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Sample records for native atrial myocytes

  1. Evidence for functional expression of TRPM7 channels in human atrial myocytes.

    PubMed

    Zhang, Yan-Hui; Sun, Hai-Ying; Chen, Kui-Hao; Du, Xin-Ling; Liu, Bo; Cheng, Lik-Cheung; Li, Xin; Jin, Man-Wen; Li, Gui-Rong

    2012-09-01

    Transient receptor potential melastatin-7 (TRPM7) channels have been recently reported in human atrial fibroblasts and are believed to mediate fibrogenesis in human atrial fibrillation. The present study investigates whether TRPM7 channels are expressed in human atrial myocytes using whole-cell patch voltage-clamp, RT-PCR and Western blotting analysis. It was found that a gradually activated TRPM7-like current was recorded with a K(+)- and Mg(2+)-free pipette solution in human atrial myocytes. The current was enhanced by removing extracellular Ca(2+) and Mg(2+), and the current increase could be inhibited by Ni(2+) or Ba(2+). The TRPM7-like current was potentiated by acidic pH and inhibited by La(3+) and 2-aminoethoxydiphenyl borate. In addition, Ca(2+)-activated TRPM4-like current was recorded in human atrial myocytes with the addition of the Ca(2+) ionophore A23187 in bath solution. RT-PCR and Western immunoblot analysis revealed that in addition to TRPM4, TRPM7 channel current, mRNA and protein expression were evident in human atrial myocytes. Interestingly, TRPM7 channel protein, but not TRPM4 channel protein, was significantly increased in human atrial specimens from the patients with atrial fibrillation. Our results demonstrate for the first time that functional TRPM7 channels are present in human atrial myocytes, and the channel expression is upregulated in the atria with atrial fibrillation. PMID:22802050

  2. Characterization of Mg2+-regulated TRPM7-like current in human atrial myocytes

    PubMed Central

    2012-01-01

    Background TRPM7 (Transient Receptor Potential of the Melastatin subfamily) proteins are highly expressed in the heart, however, electrophysiological studies, demonstrating and characterizing these channels in human cardiomyocytes, are missing. Methods We have used the patch clamp technique to characterize the biophysical properties of TRPM7 channel in human myocytes isolated from right atria small chunks obtained from 116 patients in sinus rhythm during coronary artery and valvular surgery. Under whole-cell voltage-clamp, with Ca2+ and K+ channels blocked, currents were generated by symmetrical voltage ramp commands to potentials between -120 and +80 mV, from a holding potential of -80 mV. Results We demonstrate that activated native current has dual control by intracellular Mg2+ (free-Mg2+ or ATP-bound form), and shows up- or down-regulation by its low or high levels, respectively, displaying outward rectification in physiological extracellular medium. High extracellular Mg2+ and Ca2+ block the outward current, while Gd3+, SpM4+, 2-APB, and carvacrol inhibit both (inward and outward) currents. Besides, divalents also permeate the channel, and the efficacy sequence, at 20 mM, was Mg2+>Ni2+>Ca2+>Ba2+>Cd2+ for decreasing outward and Ni2+>Mg2+>Ba2+≥Ca2+>Cd2+ for increasing inward currents. The defined current bears many characteristics of heterologously expressed or native TRPM7 current, and allowed us to propose that current under study is TRPM7-like. However, the time of beginning and time to peak as well steady state magnitude (range from 1.21 to 11.63 pA/pF, ncells/patients = 136/77) of induced TRPM7-like current in atrial myocytes from different patients showed a large variability, while from the same sample of human atria all these parameters were very homogenous. We present new information that TRPM7-like current in human myocytes is less sensitive to Mg2+. In addition, in some myocytes (from 24 out of 77 patients) that current was already up

  3. Identification, localization and interaction of SNARE proteins in atrial cardiac myocytes.

    PubMed

    Peters, Christian G; Miller, Daniel F; Giovannucci, David R

    2006-03-01

    Atrial cardiac myocytes secrete the vasoactive hormone atrial natriuretic peptide (ANP) by both constitutive and regulated exocytotic fusion of ANP-containing large dense core vesicles (LDCV) with the sarcolemma. Detailed information, however, regarding the identity and function of specific membrane fusion proteins (SNARE proteins) involved in exocytosis in the endocrine heart is lacking. In the current study, we identified SNARE proteins and determined their association with ANP-containing secretory granules using primary cultures of neonatal and adult rat atrial cardiac myocytes. Using RT-PCR, cardiac myocytes were screened for SNARE and SNARE-associated transcripts. Identified SNARE proteins that have been implicated in exocytosis in neuroendocrine cells were further characterized by Western blot analysis. Functional interaction between SNARE proteins was demonstrated using immunoprecipitation. Using cell fractionation and immunocytochemical methods, it was revealed that VAMP-1, VAMP-2 and synaptotagmin-1 (the putative Ca(2+) sensor) localized to subpopulations of ANP-containing secretory granules in atrial myocytes. Currently, there is conflicting data regarding the role of Ca(2+) in ANP exocytosis. To judge whether secretory activity could be evoked by intracellular Ca(2+) elevation, time-resolved membrane capacitance measurements were used in combination with the flash photolysis of caged compounds to follow the exocytotic activity of single neonatal atrial myocytes. These studies demonstrated that multiple SNARE proteins are present in neonatal and adult cardiac myocytes and suggest the importance of Ca(2+) in exocytosis of ANP from neonatal atrial cardiac myocytes. PMID:16458920

  4. Functional Role and Mechanism of microRNA-28b in Atrial Myocyte in a Persistent Atrial Fibrillation Rat Model

    PubMed Central

    Wang, Yongbin; Kang, Weiqiang; Wang, Xu; Chen, Meina; Qin, Qiaoji; Guo, Minglei; Ge, Zhiming

    2016-01-01

    Background Persistent atrial fibrillation has been indicated to be related with microRNA-28b. However, the exact role of microRNA-28b in persistent atrial fibrillation needs to be further elucidated. Therefore, this study aimed to establish a rat model of persistent atrial fibrillation to investigate the level of microRNA-28b in atrial myocytes and to explore the molecular mechanism involved. Material/Methods A persistent atrial fibrillation model was established in rats by using chronic rapid atrial pacing induction. The size of the heart was measured by ultrasonic method. The expression of microRNA-28b in left atrial myocytes was quantified by RT-PCR. Cardiomyocytes were isolated and cultured to detect cell proliferation and apoptosis by MTT and flow cytometry, respectively. The specific inhibitor of ERK signaling pathway, PD98059, was used to further illustrate the role of ERK signaling pathway in the modulation of cardiomyocytes in persistent atrial fibrillation. Results MicroRNA-28b was up-regulated in the experimental rat model with persistent atrial fibrillation. The proliferation of cardiomyocytes was significantly inhibited with potentiated apoptosis. Blockage of the ERK pathway suppressed the microRNA-28b expression and inhibited cell apoptosis. Conclusions microRNA-28b-induced growth inhibition and cell apoptosis of atrial myocytes was observed in the rat model with persistent atrial fibrillation, via activation of the ERK signaling pathway. PMID:27574952

  5. Multimodality of Ca2+ signaling in rat atrial myocytes.

    PubMed

    Morad, Martin; Javaheri, Ashkan; Risius, Tim; Belmonte, Steve

    2005-06-01

    It has been suggested that the multiplicity of Ca(2+) signaling pathways in atrial myocytes may contribute to the variability of its function. This article reports on a novel Ca(2+) signaling cascade initiated by mechanical forces induced by "puffing" of solution onto the myocytes. Ca(i) transients were measured in fura-2 acetoxymethyl (AM) loaded cells using alternating 340- and 410-nm excitation waves at 1.2 kHz. Pressurized puffs of bathing solutions, applied by an electronically controlled micro-barrel system, activated slowly (approximately 300 ms) developing Ca(i) transients that lasted 1,693 +/- 68 ms at room temperature. Subsequent second and third puffs, applied at approximately 20 s intervals activated significantly smaller or no Ca(i) transients. Puff-triggered Ca(i) transients could be reactivated once again following caffeine (10 mM)-induced release of Ca(2+) from sarcoplasmic reticulum (SR). Puff-triggered Ca(i) transients were independent of [Ca(2+)](o), and activation of voltage-gated Ca(2+) or cationic stretch channels or influx of Ca(2+) on Na(+)/Ca(2+)exchanger, because puffing solution containing no Ca(2+), 10 microM diltiazem, 1 mM Cd(2+), 5 mM Ni(2+), or 100 microM Gd(3+) failed to suppress them. Puff-triggered Ca(i) transients were enhanced in paced compared to quiescent myocytes. Electrically activated Ca(i) transients triggered during the time course of puff-induced transients were unaltered, suggesting functionally separate Ca(2+) pools. Contribution of inositol 1,4,5-triphosphate (IP(3))-gated or mitochondrial Ca(2+) pools or modulation of SR stores by nitric oxide/nitric oxide synthase (NO/NOS) signaling were evaluated using 0.5 to 500 microM 2-aminoethoxydiphenyl borate (2-APB) and 0.1 to 1 microM carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and 1 mM Nomega-Nitro-L-arginine methyl ester (L-NAME) and 7-nitroindizole, respectively. Only FCCP appeared to significantly suppress the puff-triggered Ca(i) transients. It was

  6. Modulation of local Ca2+ release sites by rapid fluid puffing in rat atrial myocytes.

    PubMed

    Woo, Sun-Hee; Risius, Tim; Morad, Martin

    2007-04-01

    Atrial myocytes that lack t-tubules appear to have two functionally separate sarcoplasmic Ca2+ stores: a peripheral store associated with plasmalemmal L-type calcium channels and a central store with no apparent proximity to L-type calcium channels. Here we describe a set of calcium sparks and waves that are triggered by puffing of pressurized (200-400 mmH2O) bathing solutions onto resting isolated rat atrial myocytes. Puffing of pressurized (200 mmH2O) solutions, identical to those bathing the myocytes from distances of approximately 150 microm onto the surface of a single myocyte triggered or enhanced spontaneously occurring peripheral sparks by five- to six-fold and central Ca2+ sparks by two- to three-fold, without altering the unitary spark properties. Exposure to higher pressure flows (400 mmH2O) often triggered longitudinally spreading Ca2+ waves. These results suggest that pressurized flows may directly modulate Ca2+ signaling of atrial myocytes by activating the intracellular Ca2+ release sites. PMID:17087992

  7. Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

    PubMed Central

    Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

    2012-01-01

    The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

  8. High efficiency activation of L-type Ca2+ current by 5-HT in human atrial myocytes.

    PubMed

    Di Scala, Emmanuella; Findlay, Ian; Rose, Stephanie; Aupart, Michel; Argibay, Jorge; Cosnay, Pierre; Bozon, Veronique

    2004-01-01

    In human atrial myocytes, serotonin rather than sympathetic, stimulation is more frequently associated with atrial fibrillation. So does the arrhythmogenic effect of serotonin result from the mechanism of action of the receptor or the context of its action upon cardiac myocytes? The capacity of agonists to produce cAMP followed the sequence 5-HT < Iso < Forskolin to increase ICaL with 5-HT = Iso = Forskolin. The simultaneous application of threshold concentrations of 5-HT and Iso maximally increased ICaL. We will show that the effect of 5-HT upon human atrial myocytes is an imbalance between low production of cAMP and maximal activation of ICaL. PMID:15989080

  9. Diversity of atrial local Ca2+ signalling: evidence from 2-D confocal imaging in Ca2+-buffered rat atrial myocytes.

    PubMed

    Woo, Sun-Hee; Cleemann, Lars; Morad, Martin

    2005-09-15

    Atrial myocytes, lacking t-tubules, have two functionally separate groups of ryanodine receptors (RyRs): those at the periphery colocalized with dihydropyridine receptors (DHPRs), and those at the cell interior not associated with DHPRs. We have previously shown that the Ca(2+) current (I(Ca))-gated central Ca(2+) release has a fast component that is followed by a slower and delayed rising phase. The mechanisms that regulate the central Ca(2+) releases remain poorly understood. The fast central release component is highly resistant to dialysed Ca(2+) buffers, while the slower, delayed component is completely suppressed by such exogenous buffers. Here we used dialysis of Ca(2+) buffers (EGTA) into voltage-clamped rat atrial myocytes to isolate the fast component of central Ca(2+) release and examine its properties using rapid (240 Hz) two-dimensional confocal Ca(2+) imaging. We found two populations of rat atrial myocytes with respect to the ratio of central to peripheral Ca(2+) release (R(c/p)). In one population ('group 1', approximately 60% of cells), R(c/p) converged on 0.2, while in another population ('group 2', approximately 40%), R(c/p) had a Gaussian distribution with a mean value of 0.625. The fast central release component of group 2 cells appeared to result from in-focus Ca(2+) sparks on activation of I(Ca). In group 1 cells intracellular membranes associated with t-tubular structures were never seen using short exposures to membrane dyes. In most of the group 2 cells, a faint intracellular membrane staining was observed. Quantification of caffeine-releasable Ca(2+) pools consistently showed larger central Ca(2+) stores in group 2 and larger peripheral stores in group 1 cells. The R(c/p) was larger at more positive and negative voltages in group 1 cells. In contrast, in group 2 cells, the R(c/p) was constant at all voltages. In group 1 cells the gain of peripheral Ca(2+) release sites (Delta[Ca(2+)]/I(Ca)) was larger at -30 than at +20 mV, but

  10. The proarrhythmic antihistaminic drug terfenadine increases spontaneous calcium release in human atrial myocytes.

    PubMed

    Hove-Madsen, Leif; Llach, Anna; Molina, Cristina E; Prat-Vidal, Cristina; Farré, Jordi; Roura, Santiago; Cinca, Juan

    2006-12-28

    Spontaneous calcium release from the sarcoplasmic reticulum in cardiac myocytes plays a central role in cardiac arrhythmogenesis. Compounds intended for therapeutical use that interfere with intracellular calcium handling may therefore have an undesired proarrhythmic potential. Here we have used isolated human atrial myocytes to compare the effect of the proarrhythmic antihistaminic drug terfenadine with the non-proarrhythmic antihistaminic drugs fexofenadine and rupatadine on intracellular calcium homeostasis. Perforated patch-clamp technique was used to measure ionic currents and to detect spontaneous calcium release from the sarcoplasmic reticulum. Our results show that the compound terfenadine, with known arrhythmogenic effects, inhibits L-type calcium current (I(Ca)) with an IC(50) of 185 nM when cells are stimulated at 1.0 Hz. The inhibitory effect of 0.3 muM terfenadine increased from 19+/-4% at stimulation frequency of 0.2 Hz to 63+/-6% at 2.0 Hz. Moreover, terfenadine also increased spontaneous calcium release from the sarcoplasmic reticulum. At a concentration of 1 muM, terfenadine significantly increased the spontaneous Na-Ca exchange current (I(NCX)) frequency from 0.48+/-0.25 to 1.93+/-0.67 s(-1). In contrast, fexofenadine and rupatadine did not change I(Ca) or the frequency of spontaneous I(NCX). We conclude that the proarrhythmic antihistaminic drug terfenadine alters intracellular calcium handling in isolated human atrial myocytes. This experimental model may be suitable to screen for potential arrhythmogenic side-effects of compounds intended for therapeutical use. PMID:17078945

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

    PubMed

    Lombardo, Daniel M; Fenton, Flavio H; Narayan, Sanjiv M; Rappel, Wouter-Jan

    2016-08-01

    Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy. PMID:27494252

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

    PubMed Central

    Fenton, Flavio H.; Narayan, Sanjiv M.; Rappel, Wouter-Jan

    2016-01-01

    Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy. PMID:27494252

  13. Endothelin-stimulated secretion of natriuretic peptides by rat atrial myocytes is mediated by endothelin A receptors.

    PubMed

    Thibault, G; Doubell, A F; Garcia, R; Larivière, R; Schiffrin, E L

    1994-03-01

    Endothelin (ET), a potent vasoconstrictor peptide, is known to enhance the secretion of atrial natriuretic factor (ANF) by the heart. In the present study, we investigated the potency of ET isopeptides to stimulate ANF and brain natriuretic peptide (BNP) secretion in primary cultures of neonatal atrial myocytes, and we characterized the receptor mediating these effects. All ET isopeptides caused a twofold increase of ANF and BNP secretion with the following order of potency: ET-1 approximately ET-2 > sarafotoxin 6b > ET-3. Secretion of the natriuretic peptides was blocked by BQ-123, an ETA-receptor antagonist, but was not affected by either IRL-1620 or [Ala1,3,11,15]ET-1, two ETB-receptor agonists. ET receptors were localized by autoradiography on the surface of atrial myocytes, indicating that contaminating cells were not responsible for 125I-ET-1 binding. Competition binding analyses were then used to assess the ET-receptor subtype on atrial myocyte membrane preparations. A high-affinity (100 pmol/L) binding site with high density (approximately 1500 fmol/mg) was found to preferentially bind the ET isopeptides in the following order: ET-1 > or = ET-2 > or = sarafotoxin 6b > ET-3. Binding was totally displaced by BQ-123 but not by IRL-1620. The ET binding site therefore had the characteristics of an ETA-like receptor. Analysis by cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that it possessed a molecular mass of approximately 50 kD. Northern blot analysis of both ETA- and ETB-receptor mRNAs allowed only the detection of the former, indicating that the ETB receptor may be expressed in very small amounts. These results demonstrate that ANF and BNP secretion by atrial myocytes is enhanced by ET via binding to an ETA-like receptor. PMID:8118954

  14. Fibroblast–myocyte electrotonic coupling: Does it occur in native cardiac tissue?☆

    PubMed Central

    Kohl, Peter; Gourdie, Robert G.

    2014-01-01

    Heterocellular electrotonic coupling between cardiac myocytes and non-excitable connective tissue cells has been a long-established and well-researched fact in vitro. Whether or not such coupling exists in vivo has been a matter of considerable debate. This paper reviews the development of experimental insight and conceptual views on this topic, describes evidence in favour of and against the presence of such coupling in native myocardium, and identifies directions for further study needed to resolve the riddle, perhaps less so in terms of principal presence which has been demonstrated, but undoubtedly in terms of extent, regulation, patho-physiological context, and actual relevance of cardiac myocyte–non-myocyte coupling in vivo. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium." PMID:24412581

  15. Cyclic GMP regulation of the L-type Ca2+ channel current in human atrial myocytes

    PubMed Central

    Vandecasteele, Grégoire; Verde, Ignacio; Rücker-Martin, Catherine; Donzeau-Gouge, Patrick; Fischmeister, Rodolphe

    2001-01-01

    The regulation of the L-type Ca2+ current (ICa) by intracellular cGMP was investigated in human atrial myocytes using the whole-cell patch-clamp technique. Intracellular application of 0.5 μm cGMP produced a strong stimulation of basal ICa (+64 ± 5%, n = 60), whereas a 10-fold higher cGMP concentration induced a 2-fold smaller increase (+36 ± 8%, n = 35). The biphasic response of ICa to cGMP was not mimicked by the cGMP-dependent protein kinase (PKG) activator 8-bromoguanosine 3′,5′ cyclic monophosphate (8-bromo-cGMP, 0.5 or 5 μm), and was not affected by the PKG inhibitor KT 5823 (100 nm). In contrast, cGMP stimulation of ICa was abolished by intracellular perfusion with PKI (10 μm), a selective inhibitor of the cAMP-dependent protein kinase (PKA). Selective inhibition of the cGMP-inhibited phosphodiesterase (PDE3) by extracellular cilostamide (100 nm) strongly enhanced basal ICa in control conditions (+78 ± 13%, n = 7) but had only a marginal effect in the presence of intracellular cGMP (+22 ± 7% in addition to 0.5 μm cGMP, n = 11; +20 ± 22% in addition to 5 μm cGMP, n = 7). Application of erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA, 30 μm), a selective inhibitor of the cGMP-stimulated phosphodiesterase (PDE2), fully reversed the secondary inhibitory effect of 5 μm cGMP on ICa (+99 ± 16% stimulation, n = 7). Altogether, these data indicate that intracellular cGMP regulates basal ICa in human atrial myocytes in a similar manner to NO donors. The effect of cGMP involves modulation of the cAMP level and PKA activity via opposite actions of the nucleotide on PDE2 and PDE3. PMID:11389195

  16. Isoprenaline can activate the acetylcholine-induced K+ current in canine atrial myocytes via Gs-derived betagamma subunits.

    PubMed

    Sorota, S; Rybina, I; Yamamoto, A; Du, X Y

    1999-01-15

    1. G protein betagamma subunits activate the acetylcholine-induced potassium current IK,ACh. There is no evidence of specificity at the level of the betagamma subunits. Therefore all G protein-coupled receptors in atrial myocytes should be able to activate IK,ACh. Paradoxically, it is often stated that isoprenaline does not activate IK,ACh. Rationales to explain this negative result include insufficient concentrations of Gs in the atrium or restricted access of Gs-derived betagamma subunits to the IK,ACh channel. We took advantage of a non-specific increase in Gs that results after infection with adenovirus. 2. Adenoviral infection unmasked a 1 microM isoprenaline-induced IK,ACh which was prevented by propranolol. Isoprenaline occasionally activated IK,ACh in uninfected and freshly dissociated atrial myocytes but the effect was larger and more consistent in infected myocytes. 3. Pertussis toxin pretreatment (100 ng ml-1 overnight) did not block the effect of isoprenaline. The effect of isoprenaline became persistent if cells were pretreated with cholera toxin (200 ng nl-1). 4. Signal transduction events distal to adenylyl cyclase were not involved in isoprenaline-induced IK,ACh. Forskolin (10 microM) did not activate IK,ACh. Inhibition of adenylyl cyclase with cytoplasmic application of 300 microM 2'-deoxyadenosine 3'-monophosphate did not prevent the activation of IK,ACh by isoprenaline. 5. Cytoplasmic application of a betagamma binding peptide derived from the C terminus of beta-adrenergic receptor kinase 1 (50 microM) prevented the effect of isoprenaline on IK,ACh. The peptide did not prevent the stimulation of the L-type calcium current by isoprenaline. 6. The results indicate that beta-adrenoceptors can activate IK,ACh in atrial myocytes through the release of betagamma subunits from Gs. PMID:9852323

  17. Immunoreactive atrial natriuretic peptide and dopamine beta-hydroxylase in myocytes and chromaffin cells of the heart of the African lungfish, Protopterus aethiopicus.

    PubMed

    Larsen, T H; Helle, K B; Saetersdal, T

    1994-07-01

    The heart of the African lungfish, Protopterus aethiopicus, was examined for immunoreactive atrial natriuretic peptide (ANP) and dopamine beta-hydroxylase (D beta H) as markers for hormone secreting myocytes and chromaffin cells, respectively. Specific antibodies raised against rat alpha-ANP and rat D beta H were used for immunofluorescence microscopy and immunogold electron microscopy. D beta H-immunoreactive cells were restricted to subendocardial areas of the atrium whereas ANP immunoreactivity occurred throughout both the atrial and the ventricular myocardium, showing particularly strong staining intensity in the atrial myocytes. The granular ANP immunostaining in the atrial myocytes was frequently accumulated in the sarcoplasm. In the ventricular myocytes ANP immunoreactivity occurred as scattered granular staining throughout the sarcoplasm. ANP and D beta H immunofluorescence staining coincided with the presence of immunoreactive specific granules and secretory vesicles in the cardiac myocytes and chromaffin cells, respectively, as revealed by electron microscopy. The number of ANP-containing specific granules was generally high in the atrial myocytes, and they were frequently observed in clusters in subsarcolemmal areas. Granular frequency was considerably lower and the mean granular diameter was smaller (0.142 +/- 0.045 micron versus 0.213 +/- 0.049 micron) in the ventricular than in the atrial myocytes. The present results indicate that ANP and D beta H are phylogenetically highly conserved proteins from the dipnoi to the rat. The large amounts of ANP and of specific granules are consistent with an endocrine myocardium in the Protopterus heart. The presence of D beta H and secretory vesicles in the subendocardial chromaffin cells of the atrium suggests a local production of catecholamines from dopamine in the heart of this dipnoan. PMID:7926645

  18. Cellular Hypertrophy and Increased Susceptibility to Spontaneous Calcium-Release of Rat Left Atrial Myocytes Due to Elevated Afterload

    PubMed Central

    Zhang, Haifei; Cannell, Mark B.; Kim, Shang Jin; Watson, Judy J.; Norman, Ruth; Calaghan, Sarah C.; Orchard, Clive H.; James, Andrew F.

    2015-01-01

    Atrial remodeling due to elevated arterial pressure predisposes the heart to atrial fibrillation (AF). Although abnormal sarcoplasmic reticulum (SR) function has been associated with AF, there is little information on the effects of elevated afterload on atrial Ca2+-handling. We investigated the effects of ascending aortic banding (AoB) on Ca2+-handling in rat isolated atrial myocytes in comparison to age-matched sham-operated animals (Sham). Myocytes were either labelled for ryanodine receptor (RyR) or loaded with fluo-3-AM and imaged by confocal microscopy. AoB myocytes were hypertrophied in comparison to Sham controls (P<0.0001). RyR labeling was localized to the z-lines and to the cell edge. There were no differences between AoB and Sham in the intensity or pattern of RyR-staining. In both AoB and Sham, electrical stimulation evoked robust SR Ca2+-release at the cell edge whereas Ca2+ transients at the cell center were much smaller. Western blotting showed a decreased L-type Ca channel expression but no significant changes in RyR or RyR phosphorylation or in expression of Na+/Ca2+ exchanger, SR Ca2+ ATPase or phospholamban. Mathematical modeling indicated that [Ca2+]i transients at the cell center were accounted for by simple centripetal diffusion of Ca2+ released at the cell edge. In contrast, caffeine (10 mM) induced Ca2+ release was uniform across the cell. The caffeine-induced transient was smaller in AoB than in Sham, suggesting a reduced SR Ca2+-load in hypertrophied cells. There were no significant differences between AoB and Sham cells in the rate of Ca2+ extrusion during recovery of electrically-stimulated or caffeine-induced transients. The incidence and frequency of spontaneous Ca2+-transients following rapid-pacing (4 Hz) was greater in AoB than in Sham myocytes. In conclusion, elevated afterload causes cellular hypertrophy and remodeling of atrial SR Ca2+-release. PMID:26713852

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

    PubMed

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

    2016-01-01

    Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p < 0.01 for beta-adrenergic receptors and from 1.4 ± 0.1 to 0.5 ± 0.1 Hz; p < 0.05 for A2ARs. The latter was linked to increased spontaneous calcium release and after-depolarizations. Moreover, A2AR activation increased the fraction of non-uniformly responding cells in HL-1 myocyte cultures from 19 ± 3 to 51 ± 9 %; p < 0.02, and electrical mapping in perfused porcine atria revealed that adenosine induced electrical alternans at longer cycle lengths, doubled the fraction of electrodes showing alternation, and increased the amplitude of alternations. Importantly, protein kinase A inhibition increased the highest frequency where uniform responses could be maintained from 0.84 ± 0.12 to 1.86 ± 0.11 Hz; p < 0.001 and prevention of A2AR-activation with exogenous adenosine deaminase selectively increased the threshold from 0.8 ± 0.1 to 1.2 ± 0.1 Hz; p = 0.001 in myocytes from patients with AF. In conclusion, A2AR-activation promotes beat-to-beat irregularities in the calcium transient in human atrial myocytes, and prevention of A2AR activation may be a novel means to maintain uniform beat-to-beat responses at higher beating frequencies in patients with atrial fibrillation. PMID:26611209

  20. Effects of mitochondrial uncoupling on Ca2+ signaling during excitation-contraction coupling in atrial myocytes

    PubMed Central

    Zima, Aleksey V.; Pabbidi, Malikarjuna R.; Lipsius, Stephen L.

    2013-01-01

    Mitochondria play an important role in intracellular Ca2+ concentration ([Ca2+]i) regulation in the heart. We studied sarcoplasmic reticulum (SR) Ca2+ release in cat atrial myocytes during depolarization of mitochondrial membrane potential (ΔΨm) induced by the protonophore FCCP. FCCP caused an initial decrease of action potential-induced Ca2+ transient amplitude and frequency of spontaneous Ca2+ waves followed by partial recovery despite partially depleted SR Ca2+ stores. In the presence of oligomycin, FCCP only exerted a stimulatory effect on Ca2+ transients and Ca2+ wave frequency, suggesting that the inhibitory effect of FCCP was mediated by ATP consumption through reverse-mode operation of mitochondrial F1F0-ATPase. ΔΨm depolarization was accompanied by cytosolic acidification, increases of diastolic [Ca2+]i, intracellular Na+ concentration ([Na+]i), and intracellular Mg2+ concentration ([Mg2+]i), and a decrease of intracellular ATP concentration ([ATP]i); however, glycolytic ATP production partially compensated for the exhaustion of mitochondrial ATP supplies. In conclusion, the initial inhibition of Ca2+ transients and waves resulted from suppression of ryanodine receptor SR Ca2+ release channel activity by a decrease in [ATP], an increase of [Mg2+]i, and cytoplasmic acidification. The later stimulation resulted from reduced mitochondrial Ca2+ buffering and cytosolic Na+ and Ca2+ accumulation, leading to enhanced Ca2+-induced Ca2+ release and spontaneous Ca2+ release in the form of Ca2+ waves. ΔΨm depolarization and the ensuing consequences of mitochondrial uncoupling observed here (intracellular acidification, decrease of [ATP]i, increase of [Na+]i and [Mg2+]i, and Ca2+ overload) are hallmarks of ischemia. These findings may therefore provide insight into the consequences of mitochondrial uncoupling for ion homeostasis, SR Ca2+ release, and excitation-contraction coupling in ischemia at the cellular and subcellular level. PMID:23376829

  1. High-fat diet-dependent modulation of the delayed rectifier K(+) current in adult guinea pig atrial myocytes.

    PubMed

    Aromolaran, Ademuyiwa S; Colecraft, Henry M; Boutjdir, Mohamed

    2016-06-01

    Obesity is associated with hyperlipidemia, electrical remodeling of the heart, and increased risk of supraventricular arrhythmias in both male and female patients. The delayed rectifier K(+) current (IK), is an important regulator of atrial repolarization. There is a paucity of studies on the functional role of IK in response to obesity. Here, we assessed the obesity-mediated functional modulation of IK in low-fat diet (LFD), and high-fat diet (HFD) fed adult guinea pigs. Guinea pigs were randomly divided into control and obese groups fed, ad libitum, with a LFD (10 kcal% fat) or a HFD (45 kcal% fat) respectively. Action potential duration (APD), and IK were studied in atrial myocytes and IKr and IKs in HEK293 cells using whole-cell patch clamp electrophysiology. HFD guinea pigs displayed a significant increase in body weight, total cholesterol and total triglycerides within 50 days. Atrial APD at 30% (APD30) and 90% (APD90) repolarization were shorter, while atrial IK density was significantly increased in HFD guinea pigs. Exposure to palmitic acid (PA) increased heterologously expressed IKr and IKs densities, while oleic acid (OA), severely reduced IKr and had no effect on IKs. The data are first to show that in obese guinea pigs abbreviated APD is due to increased IK density likely through elevations of PA. Our findings may have crucial implications for targeted treatment options for obesity-related arrhythmias. PMID:27130822

  2. MMP9 Rs3918242 Polymorphism Affects Tachycardia-Induced MMP9 Expression in Cultured Atrial-Derived Myocytes but Is Not a Risk Factor for Atrial Fibrillation among the Taiwanese.

    PubMed

    Hsiao, Fu-Chih; Yeh, Yung-Hsin; Chen, Wei-Jan; Chan, Yi-Hsin; Kuo, Chi-Tai; Wang, Chun-Li; Chang, Chi-Jen; Tsai, Hsin-Yi; Tsai, Feng-Chun; Hsu, Lung-An

    2016-01-01

    Matrix metalloproteinase (MMP) plays an important role in the pathogenesis of atrial fibrillation (AF). The MMP9 promoter has a functional polymorphism rs3918242 that can regulate the level of gene transcription. This study recruited 200 AF patients and 240 controls. The MMP9 rs3918242 was examined by polymerase chain reactions. HL-1 atrial myocytes were cultured and electrically stimulated. Right atrial appendages were obtained from six patients with AF and three controls with sinus rhythm undergoing open heart surgery. The MMP9 expression and activity were determined using immunohistochemical analysis and gelatin zymography, respectively. Rapid pacing induces MMP9 secretion from HL-1 myocytes in a time- and dose-dependent manner. The responsiveness of MMP9 transcriptional activity to tachypacing was significantly enhanced by rs3918242. The expression of MMP9 was increased in fibrillating atrial tissue than in sinus rhythm. However, the distribution of rs3918242 genotypes and allele frequencies did not significantly differ between the control and AF groups. HL-1 myocyte may secrete MMP9 in response to rapid pacing, and the secretion could be modulated by rs3918242. Although the MMP9 expression of human atrial myocyte is associated with AF, our study did not support the association of susceptibility to AF among Taiwanese subjects with the MMP9 rs3918242 polymorphism. PMID:27070579

  3. MMP9 Rs3918242 Polymorphism Affects Tachycardia-Induced MMP9 Expression in Cultured Atrial-Derived Myocytes but Is Not a Risk Factor for Atrial Fibrillation among the Taiwanese

    PubMed Central

    Hsiao, Fu-Chih; Yeh, Yung-Hsin; Chen, Wei-Jan; Chan, Yi-Hsin; Kuo, Chi-Tai; Wang, Chun-Li; Chang, Chi-Jen; Tsai, Hsin-Yi; Tsai, Feng-Chun; Hsu, Lung-An

    2016-01-01

    Matrix metalloproteinase (MMP) plays an important role in the pathogenesis of atrial fibrillation (AF). The MMP9 promoter has a functional polymorphism rs3918242 that can regulate the level of gene transcription. This study recruited 200 AF patients and 240 controls. The MMP9 rs3918242 was examined by polymerase chain reactions. HL-1 atrial myocytes were cultured and electrically stimulated. Right atrial appendages were obtained from six patients with AF and three controls with sinus rhythm undergoing open heart surgery. The MMP9 expression and activity were determined using immunohistochemical analysis and gelatin zymography, respectively. Rapid pacing induces MMP9 secretion from HL-1 myocytes in a time- and dose-dependent manner. The responsiveness of MMP9 transcriptional activity to tachypacing was significantly enhanced by rs3918242. The expression of MMP9 was increased in fibrillating atrial tissue than in sinus rhythm. However, the distribution of rs3918242 genotypes and allele frequencies did not significantly differ between the control and AF groups. HL-1 myocyte may secrete MMP9 in response to rapid pacing, and the secretion could be modulated by rs3918242. Although the MMP9 expression of human atrial myocyte is associated with AF, our study did not support the association of susceptibility to AF among Taiwanese subjects with the MMP9 rs3918242 polymorphism. PMID:27070579

  4. Cytosolic and nuclear calcium signaling in atrial myocytes: IP3-mediated calcium release and the role of mitochondria

    PubMed Central

    Hohendanner, Felix; Maxwell, Joshua T; Blatter, Lothar A

    2015-01-01

    In rabbit atrial myocytes Ca signaling has unique features due to the lack of transverse (t) tubules, the spatial arrangement of mitochondria and the contribution of inositol-1,4,5-trisphosphate (IP3) receptor-induced Ca release (IICR). During excitation-contraction coupling action potential-induced elevation of cytosolic [Ca] originates in the cell periphery from Ca released from the junctional sarcoplasmic reticulum (j-SR) and then propagates by Ca-induced Ca release from non-junctional (nj-) SR toward the cell center. The subsarcolemmal region between j-SR and the first array of nj-SR Ca release sites is devoid of mitochondria which results in a rapid propagation of activation through this domain, whereas the subsequent propagation through the nj-SR network occurs at a velocity typical for a propagating Ca wave. Inhibition of mitochondrial Ca uptake with the Ca uniporter blocker Ru360 accelerates propagation and increases the amplitude of Ca transients (CaTs) originating from nj-SR. Elevation of cytosolic IP3 levels by rapid photolysis of caged IP3 has profound effects on the magnitude of subcellular CaTs with increased Ca release from nj-SR and enhanced CaTs in the nuclear compartment. IP3 uncaging restricted to the nucleus elicites ‘mini’-Ca waves that remain confined to this compartment. Elementary IICR events (Ca puffs) preferentially originate in the nucleus in close physical association with membrane structures of the nuclear envelope and the nucleoplasmic reticulum. The data suggest that in atrial myocytes the nucleus is an autonomous Ca signaling domain where Ca dynamics are primarily governed by IICR. PMID:25891132

  5. Shear stress induces a longitudinal Ca(2+) wave via autocrine activation of P2Y1 purinergic signalling in rat atrial myocytes.

    PubMed

    Kim, Joon-Chul; Woo, Sun-Hee

    2015-12-01

    Atrial myocytes are exposed to shear stress during the cardiac cycle and haemodynamic disturbance. In response, they generate a longitudinally propagating global Ca(2+) wave. Here, we investigated the cellular mechanisms underlying the shear stress-mediated Ca(2+) wave, using two-dimensional confocal Ca(2+) imaging combined with a pressurized microflow system in single rat atrial myocytes. Shear stress of ∼16 dyn cm(-2) for 8 s induced ∼1.2 aperiodic longitudinal Ca(2+) waves (∼79 μm s(-1)) with a delay of 0.2-3 s. Pharmacological blockade of ryanodine receptors (RyRs) or inositol 1,4,5-trisphosphate receptors (IP3 Rs) abolished shear stress-induced Ca(2+) wave generation. Furthermore, in atrial myocytes from type 2 IP3R (IP3R2) knock-out mice, shear stress failed to induce longitudinal Ca(2+) waves. The phospholipase C (PLC) inhibitor U73122, but not its inactive analogue U73343, abolished the shear-induced longitudinal Ca(2+) wave. However, pretreating atrial cells with blockers for stretch-activated channels, Na(+)-Ca(2+) exchanger, transient receptor potential melastatin subfamily 4, or nicotinamide adenine dinucleotide phosphate oxidase did not suppress wave generation under shear stress. The P2 purinoceptor inhibitor suramin, and the potent P2Y1 receptor antagonist MRS 2179, both suppressed the Ca(2+) wave, whereas the P2X receptor antagonist, iso-PPADS, did not alter it. Suppression of gap junction hemichannels permeable to ATP or extracellular application of ATP-metabolizing apyrase inhibited the wave. Removal of external Ca(2+) to enhance hemichannel opening facilitated the wave generation. Our data suggest that longitudinally propagating, regenerative Ca(2+) release through RyRs is triggered by P2Y1-PLC-IP3R2 signalling that is activated by gap junction hemichannel-mediated ATP release in atrial myocytes under shear stress. PMID:26377030

  6. Calcium transients caused by calcium entry are influenced by the sarcoplasmic reticulum in guinea-pig atrial myocytes.

    PubMed Central

    Lipp, P; Pott, L; Callewaert, G; Carmeliet, E

    1992-01-01

    1. Single atrial myocytes obtained by enzyme perfusion from hearts of adult guinea-pigs were investigated using whole-cell voltage clamp and Indo-1 micro-fluorometry. 2. In myocytes loaded with a solution containing citrate as a low-affinity, non-saturable Ca2+ chelator, two types of [Ca2+]i transients could be recorded during repetitive activation of L-type Ca2+ current. Both large and small [Ca2+]i transients occurred; large transients reached peak values of about 1 microM, and small transients were about 100 nM or less in amplitude. 3. In the case of the large transients, peak [Ca2+]i was usually reached with a variable delay after repolarization from a voltage step that activated calcium current (ICa). For the small transients the rise in [Ca2+]i paralleled ICa. Upon repolarization [Ca2+]i started to decay. 4. The small transients reflect entry of Ca2+ through Ca2+ channels (entry transients), whereas the large transients are due to entry and release from the sarcoplasmic reticulum (release transients). 5. The entry transients displayed a positive staircase pattern during trains of depolarizing voltage steps despite constant or even decreasing amplitude of ICa. The steepness of the staircase was increased by elevation of [Ca2+]o. Entry transients were always smallest immediately after a release transient. 6. After functional removal of the sarcoplasmic reticulum by caffeine (1-5 mM) the staircase pattern of the transients reflecting Ca2+ entry was abolished. 7. It is concluded that the staircase pattern is due to rapid uptake by the sarcoplasmic reticulum of Ca2+ entering the cell, resulting in an attenuation of the signal. The attenuation is strongest shortly after a release signal, when the rate of sequestration of Ca2+ by the SR should be highest. 8. Evidence is provided that a compartment of the SR is involved in attenuation of the entry transients. This compartment has been identified recently as a peripheral release compartment. PMID:1335504

  7. Ionic currents during sustained pacemaker activity in rabbit sino-atrial myocytes.

    PubMed Central

    Zaza, A; Micheletti, M; Brioschi, A; Rocchetti, M

    1997-01-01

    1. The contribution of various ionic currents to diastolic depolarization (DD) in rabbit sinoatrial myocytes was evaluated by the action potential clamp technique. Individual currents were identified, during sustained pacemaking activity reproduced under voltage clamp conditions, according to their sensitivity to specific channel blockers. 2. The current sensitive to dihydropyridines (DHPs), blockers of L-type Ca2+ current (ICa,L), was small and outward during most of DD. Diastolic DHP-sensitive current was affected by changes in the driving force for K+, but it was insensitive to E-4031, which blocks the current termed IK,r; it was abolished by cell dialysis with a Ca2+ chelator. 3. The current sensitive to 2 mM Cs+ (ICs), a blocker of hyperpolarization-activated current (I(f)), was inward during the whole DD and it was substantially larger than the net inward current flowing during this phase. However, diastolic IK,r, identified in the same cells as the current sensitive to the blocker E-4031, exceeded ICs 2-fold. 4. These findings suggest that: (a) Ca2+ influx during the pacemaker cycle increases a K+ conductance, thus inverting the direction of the net current generated by L-type Ca2+ channel activity during DD; (b) the magnitude of I(f) would be adequate to account fully for DD; however, the coexistence of a larger IK,r suggests that other channels besides I(f) contribute inward current during this phase. PMID:9457645

  8. Activation of f-channels by cAMP analogues in macropatches from rabbit sino-atrial node myocytes.

    PubMed Central

    Bois, P; Renaudon, B; Baruscotti, M; Lenfant, J; DiFrancesco, D

    1997-01-01

    1. The action of the two diastereometric phosphorothioate derivatives of cAMP, Rp-cAMPs and Sp-cAMPs, was investigated on hyperpolarization-activated 'pacemaker' current (i(f)) recorded in inside-out macropatches from rabbit sino-atrial (SA) node myocytes. 2. When superfused on the intracellular side of f-channels at the concentration of 10 microM, both cAMP derivatives accelerated i(f) activation; their action was moderately less pronounced than that due to the same concentration of cAMP. 3. The measurement of the i(f) conductance-voltage relation by voltage ramp protocols indicated that both cAMP analogues shift the activation curve of i(f) to more positive voltages with no change in maximal (fully activated) conductance. 4. Dose-response relationships of the shift of the i(f) activation curve showed that both Rp-cAMPs and Sp-cAMPs act as agonists in the cAMP-dependent direct f-channel activation. Fitting data to the Hill equation resulted in maximal shifts of 9.6 and 9.5 mV, apparent dissociation constants of 0.82 and 5.4 microM, and Hill coefficients of 0.82 and 1.12 for Sp-cAMPs and Rp-cAMPs, respectively. 5. The activating action of Rp-cAMPs, a known antagonist of cAMP in the activation of cAMP-dependent protein kinase, confirms previously established evidence that f-channel activation does not involve phosphorylation. These results also suggest that the cAMP binding site of f-channels may be structurally similar to the cyclic nucleotide binding site of olfactory receptor channels. PMID:9218217

  9. Direct Evidence for Microdomain-Specific Localization and Remodeling of Functional L-Type Calcium Channels in Rat and Human Atrial Myocytes

    PubMed Central

    Glukhov, Alexey V.; Balycheva, Marina; Sanchez-Alonso, Jose L.; Ilkan, Zeki; Alvarez-Laviada, Anita; Bhogal, Navneet; Diakonov, Ivan; Schobesberger, Sophie; Sikkel, Markus B.; Bhargava, Anamika; Faggian, Giuseppe; Punjabi, Prakash P.; Houser, Steven R.

    2015-01-01

    Background— Distinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption of cellular structure may affect LTCC in a microdomain-specific manner and contribute to the pathophysiology of cardiac diseases, especially in cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs). Methods and Results— Isolated rat and human AMs were characterized by scanning ion conductance, confocal, and electron microscopy. Half of AMs possessed T-tubules and structured topography, proportional to cell width. A bigger proportion of myocytes in the left atrium had organized T-tubules and topography than in the right atrium. Super-resolution scanning patch clamp showed that LTCCs distribute equally in T-tubules and crest areas of the sarcolemma, whereas, in ventricular myocytes, LTCCs primarily cluster in T-tubules. Rat, but not human, T-tubule LTCCs had open probability similar to crest LTCCs, but exhibited ≈40% greater current. Optical mapping of Ca2+ transients revealed that rat AMs presented ≈3-fold as many spontaneous Ca2+ release events as ventricular myocytes. Occurrence of crest LTCCs and spontaneous Ca2+ transients were eliminated by either a caveolae-targeted LTCC antagonist or disrupting caveolae with methyl-β-cyclodextrin, with an associated ≈30% whole-cell ICa,L reduction. Heart failure (16 weeks post–myocardial infarction) in rats resulted in a T-tubule degradation (by ≈40%) and significant elevation of spontaneous Ca2+ release events. Although heart failure did not affect LTCC occurrence, it led to ≈25% decrease in T-tubule LTCC amplitude. Conclusions— We provide the first direct evidence for the existence of 2 distinct subpopulations of functional LTCCs in rat and human AMs, with their biophysical properties modulated in heart failure in a microdomain-specific manner. PMID:26450916

  10. Native atrial septal restriction after Fontan palliation successfully treated with transcatheter Diabolo stent

    PubMed Central

    Aldoss, Osamah; Reinking, Benjamin E; Divekar, Abhay

    2016-01-01

    A 6-year-old male child born with hypoplastic left heart syndrome (HLHS) was palliated with an extracardiac nonfenestrated Fontan procedure (18-mm Gore-Tex tube graft). He developed low-pressure (mean Fontan pressure 10 mmHg) protein-losing enteropathy 6 months after Fontan palliation. After initially responding to medical therapy and transcatheter pulmonary artery stent implantation, he developed medically refractory protein-losing enteropathy. At this time, his transthoracic echocardiogram showed new restriction across his native atrial septum with an 8 mmHg mean gradient. Cardiac catheterization now showed high-pressure (mean Fontan pressure 18-20 mmHg) protein-losing enteropathy and a new 6 mmHg mean gradient across the atrial septum. To avoid cardiopulmonary bypass, he underwent successful transcatheter relief of atrial septal restriction and creation of a fenestration with rapid clinical and biochemical improvement of his protein-losing enteropathy. PMID:27011693

  11. Ca2+ current-gated focal and local Ca2+ release in rat atrial myocytes: evidence from rapid 2-D confocal imaging.

    PubMed

    Woo, Sun-Hee; Cleemann, Lars; Morad, Martin

    2002-09-01

    In atrial myocytes immunocytochemistry has shown two groups of ryanodine receptors (RyRs): those at the periphery colocalized with dihydropyridine receptors (DHPRs) and those at the cell interior not associated with DHPRs. The extent to which the two sets of RyRs are controlled by Ca2+ current (I(Ca)) or Ca2+ diffusion remains to be determined. Here, using rapid (240 Hz) two-dimensional confocal Ca2+ imaging in rat atrial myocytes, we examine directly the role of I(Ca) on the two-dimensional patterns of local and focal Ca2+ releases. I(Ca) evoked peripheral Ca2+ release within 1-4 ms, causing a rapid monophasic local rise of Ca2+, which then propagated into the cell interior along sarcomeric lines (approximately 2 microm) with a velocity of approximately 230 microm s(-1), even though we found no evidence for organized t-tubules using di-8-ANEPPS staining. I(Ca)-triggered Ca2+ release in the cell centre, on the other hand, had both a rapid (12 ms) and slower delayed components (12-50 ms). The voltage dependence of peripheral Ca2+ release and the two components of central release was bell shaped, and the magnitude of each release component was linearly related to I(Ca). Premature termination (2-10 ms) of I(Ca) was equally effective in abbreviating both the peripheral and slow central Ca2+ release. High concentration of Ca2+ buffers (2-5 mM EGTA plus 1 mM fluo-3) completely abolished the I(Ca)-gated propagation wave and the slow delayed component of Ca2+ release, but had little or no effect on the rapid component of central release. The efficacy of I(Ca) to trigger Ca2+ release in periphery of the myocyte was approximately 5 times higher than in the centre, consistent with the smaller measured central Ca2+ release. The quantification of central Ca2+ release as a function of peripheral release suggests a cooperative gating mechanism(s) for central release. These findings indicate that both I(Ca) and diffusion of Ca2+ from the peripheral sites contribute to the gating

  12. The role of inositol 1,4,5-trisphosphate receptors in Ca(2+) signalling and the generation of arrhythmias in rat atrial myocytes.

    PubMed

    Mackenzie, Lauren; Bootman, Martin D; Laine, Mika; Berridge, Michael J; Thuring, Jan; Holmes, Andrew; Li, Wen-Hong; Lipp, Peter

    2002-06-01

    Various cardio-active stimuli, including endothelin-1 (ET-1), exhibit potent arrhythmogenicity, but the underlying cellular mechanisms of their actions are largely unclear. We used isolated rat atrial myocytes and related changes in their subcellular Ca(2+) signalling to the ability of various stimuli to induce diastolic, premature extra Ca(2+) transients (ECTs). For this, we recorded global and spatially resolved Ca(2+) signals in indo-1- and fluo-4-loaded atrial myocytes during electrical pacing. ET-1 exhibited a higher arrhythmogenicity (arrhythmogenic index; ratio of number of ECTs over fold-increase in Ca(2+) response, 8.60; n = 8 cells) when compared with concentrations of cardiac glycosides (arrhythmogenic index, 4.10; n = 8 cells) or the beta-adrenergic agonist isoproterenol (arrhythmogenic index, 0.11; n = 6 cells) that gave similar increases in the global Ca(2+) responses. Seventy-five percent of the ET-1-induced arrhythmogenic Ca(2+) transients were accompanied by premature action potentials, while for digoxin this proportion was 25 %. The beta-adrenergic agonist failed to elicit a significant number of ECTs. Direct activation of inositol 1,4,5-trisphosphate (InsP(3)) receptors with a membrane-permeable InsP(3) ester (InsP(3) BM) mimicked the effect of ET-1 (arrhythmogenic index, 14.70; n = 6 cells). Inhibition of InsP(3) receptors using 2 microM 2-aminoethoxydiphenyl borate, which did not display any effects on Ca(2+) signalling under control conditions, specifically suppressed the arrhythmogenic action of ET-1 and InsP(3) BM. Immunocytochemistry indicated a co-localisation of peripheral, junctional ryanodine receptors with InsP(3)Rs. Thus, the pronounced arrhythmogenic potency of ET-1 is due to the spatially specific recruitment of Ca(2+) sparks by subsarcolemmal InsP(3)Rs. Summation of such sparks efficiently generates delayed after depolarisations that trigger premature action potentials. We conclude that the particular spatial profile of cellular Ca

  13. 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

    SciTech Connect

    Liang, B.T.

    1989-06-01

    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).

  14. Ins(1,4,5)P3 interacts with PIP2 to regulate activation of TRPC6/C7 channels by diacylglycerol in native vascular myocytes

    PubMed Central

    Ju, Min; Shi, Jian; Saleh, Sohag N; Albert, Anthony P; Large, William A

    2010-01-01

    We investigated synergism between inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG) on TRPC6-like channel activity in rabbit portal vein myocytes using single channel recording and immunoprecipitation techniques. Ins(1,4,5)P3 at 10 μm increased 3-fold TRPC6-like activity induced by 10 μm 1-oleoyl-2-acetyl-sn-glycerol (OAG), a DAG analogue. Ins(1,4,5)P3 had no effect on OAG-induced TRPC6 activity in mesenteric artery myocytes. Anti-TRPC6 and anti-TRPC7 antibodies blocked channel activity in portal vein but only anti-TRPC6 inhibited activity in mesenteric artery. TRPC6 and TRPC7 proteins strongly associated in portal vein but only weakly associated in mesenteric artery tissue lysates. Therefore in portal vein the conductance consists of TRPC6/C7 subunits, while OAG activates a homomeric TRPC6 channel in mesenteric artery myocytes. Wortmannin at 20 μm reduced phosphatidylinositol 4,5-bisphosphate (PIP2) association with TRPC6 and TRPC7, and produced a 40-fold increase in OAG-induced TRPC6/C7 activity. Anti-PIP2 antibodies evoked TRPC6/C7 activity, which was blocked by U73122, a phospholipase C inhibitor. DiC8-PIP2, a water-soluble PIP2 analogue, inhibited OAG-induced TRPC6/C7 activity with an IC50 of 0.74 μm. Ins(1,4,5)P3 rescued OAG-induced TRPC6/C7 activity from inhibition by diC8-PIP2 in portal vein myocytes, and this was not prevented by the Ins(1,4,5)P3 receptor antagonist heparin. In contrast, Ins(1,4,5)P3 did not overcome diC8-PIP2-induced inhibition of TRPC6 activity in mesenteric artery myocytes. 2,3,6-Tri-O-butyryl-Ins(1,4,5)P3/AM (6-Ins(1,4,5)P3), a cell-permeant analogue of Ins(1,4,5)P3, at 10 μm increased TRPC6/C7 activity in portal vein and reduced association between TRPC7 and PIP2, but not TRPC6 and PIP2. In contrast, 10 μm OAG reduced association between TRPC6 and PIP2, but not between TRPC7 and PIP2. The present work provides the first evidence that Ins(1,4,5)P3 modulates native TRPC channel activity through removal of the

  15. Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both PIP3 and PIP2 in rabbit coronary artery myocytes

    PubMed Central

    Saleh, Sohag N; Albert, Anthony P; Large, William A

    2009-01-01

    We investigate activation mechanisms of native TRPC1/C5/C6 channels (termed TRPC1 channels) by stimulation of endothelin-1 (ET-1) receptor subtypes in freshly dispersed rabbit coronary artery myocytes using single channel recording and immunoprecipitation techniques. ET-1 evoked non-selective cation channel currents with a unitary conductance of 2.6 pS which were not inhibited by either ETA or ETB receptor antagonists, respectively BQ-123 and BQ788, when administered separately. However, in the presence of both antagonists, ET-1-evoked channel activity was abolished indicating that both ETA and ETB receptor stimulation activate this conductance. Stimulation of both ETA and ETB receptors evoked channel activity which was inhibited by the protein kinase C (PKC) inhibitor chelerythrine and by anti-TRPC1 antibodies indicating that activation of both receptor subtypes causes TRPC1 channel activation by a PKC-dependent mechanism. ETA receptor-mediated TRPC1 channel activity was selectively inhibited by phosphoinositol-3-kinase (PI-3-kinase) inhibitors wortmannin (50 nm) and PI-828 and by antibodies raised against phosphoinositol-3,4,5-trisphosphate (PIP3), the product of PI-3-kinase-mediated phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2). Moreover, exogenous application of diC8-PIP3 stimulated PKC-dependent TRPC1 channel activity. These results indicate that stimulation of ETA receptors evokes PKC-dependent TRPC1 channel activity through activation of PI-3-kinase and generation of PIP3. In contrast, ETB receptor-mediated TRPC1 channel activity was inhibited by the PI-phospholipase C (PI-PLC) inhibitor U73122. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), an analogue of diacylglycerol (DAG), which is a product of PI-PLC, also activated PKC-dependent TRPC1 channel activity. OAG-induced TRPC1 channel activity was inhibited by anti-phosphoinositol-4,5-bisphosphate (PIP2) antibodies and high concentrations of wortmannin (20 μm) which depleted tissue PIP2 levels. In

  16. 5-azacytidine promotes the transdifferentiation of cardiac cells to skeletal myocytes.

    PubMed

    Kaur, Keerat; Yang, Jinpu; Eisenberg, Carol A; Eisenberg, Leonard M

    2014-10-01

    The DNA methylation inhibitor 5-azacytidine is widely used to stimulate the cardiac differentiation of stem cells. However, 5-azacytidine has long been employed as a tool for stimulating skeletal myogenesis. Yet, it is unclear whether the ability of 5-azacytidine to promote both cardiac and skeletal myogenesis is dependent strictly on the native potential of the starting cell population or if this drug is a transdifferentiation agent. To address this issue, we examined the effect of 5-azacytidine on cultures of adult mouse atrial tissue, which contains cardiac but not skeletal muscle progenitors. Exposure to 5-azacytidine caused atrial cells to elongate and increased the presence of fat globules within the cultures. 5-Azacytidine also induced expression of the skeletal myogenic transcription factors MyoD and myogenin. 5-Azacytidine pretreatments allowed atrial cells to undergo adipogenesis or skeletal myogenesis when subsequently cultured with either insulin and dexamethasone or low-serum media, respectively. The presence of skeletal myocytes in atrial cultures was indicated by dual staining for myogenin and sarcomeric α-actin. These data demonstrate that 5-azacytidine converts cardiac cells to noncardiac cell types and suggests that this drug has a compromised efficacy as a cardiac differentiation factor. PMID:25090621

  17. Differential control of the hyperpolarization-activated current (i(f)) by cAMP gating and phosphatase inhibition in rabbit sino-atrial node myocytes.

    PubMed Central

    Accili, E A; Redaelli, G; DiFrancesco, D

    1997-01-01

    1. The actions of the phosphatase inhibitor calyculin A on the hyperpolarization-activated cardiac 'pacemaker' current (i(f)) were determined in single cells isolated from the sino-atrial (SA) node of the rabbit. 2. Cells were incubated for 8 min in Tyrode solution containing calyculin A (0.5 microM) and then superfused with normal Tyrode solution. The mean normalized i(f) measured in eight cells at mid-activation voltages during and after exposure to calyculin A increased maximally by 47% with a time constant of 466 s, a time much longer than that required for cAMP-mediated i(f) stimulation (about 8 s). 3. In two-pulse protocols, calyculin A treatment increased i(f) at full as well as at mid-activation voltages, indicating a higher i(f) conductance. 4. Measurement of the conductance-voltage (gf(V)) relation by voltage ramp protocols confirmed a conductance increase by calyculin A, with no significant change in the position of the activation curve on the voltage axis. Data pooled together from ramp and two-pulse protocols yielded a calyculin A-induced increase in fully activated i(f) conductance of 39.6 +/- 6.4% (n = 16 cells). 5. The positive and negative shift of i(f) voltage dependence in response to beta-adrenergic (1 microM isoprenaline) and muscarinic stimulation (1 microM acetylcholine), respectively, was preserved after the calyculin A-induced increase in conductance. The shift of the i(f) activation curve induced by 1 microM isoprenaline was significantly larger in calyculin A-treated cells (8.8 vs. 5.8 mV). 6. These data indicate that phosphatase inhibition increases i(f) in a manner distinct from the direct cAMP pathway and potentiates the beta-adrenergic-mediated i(f) modulation. PMID:9161982

  18. Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban

    PubMed Central

    Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D; Hellkamp, Anne S; Piccini, Jonathan P; Lokhnygina, Yuliya; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Califf, Robert M; Fox, Keith A A; Patel, Manesh R

    2016-01-01

    Objective To compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD). Methods Using Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis. Results Among 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD. After adjusting for prognostic factors, the composite of stroke, systemic embolism or vascular death increased approximately twofold in patients with AS (AS 10.84, MR or AR 4.54 and no SVD 4.31 events per 100 patient-years, p=0.0001). All-cause death also significantly increased (AS 11.22, MR or AR 4.90 and no SVD 4.39 events per 100 patient-years, p=0.0003). Major bleeding occurred more frequently in AS (adjusted HR 1.61, confidence intervals (CI) 1.03 to 2.49, p<0.05) and MR or AR (HR 1.30, 1.07 to 1.57, p<0.01) than in no SVD, but there was no difference between AS and MR or AR (HR 1.24, 0.78 to 1.97). The relative efficacy of rivaroxaban versus warfarin was consistent among patients with and without valvular disease. Rivaroxaban was associated with higher rates of major bleeding than warfarin in patients with MR or AR (HR 1.63, 1.15 to 2.31). Conclusions We found that patients with AF and AS on oral anticoagulants may have distinctly different efficacy and safety outcomes than patients with MR or AR or no SVD. Trial registration number NCT00403767; Post-results. PMID:26888572

  19. RyR2 Modulates a Ca2+-Activated K+ Current in Mouse Cardiac Myocytes

    PubMed Central

    Mu, Yong-hui; Zhao, Wen-chao; Duan, Ping; Chen, Yun; Zhao, Wei-da; Wang, Qian; Tu, Hui-yin; Zhang, Qian

    2014-01-01

    In cardiomyocytes, Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) binds to and activates RyR2 channels, resulting in subsequent Ca2+ release from the sarcoplasmic reticulum (SR) and cardiac contraction. Previous research has documented the molecular coupling of small-conductance Ca2+-activated K+ channels (SK channels) to VDCCs in mouse cardiac muscle. Little is known regarding the role of RyRs-sensitive Ca2+ release in the SK channels in cardiac muscle. In this study, using whole-cell patch clamp techniques, we observed that a Ca2+-activated K+ current (IK,Ca) recorded from isolated adult C57B/L mouse atrial myocytes was significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2 (RyR2), or by the co-application of ryanodine and thapsigargin, an inhibitor of the sarcoplasmic reticulum calcium ATPase (SERCA) (p<0.05, p<0.01, respectively). The activation of RyR2 by caffeine increased the IK,Ca in the cardiac cells (p<0.05, p<0.01, respectively). We further analyzed the effect of RyR2 knockdown on IK,Ca and Ca2+ in isolated adult mouse cardiomyocytes using a whole-cell patch clamp technique and confocal imaging. RyR2 knockdown in mouse atrial cells transduced with lentivirus-mediated small hairpin interference RNA (shRNA) exhibited a significant decrease in IK,Ca (p<0.05) and [Ca2+]i fluorescence intensity (p<0.01). An immunoprecipitated complex of SK2 and RyR2 was identified in native cardiac tissue by co-immunoprecipitation assays. Our findings indicate that RyR2-mediated Ca2+ release is responsible for the activation and modulation of SK channels in cardiac myocytes. PMID:24747296

  20. Tissue-specific expression of the human brain natriuretic peptide gene in cardiac myocytes.

    PubMed

    LaPointe, M C; Wu, G; Garami, M; Yang, X P; Gardner, D G

    1996-03-01

    Brain natriuretic peptide (BNP) is a cardiac hormone constitutively expressed in the adult heart. To identify the cis-acting elements involved in regulation of the human BNP gene, we subcloned the full-length promoter (-1818 to +100) and deletions thereof upstream from a luciferase reporter gene and transiently transfected them into primary cultures of neonatal rat atrial and ventricular myocytes and myocardial fibroblasts. Luciferase activity of the full-length construct was higher in ventricular (39064 +/- 8488 relative light units, N=11) and atrial (11225 +/- 1907, N=17) myocytes than myocardial fibroblasts (329 +/- 113, n=5). Maximal promoter activity in ventricular and atrial myocytes was maintained by sequences positioned between -1818 and -1283 relative to the transcription start site. Deletion to -1175 resulted in a decrease, whereas further deletion to -500 effected an increase in reporter activity in both cell types. In ventricular and atrial myocytes, deletion from -500 to -40 reduced luciferase activity 20-fold and 2-fold, respectively, whereas in myocardial fibroblasts, deletion to -40 upregulated the BNP promoter 2-fold. Of note, deleting 16 bp between -127 and -111 reduced luciferase activity 7-fold and 4-fold in ventricular and atrial myocytes, respectively, but had essentially no effect on luciferase activity in fibroblasts. Placement of sequences lying between -127 and -40 upstream from a heterologous thymidine kinase promoter resulted in reporter expression that was 7.4-fold greater than the vector alone in ventricular myocytes, approximately 2-fold greater in atrial myocytes, and equivalent to the vector alone in fibroblasts. For study of activity of the human BNP promoter in adult myocytes, either 408 or 97 bp of 5' flanking sequence coupled to the luciferase reporter gene was injected into the apex of adult male Sprague-Dawley rat hearts. After 7 days, luciferase activity in the injected myocardium was 9.8-fold higher for the longer construct

  1. A rabbit pulmonary vein myocyte isolation method based on simultaneous heart and pulmonary vein perfusion.

    PubMed

    Gao, Lin-Lin; Zhang, Miao-Miao; Zhang, Liang-Pin; Yang, Shu-Lin; Yao, Ke-Jun; Song, Yuan-Long

    2016-02-25

    Myocytes in the pulmonary veins (PV) play a pivotal role in the development of paroxysmal atrial fibrillation (AF). It is therefore important to understand physiological characteristics of these cells. Studies on these cells are, however, markedly impeded by the fact that single PV myocytes are very difficult to obtain due to lack of effective isolation methods. In this study, we described a novel PV myocyte isolation method. The key aspect of this method is to establish a combination of retrograde heart perfusion (via the aorta) and anterograde PV perfusion (via the pulmonary artery). With this simultaneous perfusion method, a better perfusion of the PV myocytes can be obtained. As results, the output and viability of single myocytes isolated by simultaneous heart and PV perfusion method were increased compared with those in conventional retrograde heart perfusion method. PMID:26915322

  2. Allicin inhibits transient outward potassium currents in mouse ventricular myocytes

    PubMed Central

    CAO, HONG; HUANG, CONGXIN; WANG, XIN

    2016-01-01

    Allicin is the active constituent of garlic, a widely used spice and food. The remedial properties of garlic have also been extensively researched and it has been demonstrated that allicin is able to inhibit the transient outward potassium current (Ito) in atrial myocytes. However, the direct effect of allicin on Ito in ventricular myocytes has yet to be elucidated. In the present study, the effects of allicin on Ito in ventricular myocytes isolated from mice were investigated, using the whole-cell patch recording technique. The results revealed that Ito current was not significantly suppressed by allicin in the low-dose group (10 µmol/l; P>0.05). However, Ito was significantly inhibited by higher doses of allicin (30, 100 and 300 µmol/l; P<0.05 vs. control; n=6) in a concentration-dependent manner (IC50=41.6 µmol/l). In addition, a high concentration of allicin (≥100 µmol/l) was able to accelerate the voltage-dependent inactivation of Ito in mouse ventricular myocytes. In conclusion, the present study revealed that allicin inhibited the Ito in mouse ventricular myocytes, which may be the mechanism through which allicin exerts its antiarrhythmic effect. PMID:27168824

  3. Atrial remodeling, fibrosis, and atrial fibrillation.

    PubMed

    Jalife, José; Kaur, Kuljeet

    2015-08-01

    The fundamental mechanisms governing the perpetuation of atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, are poorly understood, which explains in part why AF prevention and treatment remain suboptimal. Although some clinical parameters have been identified as predicting a transition from paroxysmal to persistent AF in some patients, the molecular, electrophysiological, and inflammation changes leading to such a progression have not been described in detail. Oxidative stress, atrial dilatation, calcium overload, inflammation, microRNAs, and myofibroblast activation are all thought to be involved in AF-induced atrial remodeling. However, it is unknown to what extent and at which time points such alterations influence the remodeling process that perpetuates AF. Here we postulate a working model that might open new pathways for future investigation into mechanisms of AF perpetuation. We start from the premise that the progression to AF perpetuation is the result of interplay among manifold signaling pathways with differing kinetics. Some such pathways have relatively fast kinetics (e.g., oxidative stress-mediated shortening of refractory period); others likely depend on molecular processes with slower kinetics (e.g., transcriptional changes in myocyte ion channel protein expression mediated through inflammation and fibroblast activation). We stress the need to fully understand the relationships among such pathways should one hope to identify novel, truly effective targets for AF therapy and prevention. PMID:25661032

  4. Usefulness of New-Onset Atrial Fibrillation, as a Strong Predictor of Heart Failure and Death in Patients With Native Left-Sided Infective Endocarditis.

    PubMed

    Ferrera, Carlos; Vilacosta, Isidre; Fernández, Cristina; López, Javier; Sarriá, Cristina; Olmos, Carmen; Vivas, David; Sáez, Carmen; Sánchez-Enrique, Cristina; Ortiz-Bautista, Carlos; San Román, José Alberto

    2016-02-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults and has been independently related to increased morbidity and mortality. AF is a frequent arrhythmia in infective endocarditis (IE). Nevertheless, there are no data on how AF affects the clinical outcome of patients with endocarditis. Our purpose was to investigate patient characteristics, microbiology, echocardiographic findings, in-hospital course, and prognosis of patients with IE who develop new-onset AF (NAF) and compare them with those who remained in sinus rhythm (SR) or had previous AF (PAF). From 1997 to 2014, 507 consecutive patients with native left-sided IE were prospectively recruited at 3 tertiary care centers. We distinguished 3 groups according to the type of baseline heart rhythm during hospitalization and previous history of AF: NAF group (n = 52), patients with no previous history of AF and who were diagnosed as having NAF during hospitalization; SR group (n = 380), patients who remained in SR; and PAF group (n = 75), patients with PAF. Patients with NAF were older than those who remained in SR (68.3 vs 59.6 years, p <0.001). At admission, heart failure was more common in NAF group (53% vs 34.3%, p <0.001), whereas stroke (p = 0.427) was equally frequent in all groups. During hospitalization, embolic events occurred similarly (p = 0.411). In the multivariate analysis, NAF was independently associated with heart failure (odds ratio 3.56, p <0.01) and mortality (odds ratio 1.91, p = 0.04). In conclusion, the occurrence of NAF in patients with IE was strongly associated with heart failure and higher in-hospital mortality independently from other relevant clinical variables. PMID:26762724

  5. Distinct patterns of constitutive phosphodiesterase activity in mouse sinoatrial node and atrial myocardium.

    PubMed

    Hua, Rui; Adamczyk, Andrew; Robbins, Courtney; Ray, Gibanananda; Rose, Robert A

    2012-01-01

    Phosphodiesterases (PDEs) are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca(2+) current (I(Ca,L)) is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP) properties and I(Ca,L) in the sinoatrial node (SAN) and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX) and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on I(Ca,L) in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA), the PDE3 inhibitor milrinone (Mil) and the PDE4 inhibitor rolipram (Rol). In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased I(Ca,L) in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate I(Ca,L) in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased I(Ca,L) in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial I(Ca,L). In complete contrast, no selective PDE inhibitors increased I(Ca,L) in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium. PMID:23077656

  6. Distinct Patterns of Constitutive Phosphodiesterase Activity in Mouse Sinoatrial Node and Atrial Myocardium

    PubMed Central

    Robbins, Courtney; Ray, Gibanananda; Rose, Robert A.

    2012-01-01

    Phosphodiesterases (PDEs) are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca2+ current (ICa,L) is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP) properties and ICa,L in the sinoatrial node (SAN) and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX) and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on ICa,L in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA), the PDE3 inhibitor milrinone (Mil) and the PDE4 inhibitor rolipram (Rol). In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased ICa,L in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate ICa,L in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased ICa,L in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial ICa,L. In complete contrast, no selective PDE inhibitors increased ICa,L in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium. PMID:23077656

  7. Effects of spironolactone towards rabbit atrial remodeling with rapid pacing.

    PubMed

    Wang, Lian-Fa; Gu, Lei; Huang, Meng-Xun; Zhou, Wen-Bing; Li, Hua; Zhang, Bang-Zhu

    2016-01-01

    This study aimed to observe the effects of spironolactone towards the rabbit atrial remodeling with rapid atrial pacing (RAP). 30 rabbits were randomly divided into control group, RAP group and spironolactone group, with 10 rabbits in each group. RAP was performed at the speed of 800 beats/min for 8 h, atrial effective refractory period (AERP) was determined before and at the 1(st), 2(nd), 4(th), 6(th) and 8(th) of the pacing, the expressions of atrial muscular calcium channel α1C subunit and β1 subunit mRNA were performed the RT-PCR detection, and ultrastructural changes of atrial myocytes were observed. AERP of RAP group shortened, with poor frequency adaptability; the expressions of calcium channel α1C subunit and β1 subunit mRNA decreased 22% and 26%, respectively, when compared with the control group; ultrastructure of atrial myocytes changed significantly. AERP of spironotlactone group shortened less that RAP group, and the frequency adaptability was maintained, the decreased expressions of calcium channel α1C subunit and β1 subunit mRNA significantly reduced. RAP could cause atrial remodeling, while spironolactone could inhibit RAP-induced atrial remodeling. PMID:26826809

  8. The stimulus interval-tension relation in enzymatically isolated single myocytes of the frog heart.

    PubMed Central

    Cecchi, G; Colomo, F; Poggesi, C; Tesi, C

    1992-01-01

    1. Apparatus for recording the small tensions developed by electrically stimulated single intact myocytes of frog heart is described. A laser-light optoelectronic transducer was used. The compliance of the force probes was 10-20 nm/nN, with a frequency response of 600-900 Hz in Ringer solution. The myocyte shortening during an ordinary twitch contraction was no greater than 1% of the slack length. The overall sensitivity of the transducer system was 5-10 mV/nN, with a total noise of 0.5-1 nN peak to peak. The experiments were performed at 20-23 degrees C on either atrial or ventricular myocytes at 2.15-2.2 microns sarcomere length, in 1 mM-Ca2+ Ringer solution. 2. Isoprenaline (5 microM), increases in external Ca2+ concentration ([Ca2+]o), and shortening of stimulus interval potentiated the myocyte twitch tension. The dependence of twitch characteristics on these inotropic interventions for all the atrial and ventricular myocytes tested was comparable to that of multicellular preparations under similar experimental conditions. This implies that the enzymatic isolation procedure had not altered the physiological properties of the myocytes. 3. The stimulus interval-tension relation for premature twitches of atrial and ventricular myocytes showed (i) a very steep rising phase in the region of intervals just longer than 0.52 and 0.66 s (the duration of the mechanical refractoriness in atrial or ventricular cells), (ii) a peak, at intervals of 0.7-0.8 s, where the twitch tension was strongly potentiated compared to that of the controls, and (iii) as the stimulus interval was further increased, a progressive return to the control level. The stimulus interval-tension relation for steady-state conditions exhibited similar characteristics. 4. The degree of tension potentiation by isoprenaline was greater in the controls than in the earliest test twitches. The result was that the stimulus interval-tension relations for isoprenaline-treated myocytes showed a gentler rise and

  9. Gene Transfer into Cardiac Myocytes

    PubMed Central

    Lang, Sarah E.; Westfall, Margaret V.

    2016-01-01

    Traditional methods for DNA transfection are often inefficient and toxic for terminally differentiated cells, such as cardiac myocytes. Vector-based gene transfer is an efficient approach for introducing exogenous cDNA into these types of primary cell cultures. In this chapter, separate protocols for adult rat cardiac myocyte isolation and gene transfer with recombinant adenovirus are provided and are routinely utilized for studying the effects of sarcomeric proteins on myofilament function. PMID:25836585

  10. VAMP-1, VAMP-2, and syntaxin-4 regulate ANP release from cardiac myocytes.

    PubMed

    Ferlito, Marcella; Fulton, William B; Zauher, Mohamed A; Marbán, Eduardo; Steenbergen, Charles; Lowenstein, Charles J

    2010-11-01

    ANP is a peptide released by cardiac myocytes that regulates blood pressure and natriuresis. However, the molecular mechanisms controlling ANP release from cardiac myocytes are not defined. We now identify three components of the exocytic machinery that regulate ANP release from atrial myocytes. We found that cardiac myocytes express N-ethylmaleimide sensitive factor (NSF), soluble NSF attachment protein (α-SNAP), and SNAP receptors (SNAREs). Additionally we found that specific SNARE molecules, VAMP-1 and VAMP-2, both co-sediment and co-localize with ANP. Also, one SNARE molecule, syntaxin-4, partially co-sediments and partially co-localizes with ANP. Furthermore, these three SNAREs, syntaxin-4 and VAMP-1 and VAMP-2, form a SNARE complex inside cardiac myocytes. Finally, knockdown of VAMP-1, VAMP-2, or syntaxin-4 blocks regulated release of ANP. In contrast, silencing of VAMP-3 did not have an effect on ANP release. Our data suggest that three specific SNAREs regulate cardiac myocyte exocytosis of ANP. Pathways that modify the exocytic machinery may influence natriuresis and blood pressure. PMID:20801128

  11. Cardiac mast cells regulate myocyte ANP release via histamine H2 receptor in beating rabbit atria.

    PubMed

    Li, Dan; Wen, Jin Fu; Jin, Jing Yu; Quan, He Xiu; Cho, Kyung Woo

    2009-06-01

    It has been shown that histamine inhibits atrial natriuretic peptide (ANP) release. Because cardiac mast cells are the principal source of histamine in the heart, we hypothesized that cardiac mast cells are involved in the regulation of atrial ANP release. To test the hypothesis, experiments were performed in perfused beating rabbit atria allowing atrial pacing and measurements of changes in atrial stroke volume, intraatrial pulse pressure and myocyte ANP release. Mast cell degranulation with Compound 48/80 decreased atrial myocyte ANP release, and the response was blocked by a selective histamine H(2) receptor blocker, cimetidine, indicating that histamine was responsible for the decrease in ANP release. Mast cell stabilization with cromolyn blocked the Compound 48/80-induced decrease in ANP release. These data suggest that mast cell-derived histamine is involved in the regulation of cardiac ANP release. Thus, the cardiac mast cell-cardiomyocyte communication via the histamine-ANP pathway may implicate in the cardiac disorder associated with mast cell degranulation such as in acute coronary syndrome or cardiac hypertrophy. PMID:19328828

  12. Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

    NASA Technical Reports Server (NTRS)

    Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

    1998-01-01

    Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists

  13. Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts

    NASA Technical Reports Server (NTRS)

    Ito, Kenta; Nakayama, Masaharu; Hasan, Faisal; Yan, Xinhua; Schneider, Michael D.; Lorell, Beverly H.

    2003-01-01

    BACKGROUND: Chronic cardiac unloading of the normal heart results in the reduction of left ventricular (LV) mass, but effects on myocyte contractile function are not known. METHODS AND RESULTS: Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. Contractility and [Ca(2+)](i) regulation in LV myocytes were studied at both 2 and 5 weeks after transplantation. Native in situ hearts from recipient animals were used as the controls for all experiments. Contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 Hz, 1.2 mmol/L [Ca(2+)](o), and 36 degrees C) and in response to stimulation with high [Ca(2+)](o) (range 2.5 to 4.0 mmol/L). In myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic [Ca(2+)](i) at baseline; however, time to 50% relengthening and time to 50% decline in [Ca(2+)](i) were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca(2+)](i) were elicited in myocytes from 5-week unloaded hearts in response to high [Ca(2+)](o). However, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. In 5-week unloaded hearts, but not in 2-week unloaded hearts, LV protein levels of phospholamban were increased (345% of native heart values). Protein levels of sarcoplasmic reticulum Ca(2+) ATPase and the Na(+)/Ca(2+) exchanger were not changed. CONCLUSIONS: Chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.

  14. Inactivation of calcium current in bull-frog atrial myocytes.

    PubMed Central

    Campbell, D L; Giles, W R; Hume, J R; Shibata, E F

    1988-01-01

    1. A single-microelectrode technique has been used to study the voltage dependence and the kinetics of inactivation and reactivation of a tetrodotoxin-resistant inward current (ICa) in single cells from bull-frog atrium. 2. In most cases the kinetics of both inactivation and reactivation can be well described as a single-exponential process. 3. Several different observations indicate that inactivation of ICa in these cells is controlled by both voltage-dependent and current-dependent processes, as has been demonstrated previously in heart (Kass & Sanguinetti, 1984; Lee, Marban & Tsien, 1985) and in other tissues (Hagiwara & Byerly, 1981; Tsien, 1983; Eckert & Chad, 1984). 4. Evidence in favour of a voltage-dependent inactivation mechanism included: (a) In paired-pulse measurements of steady-state inactivation ('f infinity') a 'conventional' steady-state f infinity vs. membrane potential (Vm) relationship was obtained in the range of membrane potentials from -60 to 0 mV. (b) Increasing [Ca2+]o from 2.5 to 7.5 mM, which resulted in a 2-3-fold increase in ICa, did not produce any significant increase in the amount of inactivation. (c) Using a 'gapped' double-pulse protocol non-monotonic U-shaped inactivation relationships were obtained, i.e. positive to approximately +20 mV some removal of inactivation occurred. However, f never approached a value near 1.00 at very depolarized potentials; it reached a maximum between 0.5 and 0.6. (d) In constant [Ca2+]o and at fixed Vm, the kinetics of ICa inactivation were independent of peak size of ICa. This was demonstrated by: (i) varying the holding potential (-90 to -30 mV), (ii) using paired-pulse 'recovery' protocols, and (iii) partial block by La3+ (1-10 microM) and Cd2+ (0.1 mM). (e) Influx of Ca2+ ions was not an obligatory prerequisite for development of inactivation. In all ionic conditions (Ca2+, Sr2+, Ba2+, Na+-free and Ca2+-free Ringer solutions) currents displayed inactivation phenomena, although the extent and kinetics of inactivation were dependent upon ionic conditions. Outward currents recorded above the reversal potential for ICa exhibited time- and voltage-dependent inactivation, and could be inactivated by brief depolarizing pre-pulses that produced no net inward current flow. Evidence against a possible role of the electrogenic Na+-Ca2+ exchanger in producing inactivation of these outward currents was obtained.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2855343

  15. Three-Dimensional Distribution of Ryanodine Receptor Clusters in Cardiac Myocytes

    PubMed Central

    Chen-Izu, Ye; McCulle, Stacey L.; Ward, Chris W.; Soeller, Christian; Allen, Bryan M.; Rabang, Cal; Cannell, Mark B.; Balke, C. William; Izu, Leighton T.

    2006-01-01

    The clustering of ryanodine receptors (RyR2) into functional Ca2+ release units is central to current models for cardiac excitation-contraction (E-C) coupling. Using immunolabeling and confocal microscopy, we have analyzed the distribution of RyR2 clusters in rat and ventricular atrial myocytes. The resolution of the three-dimensional structure was improved by a novel transverse sectioning method as well as digital deconvolution. In contrast to earlier reports, the mean RyR2 cluster transverse spacing was measured 1.05 μm in ventricular myocytes and estimated 0.97 μm in atrial myocytes. Intercalated RyR2 clusters were found interspersed between the Z-disks on the cell periphery but absent in the interior, forming double rows flanking the local Z-disks on the surface. The longitudinal spacing between the adjacent rows of RyR2 clusters on the Z-disks was measured to have a mean value of 1.87 μm in ventricular and 1.69 μm in atrial myocytes. The measured RyR2 cluster distribution is compatible with models of Ca2+ wave generation. The size of the typical RyR2 cluster was close to 250 nm, and this suggests that ∼100 RyR2s might be present in a cluster. The importance of cluster size and three-dimensional spacing for current E-C coupling models is discussed. PMID:16603500

  16. Protective role of heme oxygenase-1 in atrial remodeling.

    PubMed

    Yeh, Yung-Hsin; Hsu, Lung-An; Chen, Ying-Hwa; Kuo, Chi-Tai; Chang, Gwo-Jyh; Chen, Wei-Jan

    2016-09-01

    Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 cell line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-β (TGF-β) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-β enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-β, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1(-/-) mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1(-/-) mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development. PMID:27562817

  17. Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles

    PubMed Central

    Kohl, Tobias; Lehnart, Stephan E.

    2014-01-01

    In cardiac myocytes a complex network of membrane tubules - the transverse-axial tubule system (TATS) - controls deep intracellular signaling functions. While the outer surface membrane and associated TATS membrane components appear to be continuous, there are substantial differences in lipid and protein content. In ventricular myocytes (VMs), certain TATS components are highly abundant contributing to rectilinear tubule networks and regular branching 3D architectures. It is thought that peripheral TATS components propagate action potentials from the cell surface to thousands of remote intracellular sarcoendoplasmic reticulum (SER) membrane contact domains, thereby activating intracellular Ca2+ release units (CRUs). In contrast to VMs, the organization and functional role of TATS membranes in atrial myocytes (AMs) is significantly different and much less understood. Taken together, quantitative structural characterization of TATS membrane networks in healthy and diseased myocytes is an essential prerequisite towards better understanding of functional plasticity and pathophysiological reorganization. Here, we present a strategic combination of protocols for direct quantitative analysis of TATS membrane networks in living VMs and AMs. For this, we accompany primary cell isolations of mouse VMs and/or AMs with critical quality control steps and direct membrane staining protocols for fluorescence imaging of TATS membranes. Using an optimized workflow for confocal or superresolution TATS image processing, binarized and skeletonized data are generated for quantitative analysis of the TATS network and its components. Unlike previously published indirect regional aggregate image analysis strategies, our protocols enable direct characterization of specific components and derive complex physiological properties of TATS membrane networks in living myocytes with high throughput and open access software tools. In summary, the combined protocol strategy can be readily applied

  18. Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium produces a lethal phenotype associated with myocyte hyperplasia and heart block

    PubMed Central

    Hein, Lutz; Stevens, Mary E.; Barsh, Gregory S.; Pratt, Richard E.; Kobilka, Brian K.; Dzau, Victor J.

    1997-01-01

    Previous studies have suggested that angiotensin II (Ang II) modulates cardiac contractility, rhythm, metabolism, and structure. However, it is unclear whether the cardiac effects are due to direct actions of Ang II on the myocardium or if they are due to secondary effects mediated through the hemodynamic actions of Ang II. In this study, we used the α-myosin heavy chain (αMHC) promoter to generate transgenic mice overexpressing angiotensin II type 1 (AT1a) receptor selectively in cardiac myocytes. The specificity of transgene expression in the transgenic offspring was confirmed by radioligand binding studies and reverse transcription–PCR. The offspring displayed massive atrial enlargement with myocyte hyperplasia at birth, developed significant bradycardia with heart block, and died within the first weeks after birth. Thus, direct activation of AT1 receptor signaling in cardiac myocytes in vivo is sufficient to induce cardiac myocyte growth and alter electrical conduction. PMID:9177228

  19. Heart rate variability effect on the myocyte action potential duration restitution: insights from switched systems theory.

    PubMed

    Dvir, Hila; Zlochiver, Sharon

    2011-01-01

    The physiological heart rate presents a stochastic behavior known as heart rate variability (HRV). In this framework the influence of HRV on the action potential duration (APD) of the atrial myocyte is analyzed in a computer model. We have found that introducing HRV into the myocyte action potential model decreases the APD of the extra beat S2 in an S1-S2 protocol compared to constant heart rate. A possible theoretical explanation for this is also presented and is derived from switched systems theory. It is suggested to consider the myocyte action potential phase 4 and phase 2 as two operation modes of a switching system and analyze the stability of switching between them. Since random switching is known to have a stabilization effect on a switching system, this might explain why HRV has a stabilization effect on the myocyte APD restitution. Implications of this finding include reduced system stability for conditions with low HRV. A possible application for this phenomenon regards artificial pacemakers, where a preset added HRV is predicted to reduce susceptibility to arrhythmias. PMID:22254402

  20. Atrial Fibrillation and Stroke

    MedlinePlus

    ... Find People About NINDS NINDS Atrial Fibrillation and Stroke Information Page Table of Contents (click to jump ... done? Clinical Trials What is Atrial Fibrillation and Stroke? Atrial fibrillation (AF) describes the rapid, irregular beating ...

  1. Living with Atrial Fibrillation

    MedlinePlus

    ... Topics » Atrial Fibrillation » Living With Atrial Fibrillation Explore Atrial Fibrillation What Is... Types Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Arrhythmia ...

  2. Extra-atrial expression of the gene for atrial natriuretic factor.

    PubMed Central

    Gardner, D G; Deschepper, C F; Ganong, W F; Hane, S; Fiddes, J; Baxter, J D; Lewicki, J

    1986-01-01

    Atrial natriuretic factor (ANF) is a group of peptides, originally isolated from the cardiac atria, that have a number of important effects on blood pressure, renal function, and salt balance. In the current study, expression of the ANF gene in certain extra-atrial tissues of the rat has been examined by radioimmunoassay of extracted ANF protein and by blot-hybridization, nuclease S1 analysis, and primer-extension analysis of the ANF mRNA. ANF peptides and mRNA were detected in cardiac ventricles, lung, and pituitary gland at levels generally less than or equal to 1% those of cardiac atria. The ANF transcripts in extra-atrial tissue appear to be very similar to those synthesized in the atria. They are polyadenylylated, are equivalent in overall length (950-1050 nucleotides), and have identical 5' termini. A secondary transcription start site mapping approximately 80 base pairs upstream from the primary start site is employed in atria and to a lesser extent in other tissues. The ANF transcript is present throughout the cardiac ventricles from apex to base and in the septum as well as the ventricular free walls. The transcript is more prevalent in the left ventricle and interventricular septum than in the right ventricle. Immunocytochemistry using various anti-rat ANF antibodies localized ANF immunoreactivity to the atrial myocytes; the ventricular myocytes, particularly along the endothelial surface of the ventricular chamber; perialveolar cells in the lung; and the gonadotropin-producing cells of the pituitary. The data indicate that the capacity for ANF gene expression extends beyond atrial tissue, albeit at much reduced levels, and may suggest alternative, perhaps paraendocrine, functions for the peptide in these tissues. Images PMID:2428040

  3. Imaging atrial arrhythmic intracellular calcium in intact heart

    PubMed Central

    Xie, Wenjun; Santulli, Gaetano; Guo, Xiaoxiao; Gao, Melanie; Chen, Bi-Xing; Marks, Andrew R.

    2014-01-01

    Abnormalities in intracellular Ca2+ signaling have been proposed to play an essential role in the pathophysiology of atrial arrhythmias. However, a direct observation of intracellular Ca2+ in atrial myocytes during atrial arrhythmias is lacking. Here, we have developed an ex vivo model of simultaneous Ca2+ imaging and electrocardiographic recording in cardiac atria. Using this system we were able to record atrial arrhythmic intracellular Ca2+ activities. Our results indicate that atrial arrhythmias can be tightly linked to intracellular Ca2+ waves and Ca2+ alternans. Moreover, we applied this strategy to analyze Ca2+ signals in the hearts of WT and knock-in mice harboring a ‘leaky’ type 2 ryanodine receptor (RyR2-R2474S). We showed that sarcoplasmic reticulum (SR) Ca2+ leak increases the susceptibility to Ca2+ alternans and Ca2+ waves increasing the incidence of atrial arrhythmias. Reduction of SR Ca2+ leak via RyR2 by acute treatment with S107 reduced both Ca2+ alternans and Ca2+ waves, and prevented atrial arrhythmias. PMID:24041536

  4. Atrial fibrillation or flutter

    MedlinePlus

    ... causes of atrial fibrillation include: Alcohol use (especially binge drinking) Coronary artery disease Heart attack or heart ... conditions that cause atrial fibrillation and flutter. Avoid binge drinking.

  5. Modeling the isolated cardiac myocyte.

    PubMed

    Puglisi, Jose L; Wang, Fei; Bers, Donald M

    2004-01-01

    Computer modeling of cardiac myocytes has flourished in recent years. Models have evolved from mathematical descriptions of ionic channels alone to more sophisticated formulations that include calcium transport mechanisms, ATP production and metabolic pathways. The increased complexity is fueled by the new data available in the field. The continuous production of experimental data has led to the evolution of increasingly refined descriptions of the phenomena by modelers. Integrating the numerous systems involved in cardiac myocyte homeostasis makes the use of computer models necessary due to the unreliability of intuitive approaches. However the complexity of the model should not imply a cumbersome operation of the program. As with any tool, computer models have to be easy to operate or their strength will be diminished and potential users will not benefit fully from them. The contribution of the computer modeler to their respective biological fields will be more successful and enduring if modelers devote sufficient time to implement their equations into a model with user-friendly characteristics. PMID:15142742

  6. Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation

    PubMed Central

    Christ, Torsten; Rozmaritsa, Nadiia; Engel, Andreas; Berk, Emanuel; Knaut, Michael; Metzner, Katharina; Canteras, Manuel; Ravens, Ursula; Kaumann, Alberto

    2014-01-01

    Atrial fibrillation (AF) is the most common heart rhythm disorder. Transient postoperative AF can be elicited by high sympathetic nervous system activity. Catecholamines and serotonin cause arrhythmias in atrial trabeculae from patients with sinus rhythm (SR), but whether these arrhythmias occur in patients with chronic AF is unknown. We compared the incidence of arrhythmic contractions caused by norepinephrine, epinephrine, serotonin, and forskolin in atrial trabeculae from patients with SR and patients with AF. In the patients with AF, arrhythmias were markedly reduced for the agonists and abolished for forskolin, whereas maximum inotropic responses were markedly blunted only for serotonin. Serotonin and forskolin produced spontaneous diastolic Ca2+ releases in atrial myocytes from the patients with SR that were abolished or reduced in myocytes from the patients with AF. For matching L-type Ca2+-current (ICa,L) responses, serotonin required and produced ∼100-fold less cAMP/PKA at the Ca2+ channel domain compared with the catecholamines and forskolin. Norepinephrine-evoked ICa,L responses were decreased by inhibition of Ca2+/calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was reduced in trabeculae from patients with AF. The decreased CaMKII activity may contribute to the blunting of agonist-evoked arrhythmias in the atrial myocardium of patients with AF. PMID:25024212

  7. Atrial fibrillation

    PubMed Central

    Munger, Thomas M.; Wu, Li-Qun; Shen, Win K.

    2014-01-01

    Atrial fibrillation is the most common arrhythmia affecting patients today. Disease prevalence is increasing at an alarming rate worldwide, and is associated with often catastrophic and costly consequences, including heart failure, syncope, dementia, and stroke. Therapies including anticoagulants, anti-arrhythmic medications, devices, and non-pharmacologic procedures in the last 30 years have improved patients' functionality with the disease. Nonetheless, it remains imperative that further research into AF epidemiology, genetics, detection, and treatments continues to push forward rapidly as the worldwide population ages dramatically over the next 20 years. PMID:24474959

  8. Atrial fibrillation.

    PubMed

    Lip, Gregory Y H; Fauchier, Laurent; Freedman, Saul B; Van Gelder, Isabelle; Natale, Andrea; Gianni, Carola; Nattel, Stanley; Potpara, Tatjana; Rienstra, Michiel; Tse, Hung-Fat; Lane, Deirdre A

    2016-01-01

    Atrial fibrillation (AF) is the most common sustained cardiac rhythm disorder, and increases in prevalence with increasing age and the number of cardiovascular comorbidities. AF is characterized by a rapid and irregular heartbeat that can be asymptomatic or lead to symptoms such as palpitations, dyspnoea and dizziness. The condition can also be associated with serious complications, including an increased risk of stroke. Important recent developments in the clinical epidemiology and management of AF have informed our approach to this arrhythmia. This Primer provides a comprehensive overview of AF, including its epidemiology, mechanisms and pathophysiology, diagnosis, screening, prevention and management. Management strategies, including stroke prevention, rate control and rhythm control, are considered. We also address quality of life issues and provide an outlook on future developments and ongoing clinical trials in managing this common arrhythmia. PMID:27159789

  9. TASK-1 current is inhibited by phosphorylation during human and canine chronic atrial fibrillation.

    PubMed

    Harleton, Erin; Besana, Alessandra; Chandra, Parag; Danilo, Peter; Rosen, Tove S; Rosen, Michael R; Argenziano, Michael; Robinson, Richard B; Feinmark, Steven J

    2015-01-15

    Atrial fibrillation (AF) is a common arrhythmia with significant morbidities and only partially adequate therapeutic options. AF is associated with atrial remodeling processes, including changes in the expression and function of ion channels and signaling pathways. TWIK protein-related acid-sensitive K+ channel (TASK)-1, a two-pore domain K+ channel, has been shown to contribute to action potential repolarization as well as to the maintenance of resting membrane potential in isolated myocytes, and TASK-1 inhibition has been associated with the induction of perioperative AF. However, the role of TASK-1 in chronic AF is unknown. The present study investigated the function, expression, and phosphorylation of TASK-1 in chronic AF in atrial tissue from chronically paced canines and in human subjects. TASK-1 current was present in atrial myocytes isolated from human and canine hearts in normal sinus rhythm but was absent in myocytes from humans with AF and in canines after the induction of AF by chronic tachypacing. The addition of phosphatase to the patch pipette rescued TASK-1 current from myocytes isolated from AF hearts, indicating that the change in current is phosphorylation dependent. Western blot analysis showed that total TASK-1 protein levels either did not change or increased slightly in AF, despite the absence of current. In studies of perioperative AF, we have shown that phosphorylation of TASK-1 at Thr383 inhibits the channel. However, phosphorylation at this site was unchanged in atrial tissue from humans with AF or in canines with chronic pacing-induced AF. We conclude that phosphorylation-dependent inhibition of TASK-1 is associated with AF, but the phosphorylation site responsible for this inhibition remains to be identified. PMID:25437921

  10. Atrial Fibrillation in Children

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Atrial Fibrillation in Children Updated:Jul 18,2016 Does your ... content was last reviewed on 04/16/14. Atrial Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • ...

  11. Effect of ethanol and acetaldehyde at clinically relevant concentrations on atrial inward rectifier potassium current IK1: separate and combined effect.

    PubMed

    Horakova, Z; Matejovic, P; Pasek, M; Hosek, J; Simurdova, M; Simurda, J; Bebarova, M

    2016-06-01

    Atrial fibrillation is the most common arrhythmia at alcohol consumption. Its pathogenesis is complex, at least partly related to changes of cardiac inward rectifier potassium currents including IK1. Both ethanol and acetaldehyde have been demonstrated to considerably modify IK1 in rat ventricular myocytes. However, analogical data on the atrial IK1 are lacking. The present study aimed to analyse IK1 changes induced by ethanol and acetyldehyde in atrial myocytes. The experiments were performed by the whole cell patch-clamp technique at 23 ± 1°C on enzymatically isolated rat and guinea-pig atrial myocytes as well as on expressed human Kir2.3 channels. Ethanol (8 - 80 mM) caused a dual effect on the atrial IK1 showing the steady-state activation in some cells but inhibition in others in agreement with the ventricular data; on average, the activation was observed (at 20 mM by 4.3 and 4.5% in rat and guinea-pig atrial myocytes, respectively). The effect slightly increased with depolarization above -60 mV. In contrast, the current through human Kir2.3 channels (prevailing atrial IK1 subunit) was inhibited in all measured cells. Unlike ethanol, acetaldehyde (3 μM) markedly inhibited the rat atrial IK1 (by 15.1%) in a voltage-independent manner, comparably to the rat ventricular IK1. The concurrent application of ethanol (20 mM) and acetaldehyde (3 μM) resulted in the steady-state IK1 activation by 2.1% on average. We conclude that ethanol and even more acetaldehyde affected IK1 at clinically relevant concentrations if applied separately. Their combined effect did not significantly differ from the effect of ethanol alone. PMID:27511995

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

    PubMed Central

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

    2015-01-01

    Background 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. Methods 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. Results As predicted, SR Ca2+ reuptake was enhanced with SERCA2a overexpression (p< 0.05) and reduced with SERCA2a inhibition (p<0.05). Surprisingly, there was no difference in susceptibility to Ca-ALT with either SERCA2a overexpression 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 < 0.05) and concomitant increase in SR Ca2+ load (p<0.05). Based on these observations we tested in-vivo atrial arrhythmia inducibility in control and Ad.SERCA2a animals using an esophageal atrial burst pacing protocol. There were no inducible atrial arrhythmias in Ad.GFP (n = 4) animals though 20% of Ad.SERCA2a (n = 5) animals had inducible atrial arrhythmias (p = 0.20). Conclusions Our findings suggest that unlike the ventricle, SERCA2a is not a key regulator of cardiac alternans in the atrium. Importantly, SERCA2a overexpression in atrial myocytes can increase SCR, which may be arrhythmogenic. PMID:26352986

  13. Annexins V and VI: major calcium-dependent atrial secretory granule-binding proteins.

    PubMed

    Doubell, A F; Bester, A J; Thibault, G

    1991-11-01

    Atrial natriuretic peptide is stored by atrial myocytes in secretory granules, known as atrial specific granules, and is released from these granules by exocytosis. We have isolated a group of atrial proteins by affinity chromatography that bind to atrial specific granules in a calcium-dependent manner. The two major proteins isolated (32.5 kd and 67 kd) are calcium-binding proteins and have been identified as annexins V and VI by immunoblotting with specific antisera. The calcium dependence of their binding to atrial specific granules has been characterized in vitro and indicates that this interaction takes place at micromolar levels of calcium. In addition, the group of proteins isolated includes another calcium-binding protein of 20 kd, as well as GTP-binding proteins of 22 to 26 kd. Membrane interactions during exocytosis are presumably mediated by the interaction of specific proteins with the granule membrane. The properties of the proteins described here, and their ability to bind to atrial specific granules in a calcium-dependent manner, make them likely candidates in the search for regulatory proteins mediating atrial natriuretic peptide secretion. PMID:1834552

  14. [Atrial fibrillation].

    PubMed

    Colín Lizalde, L J

    2001-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia. AF has now been exhaustively studied: more is known about its mechanism and research is moving towards new forms of treatment. For chronic AF, basically the control of ventricular rate and the brain protection are the main issues. It is well known that with the identification of high risk group for embolism, oral anticoagulation should be administered. Ventricular rate control can be achieved by using betablockers or calcium channel blockers, unless these are contraindicated for the elderly. Oral anticoagulation prevents the stroke. The main mechanism of AF is the re-entry of multiple wavelets, but now it is more frequently found on patients with focal AF. Therapies are employed to bring the patient to a sinusal rhythm as soon as possible with antiarryhthmics or electric cardioversion externally or internally. The internal procedure includes 1 to 15 J and the success rate is of 91% vs 67% in relation to the external one. The introduction of the catheter ablation has opened new frontiers for the treatment of AF, first as the ablate-and-pace technique and now trying to mimic the maze procedure or with the ablation of the focal tachycardia. The stimulation for prevention of AF under research, as well as the implantable dysfibrillation for selected patients. On going studies will show the possible benefit of this type of benefits. PMID:11565343

  15. bcl-2 overexpression promotes myocyte proliferation

    PubMed Central

    Limana, Federica; Urbanek, Konrad; Chimenti, Stefano; Quaini, Federico; Leri, Annarosa; Kajstura, Jan; Nadal-Ginard, Bernardo; Izumo, Seigo; Anversa, Piero

    2002-01-01

    To determine the influence of Bcl-2 on the developmental biology of myocytes, we analyzed the population dynamics of this cell type in the heart of transgenic (TG) mice overexpressing Bcl-2 under the control of the α-myosin heavy chain promoter. TG mice and non-TG (wild type, WT) mice were studied at 24 days, 2 months, and 4 months after birth. Bcl-2 overexpression produced a significant increase in the percentage of cycling myocytes and their mitotic index. These effects were strictly connected to the expression of the transgene, as demonstrated in isolated myocytes. The formation of mitotic spindle and contractile ring was identified in replicating cells. These typical aspects of mitosis were complemented with the demonstration of karyokinesis and cytokinesis to provide structural evidence of cell division. Apoptosis was low at all ages and was not affected by Bcl-2. The higher cell replication rate in TG was conditioned by a decrease in the expression of the cell-cycle inhibitors, p21WAF1 and p16INK4a, and by an increase in Mdm2-p53 complexes. In comparison with WT, TG had 0.4 × 106, 0.74 × 106, and 1.2 × 106 more myocytes in the left ventricle at 24 days, 2 months, and 4 months, respectively. Binucleated myocytes were 12% and 25% larger in WT than in TG mice at 2 and 4 months of age. Taken together, these observations reveal a previously uncharacterized replication-enhancing function of Bcl-2 in myocytes in vivo in the absence of stressful conditions. PMID:11983915

  16. Cocaine causes atrial Purkinje fiber damage.

    PubMed

    Gilloteaux, Jacques; Ekwedike, Nelson N

    2010-04-01

    Comparisons of atrial tissues from Syrian hamster offspring born from cocaine-treated mothers during the last days of pregnancy with sham-treated ones demonstrate irreversible focal ischemic damage in the Purkinje myofibers and minor endocardial damages as well as minute cardiomyocyte vacuolization. These defects are consistent with the pharmacotoxicity of cocaine or its metabolites. The damaged Purkinje myocytes apparently remain in contact with adjacent cardiomyocytes but undergo autolytic process similar to that found in autoschizic cell death. Adjacent cell type(s) appear to segregate or engulf the injured cells. Data collected in this report demonstrate why clinical bradyarrhythmias, arrhythmias, or sudden death as cardiac arrest can be found in pre- and postnatal cocaine-abused babies as well as those found in young individuals caused by acute or chronic cocaine abuse. PMID:20192706

  17. Altered properties of volume-sensitive osmolyte and anion channels (VSOACs) and membrane protein expression in cardiac and smooth muscle myocytes from Clcn3−/− mice

    PubMed Central

    Yamamoto-Mizuma, Shintaro; Wang, Ge-Xin; Liu, Luis L; Schegg, Kathleen; Hatton, William J; Duan, Dayue; Horowitz, Burton; Lamb, Fred S; Hume, Joseph R

    2004-01-01

    ClC-3, a member of the large superfamily of ClC voltage-dependent Cl– channels, has been proposed as a molecular candidate responsible for volume-sensitive osmolyte and anion channels (VSOACs) in some cells, including heart and vascular smooth muscle. However, the reported presence of native VSOACs in at least two cell types from transgenic ClC-3 disrupted (Clcn3−/−) mice casts considerable doubt on this proposed role for ClC-3. We compared several properties of native VSOACs and examined mRNA transcripts and membrane protein expression profiles in cardiac and pulmonary arterial smooth muscle cells from Clcn3+/+ and Clcn3−/− mice to: (1) test the hypothesis that native VSOACs are unaltered in cells from Clcn3−/− mice, and (2) test the possibility that targeted inactivation of the Clcn3 gene using a conventional murine global knock-out approach may result in compensatory changes in expression of other membrane proteins. Our experiments demonstrate that VSOAC currents in myocytes from Clcn3+/+ and Clcn3−/− mice are remarkably similar in terms of activation and inactivation kinetics, steady-state current densities, rectification, anion selectivity (I− > Cl− ≫ Asp−) and sensitivity to block by glibenclamide, niflumic acid, DIDS and extracellular ATP. However, additional experiments revealed several significant differences in other fundamental properties of native VSOACs recorded from atrial and smooth muscle cells from Clcn3−/− mice, including: differences in regulation by endogenous protein kinase C, differential sensitivity to block by anti-ClC-3 antibodies, and differential sensitivities to [ATP]i and free [Mg2+]i. These results suggest that in response to Clcn3 gene deletion, there may be compensatory changes in expression of other proteins that alter VSOAC channel subunit composition or associated regulatory subunits that give rise to VSOACs with different properties. Consistent with this hypothesis, in atria from Clcn3−/− mice

  18. Mechanically induced orientation of adult rat cardiac myocytes in vitro

    NASA Technical Reports Server (NTRS)

    Samuel, J.-L.; Vandenburgh, H. H.

    1990-01-01

    The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

  19. Estrogen receptor profiling and activity in cardiac myocytes.

    PubMed

    Pugach, Emily K; Blenck, Christa L; Dragavon, Joseph M; Langer, Stephen J; Leinwand, Leslie A

    2016-08-15

    Estrogen signaling appears critical in the heart. However a mechanistic understanding of the role of estrogen in the cardiac myocyte is lacking. Moreover, there are multiple cell types in the heart and multiple estrogen receptor (ER) isoforms. Therefore, we studied expression, localization, transcriptional and signaling activity of ERs in isolated cardiac myocytes. We found only ERα RNA (but no ERβ RNA) in cardiac myocytes using two independent methods. The vast majority of full-length ERα protein (ERα66) localizes to cardiac myocyte nuclei where it is competent to activate transcription. Alternate isoforms of ERα encoded by the same genomic locus (ERα46 and ERα36) have differential transcriptional activity in cardiac myocytes but also primarily localize to nuclei. In contrast to other reports, no ERα isoform is competent to activate MAPK or PI3K signaling in cardiac myocytes. Together these data support a role for ERα at the level of transcription in cardiac myocytes. PMID:27164442

  20. Atrial fibrillation.

    PubMed

    Bang, Casper N

    2013-10-01

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

  1. Atrial Septal Defect (For Teens)

    MedlinePlus

    ... I Help a Friend Who Cuts? Atrial Septal Defect KidsHealth > For Teens > Atrial Septal Defect Print A ... Care of Yourself What Is an Atrial Septal Defect? Having a doctor listen to your heart is ...

  2. Restrictive atrial septum after the Fontan procedure.

    PubMed

    Penford, Gemma; Quandt, Daniel; Stumper, Oliver

    2016-03-01

    In this study, three patients presenting with early or late postoperative Fontan complications were identified to suffer from restriction of the native atrial septum. This caused significant obstruction to pulmonary venous return and elevated systemic venous pressure. Dobutamine stress testing was used in one patient to identify this lesion. Transcatheter stenting was performed in the other two patients. Patients improved after relief of the obstruction. PMID:26175163

  3. Simulating the effects of atrial fibrillation induced electrical remodeling: a comprehensive simulation study.

    PubMed

    Kharche, Sanjay; Zhang, Henggui

    2008-01-01

    Mechanisms underlying atrial fibrillation (AF) are poorly understood. In this study, we computationally evaluated the functional roles of AF induced electrical remodeling (AFER) on atrial electrical excitations. Experimental data of AFER on human atrial myocytes were incorporated into a biophysically detailed model of human atrial cells to simulate the effects of AFER at cellular and tissue levels. Our results show that AFER dramatically abbreviated atrial action potential duration (APD90) and effective refractory period that were quantitatively consistent with experimental data. A typical feature of loss in rate dependent accommodation of APD90 was observed. AFER slowed down atrial conduction velocity, but facilitated atrial conduction at high excitation rates. AFER increased tissue's spatial vulnerability for initiation and maintenance of AF remarkably. The overall susceptibility of human atrium to arrhythmia was increased. Most importantly AFER increased the stability of reentrant waves in 2D and 3D models prolonging their lifespan. While reentrant excitation waves self-terminated under Control conditions, the same became persistent or degenerated into multiple wavelets leading to spatio-temporal chaos under AFER conditions with accelerated re-entrant excitation rates. There was an increase in dominant frequency. In conclusion, our simulations substantiated a link between AFER and persistence of AF, providing mechanistic insights towards better understanding of "AF begets AF". PMID:19162725

  4. Effect of overexpressed adenylyl cyclase VI on β1- and β2-adrenoceptor responses in adult rat ventricular myocytes

    PubMed Central

    Stark, Joalice C C; Haydock, Stephen F; Foo, Roger; Brown, Morris J; Harding, Sian E

    2004-01-01

    Adenylyl cyclase VI (ACVI) is one of the most abundantly expressed β adrenergic receptor (βAR)-coupled cyclases responsible for cyclic AMP (cAMP) production within the mammalian myocardium. We investigated the role of ACVI in the regulation of cardiomyocyte contractility and whether it is functionally coupled with β1 adrenergic receptor (β1AR). Recombinant adenoviruses were generated for ACVI and for antisense to ACVI (AS). Adult rat ventricular myocytes were transfected with ACVI virus, AS or both (SAS). Adenovirus for green fluorescent protein (GFP) served as control. Myocyte contraction amplitudes (% shortening) and relaxation times (R50) were analysed. ACVI function was determined using cAMP assays. ACVI-transfected cells demonstrated a strong 139 kDa ACVI protein band compared to controls. ACVI myocytes had higher steady-state intracellular cAMP levels than GFP myocytes when unstimulated (GFP vs ACVI=6.60±0.98 vs 14.2±2.1 fmol cAMP/viable cell, n=4, P<0.05) and in the presence of 1 μM isoprenaline or 10 μM forskolin. ACVI myocytes had increased basal contraction (% shortening: GFP vs ACVI: 1.90±1.36 vs 3.91±2.29, P<0.0001) and decreased basal R50 (GFP vs ACVI: 62.6±24.2 ms (n=50) vs 45.0±17.2 ms (n=248), P<0.0001). ACVI myocyte responses were increased for forskolin (Emax: GFP=6.70±1.59 (n=6); ACVI=9.06±0.69 (n=14), P<0.01) but not isoprenaline. ACVI myocyte responses were increased (Emax: GFP vs ACVI=3.16±0.77 vs 5.10±0.60, P<0.0001) to xamoterol (a partial β1AR-selective agonist) under β2AR blockade (+50 nM ICI 118, 551). AS decreased both control and ACVI-stimulated xamoterol responses (Emax: AS=2.59±1.42, SAS=1.38±0.5). ACVI response was not mimicked by IBMX. Conversely, response through β2 adrenergic receptor (β2AR) was decreased in ACVI myocytes. In conclusion, ACVI overexpression constitutively increases myocyte contraction amplitudes by raising cAMP levels. Native ACVI did not contribute to basal cAMP production or contraction

  5. Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis

    PubMed Central

    Jiang, Jianming; Burgon, Patrick G.; Wakimoto, Hiroko; Onoue, Kenji; Gorham, Joshua M.; O’Meara, Caitlin C.; Fomovsky, Gregory; McConnell, Bradley K.; Lee, Richard T.; Seidman, J. G.; Seidman, Christine E.

    2015-01-01

    Homozygous cardiac myosin binding protein C-deficient (Mybpct/t) mice develop dramatic cardiac dilation shortly after birth; heart size increases almost twofold. We have investigated the mechanism of cardiac enlargement in these hearts. Throughout embryogenesis myocytes undergo cell division while maintaining the capacity to pump blood by rapidly disassembling and reforming myofibrillar components of the sarcomere throughout cell cycle progression. Shortly after birth, myocyte cell division ceases. Cardiac MYBPC is a thick filament protein that regulates sarcomere organization and rigidity. We demonstrate that many Mybpct/t myocytes undergo an additional round of cell division within 10 d postbirth compared with their wild-type counterparts, leading to increased numbers of mononuclear myocytes. Short-hairpin RNA knockdown of Mybpc3 mRNA in wild-type mice similarly extended the postnatal window of myocyte proliferation. However, adult Mybpct/t myocytes are unable to fully regenerate the myocardium after injury. MYBPC has unexpected inhibitory functions during postnatal myocyte cytokinesis and cell cycle progression. We suggest that human patients with homozygous MYBPC3-null mutations develop dilated cardiomyopathy, coupled with myocyte hyperplasia (increased cell number), as observed in Mybpct/t mice. Human patients, with heterozygous truncating MYBPC3 mutations, like mice with similar mutations, have hypertrophic cardiomyopathy. However, the mechanism leading to hypertrophic cardiomyopathy in heterozygous MYBPC3+/− individuals is myocyte hypertrophy (increased cell size), whereas the mechanism leading to cardiac dilation in homozygous Mybpc3−/− mice is primarily myocyte hyperplasia. PMID:26153423

  6. Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis.

    PubMed

    Jiang, Jianming; Burgon, Patrick G; Wakimoto, Hiroko; Onoue, Kenji; Gorham, Joshua M; O'Meara, Caitlin C; Fomovsky, Gregory; McConnell, Bradley K; Lee, Richard T; Seidman, J G; Seidman, Christine E

    2015-07-21

    Homozygous cardiac myosin binding protein C-deficient (Mybpc(t/t)) mice develop dramatic cardiac dilation shortly after birth; heart size increases almost twofold. We have investigated the mechanism of cardiac enlargement in these hearts. Throughout embryogenesis myocytes undergo cell division while maintaining the capacity to pump blood by rapidly disassembling and reforming myofibrillar components of the sarcomere throughout cell cycle progression. Shortly after birth, myocyte cell division ceases. Cardiac MYBPC is a thick filament protein that regulates sarcomere organization and rigidity. We demonstrate that many Mybpc(t/t) myocytes undergo an additional round of cell division within 10 d postbirth compared with their wild-type counterparts, leading to increased numbers of mononuclear myocytes. Short-hairpin RNA knockdown of Mybpc3 mRNA in wild-type mice similarly extended the postnatal window of myocyte proliferation. However, adult Mybpc(t/t) myocytes are unable to fully regenerate the myocardium after injury. MYBPC has unexpected inhibitory functions during postnatal myocyte cytokinesis and cell cycle progression. We suggest that human patients with homozygous MYBPC3-null mutations develop dilated cardiomyopathy, coupled with myocyte hyperplasia (increased cell number), as observed in Mybpc(t/t) mice. Human patients, with heterozygous truncating MYBPC3 mutations, like mice with similar mutations, have hypertrophic cardiomyopathy. However, the mechanism leading to hypertrophic cardiomyopathy in heterozygous MYBPC3(+/-) individuals is myocyte hypertrophy (increased cell size), whereas the mechanism leading to cardiac dilation in homozygous Mybpc3(-/-) mice is primarily myocyte hyperplasia. PMID:26153423

  7. Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation.

    PubMed

    Xu, Guo-Jun; Gan, Tian-Yi; Tang, Bao-Peng; Chen, Zu-Heng; Mahemuti, Ailiman; Jiang, Tao; Song, Jian-Guo; Guo, Xia; Li, Yao-Dong; Zhou, Xian-Hui; Zhang, Yu; Li, Jin-Xin

    2013-11-01

    The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L-type Ca2+ current (ICa-L) in cells in the left atrium. The mRNA and protein expression of the L-type calcium channel alc subunit (LVDCCa1c) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD90), lower AP plateau potential and peak ICa-L current densities (P<0.05). In the adult and aged groups, AF led to a higher maximum diastolic potential, an increase in AP amplitude and decreases in APD90, AP plateau potential and peak ICa-L densities (P<0.05). Compared with the control group, the mRNA and protein expression levels of LVDCCa1c were decreased in the aged groups; however, the mRNA and protein expression of calpain 1 was increased in the adult and the aged groups with AF (P<0.05). Samples of atrial tissue exhibited abnormal histopathological and ultrastructural changes, such as accelerated fibrosis and apoptosis with aging and in AF. Age-related alterations in atrial tissues were attributed to the increased expression of calpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF. PMID:24043247

  8. Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation.

    PubMed

    Hodgson-Zingman, Denice M; Karst, Margaret L; Zingman, Leonid V; Heublein, Denise M; Darbar, Dawood; Herron, Kathleen J; Ballew, Jeffrey D; de Andrade, Mariza; Burnett, John C; Olson, Timothy M

    2008-07-10

    Atrial fibrillation is a common arrhythmia that is hereditary in a small subgroup of patients. In a family with 11 clinically affected members, we mapped an atrial fibrillation locus to chromosome 1p36-p35 and identified a heterozygous frameshift mutation in the gene encoding atrial natriuretic peptide. Circulating chimeric atrial natriuretic peptide (ANP) was detected in high concentration in subjects with the mutation, and shortened atrial action potentials were seen in an isolated heart model, creating a possible substrate for atrial fibrillation. This report implicates perturbation of the atrial natriuretic peptide-cyclic guanosine monophosphate (cGMP) pathway in cardiac electrical instability. PMID:18614783

  9. Atrial mass: a myxoma?

    PubMed

    Chatzis, Andrew C; Kostopanagiotou, Kostas; Kousi, Theofili; Mitropoulos, Fotios

    2016-08-01

    A middle-aged woman with a history of resected colorectal cancer and receiving chemotherapy presented with a right atrial mass and the provisional diagnosis of myxoma supported by echocardiography, computed tomography, and magnetic resonance imaging. Successful surgical removal revealed organized thrombus instead. Atrial thrombus may be mistaken for myxoma and long-term intracardiac indwelling catheters can be thrombogenic. PMID:27525099

  10. ANTIARRHYTHMIC DRUG-INDUCED INTERNALIZATION OF THE ATRIAL SPECIFIC K+ CHANNEL, Kv1.5

    PubMed Central

    Schumacher, Sarah M.; McEwen, Dyke P.; Zhang, Lian; Arendt, Kristin L.; Van Genderen, Kristin M.; Martens, Jeffrey R.

    2009-01-01

    Conventional antiarrhythmic drugs target the ion permeability of channels, but increasing evidence suggests that functional ion channel density can also be modified pharmacologically. Kv1.5 mediates the ultrarapid potassium current (IKur) that controls atrial action potential duration. Given the atrial specific expression of Kv1.5 and its alterations in human atrial fibrillation, significant effort has been made to identify novel channel blockers. In this study, treatment of HL-1 atrial myocytes expressing Kv1.5-GFP with the class I antiarrhythmic agent quinidine, resulted in a dose-, and temperature-dependent internalization of Kv1.5, concomitant with channel block. This quinidine-induced channel internalization was confirmed in acutely dissociated neonatal myocytes. Channel internalization was subunit-dependent, activity-independent, stereospecific, and blocked by pharmacologic disruption of the endocytic machinery. Pore block and channel internalization partially overlap in the structural requirements for drug binding. Surprisingly, quinidine-induced endocytosis was calcium-dependent and therefore unrecognized by previous biophysical studies focused on isolating channel-drug interactions. Importantly, while acute quinidine-induced internalization was reversible, chronic treatment led to channel degradation. Together, these data reveal a novel mechanism of antiarrhythmic drug action and highlight the possibility for new agents that selectively modulate the stability of channel protein in the membrane as an approach for treating cardiac arrhythmias. PMID:19443837

  11. Video-assisted thoracoscopic surgery atrial clipping for atrial fibrillation.

    PubMed

    Mithiran, Harish; Sule, Jai; Sazzad, Faizus; Ong, Yilin; Kah Ti, Lian; Kofidis, Theo

    2016-05-01

    The majority of thrombi that arise due to atrial fibrillation occur in the left atrial appendage. Eliminating this cul-de-sac within the left atrium reduces the risk of stroke in these patients. We present a unique case of left atrial appendage occlusion performed via video-assisted thoracoscopic surgery, using an Atriclip to occlude the left atrial appendage in a patient with atrial fibrillation in whom anticoagulation was contraindicated due to a history of recurrent upper gastrointestinal bleeding. PMID:25504982

  12. Expression and protective effects of urocortin in cardiac myocytes.

    PubMed

    Okosi, A; Brar, B K; Chan, M; D'Souza, L; Smith, E; Stephanou, A; Latchman, D S; Chowdrey, H S; Knight, R A

    1998-04-01

    Reverse transcription PCR showed that mRNA encoding the CRH-like molecule, urocortin, is expressed in a rat cardiac myocyte cell line and in primary cultures of cardiac myocytes. Identity of the amplified with the published sequence was established by restriction mapping and direct sequencing. Expression of urocortin mRNA was increased 12-18 h after thermal injury. Urocortin peptide protected cardiac myocytes from cell death induced by hypoxia. The data suggest that urocortin is an endogenous cardiac myocyte peptide which modulates the cellular response to stress. PMID:9639256

  13. [Cardioversion and atrial stunning].

    PubMed

    Dabek, Józefa; Gasior, Zbigniew; Monastyrska-Cup, Barbara; Jakubowski, Daniel

    2007-03-01

    Stunned atrium is defined as a state of temporary mechanic atrial dysfunction with preserved bioeletrical function. It may follow up to 38-80% successful cardioversions performed to convert atrial fibrillation to regular sinus rhythm. Lack of effective atrial contractility leads to hemodynamic changes, which may result in thrombus formation with subsequent thromboembolic events. It becomes a priority to research in depth the pathophysiology of stunned atrium phenomenon and form strategies to avoid complications associated with it. Studies have shown, that even patients who had no evidence of thrombotic material (as proven by transesophageal echocardiography performed prior to cardioversion), are still at increased risk of embolic events. This fact created basis for hypothesis, that conditions for clot formation may be met only when sinus rhythm is restored. 93% of thrombi are accompanied by so-called spontaneous contrast phenomenon. The purpose of our study was to find relations between factors contributing to stunned atrium and its cellular mechanisms. It is suggested, that stunned atrium results from changes in atrial muscular membrane which occur during atrial fibrillation. Stunned atrium is encountered more frequently in patients with coronary artery disease than in hypertensive heart disease or even lone atrial fibrillation. It is also associated with rheumatic valvular abnormalities and left ventricular dysfunction from other causes. Studies have shown no correlation between the frequency of stunned atrium and the mode of cardioversion. It was observed, that duration of atrial fibrillation and dimensions of atria have substantial impact on time to mechanical function recovery and magnitude of atrial stunning. Studies on subjects undergoing cardioversion due to atrial fibrillation proved that there is a higher tendency to stunned atrium in patients with atrial enlargement. Due to significant delay until full mechanical function recovery, it is of prominent

  14. 5-HT4 and 5-HT2 receptors antagonistically influence gap junctional coupling between rat auricular myocytes.

    PubMed

    Derangeon, Mickaël; Bozon, Véronique; Defamie, Norah; Peineau, Nicolas; Bourmeyster, Nicolas; Sarrouilhe, Denis; Argibay, Jorge A; Hervé, Jean-Claude

    2010-01-01

    5-hydroxytryptamine-4 (5-HT(4)) receptors have been proposed to contribute to the generation of atrial fibrillation in human atrial myocytes, but it is unclear if these receptors are present in the hearts of small laboratory animals (e.g. rat). In this study, we examined presence and functionality of 5-HT(4) receptors in auricular myocytes of newborn rats and their possible involvement in regulation of gap junctional intercellular communication (GJIC, responsible for the cell-to-cell propagation of the cardiac excitation). Western-blotting assays showed that 5-HT(4) receptors were present and real-time RT-PCR analysis revealed that 5-HT(4b) was the predominant isoform. Serotonin (1 microM) significantly reduced cAMP concentration unless a selective 5-HT(4) inhibitor (GR113808 or ML10375, both 1 microM) was present. Serotonin also reduced the amplitude of L-type calcium currents and influenced the strength of GJIC without modifying the phosphorylation profiles of the different channel-forming proteins or connexins (Cxs), namely Cx40, Cx43 and Cx45. GJIC was markedly increased when serotonin exposure occurred in presence of a 5-HT(4) inhibitor but strongly reduced when 5-HT(2A) and 5-HT(2B) receptors were inhibited, showing that activation of these receptors antagonistically regulated GJIC. The serotoninergic response was completely abolished when 5-HT(4), 5-HT(2A) and 5-HT(2B) were simultaneously inhibited. A 24 h serotonin exposure strongly reduced Cx40 expression whereas Cx45 was less affected and Cx43 still less. In conclusion, this study revealed that 5-HT(4) (mainly 5-HT(4b)), 5-HT(2A) and 5-HT(2B) receptors coexisted in auricular myocytes of newborn rat, that 5-HT(4) activation reduced cAMP concentration, I(Ca)(L) and intercellular coupling whereas 5-HT(2A) or 5-HT(2B) activation conversely enhanced GJIC. PMID:19615378

  15. Developmental stage-specific regulation of atrial natriuretic factor gene transcription in cardiac cells.

    PubMed Central

    Argentin, S; Ardati, A; Tremblay, S; Lihrmann, I; Robitaille, L; Drouin, J; Nemer, M

    1994-01-01

    Cardiac myocytes undergo a major genetic switch within the first week of postnatal development, when cell division ceases terminally and many cardiac genes are either activated or silenced. We have developed stage-specific cardiocyte cultures to analyze transcriptional control of the rat atrial natriuretic factor (ANF) gene to identify the mechanisms underlying tissue-specific and developmental regulation of this gene in the heart. The first 700 bp of ANF flanking sequences was sufficient for cardiac muscle- and stage-specific expression in both atrial and ventricular myocytes, and a cardiac muscle-specific enhancer was localized between -136 and -700 bp. Deletion of this enhancer markedly reduced promoter activity in cardiac myocytes and derepressed ANF promoter activity in nonexpressing cells. Two distinct domains of the enhancer appeared to contribute differentially to cardiac specificity depending on the differentiation stage of the myocytes. DNase I footprinting of the enhancer domain active in differentiated cells revealed four putative regulatory elements including an A+T-rich region and a CArG element. Deletion mutagenesis and promoter reconstitution assays revealed an important role for the CArG-containing element exclusively in cardiac cells, where its activity was switched on in differentiated myocytes. Transcriptional activity of the ANF-CArG box correlated with the presence of a cardiac- and stage-specific DNA-binding complex which was not recognized by the c-fos serum response element. Thus, the use of this in vitro model system representing stage-specific cardiac development unraveled the presence of different regulatory mechanisms for transcription of the ANF gene during cardiac differentiation and may be useful for studying the regulatory pathways of other genes that undergo switching during cardiac myogenesis. Images PMID:8264645

  16. Atrial fibrillation ablation.

    PubMed

    Pappone, Carlo; Santinelli, Vincenzo

    2012-06-01

    Atrial fibrillation is the commonest cardiac arrhythmia, with significant morbidity related to symptoms, heart failure, and thromboembolism, which is associated with excess mortality. Over the past 10 years, many centers worldwide have reported high success rates and few complications after a single ablation procedure in patients with paroxysmal atrial fibrillation. Recent studies indicate a short-term and long-term superiority of catheter ablation as compared with conventional antiarrhythmic drug therapy in terms of arrhythmia recurrence, quality of life, and arrhythmia progression. As a result, catheter ablation is evolving to a front-line therapy in many patients with atrial fibrillation. However, in patients with persistent long-standing atrial fibrillation catheter ablation strategy is more complex and time-consuming, frequently requiring repeat procedures to achieve success rates as high as in paroxysmal atrial fibrillation. In the near future, however, with growing experience and evolving technology, catheter ablation of atrial fibrillation may be extended also to patients with long-standing atrial fibrillation. PMID:22541284

  17. Multifocal atrial tachycardia

    MedlinePlus

    ... atrial tachycardia (MAT), many locations in the atria fire signals at the same time. Too many signals ... people with conditions that lower the amount of oxygen in the blood. These conditions include: Bacterial pneumonia ...

  18. Atrial Fibrillation Medications

    MedlinePlus

    ... think you are pregnant If you notice red, dark brown or black urine or stools If you ... Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • Understand your Risk for AFib Children • Symptoms of ...

  19. Atrial fibrillation or flutter

    MedlinePlus

    ... the mitral valve) Hypertension Medicines Overactive thyroid gland ( hyperthyroidism ) Pericarditis Sick sinus syndrome Symptoms You may not ... procedures Heart attack Heart pacemaker High blood pressure Hyperthyroidism Pericarditis Pulse Stable angina Stroke Patient Instructions Atrial ...

  20. What Is Atrial Fibrillation?

    MedlinePlus

    ... regular beat. Certain cells in your heart make electric signals that cause the heart to contract and ... read your ECG to find out if the electric signals are normal. In atrial fibrillation (AFib), the ...

  1. Chronic activation of extracellular-signal-regulated protein kinases by phenylephrine is required to elicit a hypertrophic response in cardiac myocytes.

    PubMed Central

    Barron, Anthony J; Finn, Stephen G; Fuller, Stephen J

    2003-01-01

    Extracellular-signal-regulated protein kinases (ERKs) are activated rapidly and transiently in response to phenylephrine (PE) and endothelin-1 (ET-1) in cardiac myocytes, but whether this is linked to the subsequent development of the hypertrophic phenotype remains equivocal. To investigate this, we examined the dependence of the hypertrophic response on the length of exposure to PE in neonatal myocyte cultures. In addition to the initial transient activation of ERKs (maximum at 5-10 min), PE (10 microM) induced a second, more prolonged peak of activity several hours later. The activity of a transfected atrial natriuretic factor-luciferase reporter gene was increased 10- to 24-fold by PE. This response was inhibited by the alpha(1)-antagonist prazosin (100 nM) and by U0126 (10 microM) and PD184352 (1 microM), inhibitors of ERK activation, irrespective of whether these were added before or up to 24 h after the addition of PE. Prazosin had no effect on ET-1 (50 nM)-stimulated atrial natriuretic factor-luciferase activity. Protein synthesis was enhanced by 35+/-6% by PE, and this was blocked by prazosin added 1 h after the addition of PE, but decreased only by half when added 8 h after PE. Similarly, PE (48 h) increased myocyte area by 49% and this was prevented by prazosin added 1 h after PE, but decreased only by half when added at 24 h. These results demonstrate that prolonged exposure to PE is required to elicit alterations in gene expression, protein synthesis and cell size, characteristic of hypertrophied myocytes, and they confirm that the initial peak of ERK activity is insufficient to trigger hypertrophic responses. PMID:12513686

  2. Inhibition of Thromboxane A2-Induced Arrhythmias and Intracellular Calcium Changes in Cardiac Myocytes by Blockade of the Inositol Trisphosphate Pathway

    PubMed Central

    Kosloski, L. M.; Gilbert, W. J. R.; Touchberry, C. D.; Moore, D. S.; Kelly, J. K.; Brotto, M.; Orr, J. A.

    2009-01-01

    We have recently reported that left atrial injections of the thromboxane A2 (TXA2) mimetic, (5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxy-1-octenyl]-2 -oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid (U46619), induced ventricular arrhythmias in the anesthetized rabbit. Data from this study led us to hypothesize that TXA2 may be inducing direct actions on the myocardium to induce these arrhythmias. The aim of this study was to further elucidate the mechanism responsible for these arrhythmias. We report that TXA2R is expressed at both the gene and protein levels in atrial and ventricular samples of adult rabbits. In addition, TXA2R mRNA was identified in single, isolated ventricular cardiac myocytes. Furthermore, treatment of isolated cardiac myocytes with U46619 increased intracellular calcium in a dose-dependent manner and these increases were blocked by the specific TXA2R antagonist, 7-(3-((2-((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5-heptenoic acid (SQ29548). Pretreatment of myocytes with an inhibitor of inositol trisphosphate (IP3) formation, gentamicin, or with an inhibitor of IP3 receptors, 2-aminoethoxydiphenylborate (2-APB), blocked the increase in intracellular calcium. In vivo pretreatment of anesthetized rabbits with either gentamicin or 2-APB subsequently inhibited the formation of ventricular arrhythmias elicited by U46619. These data support the hypothesis that TXA2 can induce arrhythmias via a direct action on cardiac myocytes. Furthermore, these arrhythmogenic actions were blocked by inhibitors of the IP3 pathway. In summary, this study provides novel evidence for direct TXA2-induced cardiac arrhythmias and provides a rationale for IP3 as a potential target for the treatment of TXA2-mediated arrhythmias. PMID:19741149

  3. Patterning, Prestress, and Peeling Dynamics of Myocytes

    PubMed Central

    Griffin, Maureen A.; Engler, Adam J.; Barber, Thomas A.; Healy, Kevin E.; Sweeney, H. Lee; Discher, Dennis E.

    2004-01-01

    As typical anchorage-dependent cells myocytes must balance contractility against adequate adhesion. Skeletal myotubes grown as isolated strips from myoblasts on micropatterned glass exhibited spontaneous peeling after one end of the myotube was mechanically detached. Such results indicate the development of a prestress in the cells. To assess this prestress and study the dynamic adhesion strength of single myocytes, the shear stress of fluid aspirated into a large-bore micropipette was then used to forcibly peel myotubes. The velocity at which cells peeled from the surface, Vpeel, was measured as a continuously increasing function of the imposed tension, Tpeel, which ranges from ∼0 to 50 nN/μm. For each cell, peeling proved highly heterogeneous, with Vpeel fluctuating between 0 μm/s (∼80% of time) and ∼10 μm/s. Parallel studies of smooth muscle cells expressing GFP-paxillin also exhibited a discontinuous peeling in which focal adhesions fractured above sites of strong attachment (when pressure peeled using a small-bore pipette). The peeling approaches described here lend insight into the contractile-adhesion balance and can be used to study the real-time dynamics of stressed adhesions through both physical detection and the use of GFP markers; the methods should prove useful in comparing normal versus dystrophic muscle cells. PMID:14747355

  4. Perturbed atrial calcium handling in an ovine model of heart failure: potential roles for reductions in the L-type calcium current.

    PubMed

    Clarke, Jessica D; Caldwell, Jessica L; Horn, Margaux A; Bode, Elizabeth F; Richards, Mark A; Hall, Mark C S; Graham, Helen K; Briston, Sarah J; Greensmith, David J; Eisner, David A; Dibb, Katharine M; Trafford, Andrew W

    2015-02-01

    Heart failure (HF) is commonly associated with reduced cardiac output and an increased risk of atrial arrhythmias particularly during β-adrenergic stimulation. The aim of the present study was to determine how HF alters systolic Ca(2+) and the response to β-adrenergic (β-AR) stimulation in atrial myocytes. HF was induced in sheep by ventricular tachypacing and changes in intracellular Ca(2+) concentration studied in single left atrial myocytes under voltage and current clamp conditions. The following were all reduced in HF atrial myocytes; Ca(2+) transient amplitude (by 46% in current clamped and 28% in voltage clamped cells), SR dependent rate of Ca(2+) removal (kSR, by 32%), L-type Ca(2+) current density (by 36%) and action potential duration (APD90 by 22%). However, in HF SR Ca(2+) content was increased (by 19%) when measured under voltage-clamp stimulation. Inhibiting the L-type Ca(2+) current (ICa-L) in control cells reproduced both the decrease in Ca(2+) transient amplitude and increase of SR Ca(2+) content observed in voltage-clamped HF cells. During β-AR stimulation Ca(2+) transient amplitude was the same in control and HF cells. However, ICa-L remained less in HF than control cells whilst SR Ca(2+) content was highest in HF cells during β-AR stimulation. The decrease in ICa-L that occurs in HF atrial myocytes appears to underpin the decreased Ca(2+) transient amplitude and increased SR Ca(2+) content observed in voltage-clamped cells. PMID:25463272

  5. Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes

    SciTech Connect

    Hassin, D.; Fixler, R.; Shimoni, Y.; Rubinstein, E.; Raz, S.; Gotsman, M.S.; Hasin, Y.

    1987-01-01

    The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by /sup 45/Ca tracer measurements after loading the myocytes with /sup 45/Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect.

  6. MDIMP, a novel cardiac Ca(2+) channel blocker with atrial selectivity.

    PubMed

    Santamaria-Herrera, Mireille Aline; Ríos-Pérez, Erick Benjamín; de la Rosa, Juan Antonio Manuel; García-Castañeda, Maricela; Osornio-Garduño, Diana Stephanie; Ramos-Mondragón, Roberto; Mancilla-Percino, Teresa; Avila, Guillermo

    2016-06-15

    In cardiac muscle cells both T-and L-type Ca(2+) channels (TTCCs and LTCCs, respectively) are expressed, and the latter are relevant to a process known as excitation-contraction coupling (ECC). Evidence obtained from docking studies suggests that isoindolines derived from α-amino acids bind to the LTCC CaV1.2. In the present study, we investigated whether methyl (S)-2-(1,3-dihydroisoindol-2-yl)-4-methylpentanoate (MDIMP), which is derived from L-leucine, modulates both Ca(2+) channels and ECC. To this end, mechanical properties, as well as Ca(2+) transients and currents, were all investigated in isolated cardiac myocytes. The effects of MDIMP on CaV1.2 (transiently expressed in 293T/17 cells) were also studied. In this system, evidence was found for an inhibitory action that develops and recovers in min, with an IC50 of 450µM. With respect to myocytes: atrial-TTCCs, atrial-LTCCs, and ventricular-LTCCs were also inhibited, in that order of potency. Accordingly, Ca(2+) transients, contractions, and window currents of LTCCs were all reduced more strongly in atrial cells. Interestingly, while the modulation of LTCCs was state-independent in these cells, it was state-dependent, and dual, on the ventricular ones. Furthermore, practically all of the ventricular LTCCs were closed at resting membrane potentials. This could explain their resistance to MDIMP, as they were affected in only open or inactivated states. All these features in turn explain the preferential down-regulation of the atrial ECC. Thus, our results support the view that isoindolines bind to Ca(2+) channels, improve our knowledge of the corresponding structure-function relationship, and may be relevant for conditions where decreased atrial activity is desired. PMID:27089820

  7. Atrial selectivity of antiarrhythmic drugs

    PubMed Central

    Ravens, Ursula; Poulet, Claire; Wettwer, Erich; Knaut, Michael

    2013-01-01

    New antiarrhythmic drugs for treatment of atrial fibrillation should ideally be atrial selective in order to avoid pro-arrhythmic effects in the ventricles. Currently recognized atrial selective targets include atrial Nav1.5 channels, Kv1.5 channels and constitutively active Kir3.1/3.4 channels, each of which confers atrial selectivity by different mechanisms. Na+ channel blockers with potential- and frequency-dependent action preferentially suppress atrial fibrillation because of the high excitation rate and less negative atrial resting potential, which promote drug binding in atria. Kv1.5 channels are truly atrial selective because they do not conduct repolarizing current IKur in ventricles. Constitutively active IK,ACh is predominantly observed in remodelled atria from patients in permanent atrial fibrillation (AF). A lot of effort has been invested to detect compounds which will selectively block Kir3.1/Kir3.4 in their remodelled constitutively active form. Novel drugs which have been and are being developed aim at atrial-selective targets. Vernakalant and ranolazine which mainly block atrial Na+ channels are clinically effective. Newly designed selective IKur blockers and IK,ACh blockers are effective in animal models; however, clinical benefit in converting AF into sinus rhythm (SR) or reducing AF burden remains to be demonstrated. In conclusion, atrial-selective antiarrhythmic agents have a lot of potential, but a long way to go. PMID:23732646

  8. Atrial Fibrillation (AF or AFib)

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Atrial Fibrillation (AF or AFib) Updated:Feb 10,2016 What ... to the Terms and Conditions and Privacy Policy Atrial Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • ...

  9. Anticoagulation in atrial fibrillation

    PubMed Central

    Piccini, Jonathan P

    2014-01-01

    Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin’s shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment. PMID:24733535

  10. Anticoagulation in atrial fibrillation.

    PubMed

    Steinberg, Benjamin A; Piccini, Jonathan P

    2014-01-01

    Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin's shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment. PMID:24733535

  11. A MicroRNA-Transcription Factor Blueprint for Early Atrial Arrhythmogenic Remodeling

    PubMed Central

    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

  12. A MicroRNA-Transcription Factor Blueprint for Early Atrial Arrhythmogenic Remodeling.

    PubMed

    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

  13. The contribution of pathways initiated via the Gq\\11 G-protein family to atrial fibrillation.

    PubMed

    Tinker, Andrew; Finlay, Malcom; Nobles, Muriel; Opel, Aaisha

    2016-03-01

    Atrial fibrillation is the commonest cardiac arrhythmia and leads to significant clinical morbidity and mortality. It has a complex pathophysiology but is often initiated by atrial ectopic beats and because of atrial remodelling once it occurs it can become established. Thus therapeutic interventions designed to prevent the initial occurrence of the arrhythmia are particularly needed. At the cellular level, these ectopic beats arise because of abnormal calcium release events from the sarcoplasmic reticulum leading to an inward current mediated by the sodium-calcium exchanger. There has been considerable interest in this over the last few years largely focused on the ryanodine receptor and related signalling pathways. However, atrial myocytes also possess a well-developed inositol trisphosphate (IP3) dependent calcium release system and this has been less studied. In this review we focus on pathways and molecules that couple via the Gq\\11 family of G-proteins including regulators of G-protein signalling that may influence IP3 mediated calcium release and atrial fibrillation. PMID:26773203

  14. Left Atrial Appendage Aneurysm.

    PubMed

    Hosseini, Saeid; Hashemi, Arash; Saedi, Sedigheh; Jalili, Farshad; Maleki, Majid; Jalalian, Rozita; Rezaei, Yousef

    2016-09-01

    Left atrial appendage aneurysms (LAAA) are extremely rare. This condition is usually diagnosed incidentally or after the occurrence of thrombotic events or cardiac tachyarrhythmias in the second to fourth decades of life. It can predispose to hazardous adverse events, including atrial fibrillation, myocardial infarction, and systemic thromboembolism. We report a case of LAAA in a 68-year-old woman presenting with atypical chest pain, exertional dyspnea, and episodes of sudden-onset palpitation. Aneurysmectomy with the patient under cardiac arrest with cardiopulmonary bypass was performed. In addition, we explore the diagnosis, management, and prognosis of this entity through a meticulous literature review. PMID:27549544

  15. Right atrial spleen.

    PubMed Central

    Kuijer, P; Dion, R; van Merrienboer, F

    1985-01-01

    A large cardiac tumour occupying most of the right atrium and the right ventricle and causing inflow obstruction to the right heart was confirmed by cross sectional echocardiography in a 41 year old man. After surgical resection histological examination showed that the atrial tumour had the characteristics of splenic tissue. Possible mechanisms for the development of such a tumour include an origin analogous to that of an accessory spleen or the implantation and subsequent growth of lymphoid tissue in a pre-existing superior vena caval or high right atrial angioma. Images PMID:4041304

  16. STIM1 enhances SR Ca2+ content through binding phospholamban in rat ventricular myocytes

    PubMed Central

    Zhao, Guiling; Li, Tianyu; Brochet, Didier X. P.; Rosenberg, Paul B.; Lederer, W. J.

    2015-01-01

    In ventricular myocytes, the physiological function of stromal interaction molecule 1 (STIM1), an endo/sarcoplasmic reticulum (ER/SR) Ca2+ sensor, is unclear with respect to its cellular localization, its Ca2+-dependent mobilization, and its action on Ca2+ signaling. Confocal microscopy was used to measure Ca2+ signaling and to track the cellular movement of STIM1 with mCherry and immunofluorescence in freshly isolated adult rat ventricular myocytes and those in short-term primary culture. We found that endogenous STIM1 was expressed at low but measureable levels along the Z-disk, in a pattern of puncta and linear segments consistent with the STIM1 localizing to the junctional SR (jSR). Depleting SR Ca2+ using thapsigargin (2–10 µM) changed neither the STIM1 distribution pattern nor its mobilization rate, evaluated by diffusion coefficient measurements using fluorescence recovery after photobleaching. Two-dimensional blue native polyacrylamide gel electrophoresis and coimmunoprecipitation showed that STIM1 in the heart exists mainly as a large protein complex, possibly a multimer, which is not altered by SR Ca2+ depletion. Additionally, we found no store-operated Ca2+ entry in control or STIM1 overexpressing ventricular myocytes. Nevertheless, STIM1 overexpressing cells show increased SR Ca2+ content and increased SR Ca2+ leak. These changes in Ca2+ signaling in the SR appear to be due to STIM1 binding to phospholamban and thereby indirectly activating SERCA2a (Sarco/endoplasmic reticulum Ca2+ ATPase). We conclude that STIM1 binding to phospholamban contributes to the regulation of SERCA2a activity in the steady state and rate of SR Ca2+ leak and that these actions are independent of store-operated Ca2+ entry, a process that is absent in normal heart cells. PMID:26261328

  17. A Mathematical Model of the Mouse Ventricular Myocyte Contraction

    PubMed Central

    Mullins, Paula D.; Bondarenko, Vladimir E.

    2013-01-01

    Mathematical models of cardiac function at the cellular level include three major components, such as electrical activity, Ca2+ dynamics, and cellular shortening. We developed a model for mouse ventricular myocyte contraction which is based on our previously published comprehensive models of action potential and Ca2+ handling mechanisms. The model was verified with extensive experimental data on mouse myocyte contraction at room temperature. In the model, we implemented variable sarcomere length and indirect modulation of the tropomyosin transition rates by Ca2+ and troponin. The resulting model described well steady-state force-calcium relationships, dependence of the contraction force on the sarcomere length, time course of the contraction force and myocyte shortening, frequency dependence of the contraction force and cellular contraction, and experimentally measured derivatives of the myocyte length variation. We emphasized the importance of the inclusion of variable sarcomere length into a model for ventricular myocyte contraction. Differences in contraction force and cell shortening for epicardial and endocardial ventricular myocytes were investigated. Model applicability for the experimental studies and model limitations were discussed. PMID:23671664

  18. Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes.

    PubMed

    Yan, Xinhua; Schuldt, Adam J T; Price, Robert L; Amende, Ivo; Liu, Fen-Fen; Okoshi, Katashi; Ho, Kalon K L; Pope, Adèle J; Borg, Thomas K; Lorell, Beverly H; Morgan, James P

    2008-03-01

    The role of the angiotensin II type 2 (AT2) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT2 receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT2TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice. PMID:18178728

  19. Exploiting periodicity to extract the atrial activity in atrial arrhythmias

    NASA Astrophysics Data System (ADS)

    Llinares, Raul; Igual, Jorge

    2011-12-01

    Atrial fibrillation disorders are one of the main arrhythmias of the elderly. The atrial and ventricular activities are decoupled during an atrial fibrillation episode, and very rapid and irregular waves replace the usual atrial P-wave in a normal sinus rhythm electrocardiogram (ECG). The estimation of these wavelets is a must for clinical analysis. We propose a new approach to this problem focused on the quasiperiodicity of these wavelets. Atrial activity is characterized by a main atrial rhythm in the interval 3-12 Hz. It enables us to establish the problem as the separation of the original sources from the instantaneous linear combination of them recorded in the ECG or the extraction of only the atrial component exploiting the quasiperiodic feature of the atrial signal. This methodology implies the previous estimation of such main atrial period. We present two algorithms that separate and extract the atrial rhythm starting from a prior estimation of the main atrial frequency. The first one is an algebraic method based on the maximization of a cost function that measures the periodicity. The other one is an adaptive algorithm that exploits the decorrelation of the atrial and other signals diagonalizing the correlation matrices at multiple lags of the period of atrial activity. The algorithms are applied successfully to synthetic and real data. In simulated ECGs, the average correlation index obtained was 0.811 and 0.847, respectively. In real ECGs, the accuracy of the results was validated using spectral and temporal parameters. The average peak frequency and spectral concentration obtained were 5.550 and 5.554 Hz and 56.3 and 54.4%, respectively, and the kurtosis was 0.266 and 0.695. For validation purposes, we compared the proposed algorithms with established methods, obtaining better results for simulated and real registers.

  20. Ion transfer characteristics of the calcium current in bull-frog atrial myocytes.

    PubMed Central

    Campbell, D L; Giles, W R; Shibata, E F

    1988-01-01

    1. Voltage clamp studies on single cells from bull-frog atrium have been carried out to study the ion transfer characteristics of the calcium current, ICa. In agreement with the preliminary results of Hume & Giles (1983), a TTX-resistant, 'second transient inward current' was recorded consistently. Its average peak size at 0 mV in 2.5 mM [Ca2+]o Ringer solution was approximately -200 pA, and it was blocked by Cd2+ and La3+ but not by tetrodotoxin (TTX, 3 x 10(-6) M). 2. The peak size of this current increases by approximately 4 times when [Ca2+]o is raised from 1.25 to 7.5 mM, indicating that Ca2+ is a major charge carrier. 3. A well-defined reversal potential, Erev, for ICa can be recorded in normal Ringer solution and also when Ba2+ or Sr2+ serve as the charge carriers. When [Ca2+]o is changed the shifts in Erev follow the predictions of a Nernstian Ca2+ electrode. However, all Erev values are well below those predicted from the thermodynamic Nernstian ECa values (see Campbell, Giles, Hume, Noble & Shibata, 1988a). 4. The Ca2+ current exhibits voltage-dependent inactivation, whether the direction of net current flow is inward or outward; however, the rate of inactivation is affected by the species of cation carrying the current. Inactivation is reduced substantially in Ba2+ Ringer solution. 5. Magnesium (5 mM) is not a significant carrier or blocker of ICa in normal [Ca2+]o Ringer solution; however, 5 mM [Mg2+]o can block the current carried by either Sr2+ or Ba2+. In the absence of Mg2+, equimolar substitutions of Sr2+ or Ba2+ for Ca2+ result in larger currents than those carried by Ca2+ in the normal Ringer solution. 6. Sodium appears not to be a significant charge carrier in the presence of normal [Ca2+]o. However, after free [Ca2+]o has been reduced to extremely low levels (less than 10(-6) M) Na+ can carry a significant fraction of 'ICa'. Thus, it appears that the high selectivity of ICa for Ca2+ ions depends upon the presence of Ca2+. 7. 'Slow tails' are frequently recorded after repolarizing clamp steps back to the holding potential. These 'slow tails' are prominent in normal [Na+]o, [Ca2+]o and [Sr2+]o Ringer solution; however, they are markedly reduced in [Ba2+]o, in Na+-free and Ca2+-free Ringer solutions. Experimental and theoretical work suggests these slow tails may be generated by an electrogenic Na+-Ca2+ exchanger (see Campbell, Giles, Robinson & Shibata, 1988b).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2855341

  1. Measuring mitochondrial function in intact cardiac myocytes

    PubMed Central

    Dedkova, Elena N.; Blatter, Lothar A.

    2011-01-01

    Mitochondria are involved in cellular functions that go beyond the traditional role of these organelles as the power plants of the cell. Mitochondria have been implicated in several human diseases, including cardiac dysfunction, and play a role in the aging process. Many aspects of our knowledge of mitochondria stem from studies performed on the isolated organelle. Their relative inaccessibility imposes experimental difficulties to study mitochondria in their natural environment – the cytosol of intact cells – and has hampered a comprehensive understanding of the plethora of mitochondrial functions. Here we review currently available methods to study mitochondrial function in intact cardiomyocytes. These methods primarily use different flavors of fluorescent dyes and genetically encoded fluorescent proteins in conjunction with high-resolution imaging techniques. We review methods to study mitochondrial morphology, mitochondrial membrane potential, Ca2+ and Na+ signaling, mitochondrial pH regulation, redox state and ROS production, NO signaling, oxygen consumption, ATP generation and the activity of the mitochondrial permeability transition pore. Where appropriate we complement this review on intact myocytes with seminal studies that were performed on isolated mitochondria, permeabilized cells, and in whole hearts. PMID:21964191

  2. Stem Cell Stimulation of Endogenous Myocyte Regeneration

    PubMed Central

    Weil, Brian R.; Canty, John M.

    2015-01-01

    Cell-based therapy has emerged as a promising approach to combat the myocyte loss and cardiac remodeling that characterize the progression of left ventricular dysfunction to heart failure. Several clinical trials conducted during the past decade have shown that a variety of autologous bone marrow- and peripheral blood-derived stem and progenitor cell populations can be safely administered to patients with ischemic heart disease and yield modest improvements in cardiac function. Concurrently, rapid progress has been made at the preclinical level to identify novel therapeutic cell populations, delineate the mechanisms underlying cell-mediated cardiac repair, and optimize cell-based approaches for clinical use. The following review summarizes the progress that has been made in this rapidly evolving field over the past decade and examines how our current understanding of the mechanisms involved in successful cardiac regeneration should direct future investigation in this area. Particular emphasis is placed on discussion of the general hypothesis that the benefits of cell therapy primarily result from stimulation of endogenous cardiac repair processes that have only recently been identified in the adult mammalian heart, rather than direct differentiation of exogenous cells. Continued scientific investigation in this area will guide the optimization of cell-based approaches for myocardial regeneration, with the ultimate goal of clinical implementation and substantial improvement in our ability to restore cardiac function in ischemic heart disease patients. PMID:23577634

  3. Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation

    PubMed Central

    Baczko, Istvan; Liknes, David; Yang, Wei; Hamming, Kevin C; Searle, Gavin; Jaeger, Kristian; Husti, Zoltan; Juhasz, Viktor; Klausz, Gergely; Pap, Robert; Saghy, Laszlo; Varro, Andras; Dolinsky, Vernon; Wang, Shaohua; Rauniyar, Vivek; Hall, Dennis; Dyck, Jason RB; Light, Peter E

    2014-01-01

    BACKGROUND AND PURPOSE Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk for stroke, heart failure and cardiovascular-related mortality. Candidate targets for anti-AF drugs include a potassium channel Kv1.5, and the ionic currents IKACh and late INa, along with increased oxidative stress and activation of NFAT-mediated gene transcription. As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways. EXPERIMENTAL APPROACH We made whole-cell patch-clamp recordings of recombinant ion channels, human atrial IKur, rat atrial IKACh, cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. We also used a model of inducible AF in dogs. KEY RESULTS C1 inhibited human peak and late Kv1.5 currents, frequency-dependently, with IC50 of 0.36 and 0.11 μmol·L−1 respectively. C1 inhibited IKACh (IC50 of 1.9 μmol·L−1) and the Nav1.5 sodium channel current (IC50s of 3 and 1 μmol·L−1 for peak and late components respectively). C1 (1 μmol·L−1) significantly delayed contractile and calcium dysfunction in rat ventricular myocytes treated with 3 nmol·L−1 sea anemone toxin (ATX-II). C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT-inhibitory properties comparable to the parent molecule, resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg·kg−1) reduced the average and total AF duration. CONCLUSION AND IMPLICATIONS C1 behaved as a promising multifunctional small molecule targeting a number of key pathways involved in AF. PMID:24102184

  4. Clinical implications of atrial isomerism.

    PubMed Central

    Chiu, I S; How, S W; Wang, J K; Wu, M H; Chu, S H; Lue, H C; Hung, C R

    1988-01-01

    Right atrial isomerism or left atrial isomerism is frequently diagnosed as situs ambiguous without further discrimination of the specific morbid anatomy. Thirty six cases of right atrial isomerism and seven cases of left atrial isomerism were collected from the records and pathological museum at the National Taiwan University Hospital. There was a necropsy report for 18 cases. In all patients one or more of the following conditions was met: (a) isomeric bronchial anatomy, (b) echocardiographic and angiocardiographic evidence of isomerism, and (c) surgical or necropsy evidence of abnormal atrial anatomy. An anomalous pulmonary venous connection was present in 55% of patients with right atrial isomerism; in left atrial isomerism one case (14%) had a partial anomalous pulmonary venous connection. Forty per cent of cases of anomalous pulmonary venous connection with right atrial isomerism had obstruction. Six (86%) of seven cases with left atrial isomerism had an ambiguous biventricular atrioventricular connection. In contrast, univentricular atrioventricular connection (26 of 36, 72%) was significantly more common in right atrial isomerism. A common atrioventricular valve was the most frequent mode of connection in both forms. Two discrete atrioventricular valves were significantly more common in left atrial isomerism. Atrioventricular valve regurgitation was detected in 14 cases. Double outlet right ventricle was the most common type of ventriculoarterial connection. The most commonly cited causes of death after either palliative or definitive operation were undetected anomalous pulmonary venous connection, pulmonary venous stricture, and uncorrected atrioventricular valve or aortic regurgitation complicated by abnormal coagulation. Although the prognosis is poor, successful operation depends on knowledge of the precise anatomical arrangement associated with atrial isomerism. Images Fig 1 Fig 2 Fig 3 PMID:3408620

  5. Nuclear Morphology and Deformation in Engineered Cardiac Myocytes and Tissues

    PubMed Central

    Bray, Mark-Anthony; Adams, William J.; Geisse, Nicholas A.; Feinberg, Adam W.; Sheehy, Sean P.; Parker, Kevin Kit

    2010-01-01

    Cardiac tissue engineering requires finely-tuned manipulation of the extracellular matrix (ECM) microenvironment to optimize internal myocardial organization. The myocyte nucleus is mechanically connected to the cell membrane via cytoskeletal elements, making it a target for the cellular response to perturbation of the ECM. However, the role of ECM spatial configuration and myocyte shape on nuclear location and morphology is unknown. In this study, printed ECM proteins were used to configure the geometry of cultured neonatal rat ventricular myocytes. Engineered one- and two-dimensional tissue constructs and single-myocyte islands were assayed using live fluorescence imaging to examine nuclear position, morphology and motion as a function of the imposed ECM geometry during diastolic relaxation and systolic contraction. Image analysis showed that anisotropic tissue constructs cultured on microfabricated ECM lines possessed a high degree of nuclear alignment similar to that found in vivo; nuclei in isotropic tissues were polymorphic in shape with an apparently random orientation. Nuclear eccentricity was also increased for the anisotropic tissues, suggesting that intracellular forces deform the nucleus as the cell is spatially confined. During systole, nuclei experienced increasing spatial confinement in magnitude and direction of displacement as tissue anisotropy increased, yielding anisotropic deformation. Thus, the nature of nuclear displacement and deformation during systole appears to rely on a combination of the passive myofibril spatial organization and the active stress fields induced by contraction. Such findings have implications in understanding the genomic consequences and functional response of cardiac myocytes to their ECM surroundings under conditions of disease. PMID:20382423

  6. Myomaker mediates fusion of fast myocytes in zebrafish embryos

    SciTech Connect

    Landemaine, Aurélie; Rescan, Pierre-Yves; Gabillard, Jean-Charles

    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.

  7. Cytoskeletal prestress regulates nuclear shape and stiffness in cardiac myocytes

    PubMed Central

    Lee, Hyungsuk; Adams, William J; Alford, Patrick W; McCain, Megan L; Feinberg, Adam W; Sheeny, Sean P; Goss, Josue A

    2015-01-01

    Mechanical stresses on the myocyte nucleus have been associated with several diseases and potentially transduce mechanical stimuli into cellular responses. Although a number of physical links between the nuclear envelope and cytoplasmic filaments have been identified, previous studies have focused on the mechanical properties of individual components of the nucleus, such as the nuclear envelope and lamin network. The mechanical interaction between the cytoskeleton and chromatin on nuclear deformability remains elusive. Here, we investigated how cytoskeletal and chromatin structures influence nuclear mechanics in cardiac myocytes. Rapid decondensation of chromatin and rupture of the nuclear membrane caused a sudden expansion of DNA, a consequence of prestress exerted on the nucleus. To characterize the prestress exerted on the nucleus, we measured the shape and the stiffness of isolated nuclei and nuclei in living myocytes during disruption of cytoskeletal, myofibrillar, and chromatin structure. We found that the nucleus in myocytes is subject to both tensional and compressional prestress and its deformability is determined by a balance of those opposing forces. By developing a computational model of the prestressed nucleus, we showed that cytoskeletal and chromatin prestresses create vulnerability in the nuclear envelope. Our studies suggest the cytoskeletal–nuclear–chromatin interconnectivity may play an important role in mechanics of myocyte contraction and in the development of laminopathies by lamin mutations. PMID:25908635

  8. Transcriptomic alterations in Trypanosoma cruzi-infected cardiac myocytes

    PubMed Central

    Goldenberg, Regina Coeli dos Santos; Iacobas, Dumitru A.; Iacobas, Sanda; Rocha, Leonardo Lima; de Azevedo Fortes, Fabio da Silva; Vairo, Leandro; Nagajyothi, Fnu; de Carvalho, Antonio Carlos Campos; Tanowitz, Herbert B.; Spray, David C.

    2010-01-01

    Trypanosoma cruzi infection is a major cause of cardiomyopathy. Previous gene profiling studies of infected mouse hearts have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 h post-infection. Statistical comparison of gene expression levels of 7624 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected substantial (≥1.5 absolute fold changes) in 420 (5.5%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. These findings on infected cardiac myocytes in culture reveal that alterations in cardiac gene expression described in Chagas disease are the consequence of both direct infection of the myocytes themselves as well as resulting from the presence of other cell types in the myocardium and systemic effects of infection. PMID:19729072

  9. Oxidative stress decreases microtubule growth and stability in ventricular myocytes.

    PubMed

    Drum, Benjamin M L; Yuan, Can; Li, Lei; Liu, Qinghang; Wordeman, Linda; Santana, L Fernando

    2016-04-01

    Microtubules (MTs) have many roles in ventricular myocytes, including structural stability, morphological integrity, and protein trafficking. However, despite their functional importance, dynamic MTs had never been visualized in living adult myocytes. Using adeno-associated viral vectors expressing the MT-associated protein plus end binding protein 3 (EB3) tagged with EGFP, we were able to perform live imaging and thus capture and quantify MT dynamics in ventricular myocytes in real time under physiological conditions. Super-resolution nanoscopy revealed that EB1 associated in puncta along the length of MTs in ventricular myocytes. The vast (~80%) majority of MTs grew perpendicular to T-tubules at a rate of 0.06μm∗s(-1) and growth was preferentially (82%) confined to a single sarcomere. Microtubule catastrophe rate was lower near the Z-line than M-line. Hydrogen peroxide increased the rate of catastrophe of MTs ~7-fold, suggesting that oxidative stress destabilizes these structures in ventricular myocytes. We also quantified MT dynamics after myocardial infarction (MI), a pathological condition associated with increased production of reactive oxygen species (ROS). Our data indicate that the catastrophe rate of MTs increases following MI. This contributed to decreased transient outward K(+) currents by decreasing the surface expression of Kv4.2 and Kv4.3 channels after MI. On the basis of these data, we conclude that, under physiological conditions, MT growth is directionally biased and that increased ROS production during MI disrupts MT dynamics, decreasing K(+) channel trafficking. PMID:26902968

  10. Cytoskeletal prestress regulates nuclear shape and stiffness in cardiac myocytes.

    PubMed

    Lee, Hyungsuk; Adams, William J; Alford, Patrick W; McCain, Megan L; Feinberg, Adam W; Sheehy, Sean P; Goss, Josue A; Parker, Kevin Kit

    2015-11-01

    Mechanical stresses on the myocyte nucleus have been associated with several diseases and potentially transduce mechanical stimuli into cellular responses. Although a number of physical links between the nuclear envelope and cytoplasmic filaments have been identified, previous studies have focused on the mechanical properties of individual components of the nucleus, such as the nuclear envelope and lamin network. The mechanical interaction between the cytoskeleton and chromatin on nuclear deformability remains elusive. Here, we investigated how cytoskeletal and chromatin structures influence nuclear mechanics in cardiac myocytes. Rapid decondensation of chromatin and rupture of the nuclear membrane caused a sudden expansion of DNA, a consequence of prestress exerted on the nucleus. To characterize the prestress exerted on the nucleus, we measured the shape and the stiffness of isolated nuclei and nuclei in living myocytes during disruption of cytoskeletal, myofibrillar, and chromatin structure. We found that the nucleus in myocytes is subject to both tensional and compressional prestress and its deformability is determined by a balance of those opposing forces. By developing a computational model of the prestressed nucleus, we showed that cytoskeletal and chromatin prestresses create vulnerability in the nuclear envelope. Our studies suggest the cytoskeletal-nuclear-chromatin interconnectivity may play an important role in mechanics of myocyte contraction and in the development of laminopathies by lamin mutations. PMID:25908635

  11. The Multi-Domain Fibroblast/Myocyte Coupling in the Cardiac Tissue: A Theoretical Study.

    PubMed

    Greisas, Ariel; Zlochiver, Sharon

    2016-09-01

    Cardiac fibroblast proliferation and concomitant collagenous matrix accumulation (fibrosis) develop during multiple cardiac pathologies. Recent studies have demonstrated direct electrical coupling between myocytes and fibroblasts in vitro, and assessed the electrophysiological implications of such coupling. However, in the living tissues, such coupling has not been demonstrated, and only indirect coupling via the extracellular space is likely to exist. In this study we employed a multi-domain model to assess the modulation of the cardiac electrophysiological properties by neighboring fibroblasts assuming only indirect coupling. Numerical simulations in 1D and 2D human atrial models showed that extracellular coupling sustains a significant impact on conduction velocity (CV) and a less significant effect on the action potential duration. Both CV and the slope of the CV restitution increased with increasing fibroblast density. This effect was more substantial for lower extracellular conductance. In 2D, spiral waves exhibited reduced frequency with increasing fibroblast density, and the propensity of wavebreaks and complex dynamics at high pacing rates significantly increased. PMID:27150222

  12. Atrial fibrillation case study.

    PubMed

    Johnson, Sarah; Wilson, Tracey

    2016-03-01

    This article discusses the irregular heart rhythm caused by atrial fibrillation (AF). A brief overview of the pathophysiology will be provided. A case study is discussed to highlight the treatment and management of AF. The care provision describes common signs and symptoms and also the treatment and management of AF within the maternity care setting. The importance of maintaining the mother-baby dyad is highlighted. For the purpose of maintaining confidentiality the woman will be referred to as Shama. PMID:27044188

  13. Atrial fibrillation and inflammation

    PubMed Central

    Ozaydin, Mehmet

    2010-01-01

    Atrial fibrillation (AF) is the most common clinical arrhythmia. Recent investigations have suggested that inflammation might have a role in the pathophysiology of AF. In this review, the association between inflammation and AF, and the effects of several agents that have anti-inflammatory actions, such as statins, polyunsaturated fatty acids, corticosteroids and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have been investigated. PMID:21160591

  14. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    PubMed Central

    Lasher, Richard A; Pahnke, Aric Q; Johnson, Jeffrey M; Sachse, Frank B

    2012-01-01

    Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06) but less than half of the native postnatal day 12 (0.90 ± 0.06) and adult (0.91 ± 0.04) myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal that the

  15. Hyperuricemia and Atrial Fibrillation.

    PubMed

    Maharani, Nani; Kuwabara, Masanari; Hisatome, Ichiro

    2016-07-27

    The importance of atrial fibrillation (AF) as a cause of mortality and morbidity has prompted research on its pathogenesis and treatment. Recognition of AF risk factors is essential to prevent it and reduce the risk of death. Hyperuricemia has been widely accepted to be associated with the incidence of paroxysmal or persistent AF, as well as to the risk of AF in post cardiovascular surgery patients. The possible explanations for this association have been based on their relation with either oxidative stress or inflammation. To investigate the link between hyperuricemia and AF, it is necessary to refer to hyperuricemia-induced atrial remodeling. So far, both ionic channel and structural remodeling caused by hyperuricemia might be plausible explanations for the occurrence of AF. Inhibition of xanthine oxidase and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, or the use of antioxidants, along with serum uric acid (SUA) level reduction to prevent inflammation, might be useful. Uric acid transporters (UATs) play a key role in the regulation of intracellular uric acid concentration. Intracellular rather than serum uric acid level is considered more important for the pathogenesis of AF. Identification of UATs expressed in cells is thus important, and targeting UATs might become a potential strategy to reduce the risk of hyperuricemia-induced atrial fibrillation. PMID:27396561

  16. Contribution of phosphodiesterase isozymes to the regulation of the L-type calcium current in human cardiac myocytes

    PubMed Central

    Kajimoto, Katsuya; Hagiwara, Nobuhisa; Kasanuki, Hiroshi; Hosoda, Saichi

    1997-01-01

    To determine the contribution of the various phosphodiesterase (PDE) isozymes to the regulation of the L-type calcium current (ICa(L)) in the human myocardium, we investigated the effect of selective and non-selective PDE inhibitors on ICa(L) in single human atrial cells by use of the whole-cell patch-clamp method. We repeated some experiments in rabbit atrial myocytes, to make a species comparison. In human atrial cells, 100 μM pimobendan increased ICa(L) (evoked by depolarization to +10 mV from a holding potential of −40 mV) by 250.4±45.0% (n=15), with the concentration for half-maximal stimulation (EC50) being 1.13 μM. ICa(L) was increased by 100 μM UD-CG 212 by 174.5±30.2% (n=10) with an EC50 value of 1.78 μM in human atrial cells. These two agents inhibit PDE III selectively. A selective PDE IV inhibitor, rolipram (1–100 μM), did not itself affect ICa(L) in human atrial cells. However, 100 μM rolipram significantly enhanced the effect of 100 μM UD-CG 212 on ICa(L) (increase with UD-CG 212 alone, 167.9±33.9, n=5; increase with the two agents together, 270.0±52.2%; n=5, P<0.05). Rolipram also enhanced isoprenaline (5 nM)-stimulated ICa(L) by 52.9±9.3% (n=5) in human atrial cells. In rabbit atrial cells, ICa(L) at +10 mV was increased by 22.1±9.0% by UD-CG 212 (n=10) and by 67.4±12.0% (n=10) by pimobendan (each at 100 μM). These values were significantly lower than those obtained in human atrial cells (P<0.0001). Rolipram (1–100 μM) did not itself affect ICa(L) in rabbit atrial cells. However, ICa(L) was increased by 215.7±65.2% (n=10) by the combination of 100 μM UD-CG 212 and 100 μM rolipram. This value was almost 10 times larger than that obtained for the effect of 100 μM UD-CG 212 alone. These results imply a species difference: in the human atrium, the PDE III isoform seems dominant, whereas PDE IV may be more important in the rabbit atrium for regulating ICa(L). However, PDE IV might contribute

  17. Future perspectives and potential implications of cardiac myocyte apoptosis.

    PubMed

    Haunstetter, A; Izumo, S

    2000-02-01

    Recent advances in the understanding of the molecular mechanisms of apoptosis has gained increasing interest in the cardiovascular research community. Apoptotic myocyte loss has been detected in different cardiac disease states such as ischemic heart disease and congestive heart failure. In addition, some evidence for the molecular mechanisms in cardiac myocyte apoptosis has been evolving, although at present the implications thereof for clinical cardiac disease are not known in most of the cases. Based on these new insights, it is the intention of this article to highlight some topics in apoptosis research that might be of particular interest to define the future role and potentials of new therapeutic approaches aimed at preventing myocyte apoptosis. PMID:10728403

  18. [Catheter ablation of atrial flutter and paroxysmal atrial fibrillation].

    PubMed

    Márquez, Manlio F

    2003-01-01

    Radiofrequency catheter ablation has emerged as a curative therapy for atrial flutter based on studies demonstrating the role of the cavotricuspid isthmus. With a high rate of success and minimal complications, catheter ablation is the therapy of choice for patients with the common type of atrial flutter. Left atrial flutter, non-cavotricuspid isthmus dependent, and those associated with heart disease have a worst outcome with catheter ablation. Radiofrequency catheter ablation has also emerged as a curative therapy for paroxysmal atrial fibrillation based on studies demonstrating the role of triggering foci in the pulmonary veins for the initiation of atrial fibrillation. Catheter ablation is performed by a transseptal approach using radiofrequency energy at the ostium of each pulmonary vein. Mapping is guided by special catheters. Sequential radiofrequency applications eliminates or dissociates pulmonary vein muscle activity. Although complications exists, this is the only curative method for these patients. PMID:12966653

  19. Sinus Node and Atrial Arrhythmias.

    PubMed

    John, Roy M; Kumar, Saurabh

    2016-05-10

    Although sinus node dysfunction (SND) and atrial arrhythmias frequently coexist and interact, the putative mechanism linking the 2 remain unclear. Although SND is accompanied by atrial myocardial structural changes in the right atrium, atrial fibrillation (AF) is a disease of variable interactions between left atrial triggers and substrate most commonly of left atrial origin. Significant advances have been made in our understanding of the genetic and pathophysiologic mechanism underlying the development and progression of SND and AF. Although some patients manifest SND as a result of electric remodeling induced by periods of AF, others develop progressive atrial structural remodeling that gives rise to both conditions together. The treatment strategy will thus vary according to the predominant disease phenotype. Although catheter ablation will benefit patients with predominantly AF and secondary SND, cardiac pacing may be the mainstay of therapy for patients with predominant fibrotic atrial cardiomyopathy. This contemporary review summarizes current knowledge on sinus node pathophysiology with the broader goal of yielding insights into the complex relationship between sinus node disease and atrial arrhythmias. PMID:27166347

  20. Remodelling of cellular excitation (reaction) and intercellular coupling (diffusion) by chronic atrial fibrillation represented by a reaction-diffusion system

    NASA Astrophysics Data System (ADS)

    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.

  1. Mechanical and electrophysiological effects of 8-oxoberberine (JKL1073A) on atrial tissue.

    PubMed Central

    Chi, J. F.; Chu, S. H.; Lee, C. S.; Chou, N. K.; Su, M. J.

    1996-01-01

    The effects of 8-oxoberberine (JKL1073A) on contractions and electrophysiological characteristics of atrial tissues were examined. In driven left atria of the rat JKL1073A (10-100 microM) increased twitch tension dose-dependently. In spontaneously beating right atria, JKL1073A increased twitch tension but decreased beating rate slightly. The positive inotropic and the negative chronotropic effect of 30 microM JKL1073A was not affected by prazosin (1 microM), propranolol (1 microM) and 3-isobutyl-1-methyl-xanthine (10 microM) but significantly suppressed by 4-aminopyridine (2 mM 4-AP). Current-clamp study revealed that JKL1073A prolonged rat atrial action potential duration (APD). This prolongation of APD by JKL1073A was decreased by pretreating the cells with 2 mM 4-AP. Voltage-clamp study showed that JKL1073A inhibited the integral of the transient outward current (I(to)) dose-dependently with a KD value of 3.66 +/- 0.93 microM in rat atrial myocytes. The equilibrium dissociation constant (Kd) for JKL1073A bindings to open state I(to) was 0.50 +/- 0.08 microM. The suppression of I(to) by 3 microM JKL1073A was accompanied by shortening of its inactivation time constant from 52.5 +/- 0.9 ms to 16.8 +/- 0.7 ms. V(0.5) for the steady-state inactivation curve of I(to) was shifted from -25.7 +/- 3.3 mV to -34.8 +/- 3.2 mV. In human atrial cells, similar inhibition of I(to) and prolongation of APD by JKL1073A was found. The KD value of JKL1073A for inhibition of the integral of I(to) in human atrial cells is 4.03 +/- 0.02 microM. The Kd for bindings to open state I(to) is 0.5 microM. Currents through K1 channels of rat and human atrial myocytes were not inhibited by JKL1073A at concentrations up to 10 microM. These results indicate that JKL1073A exerts a positive inotropic effect by inhibition of I(to). JKL1073A inhibit I(to) by binding to open state channels or shifting of the steady-state inactivation curve of I(to). PMID:8762071

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

    SciTech Connect

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

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer 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 {gamma}-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.

  3. Ryanodine receptor cluster fragmentation and redistribution in persistent atrial fibrillation enhance calcium release

    PubMed Central

    Macquaide, Niall; Tuan, Hoang-Trong Minh; Hotta, Jun-ichi; Sempels, Wouter; Lenaerts, Ilse; Holemans, Patricia; Hofkens, Johan; Jafri, M. Saleet; Willems, Rik; Sipido, Karin R.

    2015-01-01

    Aims In atrial fibrillation (AF), abnormalities in Ca2+ release contribute to arrhythmia generation and contractile dysfunction. We explore whether ryanodine receptor (RyR) cluster ultrastructure is altered and is associated with functional abnormalities in AF. Methods and results Using high-resolution confocal microscopy (STED), we examined RyR cluster morphology in fixed atrial myocytes from sheep with persistent AF (N = 6) and control (Ctrl; N = 6) animals. RyR clusters on average contained 15 contiguous RyRs; this did not differ between AF and Ctrl. However, the distance between clusters was significantly reduced in AF (288 ± 12 vs. 376 ± 17 nm). When RyR clusters were grouped into Ca2+ release units (CRUs), i.e. clusters separated by <150 nm, CRUs in AF had more clusters (3.43 ± 0.10 vs. 2.95 ± 0.02 in Ctrl), which were more dispersed. Furthermore, in AF cells, more RyR clusters were found between Z lines. In parallel experiments, Ca2+ sparks were monitored in live permeabilized myocytes. In AF, myocytes had >50% higher spark frequency with increased spark time to peak (TTP) and duration, and a higher incidence of macrosparks. A computational model of the CRU was used to simulate the morphological alterations observed in AF cells. Increasing cluster fragmentation to the level observed in AF cells caused the observed changes, i.e. higher spark frequency, increased TTP and duration; RyR clusters dispersed between Z-lines increased the occurrence of macrosparks. Conclusion In persistent AF, ultrastructural reorganization of RyR clusters within CRUs is associated with overactive Ca2+ release, increasing the likelihood of propagating Ca2+ release. PMID:26490742

  4. Atrial Cardiopathy: A Broadened Concept of Left Atrial Thromboembolism Beyond Atrial Fibrillation

    PubMed Central

    Kamel, Hooman; Okin, Peter M.; Longstreth, W. T.; Elkind, Mitchell S.V.; Soliman, Elsayed Z.

    2016-01-01

    Atrial fibrillation (AF) has long been associated with a heightened risk of ischemic stroke and systemic thromboembolism, but recent data require a re-evaluation of our understanding of the nature of this relationship. New findings about the temporal connection between AF and stroke, alongside evidence linking markers of left atrial abnormalities with stroke in the absence of apparent AF, suggest that left atrial thromboembolism may occur even without AF. These observations undermine the hypothesis that the dysrhythmia that defines AF is necessary and sufficient to cause thromboembolism. In this commentary, we instead suggest that the substrate for thromboembolism may often be the anatomic and physiological atrial derangements associated with AF. Therefore, our understanding of cardioembolic stroke may be more complete if we shift our representation of its origin from AF to the concept of atrial cardiopathy. PMID:26021638

  5. Extracellular Ubiquitin: Role in Myocyte Apoptosis and Myocardial Remodeling.

    PubMed

    Scofield, Stephanie L C; Amin, Parthiv; Singh, Mahipal; Singh, Krishna

    2015-01-01

    Ubiquitin (UB) is a highly conserved low molecular weight (8.5 kDa) protein. It consists of 76 amino acid residues and is found in all eukaryotic cells. The covalent linkage of UB to a variety of cellular proteins (ubiquitination) is one of the most common posttranslational modifications in eukaryotic cells. This modification generally regulates protein turnover and protects the cells from damaged or misfolded proteins. The polyubiquitination of proteins serves as a signal for degradation via the 26S proteasome pathway. UB is present in trace amounts in body fluids. Elevated levels of UB are described in the serum or plasma of patients under a variety of conditions. Extracellular UB is proposed to have pleiotropic roles including regulation of immune response, anti-inflammatory, and neuroprotective activities. CXCR4 is identified as receptor for extracellular UB in hematopoietic cells. Heart failure represents a major cause of morbidity and mortality in western society. Cardiac remodeling is a determinant of the clinical course of heart failure. The components involved in myocardial remodeling include-myocytes, fibroblasts, interstitium, and coronary vasculature. Increased sympathetic nerve activity in the form of norepinephrine is a common feature during heart failure. Acting via β-adrenergic receptor (β-AR), norepinephrine is shown to induce myocyte apoptosis and myocardial fibrosis. β-AR stimulation increases extracellular levels of UB in myocytes, and UB inhibits β-AR-stimulated increases in myocyte apoptosis and myocardial fibrosis. This review summarizes intracellular and extracellular functions of UB with particular emphasis on the role of extracellular UB in cardiac myocyte apoptosis and myocardial remodeling. PMID:26756642

  6. A modular instrument for exploring the mechanics of cardiac myocytes.

    PubMed

    Garcia-Webb, M G; Taberner, A J; Hogan, N C; Hunter, I W

    2007-07-01

    The cardiac ventricular myocyte is a key experimental system for exploring the mechanical properties of the diseased and healthy heart. Millions of primary myocytes, which remain viable for 4-6 h, can be readily isolated from animal models. However, currently available instrumentation allows the mechanical properties of only a few physically loaded myocytes to be explored within 4-6 h. Here we describe a modular and inexpensive prototype instrument that could form the basis of an array of devices for probing the mechanical properties of single mammalian myocytes in parallel. This device would greatly increase the throughput of scientific experimentation and could be applied as a high-content screening instrument in the pharmaceutical industry. The instrument module consists of two independently controlled Lorentz force actuators-force transducers in the form of 0.025 x 1 x 5 mm stainless steel cantilevers with 0.5 m/N compliance and 360-Hz resonant frequency. Optical position sensors focused on each cantilever provide position and force resolution of <1 nm/ radicalHz and <2 nN/ radicalHz, respectively. The motor structure can produce peak displacements and forces of +/-200 mum and +/-400 microN, respectively. Custom Visual Basic.Net software provides data acquisition, signal processing, and digital control of cantilever position. The functionality of the instrument was demonstrated by implementation of novel methodologies for loading and attaching healthy mammalian ventricular myocytes to the force sensor and actuator and use of stochastic system identification techniques to measure their passive dynamic stiffness at various sarcomere lengths. PMID:17308002

  7. [Anticoagulation in atrial fibrillation].

    PubMed

    Schwarz, M; Bode, Ch

    2008-10-01

    In this overview the actual guideline-recommendations for anticoagulation in atrial fibrillation and the problems of the currently available therapy are discussed. Furthermore an outlook over future developments in this field is given. Effective anticoagulation can prohibit thrombembolic events and is thus essential for the prognosis of patients suffering from atrial fibrillation. Until now vitamin-K-antagonists (VKAs) and acetylsalicylic acid (ASA) are available for oral anticoagulation in these patients. VKAs demonstrate a satisfying efficiency combined with rather high bleeding hazard. ASA on the other hand allows only moderate risk reduction with minimal side effects. Thus the guidelines recommend anticoagulation tailored to the individual risk, which can be evaluated by the CHADS2-Score. New therapeutic strategies, like the factor Xa inhibitor rivaroxaban or the factor II inhibitor dabigatran, are actually evaluated in phase III studies. These drugs bear the hope of higher efficiency combined with improved safety and much more comfortable use in the daily practice (e. g. no need for INR measurement, no dose adaptation). PMID:18836647

  8. Type 2 Diabetes Induces Prolonged P-wave Duration without Left Atrial Enlargement

    PubMed Central

    2016-01-01

    Prolonged P-wave duration has been observed in diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to elucidate the possible mechanisms. A rat model of type 2 diabetes mellitus (T2DM) was used. P-wave durations were obtained using surface electrocardiography and sizes of the left atrium were determined using echocardiography. Cardiac inward rectifier K+ currents (Ik1), Na+ currents (INa), and action potentials were recorded from isolated left atrial myocytes using patch clamp techniques. Left atrial tissue specimens were analyzed for total connexin-40 (Cx40) and connexin-43 (Cx43) expression levels on western-blots. Specimens were also analyzed for Cx40 and Cx43 distribution and interstitial fibrosis by immunofluorescent and Masson trichrome staining, respectively. The mean P-wave duration was longer in T2DM rats than in controls; however, the mean left atrial sizes of each group of rats were similar. The densities of Ik1 and INa were unchanged in T2DM rats compared to controls. The action potential duration was longer in T2DM rats, but there was no significant difference in resting membrane potential or action potential amplitude compared to controls. The expression level of Cx40 protein was significantly lower, but Cx43 was unaltered in T2DM rats. However, immunofluorescent labeling of Cx43 showed a significantly enhanced lateralization. Staining showed interstitial fibrosis was greater in T2DM atrial tissue. Prolonged P-wave duration is not dependent on the left atrial size in rats with T2DM. Dysregulation of Cx40 and Cx43 protein expression, as well as fibrosis, might partly account for the prolongation of P-wave duration in T2DM. PMID:27051235

  9. Type 2 Diabetes Induces Prolonged P-wave Duration without Left Atrial Enlargement.

    PubMed

    Li, Bin; Pan, Yilong; Li, Xiaodong

    2016-04-01

    Prolonged P-wave duration has been observed in diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to elucidate the possible mechanisms. A rat model of type 2 diabetes mellitus (T2DM) was used. P-wave durations were obtained using surface electrocardiography and sizes of the left atrium were determined using echocardiography. Cardiac inward rectifier K(+) currents (Ik1), Na(+) currents (INa), and action potentials were recorded from isolated left atrial myocytes using patch clamp techniques. Left atrial tissue specimens were analyzed for total connexin-40 (Cx40) and connexin-43 (Cx43) expression levels on western-blots. Specimens were also analyzed for Cx40 and Cx43 distribution and interstitial fibrosis by immunofluorescent and Masson trichrome staining, respectively. The mean P-wave duration was longer in T2DM rats than in controls; however, the mean left atrial sizes of each group of rats were similar. The densities of Ik1 and INa were unchanged in T2DM rats compared to controls. The action potential duration was longer in T2DM rats, but there was no significant difference in resting membrane potential or action potential amplitude compared to controls. The expression level of Cx40 protein was significantly lower, but Cx43 was unaltered in T2DM rats. However, immunofluorescent labeling of Cx43 showed a significantly enhanced lateralization. Staining showed interstitial fibrosis was greater in T2DM atrial tissue. Prolonged P-wave duration is not dependent on the left atrial size in rats with T2DM. Dysregulation of Cx40 and Cx43 protein expression, as well as fibrosis, might partly account for the prolongation of P-wave duration in T2DM. PMID:27051235

  10. [Vectorcardiographic manifestations of atrial enlargements].

    PubMed

    de Micheli, A; Medrano, G A

    1990-01-01

    Rational interpretation of changes of the P loop due to atrial enlargements must to rely on the magnitude and spatial orientation of main resultant vectors of the activation sequence of the atria. Under normal conditions, these vectors give rise to a mean vector oriented to the left downward and discretely forward with respect to their point of origin. In the presence of right atrial enlargement, the manifestation of the first vector of atrial depolarization, oriented downward and forward, is increased. This one moves in the same direction as the mean vector of atrial depolarization, originating an elongated P loop of more than 100 mcv in the three planes. Nevertheless, in the horizontal plane, increase of the P loop voltage predominates when hypertrophy exists, while augmentation of its area predominates when dilatation exists. In left atrial enlargement, the manifestation of the second vector of atrial depolarization, oriented to the left and backward, is augmented, and it moves in the same direction as the mean vector of atrial depolarization. For this, the PF loop acquires a characteristic aspect of a boxing glove, an the PH loop becomes diphasic, with its posterior area more or less prominent, or with a typical figure-eight conformation. If a biatrial enlargement is present, the manifestation of both the main resultant vectors of atrial depolarization is accentuated. Therefore the voltage of the diphasic P loop increases. Moreover the Ps loop has a triangular configuration, with its base of 30 msc or more, located below its point of origin. Generally disturbances of interatrial and intraatrial conduction coexist owing to myocardial damage. PMID:2146934

  11. Genomics of Atrial Fibrillation.

    PubMed

    Gutierrez, Alejandra; Chung, Mina K

    2016-06-01

    Atrial fibrillation (AF) is a common clinical arrhythmia that appears to be highly heritable, despite representing a complex interplay of several disease processes that generally do not manifest until later in life. In this manuscript, we will review the genetic basis of this complex trait established through studies of familial AF, linkage and candidate gene studies of common AF, genome wide association studies (GWAS) of common AF, and transcriptomic studies of AF. Since AF is associated with a five-fold increase in the risk of stroke, we also review the intersection of common genetic factors associated with both of these conditions. Similarly, we highlight the intersection of common genetic markers associated with some risk factors for AF, such as hypertension and obesity, and AF. Lastly, we describe a paradigm where genetic factors predispose to the risk of AF, but which may require additional stress and trigger factors in older age to allow for the clinical manifestation of AF. PMID:27139902

  12. Rhythm control in atrial fibrillation.

    PubMed

    Piccini, Jonathan P; Fauchier, Laurent

    2016-08-20

    Many patients with atrial fibrillation have substantial symptoms despite ventricular rate control and require restoration of sinus rhythm to improve their quality of life. Acute restoration (ie, cardioversion) and maintenance of sinus rhythm in patients with atrial fibrillation are referred to as rhythm control. The decision to pursue rhythm control is based on symptoms, the type of atrial fibrillation (paroxysmal, persistent, or long-standing persistent), patient comorbidities, general health status, and anticoagulation status. Many patients have recurrent atrial fibrillation and require further intervention to maintain long term sinus rhythm. Antiarrhythmic drug therapy is generally recommended as a first-line therapy and drug selection is on the basis of the presence or absence of structural heart disease or heart failure, electrocardiographical variables, renal function, and other comorbidities. In patients who continue to have recurrent atrial fibrillation despite medical therapy, catheter ablation has been shown to substantially reduce recurrent atrial fibrillation, decrease symptoms, and improve quality of life, although recurrence is common despite continued advancement in ablation techniques. PMID:27560278

  13. Rate control in atrial fibrillation.

    PubMed

    Van Gelder, Isabelle C; Rienstra, Michiel; Crijns, Harry J G M; Olshansky, Brian

    2016-08-20

    Control of the heart rate (rate control) is central to atrial fibrillation management, even for patients who ultimately require control of the rhythm. We review heart rate control in patients with atrial fibrillation, including the rationale for the intervention, patient selection, and the treatments available. The choice of rate control depends on the symptoms and clinical characteristics of the patient, but for all patients with atrial fibrillation, rate control is part of the management. Choice of drugs is patient-dependent. β blockers, alone or in combination with digoxin, or non-dihydropyridine calcium-channel blockers (not in heart failure) effectively lower the heart rate. Digoxin is least effective, but a reasonable choice for physically inactive patients aged 80 years or older, in whom other treatments are ineffective or are contraindicated, and as an additional drug to other rate-controlling drugs, especially in heart failure when instituted cautiously. Atrioventricular node ablation with pacemaker insertion for rate control should be used as an approach of last resort but is also an option early in the management of patients with atrial fibrillation treated with cardiac resynchronisation therapy. However, catheter ablation of atrial fibrillation should be considered before atrioventricular node ablation. Although rate control is a top priority and one of the first management issues for all patients with atrial fibrillation, many issues remain. PMID:27560277

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

    PubMed Central

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

    2016-01-01

    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. PMID:26786158

  15. Current-Voltage Relationship for Late Na(+) Current in Adult Rat Ventricular Myocytes.

    PubMed

    Clark, R B; Giles, W R

    2016-01-01

    It is now well established that the slowly inactivating component of the Na(+) current (INa-L) in the mammalian heart is a significant regulator of the action potential waveform. This insight has led to detailed studies of the role of INa-L in a number of important and challenging pathophysiological settings. These include genetically based ventricular arrhythmias (LQT 1, 2, and 3), ventricular arrhythmias arising from progressive cardiomyopathies (including diabetic), and proarrhythmic abnormalities that develop during local or global ventricular ischemia. Inhibition of INa-L may also be a useful strategy for management of atrial flutter and fibrillation. Many important biophysical parameters that characterize INa-L have been identified; and INa-L as an antiarrhythmia drug target has been studied extensively. However, relatively little information is available regarding (1) the ion transfer or current-voltage relationship for INa-L or (2) the time course of its reactivation at membrane potentials similar to the resting or diastolic membrane potential in mammalian ventricle. This chapter is based on our preliminary findings concerning these two very important physiological/biophysical descriptors for INa-L. Our results were obtained using whole-cell voltage clamp methods applied to enzymatically isolated rat ventricular myocytes. A chemical agent, BDF 9148, which was once considered to be a drug candidate in the Na(+)-dependent inotropic agent category has been used to markedly enhance INa-L current. BDF acts in a potent, selective, and reversible fashion. These BDF 9148 effects are compared and contrasted with the prototypical activator of INa-L, a sea anemone toxin, ATX II. PMID:27586292

  16. VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium

    PubMed Central

    Zhao, Tieqiang; Zhao, Wenyuan; Meng, Weixin; Liu, Chang; Chen, Yuanjian; Gerling, Ivan C; Weber, Karl T; Bhattacharya, Syamal K; Kumar, Rahul; Sun, Yao

    2015-01-01

    Background: Numerous studies have shown that in addition to angio/lymphangiogenesis, the VEGF family is involved in other cellular actions. We have recently reported that enhanced VEGF-C and VEGFR-3 in the infarcted rat myocardium, suggesting the paracrine/autocrine function of VEGF-C on cardiac remodeling. The current study was designed to test the hypothesis that VEGF-C regulates cardiomyocyte growth and survival in the infarcted myocardium. Methods and results: Gene profiling and VEGFR-3 expression of cardiomyocytes were assessed by laser capture microdissection/microarray and immunohistochemistry in the normal and infarcted myocardium. The effect of VEGF-C on myocyte hypertrophy and apoptosis during normoxia and hypoxia was detected by RT-PCR and western blotting in cultured rat neonatal cardiomyocytes. VEGFR-3 was minimally expressed in cardiomyocytes of the normal and noninfarcted myocardium, while markedly elevated in the surviving cardiomyocytes of the infarcted myocardium and border zone. Genes altered in the surviving cardiomyocytes were associated with the networks regulating cellular growth and survival. VEGF-C significantly increased the expression of atrial natriuretic factor (ANP), brain natriuretic factor (BNP), and β-myosin heavy chain (MHC), markers of hypertrophy, in neonatal cardiomyocytes. Hypoxia caused neonatal cardiomyocyte atrophy, which was prevented by VEGF-C treatment. Hypoxia significantly enhanced apoptotic mediators, including cleaved caspase 3, 8, and 9, and Bax in neonatal cardiomyocytes, which were abolished by VEGF-C treatment. Conclusion: Our findings indicate that VEGF-C/VEGFR-3 pathway exerts a beneficial role in the infarcted myocardium by promoting compensatory cardiomyocyte hypertrophy and survival. PMID:26064438

  17. Atrial Remodeling and Atrial Tachyarrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy.

    PubMed

    Wu, Lingmin; Guo, Jinrui; Zheng, Lihui; Chen, Gang; Ding, Ligang; Qiao, Yu; Sun, Wei; Yao, Yan; Zhang, Shu

    2016-09-01

    Less is known about atrial remodeling and atrial tachyarrhythmias (ATa) in arrhythmogenic right ventricular cardiomyopathy (ARVC); this cross-sectional study aimed to determine the prevalence, characterization, and predictors of atrial remodeling and ATa in a large series of patients with ARVC. From February 2004 to September 2014, 294 consecutive patients who met the task force criteria for ARVC were enrolled. The prevalence, characterization, and predictors of atrial dilation and ATa were investigated. Right atrium (RA) dilation was identified in 160 patients (54.4%) and left atrium dilation in 66 patients (22.4%). Both RA and left atrium dilation were found in 44 patients (15.0%). Twenty-five patients (8.5%) had atrial fibrillation (AF), whereas 19 patients (6.5%) had atrial flutter (AFL). Of which, 7 patients (2.4%) had both AF and AFL. Multivariate analysis showed that AFL (odds ratio [OR] 10.309; 95% confidence interval [CI] 2.770 to 38.462; p <0.001), hypertension (OR 9.174; 95% CI 2.364 to 35.714; p = 0.001), and RA dilation (OR 6.993; 95% CI 1.623 to 30.303; p = 0.009) were associated with increased risk for AF. AF (OR 10.526; 95% CI 2.786 to 40.000; p = 0.001) increased the risk of AFL. In conclusion, atrial remodeling and ATa were common in patients with ARVC. PMID:27378141

  18. Biology of the cardiac myocyte in heart disease.

    PubMed

    Peter, Angela K; Bjerke, Maureen A; Leinwand, Leslie A

    2016-07-15

    Cardiac hypertrophy is a major risk factor for heart failure, and it has been shown that this increase in size occurs at the level of the cardiac myocyte. Cardiac myocyte model systems have been developed to study this process. Here we focus on cell culture tools, including primary cells, immortalized cell lines, human stem cells, and their morphological and molecular responses to pathological stimuli. For each cell type, we discuss commonly used methods for inducing hypertrophy, markers of pathological hypertrophy, advantages for each model, and disadvantages to using a particular cell type over other in vitro model systems. Where applicable, we discuss how each system is used to model human disease and how these models may be applicable to current drug therapeutic strategies. Finally, we discuss the increasing use of biomaterials to mimic healthy and diseased hearts and how these matrices can contribute to in vitro model systems of cardiac cell biology. PMID:27418636

  19. Cardiac myocyte exosomes: stability, HSP60, and proteomics

    PubMed Central

    Malik, Z. A.; Kott, K. S.; Poe, A. J.; Kuo, T.; Chen, L.; Ferrara, K. W.

    2013-01-01

    Exosomes, which are 50- to 100-nm-diameter lipid vesicles, have been implicated in intercellular communication, including transmitting malignancy, and as a way for viral particles to evade detection while spreading to new cells. Previously, we demonstrated that adult cardiac myocytes release heat shock protein (HSP)60 in exosomes. Extracellular HSP60, when not in exosomes, causes cardiac myocyte apoptosis via the activation of Toll-like receptor 4. Thus, release of HSP60 from exosomes would be damaging to the surrounding cardiac myocytes. We hypothesized that 1) pathological changes in the environment, such as fever, change in pH, or ethanol consumption, would increase exosome permeability; 2) different exosome inducers would result in different exosomal protein content; 3) ethanol at “physiological” concentrations would cause exosome release; and 4) ROS production is an underlying mechanism of increased exosome production. We found the following: first, exosomes retained their protein cargo under different physiological/pathological conditions, based on Western blot analyses. Second, mass spectrometry demonstrated that the protein content of cardiac exosomes differed significantly from other types of exosomes in the literature and contained cytosolic, sarcomeric, and mitochondrial proteins. Third, ethanol did not affect exosome stability but greatly increased the production of exosomes by cardiac myocytes. Fourth, ethanol- and hypoxia/reoxygenation-derived exosomes had different protein content. Finally, ROS inhibition reduced exosome production but did not completely inhibit it. In conclusion, exosomal protein content is influenced by the cell source and stimulus for exosome formation. ROS stimulate exosome production. The functions of exosomes remain to be fully elucidated. PMID:23376832

  20. Electrochemical properties and myocyte interaction of carbon nanotube microelectrodes.

    PubMed

    Fung, Andrew O; Tsiokos, Christos; Paydar, Omeed; Chen, Li Han; Jin, Sungho; Wang, Yibin; Judy, Jack W

    2010-11-10

    Arrays of carbon nanotube (CNT) microelectrodes (nominal geometric surface areas 20-200 μm(2)) were fabricated by photolithography with chemical vapor deposition of randomly oriented CNTs. Raman spectroscopy showed strong peak intensities in both G and D bands (G/D = 0.86), indicative of significant disorder in the graphitic layers of the randomly oriented CNTs. The impedance spectra of gold and CNT microelectrodes were compared using equivalent circuit models. Compared to planar gold surfaces, pristine nanotubes lowered the overall electrode impedance at 1 kHz by 75%, while nanotubes treated in O(2) plasma reduced the impedance by 95%. Cyclic voltammetry in potassium ferricyanide showed potential peak separations of 133 and 198 mV for gold and carbon nanotube electrodes, respectively. The interaction of cultured cardiac myocytes with randomly oriented and vertically aligned CNTs was investigated by the sectioning of myocytes using focused-ion-beam milling. Vertically aligned nanotubes deposited by plasma-enhanced chemical vapor deposition (PECVD) were observed to penetrate the membrane of neonatal-rat ventricular myocytes, while randomly oriented CNTs remained external to the cells. These results demonstrated that CNT electrodes can be leveraged to reduce impedance and enhance biological interfaces for microelectrodes of subcellular size. PMID:20954739

  1. Models of Excitation–Contraction Coupling in Cardiac Ventricular Myocytes

    PubMed Central

    Jafri, M. Saleet

    2012-01-01

    Excitation–contraction coupling describes the processes relating to electrical excitation through force generation and contraction in the heart. It occurs at multiple levels from the whole heart, to single myocytes and down to the sarcomere. A central process that links electrical excitation to contraction is calcium mobilization. Computational models that are well grounded in experimental data have been an effective tool to understand the complex dynamics of the processes involved in excitation–contraction coupling. Presented here is a summary of some computational models that have added to the understanding of the cellular and subcellular mechanisms that control ventricular myocyte calcium dynamics. Models of cardiac ventricular myocytes that have given insight into termination of calcium release and interval–force relations are discussed in this manuscript. Computational modeling of calcium sparks, the elementary events in cardiac excitation–contraction coupling, has given insight into mechanism governing their dynamics and termination as well as their role in excitation–contraction coupling and is described herein. PMID:22821602

  2. Mechanical properties of adult feline ventricular myocytes in culture.

    PubMed

    Pollack, P S; Carson, N L; Nuss, H B; Marino, T A; Houser, S R

    1991-01-01

    The contractile and electrophysiological properties of cultured adult feline ventricular myocytes were studied. Cells were field stimulated and contraction was measured using a video-based edge detector. The magnitude of contraction decreased by 36% and the rate of contraction decreased by 52% 2 h after the cells were plated on laminin-coated cover slips. The magnitude and rate of contraction then remained stable for 1 wk. The duration of contraction prolonged and a second component to the twitch frequently, but not invariably, developed after 5 days in culture. This was associated with prolongation of the action potential duration. After 7 days in culture, cells could be divided into two groups based on resting membrane potential. Norepinephrine increased the magnitude of contraction for 5 days after plating. Cultured ventricular myocytes became unresponsive to the effects of norepinephrine after 7 days. Adult cardiac myocytes maintained in primary culture continue to respond to field stimulation and retain many contractile properties for up to 7 days; however, the functional characteristics of these cells do not remain uniform during this time period. PMID:1992803

  3. Trophic effect of human pericardial fluid on adult cardiac myocytes. Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy.

    PubMed

    Corda, S; Mebazaa, A; Gandolfini, M P; Fitting, C; Marotte, F; Peynet, J; Charlemagne, D; Cavaillon, J M; Payen, D; Rappaport, L; Samuel, J L

    1997-11-01

    Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [14C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9 +/- 8.2% [n = 17]; serum, +14.9 +/- 6.5% [n = 13]; both P < .01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum (P < .01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-beta (TGF-beta), suggesting a relationship to FGF2. In addition, FGF2 concentration in PF was 20 times greater than in serum. On the other hand, the LV mass-dependent trophic effect, present in both fluids, was independent of FGF2 concentration or other factors, such as angiotensin II, atrial natriuretic factor, and TGF-beta. These data suggest that FGF2 in human PF is a major determining factor in normal myocyte growth, whereas unidentified LV mass-dependent factor(s), present in both PF and serum, participates in the development of ventricular hypertrophy. PMID:9351441

  4. Finite Element Model to Study One Dimensional Calcium Dyanmics in Cardiac Myocytes

    NASA Astrophysics Data System (ADS)

    Pathak, Kunal B.; Adlakha, Neeru

    2015-12-01

    The multi physical process involving calcium ions regulate expansion and contraction of cardiac myocytes. This mechanism of expansion and contraction of cardiac myocytes is responsible for contraction and expansion of heart for pumping of blood into arteries and receiving blood into heart from vein. Thus calcium dynamics in cardiac myocytes is responsible for the activities of the myocytes cells and functioning of the heart. The specific spatiotemporal calcium ion dynamics is required to trigger, sustain and terminate activity of the cell. In this paper an attempt has been done to propose a model to study calcium dynamics in cardiac myocytes for a one-dimensional unsteady state case. The model incorporates the process like diffusion, reaction involving source and excess buffers. Appropriate boundary conditions and initial conditions have been framed. The finite element method has been employed to obtain the solution. The numerical results have been used to study the effect of buffers and source influx on calcium dynamics in cardiac myocytes.

  5. Who Is at Risk for Atrial Fibrillation?

    MedlinePlus

    ... from the NHLBI on Twitter. Who Is at Risk for Atrial Fibrillation? Atrial fibrillation (AF) affects millions ... than 75. AF is uncommon in children. Major Risk Factors AF is more common in people who ...

  6. Genetics Home Reference: familial atrial fibrillation

    MedlinePlus

    ... fibrillation also increases the risk of stroke and sudden death. Complications of familial atrial fibrillation can occur at ... beats , increasing the risk of syncope, stroke, and sudden death. Most cases of atrial fibrillation are not caused ...

  7. R4496C RyR2 mutation impairs atrial and ventricular contractility

    PubMed Central

    Coppini, Raffaele; Scellini, Beatrice; Ferrara, Claudia; Pioner, Josè Manuel; Mazzoni, Luca; Priori, Silvia; Cerbai, Elisabetta; Tesi, Chiara; Poggesi, Corrado

    2016-01-01

    Ryanodine receptor (RyR2) is the major Ca2+ channel of the cardiac sarcoplasmic reticulum (SR) and plays a crucial role in the generation of myocardial force. Changes in RyR2 gating properties and resulting increases in its open probability (Po) are associated with Ca2+ leakage from the SR and arrhythmias; however, the effects of RyR2 dysfunction on myocardial contractility are unknown. Here, we investigated the possibility that a RyR2 mutation associated with catecholaminergic polymorphic ventricular tachycardia, R4496C, affects the contractile function of atrial and ventricular myocardium. We measured isometric twitch tension in left ventricular and atrial trabeculae from wild-type mice and heterozygous transgenic mice carrying the R4496C RyR2 mutation and found that twitch force was comparable under baseline conditions (30°C, 2 mM [Ca2+]o, 1 Hz). However, the positive inotropic responses to high stimulation frequency, 0.1 µM isoproterenol, and 5 mM [Ca2+]o were decreased in R4496C trabeculae, as was post-rest potentiation. We investigated the mechanisms underlying inotropic insufficiency in R4496C muscles in single ventricular myocytes. Under baseline conditions, the amplitude of the Ca2+ transient was normal, despite the reduced SR Ca2+ content. Under inotropic challenge, however, R4496C myocytes were unable to boost the amplitude of Ca2+ transients because they are incapable of properly increasing the amount of Ca2+ stored in the SR because of a larger SR Ca2+ leakage. Recovery of force in response to premature stimuli was faster in R4496C myocardium, despite the unchanged rates of recovery of L-type Ca2+ channel current (ICa-L) and SR Ca2+ content in single myocytes. A faster recovery from inactivation of the mutant R4496C channels could explain this behavior. In conclusion, changes in RyR2 channel gating associated with the R4496C mutation could be directly responsible for the alterations in both ventricular and atrial contractility. The increased RyR2 Po

  8. Surgical Ablation of Atrial Fibrillation.

    PubMed

    Ramlawi, Basel; Abu Saleh, Walid K

    2015-01-01

    The Cox-maze procedure for the restoration of normal sinus rhythm, initially developed by Dr. James Cox, underwent several iterations over the years. The main concept consists of creating a series of transmural lesions in the right and left atria that disrupt re-entrant circuits responsible for propagating the abnormal atrial fibrillation rhythm. The left atrial appendage is excluded as a component of the Maze procedure. For the first three iterations of the Cox- maze procedure, these lesions were performed using a surgical cut-and-sew approach that ensured transmurality. The Cox-Maze IV is the most currently accepted iteration. It achieves the same lesion set of the Cox- maze III but uses alternative energy sources to create the transmural lesions, potentially in a minimally invasive approach on the beating heart. High-frequency ultrasound, microwave, and laser energy have all been used with varying success in the past. Today, bipolar radiofrequency heat or cryotherapy cooling are the most accepted sources for creating linear lesions with consistent safety and transmurality. The robust and reliable nature of these energy delivery methods has yielded a success rate reaching 90% freedom from atrial fibrillation at 12 months. Such approaches offer a significant long-term advantage over catheter-based ablation, especially in patients having longstanding, persistent atrial fibrillation with characteristics such as dilated left atrial dimensions, poor ejection fraction, and failed catheter ablation. Based on these improved results, there currently is significant interest in developing a hybrid ablation strategy that incorporates the superior transmural robust lesions of surgical ablation, the reliable stroke prevention potential of epicardial left atrial appendage exclusion, and sophisticated mapping and confirmatory catheter-based ablation technology. Such a minimally invasive hybrid strategy for ablation may lead to the development of multidisciplinary "Afib teams" to

  9. Surgical Treatment of Atrial Myxomas

    PubMed Central

    Cho, Bum Koo; Lee, Doo Yun; Pezzella, A. Thomas; Hong, Sung Nok; Hong, Pill Whoon

    1989-01-01

    Twenty atrial myxomas were resected in 20 patients with the use of cardiopulmonary bypass, from the beginning of July 1966 through the end of June 1985, at Severance Hospital, Seoul, Korea. Nineteen patients had left atrial myxomas; 1 had a right atrial myxoma. Left atrial myxomas arose from the intra-atrial septum in 17 patients and from the left atrial appendage in 2 patients. The right atrial myxoma arose from the fossa ovalis. The 13 female and 7 male patients ranged in age from 14 to 63 years. Symptoms most often reported on presentation were those associated with mitral valve obstruction; other symptoms were associated with systemic embolization. The 1st 4 patients were tested with angiocardiography alone, and 3 of these were misdiagnosed. The last 16 were tested by angiocardiography, M-mode echocardiography, and 2-dimensional echocardiography, alone or in various combinations, and there were no further misdiagnoses. In our experience, 2-dimensional echocardiography was the most accurate method of diagnosing cardiac tumors. In 19 patients, surgical approach was through a median sternotomy; in the 20th patient, approach was through a left thoracotomy, due to a preoperative misdiagnosis of mitral stenosis. No intraoperative embolizations or deaths occurred. On follow-up of 17 patients during periods ranging from 6 months to 6 years, we had no late deaths, and only 2 patients suffered late complications: 1 had sudden right hemiparesis caused by an embolus 4 months after surgery (this improved upon conservative treatment); and 1 had a recurrence of tumor 3 years after surgery (the new myxoma was successfully resected). We conclude that patients who have undergone complete excision of benign myxomas now have an excellent prognosis, with minimal risk of intraoperative embolization and late recurrence. We conclude also that 2-dimensional echocardiography is an extremely accurate tool both in early diagnosis of intracardiac myxomas and in late follow-up after

  10. Generating Primary Cultures of Murine Cardiac Myocytes and Cardiac Fibroblasts to Study Viral Myocarditis

    PubMed Central

    Sherry, Barbara

    2016-01-01

    Viruses can induce direct damage to cardiac myocytes and cardiac fibroblasts resulting in myocarditis and impaired cardiac function. Cardiac myocytes and cardiac fibroblasts display different capacities to support viral infection and generate a protective antiviral response. This chapter provides detailed protocols for generation and characterization of primary cultures of murine cardiac myocytes and cardiac fibroblasts, offering a powerful tool to probe cell type-specific responses that determine protection against viral myocarditis. PMID:25836571

  11. Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts.

    PubMed

    Gadeberg, Hanne C; Bryant, Simon M; James, Andrew F; Orchard, Clive H

    2016-01-15

    In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (INCX) and l-type Ca current (ICa) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca]i) was monitored simultaneously using fluo-4. INCX was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell INCX was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of INCX and ICa away from the T tubules to the cell surface and an increase in t-tubular INCX/ICa density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular INCX in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between INCX and [Ca]i, which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes. PMID:26566728

  12. Altered Na/Ca exchange distribution in ventricular myocytes from failing hearts

    PubMed Central

    Gadeberg, Hanne C.; Bryant, Simon M.; James, Andrew F.

    2015-01-01

    In mammalian cardiac ventricular myocytes, Ca efflux via Na/Ca exchange (NCX) occurs predominantly at T tubules. Heart failure is associated with disrupted t-tubular structure, but its effect on t-tubular function is less clear. We therefore investigated t-tubular NCX activity in ventricular myocytes isolated from rat hearts ∼18 wk after coronary artery ligation (CAL) or corresponding sham operation (Sham). NCX current (INCX) and l-type Ca current (ICa) were recorded using the whole cell, voltage-clamp technique in intact and detubulated (DT) myocytes; intracellular free Ca concentration ([Ca]i) was monitored simultaneously using fluo-4. INCX was activated and measured during application of caffeine to release Ca from sarcoplasmic reticulum (SR). Whole cell INCX was not significantly different in Sham and CAL myocytes and occurred predominantly in the T tubules in Sham myocytes. CAL was associated with redistribution of INCX and ICa away from the T tubules to the cell surface and an increase in t-tubular INCX/ICa density from 0.12 in Sham to 0.30 in CAL myocytes. The decrease in t-tubular INCX in CAL myocytes was accompanied by an increase in the fraction of Ca sequestered by SR. However, SR Ca content was not significantly different in Sham, Sham DT, and CAL myocytes but was significantly increased by DT of CAL myocytes. In Sham myocytes, there was hysteresis between INCX and [Ca]i, which was absent in DT Sham but present in CAL and DT CAL myocytes. These data suggest altered distribution of NCX in CAL myocytes. PMID:26566728

  13. Differential effects of lysophosphatidylcholine and ACh on muscarinic K(+),non-selective cation and Ca(2+) currents in guinea-pig atrial cells.

    PubMed

    Li, Libing; Matsuoka, Isao; Sakamoto, Kazuho; Kimura, Junko

    2016-06-01

    We compared the effects of lysophosphatidylcholine (LPC) and acetylcholine (ACh) on IK(ACh), ICa and a non-selective cation current (INSC) in guinea-pig atrial myocytes to clarify whether LPC and ACh activate similar Gi/o-coupled effector systems. IK(ACh), ICa and INSC were analyzed in single atrial myocytes by the whole cell patch-clamp. LPC induced INSC in a concentration-dependent manner in atrial cells. ACh activated IK(ACh), but failed to evoke INSC. LPC also activated IK(ACh) but with significantly less potency than ACh. The effects of both ligands on IK(ACh) were inhibited by intracellular loading of pre-activated PTX. This treatment also inhibited LPC-induced INSC, indicating that IK(ACh) and INSC induced by LPC are both mediated by Gi/o. LPC and ACh had similar potencies in inhibiting ICa, which was pre-augmented by forskolin, indicating that LPC and ACh activate similar amounts of α-subunits of Gi/o. The different effects of LPC and ACh on IK(ACh) and INSC may suggest that LPC and ACh activate Gi/o having different types of βγ subunits, and that LPC-induced INSC may be mediated by βγ subunits of Gi/o, which are less effective in inducing IK(ACh). PMID:26911304

  14. Native Intelligence

    ERIC Educational Resources Information Center

    Seven, Richard

    2006-01-01

    Amid concerns from tribal leaders that No Child Left Behind testing is squeezing out electives that have traditionally covered their history and cultures, an ambitious brace of programs is making Native America part of the core curriculum at David Wolfle Elementary School and other schools in the western Washington State. By tapping into…

  15. Obstructive sleep apnea in atrial fibrillation patients.

    PubMed

    Arias, Miguel A; Alonso-Fernández, Alberto; García-Río, Francisco; Sánchez, Ana; López, Juana M; Pagola, Carlos

    2006-06-28

    A high prevalence of obstructive sleep apnea has been demonstrated in patients with atrial fibrillation. Our comments want to emphasize the importance of identifying and treating a large proportion of patients with atrial fibrillation who have undiagnosed obstructive sleep apnea as an additional preventive strategy for atrial fibrillation patients. PMID:16309764

  16. Atriocaval Rupture After Right Atrial Isthmus Ablation for Atrial Flutter.

    PubMed

    Vloka, Caroline; Nelson, Daniel W; Wetherbee, Jule

    2016-06-01

    A patient with symptomatic typical atrial flutter (AFL) underwent right atrial isthmus ablation with an 8-mm catheter. Eight months later, his typical AFL recurred. Ten months later, he underwent a repeat right atrial isthmus ablation with an irrigated tip catheter and an 8-mm tip catheter. Six weeks after his second procedure, while performing intense sprint intervals on a treadmill, he developed an abrupt onset of chest pain, hypotension, and cardiac tamponade. He underwent emergency surgery to repair an atriocaval rupture and has done well since. Our report suggests that an association of multiple radiofrequency ablations with increased risk for delayed atriocaval rupture occurring 1 to 3 months after ablation. In conclusion, although patients generally were advised to limit exercise for 1 to 2 weeks after AFL ablation procedures in the past, it may be prudent to avoid intense exercise for at least 3 months after procedure. PMID:27112285

  17. Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C

    PubMed Central

    Egom, Emmanuel E; Vella, Kimberly; Hua, Rui; Jansen, Hailey J; Moghtadaei, Motahareh; Polina, Iuliia; Bogachev, Oleg; Hurnik, Rhea; Mackasey, Martin; Rafferty, Sara; Ray, Gibanananda; Rose, Robert A

    2015-01-01

    , function and arrhythmogenesis using NPR-C knockout (NPR-C−/−) mice. NPR-C−/− mice are characterized by sinoatrial node (SAN) dysfunction and a profound increase in susceptibility to atrial fibrillation. Increased susceptibility to arrhythmias in NPR-C−/− mice was associated with slowed electrical conduction in the SAN as well as the right and left atria due to enhanced collagen expression and deposition in the atria (structural remodelling), but without changes in action potential morphology (electrical remodelling) in isolated SAN or atrial myocytes. This study demonstrates a critical protective role for NPR-C in the heart. PMID:25641115

  18. Incidence and predictive factors of atrial fibrillation after ablation of typical atrial flutter.

    PubMed

    Laurent, Valérie; Fauchier, Laurent; Pierre, Bertrand; Grimard, Caroline; Babuty, Dominique

    2009-03-01

    Although cavotricuspid isthmus radiofrequency catheter ablation is considered curative therapy for typical atrial flutter, many patients develop an atrial fibrillation after ablation. The purpose of our study was to determine the incidence and the predictive factors of post-ablation atrial fibrillation. One hundred and forty eight consecutive patients underwent cavotricuspid isthmus ablation for the treatment of typical atrial flutter between January 2004 and December 2005 in our electrophysiological department. Complete cavotricuspid isthmus block was successfully obtained in 96.6% of the patients. At the end of the electrophysiological study a sustained atrial fibrillation was inducible in 20 patients (13.5%). During an average follow-up of 21.3 +/- 8.2 months, atrial fibrillation occurred in 27% of the patients. Univariate analysis identified four parameters correlated with post-ablation atrial fibrillation among the 21 parameters tested: the young age of the patients, a prior history of atrial fibrillation, an inducible atrial fibrillation, and a paroxysmal atrial flutter. Only inducible atrial fibrillation and paroxysmal atrial flutter were independent factors linked to atrial fibrillation after ablation. In our study the incidence of atrial fibrillation after cavotricuspid isthmus radiofrequency catheter ablation is 152 per 1,000 patient-years, i.e. 25 times higher than the incidence of atrial fibrillation in the general population of the same age. Twenty five percent of the patients who had neither prior history of atrial fibrillation nor structural heart disease suffered from atrial fibrillation during a mean follow-up of 21.3 +/- 8.2 months. All these results suggest that atrial flutter and fibrillation could be manifestations of a more general electrophysiologic disease. They emphasize the need for all these patients to benefit from regular, long-term cardiological follow-up after cavotricuspid isthmus ablation because of the high incidence of atrial

  19. Cryoballoon Ablation for Atrial Fibrillation

    PubMed Central

    Andrade, Jason G; Dubuc, Marc; Guerra, Peter G; Macle, Laurent; Rivard, Lena; Roy, Denis; Talajic, Mario; Thibault, Bernard; Khairy, Paul

    2012-01-01

    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. PMID:22557842

  20. Accelerated fibrosis and apoptosis with ageing and in atrial fibrillation: Adaptive responses with maladaptive consequences.

    PubMed

    Xu, Guo-Jun; Gan, Tian-Yi; Tang, Bao-Peng; Chen, Zu-Heng; Mahemuti, Ailiman; Jiang, Tao; Song, Jian-Guo; Guo, Xia; Li, Yao-Dong; Miao, Hai-Jun; Zhou, Xian-Hui; Zhang, Yu; Li, Jin-Xin

    2013-03-01

    The aim of this study was to investigate whether abnormal expression of matrix metalloproteinase (MMP)-9/tissue inhibitors of MMPs (TIMP)-1 and B cell lymphoma 2 (BCL-2)/BCL-2-associated X protein (BAX) are correlated with the characteristic accelerated fibrosis and apoptosis during ageing and in atrial fibrillation (AF). Four groups of dogs were studied: adult dogs in sinus rhythm (SR), aged dogs in SR, adult dogs with AF induced by rapid atrial pacing and aged dogs with AF induced by rapid atrial pacing. The mRNA and protein expression levels of the target gene in the left atrium were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Pathohistological and ultrastructural changes were assessed by light and electron microscopy. The apoptotic indices of myocytes were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL). The mRNA and protein expression levels of MMP-9 and BAX and those of TIMP-1 and BCL-2 were significantly upregulated and down-regulated, respectively, in the aged groups compared with the adult groups. Compared with the control groups, the adult and aged groups with AF exhibited significantly increased mRNA and protein expression levels of MMP-9 and BAX and decreased expression levels of TIMP-1 and BCL-2. Samples of atrial tissue demonstrated abnormal pathohistological and ultrastructural changes, accelerated fibrosis and apoptosis. MMP-9/TIMP-1 and BCL-2/BAX hold potential for use as substrates conducive to AF and their abnormal expression plays a major role in structural remodeling of the atrium. PMID:23403858

  1. Role of atrial tissue remodeling on rotor dynamics: an in vitro study.

    PubMed

    Climent, Andreu M; Guillem, María S; Fuentes, Lucia; Lee, Peter; Bollensdorff, Christian; Fernández-Santos, María Eugenia; Suárez-Sancho, Susana; Sanz-Ruiz, Ricardo; Sánchez, Pedro Luis; Atienza, Felipe; Fernández-Avilés, Francisco

    2015-12-01

    The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P < 0.01), which was associated with changes in the electrical reentrant patterns (i.e., decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF. PMID:26408535

  2. Effects of aluminium on electrical and mechanical properties of frog atrial muscle.

    PubMed Central

    Meiri, H.; Shimoni, Y.

    1991-01-01

    1. The effects of aluminium on membrane ionic currents were studied in single cardiac myocytes. Most of the work was done on frog atrial cells, but some experiments were also carried out on single cells isolated from rabbit ventricles and atria. 2. The effects of aluminium on the force of contraction of frog atrial trabeculae were also investigated. 3. Aluminium was prepared from AlCl3 as a stock 0.5 M solution which has a pH of 3.5. Before each experiment, this solution was added to the control solution, to give a final concentration of 20-100 micrograms ml-1 aluminium (0.75-3.75 mM AlCl3). The solutions were brought to a pH of 7.4 or 7.6. at which they consist of a mixture of amorphous aluminium hydroxides and a very small amount of soluble ionic aluminium complexes: free aluminium cations (less than 10 pM), aluminohydroxide anions (less than 8 microM). The addition of this suspension reduced the peak inward calcium currents in single rabbit atrial and ventricular cells and in frog atrial cells. In the latter, the peak current was reduced (at + 10 mV) to 45% of control (mean of 9 cells). This effect was reversible upon washout, and was obtained at all membrane potentials, with no shift of the calcium current voltage relationship along the voltage axis. 4. Aluminium also reduced the time-dependent potassium current IK. This reduction was observed at all membrane potentials. For example, at + 10 mV, the mean reduction of IK (n = 9) was to 69% of the control amplitude. This effect, which was very difficult to reverse, was not due to IK rundown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2015425

  3. Native Skies

    NASA Astrophysics Data System (ADS)

    Benningfield, Damond

    2001-03-01

    People native to North America practiced their own version of astronomy. They tracked the motions of the Sun to help them decide when to plant crops, move their camps, and stage sacred rituals. Some tribes built great circles of stones to help them predict the changing seasons. Others built great mounds of earth to reflect the patterns they saw in the heavens and to align their ceremonial centers with the Sun and the Moon.

  4. Fibrinolytic function and atrial fibrillation.

    PubMed

    Marín, Francisco; Roldán, Vanessa; Lip, Gregory Y H

    2003-03-15

    Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia, which is associated with a substantial risk of stroke and thromboembolism. A prothrombotic or hypercoagulable state has been observed in these patients, although previous studies have mainly focused on various clotting factors, endothelial damage or dysfunction markers and platelet activation. However, fibrinolytic function has been less frequently studied, despite the fibrinolytic system playing an important role in preventing intravascular thrombosis. Indeed, increasing evidence suggests that an imbalance between the fibrinolytic function is of great importance in cardiovascular disease. This review will begin by providing a brief approach to fibrinolytic function and examine previous studies about fibrinolytic activity and atrial fibrillation. PMID:12818244

  5. A review of atrial fibrillation.

    PubMed Central

    Dang, David; Arimie, Raluca; Haywood, L. Julian

    2002-01-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and accounts for more physician visits and hospital days than any other cardiac rhythm disturbance. Atrial filbrillation is incresing in frequency as the population ages, and therefore, a knowledge of the clinical spectrum and available treatment regimen is essential. Here, we review the pathophysiology, clinical presentation, and current status of management. Experience is being rapidly accumulated in all of the areas discussed in the management of this important clinical entity. Images Figure 1 Figure 2 PMID:12510703

  6. CT findings of atrial myxoma

    SciTech Connect

    Tsuchiya, F.; Kohno, A.; Saitoh, R.; Shigeta, A.

    1984-04-01

    The computed tomographic (CT) appearance of six atrial myxomas was analyzed. Five of the myxomas were located in the left atrium and one was in the right atrium. The margin of the myxoma was at least slightly lobulated in five cases and the content was inhomogeneous in all. Calcification was demonstrated in three cases. The site of attachment of the myxoma was demonstrated by CT to be the arial septum in all cases. The CT finding correlated well with the operative findings. It is concluded that it is possible with CT to diagnose atrial myxoma by the location and nature of the intracardiac mass and to differentiate it from thrombus.

  7. Atrial Fibrillation in Ten Cows

    PubMed Central

    Brightling, P.; Townsend, H. G. G.

    1983-01-01

    An irregular cardiac rhythm was identified in ten adult cows during auscultation of the heart and was subsequently characterized as atrial fibrillation by electrocardiography. The occurrence of the arrhythmia was associated with primary, organic disease of the heart in two animals which had valvular endocarditis. In seven of the other cows secondary or “functional” atrial fibrillation occurred in association with disorders of abdominal origin, six gastrointestinal disorders and one uterine torsion. Spontaneous conversion to normal sinus rhythm occurred in six cows after elimination of the primary disease. ImagesFigure 1b.Figure 3a.Figure 3b. PMID:17422324

  8. [Atrial fibrillation and physical activity].

    PubMed

    Apor, Péter

    2013-03-31

    Atrial fibrillation is the most frequent arrhythmia. Its "lone" form (when underlying pathology is not discovered) can be detected in a small percentage of endurance sports participants, and in growing numbers among veterans, probably as a result of some cardiac or other irregularities. Enhanced vagal tone and sudden sympathetic impulse, repetitive oxidative stress, inflammatory processes, enlarged atria, electric instabilization can explain the higher occurrence. Treatment of atrial fibrillation enables the affected persons to participate in regular medium-intensity exercise, 3-5 hours a week, which offers a protective role against cardiovascular, metabolic and mental illnesses. PMID:23524234

  9. Laser Atrial Septostomy: An Engineering Problem

    NASA Astrophysics Data System (ADS)

    Ben-Shachar, Giora; Cohen, Mark H.; Riemenschneider, Thomas A.; Beder, Stanley D.

    1987-04-01

    The purpose of this study was to develop a reproducible method for atrial septostomy in live animals, which would be independent of both atrial septal thickness and left atrial size. Seven mongrel dogs monitored electrocardiographically were anesthetized and instrumented with systemic and pulmonary arterial lines. A modified Mullin's transseptal sheath was advanced under fluoroscopic control to interrogate the left atrium and atrial septum. A 400 micron regular quartz or a laser heated metallic tip fiber was passed through the sheath up to the atrial septum. Lasing of the atrial septum was done with an Argon laser at power output of 5 watts. In three dogs, an atrial septosomy catheter was passed to the left atrium through the laser atrial septostomy and balloon atrial septostomy was performed. The laser atrial septostomy measured 3 x 5 mm in diameter. This interatrial communication could be enlarged with a balloon septostomy to over one cm in diameter. Hemodynamic and electrocardiographic monitoring were stable during the procedure. Engineering problems included: 1) radioluscency of the laser fibers thus preventing fluoroscopic localization of the fiber course; and 2) the inability to increase lateral vaporization of the atrial septum. It is concluded that further changes in the lasing fibers need to be made before the method can be considered for clinical use.

  10. Defining nonvalvular atrial fibrillation: A quest for clarification.

    PubMed

    Martins, Raphaël P; Galand, Vincent; Colette, Edouard; Behar, Nathalie; Pavin, Dominique; Leclercq, Christophe; Daubert, Jean-Claude; Mabo, Philippe

    2016-08-01

    Non-vitamin K oral anticoagulants (NOACs) are currently recommended for patients with nonvalvular atrial fibrillation since the publication of the 4 major pivotal trials evaluating the efficacy and safety of factor IIa and factor Xa inhibitors. The definition of nonvalvular atrial fibrillation is unclear, varying from one trial to another and even between North American and European guidelines, which is a source of uncertainties in clinical practice. However, many patients with atrial fibrillation present signs of valvular involvement, and clarification of this term is needed to not deny NOACs to patients based on the wrong perception that they may have valvular atrial fibrillation. The currently unique contraindications to NOACs are patients with mechanical heart valves and those with moderate-to-severe mitral stenosis, as stated by the recent 2015 position paper of the European Heart Rhythm Association. Patients with native heart valve involvement, regardless of their severity, are suitable for NOAC therapy. Patients with bioprosthetic heart valves and mitral valve repair may be suitable for NOACs except for the first 3 and the first 3-6 months postoperatively, respectively. Patients with transaortic valve implantation or percutaneous transluminal aortic valvuloplasty are also considered as being eligible for NOACs, although the bleeding risk has to be carefully considered in this population often requiring a combination with antiplatelet therapy. Future studies are warranted to increase the level of evidence of use of NOACs, particularly in patients with transaortic valve implantation and valvular surgery, and to determine whether they could be used in the future in the only 2 remaining contraindications. PMID:27502864

  11. Resveratrol reduces intracellular free calcium concentration in rat ventricular myocytes.

    PubMed

    Liu, Zheng; Zhang, Li-Ping; Ma, Hui-Jie; Wang, Chuan; Li, Ming; Wang, Qing-Shan

    2005-10-25

    Resveratrol (trans-3, 4', 5-trihydroxy stilbene), a phytoalexin found in grape skins and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that resveratrol may have cardioprotective activity. The objective of our study was to investigate the effects of resveratrol on intracellular calcium concentration ([Ca(2+)](i)) in rat ventricular myocytes. [Ca(2+)](i) was detected by laser scanning confocal microscopy. The results showed that resveratrol (15~60 mumol/L) reduced [Ca(2+)](i) in normal and Ca(2+)-free Tyrode's solution in a concentration-dependent manner. The effects of resveratrol on [Ca(2+)](i) in normal Tyrode's solution was partially inhibited by pretreatment with sodium orthovanadate (Na3VO4, 1.0 mmol/L, P<0.01), an inhibitor of protein tyrosine phosphatase, or L-type Ca(2+) channel agonist Bay K8644 (10 mumol/L, P<0.05), but could not be antagonized by NO synthase inhibitor L-NAME (1.0 mmol/L). Resveratrol also markedly inhibited the ryanodine-induced [Ca(2+)](i) increase in Ca(2+)-free Tyrode's solution (P<0.01). When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, resveratrol (60 mumol/L) could reduce the velocity and duration of propagating waves, and block the propagating waves of elevated [Ca(2+)](i). These results suggest that resveratrol may reduce the [Ca(2+)](i) in isolated rat ventricular myocytes. The inhibition of voltage-dependent Ca(2+) channel and tyrosine kinase, and alleviation of Ca(2+) release from sarcoplasmic reticulum (SR) are possibly involved in the effects of resveratrol on rat ventricular myocytes. These findings could help explain the protective activity of resveratrol against cardiovascular disease. PMID:16220198

  12. Myocyte Dedifferentiation Drives Extraocular Muscle Regeneration in Adult Zebrafish

    PubMed Central

    Saera-Vila, Alfonso; Kasprick, Daniel S.; Junttila, Tyler L.; Grzegorski, Steven J.; Louie, Ke'ale W.; Chiari, Estelle F.; Kish, Phillip E.; Kahana, Alon

    2015-01-01

    Purpose The purpose of this study was to characterize the injury response of extraocular muscles (EOMs) in adult zebrafish. Methods Adult zebrafish underwent lateral rectus (LR) muscle myectomy surgery to remove 50% of the muscle, followed by molecular and cellular characterization of the tissue response to the injury. Results Following myectomy, the LR muscle regenerated an anatomically correct and functional muscle within 7 to 10 days post injury (DPI). Following injury, the residual muscle stump was replaced by a mesenchymal cell population that lost cell polarity and expressed mesenchymal markers. Next, a robust proliferative burst repopulated the area of the regenerating muscle. Regenerating cells expressed myod, identifying them as myoblasts. However, both immunofluorescence and electron microscopy failed to identify classic Pax7-positive satellite cells in control or injured EOMs. Instead, some proliferating nuclei were noted to express mef2c at the very earliest point in the proliferative burst, suggesting myonuclear reprogramming and dedifferentiation. Bromodeoxyuridine (BrdU) labeling of regenerating cells followed by a second myectomy without repeat labeling resulted in a twice-regenerated muscle broadly populated by BrdU-labeled nuclei with minimal apparent dilution of the BrdU signal. A double-pulse experiment using BrdU and 5-ethynyl-2′-deoxyuridine (EdU) identified double-labeled nuclei, confirming the shared progenitor lineage. Rapid regeneration occurred despite a cell cycle length of 19.1 hours, whereas 72% of the regenerating muscle nuclei entered the cell cycle by 48 hours post injury (HPI). Dextran lineage tracing revealed that residual myocytes were responsible for muscle regeneration. Conclusions EOM regeneration in adult zebrafish occurs by dedifferentiation of residual myocytes involving a muscle-to-mesenchyme transition. A mechanistic understanding of myocyte reprogramming may facilitate novel approaches to the development of molecular

  13. HISTONE DEACETYLASE 7 (HDAC7) REGULATES MYOCYTE MIGRATION AND DIFFERENTIATION

    PubMed Central

    Gao, Chengzhuo; Liu, Yu; Lam, Minh; Kao, Hung-Ying

    2010-01-01

    Summary Class IIa HDACs including HDAC7 play a role in gene expression, cell differentiation, and animal development through their association with transcription factors such as myogenic enhancer factors 2 (MEF2s). In this study, we show that endogenous HDAC7 localizes to both the nucleus and the cytoplasm of C2C12 myoblasts, but is exclusively retained in the cytoplasm of myotubes after completion of differentiation process. To elucidate the role of differential distribution of HDAC7 during myogenesis, we examined the effects of stably expressed HDAC7 mutants on myogenesis. Expression of nuclear-retained HDAC7 mutants significantly inhibits myogenesis in C2C12 cells and reduces the expression of muscle-specific myosin heavy chain (MHC) and myogenin. The inhibition in myocyte differentiation can be partially relieved by introduction of a mutation disrupting HDAC7:MEF2 interaction. Since phosphorylation of HDAC7 plays an important role in its nucleocytoplasmic shuttling, we further investigated the expression and distribution of phosphorylated HDAC7. To our surprise, the phosphorylation levels of HDAC7 at S344 and S479 were slightly decreased upon differentiation, whereas the phosphorylation of S178 was unchanged. Interestingly, a significant fraction of pS344- and/or pS479-HDAC7 localizes to plasma membrane of myotubes. In addition, Ser178-phosphorylated (pS178) HDAC7 shows a predominant actin filament-like staining prior to muscle differentiation and cytoplasmic and plasma membrane staining after differentiation. Consistent with this notion, HDAC7 partially co-localizes with actin filaments; in particular, pS178-HDAC7 largely colocalizes with actin filaments as indicated by phalloidin counter staining in myocytes. Furthermore, C2C12 cells expressing nuclear-retained HDAC7 display defects in migration. Our results provide novel insight into the mechanisms that regulate myocyte differentiation and migration by controlling the subcellular distribution of HDAC7 in

  14. A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide

    PubMed Central

    Klaiber, Michael; Dankworth, Beatrice; Kruse, Martin; Hartmann, Michael; Nikolaev, Viacheslav O.; Yang, Ruey-Bing; Völker, Katharina; Gaßner, Birgit; Oberwinkler, Heike; Feil, Robert; Freichel, Marc; Groschner, Klaus; Skryabin, Boris V.; Frantz, Stefan; Birnbaumer, Lutz; Pongs, Olaf; Kuhn, Michaela

    2011-01-01

    Cardiac atrial natriuretic peptide (ANP) regulates arterial blood pressure, moderates cardiomyocyte growth, and stimulates angiogenesis and metabolism. ANP binds to the transmembrane guanylyl cyclase (GC) receptor, GC-A, to exert its diverse functions. This process involves a cGMP-dependent signaling pathway preventing pathological [Ca2+]i increases in myocytes. In chronic cardiac hypertrophy, however, ANP levels are markedly increased and GC-A/cGMP responses to ANP are blunted due to receptor desensitization. Here we show that, in this situation, ANP binding to GC-A stimulates a unique cGMP-independent signaling pathway in cardiac myocytes, resulting in pathologically elevated intracellular Ca2+ levels. This pathway involves the activation of Ca2+‐permeable transient receptor potential canonical 3/6 (TRPC3/C6) cation channels by GC-A, which forms a stable complex with TRPC3/C6 channels. Our results indicate that the resulting cation influx activates voltage-dependent L-type Ca2+ channels and ultimately increases myocyte Ca2+i levels. These observations reveal a dual role of the ANP/GC-A–signaling pathway in the regulation of cardiac myocyte Ca2+i homeostasis. Under physiological conditions, activation of a cGMP-dependent pathway moderates the Ca2+i-enhancing action of hypertrophic factors such as angiotensin II. By contrast, a cGMP-independent pathway predominates under pathophysiological conditions when GC-A is desensitized by high ANP levels. The concomitant rise in [Ca2+]i might increase the propensity to cardiac hypertrophy and arrhythmias. PMID:22027011

  15. Illuminating Myocyte-Fibroblast Homotypic and Heterotypic Gap Junction Dynamics Using Dynamic Clamp.

    PubMed

    Brown, Tashalee R; Krogh-Madsen, Trine; Christini, David J

    2016-08-23

    Fibroblasts play a significant role in the development of electrical and mechanical dysfunction of the heart; however, the underlying mechanisms are only partially understood. One widely studied mechanism suggests that fibroblasts produce excess extracellular matrix, resulting in collagenous septa that slow propagation, cause zig-zag conduction paths, and decouple cardiomyocytes, resulting in a substrate for cardiac arrhythmia. An emerging mechanism suggests that fibroblasts promote arrhythmogenesis through direct electrical interactions with cardiomyocytes via gap junction (GJ) channels. In the heart, three major connexin (Cx) isoforms, Cx40, Cx43, and Cx45, form GJ channels in cell-type-specific combinations. Because each Cx is characterized by a unique time- and transjunctional voltage-dependent profile, we investigated whether the electrophysiological contributions of fibroblasts would vary with the specific composition of the myocyte-fibroblast (M-F) GJ channel. Due to the challenges of systematically modifying Cxs in vitro, we coupled native cardiomyocytes with in silico fibroblast and GJ channel electrophysiology models using the dynamic-clamp technique. We found that there is a reduction in the early peak of the junctional current during the upstroke of the action potential (AP) due to GJ channel gating. However, effects on the cardiomyocyte AP morphology were similar regardless of the specific type of GJ channel (homotypic Cx43 and Cx45, and heterotypic Cx43/Cx45 and Cx45/Cx43). To illuminate effects at the tissue level, we performed multiscale simulations of M-F coupling. First, we developed a cell-specific model of our dynamic-clamp experiments and investigated changes in the underlying membrane currents during M-F coupling. Second, we performed two-dimensional tissue sheet simulations of cardiac fibrosis and incorporated GJ channels in a cell type-specific manner. We determined that although GJ channel gating reduces junctional current, it does not

  16. Surgical Ablation of Atrial Fibrillation

    PubMed Central

    Ramlawi, Basel; Abu Saleh, Walid K.

    2015-01-01

    The Cox-maze procedure for the restoration of normal sinus rhythm, initially developed by Dr. James Cox, underwent several iterations over the years. The main concept consists of creating a series of transmural lesions in the right and left atria that disrupt re-entrant circuits responsible for propagating the abnormal atrial fibrillation rhythm. The left atrial appendage is excluded as a component of the Maze procedure. For the first three iterations of the Cox- maze procedure, these lesions were performed using a surgical cut-and-sew approach that ensured transmurality. The Cox-Maze IV is the most currently accepted iteration. It achieves the same lesion set of the Cox- maze III but uses alternative energy sources to create the transmural lesions, potentially in a minimally invasive approach on the beating heart. High-frequency ultrasound, microwave, and laser energy have all been used with varying success in the past. Today, bipolar radiofrequency heat or cryotherapy cooling are the most accepted sources for creating linear lesions with consistent safety and transmurality. The robust and reliable nature of these energy delivery methods has yielded a success rate reaching 90% freedom from atrial fibrillation at 12 months. Such approaches offer a significant long-term advantage over catheter-based ablation, especially in patients having longstanding, persistent atrial fibrillation with characteristics such as dilated left atrial dimensions, poor ejection fraction, and failed catheter ablation. Based on these improved results, there currently is significant interest in developing a hybrid ablation strategy that incorporates the superior transmural robust lesions of surgical ablation, the reliable stroke prevention potential of epicardial left atrial appendage exclusion, and sophisticated mapping and confirmatory catheter-based ablation technology. Such a minimally invasive hybrid strategy for ablation may lead to the development of multidisciplinary “Afib teams

  17. Management of atrial fibrillation in bradyarrhythmias.

    PubMed

    Boriani, Giuseppe; Padeletti, Luigi

    2015-06-01

    Sinus node disease (SND), a common indication to implant a pacemaker, is frequently associated with atrial fibrillation (AF), either at implantation (paroxysmal AF) or during follow-up, which often evolves to persistent or permanent AF. Pacemakers with an atrial lead allow continuous monitoring of the atrial rhythm and enable detection of the burden of AF. Asymptomatic atrial tachyarrhythmias, being associated with increased risk of stroke, have important prognostic implications, and their detection could guide decision-making about antithrombotic prophylaxis. Pacing mode and pacing algorithms can influence the occurrence of AF and atrial tachyarrhythmias. In DDD/DDDR pacing mode, reduction of unnecessary right ventricular pacing positively affects the occurrence and evolution of AF, but patients with a history of atrial tachyarrhythmias maintain an increased risk of arrhythmic events. In the MINERVA study, the use of algorithms that act in the atrium for preventive pacing and atrial antitachycardia pacing while minimizing right ventricular pacing was beneficial in patients with SND and previous atrial tachyarrhythmias, and was associated with a significant reduction in evolution to permanent AF. New information available on therapies delivered at the atrial level by implanted devices suggests clinical advantages that could improve current guidelines for the management of AF and atrial tachyarrhythmias. PMID:25781413

  18. Ryanodol action on calcium sparks in ventricular myocytes

    PubMed Central

    Ramos-Franco, Josefina; Gomez, Ana M.; Nani, Alma; Liu, Yiwei; Copello, Julio A.; Fill, Michael

    2012-01-01

    The action of ryanodol on single cardiac ryanodine receptor (RyR2) channels in bilayers and local RyR2-mediated Ca2+ release events (Ca2+ sparks) in ventricular myocytes was defined. At the single channel level, ryanodol intermittently modified single channels into a long lived sub-conductance state with an average duration of 3.8±0.2 s. Unlike ryanodine, ryanodol did not change the open probability (Po) of unmodified channels and high concentrations did not promote full channel closure. Ryanodol action was Po dependent with the KD varying roughly from 20 to 80 μM as Po changed from ~0.2 to 1, respectively. Ryanodol preferentially bound during long channel openings. In intact and permeabilized rat myocytes, ryanodol evoked trains of sparks at active release sites resulting in a significant increase in overall spark frequency. Ryanodol did not increase the number of active release sites. Long lived Ca2+ release events were observed but infrequently and ryanodol action was readily reversed upon drug washout. We propose that ryanodol modifies a few channels during a Ca2+ spark. These modified channels mediate a sustained low intensity Ca2+ release that repeatedly triggers sparks at the same release site. We conclude that ryanodol is an easily generated reversible probe that can be effectively used to explore RyR2-mediated Ca2+ release in cells. PMID:20419313

  19. Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content

    PubMed Central

    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

  20. Myocyte repolarization modulates myocardial function in aging dogs.

    PubMed

    Sorrentino, Andrea; Signore, Sergio; Qanud, Khaled; Borghetti, Giulia; Meo, Marianna; Cannata, Antonio; Zhou, Yu; Wybieralska, Ewa; Luciani, Marco; Kannappan, Ramaswamy; Zhang, Eric; Matsuda, Alex; Webster, Andrew; Cimini, Maria; Kertowidjojo, Elizabeth; D'Alessandro, David A; Wunimenghe, Oriyanhan; Michler, Robert E; Royer, Christopher; Goichberg, Polina; Leri, Annarosa; Barrett, Edward G; Anversa, Piero; Hintze, Thomas H; Rota, Marcello

    2016-04-01

    Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions. PMID:26801307

  1. Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content.

    PubMed

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

    2016-01-01

    Beetroot ( 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

  2. Atrial Fibrillation Treatment | NIH MedlinePlus the Magazine

    MedlinePlus

    ... 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 ...

  3. Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.

    PubMed Central

    Kagaya, Y; Weinberg, E O; Ito, N; Mochizuki, T; Barry, W H; Lorell, B H

    1995-01-01

    We tested the hypothesis that glycolytic inhibition by 2-deoxyglucose causes greater impairment of diastolic relaxation and intracellular calcium handling in well-oxygenated hypertrophied adult rat myocytes compared with control myocytes. We simultaneously measured cell motion and intracellular free calcium concentration ([Ca2+]i) with indo-1 in isolated paced myocytes from aortic-banded rats and sham-operated rats. There was no difference in either the end-diastolic or peak-systolic [Ca2+]i between control and hypertrophied myocytes (97 +/- 18 vs. 105 +/- 15 nM, 467 +/- 92 vs. 556 +/- 67 nM, respectively). Myocytes were first superfused with oxygenated Hepes-buffered solution containing 1.2 mM CaCl2, 5.6 mM glucose, and 5 mM acetate, and paced at 3 Hz at 36 degrees C. Exposure to 20 mM 2-deoxyglucose as substitution of glucose for 15 min caused an upward shift of end-diastolic cell position in both control (n = 5) and hypertrophied myocytes (n = 10) (P < 0.001 vs. baseline), indicating an impaired extent of relaxation. Hypertrophied myocytes, however, showed a greater upward shift in end-diastolic cell position and slowing of relaxation compared with control myocytes (delta 144 +/- 28 vs. 55 +/- 15% of baseline diastolic position, P < 0.02). Exposure to 2-deoxyglucose increased end-diastolic [Ca2+]i in both groups (P < 0.001 vs. baseline), but there was no difference between hypertrophied and control myocytes (218 +/- 38 vs. 183 +/- 29 nM, respectively). The effects of 2-deoxyglucose were corroborated in isolated oxygenated perfused hearts in which glycolytic inhibition which caused severe elevation of isovolumic diastolic pressure and prolongation of relaxation in the hypertrophied hearts compared with controls. In summary, the inhibition of the glycolytic pathway impairs diastolic relaxation to a greater extent in hypertrophied myocytes than in control myocytes even in well-oxygenated conditions. The severe impairment of diastolic relaxation induced by 2

  4. Effect of the atrial blanking time on the detection of atrial fibrillation in dual chamber pacing.

    PubMed

    Nowak, B; Kracker, S; Rippin, G; Horstick, G; Vincent, A; Geil, S; Himmrich, E; Meyer, J

    2001-04-01

    Patients with paroxysmal atrial fibrillation (PAF) and dual chamber pacemakers frequently have short postventricular atrial blanking times and sensitive atrial sensing thresholds used to provide reliable detection and mode switching during AF. However, short atrial blanking times increase the risk of atrial sensing of ventricular far-field signals. We evaluated if the length of the atrial blanking time influences the detection of AF. The study included ten patients with a VDDR (n = 7) or DDDR system (n = 3), who presented with AF at 18 follow-up visits. Bipolar atrial sensing was programmed to the most sensitive value. Atrial blanking times were programmed from 100 to 200 ms in 25-ms steps in each patient. Using marker annotation, the following parameters were measured at ten consecutive ventricular beats: VAF = the interval between ventricular stimulus and first sensing of AF; AFS = the number of atrial-sensed events between two ventricular events; and XAF = the interpolated number of atrial-sensed events during atrial blanking time. The intervals between ventricular events and between atrial-sensed event markers showed no significant differences for the five blanking times tested. There was no significant influence of the atrial blanking time onto the measured parameters (least square means +/- standard error) with VAF between 281 +/- 12 and 300 +/- 12 ms (P = NS), AFs between 3.4 +/- 0.2 and 3.6 +/- 0.2 beats (P = NS) and XAF between 1.84 +/- 0.12 and 2.03 +/- 0.12 beats (P = NS). At ventricular rates < 100/min, the atrial sensing of AF in dual chamber pacemakers demonstrated no evidence for deterioration by an increase of the atrial blanking time from 100 to 200 ms. Thus, the risk of ventricular far-field sensing may be reduced without compromising atrial sensing. PMID:11341088

  5. Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes.

    PubMed Central

    Bassel-Duby, R; Hernandez, M D; Yang, Q; Rochelle, J M; Seldin, M F; Williams, R S

    1994-01-01

    A sequence motif (CCAC box) within an upstream enhancer region of the human myoglobin gene is essential for transcriptional activity in both cardiac and skeletal muscle. A cDNA clone, myocyte nuclear factor (MNF), was isolated from a murine expression library on the basis of sequence-specific binding to the myoglobin CCAC box motif and was found to encode a novel member of the winged-helix or HNF-3/fork head family of transcription factors. Probes based on this sequence identify two mRNA species that are upregulated during myocyte differentiation, and antibodies raised against recombinant MNF identify proteins of approximately 90, 68, and 65 kDa whose expression is regulated following differentiation of myogenic cells in culture. In addition, the 90-kDa form of MNF is phosphorylated and is upregulated in intact muscles subjected to chronic motor nerve stimulation, a potent stimulus to myoglobin gene regulation. Amino acid residues 280 to 389 of MNF demonstrate 35 to 89% sequence identity to the winged-helix domain from other known members of this family, but MNF is otherwise divergent. A proline-rich amino-terminal region (residues 1 to 206) of MNF functions as a transcriptional activation domain. These studies provide the first evidence that members of the winged-helix family of transcription factors have a role in myogenic differentiation and in remodeling processes of adult muscles that occur in response to physiological stimuli. Images PMID:8007964

  6. [Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure].

    PubMed

    Zeus, Tobias; Kelm, Malte; Bode, Christoph

    2015-08-01

    Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. PMID:26261929

  7. Calcium and IP3 dynamics in cardiac myocytes: experimental and computational perspectives and approaches

    PubMed Central

    Hohendanner, Felix; McCulloch, Andrew D.; Blatter, Lothar A.; Michailova, Anushka P.

    2014-01-01

    [Ca2+] in the nuclear and cytosolic compartment. In this review, we discuss the state of knowledge regarding the origin and the physiological implications of nuclear Ca2+ transients in different cardiac cell types (adult atrial and ventricular myocytes) as well as experimental and mathematical approaches to study Ca2+ and IP3 signaling in the cytosol and nucleus. In particular, we focus on the concept that highly localized Ca2+ signals are required to translocate and activate Ca2+-dependent transcription factors (e.g., nuclear factor of activated T-cells, NFAT; histone deacetylase, HDAC) through phosphorylation/dephosphorylation processes. PMID:24639654

  8. Almanac 2015: atrial fibrillation research in Heart.

    PubMed

    Jawad-Ul-Qamar, Muhammad; Kirchhof, Paulus

    2016-04-01

    Atrial fibrillation continues to attract interest in the cardiovascular community and in Heart Over 60 original research and review papers published in Heart in 2014-2015 cover various aspects of atrial fibrillation, from associated conditions and precipitating factors to new approaches to management. Here, we provide an overview of articles on atrial fibrillation published in Heart in 2014-2015, highlighting new developments, emerging concepts and novel approaches to treatment. PMID:26791994

  9. Almanac 2015: atrial fibrillation research in Heart

    PubMed Central

    Jawad-Ul-Qamar, Muhammad; Kirchhof, Paulus

    2016-01-01

    Atrial fibrillation continues to attract interest in the cardiovascular community and in Heart. Over 60 original research and review papers published in Heart in 2014–2015 cover various aspects of atrial fibrillation, from associated conditions and precipitating factors to new approaches to management. Here, we provide an overview of articles on atrial fibrillation published in Heart in 2014–2015, highlighting new developments, emerging concepts and novel approaches to treatment. PMID:26791994

  10. Aspirin Often Wrongly Prescribed for Atrial Fibrillation

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159459.html Aspirin Often Wrongly Prescribed for Atrial Fibrillation Blood thinners -- not aspirin -- dramatically cut the risk of stroke, researchers say ...

  11. Hypoxia induces hypersensitivity and hyperreactivity to thromboxane receptor agonist in neonatal pulmonary arterial myocytes.

    PubMed

    Hinton, M; Mellow, L; Halayko, A J; Gutsol, A; Dakshinamurti, S

    2006-02-01

    PPHN, caused by perinatal hypoxia or inflammation, is characterized by an increased thromboxane-prostacyclin ratio and pulmonary vasoconstriction. We examined effects of hypoxia on myocyte thromboxane responsiveness. Myocytes from 3rd-6th generation pulmonary arteries of newborn piglets were grown to confluence and synchronized in contractile phenotype by serum deprivation. On the final 3 days of culture, myocytes were exposed to 10% O2 for 3 days; control myocytes from normoxic piglets were cultured in 21% O2. PPHN was induced in newborn piglets by 3-day hypoxic exposure (Fi(O2) 0.10); pulmonary arterial myocytes from these animals were maintained in normoxia. Ca2+ mobilization to thromboxane mimetic U-46619 and ATP was quantified using fura-2 AM. Three-day hypoxic exposure in vitro results in increased basal [Ca2+]i, faster and heightened peak Ca2+ response, and decreased U-46619 EC50. These functional changes persist in myocytes exposed to hypoxia in vivo but cultured in 21% O2. Blockade of Ca2+ entry and store refilling do not alter peak U-46619 Ca2+ responses in hypoxic or normoxic myocytes. Blockade of ryanodine-sensitive or IP3-gated intracellular Ca2+ channels inhibits hypoxic augmentation of peak U-46619 response. Ca2+ response to ryanodine alone is undetectable; ATP-induced Ca2+ mobilization is unaltered by hypoxia, suggesting no independent increase in ryanodine-sensitive or IP3-linked intracellular Ca2+ pool mobilization. We conclude hypoxia has a priming effect on neonatal pulmonary arterial myocytes, resulting in increased resting Ca2+, thromboxane hypersensitivity, and hyperreactivity. We postulate that hypoxia increases agonist-induced TP-R-linked IP3 pathway activation. Myocyte thromboxane hyperresponsiveness persists in culture after removal from the initiating hypoxic stimulus, suggesting altered gene expression. PMID:16214814

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

    SciTech Connect

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

    2009-04-01

    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{sup 2+}]{sub i} was measured by flow cytometry using fluo-3. Mitochondrial [Ca{sup 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{sup 2+} uptake, and increased the susceptibility of mitochondria to the MPT. CSE 0.1% increased DCF fluorescence in isolated myocytes, and increased [Ca{sup 2+}]{sub 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{sup 2+}]{sub i} during P-MI was also prevented by ranolazine. Conclusions: CSE in clinically relevant concentrations increases myocyte [Ca{sup 2+}]{sub 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.

  13. Azathioprine-induced atrial fibrillation

    PubMed Central

    Dogan, Pinar; Grbovic, Enis; Inci, Sinan; Bayraktar, Fatih; Cagli, Kumral

    2015-01-01

    Summary Azathioprine, a purine analogue that competitively inhibits the biosynthesis of purine nucleotides, is used in a wide range of conditions. Although its side-effects are well known, cardiac side effects like paroxysmal atrial fibrillation (AF) are based on only a few case reports. We describe here the case of a 55-year-old woman with primary biliary cirrhosis who presented a first-detected, symptomatic AF 2 h after azathioprine therapy which resolved after discontinuation of the drug with no predisposing factors for supraventricular arrhythmias (systemic hypertension, diabetes or coronary artery disease). The temporal coincidence of atrial fibrillation and azathioprine intake and disappearance of the AF episode after discontinuation of therapy allows us to suggest an intrinsic pro-arrhythmic effect of azathioprine. Therefore, physicians should be aware of this problem when this drug is administered. PMID:26668782

  14. Atrial fibrillation: inflammation in disguise?

    PubMed

    Lappegård, K T; Hovland, A; Pop, G A M; Mollnes, T E

    2013-08-01

    Atrial fibrillation is highly prevalent, and affected patients are at an increased risk of a number of complications, including heart failure and thrombo-embolism. Over the past years, there has been increasing interest in the role of inflammatory processes in atrial fibrillation, from the first occurrence of the arrhythmia to dreaded complications such as strokes or peripheral emboli. As the standard drug combination which aims at rate control and anticoagulation only offers partial protection against complications, newer agents are needed to optimize treatment. In this paper, we review recent knowledge regarding the impact of inflammation on the occurrence, recurrence, perpetuation and complications of the arrhythmia, as well as the role of anti-inflammatory therapies in the treatment for the disease. PMID:23672430

  15. Vector-averaged gravity alters myocyte and neuron properties in cell culture

    NASA Technical Reports Server (NTRS)

    Gruener, Raphael; Hoeger, Glenn

    1991-01-01

    The effect of changes in the gravitational field of developing neurons and myocytes on the development of these cells was investigated using observations of rotated cultures of embryonic spinal neurons and myocytes in a horizontal clinostat, in which rotation produces, from the cells' perspective, a 'vector-free' gravity environment by continous averaging of the vector, thus simulating the microgravity of space. It was found that, at rotation rates between 1 and 50 rpm, cellular and nuclear areas of myocytes become significantly enlarged and the number of presumptive nucleoli increase; in neurons, frequent and large swellings appeared along neuritic shafts. Some of these changes were reversible after the cessation of rotation.

  16. l-Arginine currents in rat cardiac ventricular myocytes

    PubMed Central

    Peluffo, R Daniel

    2007-01-01

    l-Arginine (l-Arg) is a basic amino acid that plays a central role in the biosynthesis of nitric oxide, creatine, agmantine, polyamines, proline and glutamate. Most tissues, including myocardium, must import l-Arg from the circulation to ensure adequate intracellular levels of this amino acid. This study reports novel l-Arg-activated inward currents in whole-cell voltage-clamped rat ventricular cardiomyocytes. Ion-substitution experiments identified extracellular l-Arg as the charge-carrying cationic species responsible for these currents, which, thus, represent l-Arg import into cardiac myocytes. This result was independently confirmed by an increase in myocyte nitric oxide production upon extracellular application of l-Arg. The inward movement of Arg molecules was found to be passive and independent of Na2+, K2+, Ca2+ and Mg2+. The process displayed saturation and membrane potential (Vm)-dependent kinetics, with a K0.5 for l-Arg that increased from 5 mm at hyperpolarizing Vm to 20 mm at +40 mV. l-Lysine and l-ornithine but not d-Arg produced currents with characteristics similar to that activated by l-Arg indicating that the transport process is stereospecific for cationic l-amino acids. l-Arg current was fully blocked after brief incubation with 0.2 mmN-ethylmaleimide. These features suggest that the activity of the low-affinity, high-capacity CAT-2A member of the y2+ family of transporters is responsible for l-Arg currents in acutely isolated cardiomyocytes. Regardless of the mechanism, we hypothesize that a low-affinity arginine transport process in heart, by ensuring substrate availability for sustained NO production, might play a cardio-protective role during catabolic states known to increase Arg plasma levels severalfold. PMID:17303641

  17. Wavelength index at three atrial sites in patients with paroxysmal atrial fibrillation.

    PubMed

    Padeletti, L; Michelucci, A; Giovannini, T; Porciani, M C; Bamoshmoosh, M; Mezzani, A; Chelucci, A; Pieragnoli, P; Gensini, G F

    1995-06-01

    The purpose of this study was to evaluate the wavelength index (WLI) at three atrial sites in a group of 23 patients with recurrent episodes of lone paroxysmal atrial fibrillation (LPAF) and a control group (n = 20). All patients underwent programmed atrial stimulation (paced cycle length = 600 ms) at high, medium, and low lateral right atrial wall. P wave duration, sinus cycle length, and corrected sinus node recovery time were not significantly different between the two study groups. WLI was calculated according to the following formulas: atrial effective refractory period (AERP)/duration of atrial extrastimulus electrogram (A2) or AERP/A2 + atrial latency; and atrial functional refractory period (AFRP)/A2. WLI was significantly shorter in LPAF than in the control group at each of the paced atrial sites independently of the formula used. Duration of premature atrial electrogram appeared to play the major role in determining the difference in WLI between patients with paroxysmal atrial fibrillation and the control group. PMID:7659580

  18. Atrial distension of isolated rabbit hearts and release of atrial natriuretic factor

    SciTech Connect

    Synhorst, D.P.; Gutkowska, J. Clinical Research Institute of Montreal, Quebec )

    1988-08-01

    Interventions that increase atrial pressures in humans or laboratory animals release atrial natriuretic factor (ANF) into the circulation. The authors studied the relation between distension of the right or left atrium and release of ANF in retrograde-perfused isolated rabbit hearts. A fluid-filled balloon within the right or left atrium was inflated to a mean pressure of 5, 10, 15, or 20 mmHg, and ANF in the cardiac effluent was measured by radioimmunoassay. The slope of the regression line relating ANF release to atrial distending pressure was steeper for the left than right atrium, indicating that, at comparable increases in mean pressures, the left atrium releases more ANF than does the right atrium. Left atrial tissue concentration ANF was greater than right atrial. In contrast to previous studies showing right atrial dominance in rats, the left atria of isolated, perfused rabbit hearts contain more ANF and release more in response to atrial distension.

  19. Robotic-assisted left atrial ligation for stroke reduction in chronic atrial fibrillation: a case report.

    PubMed

    Kiaii, Bob; McClure, R Scott; Skanes, Alan C; Ross, Ian G; Spouge, Alison R; Swinamer, Stuart; Rayman, Reiza; Bainbridge, Daniel T; Iglesias, Ivan; Novick, Richard J

    2006-01-01

    Patients with atrial fibrillation are at significant risk for sustaining a thromboembolic stroke. More than 90% of thromboemboli form in the left atrial appendage. Ligation of the left atrial appendage to reduce the risk of stroke is often performed in connection with other cardiac surgical procedures. As a stand-alone procedure, however, left atrial ligation has generally been deemed too invasive and has gained little support as an alternative therapeutic option. We report a case of port-access robotic-assisted left atrial ligation as a stand-alone procedure in a patient with chronic atrial fibrillation in whom anticoagulation was a contraindication. To our knowledge, this is the first reported case of stand-alone robotic-assisted left atrial ligation in the literature. PMID:16387671

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

    PubMed Central

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

    2014-01-01

    Aim 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). Methods and results 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 Ca2+ 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. Conclusion 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. PMID:24336332

  1. The mechanism of PDT-induced electrical blockade: the dependence of time-lapse localization of talaporfin sodium on the cell death phenotypes in rat cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Ito, A.; Matsuo, H.; Suenari, T.; Miyoshi, S.; Takatsuki, S.; Ogawa, S.; Arai, T.

    2009-02-01

    We have proposed a new type of atrial fibrillation treatment with the early state photodynamic therapy (PDT), in which the interval time between the photosensitizer injection and irradiation is shorter than that in conventional way. We had demonstrated the acute electrical blockade by the PDT with talaporfin sodium and a red (670 nm) diode laser in ex vivo and in vivo experiment using rat normal myocardial tissue. The previous study of intracellular Ca2+ concentration measurement in rat cardiac myocytes during the PDT indicated that Ca2+ influx induced by the plasma membrane damage might be the main cause of the acute reaction of myocardial tissue. We found that the cell damage of cardiac myocytes triggered by the PDT was mainly influenced by the site where the photosensitizer exists. In this study, we examined the relationship between the sites of talaporfin sodium existing and cell death phenotypes in response to the PDT, in order to clarify the mechanism of the acute electrical blockade induced by the PDT in myocardial tissue. The talaporfin sodium fluorescence was observed after the various incubation times to visualize the time-lapse intracellular photosensitizer localization. The distribution of the photosensitizer was dependent on the incubation time. The change in intracellular Ca2+ concentration during the PDT was examined with a fluorescent Ca2+ indicator by a high-speed Nipkow confocal laser microscope (CSU-X1, Yokogawa Electric Company). We obtained the Ca2+ dynamics during the PDT which can explain the PDT-induced cell death pathways. We concluded that the Ca2+ influx induced by plasma membrane damage is the possible mechanism of the electrical blockade by the early state PDT.

  2. There and back again: Iterating between population-based modeling and experiments reveals surprising regulation of calcium transients in rat cardiac myocytes.

    PubMed

    Devenyi, Ryan A; Sobie, Eric A

    2016-07-01

    While many ion channels and transporters involved in cardiac cellular physiology have been identified and described, the relative importance of each in determining emergent cellular behaviors remains unclear. Here we address this issue with a novel approach that combines population-based mathematical modeling with experimental tests to systematically quantify the relative contributions of different ion channels and transporters to the amplitude of the cellular Ca(2+) transient. Sensitivity analysis of a mathematical model of the rat ventricular cardiomyocyte quantified the response of cell behaviors to changes in the level of each ion channel and transporter, and experimental tests of these predictions were performed to validate or invalidate the predictions. The model analysis found that partial inhibition of the transient outward current in rat ventricular epicardial myocytes was predicted to have a greater impact on Ca(2+) transient amplitude than either: (1) inhibition of the same current in endocardial myocytes, or (2) comparable inhibition of the sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA). Experimental tests confirmed the model predictions qualitatively but showed some quantitative disagreement. This guided us to recalibrate the model by adjusting the relative importance of several Ca(2+) fluxes, thereby improving the consistency with experimental data and producing a more predictive model. Analysis of human cardiomyocyte models suggests that the relative importance of outward currents to Ca(2+) transporters is generalizable to human atrial cardiomyocytes, but not ventricular cardiomyocytes. Overall, our novel approach of combining population-based mathematical modeling with experimental tests has yielded new insight into the relative importance of different determinants of cell behavior. PMID:26235057

  3. A novel and simple atrial retractor.

    PubMed

    Kofidis, Theo; Lee, Chuen Neng

    2011-05-01

    Minimally invasive cardiac operations require specialized equipment. Atrial retractors are a frequently used tool to expose heart valves for minimally invasive and open procedures. The models currently available in the market are efficient; however, they may be complex, bulky, or expensive. We introduce a novel, very simple atrial retractor we designed using ubiquitously available materials. PMID:21524488

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

    PubMed

    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. PMID:26846223

  5. Blocked atrial bigeminy presenting with bradycardia.

    PubMed

    Akdeniz, Celal; Tanidir, Ibrahim Cansaran; Tuzcu, Volkan

    2012-01-01

    Blocked premature atrial contractions can cause bradycardia by resetting sinoatrial node and prolonging the RR intervals. Herein, we report the management of a patient with frequent premature atrial contractions in bigeminal pattern. The patient presented with symptomatic bradycardia and was successfully treated with propafenone. PMID:22469245

  6. Atrial Arrhythmia Summit: Post Summit Report

    NASA Technical Reports Server (NTRS)

    Barr, Yael

    2010-01-01

    The Atrial Arrhythmia Summit brought together nationally and internationally recognized experts in cardiology, electrophysiology, exercise physiology, and space medicine in an effort to elucidate the mechanisms, risk factors, and management of atrial arrhythmias in the unique occupational cohort of the U.S. astronaut corps.

  7. Minimally Invasive Surgical Therapies for Atrial Fibrillation

    PubMed Central

    Nakamura, Yoshitsugu; Kiaii, Bob; Chu, Michael W. A.

    2012-01-01

    Atrial fibrillation is the most common sustained arrhythmia and is associated with significant risks of thromboembolism, stroke, congestive heart failure, and death. There have been major advances in the management of atrial fibrillation including pharmacologic therapies, antithrombotic therapies, and ablation techniques. Surgery for atrial fibrillation, including both concomitant and stand-alone interventions, is an effective therapy to restore sinus rhythm. Minimally invasive surgical ablation is an emerging field that aims for the superior results of the traditional Cox-Maze procedure through a less invasive operation with lower morbidity, quicker recovery, and improved patient satisfaction. These novel techniques utilize endoscopic or minithoracotomy approaches with various energy sources to achieve electrical isolation of the pulmonary veins in addition to other ablation lines. We review advancements in minimally invasive techniques for atrial fibrillation surgery, including management of the left atrial appendage. PMID:22666609

  8. GENERAL: Stochastic Alternating Dynamics for Synchronous EAD-Like Beating Rhythms in Cultured Cardiac Myocytes

    NASA Astrophysics Data System (ADS)

    Zhang, Ning; Zhang, Hui-Min; Liu, Zhi-Qiang; Ding, Xue-Li; Yang, Ming-Hao; Gu, Hua-Guang; Ren, Wei

    2009-11-01

    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.

  9. Left atrial strain: A useful index in atrial fibrillation.

    PubMed

    Cameli, Matteo; Mandoli, Giulia Elena; Loiacono, Ferdinando; Sparla, Stefania; Iardino, Elisabetta; Mondillo, Sergio

    2016-10-01

    Left atrial (LA) strain is a speckle tracking echocardiography (STE)-derived parameter applied to the analysis of chamber function that provides highly reproducible measures of LA deformation by a non-Doppler, angle-independent quantification. In recent years, data regarding accuracy and clinical application of LA strain are rapidly increasing. This review describes the main features of LA strain and examines the role of STE in the evaluation of various aspects of AF, as the risk of developing the arrhythmia in general population, the evaluation of LA fibrosis and LA impairment, the quantification of cardioembolic risk and of recurrence after cardioversion or ablation therapies. PMID:27389443

  10. Myocyte-Depleted Engineered Cardiac Tissues Support Therapeutic Potential of Mesenchymal Stem Cells

    PubMed Central

    Serrao, Gregory W.; Turnbull, Irene C.; Ancukiewicz, Damian; Kim, Do Eun; Kao, Evan; Cashman, Timothy J.; Hadri, Lahouaria; Hajjar, Roger J.

    2012-01-01

    The therapeutic potential of mesenchymal stem cells (MSCs) for restoring cardiac function after cardiomyocyte loss remains controversial. Engineered cardiac tissues (ECTs) offer a simplified three-dimensional in vitro model system to evaluate stem cell therapies. We hypothesized that contractile properties of dysfunctional ECTs would be enhanced by MSC treatment. ECTs were created from neonatal rat cardiomyocytes with and without bone marrow-derived adult rat MSCs in a type-I collagen and Matrigel scaffold using custom elastomer molds with integrated cantilever force sensors. Three experimental groups included the following: (1) baseline condition ECT consisting only of myocytes, (2) 50% myocyte-depleted ECT, modeling a dysfunctional state, and (3) 50% myocyte-depleted ECT plus 10% MSC, modeling dysfunctional myocardium with intervention. Developed stress (DS) and pacing threshold voltage (VT) were measured using 2-Hz field stimulation at 37°C on culture days 5, 10, 15, and 20. By day 5, DS of myocyte-depleted ECTs was significantly lower than baseline, and VT was elevated. In MSC-supplemented ECTs, DS and VT were significantly better than myocyte-depleted values, approaching baseline ECTs. Findings were similar through culture day 15, but lost significance at day 20. Trends in DS were partly explained by changes in the cell number and alignment with time. Thus, supplementing myocyte-depleted ECTs with MSCs transiently improved contractile function and compensated for a 50% loss of cardiomyocytes, mimicking recent animal studies and clinical trials and supporting the potential of MSCs for myocardial therapy. PMID:22500611

  11. Myocyte-depleted engineered cardiac tissues support therapeutic potential of mesenchymal stem cells.

    PubMed

    Serrao, Gregory W; Turnbull, Irene C; Ancukiewicz, Damian; Kim, Do Eun; Kao, Evan; Cashman, Timothy J; Hadri, Lahouaria; Hajjar, Roger J; Costa, Kevin D

    2012-07-01

    The therapeutic potential of mesenchymal stem cells (MSCs) for restoring cardiac function after cardiomyocyte loss remains controversial. Engineered cardiac tissues (ECTs) offer a simplified three-dimensional in vitro model system to evaluate stem cell therapies. We hypothesized that contractile properties of dysfunctional ECTs would be enhanced by MSC treatment. ECTs were created from neonatal rat cardiomyocytes with and without bone marrow-derived adult rat MSCs in a type-I collagen and Matrigel scaffold using custom elastomer molds with integrated cantilever force sensors. Three experimental groups included the following: (1) baseline condition ECT consisting only of myocytes, (2) 50% myocyte-depleted ECT, modeling a dysfunctional state, and (3) 50% myocyte-depleted ECT plus 10% MSC, modeling dysfunctional myocardium with intervention. Developed stress (DS) and pacing threshold voltage (VT) were measured using 2-Hz field stimulation at 37°C on culture days 5, 10, 15, and 20. By day 5, DS of myocyte-depleted ECTs was significantly lower than baseline, and VT was elevated. In MSC-supplemented ECTs, DS and VT were significantly better than myocyte-depleted values, approaching baseline ECTs. Findings were similar through culture day 15, but lost significance at day 20. Trends in DS were partly explained by changes in the cell number and alignment with time. Thus, supplementing myocyte-depleted ECTs with MSCs transiently improved contractile function and compensated for a 50% loss of cardiomyocytes, mimicking recent animal studies and clinical trials and supporting the potential of MSCs for myocardial therapy. PMID:22500611

  12. Aliskiren protecting atrial structural remodeling from rapid atrial pacing in a canine model.

    PubMed

    Zhao, Zhiqiang; Chen, Yan; Li, Weimin; Wang, Xinghua; Li, Jian; Yang, Wansong; Cheng, Lijun; Liu, Tong; Liu, Enzhao; Li, Guangping

    2016-08-01

    Atrial fibrillation (AF) contributing to the increasing mortality risk is the most common disease in clinical practice. Owing to the side effects and relative inefficacy of current antiarrhythmic drugs, some research focuses on renin-angiotensin-aldosterone system (RAS) for finding out the new treatment of AF. The purpose of this study is to confirm whether aliskiren as a proximal inhibitor of renin, which completely inhibits RAS, has beneficial effects on atrial structural remodeling in AF. In this study, rapid atrial pacing was induced at 500 beats per minute for 2 weeks in a canine model. A different dose of aliskiren was given orally for 2 weeks before rapid atrial pacing. HE staining and Masson's staining were used for analysis of myocardial fibrosis. TGF-β1, signal pathways, and pro-inflammatory cytokines were shown for the mechanism of structural remodeling after the treatment of aliskiren. Serious atrial fibrosis was induced by rapid atrial pacing, followed by the elevated TGF-β1, upregulated MEK and ERK1/2, and increased inflammatory factors. Aliskiren could apparently improve myocardial fibrosis by reducing the expression of TGF-β1, inhibiting MEK and ERK1/2 signal pathways, and decreasing IL-18 and TLR4 in both serum and atrial tissue. In conclusion, aliskiren could prevent atrial structural remodeling from rapid atrial pacing for 2 weeks. Aliskiren may play a potential beneficial role in the treatment of AF induced by rapid atrial pacing. PMID:27118660

  13. Atrial fibrillation and physical activity

    PubMed Central

    Bosomworth, N. John

    2015-01-01

    Objective To review the evidence on the effects of various levels of physical activity (PA) on the incidence of atrial fibrillation (AF) in both the general population and in endurance athletes. Data sources A PubMed search was done initially using the MeSH headings or text words (with the search-field descriptor TIAB [title and abstract]) atrial fibrillation and exercise or physical activity or athlet* or sport*, without additional filters. Conclusions regarding quality and strength of evidence were based on the GRADE (grading of recommendations, assessment, development, and evaluation) system. Study selection No interventional studies were available. Observational studies were therefore considered acceptable, and, although larger long-term prospective cohort studies were preferred, case-control or cross-sectional trials were also included in this review. Synthesis Available evidence suggests a dose-response association linking increased exercise levels with reduced incident AF in women. The same is true in men at low and moderate levels of exertional activity. In men only, high levels of PA are associated with increased risk of AF in most, but not all, studies. This risk is moderate, with a hazard ratio of 1.29 in one of the better studies. The risk of AF for most people who exercise regularly is lower than that of a matched sedentary population. Conclusion Atrial fibrillation is probably less common as PA increases, with a demonstrable dose-response relationship. Exercise at any level should be promoted for its effect on physical well-being and mortality reduction. In men exercising at high levels, beneficial effects on AF might be lost and risk might exceed that of the sedentary population; however, the evidence is neither robust nor consistent. These men should be made aware of this modest increase in risk should they choose to continue to engage in high levels of PA. PMID:26668285

  14. Native American Discursive Tactic

    ERIC Educational Resources Information Center

    Black, Jason Edward

    2013-01-01

    This essay derives from a course called ‘"The Rhetoric of Native America,’" which is a historical-critical survey of Native American primary texts. The course examines the rhetoric employed by Natives to enact social change and to build community in the face of exigencies. The main goal of exploring a native text (particularly, Simon Pokagon's…

  15. Advances in Atrial Fibrillation Ablation

    PubMed Central

    Darge, Alicia; Reynolds, Matthew R.; Germano, Joseph J.

    2009-01-01

    Atrial Fibrillation (AF) is an increasingly common and costly medical problem.1–3 Given the disappointing efficacy and side effects associated with pharmacological therapy for AF, new treatment options are needed. Over the last decade, advances in our understanding of the mechanisms of AF, coupled with iterative improvements in catheter ablation techniques, have spurred the evolution of catheter ablation for AF from an experimental procedure to an increasingly important treatment option.4 This paper will review recent advances in the approaches and outcomes of AF ablation. PMID:19411729

  16. Atrial Fibrillation Ablation and Stroke.

    PubMed

    Aagaard, Philip; Briceno, David; Csanadi, Zoltan; Mohanty, Sanghamitra; Gianni, Carola; Trivedi, Chintan; Nagy-Baló, Edina; Danik, Stephan; Barrett, Conor; Santoro, Francesco; Burkhardt, J David; Sanchez, Javier; Natale, Andrea; Di Biase, Luigi

    2016-05-01

    Catheter ablation has become a widely available and accepted treatment to restore sinus rhythm in atrial fibrillation patients who fail antiarrhythmic drug therapy. Although generally safe, the procedure carries a non-negligible risk of complications, including periprocedural cerebral insults. Uninterrupted anticoagulation, maintenance of an adequate ACT during the procedure, and measures to avoid and detect thrombus build-up on sheaths and atheters during the procedure, appears useful to reduce the risk of embolic events. This is a review of the incidence, mechanisms, impact, and methods to reduce catheter ablation related cerebral insults. PMID:27150179

  17. Surgical Treatment of Concomitant Atrial Fibrillation: Focus onto Atrial Contractility

    PubMed Central

    Loardi, Claudia; Alamanni, Francesco; Galli, Claudia; Naliato, Moreno; Veglia, Fabrizio; Zanobini, Marco; Pepi, Mauro

    2015-01-01

    Background. Maze procedure aims at restoring sinus rhythm (SR) and atrial contractility (AC). This study evaluated multiple aspects of AC recovery and their relationship with SR regain after ablation. Methods. 122 mitral and fibrillating patients underwent radiofrequency Maze. Rhythm check and echocardiographic control of biatrial contractility were performed at 3, 6, 12, and 24 months postoperatively. A multivariate Cox analysis of risk factors for absence of AC recuperation was applied. Results. At 2-years follow-up, SR was achieved in 79% of patients. SR-AC coexistence increased from 76% until 98%, while biatrial contraction detection augmented from 84 to 98% at late stage. Shorter preoperative arrhythmia duration was the only common predictor of SR-AC restoring, while pulmonary artery pressure (PAP) negatively influenced AC recuperation. Early AC restoration favored future freedom from arrhythmia recurrence. Minor LA dimensions correlated with improved future A/E value and vice versa. Right atrial (RA) contractility restoring favored better left ventricular (LV) performance and volumes. Conclusions. SR and left AC are two interrelated Maze objectives. Factors associated with arrhythmia “chronic state” (PAP and arrhythmia duration) are negative predictors of procedural success. Our results suggest an association between postoperative LA dimensions and “kick” restoring and an influence of RA contraction onto LV function. PMID:26229956

  18. An Experimental Model Using Cultured Cardiac Myocytes for a Study of the Generation of Premature Ventricular Contractions Under Ultrasound Exposure

    NASA Astrophysics Data System (ADS)

    Kudo, Nobuki; Yamamoto, Masaya

    2011-09-01

    It is known that use of a contrast agents in echocardiography increases the probability of generation of premature ventricular contractions (PVCs). As a basic study to elucidate the mechanisms and to reduce adverse effects, the generation of PVCs was investigated using cultured cardiac myocytes instead of the intact heart in vivo. Cardiac myocytes were isolated from neonatal rats and cultured on a cover slip. The myocyte sample was exposed to pulsed ultrasound with microbubbles adjacent to the myocytes, and generation of PVCs was examined with ultrasound exposure at various delay times after onset of myocyte contraction. The experimental results showed that generation of PVCs had a stable threshold delay time and that PVCs were generated only when myocytes were exposed to ultrasound with delay times longer than the threshold. The results indicate that the model used in this study is useful for revealing the mechanisms by which PVCs are induced by ultrasound exposure.

  19. Physiological pathway of magnesium influx in rat ventricular myocytes.

    PubMed

    Tashiro, Michiko; Inoue, Hana; Konishi, Masato

    2014-11-01

    Cytoplasmic free Mg(2+) concentration ([Mg(2+)]i) was measured in rat ventricular myocytes with a fluorescent indicator furaptra (mag-fura-2) introduced by AM-loading. By incubation of the cells in a high-K(+) (Ca(2+)- and Mg(2+)-free) solution, [Mg(2+)]i decreased from ? 0.9 mM to 0.2 to 0.5 mM. The lowered [Mg(2+)]i was recovered by perfusion with Ca(2+)-free Tyrode's solution containing 1 mM Mg(2+). The time course of the [Mg(2+)]i recovery was fitted by a single exponential function, and the first derivative at time 0 was analyzed as being proportional to the initial Mg(2+) influx rate. The Mg(2+) influx rate was inversely related to [Mg(2+)]i, being higher at low [Mg(2+)]i. The Mg(2+) influx rate was augmented by the high extracellular Mg(2+) concentration (5 mM), whereas it was greatly reduced by cell membrane depolarization caused by high K(+). Known inhibitors of TRPM7 channels, 2-aminoethoxydiphenyl borate (2-APB), NS8593, and spermine reduced the Mg(2+) influx rate with half inhibitory concentrations (IC50) of, respectively, 17 ?M, 2.0 ?M, and 22 ?M. We also studied Ni(2+) influx by fluorescence quenching of intracellular furaptra by Ni(2+). The Ni(2+) influx was activated by lowering intra- and extracellular Mg(2+) concentrations, and it was inhibited by 2-APB and NS8593 with IC50 values comparable with those for the Mg(2+) influx. Intracellular alkalization (caused by pulse application of NH4Cl) enhanced, whereas intracellular acidification (induced after the removal of NH4Cl) slowed the Mg(2+) influx. Under the whole-cell patch-clamp configuration, the removal of intracellular and extracellular divalent cations induced large inward and outward currents, MIC (Mg-inhibited cation) currents or IMIC, carried by monovalent cations likely via TRPM7 channels. IMIC measured at -120 mV was diminished to ? 50% by 100 ?M 2-APB or 10 ?M NS8593. These results suggest that TRPM7/MIC channels serve as a major physiological pathway of Mg(2+) influx in rat

  20. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    PubMed Central

    2010-01-01

    Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics

  1. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

    PubMed Central

    Pilarczyk, Götz; Raulf, Alexandra; Gunkel, Manuel; Fleischmann, Bernd K.; Lemor, Robert; Hausmann, Michael

    2016-01-01

    The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds. PMID:26751484

  2. Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes.

    PubMed

    Pilarczyk, Götz; Raulf, Alexandra; Gunkel, Manuel; Fleischmann, Bernd K; Lemor, Robert; Hausmann, Michael

    2016-01-01

    The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds. PMID:26751484

  3. Stroke risk assessment in atrial fibrillation: risk factors and markers of atrial myopathy.

    PubMed

    Calenda, Brandon W; Fuster, Valentin; Halperin, Jonathan L; Granger, Christopher B

    2016-09-01

    Atrial fibrillation (AF) is a complex phenomenon associated with electrical, mechanical, and structural abnormalities of the atria. Ischaemic stroke in AF is only partially understood, but the mechanisms are known to be related to the atrial substrate as well as the atrial rhythm. The temporal dissociation between timing of AF and occurrence of stroke has led to the hypothesis that fibrotic, prothrombotic atrial tissue is an important cause of thrombus formation in patients with AF, independent of the atrial rhythm. Current stroke risk scores are practical, but limited in their capacity to predict stroke risk accurately in individual patients. Stroke prediction might be improved by the addition of emerging risk factors, many of which are expressions of atrial fibrosis. The use of novel parameters, including clinical criteria, biomarkers, and imaging data, might improve stroke risk prediction and inform on optimal treatment for patients with AF and perhaps individuals only at risk of AF. PMID:27383079

  4. Atrial natriuretic peptide suppresses endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4-dependent mechanism

    PubMed Central

    Glenn, Denis J.; Rahmutula, Dolkun; Nishimoto, Minobu; Liang, Faquan; Gardner, David G.

    2009-01-01

    Aims Atrial natriuretic peptide (ANP) is a hormone that has both antihypertrophic and antifibrotic properties in the heart. We hypothesized that myocyte-derived ANP inhibits endothelin (ET) gene expression in fibroblasts. Methods and results We have investigated the mechanism(s) involved in the antiproliferative effect of ANP on cardiac fibroblasts in a cell culture model. We found that cardiac myocytes inhibited DNA synthesis in co-cultured cardiac fibroblasts as did treatment with the ET-1 antagonist BQ610. The effect of co-culture was reversed by antibody directed against ANP or the ANP receptor antagonist HS-142-1. ANP inhibited the expression of the ET-1 gene and ET-1 gene promoter activity in cultured fibroblasts. The site of the inhibition was localized to a GATA-binding site positioned between −132 and −135 upstream from the transcription start site. GATA4 expression was demonstrated in cardiac fibroblasts, GATA4 bound the ET-1 promoter both in vitro and in vivo, and siRNA-mediated knockdown of GATA4 inhibited ET-1 expression. ET-1 treatment resulted in increased levels of phospho-serine105 GATA4 in cardiac fibroblasts and this induction was partially suppressed by co-treatment with ANP. Conclusion Collectively, these findings suggest that locally produced ET-1 serves as an autocrine stimulator of fibroblast proliferation, that ANP produced in neighbouring myocytes serves as a paracrine inhibitor of this proliferation, and that the latter effect operates through a reduction in GATA4 phosphorylation and coincident reduction in GATA4-dependent transcriptional activity. PMID:19546173

  5. Acute treatment of atrial fibrillation.

    PubMed

    Kowey, P R; Marinchak, R A; Rials, S J; Filart, R A

    1998-03-12

    Atrial fibrillation (AFib) is a common clinical entity, responsible for significant morbidity and mortality, but it also accounts for a large percentage of healthcare dollar expenditures. Efforts to treat this arrhythmia in the past have focused on subacute antithrombotic therapy and eventually use of antiarrhythmic drugs for maintenance of sinus rhythm. However, there has been a growing interest in the concept of acute electrical and pharmacologic conversion. This treatment strategy has a number of benefits, including immediate alleviation of patient symptoms, avoidance of antithrombotic therapy, and prevention of electrophysiologic remodeling, which is thought to contribute to the perpetuation of the arrhythmia. There is also increasing evidence that this is a cost-effective strategy in that it may obviate admission to the hospital and the cost of long-term therapy. This article represents a summary of the treatments that may be used acutely to control the ventricular response to AFib, prevent thromboembolic events, and provide for acute conversion either pharmacologically or electrically. It includes information on modalities that are currently available and those that are under active development. We anticipate that an active, acute treatment approach to AFib and atrial flutter will become the therapeutic norm in the next few years, especially as the benefits of these interventions are demonstrated in clinical trials. PMID:9525568

  6. The atrial T wave: The elusive electrocardiographic wave exposed by a case of shifting atrial pacemaker.

    PubMed

    Langley, Philip; Caldwell, Jane

    2016-01-01

    The atrial T wave (Ta wave) is the body surface manifestation of atrial repolarisation and, unlike the P wave (atrial depolarisation), is little recognised. We report the case of a patient with shifting pacemaker which clearly demonstrates the effect of the Ta wave on ST segment and T wave. A simple conceptual model is used to explain the observed phenomenon. The case serves as a reminder of this often forgotten ECG wave and its potential effects on other ECG features. PMID:27215648

  7. Relaxation in ferret ventricular myocytes: unusual interplay among calcium transport systems.

    PubMed Central

    Bassani, R A; Bassani, J W; Bers, D M

    1994-01-01

    Transport systems responsible for removing Ca2+ from the myoplasm during relaxation in isolated ferret ventricular myocytes were studied using caffeine-induced contractures. Internal calcium concentration ([Ca2+]i) was measured with the fluorescent calcium indicator indo-1, and the results were compared with our recent detailed characterizations in rabbit and rat myocytes. Relaxation and [Ca2+]i decline during a twitch in ferret myocytes were fast and similar to that in rat myocytes (i.e. half-time, t 1/2 approximately 100-160 ms). During a caffeine-induced contracture (SR Ca2+ accumulation prevented), relaxation was still relatively fast (t 1/2 = 0.57 s) and similar to relaxation in rabbit supported mainly by a strong Na(+)-Ca2+ exchange. When both the SR Ca2+ uptake and Na(+)-Ca2+ exchange are blocked (by caffeine and 0 Na+, 0 Ca2+ solution) relaxation in the ferret myocyte is remarkably fast (approximately 5-fold) compared with rabbit and rat myocytes. The decline of the Cai2+ transient was also fast under these conditions. These values were similar to those in rat under conditions where relaxation is due primarily to Na(+)-Ca2+ exchange. Additional inhibition of either the sarcolemmal Ca(2+)-ATPase or mitochondrial Ca2+ uptake caused only modest slowing of the relaxation of caffeine-induced contracture in 0 Na+, 0 Ca2+ (t 1/2 increased to approximately 3 s). In rabbit myocytes the relaxation t 1/2 is slowed to 20-30 s by these procedures. Even when the systems responsible for slow relaxation in rabbit ventricular myocytes are inhibited (i.e. sarcolemmal Ca(2+)-ATPase and mitochondrial Ca2+ uptake) along with the SR Ca(2+)-ATPase and Na(+)-Ca2+ exchange, relaxation and [Ca2+]i decline in ferret myocytes remain rapid compared with rabbit myocytes. Ca2+ taken up by mitochondria in rabbit myocytes during a caffeine contracture in 0 Na+, 0 Ca2+ solution gradually returns to the SR after caffeine removal, but this component appears to be much smaller in ferret

  8. Calcium Movements Inside the Sarcoplasmic Reticulum of Cardiac Myocytes

    PubMed Central

    Bers, Donald M.; Shannon, Thomas R.

    2013-01-01

    Sarcoplasmic reticulum (SR) Ca content ([Ca]SRT) is critical to both normal cardiac function and electrophysiology, and changes associated with pathology contribute to systolic and diastolic dysfunction and arrhythmias. The intra-SR free [Ca] ([Ca]SR) dictates the [Ca]SRT, the driving force for Ca release and regulates release channel gating. We discuss measurement of [Ca]SR and [Ca]SRT, how [Ca]SR regulates activation and termination of release, and how Ca diffuses within the SR and influences SR Ca release during excitation-contraction coupling, Ca sparks and Ca waves. The entire SR network is connected and its lumen is also continuous with the nuclear envelope. Rapid Ca diffusion within the SR could stabilize and balance local [Ca]SR within the myocyte, but restrictions to diffusion can create spatial inhomogeneities. Experimental measurements and mathematical models of [Ca]SR to date have greatly enriched our understanding of these [Ca]SR dynamics, but controversies exist and may stimulate new measurements and analysis. PMID:23321551

  9. MicroRNA-27b Regulates Mitochondria Biogenesis in Myocytes

    PubMed Central

    Zhang, Shunhua; Du, Jingjing; Bai, Lin; Zhang, Yi; Jiang, Yanzhi; Li, Xuewei; Wang, Jinyong; Zhu, Li

    2016-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that affect the post-transcriptional regulation of various biological pathways. To date, it is not fully understood how miRNAs regulate mitochondrial biogenesis. This study aimed at the identification of the role of miRNA-27b in mitochondria biogenesis. The mitochondria content in C2C12 cells was significantly increased during myogenic differentiation and accompanied by a marked decrease of miRNA-27b expression. Furthermore, the expression of the predicted target gene of miRNA-27b, forkhead box j3 (Foxj3), was also increased during myogenic differentiation. Luciferase activity assays confirmed that miRNA-27b directly targets the 3’-untranslated region (3’-UTR) of Foxj3. Overexpression of miRNA-27b provoked a decrease of mitochondria content and diminished expression of related mitochondrial genes and Foxj3 both at mRNA and protein levels. The expression levels of downstream genes of Foxj3, such as Mef2c, PGC1α, NRF1 and mtTFA, were also decreased in C2C12 cells upon overexpression of miRNA-27b. These results suggested that miRNA-27b may affect mitochondria biogenesis by down-regulation of Foxj3 during myocyte differentiation. PMID:26849429

  10. Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts

    NASA Technical Reports Server (NTRS)

    Ito, K.; Yan, X.; Tajima, M.; Su, Z.; Barry, W. H.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. Myocyte contraction and [Ca(2+)](i) transients with fluo-3 were measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C), the amplitude of myocyte shortening and peak-systolic [Ca(2+)](i) in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca(2+)](i) transients were slower. In response to the challenge of high [Ca(2+)](o), fractional cell shortening was severely depressed with reduced peak-systolic [Ca(2+)](i) in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca(2+)](i) increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca(2+)](o) and rapid pacing in 4-week AS were similar to those of controls. Although protein levels of Na(+)-Ca(2+) exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca(2+)-ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca(2+) load during high work states in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca(2+)](i) and SR Ca(2+) load and simulates findings in human failing myocytes.