the associated morbidity and mortality, reducing stroke burden is the most important part of AF management. While warfarin significantly reduces the risk of AF-related stroke, perceived bleeding risks and compliance limit its widespread use in the high-risk AF population. The left atrial appendage is believed to be the “culprit” for thrombogenesis in nonvalvular AF and is a new therapeutic target for stroke prevention. The purpose of this review is to explore the evolving field of percutaneous LAA occlusion. After briefly highlighting the risk of stroke with AF, problems with warfarin, and the role of the LAA in clot formation, this article discusses the feasibility and efficacy of various devices which have been developed for percutaneous LAA occlusion.

Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

Science.gov (United States)

Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

1996-08-01

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

Usefulness of high-resolution sonography in early diagnosis of rabbit clonorchiasis

International Nuclear Information System (INIS)

Lim, Jae Hoon; Choi, Don Gil; Chung, Il Gyu; Phyun, Lae Hyun; Pyeun, Yong Seon; Hong, Sung Tae; Lee, Me Jeong

1999-01-01

To determine the role of high-resolution sonography in the early diagnosis of experimentally induced clonorchiasis in rabbits. We performed sonographic examination weekly in 22 lightly-infected rabbits (10 rabbits infected with 10 metacercariae, 6 rabbits infected with 20 metacercariae, and 6 rabbits infected with 40 metacercariae), and 10 heavily-infected rabbits (500 metacercariae). The sonographic criterion of diagnosis with dilatation of the intrahepatic ducts. We sacrificed lightly-infected rabbits and counted numbers of adult worms of clonorchis sinensis 9 weeks after infection. Sonographic abnormalities were found 3 weeks after infection in 2 lightly-infected rabbits and 5 heavily-infected rabbits. On sonography at 9 weeks after infection, we observed dilatation of the intrahepatic ducts in 11 (65%) of 17 lightly-infected rabbits and all of 10 heavily-infected rabbits. High-resolution sonography is very useful in early diagnosis of rabbits clonorchiasis.

Usefulness of high-resolution sonography in early diagnosis of rabbit clonorchiasis

Energy Technology Data Exchange (ETDEWEB)

Lim, Jae Hoon; Choi, Don Gil; Chung, Il Gyu; Phyun, Lae Hyun; Pyeun, Yong Seon [Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of); Hong, Sung Tae; Lee, Me Jeong [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1999-09-15

To determine the role of high-resolution sonography in the early diagnosis of experimentally induced clonorchiasis in rabbits. We performed sonographic examination weekly in 22 lightly-infected rabbits (10 rabbits infected with 10 metacercariae, 6 rabbits infected with 20 metacercariae, and 6 rabbits infected with 40 metacercariae), and 10 heavily-infected rabbits (500 metacercariae). The sonographic criterion of diagnosis with dilatation of the intrahepatic ducts. We sacrificed lightly-infected rabbits and counted numbers of adult worms of clonorchis sinensis 9 weeks after infection. Sonographic abnormalities were found 3 weeks after infection in 2 lightly-infected rabbits and 5 heavily-infected rabbits. On sonography at 9 weeks after infection, we observed dilatation of the intrahepatic ducts in 11 (65%) of 17 lightly-infected rabbits and all of 10 heavily-infected rabbits. High-resolution sonography is very useful in early diagnosis of rabbits clonorchiasis.

Diagnosis and therapy of atrial tachyarrhythmias in the dual chamber implantable cardioverter defibrillator.

Science.gov (United States)

Dijkman, B; Wellens, H J

2000-11-01

Devices capable of monitoring and treating atrial tachyarrhythmias provide information about the natural history of the arrhythmias and potentially can influence their natural course by electrical therapy early after onset. Types of atrial arrhythmias and efficacy of device therapies were evaluated in 30 patients implanted with the Medtronic model 7250 Jewel AF implantable cardioverter defibrillator (ICD). All patients had structural heart disease and documented sustained ventricular and atrial arrhythmias (27 with atrial fibrillation [AF]) before implant. Twenty patients were taking amiodarone, and three were taking sotalol. During 20+/-10 months of follow-up, 600 atrial arrhythmia recurrences were documented in 50% of patients. AF was diagnosed in 19%, fast polymorphic atrial tachycardia (AT) in 20%, fast monomorphic AT in 57%, and slow AT in 4% of episodes. The two adaptive pacing therapies, burst and ramp, together with the 50-Hz burst, were successful in 57% of detected atrial arrhythmias. Burst and ramp were responsible for 49% and 50-Hz burst for 51% of successfully treated arrhythmias; 33% of the episodes terminated spontaneously. No ventricular proarrhythmia was observed due to atrial pacing therapies. In 30% of episodes, dual chamber pacing was required due to post termination bradycardia. Atrial arrhythmia recurrences in patients with dilated cardiomyopathy were not amenable to pacing therapies. Several aspects of atrial arrhythmia diagnosis, therapy, and documentation that are specific for functioning of the Jewel AF are discussed. Atrial arrhythmias in ICD patients with diseased hearts who are taking Class III antiarrhythmics frequently had longer cycle lengths than AF. Half of these arrhythmias could be terminated with pacing therapies; one third terminated spontaneously.

Rapid pacing results in changes in atrial but not in ventricular refractoriness

NARCIS (Netherlands)

Schoonderwoerd, BA; Van Gelder, IC; Tieleman, RG; Bel, KJ; Crijns, HJGM

It is well known that atrial tachycardia causes atrial electrical remodeling, characterized by shortening of atrial effective refractory periods (AERPs) and loss of physiological adaptation of AERP to rate. However, the nature and time course of changes in ventricular effective refractory periods

Innate resistance to myxomatosis in wild rabbits in England*

Science.gov (United States)

Ross, J.; Sanders, M. F.

1977-01-01

Wild rabbits (Oryctolagus cuniculus) from one study area in England have been used over a period of 11 years to investigate the possible appearance of innate resistance to myxomatosis. Rabbits of 4-6 weeks old were captured alive, retained in the laboratory until at least 4 months old, and then infected with a type of myxoma virus which kills 90-95% of laboratory rabbits. Observations were made of symptoms, mortality rate and survival times. In the first 4 years of the study (1966-9), mortality rates were not significantly different from those of laboratory rabbits, although survival times of wild rabbits were appreciably longer. In 1970, the mortality rate amongst wild rabbits was 59%, in 1974 it was 17%, and in 1976 it was 20%, thus showing that a considerable degree of inherited resistance to myxomatosis has developed. The types of myxoma virus most commonly isolated from wild rabbits in Great Britain in recent years have been those which cause 70-95% mortality in laboratory rabbits. Therefore, if the degree of innate resistance demonstrated is widespread in Great Britain, there are serious implications regarding the size of the rabbit population, because myxomatosis has been an important factor in holding rabbit numbers at a relatively low level. PMID:270526

Innate resistance to myxomatosis in wild rabbits in England.

Science.gov (United States)

Ross, J; Sanders, M F

1977-12-01

Wild rabbits (Oryctolagus cuniculus) from one study area in England have been used over a period of 11 years to investigate the possible appearance of innate resistance to myxomatosis. Rabbits of 4-6 weeks old were captured alive, retained in the laboratory until at least 4 months old, and then infected with a type of myxoma virus which kills 90-95% of laboratory rabbits. Observations were made of symptoms, mortality rate and survival times.In the first 4 years of the study (1966-9), mortality rates were not significantly different from those of laboratory rabbits, although survival times of wild rabbits were appreciably longer. In 1970, the mortality rate amongst wild rabbits was 59%, in 1974 it was 17%, and in 1976 it was 20%, thus showing that a considerable degree of inherited resistance to myxomatosis has developed.The types of myxoma virus most commonly isolated from wild rabbits in Great Britain in recent years have been those which cause 70-95% mortality in laboratory rabbits. Therefore, if the degree of innate resistance demonstrated is widespread in Great Britain, there are serious implications regarding the size of the rabbit population, because myxomatosis has been an important factor in holding rabbit numbers at a relatively low level.

Detection of Rapid Atrial Arrhythmias in SQUID Magnetocardiography

Energy Technology Data Exchange (ETDEWEB)

Kim, Ki Woong; Kwon, Hyuk Chan; Kim, Ki Dam; Lee, Yong Ho; Kim, Jin Mok; Kim, In Seon; Lim, Hyun Kyoon; Park, Yong Ki [Biomagnetism Research, Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of); Kim, Doo Sang [Seoul Veterans Hospital, Seoul (Korea, Republic of); Lim, Seung Pyung [Chungnam National University Hospital, Daejeon (Korea, Republic of)

2005-10-15

We propose a method to measure atrial arrhythmias (AA) such as atrial fibrillation (Afb) and atrial flutter (Afl) with a SQUID magnetocardiograph (MCG) system. To detect AA is one of challenging topics in MCG. As the AA generally have irregular rhythm and atrio-ventricular conduction, the MCG signal cannot be improved by QRS averaging; therefore a SQUID MCG system having a high SNR is required to measure informative atrial excitation with a single scan. In the case of Afb, diminished f waves are much smaller than normal P waves because the sources are usually located on the posterior wall of the heart. In this study, we utilize an MCG system measuring tangential field components, which is known to be more sensitive to a deeper current source. The average noise spectral density of the whole system in a magnetic shielded room was 10 fT/Hz(a) 1 Hz and 5 fT/Hz(a) 100 Hz. We measured the MCG signals of patients with chronic Afb and Afl. Before the AA measurement, the comparison between the measurements in supine and prone positions for P waves has been conducted and the experiment gave a result that the supine position is more suitable to measure the atrial excitation. Therefore, the AA was measured in subject's supine position. Clinical potential of AA measurement in MCG is to find an aspect of a reentry circuit and to localize the abnormal stimulation noninvasively. To give useful information about the abnormal excitation, we have developed a method, separative synthetic aperture magnetometry (sSAM). The basic idea of sSAM is to visualize current source distribution corresponding to the atrial excitation, which are separated from the ventricular excitation and the Gaussian sensor noises. By using sSAM, we localized the source of an Afl successfully.

Evaluation of atrial electromechanical delay and diastolic functions in patients with hyperthyroidism.

Science.gov (United States)

Sokmen, Abdullah; Acar, Gurkan; Sokmen, Gulizar; Akcay, Ahmet; Akkoyun, Murat; Koroglu, Sedat; Nacar, Alper Bugra; Ozkaya, Mesut

2013-11-01

Hyperthyroidism is a well-known cause of atrial fibrillation (AF) which is associated with increased morbidity and mortality. Atrial electromechanical delay (EMD) is a significant predictor of AF. The aim of this study was to assess the atrial EMD and diastolic functions in subclinical and overt hyperthyroidism by using tissue Doppler imaging (TDI). The study population consisted of 3 groups: group I (30 healthy subjects), group II (38 patients with subclinical hyperthyroidism), and group III (25 patients with overt hyperthyroidism). Atrial electromechanical coupling was measured with TDI. Standard echocardiographic measurements and parameters of diastolic function were obtained by conventional echocardiography and TDI. Intra- and inter-atrial EMD were significantly prolonged in subclinical and overt hyperthyroidism compared with control group (P = 0.03 and P hyperthyroidism. TSH level and mitral Em /Am ratio were found as independent predictors of atrial EMD. © 2013, Wiley Periodicals, Inc.

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....

Surgical Ablation of Atrial Fibrillation Using Energy Sources.

Science.gov (United States)

Brick, Alexandre Visconti; Braile, Domingo Marcolino

2015-01-01

Surgical ablation, concomitant with other operations, is an option for treatment in patients with chronic atrial fibrillation. The aim of this study is to present a literature review on surgical ablation of atrial fibrillation in patients undergoing cardiac surgery, considering energy sources and return to sinus rhythm. A comprehensive survey was performed in the literature on surgical ablation of atrial fibrillation considering energy sources, sample size, study type, outcome (early and late), and return to sinus rhythm. Analyzing studies with immediate results (n=5), the percentage of return to sinus rhythm ranged from 73% to 96%, while those with long-term results (n=20) (from 12 months on) ranged from 62% to 97.7%. In both of them, there was subsequent clinical improvement of patients who underwent ablation, regardless of the energy source used. Surgical ablation of atrial fibrillation is essential for the treatment of this arrhythmia. With current technology, it may be minimally invasive, making it mandatory to perform a procedure in an attempt to revert to sinus rhythm in patients requiring heart surgery.

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.

Welfare assessment in pet rabbits

NARCIS (Netherlands)

Schepers, F.; Koene, P.; Beerda, B.

2009-01-01

One million pet rabbits are kept in The Netherlands, but there are no data available on their behaviour and welfare. This study seeks to assess the welfare of pet rabbits in Dutch households and is a first step in the development of a welfare assessment system. In an internet survey, housing

PGC-1α accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes

International Nuclear Information System (INIS)

Chen, Min; Wang, Yanru; Qu, Aijuan

2010-01-01

Energy metabolism and Ca 2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1α in cardiac Ca 2+ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1α via adenoviral transduction. Our data shows that overexpressing PGC-1α improved myocyte contractility without increasing the amplitude of Ca 2+ transients, suggesting that myofilament sensitivity to Ca 2+ increased. Interestingly, the decay kinetics of global Ca 2+ transients and Ca 2+ waves accelerated in PGC-1α-expressing cells, but the decay rate of caffeine-elicited Ca 2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca 2+ -ATPase (SERCA2a), but not Na + /Ca 2+ exchange (NCX) contribute to PGC-1α-induced cytosolic Ca 2+ clearance. Furthermore, PGC-1α induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1α did not disturb cardiac Ca 2+ homeostasis, because SR Ca 2+ load and the propensity for Ca 2+ waves remained unchanged. These data suggest that PGC-1α can ameliorate cardiac Ca 2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1α-calcium handing pathway sheds new light on the role of PGC-1α in the therapy of cardiac diseases.

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

Science.gov (United States)

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

2003-12-01

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

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...

Atrial Fibrillation and Gastro-Oesophageal Reflux Disease - Controversies and Challenges.

Science.gov (United States)

Floria, Mariana; Barboi, Oana; Rezus, Ciprian; Ambarus, Valentin; Cijevschi-Prelipcean, Cristina; Balan, Gheorghe; Drug, Vasile Liviu

2015-01-01

Atrial fibrillation and gastro-oesophageal reflux are common manifestations in daily practice. The atria and the oesophagus are closely located and have similar nerve innervations. Over the last years, it has been observed that atrial fibrillation development and reflux disease could be related. Atrial fibrillation occurrence could be due to vagal nerve overstimulation. This, in association with vagal nerve-mediated parasympathetic stimulation, has also been observed in patients with gastro-oesophageal reflux. These mechanisms, in addition to inflammation, seem to be implicated in the pathophysiology of both diseases. Despite these associations supported by clinical and experimental studies, this relationship is still considered controversial. This review summarizes critical data regarding the association of gastro-oesophageal reflux and atrial fibrillation as well as their clinical implications.

Women Sex Importance in Stroke Patients with Atrial Fibrillation

Directory of Open Access Journals (Sweden)

Cemile Handan Mısırlı

2014-08-01

Full Text Available OBJECTIVE: It was shown the differences in age, risk factors and treatment between women and men in stroke patients with atrial fibrillation METHODS: The stroke patients with atrial fibrillation who were hospitalized in our department at the last 2 years were seperated into 2 groups of aged above 75 and below 75, investigated with CHADS2 and CHA2DS2VASc scores and looked at the sex differences of women and men. RESULTS: Stroke ratio according to sex was statistically meaningful especially in women above the age of 75. Risc factors also were founded in elderly women and CHA2DS2VASc scores were higher in women than men so more anticoagulan treatment were begun. No differences were shown between sexes at lone atrial fibrillation and no treatment were begun. CONCLUSION: Women with atrial fibrillation had more risk factors, higher stroke rate and higher anticoagulation treatment.

Atrial electrogram interpretation improves after an innovative education program.

Science.gov (United States)

Preston, Julie L; Currey, Judy; Considine, Julie

2015-01-01

To avoid adverse patient outcomes from inappropriate treatment, it is recommended that an atrial electrogram (AEG) be recorded whenever atrial arrhythmias develop in patients after cardiac surgery. However, AEGs are not commonly performed because nurses lack knowledge about differentiating atrial rhythms on AEGs. To investigate whether completing a novel online evidence-based education program on interpreting AEGs would improve critical care nurses' AEG interpretation. Specialized critical care nurses were taught about obtaining and interpreting atrial rhythms on AEGs using a 42-minute online mini-movie. AEG interpretation was assessed pre and two and eight weeks post-intervention. AEG interpretation increased two weeks post intervention and was retained at eight weeks. Some participants used this newly acquired knowledge to interpret arrhythmias that were not taught during the education program. Accurate interpretation of AEGs is an easy skill for specialized critical care nurses to learn via an online education program.

Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study.

Science.gov (United States)

Pallisgaard, Jannik L; Schjerning, Anne-Marie; Lindhardt, Tommi B; Procida, Kristina; Hansen, Morten L; Torp-Pedersen, Christian; Gislason, Gunnar H

2016-04-01

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. 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 population and 253,374 (5%) in the diabetes group. Incidence rates of atrial fibrillation per 1000 person years were stratified in four age groups from 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years giving incidence rates (95% confidence intervals) of 0.02 (0.02-0.02), 0.99 (0.98-1.01), 8.89 (8.81-8.98) and 20.0 (19.9-20.2) in the background population and 0.13 (0.09-0.20), 2.10 (2.00-2.20), 8.41 (8.10-8.74) and 20.1 (19.4-20.8) in the diabetes group, respectively. The adjusted incidence rate ratios in the diabetes group with the background population as reference were 2.34 (1.52-3.60), 1.52 (1.47-1.56), 1.20 (1.18-1.23) and 0.99 (0.97-1.01) in the four age groups, respectively. Diabetes is an independent risk factor for developing atrial fibrillation/flutter, most pronounced in young diabetes patients. Routine screening for atrial fibrillation/flutter in diabetes patients might be beneficial and have therapeutic implications, especially in younger diabetes patients. Diabetes increases the risk of developing atrial fibrillation and especially young diabetes patients have a high

Market Driving to Develop Rabbit Meat Products in Indonesia

OpenAIRE

Atien Priyanti; Yono Cahyo Rahadjo

2012-01-01

Rabbit meat is a nutritional food containing high protein and low cholesterol, fat and sodium. Current research in rabbit production is aimed for developing production strategies to increase the nutritional and economic values of rabbit meat products as functional food. Nowadays, producing rabbit is a popular farming activity in many parts of Indonesia as a small and medium scale operation for food security and cash income. Rabbit farming is to produce meat, skin and hides, fur, organic ferti...

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....

Oclusão percutânea do apêndice atrial esquerdo com o Amplatzer Cardiac PlugTM na fibrilação atrial

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Márcio José Montenegro

2012-02-01

Full Text Available Fundamento: A fibrilação atrial está associada a acidentes vasculares embólicos que frequentemente resultam em morte ou invalidez. Eficaz na redução desses eventos, a anticoagulação possui várias limitações e vem sendo amplamente subutilizada. Mais de 90% dos trombos identificados nos portadores de fibrilação atrial sem doença valvar se originam no apêndice atrial esquerdo, cuja oclusão é investigada como uma alternativa à anticoagulação. Objetivo: Determinar a viabilidade da oclusão percutânea do apêndice atrial esquerdo em pacientes com alto risco de eventos embólicos e limitações ao uso de anticoagulação. Métodos: Relatamos a experiência inicial com o Amplatzer Cardiac PlugTM (St. Jude Medical Inc., Saint Paul, Estados Unidos em pacientes com fibrilação atrial não valvar. Foram selecionados pacientes com alto risco de tromboembolia, sangramentos maiores e contraindicações ao uso ou grande labilidade na resposta ao anticoagulante. Os procedimentos foram realizados por via percutânea, sob anestesia geral e com ecocardiografia transesofágica. O desfecho primário foi a presença de complicações periprocedimento e o seguimento programado incluiu reavaliação clínica e ecocardiográfica em 30 dias e por contato telefônico após nove meses. Resultados: Nos cinco pacientes selecionados se conseguiu a oclusão do apêndice atrial esquerdo sem complicações periprocedimento. Não houve eventos clínicos no seguimento. Conclusão: Ensaios clínicos controlados são necessários antes que o fechamento percutâneo do apêndice atrial esquerdo constitua uma alternativa à anticoagulação na fibrilação atrial não associada a doença valvar. Mas o dispositivo se mostrou promissor em pacientes com alto risco de embolia e restrições ao uso de anticoagulantes.

Time to implement fitness and reduction of fatness in atrial fibrillation therapy

NARCIS (Netherlands)

Van Gelder, Isabelle C.; Hobbelt, Anne H.; Brugemann, Johan; Rienstra, Michiel

This editorial refers to ‘Self-reported physical activity and major adverse events in patients with atrial fibrillation: a report from the EURObservational Research Programme Pilot Survey on Atrial Fibrillation (EORP-AF) General Registry’ by M. Proietti et al. , doi:10.1093/europace/euw150. Atrial

Decision-making interventions to stop the global atrial fibrillation-related stroke tsunami.

Science.gov (United States)

Cerasuolo, Joshua O; Montero-Odasso, Manuel; Ibañez, Agustin; Doocy, Shannon; Lip, Gregory Yh; Sposato, Luciano A

2017-04-01

Atrial fibrillation affects 33.5 million people worldwide and its prevalence is expected to double by 2050 because of the aging population. Atrial fibrillation confers a 5-fold higher risk of ischemic stroke compared to sinus rhythm. We present our view of the role of shared medical decision-making to combat global underutilization of oral anticoagulation for stroke prevention in atrial fibrillation patients. Oral anticoagulation underuse is widespread as it is present within atrial fibrillation patients of all risk strata and in countries across all income levels. Reasons for oral anticoagulation underuse include but are probably not limited to poor risk stratification, over-interpretation of contraindications, and discordance between physician prescription preferences and actual administration. By comparing a catastrophic event to the consequences of atrial fibrillation related strokes, it may help physicians and patients understand the negative outcomes associated with oral anticoagulation under-utilization and the magnitude to which oral anticoagulations neutralize atrial fibrillation burden.

Assessment of the effect of left atrial cryoablation enhanced by ganglionated plexi ablation in the treatment of atrial fibrillation in patients undergoing open heart surgery.

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Bárta, Jiří; Brát, Radim

2017-08-17

The aim of our study was to investigate, whether enhancement of left atrial cryoablation by ablation of the autonomic nervous system of left atrium leads to influencing the outcomes of surgical treatment of atrial fibrillation in patients with structural heart disease undergoing open-heart surgery. The observed patient file consisted of 100 patients, who have undergone a combined open-heart surgery at our department between July 2012 and December 2014. The patients were indicated for the surgical procedure due to structural heart disease, and suffered from paroxysmal, persistent, or long-standing persistent atrial fibrillation. In all cases, left atrial cryoablation was performed in the extent of isolation of pulmonary veins, box lesion, connecting lesion with mitral annulus, amputation of the left atrial appendage and connecting lesion of the appendage base with left pulmonary veins. Furthermore, 35 of the patients underwent mapping and radiofrequency ablation of ganglionated plexi, together with discision and ablation of the ligament of Marshall (Group GP). A control group was consisted of 65 patients without ganglionated plexi intervention (Group LA). The main primary outcome was establishment and duration of sinus rhythm in the course of one-year follow-up. Evaluation of the number of patients with a normal sinus rhythm in per cent has shown comparable values in both groups (Group GP - 93.75%, Group LA - 86.67%, p = 0.485); comparable results were also observed in patients with normal sinus rhythm without anti-arrhythmic treatment in the 12th month (Group GP - 50%, Group LA - 47%, p = 0.306). We have not observed any relation between the recurrence of atrial fibrillation and the presence of a mitral valve surgery, or between the presence of a mitral and tricuspid valves surgery and between the left atrial diameter > 50 mm. Enhancement of left atrial cryoablation by gangionated plexi ablation did not influence the outcomes of surgical ablation due to

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

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

Confirmation and phylogenetic analysis of rabbit hemorrhagic disease virus in free-living rabbits from the Netherlands

NARCIS (Netherlands)

van de Bildt, M. W. G.; van Bolhuis, G. H.; van Zijderveld, F.; van Riel, D.; Drees, J. M.; Osterhaus, A. D. M. E.; Kuiken, T.

2006-01-01

The number of free-living European rabbits (Oryctolagus cuniculus) in the Netherlands has declined dramatically in recent years. Although rabbit hemorrhagic disease virus (RHDV) infection has been implicated as a possible cause of this decline, the definitive diagnosis has not been reported. We

Electron-beam CT diagnosis of the viscero-atrial heterotaxy syndrome

International Nuclear Information System (INIS)

Yang Youyou; Dai Ruping; Jing Baolian; He Sha; Bai Hua; Li Xiangmin; Zhou Xuhui; Peng Qian; Meng Quanfei

2002-01-01

Objective: To assess the usefulness of electron-beam CT (EBCT) in diagnosis of the viscero-atrial heterotaxy syndrome. Methods: Ten patients with the viscero-atrial heterotaxy syndrome were evaluated. The patients ranged in age from 7 months to 17 years (averaged 9.5 years). Five of the patients underwent EBCT contrast single slice mode while another 5 patients did continuous volume scan obtained from the superior aperture of thorax to the middle part of abdomen. All the patients had both angiocardiogram and echocardiogram, and 6 patients had operative outcomes. Results; (1) Eight patients with right atrial isomerism, bilaterally morphologic right atrial appendages, right lobe dominant symmetric liver, bilaterally epi-arterial bronchi, trilobed lungs, and total anomalous pulmonary venous connectional were clearly detected. Endocardial cushions defect, pulmonary stenosis, right-sided aortic arch and descending aorta were documented in 7 patients. Double outlet of right ventricle was imaged in 6 patients and hiatal hernia in 2 patients. Neither a spleen nor splenulus were found. (2) Two patients with left atrial isomerism, bilaterally morphologic left atrial appendages, left lobe dominant symmetric liver, bilaterally hyparterial bronchi, bilobed lungs, double outlet of right ventricle, pulmonary stenosis, interruption of inferior vena cave, right-sided aortic arch, and descending aorta were documented. Endocardial cushions defect was detected in 1 patient. Multiple spleens were demonstrated in the right upper abdomen in the 2 patients. (3) The number of abnormal observations detected by EBCT was 116, while that done by angiocardiogram and echocardiogram were 65 and 43 respectively. Conclusion: EBCT is a useful tool in the evaluation of patients with the syndrome of viscero-atrial heterotaxia

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

Ultrastructure of Reissner's membrane in the rabbit

DEFF Research Database (Denmark)

Qvortrup, K.; Rostgaard, Jørgen; Bretlau, P.

1994-01-01

Anatomy, Reissner's membrane, electron microscopy, tubulocisternal endoplasmic reticulum, subsurface cisterns, rabbit......Anatomy, Reissner's membrane, electron microscopy, tubulocisternal endoplasmic reticulum, subsurface cisterns, rabbit...

Atrial Function in Patients with Breast Cancer After Treatment with Anthracyclines

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Yalin Tolga Yaylali

Full Text Available Abstract Background: Atrial electromechanical delay (EMD is used to predict atrial fibrillation, measured by echocardiography. Objectives: The aim of this study was to assess atrial EMD and mechanical function after anthracycline-containing chemotherapy. Methods: Fifty-three patients with breast cancer (48 ± 8 years old who received 240 mg/m2of Adriamycin, 2400 mg/m2 of cyclophosphamide, and 960 mg/m2 of paclitaxel were included in this retrospective study, as were 42 healthy subjects (47 ± 9 years old. Echocardiographic measurements were performed 11 ± 7 months (median 9 months after treatment with anthracyclines. Results: Left intra-atrial EMD (11.4 ± 6.0 vs. 8.1 ± 4.9, p=0.008 and inter-atrial EMD (19.7 ± 7.4 vs. 14.7 ± 6.5, p=0.001 were prolonged; LA passive emptying volume and fraction were decreased (p=0.0001 and p=0.0001; LA active emptying volume and fraction were increased (p=0.0001 and p=0.0001; Mitral A velocity (0.8 ± 0.2 vs. 0.6 ± 0.2, p=0.0001 and mitral E-wave deceleration time (201.2 ± 35.6 vs. 163.7 ± 21.8, p=0.0001 were increased; Mitral E/A ratio (1.0 ± 0.3 vs. 1.3 ± 0.3, p=0.0001 and mitral Em (0.09 ± 0.03 vs. 0.11 ± 0.03, p=0.001 were decreased; Mitral Am (0.11 ± 0.02 vs. 0.09 ± 0.02, p=0.0001 and mitral E/Em ratio (8.8 ± 3.2 vs. 7.6 ± 2.6, p=0.017 were increased in the patients. Conclusions: In patients with breast cancer after anthracycline therapy: Left intra-atrial, inter-atrial electromechanical intervals were prolonged. Diastolic function was impaired. Impaired left ventricular relaxation and left atrial electrical conduction could be contributing to the development of atrial arrhythmias.

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure

NARCIS (Netherlands)

M. Rosa-Garrido (Manuel); Chapski, D.J. (Douglas J.); Schmitt, A.D. (Anthony D.); Kimball, T.H. (Todd H.); Karbassi, E. (Elaheh); Monte, E. (Emma); Balderas, E. (Enrique); Pellegrini, M. (Matteo); Shih, T.-T. (Tsai-Ting); Soehalim, E. (Elizabeth); D.A. Liem (David); Ping, P. (Peipei); N.J. Galjart (Niels); Ren, S. (Shuxun); Wang, Y. (Yibin); Ren, B. (Bing); Vondriska, T.M. (Thomas M.)

2017-01-01

textabstractBACKGROUND: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined.METHODS: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation

Left atrial thrombus following bilobectomy: a case report

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Kaya Ugur

2010-02-01

Full Text Available Abstract Introduction Left atrial free floating ball thrombus is a relatively rare event, especially without mitral valve disease. Case presentation A 61-year-old Turkish man was admitted to our hospital with a thrombus mass in his left atrium. Five months earlier, he had undergone right bilobectomy and superior bronchoplasty due to squamous cell carcinoma in the lung. The patient had no evidence of cardiac disease except atrial fibrillation and there were no defined embolizations. The thrombus mass was surgically removed. The patient was discharged from hospital on the sixth postoperative day. Conclusion Surgery with cardiopulmonary bypass is a safe method for treatment. The patient should be medicated with warfarin, especially in the presence of atrial fibrillation.

Aorto-right atrial fistula after Bentall repair.

Science.gov (United States)

Howard, Charles E; Velasco, Carlos E; Roullard, Christina P; Rafael, Aldo

2017-07-01

We describe a man with the Marfan syndrome and a prior ascending aortic aneurysm resection who presented with knee pain and concern of endocarditis. Transesophageal echocardiogram showed no vegetations, and computed tomography angiogram of the heart showed a possible pseudoaneurysm. Cardiac catheterization and aortogram revealed the diagnosis of an aorto-right atrial fistula, which was then operatively repaired. This case highlights the role that cardiac catheterization with aortogram can play in the detection of aorto-atrial fistula.

Percutaneous closure of the left atrial appendage with Watchman device: An option for patients with atrial fibrilation and high risk of bleeding with anticoagulation

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Sénior, Juan

2015-07-01

Full Text Available Atrial fibrillation is the most common arrhythmia found in clinical practice, with a population prevalence of 1% to 2%. Anticoagulation remains a fundamental part of treatment for the prevention of cerebrovascular events (stroke, but it is contraindicated in approximately 20% of patients. We report a case of non-valvular atrial fibrillation with high-risk score for stroke, a history of intracerebral bleeding, and very high risk of bleeding with long-term anticoagulation. Percutaneous closure of the left atrial appendage with the Watchman device was performed successfully without complications.