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  1. The atrial natriuretic factor.

    PubMed Central

    Genest, J

    1986-01-01

    In less than three years since the rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats was reported the factor responsible for the diuretic, natriuretic, and vasodilating activity of the atrial homogenates was isolated, its chemical structure elucidated, and its total synthesis achieved. Also the cDNA and the gene encoding for the atrial natriuretic factor in mice, rats, and man have been cloned and the chromosomal site identified. The major effects of this hormone are vasodilatation, prevention and inhibition of the contraction induced by noradrenaline and angiotensin II, diuresis, and natriuresis associated in most instances with a pronounced increase in glomerular filtration rate and filtration fraction, inhibition of aldosterone secretion, and considerable stimulation of particulate guanylate cyclase activity. High density specific binding sites have been demonstrated in the zona glomerulosa of the adrenal cortex, in the renal glomeruli, and in the collecting ducts, and in the brain areas involved in the regulation of blood pressure and of sodium and water (AV3V region, subfornical organ, nucleus tractus solitarius, area postrema). Images Fig 1 Fig 5 PMID:2945572

  2. Atrial natriuretic factor increases vascular permeability

    SciTech Connect

    Lockette, W.; Brennaman, B. )

    1990-12-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  3. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  4. Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.

    PubMed

    Ito, Shingo; Ohtsuki, Sumio; Murata, Sho; Katsukura, Yuki; Suzuki, Hiroya; Funaki, Miho; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-01-01

    Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.

  5. Atrial natriuretic factor-like activity in rat posterior pituitary

    SciTech Connect

    Gutkowska, J.; Debinski, W.; Racz, K.; Thibault, G.; Garcia, R.; Kuchel, O.; Genest, J.; Cantin, M.

    1986-03-05

    The presence of a biologically active peptide: Atrial Natriuretic Factor (ANF) has been demonstrated in rat and human circulation and ANF is considered now as a new hormone. ANF may be involved in body fluid regulation. A very sensitive radioimmunoassay for rat ANF allowed the authors to search for immunoreactive ANF (IR-ANF) in rat posterior pituitary. Serial dilutions of homogenates of rat posterior pituitary showed a good parallelism with a reference curve in a radioimmunoassay system. The IR-ANF was extracted from rat posterior pituitary homogenates by activated Vycor glass beads. The lyophilized extract was purified by HPLC on C/sub 18/ ..mu.. Bondapak column. The HPLC yielded two IR-ANF peaks. Both isolated ANF-like material showed biological activity. The IR-ANF eluted with 33% acetonitrile, inhibited ACTH-stimulated aldosterone secretion with a similar potency as synthetic (Arg 101 - Tyr 126) ANF (0.7 x 10/sup -10/M). A much less potent ANF-like material was found in the second peak eluted with 36% acetonitrile. They conclude that ANF-like material is present in rat posterior pituitary and this suggest a possible role in ANF on AVP secretion directly in situ.

  6. Endothelial actions of atrial and B-type natriuretic peptides

    PubMed Central

    Kuhn, Michaela

    2012-01-01

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

  7. Endothelial actions of atrial and B-type natriuretic peptides.

    PubMed

    Kuhn, Michaela

    2012-05-01

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

  8. Regulation of atrial natriuretic peptide receptors in the rat brain

    SciTech Connect

    Saavedra, J.M.

    1987-06-01

    We have studied the localization, kinetics, and regulation of receptors for the circulating form of the atrial natriuretic peptide (ANP; 99-126) in the rat brain. Quantitative autoradiographic techniques and a /sup 125/I-labeled ligand, /sup 125/I-ANP (99-126), were employed. After in vitro autoradiography, quantification was achieved by computerized microdensitometry followed by comparison with /sup 125/I-standards. ANP receptors were discretely localized in the rat brain, with the highest concentrations in circumventricular organs, the choroid plexus, and selected hypothalamic nuclei involved in the production of the antidiuretic hormone vasopressin and in blood-pressure control. Spontaneously (genetic) hypertensive rats showed much lower numbers of ANP receptors than normotensive controls in the subfornical organ, the area postrema, the nucleus of the solitary tract, and the choroid plexus. These changes are in contrast to those observed for receptors of angiotensin II, another circulating peptide with actions opposite to those of ANP. Under conditions of acute dehydration after water deprivation, as well as under conditions of chronic dehydration such as those present in homozygous Brattleboro rats, there was an up-regulation of ANP receptors in the subfornical organ. Our results indicate that in the brain, circumventricular organs contain ANP receptors which could respond to variations in the concentration of circulating ANP. In addition, brain areas inside the blood-brain barrier contain ANP receptors probably related to the endogenous, central ANP system. The localization of ANP receptors and the alterations in their regulation present in genetically hypertensive rats and after dehydration indicate that brain ANP receptors are probably related to fluid regulation, including the secretion of vasopressin, and to cardiovascular function.

  9. Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

    PubMed Central

    Shenker, Y; Sider, R S; Ostafin, E A; Grekin, R J

    1985-01-01

    Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake. PMID:2932471

  10. Regulation of atrial natriuretic peptide (ANP) secretion

    SciTech Connect

    Ruskoaho, H.; Toth, M.; Lang, R.E.; Unger, Th.; Garten, D.

    1986-03-05

    To investigate the role of calcium, protein kinase C and adenylate cyclase in the ANP secretion, the secretory responses from isolated perfused rat hearts to a calcium channel activator, Bay k8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluomethylphenyl)-2-pyridine-5-carboxylate), the calcium ionophore (A23187), the phorbol ester (12-0-tetradecanoylphorbol-13-acetate, TPA), and to forskolin were studied. ANP in perfusate was measured by radioimmunoassay 10 min before and during the infusion (30 min) of various agents at 2 min intervals. A23187 (5.7 x 10/sup -7/) induced a sharp increase, whereas TPA (0.15 - 1.6 x 10/sup -7/) caused a slowly progressive increase in ANP secretion. 4a-phorbol-12,13-didecanoate, a non-active phorbol ester, had no effect on ANP secretion. Bay k8644 (4 x 10/sup -7/) and forskolin (1 x 10/sup -6/) alone caused small but sustained increase in ANP secretion. The combination of TPA with Bay k8644, forskolin or A23187 stimulated ANP secretion higher than the calculated additive value for each agent. Dibuturyl-cAMP (1.6 x 10/sup -4/) pretreatment also enhanced TPA-induced ANP release. 8-Bromo-cGMP (1.3 x 10/sup -4/) and sodium nitroprusside (9 x 10/sup -5/) alone had no effect, but both attenuated the TPA-induced ANP secretion. The results suggest that atrial cardiocytes possess at least two different secretory pathways for ANP secretion, which are probably dependent on protein kinase C and cyclic AMP.

  11. Atrial natriuretic factor inhibits mitogen-induced growth in aortic smooth muscle cells.

    PubMed

    Baldini, P M; De Vito, P; Fraziano, M; Mattioli, P; Luly, P; Di Nardo, P

    2002-10-01

    Atrial natriuretic factor (ANF) is a polypeptide able to affect cardiovascular homeostasis exhibiting diuretic, natriuretic, and vasorelaxant activities. ANF shows antimitogenic effects in different cell types acting through R(2) receptor. Excessive proliferation of smooth muscle cells is a common phenomenon in diseases such as atherosclerosis, but the role of growth factors in the mechanism which modulate this process has yet to be clarified. The potential antimitogenic role of ANF on the cell growth induced by growth factors appears very intriguing. Aim of the present study was to investigate the possible involvement of ANF on rat aortic smooth muscle (RASM) cells proliferation induced by known mitogens and the mechanism involved. Our data show that ANF, at physiological concentration range, inhibits RASM cell proliferation induced by known mitogens such as PDGF and insulin, and the effect seems to be elicited through the modulation of phosphatidic acid (PA) production and MAP kinases involvement.

  12. Atrial Natriuretic Peptide and Renal Dopaminergic System: A Positive Friendly Relationship?

    PubMed Central

    Choi, Marcelo Roberto; Rukavina Mikusic, Natalia Lucía; Kouyoumdzian, Nicolás Martín; Kravetz, María Cecilia; Fernández, Belisario Enrique

    2014-01-01

    Sodium metabolism by the kidney is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Renal dopamine plays a central role in this interactive network. The natriuretic hormones, such as the atrial natriuretic peptide, mediate some of their effects by affecting the renal dopaminergic system. Renal dopaminergic tonus can be modulated at different steps of dopamine metabolism (synthesis, uptake, release, catabolism, and receptor sensitization) which can be regulated by the atrial natriuretic peptide. At tubular level, dopamine and atrial natriuretic peptide act together in a concerted manner to promote sodium excretion, especially through the overinhibition of Na+, K+-ATPase activity. In this way, different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome or hypertension, are associated with impaired action of renal dopamine and/or atrial natriuretic peptide, or as a result of impaired interaction between these two natriuretic systems. The aim of this review is to update and comment on the most recent evidences demonstrating how the renal dopaminergic system interacts with atrial natriuretic peptide to control renal physiology and blood pressure through different regulatory pathways. PMID:25013796

  13. Natriuretic peptides for the detection of paroxysmal atrial fibrillation

    PubMed Central

    Seegers, Joachim; Zabel, Markus; Grüter, Timo; Ammermann, Antje; Weber-Krüger, Mark; Edelmann, Frank; Gelbrich, Götz; Binder, Lutz; Herrmann-Lingen, Christoph; Gröschel, Klaus; Hasenfuß, Gerd; Feltgen, Nicolas; Pieske, Burkert; Wachter, Rolf

    2015-01-01

    Background and purpose Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study. Methods Natriuretic peptide levels were analysed in two independent patient cohorts (162 patients with arterial hypertension or other cardiovascular risk factors and 82 patients with retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and BNP were measured before the start of a 7-day Holter monitoring period carefully screened for AT/AF. Results 244 patients were included; 16 had paroxysmal AT/AF. After excluding patients with a history of AT/AF (n=5), 14 patients had newly diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4; 178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9 (201.4; 277.1) versus 90.8 (42.3–141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0; 58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to 0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively. Conclusions NT-proBNP and BNP levels are elevated in patients with silent AT/AF as compared with sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic peptide level initiated Holter monitoring may be a useful strategy in prevention of stroke or systemic embolism. PMID:26288739

  14. The actions of atrial natriuretic factor on the vascular wall.

    PubMed

    Vlasuk, G P; Babilon, R W; Nutt, R F; Ciccarone, T M; Winquist, R J

    1987-08-01

    The actions of atrial natriuretic factor (ANF) on the vascular wall are diverse and show a profound regional heterogeneity. ANF is a potent relaxant of aortic smooth muscle, a response which is associated with activation of particulate guanylate cyclase and elevation in tissue levels of cyclic GMP. However, many large and small muscular arteries and most veins are unresponsive to the peptide. The regional vascular heterogeneity may be due to an altered distribution of high affinity receptors and (or) alterations in the coupling of receptor activation to elevations in cyclic 3',5'-guanosine monophosphate (cGMP). Species differences exist in the structural requirements for receptor activation as well as the effects of infused ANF on peripheral resistance. Although the relaxation to ANF in vitro does not require an intact endothelium, endothelial cells contain multiple receptor subtypes for ANF. Differences amongst tissues and (or) species in the receptor profile for ANF may, in part, explain some of heterogeneity in responsiveness to ANF.

  15. Atrial natriuretic factor in neonatal hypoxic-ischemic encephalopathy.

    PubMed

    Carbonell, X; Figueras, J; Salvia, M D; Esque, M T; Delgado, M P; Jimenez, R

    1993-01-01

    The influence of perinatal asphyxia in the secretion of atrial natriuretic factor (ANF) during the first 6 days of life, and its renal consequences are discussed. Comparison between 20 healthy term neonates and 19 with first--or second--degree hypoxic-ischemic encephalopathy (HIE) is made. Daily controls were performed on clinical and neurological examinations and administration of sodium and fluids. On the first and sixth days of life, 24 hours urine collection, natremia, natriuresis, fractionated excretion of sodium and creatinine clearance were determined. The ANF was performed at 1, 2, 3 and 6 days old, by R.I.A. The full term newborns with HIE showed a peak in ANF values on day two, as does the control group, thereafter maintaining higher levels, with a significant difference on day three and six. No correlation could be found between the ANF levels and the renal variables analyzed.

  16. Amino acid sequence of atrial natriuretic peptides in human coronary sinus plasma.

    PubMed

    Yandle, T; Crozier, I; Nicholls, G; Espiner, E; Carne, A; Brennan, S

    1987-07-31

    Two atrial natriuretic peptides were purified from pooled human coronary sinus plasma by Sep-Pak extraction, immunoaffinity chromatography and reverse phase HPLC. The amino acid sequences of the two peptides were homologous with 99-126 human atrial natriuretic peptide (hANP) and 106-126 hANP, the latter being most probably linked to 99-105 ANP by the disulphide bond. The molar ratio of the peptides in plasma, as assessed by radioimmunoassay was 10:3.

  17. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

  18. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

  19. Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility.

    PubMed

    Bézie, Y; Mesnard, L; Longrois, D; Samson, F; Perret, C; Mercadier, J J; Laurent, S

    1996-09-12

    We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10(-8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 x 10(-7) M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.

  20. [The interaction of atrial natriuretic peptide with other bioregulators of kidney function in chronic glomerulonephritis in children].

    PubMed

    Kucherenko, A G; Markov, Kh M; Zokirov, N Z; Naumova, V I

    1994-01-01

    A study was made of renin-angiotensin-aldosterone system activity and plasmic concentrations of atrial natriuretic peptide (NUP) as well as antidiuretic hormone in children with primary glomerulonephritis. A close relationship was established of these parameters in regulation of water-salt homeostasis. The above systems are involved in pathogenesis of childhood glomerulonephritis. This finding should be considered in development of pathogenetically validated therapy of glomerulonephritis, including introduction of synthetic NUP.

  1. A possible role of atrial natriuretic peptide in ethanol-induced acute diuresis

    SciTech Connect

    Colantonio, D.; Casale, R.; Mammarella, M.; Pasqualetti, P. ); Desiati, P.; De Michele, G. )

    1991-01-01

    The acute effects of ethanol on plasma atrial natriuretic peptide levels were investigated in 4 clinically healthy males, aged 24-26 years, consumed either 750 ml of water as a control study, or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 99.12{plus minus}15.10 mg/dl at 60 min. Plasma atrial natriuretic peptide levels were significantly higher in the alcohol study compared to the control study at each time point, and with a peak at 10 min. Atrial natriuretic peptide levels showed a positive significant correlation with plasma antidiuretic hormone in the control group, while no relationship was found between the two peptides in the alcohol study. Moreover, a significant correlation exists between plasma atrial natriuretic peptide levels and systolic arterial blood pressure, and heart rate, and between the variations in atrial natriuretic peptide values and the variations in plasma sodium, serum ethanol, and plasma osmolality in the alcohol study. Acute ethanol intake causes an increase in urinary volume, and a decrease in urinary potassium excretion and urinary osmolality, and no change in urinary sodium excretion.

  2. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

    PubMed

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-03-31

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

  3. Atrial natriuretic factor in maternal and fetal sheep

    SciTech Connect

    Cheung, C.Y.; Gibbs, D.M.; Brace, R.A.

    1987-02-01

    To determine atrial natriuretic factor (ANF) concentrations in the circulation and body fluids of adult pregnant sheep and their fetuses, pregnant ewes were anesthetized with pentobarbital sodium, and the fetuses were exteriorized for sampling. ANF concentration, as measured by radioimmunoassay, was 47 +/- 6 (SE) pg/ml in maternal plasma, which was significantly higher than the 15 +/- 3 pg/ml in maternal urine. In the fetus, plasma ANF concentration was 265 +/- 49 pg/ml, 5.6 times that in maternal plasma. No umbilical arterial and venous difference in ANF concentration was observed. Fetal urine ANF concentration was significantly lower than that in fetal plasma, and was similar to that measured in amniotic and allantoic fluid. In chronically catheterized maternal and fetal sheep, fetal plasma ANF was again 5.1 times that in maternal plasma, and these levels were not different from those measured in acutely anesthetized animals. These results demonstrate that immunoreactive ANF is present in the fetal circulation at levels higher than those found in the mother. The low concentration of ANF in fetal urine suggests that ANF is probably metabolized and/or reabsorbed by the fetal kidney.

  4. Atrial natriuretic factor binding sites in experimental congestive heart failure

    SciTech Connect

    Bianchi, C.; Thibault, G.; Wrobel-Konrad, E.; De Lean, A.; Genest, J.; Cantin, M. )

    1989-10-01

    A quantitative in vitro autoradiographic study was performed on the aorta, renal glomeruli, and adrenal cortex of cardiomyopathic hamsters in various stages of heart failure and correlated, in some instances, with in vivo autoradiography. The results indicate virtually no correlation between the degree of congestive heart failure and the density of 125I-labeled atrial natriuretic factor ((Ser99, Tyr126)ANF) binding sites (Bmax) in the tissues examined. Whereas the Bmax was increased in the thoracic aorta in moderate and severe heart failure, there were no significant changes in the zona glomerulosa. The renal glomeruli Bmax was lower in mild and moderate heart failure compared with control and severe heart failure. The proportion of ANF B- and C-receptors was also evaluated in sections of the aorta, adrenal, and kidney of control and cardiomyopathic hamsters with severe heart failure. (Arg102, Cys121)ANF (des-(Gln113, Ser114, Gly115, Leu116, Gly117) NH2) (C-ANF) at 10(-6) M displaced approximately 505 of (Ser99, Tyr126)125I-ANF bound in the aorta and renal glomeruli and approximately 20% in the adrenal zona glomerulosa in both series of animals. These results suggest that ANF may exert a buffering effect on the vasoconstriction of heart failure and to a certain extent may inhibit aldosterone secretion. The impairment of renal sodium excretion does not appear to be related to glomerular ANF binding sites at any stage of the disease.

  5. Specific binding of atrial natriuretic factor in brain microvessels

    SciTech Connect

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-04-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

  6. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

    PubMed Central

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-01-01

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. PMID:25775533

  7. Binding sites of atrial natriuretic peptide in tree shrew adrenal gland

    SciTech Connect

    Fuchs, E.; Shigematsu, K.; Saavedra, J.M.

    1986-09-01

    Adrenal gland binding sites for atrial natriuretic peptide-(99-126) (ANP) were quantitated in tree shrew (Tupaia belangeri) by incubation of adrenal sections with (3-(/sup 125/I)-iodotyrosyl28) atrial natriuretic peptide-(99-126), followed by autoradiography with computerized microdensitometry. In the adrenal glands, there are three types of ANP binding sites. One is located in the zona glomerulosa (BMax 84 +/- 6 fmol/mg protein; Kd 122 +/- 9 pM); the second in the zona fasciculata and reticularis (BMax 29 +/- 2 fmol/mg protein; Kd 153 +/- 6 pM) and the third in the adrenal medulla (BMax 179 +/- 1 fmol/mg protein; Kd 70 +/- 2 pM). Besides the influence of ANP on the regulation of adrenocortical mineralcorticoid and glucocorticoid secretion our findings raise the possibility for a local site of action of atrial natriuretic peptide in the regulation of adrenomedullary catecholamines in the tree shrew, primates and man.

  8. Functional atrial natriuretic peptide receptor in human adrenal tumor

    SciTech Connect

    Shionoiri, H.; Hirawa, N.; Takasaki, I.; Ishikawa, Y.; Oda, H.; Minamisawa, K.; Sugimoto, K.; Matsukawa, T.; Ueda, S.; Miyajima, E.

    1989-01-01

    The effects of synthetic human atrial natriuretic peptide (ANP) on the release of catecholamines, aldosterone, or cortisol were observed in human adrenal tumors obtained surgically from patients with pheochromocytoma, primary aldosteronism, or Cushing's syndrome, respectively. Each tumor tissue or adjacent normal cortical tissue was sectioned into slices, which were incubated in medium-199 in the presence or absence of adrenocorticotrophin (ACTH) and ANP. The amounts of epinephrine, norepinephrine, aldosterone, or cortisol released into the medium were measured. Existence of ANP receptors on the adrenal tissues was examined by binding assays, affinity labeling, and immunohistochemistry. Release of catecholamines from pheochromocytoma tissues was inhibited by ANP, and the presence of the ANP receptor on pheochromocytoma was further demonstrated by both binding assays and affinity labeling; Scatchard analysis revealed a single class of binding sites for ANP with a Kd of 1.0 nM and a Bmax of 0.4 pmol/mg of protein and the molecular size was estimated as 140 and a 70 kDa under nonreducing and reducing conditions, respectively. The presence of ANP receptors in pheochromocytoma was demonstrated by immunohistochemistry. ANP inhibited both basal and ACTH-stimulated aldosterone secretion in the slices of normal cortex, and localization of ANP receptors in zona glomerulosa cells was also demonstrated. However, ANP did not inhibit basal and ACTH-stimulated aldosterone and cortisol secretion in both tissue slices from aldosteronoma and Cushing's adenoma. Consistent with these observations, the absence of ANP receptors in adenoma tissues was determined by binding assays, affinity labeling, and immunohistochemistry.

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

    SciTech Connect

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

    1986-07-01

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

  10. Responses of Plasma Atrial Natriuretic Peptide to High Intensity Submaximal Exercise in the Heat,

    DTIC Science & Technology

    1987-06-01

    Natriuretic Peptide to LnHigh Intensity Submaximal Exercise in the Heat 0 " William J. Kraemer. Lawrence E. Armstrong, Roger W. Hubbard. :I[_] Louis J...atriopeptins in rat adrenal cells. Cir Res 57: 113-118. f V-0C -- V- - IF -I 7 - % 7 -. 17 Chartier L. Schiffrin EL. Thibault G (1984). Effects of atrial

  11. Expression of natriuretic peptide receptor mRNA and functional response to atrial natriuretic peptide and C-type natriuretic peptide in rainbow trout (Oncorhynchus mykiss) head kidney leucocytes.

    PubMed

    Powell, M D; McWilliam, H; McLeod, J; Nankervis, S; Butler, R; Toop, T

    2008-04-01

    The stimulatory effect of vasomodulatory natriuretic peptide hormones on macrophages and peripheral blood leucocytes in mammals is well-established. However, the relationship in lower vertebrates has not been characterised. Expression of atrial natriuretic peptide, ventricular natriuretic peptide and C-type natriuretic peptide-1, and the guanylyl cyclase-linked (GC) natriuretic peptide receptor-A and -B-type receptors (NPR-A and NPR-B, respectively) was determined by PCR from the mRNA of rainbow trout head kidney leucocytes yielding gene fragments with 100% homology to the same respective natriuretic peptide and NPR-A and -B sequences obtained from other rainbow trout tissues. A mixed population of isolated rainbow trout head kidney leucocytes was stimulated in vitro with trout atrial natriuretic peptide (specific NPR-A agonist) and trout C-type natriuretic peptide (NPR-A and -B agonist) as well as the cGMP agonist 8-bromo-cGMP or the GC inhibitor 8-bromo-phenyl-eutheno-cGMP. Respiratory burst was stimulated by trout atrial natriuretic peptide, trout C-type natriuretic peptide-1 and 8-bromo-cGMP in a dose dependant manner with the highest activity as a result of stimulation with trout C-type natriuretic peptide-1 in excess of that achieved by phorbol myristate acetate (PMA). Equimolar concentrations of the inhibitor, inhibited the respiratory burst caused by the natriuretic peptides and 8-bromo-cGMP. The natriuretic peptide receptors on rainbow trout head kidney leucocytes appear to have a stimulatory function with regard to respiratory burst that is activated through a cGMP second messenger pathway and the natriuretic peptides expressed in the head kidney leucocytes may well act in a paracrine/autocrine manner.

  12. Atrial natriuretic peptide and vasopressin-presence in the ciliary body of eye in the pig (sus domesticus).

    PubMed

    Valentino, B; Valentino, A; Lipari, L; Lipari, A; Farina, E

    2014-01-01

    The aqueous humor is produced in the ciliary body, therefore in this study we investigated the Atrial natriuretic peptide (ANP) and vasopressin (VP)-presence in the ciliary body of the pig eye since these peptide are involved in the homeostasis of body fluids. The results show ANP-presence in the epithelial cells and in the endothelial cells of the blood vessels and VP-presence in the epithelial cells, in the endothelium of canal of Schelmm and in the muscle cells of the blood vessels. These peptides might regulate the synthesis and the composition of the aqueous humor and regulate the hydrodynamic flow and haemodynamic flow of the blood.

  13. Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

    PubMed Central

    Seidah, N G; Lazure, C; Chrétien, M; Thibault, G; Garcia, R; Cantin, M; Genest, J; Nutt, R F; Brady, S F; Lyle, T A

    1984-01-01

    A substance called atrial natriuretic factor (ANF), localized in secretory granules of atrial cardiocytes, was isolated as four homologous natriuretic peptides from homogenates of rat atria. The complete sequence of the longest form showed that it is composed of 33 amino acids. The three other shorter forms (2-33, 3-33, and 8-33) represent amino-terminally truncated versions of the 33 amino acid parent molecule as shown by analysis of sequence, amino acid composition, or both. The proposed primary structure agrees entirely with the amino acid composition and reveals no significant sequence homology with any known protein or segment of protein. The short form ANF-(8-33) was synthesized by a multi-fragment condensation approach and the synthetic product was shown to exhibit specific activity comparable to that of the natural ANF-(3-33). PMID:6232612

  14. Mechanisms underlying the diabetes-induced hyporeactivity of the rabbit carotid artery to atrial natriuretic peptide.

    PubMed

    Marrachelli, Vannina G; Miranda, Francisco J; Centeno, José M; Miranda, Ignacio; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Alborch, Enrique

    2011-03-01

    Atrial natriuretic peptide (ANP) plays an important role in the pathophysiology of the vascular complications in diabetes. The working hypothesis was that diabetes might modify the vascular actions of ANP in isolated rabbit carotid arteries and the mechanisms involved in these actions. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted carotid arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal increased the ANP-induced relaxation. Isatin inhibited the relaxation to ANP both in arteries with and without endothelium. Carotid arteries from diabetic rabbits showed a decreased natriuretic peptide receptor (NPR)-A expression and an enhanced NPR-C expression. Inhibition of NO-synthesis did not modify ANP-induced relaxation in control rabbits but inhibited it in diabetic rabbits. In arteries with endothelium indomethacin enhanced the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. In endothelium-denuded arteries indomethacin inhibited the relaxation to ANP in both groups of animals. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium inhibited the relaxation to ANP, and this inhibition was higher in diabetic than in control rabbits. These results suggest that diabetes produces hyporeactivity of the rabbit carotid artery to ANP by a mechanism that at least includes a reduced expression of NPR-A, an enhanced expression of NPR-C and a reduced participation of K(+)-channels. Furthermore, diabetes enhances endothelial NO release and diminishes the ratio thromboxane A(2)/prostacyclin. This increase of vasodilators could result from compensatory mechanisms counteracting the arterial hyporeactivity to ANP.

  15. Specific receptor binding of atrial natriuretic peptide to rat renal cortex

    SciTech Connect

    Ogura, T.; Mitsui, T.; Ogawa, N.; Ota, Z.

    1985-09-01

    Radiolabeled receptor assay (RRA) of atrial natriuretic peptide (ANP) was studied in rat kidney membranes. Binding of ( SVI)-ANP to membrane preparations of rat whole kidney was saturated and show a high affinity. Furthermore, renal cortex membrane had a higher affinity for ANP binding site than renal medulla membrane. This high affinity ANP receptor site in renal cortex membrane indicated that ANP controlled the balance of water and sodium excretion due to this receptor site in the kidney.

  16. Expression of the atrial natriuretic peptide gene in the cardiac muscle of rat extrapulmonary and intrapulmonary veins.

    PubMed Central

    Springall, D R; Bhatnagar, M; Wharton, J; Hamid, Q; Gulbenkian, S; Hedges, M; Meleagros, L; Bloom, S R; Polak, J M

    1988-01-01

    Atrial natriuretic peptide is a peptide regulating salt and water balance, originally isolated from the cardiac atrium, where it is synthesised as part of a precursor molecule in specialised myocardial cells. The myocardium extends into the extrapulmonary part of the pulmonary veins in many species, including man. In some small mammals, however, such as the rat, mouse, and bat, it extends further to veins in the peripheral parts of the lung. Since this myocardial layer is continuous with that in the atrium, we have looked for the possible expression of the atrial natriuretic peptide gene in this tissue in rats. Strong immunoreactivity was seen for both the peptide and the N terminal sequence (cardiodilatin) of its precursor in extrapulmonary veins and in intrapulmonary veins extending into the lung as far as the second branching point, where it was localised in the dense cored granules by electron microscopy; in situ hybridisation showed atrial natriuretic peptide messenger RNA at identical sites. Chromatography and radioimmunoassay of extracts of extrapulmonary and intrapulmonary veins showed most of the atrial natriuretic peptide immunoreactivity to be in the uncleaved (precursor molecule) form. Thus the peptide is synthesised in veins both outside and inside the lung, and these extra-atrial sites may be an important additional source of circulating atrial natriuretic peptide. Images PMID:2965426

  17. Increase in plasma concentrations of cardiodilatin (amino terminal pro-atrial natriuretic peptide) in cardiac failure and during recumbency.

    PubMed Central

    Meleagros, L; Gibbs, J S; Ghatei, M A; Bloom, S R

    1988-01-01

    Plasma concentrations of cardiodilatin, the peptide sequence at the amino terminal of the pro-atrial natriuretic peptide, in 17 normal subjects ranged from 59 to 202 (mean 118 (SEM) (9] pmol/l. Recumbency increased the mean (SEM) concentration to 160 (13) pmol/l. The plasma concentration of cardiodilatin in 24 patients with congestive cardiac failure was much higher (964 (175) pmol/l) than in the normal subjects. It was highest in those with heart failure in New York Heart Association functional classes III and IV and the concentration correlated both with atrial natriuretic peptide concentrations and left ventricular ejection fraction. Concentrations rose during induced tachycardia in three patients tested. Chromatography showed a single clean peak of plasma cardiodilatin immunoreactivity. It seems that cardiodilatin is a second circulating cardiac peptide that is jointly released with atrial natriuretic peptide by common stimuli. Other workers have reported that, like atrial natriuretic peptide, three partial cardiodilatin sequences can stimulate renal particulate guanylate cyclase and increase cyclic guanosine monophosphate. The simultaneous release of cardiodilatin in higher circulating concentrations than atrial natriuretic peptide may be relevant to the finding that appropriate concentrations of exogenous atrial natiuretic peptide alone do not produce the full renal effects associated with endogenous peptide release. PMID:2970269

  18. The expression of atrial natriuretic peptide in the oviduct and its functions in pig spermatozoa.

    PubMed

    Zhang, Meijia; Hong, Haiyan; Zhou, Bo; Jin, Shiying; Wang, Chao; Fu, Maoyong; Wang, Songbo; Xia, Guoliang

    2006-06-01

    Locally synthesized atrial natriuretic peptide (ANP) and its receptors have been found in reproductive tissues of various mammals, and play an important role in the acrosome reaction of human sperm. The objective of the present study was to examine the expression of ANP and its receptors in pig spermatozoa and oviduct, and the effect of ANP on pig spermatozoa function. The expression of ANP and its receptors was analyzed by RT-PCR. Only natriuretic peptide receptors-A (NPRA) mRNA was detected in fresh sperm. While the levels of natriuretic peptide receptors-C (NPRC) mRNA were low with no obvious change among different oviductal phases, the levels of ANP mRNA were high in oviduct(OT)1 , OT3 and OT5, but were very low in OT2. On the other hand, the levels of NPRA mRNA were low in OT1 and OT2, increased in OT3 and reached a maximum in OT4 and OT5. Western blot analysis revealed that the level of ANP was high in OT1, decreased in OT2 and OT3, and arrived at the nadir in OT4 and OT5. The effect of ANP on spermatozoa function was studied by the acrosome reaction and IVF. Incubation with ANP for 1 h significantly induced acrosome reaction of preincubated spermatozoa, and maximal response of acrosome reaction (34.1 +/- 2.3%) was achieved at 1 nM ANP treatment. Both C-ANP-(4-23), a selective ligand of NPRC, and caffeine had no effect on the acrosome reaction. The stimulatory effect of ANP on acrosome reaction could be mimicked by the permeable cGMP analog, 8-Br-cGMP. ANP and caffeine had a similar effect on improving the oocytes penetration rate, polyspermy rate and the average number of sperm per penetrated oocyte. Also, ANP treatment had a similar effect on cleavage rate, blastocyst formation rate and the number of cells per blastocyst as that of caffeine treatment. The effects of ANP on the acrosome reaction and the parameters of oocyte penetration could be blocked by cGMP-dependent protein kinase (PKG) inhibitors KT5823 and/or Rp-8-pCPT-cGMPS. These results suggest that

  19. Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

    SciTech Connect

    Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.; Mantyh, P.W. )

    1988-09-01

    To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific binding of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.

  20. Pro-atrial natriuretic peptide and prediction of atrial fibrillation and stroke: The Malmö Preventive Project.

    PubMed

    Berntsson, John; Smith, J Gustav; Nilsson, Peter M; Hedblad, Bo; Melander, Olle; Engström, Gunnar

    2017-01-01

    Background The increasing prevalence of atrial fibrillation and novel therapeutic tools to prevent cardioembolic stroke has increased the need for risk markers. Objectives This study explored the relationship between the midregional sequence of pro-atrial natriuretic peptide (MR-proANP) levels with the risk of atrial fibrillation and stroke, and whether measurement of MR-proANP improves the prediction of these outcomes. Methods MR-proANP was measured in fasting blood samples of 5130 subjects (69% men, mean age 69.2 ± 6.2 years) without a history of atrial fibrillation or stroke from the general population. The incidence of atrial fibrillation and stroke was monitored over a median follow-up of 5.6 years. C-statistics and net reclassification improvement was used to assess the predictive ability of MR-proANP in addition to conventional risk factors. Results Log-normalized MR-proANP was significantly associated with the incidence of atrial fibrillation ( n = 362; hazard ratio (HR); 95% confidence interval (CI) per 1 standard deviation (SD) 2.05, 1.86-2.27) and stroke from all causes ( n = 195; HR 1.30; 95% CI 1.12-1.50). The HR for stroke events related to atrial fibrillation was 1.79 (95% CI 1.25-2.58) per 1 SD. MR-proANP significantly improved the prediction of atrial fibrillation when added to a risk score of conventional risk factors (C statistic 0.69 vs. 0.75), mainly by down-classifying subjects who did not develop atrial fibrillation. A smaller improvement in predictive ability was observed for stroke (C statistic 0.66 vs. 0.68). Conclusion High plasma levels of MR-proANP are associated with the incidence of atrial fibrillation and stroke in the middle-aged and elderly population. MR-proANP may be useful to identify individuals with an increased risk of atrial fibrillation.

  1. Localization of atrial natriuretic peptide mRNA and immunoreactivity in the rat heart and human atrial appendage

    SciTech Connect

    Hamid, Q.; Wharton, J.; Terenghi, G.; Hassall, C.J.S.; Aimi, J.; Taylor, K.M.; Nakazato, H.; Dixon, J.E.; Burnstock, G.; Polak, J.M.

    1987-10-01

    The localization of mRNA encoding preproatrial natriuretic peptide was investigated in tissue sections and cultures of rat heart and in sections of human right atrial appendage using the technique of in situ hybridization with /sup 32/P- and /sup 35/S-labeled RNA probes. Rat atrial natriuretic peptide (ANP) transcripts were demonstrated in numerous atrial myocytes and, to a lesser extent, in ventricular myocytes in both tissue sections and newborn rat heart cultures. These findings are consistent with those obtained by RNA blot analysis of rat heart total RNA, indicating that a single prepro-ANP transcript of approx. 900 nucleotides was present in the ventricles as well as the atria. Using a /sup 35/S-labeled RNA probe for human ANP mRNA, ANP transcripts were also localized to the majority of myocytes in the human right atrial appendage. Only background levels of autoradiographic labeling were obtained when RNA probes identical to the coding sequence of rat or human ANP mRNA were used. A close correlation was found between the distribution of ANP immunoreactivity and prepro-ANP mRNA in these preparations. These results provide unequivocal evidence for the expression of the ANP gene in the rat ventricles, as well as the atria, because myocytes in these tissues have been established as the sites of both ANP localization and precursor biosynthesis. The combined use of cardiac cultures and in situ hybridization may be of value in future studies investigating the regulation of ANP synthesis in cardiac myocytes.

  2. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    PubMed

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium.

  3. Atrial natriuretic factor mRNA and binding sites in the adrenal gland.

    PubMed Central

    Nunez, D J; Davenport, A P; Brown, M J

    1990-01-01

    The factor inhibiting aldosterone secretion produced by the adrenal medulla may be atrial natriuretic factor (ANF), since the latter abolishes aldosterone release in response to a number of secretagogues, including angiotensin II and K+. In this study we have shown that cells in the adrenal medulla contain ANF mRNA and therefore have the potential to synthesize this peptide. The presence of binding sites for ANF predominantly in the adrenal zona glomerulosa suggests that, if ANF is synthesized in the medulla and transferred to the cortex, it may affect mineralocorticoid status. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2146954

  4. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Huls, M. H.; Sams, Clarence F.

    1989-01-01

    In view of the suggestions by Chabrier et al. (1987) and Steardo and Nathanson (1987) that atrial natriuretic peptide (ANP) may play a role in the fluid homeostasis of the brain, the ANP receptors in primary cultures of bovine brain microvessel endothelian cells were quantitated and characterized. Results of partition binding studies and the effect of cGMP additions indicated the presence of at least two types of ANP receptors, with the majority of the receptors being the nonguanylate cyclase coupled receptors. The presence of at least two ANP receptor types suggests an active role for ANP in regulating brain endothelial cell function.

  5. Immunohistochemical localization of atrial natriuretic factor (ANF) in the excretory system of the rabbit parotid gland.

    PubMed

    Valentino, B; Farina Lipari, E; Carini, F; Valenza, V

    1999-01-01

    The immunohistochemical localization of atrial natriuretic factor (ANF) in the rabbit parotid gland was performed using an antibody against rabbit ANF and avidin-biotin or streptoavidin as detector. Results showed positivity in cuboidal and columnar cells of intralobular ducts and in basal cells of extralobular and main excretory duct. These data support the hypothesis that ANF produced by intralobular ducts could act through a paracrine mechanism; ANF produced by extralobular and main ducts may play a role in the regulation of salivary composition.

  6. Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension

    NASA Astrophysics Data System (ADS)

    John, Simon W. M.; Krege, John H.; Oliver, Paula M.; Hagaman, John R.; Hodgin, Jeffrey B.; Pang, Stephen C.; Flynn, T. Geoffrey; Smithies, Oliver

    1995-02-01

    To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the proANP gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.

  7. Regulation of expression of atrial and brain natriuretic peptide, biomarkers for heart development and disease.

    PubMed

    Sergeeva, Irina A; Christoffels, Vincent M

    2013-12-01

    The mammalian heart expresses two closely related natriuretic peptide (NP) hormones, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). The excretion of the NPs and the expression of their genes strongly respond to a variety of cardiovascular disorders. NPs act to increase natriuresis and decrease vascular resistance, thereby decreasing blood volume, systemic blood pressure and afterload. Plasma levels of BNP are used as diagnostic and prognostic markers for hypertrophy and heart failure (HF), and both ANF and BNP are widely used in biomedical research to assess the hypertrophic response in cell culture or the development of HF related diseases in animal models. Moreover, ANF and BNP are used as specific markers for the differentiating working myocardium in the developing heart, and the ANF promoter serves as platform to investigate gene regulatory networks during heart development and disease. However, despite decades of research, the mechanisms regulating the NP genes during development and disease are not well understood. Here we review current knowledge on the regulation of expression of the genes for ANF and BNP and their role as biomarkers, and give future directions to identify the in vivo regulatory mechanisms. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.

  8. Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males.

    PubMed

    Skov, Jeppe; Holst, Jens Juul; Gøtze, Jens Peter; Frøkiær, Jørgen; Christiansen, Jens Sandahl

    2014-01-01

    The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1-ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma proANP concentrations were measured by an automated mid-region-directed proANP immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular E170. Urine was collected for measurements of sodium excretion. Although GLP1 infusion increased the urinary sodium excretion markedly, there were no significant changes in either proANP or proBNP concentrations. When GLP1 infusion was stopped, sodium excretion declined rapidly. As proANP concentration reflects ANP secretion, our data could not confirm the existence of a GLP1-ANP axis in humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated exclusively via ANP.

  9. Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.

    PubMed

    Gelfand, R A; Frank, H J; Levin, E; Pedram, A

    1991-08-01

    The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.

  10. Effects of natriuretic peptides on electrical conduction in the sinoatrial node and atrial myocardium of the heart.

    PubMed

    Azer, John; Hua, Rui; Krishnaswamy, Pooja S; Rose, Robert A

    2014-03-01

    Natriuretic peptides, including B-type and C-type natriuretic peptide (BNP and CNP), are powerful regulators of the cardiovascular system; however, their electrophysiological effects in the heart, particularly in the sinoatrial node (SAN), are incompletely understood. We have used high-resolution optical mapping to measure the effects of BNP and CNP, and the roles of natriuretic peptide receptors (NPR-A, NPR-B and NPR-C), on electrical conduction within the SAN and atrial myocardium. In basal conditions BNP and CNP (50-500 nm) increased conduction velocity (CV) within the SAN by ∼30% at the high dose and shifted the initial exit site superiorly. These effects sped conduction from the SAN to the surrounding atrial myocardium and were mediated by the NPR-A and NPR-B receptors. In the presence of isoproterenol (1 μm) the NPR-C receptor made a major contribution to the effects of BNP and CNP in the heart. In these conditions BNP, CNP and the NPR-C agonist cANF each decreased SAN CV and shifted the initial exit site inferiorly. The effects of cANF (30% reduction) were larger than BNP or CNP (∼15% reduction), indicating that BNP and CNP activate multiple natriuretic peptide receptors. In support of this, the inhibitory effects of BNP were absent in NPR-C knockout mice, where BNP instead elicited a further increase (∼25%) in CV. Measurements in externally paced atrial preparations demonstrate that the effects of natriuretic peptides on CV are partially independent of changes in cycle length. These data provide detailed novel insight into the complex effects of natriuretic peptides and their receptors on electrical conduction in the heart.

  11. Presence of immunoreactive atrial natriuretic peptide in follicular fluid, ovary and ovarian perfusates

    SciTech Connect

    Kim, Suhn Hee; Cho, Kyung Woo; Seul, Kyung Hwan; Ryu, Hoon; Koh, Gou Young )

    1989-01-01

    Immunoreactive atrial natriuretic peptide (ir-ANP) was measured in the follicular fluid of pig ovarian follicle, and rabbit ovarian homogenates and perfusates using a specific radioimmunoassay (RIA). Serial dilution curves made with the extracts of follicular fluid, ovarian homogenates and perfusates using Sep-Pak C18 cartridges were parallel with the RIA standard curve. On gel filtration chromatography and reverse phase HPLC, all extracted materials showed high and low molecular weight forms of ir-ANP. The amount of ir-ANP in rabbit ovary was 40.7{plus minus}0.39 pg/mg and that in follicular fluid of pig ovarian follicle was 18.88{plus minus}2.49 pg/ml.

  12. Atrial natriuretic factor (ANF) inhibits thyroid hormone secretion in the mouse

    SciTech Connect

    Ahren, B. )

    1990-01-01

    Recently, thyroid follicular cells were shown to exhibit atrial natriuretic factor (ANF)-like immunoreactivity and high affinity ANF receptors. In this study, we therefore examined the effects of synthetic rat ANF{sub 1-28} on basal and stimulated thyroid hormone secretion in the mouse, according to the McKenzie technique. Iodine deficient mice were pretreated with {sup 125}I and thyroxine. ANF (3 nmol/animal) was found to inhibit the increase in blood radioiodine levels that was induced by TSH or vasoactive intestinal polypeptide (VIP). Furthermore, ANF and norepinephrine additively inhibited the TSH-induced increase in blood radioiodine levels. It is concluded that ANF inhibits thyroid hormone secretion, which, therefore, might be locally regulated by intrathyroidal ANF.

  13. Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats

    NASA Technical Reports Server (NTRS)

    Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.

    1995-01-01

    The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

  14. Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia

    SciTech Connect

    Lubbesmeyer, H.J.; Woodson, L.; Traber, L.D.; Flynn, J.T.; Herndon, D.N.; Traber, D.L. Thomas Jefferson Medical College, Philadelphia, PA Westfaelian Wilhelms Univ., Muenster )

    1988-04-01

    A bolus of Escherichia coli endotoxin (1.5 {mu}g/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

  15. Physiological factors of atrial natriuretic polypeptide release and its neural regulation in conscious dogs.

    PubMed

    Nishida, Y; Miyata, A; Morita, H; Hosomi, H

    1988-12-01

    We have examined physiological factors in atrial natriuretic polypeptide (ANP) release and whether or not the cardiac nerves control release of ANP. Two possible factors were tested, an increase in plasma sodium level (PNa) and an increase in atrial pressure. Injection of 1.0 or 2.0 mEq/kg of sodium ions elevated PNa by 5.3 +/- 0.3 or 7.3 +/- 0.4 mEq/L, respectively, but plasma ANP level (PANP) did not change. Infusion of 18 ml/kg of 3% Dextran-40 over 5 min increased mean left atrial pressure (MLAP) by 7.6 +/- 0.9 mmHg. PANP increased from 206 +/- 17 pg/ml to 260 +/- 25 pg/ml, which was not significant. PANP, corrected for hemodilution, significantly increased to 348 +/- 34 pg/ml. These results suggest that PNa increase does not promote ANP release, but that an atrial pressure increase does. This transient volume load did not induce full response of the ANP releasing system. A prolonged volume load for 45 min increased corrected PANP to 435 +/- 73 pg/ml. A close linear correlation was found between the increases in MLAP and PANP. These facts indicate that prolonged volume expansion is necessary to induce full response of the ANP releasing system. Complete cardiac denervation did not affect the tonic level of plasma ANP, volume expansion-induced increase in PANP, or the sensitivity of the ANP releasing system. Thus we conclude that the cardiac nerves do not control ANP release caused by volume expansion.

  16. Atrial natriuretic peptide modulates the proliferation of human gastric cancer cells via KCNQ1 expression

    PubMed Central

    ZHANG, JIA; ZHAO, ZHILONG; ZU, CHAO; HU, HAIJIAN; SHEN, HUI; ZHANG, MINGXIN; WANG, JIANSHENG

    2013-01-01

    Atrial natriuretic peptide (ANP) and brain NP (BNP) belong to the NP family that regulates mammalian blood volume and blood pressure. ANP signaling through NP receptor A (NPR-A)/cyclic guanosine 3′5′-monophosphate (cGMP)/ cGMP-dependent protein kinase (PKG) activates various downstream effectors involved in cell growth, apoptosis, proliferation and inflammation. Evidence has shown the critical role of plasma K+ channels in the regulation of tumor cell proliferation. However, the role of ANP in the proliferation of gastric cancer cells is not clear. In the present study, the expression of NPR-A in the human gastric cancer cell line, AGS, and the effect of ANP on the proliferation of AGS cells were investigated using western blotting, immunofluorescence, qPCR and patch clamp assays. The K+ current was also analyzed in the effect of ANP on the proliferation of AGS cells. NPR-A was expressed in the human gastric cancer AGS cell line. Lower concentrations of ANP promoted the proliferation of the AGS cells, although higher concentrations decreased their proliferation. Significant increases in the levels of cGMP activity were observed in the AGS cells treated with 10−10, 10−9 and 10−8 M ANP compared with the controls, but no significant differences were observed in the 10−7 and 10−6 M ANP groups. The patch clamp results showed that 10−9 M ANP significantly increased the tetraethylammonium (TEA)- and 293B-sensitive K+ current, while 10−6 M ANP significantly decreased the TEA- and 293B-sensitive K+ current. The results showed that 10−10 and 10−9 M ANP significantly upregulated the expression of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) at the protein and mRNA levels, although 10−7 and 10−6 M ANP significantly downregulated the expression of KCNQ1. The data indicated that lower and higher concentrations of ANP have opposite effects on the proliferation of AGS cells through cGMP-dependent or -independent pathways. KCNQ1

  17. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats

    PubMed Central

    Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-01-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways. PMID:26515144

  18. The effect of discrete stimulation of carotid body chemoreceptors on atrial natriuretic peptide in anaesthetized dogs.

    PubMed Central

    al-Obaidi, M; Whitaker, E M; Karim, F

    1991-01-01

    1. In seven chloralose-anaesthetized and artificially ventilated beagles, the carotid sinus regions were vascularly isolated and perfused with either arterial or mixed (arterial and venous) blood (PO2 46.4 +/- 1.5 mmHg, mean +/- S.E.M.) to stimulate the chemoreceptors at constant flow and pressure. Cervical vagosympathetic trunks were ligated in all dogs, and gallamine triethiodide (2.0 mg kg-1 h-1, I.V.) was given in five dogs. Right atrial pressure was measured in all dogs, and left atrial pressure in four dogs. Mean aortic pressure was held constant (91.0 +/- 3.0 mmHg) by means of a reservoir connected to the animal via the common carotid and femoral arteries. Plasma atrial natriuretic peptide (ANP) was measured by radioimmunoassay and urinary sodium by flame photometry. 2. In seven dogs with mean carotid sinus pressure maintained at 96.0 +/- 4.3 mmHg, stimulation of the carotid chemoreceptors for 25 min produced significant increases in left atrial pressure of 41.2 +/- 3.3% (n = 4; P less than 0.005) from 5.4 +/- 0.6 cmH2O and of 30.9 +/- 4.5% (n = 7; P less than 0.002) in ANP from 31.6 +/- 2.1 pg ml-1. However, chemoreceptor stimulation produced significant decreases in urine flow rate of 26.1 +/- 1.9% (n = 9; P less than 0.001) from 0.29 +/- 0.03 ml min-1 (100 g kidney weight)-1 and sodium excretion of 29.0 +/- 2.3% (P less than 0.001) from 8.5 +/- 1.7 mumol min-1 (100 g kidney weight)-1 but right atrial pressure and heart rate did not change significantly. In three of the dogs, beta-adrenoceptor blockade by atenolol (2 mg kg-1, I.V.) greatly reduced the effects of chemoreceptor stimulation on plasma levels of ANP. 3. The results show, for the first time, that discrete stimulation of the carotid chemoreceptors caused an increase in plasma ANP levels, probably due to the reflex increase in atrial pressure that results from an inhibition of the cardiac sympathetic nerves, and an increase in venous return from a reduction of peripheral vascular capacitance. PMID

  19. Blood levels and renal effects of atrial natriuretic peptide in normal man.

    PubMed Central

    Weidmann, P; Hasler, L; Gnädinger, M P; Lang, R E; Uehlinger, D E; Shaw, S; Rascher, W; Reubi, F C

    1986-01-01

    Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important

  20. Atrial natriuretic factor in the impulse-conduction system of rat cardiac ventricles.

    PubMed

    Cantin, M; Thibault, G; Haile-Meskel, H; Ding, J; Milne, R W; Ballak, M; Charbonneau, C; Nemer, M; Drouin, J; Garcia, R

    1989-01-01

    A complex network of atrial natriuretic factor-producing cells has been delineated by biochemical and morphological techniques in the rat ventricular myocardium. The chordae tendineae spuriae (CTS; false tendons) contain ANF mRNA and the ANF propeptide (Asn 1-Tyr 126) as assessed by Northern blot analysis, high-pressure liquid chromatography and immunohisto- and -cytochemistry, using three different affinity-purified antibodies: monoclonal and polyclonal antibodies against C-terminal ANF (Arg 101-Tyr 126) and polyclonal antibodies against N-terminal ANF (Asp 11-Ala 37). Two types of cells harboring ANF-containing secretory granules constitute the CTS: the majority (Purkinje type I) have ultrastructural similarities with both atrial and classical Purkinje fibers. Purkinje type-II fibers resemble working ventricular cardiocytes. Both cell types harbor a large paranuclear Golgi complex. The subendocardial Purkinje network is also made up of these two cell types. In this location, Purkinje type-I fibers form cable-like structures while Purkinje type-II fibers are either located beneath the former or abut directly on the endocardium. The latter are not separated from adjacent working ventricular cardiocytes by connective tissue septa. Coronary arteries and arterioles, as in birds, are surrounded by a cushion of Purkinje type-II fibers which blend with the surrounding myocardium. These results indicate that, in the rat, the entire intraventricular conduction system is constituted of endocrine cells producing ANF.

  1. Atrial natriuretic factor: radioimmunoassay and effects on adrenal and pituitary glands

    SciTech Connect

    Gutkowska, J.; Horky, K.; Schiffrin, E.L.; Thibault, G.; Garcia, R.; De Lean, A.; Hamet, P.; Tremblay, J.; Anand-Srivastava, M.B.; Januszewicz, P.

    1986-06-01

    A simple and sensitive radioimmunoassay was developed for measurement of immunoreactive atrial natriuretic factor (IR-ANF) in rat and human plasma and in rat atria. The two atria contain about 20 ..mu..g ANF per rat. The right atrium contained 2.5 times more ANF than did the left. Ether anesthesia and morphine markedly increased IR-ANF in rat plasma. The concentration of IR-ANF in plasma of clinically normal human subjects was 65.3 +/- 2.5 pg/ml. Paroxysmal tachycardia and rapid atrial pacing significantly increased IR-ANF in human plasma. Two- to seven-fold higher concentrations were found in coronary sinus blood than in the peripheral circulation. In the plasma of rats and humans, circulating ANF is probably a small-molecular-weight peptide. ANF acts on the adrenal and the pituitary. ANF inhibits aldosterone secretion from rat zona glomerulosa and steroid secretion by bovine adrenal zona glomerulosa and fasciculata. ANF stimulated the basal secretion of arginine vasopressin (AVP) in vitro and inhibited KCl-stimulated release of AVP.

  2. Influence of storage conditions on in vitro stability of atrial natriuretic peptide and of anesthesia on plasma atrial natriuretic peptide concentration in cats.

    PubMed

    Heishima, Yasuhiro; Hori, Yasutomo; Chikazawa, Seishiro; Kanai, Kazutaka; Hoshi, Fumio; Itoh, Naoyuki

    2016-08-01

    OBJECTIVE To investigate the in vitro stability of atrial natriuretic peptide (ANP) in plasma samples under various storage conditions and the influence of anesthesia on plasma ANP concentration in cats. ANIMALS 1 cat with congestive heart failure and 5 healthy adult mixed-breed cats. PROCEDURES A plasma sample from the cat with heart failure was serially diluted, and dilutional parallelism of ANP concentration was evaluated. Plasma samples containing aprotinin or serum samples from the 5 healthy cats were kept at room temperature (27°C) for ≤ 12 hours. Plasma samples from the same healthy cats were stored at -70°, -20°, or 4°C for ≤ 14 days. Plasma samples were obtained from the healthy cats before and during isoflurane anesthesia. Plasma ANP concentrations were measured at a commercial laboratory by use of a human ANP chemiluminescence assay. RESULTS Intra- and interassay coefficients of variation were 1.5% and 2.5%, respectively, and dilutional parallelism was established. Although ANP concentration decreased by 82.4 ± 13.6% (mean ± SD) after sample storage for 12 hours at room temperature, this decrease was prevented by aprotinin. Plasma ANP concentrations were stable for 7 days at -20°C and for 14 days at -70°C. However, concentrations decreased markedly to 57.6 ± 6.9% at -20°C and to 18.0 ± 3.0% at 4°C after 14 days. Plasma ANP concentration decreased significantly in cats during anesthesia and was correlated with blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that aprotinin should be added routinely in preparation of plasma samples from cats for measurement of ANP concentration, and those samples, if stored, should be frozen immediately at ≤ -20°C. General anesthesia or systemic blood pressure may affect plasma ANP concentration in cats.

  3. Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium.

    PubMed Central

    Kinnunen, P.; Taskinen, T.; Järvinen, M.; Ruskoaho, H.

    1991-01-01

    1. To determine the cellular mechanisms of atrial natriuretic peptide (ANP) release from ventricular cardiomyocytes, the secretory and the cardiac effects of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase C activity in heart cells, were studied in isolated, perfused heart preparations from 2- and 21-month-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. TPA was added to the perfusion fluid for 30 min at a concentration of 46 nM after removal of atrial tissue. Additionally, atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP mRNA, the distribution of ANP within ventricles as well as the relative contribution of atria and ventricles in the release of ANP were studied. 2. Ventricular hypertrophy that gradually developed in hypertensive rats resulted in remarkable augmentation of ANP gene expression, as reflected by elevated levels of immunoreactive ANP and ANP mRNA. The total amount of IR-ANP in the ventricles of the SHR rats increased 41 fold and ANP mRNA levels 12.9 fold from the age of 2 to 21 months. At the age of 21 months, levels of IR-ANP and ANP mRNA in the ventricles of SHR rats were 5.4 fold and 3.7 fold higher, respectively, than in the normotensive WKY rats. Immunohistochemical studies demonstrated ANP granules within the hypertrophic ventricles of the old SHR rats, but not within normal ventricular tissue. 3. In isolated perfused heart preparations, the severely hypertrophied ventricular tissue of SHR rats after atrialectomy secreted more ANP into the perfusate than did the control hearts.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 PMID:1826618

  4. Effects of atrial and brain natriuretic peptides upon cyclic GMP levels, potassium transport, and receptor binding in rat astrocytes

    SciTech Connect

    Beaumont, K.; Tan, P.K. )

    1990-02-01

    The ability of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) to alter cyclic GMP levels and NaKCl cotransport in rat neocortical astrocytes was determined. At concentrations of 10(-9)-10(-6) M, rat ANP99-126 (rANF), rat ANP102-126 (auriculin B), and rat ANP103-126 (atriopeptin III) stimulated 6- to 100-fold increases in cyclic GMP levels. Porcine BNP (pBNP) and rat BNP (rBNP) were 20%-90% as effective as rANF over most of this concentration range, although 10(-6) M pBNP produced a greater effect than rANF. NaKCl cotransport as measured by bumetanide-sensitive 86Rb+ influx was not altered by exposure of astrocytes to 10(-6)M rANF, pBNP, or rBNP. Both pBNP and rBNP, as well as rat ANP103-123 (atriopeptin I) and des(gl18, ser19, gly20, leu21, gly22) ANF4-23-NH2 (C-ANF4-23) strongly competed for specific 125I-rANF binding sites in astrocyte membranes with affinities ranging from 0.03 to 0.4 nM, suggesting that virtually all binding sites measured at subnanomolar concentrations of 125I-rANF were of the ANP-C (ANF-R2) receptor subtype. These receptors are thought to serve a clearance function and may be linked to a guanylate cyclase activity that is chemically and pharmacologically distinct from that coupled to ANP-A (ANF-R1) receptors. ANP receptors on astrocytes may function in limiting the access of ANP and BNP to neurons involved in body fluid and cardiovascular regulation.

  5. Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Whitson, P. A.

    1993-01-01

    Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

  6. Plasma concentrations of adrenomedullin and atrial and brain natriuretic peptides in patients with adrenal pheochromocytoma.

    PubMed

    Hu, Wei; Shi, Lei; Zhou, Pang-Hu; Zhang, Xiao-Bin

    2015-11-01

    The present study aimed to evaluate any changes in the plasma concentrations of adrenomedullin (ADM), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with adrenal pheochromocytoma (PC). The plasma concentrations of the three peptides were measured in 45 healthy control individuals and 90 untreated patients with PC, who consisted of 20 normotensive patients, 30 borderline hypertensive patients and 40 hypertensive patients. After 4 weeks of effective antihypertensive therapy for hypertensive PC patients, the concentrations of ADM, ANP and BNP were measured again, and laparoscopic adrenalectomy was then performed for all PC patients with values that were measured 2 weeks later. The plasma concentrations of the three peptides were significantly increased in the borderline hypertensive and hypertensive patients compared with the concentrations in control individuals and normotensive patients. In addition, there were significant differences between the levels of ADM, ANP and BNP in the borderline and hypertensive groups. The plasma ADM concentration was not associated with the blood urea nitrogen levels, serum creatinine levels or glomerular filtration rate, but was correlated with the serum epinephrine, serum norepinephrine and urine vanillylmandelic acid levels. In addition, the ADM concentration was associated with the systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and plasma concentrations of ANP and BNP in the hypertensive patients with PC. After 4 weeks of antihypertensive treatment, the values of the three peptides in the hypertensive patients with PC were not significantly changed. As expected, the values in borderline and hypertensive groups were significantly decreased 2 weeks subsequent to surgery, whereas there were no significant changes in the normotensive group. ADM may participate, along with ANP and BNP, in the mechanisms that counteract further elevation

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

    SciTech Connect

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

    2011-07-08

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

  8. Characterization and purification of the detergent solubilized atrial natriuretic peptide receptor from bovine aortic smooth muscle cells

    SciTech Connect

    Schenk, D.; Phelps, M.; Scarborough, R.; Johnson, K.; Lewicki, J.

    1986-03-01

    A protein has been purified from total homogenates of cultured vascular bovine smooth muscle cells with properties indicative of the receptor for atrial natriuretic peptide (ANP). Specific /sup 125/I-ANP binding activity was solubilized quantitatively from smooth muscle cell membranes with a purified component of Triton X-100. Equilibrium binding studies of the solubilized ANP receptor reveal by Scatchard analysis a single class of binding sites with a K/sub d/ = 1.77 x 10/sup -10/ moles /sup 125/I-ANP/1 and B/sub max/ = 34.6 pmol/mg protein. The ANP receptor solubilized in this manner is stable for greater than or equal to 2 months at -70/sup 0/C. Studies investigating the ANP receptor show that it binds to wheat germ agglutinin and to CM-cellulose at pH 4.1 but not at pH 6.5. These findings imply that the ANP receptor is a neutral to mildly basic glycoprotein. Further purification studies involving affinity chromatography with ANP-Sepharose result in a 500-fold purification and reveal a single protein with a molecular mass of 58,700 daltons as determined by SDS-polyacrylamide gel electrophoresis. The size of this protein is in good agreement with that of an ANP receptor previously identified in intact smooth muscle cells by crosslinking studies with /sup 125/I-ANP.

  9. Pertussis toxin treatment does not block inhibition by atrial natriuretic factor of aldosterone secretion in cultured bovine zona glomerulosa cells

    SciTech Connect

    De Lean, A.; Cantin, M.

    1986-03-05

    The authors have previously reported that atrial natriuretic factor (ANF) potently inhibits PGE or forskolin-stimulation aldosterone secretion in bovine zona glomerulosa (ZG) by acting through specific high affinity receptors. In order to evaluate the functional role of the regulatory protein N/sub i/ and the inhibition of adenylate cyclase activity (AC) in ZG, the authors have studied the effect of treatment with PT on inhibition by ANF of aldosterone production. Primary cultures of ZG were treated for 18 hours in serum-free F12 medium with (0-100 ng/ml PT). No effect of PT pretreatment was observed either on basal, PGE-stimulated or ANF-inhibited levels of steroidogenesis. When membranes prepared from control ZG were ADP-ribosylated with (/sup 32/P) NAD in the presence of PT, two toxin-specific bands with 39 Kd and 41 Kd were documented on SDS gel. Cell pretreatment with as low as 1 ng/ml drastically reduced further labelling of these two bands while higher doses completely abolished them. Since PT treatment covalently modifies completely the toxin substrate without altering ANF inhibition of adrenal steroidogenesis, the authors conclude that N/sub i/ is not involved in the mode of action of ANF on aldosterone production.

  10. Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease.

    PubMed

    Kitagawa, H; Kitoh, K; Inoue, H; Ohba, Y; Suzuki, F; Sasaki, Y

    2000-04-01

    Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

  11. Binding, internalization, and degradation of atrial natriuretic peptide in cultured vascular smooth muscle cells of rat

    SciTech Connect

    Hirata, Y.; Takata, S.; Tomita, M.; Takaichi, S.

    1985-11-15

    Binding, internalization, and degradation of /sup 125/I-labeled-rat atrial natriuretic peptide (rANP) were studied in cultured rat aortic vascular smooth muscle cells (VSMC). At 37 degrees C, /sup 125/I-labeled-rANP rapidly bound to VSMCs, but the cell-bound radioactivity rapidly decreased upon subsequent incubation, while the binding was slow at 4 degrees C, reaching to an apparent equilibrium after 6 hrs. The cell-bound /sup 125/I-labeled-rANP at 37 degrees C is rapidly dissociated from VSMC (t 1/2: approximately 40 min) with the appearance of degradaded product(s) of radioligand in the medium, whereas the degradation was minimal at 4 degrees C. This degradative process was blocked by inhibitors of metabolic energy production (azide, dinitrophenol), inhibitors of lysosomal cathepsins (leupeptin, pepstatin), and lysosomotropic agents (NH/sub 4/Cl, chloroquine, lidocaine, methylamine, dansylcadaverine), but not by inhibitors of serine or thiol proteases. /sup 125/I-labeled-rANP initially bound to the cell-surface was rapidly internalized, and delivered to lysosomal structures, which was confirmed by autoradiographic studies. These data indicate that rANP, after binding to the cell-surface receptors, is rapidly internalized into the cells through receptor-mediated endocytosis, and subsequently degradaded by lysosomal hydrolases.

  12. Regulation of endothelial cell shape and monolayer permeability by atrial natriuretic peptide

    SciTech Connect

    Lofton-Day, C.E.

    1989-01-01

    Atrial natriuretic peptide (ANP), considered to be an important regulator of intravascular fluid volume, binds specifically to receptors on endothelial cells. In this study, the role of ANP-specific binding was investigated by examining the effect of ANP on the morphology and macromolecular permeability of monolayer cultures of bovine aortic endothelial cells. ANP alone had no observable effect on the monolayers. However, incubation of monolayers with ANP antagonized thrombin- or glucose oxidase-induced cell shape changes and intercellular gap formation. ANP pretreatment also opposed the effect of thrombin and glucose oxidase on actin filament distribution as observed by rhodamine-phalloidin staining and digital image analysis of F0actin staining. In addition, ANP reversed cell shape changes and cytoskeletal alterations induced by thrombin treatment but did not reverse alternations induced by glucose oxidase treatment. ANP significantly reduced increases in monolayer permeability to albumin resulting from thrombin or glucose oxidases treatment. Thrombin caused a 2-fold increase in monolayer permeability to {sup 125}I-labeled albumin, which was abolished by 10{sup {minus}8}-10{sup {minus}6}M ANP pretreatment. Glucose oxidase caused similar increases in permeability and was inhibited by ANP at slightly shorter time periods.

  13. Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

    SciTech Connect

    Leitman, D.C.

    1988-01-01

    The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP.

  14. Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

    SciTech Connect

    Silva, P.; Stoff, J.S.; Solomon, R.J.; Lear, S.; Kniaz, D.; Greger, R.; Epstein, F.H.

    1987-01-01

    Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallel with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.

  15. Midregional pro-atrial natriuretic peptide and procalcitonin improve survival prediction in VAP.

    PubMed

    Boeck, L; Eggimann, P; Smyrnios, N; Pargger, H; Thakkar, N; Siegemund, M; Marsch, S; Rakic, J; Tamm, M; Stolz, D

    2011-03-01

    Ventilator-associated pneumonia (VAP) affects mortality, morbidity and cost of critical care. Reliable risk estimation might improve end-of-life decisions, resource allocation and outcome. Several scoring systems for survival prediction have been established and optimised over the last decades. Recently, new biomarkers have gained interest in the prognostic field. We assessed whether midregional pro-atrial natriuretic peptide (MR-proANP) and procalcitonin (PCT) improve the predictive value of the Simplified Acute Physiologic Score (SAPS) II and Sequential Related Organ Failure Assessment (SOFA) in VAP. Specified end-points of a prospective multinational trial including 101 patients with VAP were analysed. Death <28 days after VAP onset was the primary end-point. MR-proANP and PCT were elevated at the onset of VAP in nonsurvivors compared with survivors (p = 0.003 and p = 0.017, respectively) and their slope of decline differed significantly (p = 0.018 and p = 0.039, respectively). Patients with the highest MR-proANP quartile at VAP onset were at increased risk for death (log rank p = 0.013). In a logistic regression model, MR-proANP was identified as the best predictor of survival. Adding MR-proANP and PCT to SAPS II and SOFA improved their predictive properties (area under the curve 0.895 and 0.880). We conclude that the combination of two biomarkers, MR-proANP and PCT, improve survival prediction of clinical severity scores in VAP.

  16. The role of atrial natriuretic peptide (ANP) in cold-induced diuresis (CID)

    SciTech Connect

    Agnew, J.W.; Freund, B.J.; DuBose, D.A.; McKay, J.M.; Hashiro, G.M. Tripler Army Medical Center, Honolulu, HI )

    1991-03-11

    The hormonal control of cold-induced diuresis (CID) remains unresolved. This study investigated the role of ANP, plasma vasopressin (AVP), and aldosterone (ALDO) on CID. Four semi-nude men participated in a 210 min exposure to 15C and 29C air, on separate days. These subjects drank 300 mL of water and had an intravenous saline drip throughout both exposures to replace blood and insensible fluid losses. CID was observed in 15C but not in the 29C experiment, as indicated by a greater urine output. In 15C, atrial natriuretic peptide (ANP) increased after 90 min by 41% and remained elevated for 2 h relative to 29C. No differences were observed in AVP between 15C and 29C. In the 15C versus the 29C experiment, ALDO was approximately 37% lower at the pre, 15 and 90 min time periods. Mean arterial blood pressure was generally greater but only significant at 60 min during the 15C versus the 29C experiment. Urinary NA{sup +} excretion was elevated in 15C relative to 29C while no difference in K{sup +} excretion was observed. Although pressure effects may contribute, the observed natriuresis in the absence of a kaliuresis in the cold suggests a physiological role of ANP in CID.

  17. Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

    SciTech Connect

    Ogura, T.; Mitsui, T.; Yamamoto, I.; Katayama, E.; Ota, Z.; Ogawa, N.

    1987-01-19

    To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of (/sup 125/I)-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of (/sup 3/H)-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.

  18. Studies of the penetration of the blood brain barrier by atrial natriuretic factor.

    PubMed

    Levin, E R; Frank, H J; Weber, M A; Ismail, M; Mills, S

    1987-09-30

    The atrial natriuretic factors (ANF) have been detected in various areas of the brain. To determine whether circulating blood borne ANF could contribute to the ANF content in the central nervous systems we examined the ability of ANF-99-126 or ANF-102-126 to penetrate the blood brain barrier. Carotid artery injections of [3H] inulin with [125I] ANF in anesthetized rabbits resulted in a comparably minimal brain uptake index (BUI) for each labeled substance as measured in cerebral cortex extracts. Injection of [3H] HOH and [125I] ANF resulted in a mean BUI in cortex of 4.9 +/- .6 (SEM)% for ANF relative to triated water; this low uptake was not significantly saturable. The BUI ratio for ANF/HOH in olfactory bulb was somewhat higher though still low, at 7.0 +/- 9%, possibly reflecting the high density of ANF receptors in this structure. Infusion of [125I] ANF into the carotid artery of anesthetized rabbits resulted in little radioactivity being detected in the cerebrospinal fluid. Infusion of unlabeled ANF, which raised plasma levels as high as 26.3 ng/ml, resulted in little change in CSF levels. Our results demonstrate that the uptake of ANF into the brain is minimal and supports the idea that local synthesis of ANF predominantly accounts for the brain pool of this peptide.

  19. Effect of prolonged high salt intake on atrial natriuretic factor's kinetics in rats

    SciTech Connect

    Widimsky, J.; Debinski, W.; Kuchel, O.; Buu, N.T.; Du Souich, P. )

    1990-05-01

    Plasma atrial natriuretic factor (ANF) paradoxically decreases after 5 weeks (but not after 3 weeks) of 8% NaCl intake in normotensive rats. As this phenomenon remains unaccounted for by changes in ANF production, we studied the disappearance of ({sup 125}I)ANF(99-126) from the circulation as an alternative explanation of plasma ANF decline. Following 5 weeks (but not 3 weeks) of an 8% NaCl diet, plasma concentrations of ({sup 125}I)ANF were significantly decreased and metabolic clearance rate and volume of distribution were increased compared to control rats fed a 0.8% NaCl diet. By studying ({sup 125}I)ANF tissue uptake we noted significantly greater peptide uptake after 5 weeks (but not after 3 weeks) of high salt consumption in several tissues. We hypothesize that prolonged (at least 5 weeks) 8% NaCl ingestion increases the density and/or affinity of ANF binding sites. These changes may be responsible for the previously observed decline in plasma ANF concentrations after a prolonged high salt intake.

  20. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  1. Effects of posture and ageing on circulating atrial natriuretic peptide levels in man.

    PubMed

    Haller, B G; Züst, H; Shaw, S; Gnädinger, M P; Uehlinger, D E; Weidmann, P

    1987-10-01

    Possible influences of posture or age on plasma immunoreactive atrial natriuretic peptide (irANP) levels and potential correlates were assessed in 12 young (age +/- s.e.m. 24 +/- 1 year) and 12 elderly (63 +/- 8 year) healthy subjects on a liberal sodium intake. The groups did not differ significantly in their basal 24-h urinary sodium excretion (210 +/- 23 versus 180 +/- 15 mmol/l). However, plasma irANP was five- to ninefold higher in the elderly (P less than 0.05-0.01). Plasma irANP averaged 167 +/- 31 and 24 +/- 3 pg/ml in the elderly and young, respectively, during recumbency, fell (P less than 0.05) to 101 +/- 21 and 11 +/- 1 pg/ml, respectively, with upright posture, and rose (P less than 0.01) to 250 +/- 51 and 50 +/- 9 pg/ml, respectively, after intravenous (i.v.) loading with 0.9% saline (2.14 l in 3 h). Supine blood pressure (BP) and plasma norepinephrine tended to be higher while renin and aldosterone levels were lower (P less than 0.01) in the elderly; the three latter variables rose (P less than 0.001) with upright posture. These findings demonstrate that in normal humans, circulating irANP levels vary with posture and ageing. These changes may have potential physiological relevance and should be considered when interpreting plasma irANP levels in pathological conditions.

  2. Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction.

    PubMed

    Maeda, K; Tsutamoto, T; Wada, A; Mabuchi, N; Hayashi, M; Hisanaga, T; Kamijo, T; Kinoshita, M

    2000-08-01

    To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately 12 h after the attack) (group 1) and compared data with those obtained after 1 mo (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.

  3. Role of calcium in effects of atrial natriuretic peptide on aldosterone production in adrenal glomerulosa cells

    SciTech Connect

    Chartier, L.; Schiffrin, E.L.

    1987-04-01

    Atrial natriuretic peptide (ANP) inhibits the stimulation of aldosterone secretion by isolated adrenal glomerulosa cells produced by angiotensin II (ANG II), ACTH, and potassium. The effect of ANP on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium on isolated rat adrenal glomerulosa cells was studied. In the presence of ANP the maximal response of aldosterone output stimulated by ANG II or potassium decreased and the half-maximum (EC/sub 50/) of the response to ACTH was displaced to the right. Because these effects resemble those of calcium-channel blockers, the authors investigated the effect of different concentrations of nifedipine, a dihydropyridine calcium-channel blocker, on the dose-response curve of aldosterone stimulated by ANG II, ACTH, and potassium. Nifedipine produced effects similar to ANP. The maximal response of aldosterone stimulated by ANG II and potassium was decreased and the dose-response curve to ACTH was displaced to the right. ANP decreased the maximal response of aldosterone to the dihydropyridine derivative BAY K8644, a calcium-channel activator, without change in its EC/sub 50/. In contrast, nifedipine displaced the dose-response curve to BAY K8644 to the right as expected of a competitive inhibitor. The effect of ANP and nifedipine on basal and stimulated /sup 45/Ca influx into isolated rat adrenal glomerulosa cells was studied. ANP may act on the rat adrenal glomerulosa cells at least in part by interference with calcium entry.

  4. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  5. Plasma atrial natriuretic peptide and N-terminal pro B-type natriuretic peptide concentrations in dogs with right-sided congestive heart failure

    PubMed Central

    KANNO, Nobuyuki; HORI, Yasutomo; HIDAKA, Yuichi; CHIKAZAWA, Seishiro; KANAI, Kazutaka; HOSHI, Fumio; ITOH, Naoyuki

    2015-01-01

    The clinical utility of plasma natriuretic peptide concentrations in dogs with right-sided congestive heart failure (CHF) remains unclear. We investigated whether plasma levels of atrial natriuretic peptide (ANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are useful for assessing the congestive signs of right-sided heart failure in dogs. This retrospective study enrolled 16 healthy dogs and 51 untreated dogs with presence (n=28) or absence (n=23) of right-sided CHF. Medical records of physical examinations, thoracic radiography and echocardiography were reviewed. The plasma concentration of canine ANP was measured with a chemiluminescent enzyme immunoassay. Plasma NT-proBNP concentrations were determined using an enzyme immunoassay. Plasma ANP and NT-proBNP concentrations in dogs with right-sided CHF were significantly higher than in healthy controls and those without right-sided CHF. The plasma NT-proBNP concentration >3,003 pmol/l used to identify right-sided CHF had a sensitivity of 88.5% and specificity of 90.3%. An area under the ROC curve (AUC) was 0.93. The AUC for NT-proBNP was significantly higher than the AUCs for the cardiothoracic ratio, vertebral heart score, ratio of right ventricular end-diastolic internal diameter to body surface area, tricuspid late diastolic flow and ratio of the velocities of tricuspid early to late diastolic flow. These results suggest that plasma ANP and NT-proBNP concentrations increase markedly in dogs with right-sided CHF. Particularly, NT-proBNP is simple and helpful biomarkers to assess the right-sided CHF. PMID:26607133

  6. Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet

    PubMed Central

    Della Penna, Silvana Lorena; Cao, Gabriel; Carranza, Andrea; Zotta, Elsa; Gorzalczany, Susana; Cerrudo, Carolina Susana; Rukavina Mikusic, Natalia Lucía; Correa, Alicia; Trida, Verónica; Toblli, Jorge Eduardo; Fernández, Belisario Enrique

    2014-01-01

    In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1α is involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1α compared to their control. These findings suggest that HIF-1α and ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis. PMID:24689065

  7. Gene for the rat atrial natriuretic peptide is regulated by glucocorticoids in vitro.

    PubMed Central

    Gardner, D G; Gertz, B J; Deschepper, C F; Kim, D Y

    1988-01-01

    Glucocorticoids regulate the expression of the gene for atrial natriuretic peptide (ANP) in neonatal cardiocytes. Dexamethasone (Dex) increased cytoplasmic ANP mRNA levels and media ANP immunoreactivity in a dose-dependent fashion. These effects were not shared by the other classes of steroid hormones and were reversed by the glucocorticoid antagonist RU 38486. The effect on ANP mRNA levels resulted, at least in part, from enhanced transcription of the gene. Dex effected a two-fold increase in ANP gene activity assessed using a run-on transcription assay. The turnover of the ANP transcript was approximated using a standard pulse-chase technique. The half-life of the ANP mRNA was 18 h in hormone-free media. In the presence of Dex this half-life increased modestly to 30 h, although the increase relative to the control did not reach statistical significance. The effect of Dex at the level of the individual myocardial cell was assessed by in situ hybridization analysis using a specific [3H]cRNA probe. These studies demonstrated a significant level of ANP expression within a subpopulation of cells in the cultures. Exposure of the cells to Dex for 24 h did not recruit additional cells into the expressing pool (27.3% cells/high power field vs. 31.3% for the control) but did increase the level of expression (i.e., grain density) within individual cells. These findings indicate that glucocorticoids stimulate expression of the ANP gene directly at the level of the myocardial cell. This results predominantly from transcriptional activation in cells already expressing the gene rather than through recruitment of previously quiescent cells. Images PMID:2971674

  8. Thyrotropin modulates receptor-mediated processing of the atrial natriuretic peptide receptor in cultured thyroid cells

    SciTech Connect

    Tseng, Y.L.; Burman, K.D.; Lahiri, S.; Abdelrahim, M.M.; D'Avis, J.C.; Wartofsky, L. )

    1991-03-01

    In a prior study of atrial natriuretic peptide (ANP) binding to cultured thyroid cells, we reported that at 4 C, more than 95% of bound ANP is recovered on cell membranes, with negligible ANP internalization observed. Since ANP binding was inhibited by TSH, we have further studied TSH effects on postbinding ANP processing to determine whether this phenomenon reflects enhanced endocytosis of the ANP-receptor complex. An ANP chase study was initiated by binding (125I) ANP to thyroid cells at 4 C for 2 h, followed by incubation at 37 C. ANP processing was then traced by following 125I activity at various time intervals in three fractions: cell surface membranes, incubation medium, and inside the cells. Radioactivity released into medium represented processed ANP rather than ANP dissociated from surface membranes, since prebound (125I)ANP could not be competitively dissociated by a high concentration of ANP (1 mumol/L) at 37 C. Chase study results showed that prebound ANP quickly disappeared from cell membranes down to 34% by 30 min. Internalized ANP peaked at 10 min, with 21% of initial prebound ANP found inside the cells. At the same time, radioactivity recovered in incubation medium sharply increased between 10-30 min from 8% to 52%. Preincubation of cells with chloroquine (which blocks degradation of the ANP-receptor complex by inhibiting lysosomal hydrolase) caused a 146% increase in internalized (125I)ANP by 30 min (39% compared to 15% control), while medium radioactivity decreased from 52% to 16%, suggesting that processing of the receptor complex is mediated via lysosomal enzymes. In chase studies employing cells pretreated with chloroquine, TSH stimulated the internalization rate of ANP-receptor complex. By 30 min, TSH significantly reduced the membrane-bound ANP, and the decrease was inversely correlated to the increase in internalized radioactivity.

  9. Clonidine stimulates atrial natriuretic factor (ANF) release in water-deprived rats.

    PubMed

    Baranowska, B; Tremblay, J; Gutkowska, J

    1988-01-01

    To determine the effect of clonidine, an alpha 2-adrenergic agonist, on atrial natriuretic factor (ANF) release during water deprivation, plasma immunoreactive ANF (IR-ANF) arginine vasopressin, diuresis and natriuresis were measured in rats which had been deprived of water for 24 and 48 hr after intravenous (IV) administration of 50 micrograms clonidine. In normally-hydrated rats clonidine produced a marked elevation of plasma IR-ANF from 40.5 +/- 4.6 pg/ml to 1064 +/- 22 pg/ml (mean +/- SEM) and sodium excretion from 73.3 +/- 6.8 microEq to 723.4 +/- 62.3 microEq. Clonidine evoked an increase in plasma IR-ANF from 16.6 +/- 5.9 pg/ml to 229.5 +/- 60 pg/ml (mean +/- SEM) after 24 hr water deprivation and from 13.6 +/- 7.4 pg/ml to 104.8 +/- 21 pg/ml (mean +/- SEM) after 48 hr water deprivation. Clonidine did not induce any significant changes in vasopressin levels. During 24 hr and 48 hr water deprivation vasopressin rose from 3.1 +/- 0.3 pg/ml to 7.3 +/- 1.3 pg/ml and 8.4 +/- 0.6 pg/ml (mean +/- SEM), respectively. In normally-hydrated rats clonidine produced a marked diuresis and natriuresis. These effects and urinary cGMP excretion were significantly inhibited by anti-ANF antibodies. Clonidine caused a significant increase in urine output in 24 hr water-deprived rats but the response was markedly lower than that seen in normally-hydrated rats. In conclusion, clonidine stimulates ANF release both in normally-hydrated and water-deprived rats. The diuretic effect of clonidine appears to be related to ANF release but not to inhibition of vasopressin.

  10. Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

    PubMed Central

    Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Costa, María A.; Elesgaray, Rosana; Arranz, Cristina; Tomat, Analía L.

    2015-01-01

    Objective The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay. Results Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes. Conclusions Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes. PMID:25774801

  11. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

    PubMed

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-10-15

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

  12. Atrial natriuretic peptide protects against Staphylococcus aureus-induced lung injury and endothelial barrier dysfunction

    PubMed Central

    Xing, Junjie; Moldobaeva, Nurgul

    2011-01-01

    Lung inflammation and alterations in endothelial cell (EC) permeability are key events to development of acute lung injury (ALI). Protective effects of atrial natriuretic peptide (ANP) have been shown against inflammatory signaling and endothelial barrier dysfunction induced by gram-negative bacterial wall liposaccharide. We hypothesized that ANP may possess more general protective effects and attenuate lung inflammation and EC barrier dysfunction by suppressing inflammatory cascades and barrier-disruptive mechanisms shared by gram-negative and gram-positive pathogens. C57BL/6J wild-type or ANP knockout mice (Nppa−/−) were treated with gram-positive bacterial cell wall compounds, Staphylococcus aureus-derived peptidoglycan (PepG) and/or lipoteichoic acid (LTA) (intratracheal, 2.5 mg/kg each), with or without ANP (intravenous, 2 μg/kg). In vitro, human pulmonary EC barrier properties were assessed by morphological analysis of gap formation and measurements of transendothelial electrical resistance. LTA and PepG markedly increased pulmonary EC permeability and activated p38 and ERK1/2 MAP kinases, NF-κB, and Rho/Rho kinase signaling. EC barrier dysfunction was further elevated upon combined LTA and PepG treatment, but abolished by ANP pretreatment. In vivo, LTA and PepG-induced accumulation of protein and cells in the bronchoalveolar lavage fluid, tissue neutrophil infiltration, and increased Evans blue extravasation in the lungs was significantly attenuated by intravenous injection of ANP. Accumulation of bronchoalveolar lavage markers of LTA/PepG-induced lung inflammation and barrier dysfunction was further augmented in ANP−/− mice and attenuated by exogenous ANP injection. These results strongly suggest a protective role of ANP in the in vitro and in vivo models of ALI associated with gram-positive infection. Thus ANP may have important implications in therapeutic strategies aimed at the treatment of sepsis and ALI-induced gram-positive bacterial

  13. Autoradiographic localization of atrial natriuretic peptide receptor subtypes in rat kidney

    SciTech Connect

    Brown, J.; Salas, S.P.; Singleton, A.; Polak, J.M. )

    1990-07-01

    The distribution of atrial natriuretic peptide (ANP) clearance receptors in rat kidney was investigated by in vitro autoradiography using des(Gln18,Ser19,Gly20,Leu21,Gly22)-ANP-(4- 23) (C-ANP) and 125I-Tyr0-ANP-(5-25) as relatively specific ligands of this receptor. Alpha-125I-ANP (100 pM) bound reversibly but with high affinity to glomeruli, outer medullary vasa recta bundles, and inner medulla. C-ANP (10 microM) inhibited greater than 60% of this glomerular binding but did not inhibit the binding of alpha-125I-ANP to medullary tissues. Alpha-125I-ANP also bound reversibly to the renal arteries up to the glomerulus. This arterial binding was only partly inhibited by 10 microM C-ANP. In the presence of 10 microM C-ANP, increasing concentrations of alpha-125I-ANP bound to a residue of glomerular sites with apparent dissociation constants of 0.82 +/- 0.16 to 2.73 +/- 1.20 nM at different cortical levels. 125I-Tyr0-ANP-(5-25) bound significantly to glomeruli and intrarenal arteries but not to vasa recta bundles or inner medulla. This glomerular binding also occurred with nanomolar dissociation constants. It was completely inhibited by 1 microM alpha-ANP and 10 microM C-ANP, but not by unrelated peptides such as gastrin. These results suggest that renal ANP clearance receptors are restricted in vivo to the glomeruli and renal arterial system of the rat.

  14. Synthesis, internalization, and localization of atrial natriuretic peptide in rat adrenal medulla

    SciTech Connect

    Morel, G.; Chabot, J.G.; Garcia-Caballero, T.; Gossard, F.; Dihl, F.; Belles-Isles, M.; Heisler, S.

    1988-07-01

    Some, though not all studies, have indicated that atrial natriuretic peptide (ANP) can bind to adrenal medullary cells. ANP-like immunoreactivity (ANP-LI) has also been identified in catecholamine-secreting cells. Together, these findings suggest that ANP may be taken up and/or synthesized in the adrenal medulla. The present study was designed to ascertain, by in situ hybridization, whether adrenal chromaffin cells could synthesize ANP, to define by an in vivo ultrastructural autoradiographic approach, whether ANP could, in fact, bind to rat adrenal medulla cells, to determine whether there was a cellular (noradrenaline (NA) vs. adrenaline (A)) selectivity in the binding process, and to establish whether extracellular (125I)ANP could be internalized by these cells. The cellular and subcellular distribution of endogenous ANP-LI was also investigated in both cell types by cryoultramicrotomy and immunocytochemical approaches. The in situ hybridization studies indicate the presence of mRNA to ANP in about 15% of adrenal medullary cells. Intravenous injection of (125I)ANP resulted in a 3-fold, preferential and specific radiolabeling of A-as compared to NA-containing cells. In A-containing cells, plasma membranes were significantly labeled 2 and 5 min post injection; cytoplasmic matrix, mitochondria, and secretory granules throughout the time course studied (1-30 min post injection). Lysosomes, rough endoplasmic reticulum, Golgi apparatus, and nuclei were not labeled. ANP-LI was identified in both NA- and A-containing cells; in the former, it was almost exclusively localized in secretory vesicles, in the latter it was detected in plasma membranes, cytoplasmic matrix, nuclear euchromatin, some mitochondria and relatively fewer granules than in NA-containing cells.

  15. Endothelial actions of atrial natriuretic peptide prevent pulmonary hypertension in mice.

    PubMed

    Werner, Franziska; Kojonazarov, Baktybek; Gaßner, Birgit; Abeßer, Marco; Schuh, Kai; Völker, Katharina; Baba, Hideo A; Dahal, Bhola K; Schermuly, Ralph T; Kuhn, Michaela

    2016-03-01

    The cardiac hormone atrial natriuretic peptide (ANP) regulates systemic and pulmonary arterial blood pressure by activation of its cyclic GMP-producing guanylyl cyclase-A (GC-A) receptor. In the lung, these hypotensive effects were mainly attributed to smooth muscle-mediated vasodilatation. It is unknown whether pulmonary endothelial cells participate in the homeostatic actions of ANP. Therefore, we analyzed GC-A/cGMP signalling in lung endothelial cells and the cause and functional impact of lung endothelial GC-A dysfunction. Western blot and cGMP determinations showed that cultured human and murine pulmonary endothelial cells exhibit prominent GC-A expression and activity which were markedly blunted by hypoxia, a condition known to trigger pulmonary hypertension (PH). To elucidate the consequences of impaired endothelial ANP signalling, we studied mice with genetic endothelial cell-restricted ablation of the GC-A receptor (EC GC-A KO). Notably, EC GC-A KO mice exhibit PH already under resting, normoxic conditions, with enhanced muscularization of small arteries and perivascular infiltration of inflammatory cells. These alterations were aggravated on exposure of mice to chronic hypoxia. Lung endothelial GC-A dysfunction was associated with enhanced expression of angiotensin converting enzyme (ACE) and increased pulmonary levels of Angiotensin II. Angiotensin II/AT1-blockade with losartan reversed pulmonary vascular remodelling and perivascular inflammation of EC GC-A KO mice, and prevented their increment by chronic hypoxia. This experimental study indicates that endothelial effects of ANP are critical to prevent pulmonary vascular remodelling and PH. Chronic endothelial ANP/GC-A dysfunction, e.g. provoked by hypoxia, is associated with activation of the ACE-angiotensin pathway in the lung and PH.

  16. Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

    PubMed Central

    Adnot, S; Andrivet, P; Chabrier, P E; Piquet, J; Plas, P; Braquet, P; Roudot-Thoraval, F; Brun-Buisson, C

    1989-01-01

    To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD. PMID:2522105

  17. Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery.

    PubMed

    Marrachelli, Vannina G; Centeno, José M; Miranda, Ignacio; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Miranda, Francisco J; Alborch, Enrique

    2012-11-01

    Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10(-12)-10(-7)M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal decreased the ANP-induced relaxation but inhibition of NO-synthesis did not modify ANP-induced relaxations. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium (TEA) partly inhibited the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to ANP, and these inhibitions were lower in diabetic than in control rabbits. Indomethacin potentiated the relaxation to ANP, more in control than in diabetic rabbits. In the presence of ANP the renal artery released thromboxane A(2) and prostacyclin, and the release of prostacyclin resulted decreased in diabetic rabbits. The present results suggest that diabetes produces hyporeactivity of the rabbit renal artery to ANP by mechanisms that at least include the reduced modulation by prostacyclin and a lower participation of ATP-sensitive K(+) channel (K(ATP)), voltage-sensitive K(+) channels (K(V)) and TEA-sensitive K(+) channels (K(Ca)).

  18. The renal and vascular effects of central angiotensin II and atrial natriuretic factor in the anaesthetized rat.

    PubMed Central

    Al-Barazanji, K A; Balment, R J

    1990-01-01

    1. The interaction between atrial natriuretic factor (ANF) and angiotensin II (Ang II) within the brain to influence renal function and blood pressure was studied in Inactin-anaesthetized male Sprague-Dawley rats. 2. Central infusion of ANF produced a diuresis which was associated with a significant decrease in plasma arginine vasopressin (AVP) level. There was no change in sodium excretion rate over the 80 min of intracerebroventricular ANF infusion and ANF produced no detectable change in mean arterial blood pressure. 3. Central Ang II administration produced a significant decrease in urine flow, which was associated with elevated plasma AVP, an increase in sodium excretion and a rise in mean arterial blood pressure. 4. Combined ANF and Ang II infusion produced an antidiuresis, which was associated with increased plasma AVP concentration. Both the natriuretic and vasopressor actions of central Ang II were abolished when ANF was co-administered. 5. It is concluded that ANF and Ang II interact centrally; ANF antagonizes the pressor and natriuretic effects but not the antidiuretic effects of central Ang II. These data suggest the possibility of distinct and separate sites within the brain through which Ang II influences vasopressin release and renal sodium handling and elevates blood pressure. PMID:2143782

  19. The effect of atrial natriuretic peptide infusion on intestinal injury in septic shock

    PubMed Central

    Elbaradey, Ghada F.; Elshmaa, Nagat Sayed; Hodeib, Hossam

    2016-01-01

    Background and Aims: The aim of this study is to assess the effect of atrial natriuretic peptide (ANP) on intestinal ischemia-reperfusion injury in septic shock. Material and Methods: A prospective randomized controlled, observer-blinded study was carried out in surgical Intensive Care Unit (ICU), University Hospital. Forty adult patients in septic shock were randomly divided into two groups, control group (Group C) received normal saline and ANP group (Group A) patients received ANP in the form of 1.5 mg vial added to 250 ml solvent in plastic bag (1 ml = 6 micg) given at 2 mcg/kg intravenous bolus over 1 min followed by 0.01 mcg/kg/min for 24 h. The primary outcome measurements were blood marker of intestinal hypoperfusion in form of intestinal fatty acid binding protein (I-FABP), malondialdehyde (MDA), myloperoxidase enzyme activity (MPO), protein carbonyl (PC), and glutathione peroxidase activity (GPA) measured before start of ANP infusion, 6 h, 12 h, and 24 h after start of infusion. The secondary outcome measurements were the duration of noradrenaline infusion, duration of ICU stay, hospital mortality rate, and complications related to ANP. Results: In comparison with Group C, Group A showed a significant decrease (P < 0.05) in serum level of MPO, MDA, PC, and I-FABP, with a significant increase (P < 0.05) in serum level of GPA, 6 h, 12 h, and 24 h after the start of ANP infusion. There was significant decrease (P < 0.05) in mean duration of noradrenaline infusion, the length of ICU stay and mortality rate in Group A in comparison with Group C. In Group A, seven patients had mean arterial blood pressure < 65 mmHg but respond to volume resuscitation, three patients serum sodium was 125–130 mmol/L. Conclusion: In cases of septic shock, concomitant administration of ANP with noradrenaline may have a protective effect against intestinal injury through a decrease in the level of intestinal hypoperfusion owing to its anti-inflammatory and antioxidant effect. PMID

  20. Increased atrial natriuretic peptide (6-33) binding sites in the subfornical organ of water deprived and Brattleboro rats

    SciTech Connect

    Saavedra, J.M.; Israel, A.; Correa, F.M.A.; Kurihara, M.

    1986-09-01

    Binding sites for rat atrial natriuretic eptide (6-33) (ANP) were quantitated in the subfornical organ of chronically dehydrated homozygous Brattleboro rats unable to synthesize vasopressin; heterozygous Brattleboro rats, their controls, Long Evans rats and Long Evans rats after 4 days of water deprivation. Brain sections were incubated in the presence of /sup 125/I-ANP and the results analyzed by autoradiography coupled to computerized microdensitometry and comparison to /sup 125/I-standards. Brattleboro rats and water deprived Long Evans rats presented a higher number of ANP binding sites than their normally hydrated controls. The results suggest a role of ANP binding sites in the subfornical organ in the central regulation of fluid balance and vasopressin secretion.

  1. Decreased atrial natriuretic factor receptors and impaired cGMP generation in glomeruli from the cardiomyopathic hamster.

    PubMed

    Levin, E R; Frank, H J; Chaudhari, A; Kirschenbaum, M A; Bandt, A; Mills, S

    1989-03-15

    To determine a possible basis for the decreased action of atrial natriuretic factors (ANF) in congestive heart failure, we compared the cardiomyopathic hamster (CMH) in frank congestive failure, and the age-matched, normal, F1B strain of Golden Syrian Hamsters. Scatchard analysis of competitive binding studies revealed two classes of glomerular receptors. The CMH exhibited decreased binding overall and a markedly decreased number of high affinity receptors but comparable receptor affinity compared to the F1B. In contrast, the low affinity receptor population in the CMH had a much greater affinity compared to the F1B while receptor number was similar. Plasma ANF levels were substantially elevated in the CMH compared to the F1B and in-vitro generation of cGMP was significantly lower in the CMH. Such abnormalities could contribute to the resistance to ANF in this disease.

  2. Alpha-human atrial natriuretic polypeptide (. cap alpha. -hANP) specific binding sites in bovine adrenal gland

    SciTech Connect

    Higuchi, K.; Nawata, H.; Kato, K.I.; Ibayashi, H.; Matsuo, H.

    1986-06-13

    The effects of synthetic ..cap alpha..-human atrial natriuretic polypeptide (..cap alpha..-hANP) on steroidogenesis in bovine adrenocortical cells in primary monolayer culture were investigated. ..cap alpha..-hANP did not inhibit basal aldosterone secretion. ..cap alpha..-hANP induced a significant dose-dependent inhibition of basal levels of cortisol and dehydroepiandrosterone (DHEA) secretion and also of aCTH (10/sup -8/M)-stimulated increases in aldosterone, cortisol and DHEA secretion. Visualization of (/sup 125/I) ..cap alpha..-hANP binding sites in bovine adrenal gland by an in vitro autoradiographic technique demonstrated that these sites were highly localized in the adrenal cortex, especially the zona glomerulosa. These results suggest that the adrenal cortex may be a target organ for direct receptor-mediated actions of ..cap alpha..-hANP.

  3. Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

    PubMed

    Wang, Dong; Gladysheva, Inna P; Fan, Tai-Hwang M; Sullivan, Ryan; Houng, Aiilyan K; Reed, Guy L

    2014-03-01

    Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

  4. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    PubMed Central

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  5. Role of atrial natriuretic peptide in mediating the blood pressure-independent natriuresis elicited by systemic inhibition of nitric oxide.

    PubMed

    Dobrowolski, Leszek; Kuczeriszka, Marta; Castillo, Alexander; Majid, Dewan S; Navar, L Gabriel

    2015-04-01

    While it is clearly recognized that increased intrarenal nitric oxide (NO) levels elicit natriuresis, confounding data showing that systemic nitric oxide synthase inhibition (NOSi) also increases sodium excretion (UNaV) poses a conundrum. This response has been attributed to the associated increases in arterial pressure (AP); however, the increases in AP and in UNaV are temporally dissociated. The changes in regional renal haemodynamics induced by NOSi could also contribute to the alterations of UNaV. To evaluate the roles of AP and non-AP mechanisms mediating the natriuresis, N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) was infused i.v. at doses ranging from 5 to 50 μg/kg/min in anaesthetized rats. UNaV, perfusion of the cortex (cortical blood flow, CBF) and medulla (medullary blood flow, MBF) with laser-Doppler flowmetry and glomerular filtration rate (GFR) were measured. UNaV increased from 0.6 ± 0.2 to 1.6 ± 0.1 μmol/kg/min (P < 0.05) with the lower nonpressor doses. With the higher doses, AP increased from 116 ± 4 to 122 ± 4 mmHg and UNaV increased from 1.1 ± 0.3 to 3.3 ± 0.7 μmol/min/g (P < 0.002). UNaV increased similarly in a group where renal AP was maintained at baseline levels. The associated reductions in CBF (17 ± 5 and 38 ± 5 %) and MBF (27 ± 6 and 52 ± 6 %) would be expected to attenuate rather than contribute to the natriuresis. Plasma atrial natriuretic peptide (ANP) concentrations increased significantly following NOSi. Anantin, a natriuretic peptide receptor-A blocker, prevented or reversed the L-NAME-induced natriuresis without altering the L-NAME-induced changes in AP or CBF. The results indicate that increased ANP and related natriuretic peptides mediate the AP-independent natriuresis, at least partly, elicited by systemic L-NAME infusion and help resolve the conundrum of natriuresis during systemic NOSi.

  6. Clearance and early hydrolysis of atrial natriuretic factor in vivo. Structural analysis of cleavage sites and design of an analogue that inhibits hormone cleavage.

    PubMed Central

    Condra, C L; Leidy, E A; Bunting, P; Colton, C D; Nutt, R F; Rosenblatt, M; Jacobs, J W

    1988-01-01

    This study examines the clearance and early hydrolysis of atrial natriuretic factor (ANF) in vivo. Radiolabeled ANF was cleared from the circulation of the rat with biphasic kinetics; the majority (90%) of ANF cleared with a t1/2 of 15 s, the remaining peptide was cleared with a t1/2 of 5 min. Microsequence analysis of ANF peptides recovered from the circulation of rats revealed five major degradation products of the intact hormone. The first cleavage occurred between amino acids 12 and 13 of the hormone and would inactivate ANF. Over time, additional fragments of the hormone were generated, including fragments of 6, 7, 21, and 24 amino acids in length. Whole body radioautography of rats injected with [123I]-ANF revealed the kidney as a predominant organ involved in clearance of ANF. Subsequent amino acid sequence analyses of radiolabeled ANF exposed to the kidney in vivo indicated that this organ generated four of the five major hydrolysis products observed in circulation, namely, the 6, 7, 16, and 21 amino acid fragments of the hormone. In an attempt to stabilize ANF in vivo, a synthetic analogue of the hormone was prepared that contained the amino acid analogue, aminoisobutyric acid, substituted at position 13. This analogue completely abolished the in vivo cleavage of ANF at this site. These studies demonstrate the usefulness of a protein chemistry approach in characterizing hormone metabolism in vivo and designing analogues with enhanced in vivo stability to cleavage. Images PMID:2966813

  7. Atrial natriuretic peptide in the locus coeruleus and its possible role in the regulation of arterial blood pressure, fluid and electrolyte homeostasis

    SciTech Connect

    Geiger, H.; Sterzel, R.B. ); Bahner, U.; Heidland, A. ); Palkovits, M. )

    1991-01-01

    Atrial natriuretic factor (ANP) is present in neuronal cells of the locus coeruleus and its vicinity in the pontine tegmentum and moderate amount of ANP is detectable in this area by radioimmunoassay. The ANP is known as a neuropeptide which may influence the body salt and water homeostasis and blood pressure by targeting both central and peripheral regulatory mechanisms. Whether this pontine ANP cell group is involved in any of these regulatory mechanisms, the effect of various types of hypertension and experimental alterations in the salt and water balance on ANP levels was measured by radioimmunoassay in the locus coeruleus of rats. Adrenalectomy, as well as aldosterone and dexamethasone treatments failed to alter ANP levels in the locus coeruleus. Reduced ANP levels were measured in spontaneously hypertensive rats, and in diabetes insipidus rats with vasopressin replacement. In contrast to these situations, elevated ANP levels were found in rats with DOCA-salt or 1-Kidney-1-clip hypertension. These data suggest a link between ANP levels in the locus coeruleus and fluid volume homeostasis. Whether this link is causal and connected with the major activity of locus coeruleus neurons needs further information.

  8. Salt-losing nephropathy associated with inappropriate secretion of atrial natriuretic peptide--a new clinical syndrome.

    PubMed

    Rodríguez-Soriano, J; Vallo, A

    1997-10-01

    A state of normokalemic renal sodium wasting associated with an apparently inappropriate secretion of atrial natriuretic peptide (ANP) has not been previously recognized. We here report an 11-year-old boy who presented with a chronic "salt-losing" nephropathy manifested by normonatremic or mildly hyponatremic extracellular fluid volume depletion, hypodipsia, absence of salt appetite, normokalemic metabolic alkalosis, hyper-reninemic hyperaldosteronism, hypertrophy of the juxtaglomerular apparatus, and highly conserved capacities for concentrating diluting the urine. Plasma ANP values were paradoxically elevated (between 10 and 47 fmol/ml), despite the coexistence of intravascular volume depletion and increased plasma levels of renin and aldosterone. Although the patient had some clinical similarities to Bartter's syndrome, fractional sodium chloride (NaCl) reabsorption during hypotonic saline diuresis was normal and no clinical amelioration was observed while on indomethacin therapy. Neither a tumor nor cardiac or cerebral abnormalities, which could be responsible for the increased ANP secretion, were detected. These clinical, biochemical, and histological features have not been previously described together and may represent a new clinical syndrome. The pathophysiology of this entity remains unknown, but an attractive, although unproven, hypothesis is that the renal defect in NaCl reabsorption in this patient could be related to an inappropriate and unregulated secretion of ANP.

  9. Atrial natriuretic peptide degradation by CPA47 cells - Evidence for a divalent cation-independent cell-surface proteolytic activity

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Chen, Y. M.; Whitson, P. A.

    1992-01-01

    Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88 percent of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41 percent of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

  10. Receptors for atrial natriuretic peptide (ANP) and regulation of thyroglobulin secretion by ANP in human thyroid cells

    SciTech Connect

    Sellitti, D.F.; Tseng, Y.C.L.; Wartofsky, L. Walter Reed Army Medical Center, Washington, DC )

    1989-01-01

    Specific binding sites for atrial natriuretic peptide (ANP) were identified and characterized in primary cultures of human thyroid cells. Saturation analysis using ({sup 125}I) {alpha} rat (1-28) ANP as the ligand showed a single class of high affinity binding which was inhibited by atriopeptin I and the {alpha} -human form of ANP, but not by a C-terminal fragment (13-28) of the peptide. The number of ANP binding sites in these cultures was not altered by the thyroid hormone concentration of the medium. In a dose-response experiment, thyroglobulin secretion was significantly reduced in the presence of 0.01 nM ANP and was maximally reduced with 10 nM ANP. Cyclic GMP production was increased threefold in the presence of 100 nM ANP, but was unchanged with lower doses of the peptides. The finding of receptors in thyroid follicular cells suggests a hitherto unrecognized role of ANP in the thyroid gland.

  11. An analogue of atrial natriuretic peptide (C-ANP4-23) modulates glucose metabolism in human differentiated adipocytes.

    PubMed

    Ruiz-Ojeda, Francisco Javier; Aguilera, Concepción María; Rupérez, Azahara Iris; Gil, Ángel; Gomez-Llorente, Carolina

    2016-08-15

    The present study was undertaken to investigate the effects of C-atrial natriuretic peptide (C-ANP4-23) in human adipose-derived stem cells differentiated into adipocytes over 10 days (1 μM for 4 h). The intracellular cAMP, cGMP and protein kinase A levels were determined by ELISA and gene and protein expression were determined by qRT-PCR and Western blot, respectively, in the presence or absence of C-ANP4-23. The levels of lipolysis and glucose uptake were also determined. C-ANP4-23 treatment significantly increased the intracellular cAMP levels and the gene expression of glucose transporter type 4 (GLUT4) and protein kinase, AMP-activated, alpha 1 catalytic subunit (AMPK). Western blot showed a significant increase in GLUT4 and phosphor-AMPKα levels. Importantly, the adenylate cyclase inhibitor SQ22536 abolished these effects. Additionally, C-ANP4-23 increased glucose uptake by 2-fold. Our results show that C-ANP4-23 enhances glucose metabolism and might contribute to the development of new peptide-based therapies for metabolic diseases.

  12. Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Yancy, Clyde W.; Buckey, Jay C.; Lane, Lynda D.; Hargens, Alan R.; Blomqvist, C. G.

    1992-01-01

    A hypothesis is proposed that a temporal relationship exists between increases in cardiac filling pressure and plasma artrial natriuretic peptide (ANP) concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). To test the hypothesis, 30 ml/kg isotonic saline were infused in supine male subjects over 24 min and responses were monitored for 3 h postinfusion. Results show that at end infusion, mean arterial pressure (RAP), heart rate and plasma volume exhibited peak increases of 146, 23, and 27 percent, respectively. Mean plasma ANP and UV peaked (45 and 390 percent, respectively) at 30 min postinfusion. Most cardiovascular variables had returned toward control levels by 1 h postinfusion, and net reabsorption of extravascular fluid ensued. It is concluded that since ANP was not significantly increased until 30 min postinfusion, factors other than ANP initiate responses to intravascular fluid loading. These factors include increased vascular pressures, baroreceptor-mediated vasolidation, and hemodilution of plasma proteins. ANP is suggested to mediate, in part, the renal response to saline infusion.

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

    PubMed Central

    Carillon, Julie; Gauthier, Audrey; Barial, Sandy; Tournier, Michel; Gayrard, Nathalie; Lajoix, Anne-Dominique; Jover, Bernard

    2016-01-01

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

  14. Sex Differences in the Beneficial Cardiac Effects of Chronic Treatment with Atrial Natriuretic Peptide In Spontaneously Hypertensive Rats

    PubMed Central

    Romero, Mariana; Caniffi, Carolina; Bouchet, Gonzalo; Elesgaray, Rosana; Laughlin, Myriam Mac; Tomat, Analía; Arranz, Cristina; Costa, Maria A.

    2013-01-01

    Introduction The aim of this study was to investigate both the effects of chronic treatment with atrial natriuretic peptide (ANP) on systolic blood pressure (SBP), cardiac nitric oxide (NO) system, oxidative stress, hypertrophy, fibrosis and apoptosis in spontaneously hypertensive rats (SHR), and sex-related differences in the response to the treatment. Methods 10 week-old male and female SHR were infused with ANP (100 ng/hr/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). SBP was recorded and nitrites and nitrates excretion (NOx) were determined. After treatment, NO synthase (NOS) activity, eNOS expression, thiobarbituric acid-reactive substances (TBARS) and glutathione concentration were determined in left ventricle, as well as the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). Morphological studies in left ventricle were performed in slices stained with hematoxylin-eosin or Sirius red to identify collagen as a fibrosis indicator; immunohistochemistry was employed for identification of transforming growth factor beta; and apoptosis was evaluated by Tunel assay. Results Female SHR showed lower SBP, higher NO-system activity and less oxidative stress, fibrosis and hypertrophy in left ventricle, as well as higher cardiac NOS activity, eNOS protein content and NOx excretion than male SHR. Although ANP treatment lowered blood pressure and increased NOS activity and eNOS expression in both sexes, cardiac NOS response to ANP was more marked in females. In left ventricle, ANP reduced TBARS and increased glutathione concentration and activity of CAT and SOD enzymes in both sexes, as well as GPx activity in males. ANP decreased fibrosis and apoptosis in hearts from male and female SHR but females showed less end-organ damage in heart. Chronic ANP treatment would ameliorate hypertension and end-organ damage in heart by reducing oxidative stress, increasing NO-system activity, and diminishing fibrosis and

  15. Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos.

    PubMed Central

    Kovacic-Milivojević, B; Gardner, D G

    1992-01-01

    Employing transient transfection analysis in neonatal rat cardiocytes, we have demonstrated that overexpression of c-jun results in a dose-dependent induction of the human atrial natriuretic peptide (hANP) gene promoter. Studies using a series of mutations in the hANP gene promoter identified a TRE-like, cis-acting regulatory sequence which conferred c-jun sensitivity. This same region was shown to interact with the c-jun/c-fos complex in an in vitro gel mobility shift assay. Selective mutation of this site suppressed basal activity of the hANP promoter and significantly reduced c-jun-dependent activation. Overexpression of c-fos had a biphasic effect on hANP gene promoter activity. At low levels, in concert with c-jun, it activated, while at higher levels it suppressed, transcription from the hANP gene promoter. This inhibition was both cell and promoter specific. hANP gene promoter sequences which mediate c-fos-dependent inhibition appear to be separable from those responsible for the induction. In addition, the protein domains on c-fos responsible for transcriptional activation and repression can be segregated topographically, with the inhibitory activity being localized to the carboxy-terminal domain. Thus, c-fos can activate or repress hANP gene expression through two separate functional domains that act on distinct regulatory elements in the hANP gene promoter. These data imply that the ANP gene may be a physiological target for c-fos- and c-jun-dependent activity in the heart and suggest a potential mechanism linking environmental stimuli to its expression. Images PMID:1530876

  16. The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors.

    PubMed

    Springer, Jeremy; Azer, John; Hua, Rui; Robbins, Courtney; Adamczyk, Andrew; McBoyle, Sarah; Bissell, Mary Beth; Rose, Robert A

    2012-05-01

    Natriuretic peptides (NPs) are best known for their ability to regulate blood vessel tone and kidney function whereas their electrophysiological effects on the heart are less clear. Here, we measured the effects of BNP and CNP on sinoatrial node (SAN) and atrial electrophysiology in isolated hearts as well as isolated SAN and right atrial myocytes from mice. BNP and CNP dose-dependently increased heart rate and conduction through the heart as indicated by reductions in R-R interval, P wave duration and P-R interval on ECGs. In conjunction with these ECG changes BNP and CNP (100 nM) increased spontaneous action potential frequency in isolated SAN myocytes by increasing L-type Ca(2+) current (I(Ca,L)) and the hyperpolarization-activated current (I(f)). BNP had no effect on right atrial myocyte APs in basal conditions; however, in the presence of isoproterenol (10nM), BNP increased atrial AP duration and I(Ca,L). Quantitative gene expression and immunocytochemistry data show that all three NP receptors (NPR-A, NPR-B and NPR-C) are expressed in the SAN and atrium. The effects of BNP and CNP on SAN and right atrial myocytes were maintained in mutant mice lacking functional NPR-C receptors and blocked by the NPR-A antagonist A71915 indicating that BNP and CNP function through their guanylyl cyclase-linked receptors. Our data also show that the effects of BNP and CNP are completely absent in the presence of the phosphodiesterase 3 inhibitor milrinone. Based on these data we conclude that NPs can increase heart rate and electrical conduction by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and inhibiting PDE3 activity.

  17. Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure

    PubMed Central

    Wang, Guogan; Wang, Pengbo; Li, Yishi; Liu, Wenxian; Bai, Shugong; Zhen, Yang; Li, Dongye; Yang, Ping; Chen, Yu; Hong, Lang; Sun, Jianhui; Chen, Junzhu; Wang, Xian; Zhu, Jihong; Hu, Dayi; Li, Huimin; Wu, Tongguo; Huang, Jie; Tan, Huiqiong; Zhang, Jian; Liao, Zhongkai; Yu, Litian; Mao, Yi; Ye, Shaodong; Feng, Lei; Hua, Yihong; Ni, Xinhai; Zhang, Yuhui; Wang, Yang; Li, Wei; Luan, Xiaojun; Sun, Xiaolu; Wang, Sijia

    2016-01-01

    Abstract The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863–2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (−7.74 ± 5.95 vs −1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34–4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.) PMID:26945407

  18. Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function

    NASA Technical Reports Server (NTRS)

    Yalcin, F.; Aksoy, F. G.; Muderrisoglu, H.; Sabah, I.; Garcia, M. J.; Thomas, J. D.

    2000-01-01

    BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.

  19. The natriuretic peptides.

    PubMed

    Baxter, Gary F

    2004-03-01

    The natriuretic peptides are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of actions throughout the body. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their volume regulating effects. These pleiotropic actions include local (autocrine/paracrine) regulatory actions of ANP and BNP within the heart, and of another natriuretic peptide, CNP, within the vessel wall. Effects on function and growth of the local tissue environment are likely to be of great importance, especially in disease states where tissue and circulating levels of ANP and BNP rise markedly. At present, the relevance of other natriuretic peptides (notably uroguanylin and DNP) to human physiology and pathology remain uncertain. Other articles in this issue of Basic Research in Cardiology review the molecular physiology of natriuretic peptide signalling, with a particular emphasis on the lessons from genetically targetted mice; the vascular activity of natriuretic peptides; the regulation and roles of natriuretic peptides in ischaemic myocardium; and the diagnostic, prognostic and therapeutic roles of natriuretic peptides in heart failure.

  20. Immunoreactive prohormone atrial natriuretic peptides 1-30 and 31-67 - Existence of a single circulating amino-terminal peptide

    NASA Technical Reports Server (NTRS)

    Chen, Yu-Ming; Whitson, Peggy A.; Cintron, Nitza M.

    1990-01-01

    Sep-Pak C18 extraction of human plasma and radioimmunoassay using antibodies which recognize atrial natriuretic peptide (99-128) and the prohormone sequences 1-30 and 31-67 resulted in mean values from 20 normal subjects of 26.2 (+/- 9.2), 362 (+/- 173) and 368 (+/- 160) pg/ml, respectively. A high correlation coefficient between values obtained using antibodies recognizing prohormone sequences 1-30 and 31-67 was observed (R = 0.84). Extracted plasma immunoreactivity of 1-30 and 31-67 both eluted at 46 percent acetonitrile. In contrast, chromatographic elution of synthetic peptides 1-30 and 31-67 was observed at 48 and 39 percent acetonitrile, respectively. Data suggest that the radioimmunoassay of plasma using antibodies recognizing prohormone sequences 1-30 and 31-67 may represent the measurement of a unique larger amino-terminal peptide fragment containing antigenic sites recognized by both antisera.

  1. Mechanism of vasodilation induced by alpha-human atrial natriuretic polypeptide in rabbit and guinea-pig renal arteries.

    PubMed Central

    Fujii, K; Ishimatsu, T; Kuriyama, H

    1986-01-01

    Effects of alpha-human atrial natriuretic polypeptide (alpha-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated. alpha-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, alpha-HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea-pig renal artery, alpha-HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA-induced contraction. alpha-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, alpha-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. In the rabbit renal artery, the effects of alpha-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nM-alpha-HANP was applied before and during the first application of 0.5 microM-NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM-NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, alpha-HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a

  2. A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

    PubMed

    Kamiya, Masataka; Sato, Naoki; Akiya, Mai; Okazaki, Hirotake; Takahashi, Yasuhiro; Mizuno, Kyoichi

    2013-01-01

    Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 μg/kg/minute, which did not control volume overload even at an increased dose of 0.025 μg/kg/minute. After a low dose of dopamine (DA) of 1.0 μg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

  3. Doppler index and plasma level of atrial natriuretic hormone are improved by optimizing atrioventricular delay in atrioventricular block patients with implanted DDD pacemakers.

    PubMed

    Toda, N; Ishikawa, T; Nozawa, N; Kobayashi, I; Ochiai, H; Miyamoto, K; Sumita, S; Kimura, K; Umemura, S

    2001-11-01

    Doppler index is the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and has clinical value as an index of combined systolic and diastolic myocardial performance. This crossover study compared the Doppler index and atrial natriuretic hormone (atrial natriuretic peptide) [ANP] between optimal (AV) delay and prolonged AV delay in patients with DDD pacemakers. The study included 14 patients (6 men, 8 women, age 78.4+/-9.3 [SD] years) with AV block with an implanted DDD pacemaker. AV delay was prolonged in a 25-ms, stepwise fashion starting from 125 ms to 250 ms. Pacing rate was set at 70 beats/min. Cardiac output (CO) was assessed by pulsed Doppler echocardiography, and optimal AV delay was defined as the AV delay at which CO was maximum, and an AV delay setting of 250 ms as prolonged AV delay. Plasma level of ANP and Doppler index determined by echocardiography were measured 1 week after programming. AV delay was switched to another AV delay and measurements were repeated after 1 week. Optimal AV delay was 159+/-19 ms. Doppler index was significantly lower at optimal AV delay than at prolonged AV delay (0.68+/-0.26 vs 0.92+/-0.30, P < 0.05). The plasma ANP level was significantly lower at optimal AV delay than at prolonged AV delay (29.0+/-30.7 vs 52.6+/-44.9 pg/mL, P < 0.05). In conclusion, the Doppler index and the plasma ANP level were significantly lower at optimal AV delay than at prolonged AV delay. This study shows the importance of the optimal AV delay setting in patients with an implanted DDD pacemaker, the Doppler index and plasma ANP levels are good indicators for optimizing AV delay.

  4. N-terminal pro-B-type Natriuretic Peptide is a Major Predictor of the Development of Atrial Fibrillation: The Cardiovascular Health Study

    PubMed Central

    Patton, Kristen K.; Ellinor, Patrick T.; Heckbert, Susan R.; Christenson, Robert H.; DeFilippi, Christopher; Gottdiener, John S.; Kronmal, Richard A.

    2014-01-01

    Background Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and health care expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, atrial fibrillation, and mortality. Methods and Results The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5,445 Cardiovascular Health Study participants, using relative risk regression for predicting prevalent AF, and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95%CI 17.9, 913.3, p< 0.001); and adjusted prevalence ratio of 147 for the highest quintile (95% CI 20.4, 1064.3, p<0.001) compared to the lowest. After a median follow up of 10 years (maximum of 16 years), there were 1,126 cases of incident AF (a rate of 2.2 per 100 person years). NT-proBNP was highly predictive of incident AF with an unadjusted hazard ratio of 5.2 (95% CI 4.3, 6.4, p < 0.001) for the development of AF for the highest quintile compared to the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes, and heart failure; with an adjusted hazard ratio of 4.0 (CI 3.2, 5.0, p< 0.001). Conclusions In a community based population of older adults, NT-pro BNP was a remarkable predictor of incident AF, independent of any other previously described risk factor. PMID:19841297

  5. Increased extracellular water measured by bioimpedance and by increased serum levels of atrial natriuretic peptide in RA patients-signs of volume overload.

    PubMed

    Straub, Rainer H; Ehrenstein, Boris; Günther, Florian; Rauch, Luise; Trendafilova, Nadezhda; Boschiero, Dario; Grifka, Joachim; Fleck, Martin

    2016-04-26

    The aim of the study is to investigate water compartments in patients with rheumatoid arthritis (RA). Acute inflammatory episodes such as infection stimulate water retention, chiefly implemented by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism due to expected water loss (sweating etc.). Since SNS and HPA axis are activated in RA, inflammation might be accompanied by water retention. Using bioimpedance analysis, body composition was investigated in 429 controls and 156 treatment-naïve RA patients between January 2008 and December 2014. A group of 34 RA patients was tested before and after 10 days of intensified therapy. Levels of pro-atrial natriuretic peptide (proANP) and expression of atrial natriuretic peptide in synovial tissue were investigated in 15 controls and 14 RA patients. Extracellular water was higher in RA patients than controls (mean ± SEM: 49.5 ± 0.3 vs. 36.7 ± 0.1, % of total body water, p < 0.0001). Plasma levels of proANP were higher in RA than controls. RA patients expressed ANP in synovial tissue, but synovial fluid levels and synovial tissue superfusate levels were much lower than plasma levels indicating systemic origin. Systolic/diastolic blood pressure was higher in RA patients than controls. Extracellular water levels did not change in RA patients despite 10 days of intensified treatment. This study demonstrates signs of intravascular overload in RA patients. Short-term intensification of anti-inflammatory therapy induced no change of a longer-lasting imprinting of water retention indicating the requirement of additional treatment. The study can direct attention to the area of volume overload.

  6. Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up-regulating natriuretic peptide receptor-A expression in the renal inner medullary collecting duct in decompensated heart failure.

    PubMed

    Liu, Chao; Chen, Ying; Kang, Yunxiao; Ni, Zhihua; Xiu, Heming; Guan, Jing; Liu, Kunshen

    2011-10-01

    In heart failure, the renal responsiveness to exogenous and endogenous atrial natriuretic peptide (ANP) is blunted. The mechanisms of renal hyporesponsiveness to ANP are complex, but one potential mechanism is decreased expression of natriuretic peptide receptor-A (NPR-A) in inner medullary collecting duct (IMCD) cells. Newly emerging evidence shows that glucocorticoids could produce potent diuresis and natriuresis in patients with heart failure, but the precise mechanism is unclear. In the present study, we found dexamethasone (Dex) dramatically increased the expression of NPR-A in IMCD cells in vitro. The NPR-A overexpression induced by Dex presented in a time- and dose-dependent manner, which emerged after 12 h and peaked after 48 h. The cultured IMCD cells were then stimulated with exogenous rat ANP. Consistent with the findings with NPR-A expression, Dex greatly increased cGMP (the second messenger for the ANP) generation in IMCD cells, which presented in a time- and dose-dependent manner as well. In rats with decompensated heart failure, Dex dramatically increased NPR-A expression in inner renal medulla, which was accompanied by a remarkable increase in renal cGMP generation, urine flow rate, and renal sodium excretion. It is noteworthy that Dex dramatically lowered plasma ANP, cGMP levels, and left ventricular end diastolic pressure. These favorable effects induced by Dex were glucocorticoid receptor (GR)-mediated and abolished by the GR antagonist 17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one (RU486). Collectively, glucocorticoids could improve renal responsiveness to ANP by up-regulating NPR-A expression in the IMCD and induce a potent diuretic action in rats with decompensated heart failure.

  7. Natriuretic peptide metabolism, clearance and degradation.

    PubMed

    Potter, Lincoln R

    2011-06-01

    Atrial natriuretic peptide, B-type natriuretic peptide and C-type natriuretic peptide constitute a family of three structurally related, but genetically distinct, signaling molecules that regulate the cardiovascular, skeletal, nervous, reproductive and other systems by activating transmembrane guanylyl cyclases and elevating intracellular cGMP concentrations. This review broadly discusses the general characteristics of natriuretic peptides and their cognate signaling receptors, and then specifically discusses the tissue-specific metabolism of natriuretic peptides and their degradation by neprilysin, insulin-degrading enzyme, and natriuretic peptide receptor-C.

  8. Influence of training habits on exercise-induced changes in plasma atrial and brain natriuretic peptide and urinary excretion of aquaporin-2 in healthy man.

    PubMed

    Bentzen, H; Pedersen, R S; Nyvad, O; Pedersen, E B

    2002-01-01

    The purpose of this study was to quantify the influence of training habits on the changes in plasma atrial natriuretic peptide (ANP), plasma brain natriuretic peptide (BNP) and urine aquaporin-2 (u-AQP2) during exercise by studying trained and untrained healthy subjects. Eleven trained subjects (7 males, 4 females) and 10 untrained subjects (8 males, 2 females) performed a maximal aerobic exercise test. ANP and BNP were determined every 3 min and at maximum exercise by radioimmunoassay (RIA), and u-AQP2 was determined before and after the exercise test by RIA. The absolute increase in ANP during exercise was higher in the trained subjects (trained subjects: 5.6 pmol/L; untrained subjects: 2.4 pmol/L, p < 0.05) and was positively correlated to ANP at rest (p < 0.03). The maximum absolute increase in BNP during exercise was the same in the two groups (trained subjects: 0.5 pmol/L; untrained subjects: 0.6 pmol/L, NS) and tended to correlate positively with resting BNP in the trained subjects (p = 0.07). Exercise did not change u-AQP2 excretion in either trained subjects (rest: 372 ng/mmol creatinine; exercise: 314 ng/mmol creatinine, NS) or untrained subjects (rest: 263 ng/mmol creatinine; exercise: 338 ng/mmol creatinine, NS). The absolute increase in ANP during exercise was higher in trained subjects than in untrained subjects and was positively correlated to ANP at rest. This might reflect the normal cardiovascular adaptation to exercise. The increase in BNP during exercise was unrelated to training habits. Training habits did not affect the u-AQP2 excretion during exercise.

  9. Measurement of cytoplasmic free Ca2+ concentration in rabbit aorta using the photoprotein, aequorin. Effect of atrial natriuretic peptide on agonist-induced Ca2+ signal generation.

    PubMed Central

    Takuwa, Y; Rasmussen, H

    1987-01-01

    Addition of norepinephrine, angiotensin II, or histamine leads to a transient rise in the cytoplasmic Ca2+ concentration ([Ca2+]i), as measured with aequorin, in rabbit aortic strips. Each induces a [Ca2+]i transient which peaks in 2 min and then falls either back to baseline (angiotensin II) or to a plateau (norepinephrine and histamine). The [Ca2+]i transient is due to the mobilization of Ca2+ from a caffeine-sensitive, intracellular pool. An elevation of [K+] to 35 mM leads to a monotonic sustained rise in [Ca2+]i which depends entirely on extracellular Ca2+, but an increase to 100 mM leads to a [Ca2+]i transient from the mobilization of intracellular Ca2+. Atrial natriuretic peptide does not alter basal [Ca2+]i nor inhibit the [Ca2+]i transient induced by either histamine or angiotensin II, but blocks that induced by norepinephrine, and blocks the plateau phase induced by either histamine or norepinephrine. The peptide inhibits the contractile response to all three agonists and to K+. PMID:2439545

  10. Alpha(1)- and beta-adrenoceptor stimulation differentially activate p38-MAPK and atrial natriuretic peptide production in the perfused amphibian heart.

    PubMed

    Aggeli, Ioanna-Katerina S; Gaitanaki, Catherine; Lazou, Antigone; Beis, Isidoros

    2002-08-01

    We investigated the activation of p38-MAPK by various adrenergic agents in the perfused Rana ridibunda heart. Phenylephrine (50 micromol l(-1)) rapidly induced the differential activation of all three mitogen-activated protein kinase (MAPK) subfamilies (ERK, JNKs and p38-MAPK) in this experimental system. Focusing on p38-MAPK response to phenylephrine, we found that the kinase phosphorylation reached maximal values at 30 s, declining thereafter to basal values at 15 min. p38-MAPK activation by phenylephrine was verified as exclusively alpha(1)-AR-mediated. Furthermore, SB203580 (1 micromol l(-1)) abolished the kinase phosphorylation by phenylephrine. Isoproterenol (50 micromol l(-1)) was also shown to activate p38-MAPK in a time- and temperature-dependent manner. A marked, sustained p38-MAPK activation profile was observed at 25 degrees C, while at 18 degrees C the kinase response to isoproterenol was modest. Isoproterenol effect on p38-MAPK stimulation was beta-AR-mediated. Immunohistochemical studies revealed the enhanced presence of phosphorylated p38-MAPK and atrial natriuretic peptide (ANP) in both phenylephrine- and isoproterenol-stimulated hearts, a reaction completely blocked by the respective specific antagonists, or the specific p38-MAPK inhibitor SB203580. These findings indicate a functional correlation between p38-MAPK activation and ANP accumulation in the perfused amphibian heart.

  11. Atrial natriuretic peptide-conjugated chitosan-hydrazone-mPEG copolymer nanoparticles as pH-responsive carriers for intracellular delivery of prednisone.

    PubMed

    M, Gover Antoniraj; C, Senthil Kumar; Henry, Linda Jeeva Kumari; Natesan, Subramanian; Kandasamy, Ruckmani

    2017-02-10

    A chitosan-hydrazone-mPEG (CH-Hz-mPEG) copolymer which is stable at extracellular pH and cleaves at slightly acidic intracellular pH was synthesized and characterized. Blank polymeric nanoparticles (B-PNPs) and prednisone-loaded polymeric nanoparticles (P-PNPs) were then formulated by dialysis/precipitation method. The cell-specific ligand, atrial natriuretic peptide (ANP) was then conjugated to P-PNPs (ANP-P-PNPs) by a coupling reaction. Particle size and morphological analyses revealed uniform spherical shape of PNPs. In vitro pH dependent degradation of PNPs was investigated. Drug release profile of ANP-P-PNPs indicated a slow release of prednisone at pH 7.4, but a rapid release at pH 5.0 due to the cleavage of hydrazone linkage. Cytotoxicity studies demonstrated greater compatibility of B-PNPs compared to ANP-P-PNPs. Cellular internalization of ANP-P-PNPs was higher than P-PNPs owing to receptor-mediated endocytosis. The results from this investigation support the hypothesis that chitosan based ANP-P-PNPs could act as an intracellular pH-responsive and targeted drug delivery system.

  12. The guanylyl cyclase-A receptor transduces an atrial natriuretic peptide/ATP activation signal in the absence of other proteins.

    PubMed

    Wong, S K; Ma, C P; Foster, D C; Chen, A Y; Garbers, D L

    1995-12-22

    Attempts to activate partially purified preparations of the guanylyl cyclase-A (GC-A) receptor with atrial natriuretic peptide (ANP) have previously failed, leading to speculation that essential cofactors are lost during purification procedures. The receptor was modified to contain the FLAG epitope (DYKDDDDK), expressed in Sf9 cells, and purified to apparent homogeneity (4.3 mumol cyclic GMP formed/min/mg protein; 5.8 mmol 125I-ANP binding site/mg protein) by a combination of immunoaffinity, Q-Sepharose FF, and wheat germ agglutinin batch chromatography. High initial protein/detergent ratios, the presence of glycerol (40%), and the inclusion of protein phosphatase inhibitors in all buffers resulted in the purification of a receptor that continued to transduce the ANP/ATP activation signal. Both native and purified GC-A contained a single class of high affinity ANP binding sites (Kd = 60 pM) and an equivalent EC50 for ATP (0.3 mM). Positive cooperativity as a function of MnGTP was retained during purification. Thus, GC-A is capable of transducing a ligand binding signal in the absence of other proteins.

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

    PubMed Central

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

    2017-01-01

    Remodelling in the atria could appear as a result of hypertension, diabetes or ischaemic heart disease. Galectin-3 (Gal-3) is a mediator of profibrotic pathways and a potential biomarker of cardiac remodelling. We prospectively recruited consecutive patients undergoing elective cardiac surgery. Preoperative Gal-3 levels were determined from serum samples, and the presence of fibrosis was assessed from atrial appendage tissue samples obtained during cardiac surgery. We included 100 patients with aortic valve or ischaemic heart diseases and 15 controls with permanent AF. Gal-3 levels were associated with sex, left atrial volume, previous cardiac disease, diabetes mellitus, hypertension, NYHA and NT-proBNP. We observed differences in serum Gal-3 concentrations between patients and controls with permanent AF (p = 0.020). We performed ROC curves related to fibrosis and established a cutoff point for Gal-3 >13.65 ng/ml. Multivariate analyses showed previous cardiac disease, NYHA scale and high Gal-3 to be independent predictors of fibrosis. After adjustment for confounding factors, atrial fibrosis remained the only independent factor for the development of AF (p = 0.022). High Gal-3 serum levels predict fibrosis of the atrial appendage. NYHA scale and previous cardiac disease were also associated with tissue fibrosis in patients undergoing surgery. Atrial fibrosis was the only independent predictor for post-operative AF occurrence in our model after correcting for confounding factors. PMID:28079145

  14. Atrial natriuretic peptide down-regulates LPS/ATP-mediated IL-1β release by inhibiting NF-kB, NLRP3 inflammasome and caspase-1 activation in THP-1 cells.

    PubMed

    Mezzasoma, Letizia; Antognelli, Cinzia; Talesa, Vincenzo Nicola

    2016-02-01

    Atrial natriuretic peptide (ANP) is an hormone/paracrine/autocrine factor regulating cardiovascular homeostasis by guanylyl cyclase natriuretic peptide receptor (NPR-1). ANP plays an important role also in regulating inflammatory and immune systems by altering macrophages functions and cytokines secretion. Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine involved in a wide range of biological responses, including the immunological one. Unlike other cytokines, IL-1β production is rigorously controlled. Primarily, NF-kB activation is required to produce pro-IL-1β; subsequently, NALP3 inflammasome/caspase-1 activation is required to cleave pro-IL-1β into the active secreted protein. NALP3 is a molecular platform capable of sensing a large variety of signals and a major player in innate immune defense. Due to their pleiotropism, IL-1β and NALP3 dysregulation is a common feature of a wide range of diseases. Therefore, identifying molecules regulating IL-1β/NALP3/caspase-1 expression is an important step in the development of new potential therapeutic agents. The aim of our study was to evaluate the effect of ANP on IL-1β/NALP3/caspase-1 expression in LPS/ATP-stimulated human THP1 monocytes. We provided new evidence of the direct involvement of ANP/NPR-1/cGMP axis on NF-kB/NALP3/caspase-1-mediated IL-1β release and NF-kB-mediated pro-IL-1β production. In particular, ANP inhibited both NF-kB and NALP3/caspase-1 activation leading to pro- and mature IL-1β down-regulation. Our data, pointing out a modulatory role of this endogenous peptide on IL-1β release and on NF-kB/NALP3/caspase-1 activation, indicate an important anti-inflammatory and immunomodulatory effect of ANP via these mechanisms. We suggest a possible employment of ANP for the treatment of inflammatory/immune-related diseases and IL-1β/NALP3-associated disorders, affecting millions of people worldwide.

  15. Effects of immobilizations stress with or without water immersion on the expression of atrial natriuretic peptide in the hearts of two rat strains

    PubMed Central

    Slavikova, Jana; Mistrova, Eliska; Klenerova, Vera; Kruzliak, Peter; Caprnda, Martin; Hynie, Sixtus; Sida, Pavel; Dvorakova, Magdalena Chottova

    2016-01-01

    Atrial natriuretic peptide (ANP) is produced and released by mammalian cardiomyocytes and induces natriuresis, diuresis, and lowering of blood pressure. The present study examined localization of ANP and a possible role of the hypothalamic-pituitary-adrenal axis (HPA) activity on the expression of proANP gene in the heart. The Sprague Dawley (SD) and Lewis (LE) rat strains were used. The animals were exposed to the two types of stress: immobilization and immobilization combined with water immersion for 1 hour. Localization of ANP was detected by immunohistochemistry and expression of the proANP mRNA by real-time qPCR in all heart compartments of control and stressed animals after 1 and 3 hours after stress termination (IS1, IS3, ICS1, and ICS3). Relatively high density of ANP-immunoreactivity was observed in both atria of both rat strains. In control rats of both strains, the expression of the proANP mRNA was higher in the atria than in ventricles. In SD rats with the intact HPA axis, an upregulation of ANP gene expression was observed in the right atrium after IS1, in both atria and the left ventricle after IS3 and in the left atrium and the left ventricle after ICS3. In LE rats with a blunted reactivity of the HPA axis, no increase or even a downregulation of the gene expression was observed. Thus, acute stress-induced increase in the expression of the proANP gene is related to the activity of the HPA axis. It may have relevance to ANP-induced protection of the heart. PMID:27508036

  16. Recombinant Atrial Natriuretic Peptide Prevents Aberrant Ca2+ Leakage through the Ryanodine Receptor by Suppressing Mitochondrial Reactive Oxygen Species Production Induced by Isoproterenol in Failing Cardiomyocytes

    PubMed Central

    Susa, Takehisa; Nanno, Takuma; Ishiguchi, Hironori; Myoren, Takeki; Nishimura, Shigehiko; Kato, Takayoshi; Hino, Akihiro; Oda, Tetsuro; Okuda, Shinichi; Yamamoto, Takeshi; Yano, Masafumi

    2016-01-01

    Catecholamines induce intracellular reactive oxygen species (ROS), thus enhancing diastolic Ca2+ leakage through the ryanodine receptor during heart failure (HF). However, little is known regarding the effect of atrial natriuretic peptide (ANP) on ROS generation and Ca2+ handling in failing cardiomyocytes. The aim of the present study was to clarify the mechanism by which an exogenous ANP exerts cardioprotective effects during HF. Cardiomyocytes were isolated from the left ventricles of a canine tachycardia-induced HF model and sham-operated vehicle controls. The degree of mitochondrial oxidized DNA was evaluated by double immunohistochemical (IHC) staining using an anti-VDAC antibody for the mitochondria and an anti-8-hydroxy-2′-deoxyguanosine antibody for oxidized DNA. The effect of ANP on ROS was investigated using 2,7-dichlorofluorescin diacetate, diastolic Ca2+ sparks assessed by confocal microscopy using Fluo 4-AM, and the survival rate of myocytes after 48 h. The double IHC study revealed that isoproterenol (ISO) markedly increased oxidized DNA in the mitochondria in HF and that the ISO-induced DNA damage was markedly inhibited by the co-presence of ANP. ROS production and Ca2+ spark frequency (CaSF) were increased in HF compared to normal controls, and were further increased in the presence of ISO. Notably, ANP significantly suppressed both ISO-induced ROS and CaSF without changing sarcoplasmic reticulum Ca2+ content in HF (p<0.01, respectively). The survival rate after 48 h in HF was significantly decreased in the presence of ISO compared with baseline (p<0.01), whereas it was significantly improved by the co-presence of ANP (p<0.01). Together, our results suggest that ANP strongly suppresses ISO-induced mitochondrial ROS generation, which might correct aberrant diastolic Ca2+ sparks, eventually contributing to the improvement of cardiomyocyte survival in HF. PMID:27657534

  17. Reversibly Bound Chloride in the Atrial Natriuretic Peptide Receptor Hormone Binding Domain: Possible Allosteric Regulation and a Conserved Structural Motif for the Chloride-binding Site

    SciTech Connect

    Ogawa, H.; Qiu, Y; Philo, J; Arakawa, T; Ogata, C; Misono, K

    2010-01-01

    The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.

  18. Relationship between Doppler transmitral flow velocity pattern and plasma atrial and brain natriuretic peptide concentrations in anuric patients on maintenance hemodialysis.

    PubMed

    Ito, Shigenori; Murai, Sumiko; Takada, Norio; Ozasa, Atsushi; Hanada, Mayumi; Sugiyama, Masaya; Suzuki, Kaoru; Nagae, Yuji; Inagaki, Toshiaki; Takeda, Yutaka; Fukutomi, Tatsuya; Joh, Takashi

    2006-05-01

    Plasma atrial (ANP) and brain (BNP) natriuretic peptide levels were compared to determine if transmitral flow velocity pattern is an instantaneous marker of body fluid balance in anuric patients on hemodialysis (HD). We measured plasma ANP and BNP levels and performed Doppler echocardiography in 38 anuric patients before and after HD. Patients with valvular disease, left ventricular systolic dysfunction having a fractional shortening < 0.3, arrhythmia, or left ventricular hypertrophy were excluded. The relationships between plasma ANP or BNP levels and the transmitral flow velocity pattern were evaluated. We also determined if the magnitude of the decrease in plasma ANP level was related to that in the early peak of transmitral flow velocity (peak E). The mean age of the subjects was 61.1 +/- 9.7 years. The ANP level of 213.6 +/- 146.1 pg/mL was related to peak E of 61 +/- 15 cm/s before HD (R = 0.504, P < 0.001), but not after HD. Plasma ANP level was not related to peak late transmitral flow velocity (peak A) or peak E/peak A before or after HD. BNP level was not related to the transmitral flow velocity pattern. The magnitude of decrease in hANP level during HD was significantly related to that in peak E (R = 0.342, P < 0.05). Before HD, peak E was related to the plasma ANP level, reflecting volume overload. Change in peak E showed a weak relationship with that of plasma ANP level in the same HD patient. The measurement of peak E during a HD session may potentially enable the assessment of hydration status during HD.

  19. Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

    PubMed

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei; Kangawa, Kenji

    2017-02-07

    Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

  20. Atrial natriuretic peptide: A novel mediator for TGF-β1-induced epithelial-mesenchymal transition in 16HBE-14o and A549 cells.

    PubMed

    Chu, Shuyuan; Zhang, Xiufeng; Sun, Yabing; Yu, Yuanyuan; Liang, Yaxi; Jiang, Ming; Huang, Jianwei; Ma, Libing

    2017-02-13

    Atrial natriuretic peptide (ANP) is increasingly expressed on airway and inhibits pulmonary arterial remodeling. However, the role of ANP in remodeling of respiratory system is still unclear. The role of ANP on airway remodeling and the possible mechanism was explored in this study. Both human bronchial epithelial 16HBE-14o cells and alveolar epithelial A549 cells were stimulated by TGF-β1, ANP, cGMP inhibitor, PKG inhibitor, and cGMP analogue. The expressions of epithelial markers, mesenchymal markers, and Smad3 were assessed by quantitative real-time PCR and western blotting. Immunohistochemical staining was employed to assess Smad3 expression once it was silenced by siRNA in 16HBE-14o or A549 cells. Our results showed that the mRNA and protein expressions of E-Cadherin were decreased, whereas α-SMA expressions were increased after induction by TGF-β1 in 16HBE-14o and A549 cells. The E-Cadherin expressions were increased and α-SMA expressions were decreased after ANP stimulation. Inhibition of cGMP or PKG decreased E-Cadherin expression but increased α-SMA expression, which could be reversed by cGMP analogue. Moreover, the phosphorylated Smad3 expression was consistent with α-SMA expression. After smad3 was silenced, Smad3 was mostly expressed in cytoplasm instead of nucleus as non-silenced cells during epithelial-mesenchymal transition (EMT). In conclusion, ANP inhibits TGF-β1-induced EMT in 16HBE-14o and A549 cells through cGMP/PKG signaling, by which it targets TGF-β1/Smad3 via attenuating phosphorylation of Smad3. These findings suggest the potential of ANP in the treatment on pulmonary diseases with airway remodeling.

  1. Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.

    PubMed Central

    Cody, R J; Atlas, S A; Laragh, J H; Kubo, S H; Covit, A B; Ryman, K S; Shaknovich, A; Pondolfino, K; Clark, M; Camargo, M J

    1986-01-01

    We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11 +/- 0.9 fmol/ml in NL and 71 +/- 9.9 in CHF (P less than 0.01); the latter with twofold right ventricular increment (P less than 0.05). In NL, ANF infusion of 0.10 microgram/kg per min (40 pmol/kg per min) induced increases (P less than 0.05) of absolute (from 160 +/- 23 to 725 +/- 198 mueq/min) and fractional (1-4%) sodium excretion, urine flow rate (from 10 +/- 1.6 to 20 +/- 2.6 ml/min), osmolar (from 3.2 +/- 0.6 to 6.8 +/- 1.2 ml/min) and free water (from 6.8 +/- 1.6 to 13.6 +/- 1.6 ml/min) clearances, and filtration fraction (from 20 +/- 1 to 26 +/- 2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P less than 0.01). Systolic blood pressure fell (from 112 +/- 3 to 104 +/- 5 mmHg, P less than 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11 +/- 1 to 7 +/- 1 mmHg, P less than 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P less than 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P less than 0.05) but not in CHF. Images PMID:2945832

  2. Usefulness of early diastolic mitral annular velocity to predict plasma levels of brain natriuretic peptide and transient heart failure development after device closure of atrial septal defect.

    PubMed

    Masutani, Satoshi; Taketazu, Mio; Mihara, Chihiro; Mimura, Yuko; Ishido, Hirotaka; Matsunaga, Tamotsu; Kobayashi, Toshiki; Senzaki, Hideaki

    2009-12-15

    Device closure of atrial septal defect (ASD) is sometimes followed by elevation of plasma brain natriuretic peptide (BNP), a marker of heart failure, and progression to heart failure. This study tested the hypothesis that the underlying diastolic dysfunction, assessed on tissue Doppler images (TDI) before device closure, can predict BNP level after ASD closure. The study subjects were 39 consecutive patients (age 27.5 +/- 16.3 years, range 5 to 63) who underwent device closure for ASD. Echocardiographic evaluation using TDI and 2-dimensional and pulse wave Doppler were performed, together with plasma BNP measurement 1 day before and 2 days after ASD closure. Before ASD closure, an age-dependent decrease was noted in left ventricular relaxation, assessed by early diastolic mitral annular velocity. ASD closure resulted in a decrease in early diastolic mitral annular velocity (from 14.7 to 12.3 cm/s, p <0.05) despite an increase in the left ventricular dimension (84% to 92% vs normal, p <0.05). These changes were associated with a parallel increase in BNP (17.9 to 48.4 pg/ml, p <0.05). Stepwise multivariate linear regression identified early diastolic mitral annular velocity before ASD closure and age as independent predictors of BNP levels after ASD closure (p <0.05). Consistent with this result, 2 patients with the lowest early diastolic mitral annular velocity developed exertional dyspnea after the procedure. In conclusion, our results indicate that TDI measurements could be useful to detect underlying diastolic dysfunction that can potentially cause heart failure after ASD closure and emphasize the importance of ASD closure at a young age before impairment of left ventricular relaxation.

  3. Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts. Immunohistochemical study of the endomyocardial biopsy specimens.

    PubMed

    Takemura, G; Fujiwara, H; Horike, K; Mukoyama, M; Saito, Y; Nakao, K; Matsuda, M; Kawamura, A; Ishida, M; Kida, M

    1989-11-01

    To investigate the mechanism of expression of atrial natriuretic polypeptide (ANP) in human ventricles, we conducted an immunohistochemical study of ANP in biventricular endomyocardial biopsy specimens obtained from a total of 49 patients with cardiac dilatation due to dilated cardiomyopathy (21 patients), postmyocarditis (18 patients), or volume overload (five patients) and subjects with no dilatation as controls (five patients). Four-micron thick sections were stained by an indirect immunoperoxidase method using monoclonal antibody to alpha-human ANP as the primary antibody. The frequency of ANP-present myocytes was calculated in each specimen and compared with clinical, echocardiographic, hemodynamic, angiographic, and histologic parameters. ANP-present myocytes were noted in all of the 21 patients with dilated cardiomyopathy, in 11 of the 18 patients with postmyocarditis, in four of the five patients with volume overload, and in zero of the five controls. The mean percentage of ANP-present myocytes was significantly greater in the left-side specimens (35 +/- 37%) than in the right-side ones (2 +/- 4%). The percentage of ANP-present myocytes in the left-side specimens significantly correlated with peak systolic or end-diastolic wall stress (r = 0.67 and 0.58), left ventricular end-systolic or end-diastolic volume index (r = 0.75 and 0.69), or left ventricular end-diastolic pressure (r = 0.42) and inversely correlated with ejection fraction (r = -0.73), systolic left ventricular wall thickness (r = -0.58), or cardiac index (r = -0.30). Expression of ANP was rarely seen in the cases with normal wall stresses, normal ejection fraction, normal volume, or normal myocyte size. However, it was seen frequently even in hearts with normal levels of left ventricular end-diastolic pressure and cardiac index (compensated hearts). The percent of ANP-present myocytes in both sides significantly correlated with size of myocytes (r = 0.48 at right and r = 0.57 at left side) or

  4. Serum atrial natriuretic peptide (ANP) as an objective indicator for the diagnosis of neurogenic shock: animal experiment and human case report.

    PubMed

    Zhao, Min-Zhu; Li, Yong-Guo; Zhang, Peng; Xiong, Jin-Cheng; Zhu, Shi-Sheng; Xiao, Xuan; Li, Jian-Bo

    2017-03-01

    In forensic medicine, the diagnosis of death due to neurogenic shock is considered to be an aporia, as lacking objective indicators and presenting atypical symptoms in autopsy. Medico-legal disputes and complaints occasionally result from this ambiguity. To explore potential objective indicators of neurogenic shock, we set up a model of neurogenic shock by applying an external mechanical force on the carotid sinus baroreceptor in rabbits. The serum atrial natriuretic peptide (ANP) level was measured by radioimmunoassay in the control group (n = 8), survival group (n = 15) and death group (n = 5) both before and after the insult. The serum ANP level showed a significant increase after the insult in the death group compared with the serum obtained before the insult (P = 0.006), while the serum ANP level after the insult in the survival group and control group was not statistically significant compared with the serum obtained before the insult (P = 0.332 and P = 0.492, respectively). To verify the repeatability of the model and the postmortem behavior of serum ANP, five healthy adult rabbits underwent the same procedure as the experimental group. The mortality rate was consistent with the former experiment (20 %). There were no significant changes in serum ANP level in vitro and in vivo (within 48 and 24 h, respectively). But there was a significant decrease in serum ANP level at 48 h postmortem in vivo (P = 0.001). A female patient who expired due to neurogenic shock during a hysteroscopy was reported. Neither fatal primary disease nor evidence for mechanical injuries or intoxication was found according to the autopsy. The serum ANP level was assayed as a supplementary indicator and was found to be three-fold higher than the normal maximum limit. Combined with the animal experiment, this case highlights that serum ANP has the potential to be an objective indicator for the diagnosis of death due to neurogenic shock.

  5. Cyclical stretch induces structural changes in atrial myocytes.

    PubMed

    De Jong, Anne Margreet; Maass, Alexander H; Oberdorf-Maass, Silke U; De Boer, Rudolf A; Van Gilst, Wiek H; Van Gelder, Isabelle C

    2013-06-01

    Atrial fibrillation (AF) often occurs in the presence of an underlying disease. These underlying diseases cause atrial remodelling, which make the atria more susceptible to AF. Stretch is an important mediator in the remodelling process. The aim of this study was to develop an atrial cell culture model mimicking remodelling due to atrial pressure overload. Neonatal rat atrial cardiomyocytes (NRAM) were cultured and subjected to cyclical stretch on elastic membranes. Stretching with 1 Hz and 15% elongation for 30 min. resulted in increased expression of immediate early genes and phosphorylation of Erk and p38. A 24-hr stretch period resulted in hypertrophy-related changes including increased cell diameter, reinduction of the foetal gene program and cell death. No evidence of apoptosis was observed. Expression of atrial natriuretic peptide, brain natriuretic peptide and growth differentiation factor-15 was increased, and calcineurin signalling was activated. Expression of several potassium channels was decreased, suggesting electrical remodelling. Atrial stretch-induced change in skeletal α-actin expression was inhibited by pravastatin, but not by eplerenone or losartan. Stretch of NRAM results in elevation of stress markers, changes related to hypertrophy and dedifferentiation, electrical remodelling and cell death. This model can contribute to investigating the mechanisms involved in the remodelling process caused by stretch and to the testing of pharmaceutical agents.

  6. Plasma cardiac natriuretic peptide determination as a screening test for the detection of patients with mild left ventricular impairment.

    PubMed Central

    Omland, T.; Aakvaag, A.; Vik-Mo, H.

    1996-01-01

    OBJECTIVE: To determine the usefulness of measuring the cardiac natriuretic peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide, as screening tests for identifying patients with mild left ventricular impairment. DESIGN: Cross-sectional evaluation of the diagnostic accuracy of the cardiac natriuretic peptides. SETTING: Cardiac catheterisation unit, Norwegian central hospital. PATIENTS: A consecutive series of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One hundred and twenty eight of these patients had a history of previous myocardial infarction. MAIN OUTCOME MEASURES: The presence of normal and impaired left ventricular function, as evaluated by logistic regression analysis and estimation of the area under the receiver operating characteristic (ROC) curve (an index of overall diagnostic accuracy). Ventricular function was assessed by the measurement of left ventricular end diastolic pressure and angiographically determined left ventricular ejection fraction. RESULTS: Logistic regression analysis showed that plasma brain natriuretic peptide was the best predictor of increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001), decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the combination of left ventricular ejection fraction < or = 45% and left ventricular end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC function for the detection of left ventricular dysfunction were 0.789 for brain natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N-terminal pro-atrial natriuretic factor. CONCLUSIONS: Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and

  7. Myopericarditis with predominantly right ventricular involvement with normal B-type natriuretic peptide and cardiac tamponade as the initial manifestation of systemic lupus erythematosus.

    PubMed

    Manautou, Luis; Jerjes-Sanchez, Carlos; Meraz, Manuel; Perez-Garcia, Luis F; Diaz-Cid, Antonio; de la Peña-Almaguer, Erasmo; Avila, Cesar; Sanchez, Luis

    2014-08-01

    A previously healthy young man presented with a 12-hour history of sudden dyspnea and severe chest pain at rest. Initial findings of physical examination, electrocardiogram and chest radiography showed typical pericarditis and clinical instability. Echocardiogram revealed small pericardial effusion with right ventricle dilatation. The patient was admitted in the ICU; a new echocardiogram revealed moderate pericardial effusion and diagnosis of pericarditis complicated with acute cardiac tamponade was established. The patient transiently improved after pericardial window. In the following hours, the diagnosis of myocarditis with predominantly right ventricular involvement (MPRVI) with severe right heart failure was supported by clinical, chest radiography and echocardiogram data, despite normal B-type natriuretic peptide. On day 2, cardiac troponin I detection was observed. By day 3, B-type natriuretic peptide in the range of ventricular dysfunction was identified. Cardiovascular magnetic resonance findings supported the diagnosis of MPRVI. A systematic MEDLINE/PubMed from 1993 to 2013 does not identify any cases of MPRVI related to systemic lupus erythematosus. Simultaneous acute MPRVI with normal B-type natriuretic peptide and acute cardiac tamponade heralding the diagnosis of systemic lupus erythematosus, to the best of our knowledge, has not been previously described.

  8. Signaling Pathways Involved in Renal Oxidative Injury: Role of the Vasoactive Peptides and the Renal Dopaminergic System

    PubMed Central

    Rukavina Mikusic, N. L.; Kravetz, M. C.; Kouyoumdzian, N. M.; Della Penna, S. L.; Rosón, M. I.; Fernández, B. E.; Choi, M. R.

    2014-01-01

    The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation. PMID:25436148

  9. Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

    PubMed

    Claessens, Y-E; Schmidt, J; Batard, E; Grabar, S; Jegou, D; Hausfater, P; Kierzek, G; Guérin, S; Pourriat, J-L; Dhainaut, J-F; Ginsburg, C

    2010-06-01

    Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

  10. Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic factor in heart failure: a double blind, randomised comparison of metoprolol and a third generation vasodilating beta blocker.

    PubMed Central

    Sanderson, J. E.; Chan, W. W.; Hung, Y. T.; Chan, S. K.; Shum, I. O.; Raymond, K.; Woo, K. S.

    1995-01-01

    OBJECTIVES--This study examines the acute effects of two differing beta adrenergic blocking agents (metoprolol and a third generation vasodilating beta blocker) on plasma concentrations of atrial natriuretic factor (ANF), brain (ventricular) natriuretic factor (BNF), and haemodynamic variables in patients with heart failure. SETTING--University teaching hospital. METHODS--20 patients with impaired left ventricular systolic function [ejection fraction 32 (SEM 2.3)%] were randomised in a double blind manner to receive either oral metoprolol 6.25 mg twice daily or celiprolol 25 mg daily. Haemodynamic variables were evaluated by Swan-Ganz pulmonary artery catheter over 24 hours. ANF and BNF concentrations were measured at baseline, 5 h, and 24 h by radioimmunoassay. RESULTS--At baseline ANF and BNF concentrations were considerably raised compared to the normal range. Treatment with metoprolol caused ANF to rise further to 147% of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029). This was associated with a small but non-significant rise in pulmonary capillary wedge pressure. Cardiac output and systemic vascular resistance were unchanged at 24 h. In contrast, after celiprolol ANF fell to 90% of basal levels at 5 h and to 74% of basal level at 24 h (P = 0.019), associated with a small but non-significant fall in pulmonary capillary wedge pressure [-3.3 (2.7) mm Hg] and systemic vascular resistance, and rise in cardiac output from 3.2 (0.2) to 4.0 (0.4) l/min (P = 0.04). BNF concentrations rose to 112% of baseline at 5 h (P = 0.09) after metoprolol but fell slightly, to 91% of baseline values, after celiprolol (NS). CONCLUSIONS--Metoprolol, even in very low doses (6.25 mg), produced a rise in ANF and BNF, although minimal haemodynamic changes were detected. In contrast, a vasodilating beta blocker was associated with a significant fall in ANF and BNF and a small rise in cardiac output. This study confirms both the advantages of vasodilating beta blockers

  11. Effect of atrial natriuretic factor and 8-bromo cyclic guanosine 3':5'-monophosphate on ( sup 3 H)acetylcholine outflow from myenteric-plexus longitudinal muscle of the guinea pig

    SciTech Connect

    Matusak, O.; Kuchel, O.; Hamet, P. )

    1991-04-01

    We report that atrial natriuretic factor (ANF) inhibits electrically induced cholinergic twitches of longitudinal muscle in whole intestinal segments and myenteric-plexus longitudinal muscle (MPLM) strips from the guinea pig ileum. To elucidate the possible presynaptic mechanism of ANF's action, we studied spontaneous and stimulation-evoked radiolabeled acetylcholine (ACh) outflow from MPLM after incubation with ({sup 3}H)choline. We developed a method of mounting and treating MPLM preparations, which allowed us, at the same time, to record isometric contractions and to determine ({sup 3}H)ACh outflow upon electrical stimulation by a train of three pulses. ANF (5 x 10{sup {minus} 8}M), norepinephrine (2 x 10{sup {minus} 7}) M and 8-bromoguanosine 3':5'-cyclic monophosphate (10{sup {minus} 3} M) in nearly equieffective concentrations caused a similar inhibition of cholinergic twitches. However, ANF had no effect on ({sup 3}H)ACh outflow, whereas norepinephrine was found to suppress ({sup 3}H)ACh outflow and 8-bromoguanosine 3':5'-cGMP to enhanced ({sup 3}H)ACh outflow. ANF (5 x 10{sup {minus} 8} M) caused a 7.0-fold increase of cGMP over control values, predominantly in muscle layers, whereas Escherichia coli heat-stable toxin (12.5 U/ml) elicited a 35-fold increment of cGMP in the extramuscular layer. Thus, ANF is able to elevate cGMP in intestinal smooth muscle and to inhibit cholinergic contractions of MPLM. This inhibition is mimicked by exogenous cGMP and by endogenously generated cyclic nucleotides. We suggest that the depressive action of ANF on cholinergic contractions of MPLM is mediated via its postsynaptic impact implicating elevation of cGMP in smooth muscle.

  12. Long-term outcome of patients with triphasic mitral flow with a mid-diastolic L wave: prognostic role of left atrial volume and N-terminal pro-brain natriuretic peptide.

    PubMed

    Kim, Sung-Ai; Son, Jungwoo; Shim, Chi-Young; Choi, Eui-Young; Ha, Jong-Won

    2017-03-27

    A mid-diastolic L wave has been recognized as a marker of advanced left ventricular (LV) diastolic dysfunction. However, its prognostic implication is unclear. This study assessed long-term prognosis and independent predictors of adverse outcomes in patients with a mid-diastolic L wave. A total of 144 consecutive patients (mean age 63 ± 12 years, 88 female) with a mid-diastolic L wave of ≥0.2 m/s and in sinus rhythm were identified. Patients with significant valvular heart disease, low LV ejection fraction and arrhythmias were excluded. Subjects were followed up for cardiovascular (CV) mortality and hospitalization for heart failure (HF). During follow-up for a median of 44 months (1-76), CV deaths and hospitalization for HF occurred in 41 (28%) patients. In multivariate Cox analysis, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.001), log N-terminal pro-brain natriuretic peptide (NT-proBNP)(HR 3.81; 95% CI 1.78-8.15; p = 0.001), and left atrial volume index (HR 1.02; 95% CI 1.01-1.04; p = 0.019) were independent predictors of adverse outcomes in patients with a mid-diastolic L wave. In a stepwise model, NT-proBNP showed an incremental prognostic value for prediction of adverse outcomes when added to the clinical and echocardiographic parameters (Chi square from 30.1 to 41.1, p < 0.001). Patients with a mid-diastolic L wave and clinical, biochemical, and echocardiographic evidence of advanced diastolic dysfunction showed poor long-term clinical outcome.

  13. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

    PubMed Central

    Dietrich, Johannes W.; Müller, Patrick; Schiedat, Fabian; Schlömicher, Markus; Strauch, Justus; Chatzitomaris, Apostolos; Klein, Harald H.; Mügge, Andreas; Köhrle, Josef; Rijntjes, Eddy; Lehmphul, Ina

    2015-01-01

    Background Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Methods Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Results Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. Conclusion This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms. PMID:26279999

  14. Isolated Atrial Amyloidosis in Patients with Various Types of Atrial Fibrillation.

    PubMed

    Sukhacheva, T V; Eremeeva, M V; Ibragimova, A G; Vaskovskii, V A; Serov, R A; Revishvili, A Sh

    2016-04-01

    The myocardium of the right and left atrial appendages (auricles) in patients with paroxysmal, persistent, and permanent forms of atrial fibrillation was examined by histological methods and electron microscopy. Isolated atrial amyloidosis was detected in the left (50.0-56.3% patients) and in the right (45.0-55.6% patients) atrial appendages. In all cases, immunohistochemistry revealed atrial natriuretic peptide in fibrillary amyloid deposits. Ultrastructurally, amyloid masses formed clusters of myofibrils 8-10 nm in diameter. They were chaotically located in the extracellular space along the sarcolemma as well as in membrane invaginations, dilated tubules of cardiomyocyte T-tubular system, and vascular walls. Amyloidosis was predominantly observed in women; its degree positively correlated with age of patients and duration of atrial fibrillation but negatively correlated with atrial fibrosis. The study revealed positive (in permanent atrial fibrillation) and negative (in paroxysmal atrial fibrillation) correlation of amyloidosis with myofibril content in atrial cardiomyocytes.

  15. Involvement of a novel GATA4 mutation in atrial septal defects.

    PubMed

    Liu, Xing-Yuan; Wang, Juan; Zheng, Jing-Hao; Bai, Kai; Liu, Zhong-Min; Wang, Xiao-Zhou; Liu, Xu; Fang, Wei-Yi; Yang, Yi-Qing

    2011-07-01

    Atrial septal defect (ASD) is one of the most common types of congenital heart disease and is associated with a significant increase in the morbidity and mortality of affected individuals. Accumulating evidence indicates that genetic defects play important roles in the pathogenesis of congenital ASD. However, ASD is genetically heterogeneous and the genetic determinants for ASD in the majority of the patients remain to be identified. In this study, the entire coding region of GATA4, a gene encoding a zinc-finger transcription factor crucial to embryogenesis, was initially sequenced in 120 unrelated patients with ASD. The available relatives of patients carrying the identified mutation and 200 ethnicity-matched unrelated control individuals were genotyped. The functional characteristics of the GATA4 mutant were compared to its wild-type counterpart using a luciferase reporter assay system. A novel heterozygous missense GATA4 mutation, p.G21V, was identified in 2 unrelated families with ASD, which was not detected in the control population nor reported in the human gene mutation database. Alignment of multiple GATA4 proteins displayed that the affected amino acid residue was highly conserved across species. Functional analysis showed that the p.G21V GATA4 mutation was associated with a decreased transcriptional activity. The findings underscore the pathogenic link between compromised GATA4 function and congenital ASD, providing new insight into the molecular mechanism involved in this common form of congenital cardiovascular anomalies.

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

    PubMed

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

    2017-03-08

    Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (IKv1.5) were markedly inhibited by 12.5-50.0mM ethanol in a concentration-dependent manner. Ethanol with 50.0mM could inhibit rapid delayed rectifier potassium currents (IhERG). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (IKir2.1). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of IKv1.5 and IhERG, which contributed to preventing the development and duration of AF.

  17. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein.

    PubMed

    Alqahtani, Mashael F; Smith, Craig M; Weiss, Scott L; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11). MMP-9/TIMP-1 ratios were

  18. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein

    PubMed Central

    Alqahtani, Mashael F.; Smith, Craig M.; Weiss, Scott L.; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S.

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004–0.174, 13), day 2 (0.020, 0.002–0.109, 10), and day 3 (0.018, 0.003–0.058, 23) compared with febrile (0.705, 0.187–1.778, 22) and healthy (0.7, 0.4–1.2, 29) (p< 0.05) controls. A-FaBP and mrProANP (Median, IQR ng/mL, n) were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05). The area under the curve (AUC) for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05). A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05). MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05). A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2–54.6, 7) were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3–20.6, 11). MMP-9/TIMP-1 ratios

  19. Management of atrial fibrillation.

    PubMed

    Moukabary, Talal; Gonzalez, Mario D

    2015-07-01

    Atrial fibrillation is a very common clinical problem with a high prevalence that is expected to rise over time because of increasing risk factors (eg, age, obesity, hypertension). This high prevalence is also associated with high cost, because atrial fibrillation represents about 1% of overall health care spending. The management of atrial fibrillation involves multiple facets: (1) management of underlying disease if present and the management of atrial fibrillation risk factors, (2) prevention of thromboembolism, (3) control of the ventricular rate during atrial fibrillation, and (4) restoration and maintenance of normal sinus rhythm.

  20. Involvement of prostacyclin and potassium channels in the diabetes-induced hyporeactivity of the rabbit carotid artery to B-type natriuretic peptide.

    PubMed

    Centeno, José M; Marrachelli, Vannina G; Miranda, Luis; Castelló-Ruiz, María; Burguete, María C; Jover-Mengual, Teresa; Salom, Juan B; Torregrosa, Germán; Miranda, Francisco J; Alborch, Enrique

    2013-02-15

    The relation between diabetes and stroke is bidirectional: diabetes is an important risk factor for ischemic stroke, and acute stroke frequently induces hyperglycemia. On the other hand, plasma B-type natriuretic peptide (BNP) levels are raised in diabetes and stroke. The purpose was to study how alloxan-induced diabetes might modify the effects of BNP in rabbit carotid arteries and the mechanisms involved in such actions. To do this, isometric tension in isolated rabbit carotid artery was recorded and prostanoids release and plasma NT-proBNP were measured by enzyme immunoassay. BNP induced a relaxation of phenylephrine-precontracted carotid arteries, and this relaxation was lower in diabetic than in control rabbits. Endothelium removal did not modify the relaxation to BNP in control rabbits but increased this relaxation in diabetic rabbits. In control rabbits, indomethacin inhibited the BNP-induced relaxation in the presence and in the absence of endothelium. In diabetic rabbits, indomethacin did not modify the BNP-induced relaxation in arteries with endothelium and inhibited it in arteries without endothelium. In the presence of BNP the carotid artery released thromboxane A2 and prostacyclin, and the release of endothelial prostacyclin was inhibited in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to BNP, and these inhibitions were lower in diabetic than in control rabbits. In conclusion, our results provide a new understanding concerning the mechanisms of the diabetes-induced hyporeactivity of the carotid artery to BNP, that at least include the loss of endothelial prostacyclin and a reduced participation of ATP-sensitive K(+) channels (KATP) and voltage-sensitive K(+) channels (KV).

  1. Vascular Tone Regulation Induced by C-Type Natriuretic Peptide: Differences in Endothelium-Dependent and -Independent Mechanisms Involved in Normotensive and Spontaneously Hypertensive Rats

    PubMed Central

    Caniffi, Carolina; Cerniello, Flavia M.; Gobetto, María N.; Sueiro, María L.; Arranz, Cristina

    2016-01-01

    Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hypertensive states is unclear, we hypothesized that impaired response of the nitric oxide system to CNP in spontaneously hypertensive rats (SHR) could affect vascular relaxation induced by the peptide in this model of hypertension, and that other endothelial systems or potassium channels opening could also be involved. We examined the effect of CNP on isolated SHR aortas, and the hindlimb vascular resistance (HVR) in response to CNP administration compared to normotensive rats. Aortas were mounted in an isometric organ bath and contracted with phenylephrine. CNP relaxed arteries in a concentration-dependent manner but was less potent in inducing relaxation in SHR. The action of CNP was diminished by removal of the endothelium, inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester, and inhibition of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one in both groups. In contrast, blockade of cyclooxygenase or subtype 2 bradykinin receptor increased CNP potency only in SHR. In both Wistar and SHR, CNP relaxation was blunted by tetraethylammonium and partially inhibited by BaCl2 and iberiotoxin, indicating that it was due to opening of the Kir and BKCa channels. However, SHR seem to be more sensitive to Kir channel blockade and less sensitive to BKCa channel blockade than normotensive rats. In addition, CNP decreases HVR in Wistar and SHR, but the effect of CNP increasing blood flow was more marked in SHR. We conclude that CNP induces aorta relaxation by activation of the nitric oxide system and opening of potassium channels, but the response to the peptide is impaired in conductance vessel of hypertensive rats. PMID:27936197

  2. Atrial Fibrillation

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Atrial Fibrillation? Atrial fibrillation (A-tre-al fi-bri-LA- ... Works article. Understanding the Electrical Problem in Atrial Fibrillation In AF, the heart's electrical signals don't ...

  3. Natriuretic peptides buffer renin-dependent hypertension.

    PubMed

    Demerath, Theo; Staffel, Janina; Schreiber, Andrea; Valletta, Daniela; Schweda, Frank

    2014-06-15

    The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

  4. Effect of chronic treatment with deoxycorticosterone acetate on content of a natriuretic substance in atria of rats.

    PubMed

    Hathaway, S J; Fregly, M J; Wilson, K M; Papanek, P E; Henley, W N

    1986-10-01

    Chronic (72 days) administration of deoxycorticosterone acetate (DOCA), with or without saline as the sole drinking fluid, depleted atria of rats of their diuretic and natriuretic activities. Chronic ingestion of saline as the sole drinking fluid did not affect the diuretic, natriuretic, and kaliuretic activities of atria compared with those of rats receiving water to drink. Since systolic blood pressure of the DOCA-treated group did not differ significantly from that of the untreated control group, the decrease in potency of atrial extract from DOCA-treated rats most likely occurred in response to increases in extracellular and vascular volumes. The ability of DOCA to decrease diuretic and natriuretic activities of atria was dose dependent. The decreased activities of the atria of DOCA-treated rats could reflect an increased production and turnover of atrial natriuretic factor. Additional studies revealed an increased diuretic and natriuretic responsiveness of DOCA-treated recipients to atrial extract from untreated rats. Thus, the results of these studies suggest that chronic treatment with DOCA reduced the natriuretic and diuretic potencies of atrial extract and increased renal responsiveness to it.

  5. B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics.

    PubMed

    Torres-Courchoud, I; Chen, H H

    2016-10-01

    Natriuretic peptides are a family of peptides with similar structures, but are genetically distinct with diverse actions in cardiovascular, renal and fluid homeostasis. The family consists of an atrial natriuretic peptide (ANP) and a brain natriuretic peptide (BNP) of myocardial cell origin, a C-type natriuretic peptide (CNP) of endothelial origin, and a urodilatin (Uro) which is processed from a prohormone ANP in the kidney. Nesiritide, a human recombinant BNP, was approved by the Federal Drug Administration (FDA) for the management of acute heart failure (AHF) in 2001. Human recombinant ANP (Carperitide) was approved for the same clinical indication in Japan in 1995, and human recombinant Urodilatin (Ularitide) is currently undergoing phase III clinical trial (TRUE AHF). This review will provide an update on important issues regarding the role of BNP in fluid hemostasis as a biomarker and therapeutics in AHF.

  6. Primary neural involvement in renal haemodynamic and functional responses to prolonged stimulation of atrial receptors in anaesthetized dogs.

    PubMed

    Majid, D S; Karim, F

    1995-07-01

    To determine the precise contributory role of neural and humoral factors in the efferent mechanism of the atrial receptor-renal reflex, we have examined the effects of prolonged (45 min) stimulation of left atrial receptors on renal haemodynamics and function simultaneously in both kidneys (right kidney intact and left kidney denervated) of anaesthetized dogs. Aortic pressure in these dogs was held constant by means of an arterial reservoir connected to the aorta; heart rate changes were prevented by blocking beta 1-adrenoceptor activity with atenolol (2 mg kg-1 i.v.). Localized stimulation of atrial receptors in six dogs increased renal blood flow (6 +/- 2%), creatinine clearance (11 +/- 4%), urine flow (9 +/- 3%), sodium excretion (14 +/- 7%) and osmolal excretion (10 +/- 4%), and decreased free water clearance (14 +/- 7%) in intact kidneys, but led to no changes in denervated kidneys. In an additional four dogs, cooling the vagus nerves to 6-7 degrees C or cutting them in the neck abolished the renal responses to stimulation of atrial receptors in these stabilized preparations. These data clearly demonstrate that the renal responses to prolonged stimulation of atrial receptors are primarily mediated via myelinated vagal afferents and renal sympathetic efferents.

  7. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation

    PubMed Central

    Zhang, Ke K.; Xiang, Menglan; Zhou, Lun; Liu, Jielin; Curry, Nathan; Heine Suñer, Damian; Garcia-Pavia, Pablo; Zhang, Xiaohua; Wang, Qin; Xie, Linglin

    2016-01-01

    Atrial septal defects (ASDs) are a common human congenital heart disease (CHD) that can be induced by genetic abnormalities. Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation. We hypothesized that Osr1 and Tbx5 share a common signaling networking and downstream targets for atrial septation. To identify this molecular networks, we acquired the RNA-Seq transcriptome data from the posterior SHF of wild-type, Tbx5+/−, Osr1+/−, Osr1−/− and Tbx5+/−/Osr1+/− mutant embryos. Gene set analysis was used to identify the Kyoto Encyclopedia of Genes and Genomes pathways that were affected by the doses of Tbx5 and Osr1. A gene network module involving Tbx5 and Osr1 was identified using a non-parametric distance metric, distance correlation. A subset of 10 core genes and gene–gene interactions in the network module were validated by gene expression alterations in posterior second heart field (pSHF) of Tbx5 and Osr1 transgenic mouse embryos, a time-course gene expression change during P19CL6 cell differentiation. Pcsk6 was one of the network module genes that were linked to Tbx5. We validated the direct regulation of Tbx5 on Pcsk6 using immunohistochemical staining of pSHF, ChIP-quantitative polymerase chain reaction and luciferase reporter assay. Importantly, we identified Pcsk6 as a novel gene associated with ASD via a human genotyping study of an ASD family. In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny. PMID:26744331

  8. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation.

    PubMed

    Zhang, Ke K; Xiang, Menglan; Zhou, Lun; Liu, Jielin; Curry, Nathan; Heine Suñer, Damian; Garcia-Pavia, Pablo; Zhang, Xiaohua; Wang, Qin; Xie, Linglin

    2016-03-15

    Atrial septal defects (ASDs) are a common human congenital heart disease (CHD) that can be induced by genetic abnormalities. Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation. We hypothesized that Osr1 and Tbx5 share a common signaling networking and downstream targets for atrial septation. To identify this molecular networks, we acquired the RNA-Seq transcriptome data from the posterior SHF of wild-type, Tbx5(+/) (-), Osr1(+/-), Osr1(-/-) and Tbx5(+/-)/Osr1(+/-) mutant embryos. Gene set analysis was used to identify the Kyoto Encyclopedia of Genes and Genomes pathways that were affected by the doses of Tbx5 and Osr1. A gene network module involving Tbx5 and Osr1 was identified using a non-parametric distance metric, distance correlation. A subset of 10 core genes and gene-gene interactions in the network module were validated by gene expression alterations in posterior second heart field (pSHF) of Tbx5 and Osr1 transgenic mouse embryos, a time-course gene expression change during P19CL6 cell differentiation. Pcsk6 was one of the network module genes that were linked to Tbx5. We validated the direct regulation of Tbx5 on Pcsk6 using immunohistochemical staining of pSHF, ChIP-quantitative polymerase chain reaction and luciferase reporter assay. Importantly, we identified Pcsk6 as a novel gene associated with ASD via a human genotyping study of an ASD family. In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny.

  9. Genetic variation in the natriuretic peptide system and heart failure.

    PubMed

    Lanfear, David E

    2010-05-01

    Heart failure (HF) is a modern epidemic and is one of the few cardiovascular diseases which is increasing in prevalence. The growing importance of the Natriuretic Peptide (NP) system in HF is well recognized. Laboratory tests for B-type Natriuretic Peptide (BNP) have proven value as diagnostic and prognostic tools in HF and are now part of routine clinical care. Furthermore, recombinant atrial natriuretic peptide (ANP) (carperitide) and BNP (nesiritide) and are approved HF therapies in Japan and the US, respectively and additional natriuretic peptides (e.g., CNP, urodilatin, and designer NPs) are under investigation for use in HF. Common genetic sequence variants are increasingly being recognized as determinants of disease risk or drug response and may help explain a portion of the inter-individual variation in the human NP system. This review describes current knowledge of NP system genetic variation as it pertains to HF as well as ongoing studies and where the field is expected to progress in the near future. To briefly summarize, NP system genetic variants have been associated with alterations in gene expression, NP levels, and cardiovascular disease. The next step forward will include specific investigations into how this genetic variation can advance 'Personalized Medicine', such as whether they impact the utility of diagnostic BNP testing or effectiveness of therapeutic NP infusion. This is already in progress, with pharmacogenetic studies of nesiritide currently underway. We expect that within 5 years there should be a reasonable idea of whether NP system genetic variation will have important clinical implications.

  10. [Atrial fibrillation].

    PubMed

    Cárdenas, Manuel

    2007-01-01

    Atrial fibrillation is an arrhythmia characterized by no-coordinated atrial contraction that results in an inefficient atrial systole. The clinical classification of atrial fibrillation includes: ocassional, paroxysmal, persistent, and permanent. Multiple mechanisms have been described and accounts for a single ECG manifestation. Treatment should be individualized and has to considered several aspects including age, associated heart disease, and symptoms. Treatment strategies are: rhythm control, rate control, and thromboprophylaxis.

  11. [Natriuretic peptides. History of discovery, chemical structure, mechanism of action and the removal routes. Basis of diagnostic and therapeutic use].

    PubMed

    Stryjewski, Piotr J; Nessler, Bohdan; Cubera, Katarzyna; Nessler, Jadwiga

    2013-01-01

    Natriuretic peptides (NP) are the group of proteins synthesized and secreted by the mammalian heart. All the NP are synthesized from prohormones and have 17-amino acid cyclic structures containing two cysteine residues linked by internal disulphide bond. They are characterized by a wide range of actions, mainly through their membrane receptors. The NP regulate the water and electrolyte balance, blood pressure through their diuretic, natriuretic, and relaxating the vascular smooth muscles effects. They also affect the endocrine system and the nervous system. The neurohormonal regulation of blood circulation results are mainly based on antagonism with renin--angiotensin--aldosterone system. The NP representatives are: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), urodilatine and (DNP) Dendroaspis natriuretic peptide, not found in the human body. According to the guidelines of the European Society of Cardiology determination of NT-proBNP level have found a use in the diagnosis of acute and chronic heart failure, risk stratification in acute coronary syndromes and pulmonary embolism. There are reports found in the literature, that demonstrate the usefulness of NT-proBNP determination in valvular, atrial fibrillation, and syncopes. Recombinant human ANP--Carperitid and BNP--Nesiritid, have already found a use in the adjunctive therapy of dyspnea in acute heart failure.

  12. Expression of brain natriuretic peptide by human bone marrow stromal cells.

    PubMed

    Song, S; Kamath, S; Mosquera, D; Zigova, T; Sanberg, P; Vesely, D L; Sanchez-Ramos, J

    2004-01-01

    Bone marrow stromal cells (BMSC) have been shown to generate neural cells under experimental conditions in vitro and following transplantation into animal models of stroke and traumatic CNS injury. Hastened recovery from the neurological deficit has not correlated with structural repair of the lesion in the stroke model. Secretory functions of BMSC, such as the elaboration of growth factors and cytokines, have been hypothesized to play a role in the enhanced recovery of neurological function. Using gene expression arrays, real time RT-PCR and radioimmunoassay, we have found that brain natriuretic peptide (BNP) is synthesized and released by BMSC at physiologically relevant levels in vitro. BNP, like its close homolog atrial natriuretic peptide (ANP), exerts powerful natriuretic, diuretic and vasodilatory effects. We speculate that transplanted BMSCs facilitate recovery from brain and spinal cord lesions by releasing BNP and other vasoactive factors that reduce edema, decrease intracranial pressure and improve cerebral perfusion.

  13. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy.

    PubMed

    Dunn, Michael E; Manfredi, Thomas G; Agostinucci, Kevin; Engle, Steven K; Powe, Josh; King, Nicholas M P; Rodriguez, Luis A; Gropp, Kathryn E; Gallacher, Matthew; Vetter, Frederick J; More, Vijay; Shimpi, Prajakta; Serra, David; Colton, Heidi M

    2017-02-01

    Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.

  14. Silent Atrial Fibrillation and Cryptogenic Strokes.

    PubMed

    Dalen, James E; Alpert, Joseph S

    2017-03-01

    A new suspected cause of cryptic strokes is "silent atrial fibrillation." Pacemakers and other implanted devices allow continuous recording of cardiac rhythm for months or years. They have discovered that short periods of atrial fibrillation lasting minutes or hours are frequent and usually are asymptomatic. A meta-analysis of 50 studies involving more than 10,000 patients with a recent stroke found that 7.7% had new atrial fibrillation on their admitting electrocardiogram. In 3 weeks during and after hospitalization, another 16.9% were diagnosed. A total of 23.7% of these stroke patients had silent atrial fibrillation; that is, atrial fibrillation diagnosed after hospital admission. Silent atrial fibrillation is also frequent in patients with pacemakers who do not have a recent stroke. In a pooled analysis of 3 studies involving more than 10,000 patients monitored for 24 months, 43% had at least 1 day with atrial fibrillation lasting more than 5 minutes. Ten percent had atrial fibrillation lasting at least 12 hours. Despite the frequency of silent atrial fibrillation in these patients with multiple risk factors for stroke, the annual incidence of stroke was only 0.23%. When silent atrial fibrillation is detected in patients with recent cryptogenic stroke, anticoagulation is indicated. In patients without stroke, silent atrial fibrillation should lead to further monitoring for clinical atrial fibrillation rather than immediate anticoagulation, as some have advocated.

  15. INTERACTING DISCIPLINES: Cardiac natriuretic peptides and obesity: perspectives from an endocrinologist and a cardiologist

    PubMed Central

    Ramos, Hugo R; Birkenfeld, Andreas L; de Bold, Adolfo J

    2015-01-01

    Since their discovery in 1981, the cardiac natriuretic peptides (cNP) atrial natriuretic peptide (also referred to as atrial natriuretic factor) and brain natriuretic peptide have been well characterised in terms of their renal and cardiovascular actions. In addition, it has been shown that cNP plasma levels are strong predictors of cardiovascular events and mortality in populations with no apparent heart disease as well as in patients with established cardiac pathology. cNP secretion from the heart is increased by humoral and mechanical stimuli. The clinical significance of cNP plasma levels has been shown to differ in obese and non-obese subjects. Recent lines of evidence suggest important metabolic effects of the cNP system, which has been shown to activate lipolysis, enhance lipid oxidation and mitochondrial respiration. Clinically, these properties lead to browning of white adipose tissue and to increased muscular oxidative capacity. In human association studies in patients without heart disease higher cNP concentrations were observed in lean, insulin-sensitive subjects. Highly elevated cNP levels are generally observed in patients with systolic heart failure or high blood pressure, while obese and type-2 diabetics display reduced cNP levels. Together, these observations suggest that the cNP system plays a role in the pathophysiology of metabolic vascular disease. Understanding this role should help define novel principles in the treatment of cardiometabolic disease. PMID:26115665

  16. Atrial Fibrillation: Diagnosis

    MedlinePlus

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

  17. Radiofrequency Ablation of Persistent Atrial Fibrillation

    PubMed Central

    Hussein, Ayman A.; Saliba, Walid I.; Barakat, Amr; Bassiouny, Mohammed; Chamsi-Pasha, Mohammed; Al-Bawardy, Rasha; Hakim, Ali; Tarakji, Khaldoun; Baranowski, Bryan; Cantillon, Daniel; Dresing, Thomas; Tchou, Patrick; Martin, David O.; Varma, Niraj; Bhargava, Mandeep; Callahan, Thomas; Niebauer, Mark; Kanj, Mohamed; Chung, Mina; Natale, Andrea; Lindsay, Bruce D.; Wazni, Oussama M.

    2017-01-01

    Background Various ablation strategies of persistent atrial fibrillation (PersAF) have had disappointing outcomes, despite concerted clinical and research efforts, which could reflect progressive atrial fibrillation–related atrial remodeling. Methods and Results Two-year outcomes were assessed in 1241 consecutive patients undergoing first-time ablation of PersAF (2005–2012). The time intervals between the first diagnosis of PersAF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide and C-reactive protein before the procedures. The median diagnosis-to-ablation time was 3 years (25th–75th percentiles 1–6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in recurrence rates in addition to an increase in B-type natriuretic peptide levels (P=0.01), C-reactive protein levels (P<0.0001), and left atrial size (P=0.03). The arrhythmia recurrence rates over 2 years were 33.6%, 52.6%, 57.1%, and 54.6% in the first, second, third, and fourth quartiles, respectively (Pcategorical<0.0001). In Cox Proportional Hazard analyses, B-type natriuretic peptide levels, C-reactive protein levels, and left atrial size were associated with arrhythmia recurrence. The diagnosis-to-ablation time had the strongest association with the ablation outcomes which persisted in multivariable Cox analyzes (hazard ratio for recurrence per +1Log diagnosis-to-ablation time 1.27, 95% confidence interval 1.14–1.43; P<0.0001; hazard ratio fourth versus first quartile 2.44, 95% confidence interval 1.68–3.65; Pcategorical<0.0001). Conclusions In patients with PersAF undergoing ablation, the time interval between the first diagnosis of PersAF and the catheter ablation procedure had a strong association with the ablation outcomes, such as shorter diagnosis-to-ablation times were associated with better outcomes and in direct association with markers of atrial remodeling. PMID:26763227

  18. Vascular effects and electrolyte homeostasis of the natriuretic peptide isolated from Crotalus oreganus abyssus (North American Grand Canyon rattlesnake) venom.

    PubMed

    Da Silva, S L; Dias-Junior, C A; Baldasso, P A; Damico, D C S; Carvalho, B M A; Garanto, A; Acosta, G; Oliveira, E; Albericio, F; Soares, A M; Marangoni, S; Resende, R R

    2012-08-01

    Crotalus oreganus abyssus is a rattlesnake that is usually found in the Grand Canyon, United States of America. Knowledge regarding the composition of C. o. abyssus venom is scarce. New natriuretic peptides (NPs) have been isolated and characterized from the venoms of members of the Crotalinae family. The NP family comprises three members, ANP (atrial natriuretic peptide), BNP (b-type natriuretic peptide) and CNP (c-type natriuretic peptide), and has an important role in blood pressure regulation and electrolyte homeostasis. The aim of the present study was to characterize a novel natriuretic-like peptide (Coa_NP2), isolated from C. o. abyssus venom. The Coa_NP2 presents an average molecular mass of 3419.88Da (theoretical average molecular mass 3418.94Da, monoisotopic molecular mass 3416.66Da and theoretical PI 7.78) and its amino acid sequence presents the loop region that is characteristic of natriuretic peptides. The peptide has 32 amino acids and its complete sequence is SYGISSGCFGLKLDRIGTMSGLGCWRLLQDSP. Coa_NP2 is a natriuretic peptide of the ANP/BNP-like family, since the carboxyterminal region of CNP has its own NP domain. We demonstrate, herein, that Coa_NP2 produces a dose-dependent decrease in mean arterial pressure in rats, followed by significant increases in concentrations of markers of nitric oxide formation measured in the plasma and vasorelaxation in a thoracic aortic ring bath. The structural and biological aspects confirm Coa_NP2 as a new natriuretic peptide, isolated from snake venom.

  19. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    SciTech Connect

    Higuchi, K.; Hashiguchi, T.; Ohashi, M.; Takayanagi, R.; Haji, M.; Matsuo, H.; Nawata, H.

    1989-01-01

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of (/sup 125/I)-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

  20. Atrial Fibrillation: Treatment

    MedlinePlus

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

  1. Atrial Fibrillation: Complications

    MedlinePlus

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

  2. Molecular cloning of natriuretic peptide receptor A from bullfrog (Rana catesbeiana) brain and its functional expression.

    PubMed

    Sekiguchi, T; Miyamoto, K; Mizutani, T; Yamada, K; Yazawa, T; Yoshino, M; Minegishi, T; Takei, Y; Kangawa, K; Minamino, N; Saito, Y; Kojima, M

    2001-08-08

    A comparative study of natriuretic peptide receptor (NPR) was performed by cloning the NPR-A receptor subtype from the bullfrog (Rana catesbeiana) brain and analyzing its functional expression. Like other mammalian NPR-A receptors, the bullfrog NPR-A receptor consists of an extracellular ligand binding domain, a hydrophobic transmembrane domain, a kinase-like domain and a guanylate cyclase domain. Sequence comparison among the bullfrog and mammalian receptors revealed a relatively low ( approximately 45%) similarity in the extracellular domain compared to a very high similarity ( approximately 92%) in the cytoplasmic regulatory and catalytic domains. Expression of NPR-A mRNA was detected in various bullfrog tissues including the brain, heart, lung, kidney and liver; highest levels were observed in lung. Functional expression of the receptor in COS-7 cells revealed that frog atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) elicited cyclic guanosine 3'5'-monophosphate production by stimulating the receptor in a dose-dependent manner from 10(-10) M concentrations. Rat ANP was also effective in stimulating the frog receptor whereas rat BNP and porcine BNP were less responsive to the receptor. On the other hand, frog C-type natriuretic peptide (CNP) as well as porcine CNP stimulated the receptor only at high concentrations (10(-7) M). This clearly indicates that the bullfrog receptor is a counterpart of mammalian NPR-A, and is specific for ANP or BNP but not for CNP.

  3. Atrial Fibrillation.

    PubMed

    Zimetbaum, Peter

    2017-03-07

    This issue provides a clinical overview of atrial fibrillation, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

  4. Giant right atrial thrombi treated with thrombolysis.

    PubMed

    Ruiz-Bailén, Manuel; López-Caler, Carmen; Castillo-Rivera, Ana; Rucabado-Aguilar, Luis; Ramos Cuadra, José Angel; Lara Toral, Juan; Lozano Cabezas, Cristobal; Fernández Guerrero, Juan Carlos

    2008-04-01

    The present report describes giant atrial thrombi that were treated with thrombolysis in a community hospital. Two patients with giant atrial thrombi whose treatment involved complications are presented. Both patients developed cardiogenic shock and were treated unsuccessfully with thrombolysis. Because thrombolysis of giant thrombi may be ineffective, patients in this situation may require surgery.

  5. Giant right atrial thrombi treated with thrombolysis

    PubMed Central

    Ruiz-Bailén, Manuel; López-Caler, Carmen; Castillo-Rivera, Ana; Rucabado-Aguilar, Luis; Cuadra, José Ángel Ramos; Toral, Juan Lara; Cabezas, Cristobal Lozano; Guerrero, Juan Carlos Fernández

    2008-01-01

    The present report describes giant atrial thrombi that were treated with thrombolysis in a community hospital. Two patients with giant atrial thrombi whose treatment involved complications are presented. Both patients developed cardiogenic shock and were treated unsuccessfully with thrombolysis. Because thrombolysis of giant thrombi may be ineffective, patients in this situation may require surgery. PMID:18401474

  6. Natriuretic Peptide Receptor A as a Novel Target for Prostate Cancer

    PubMed Central

    2011-01-01

    Background The receptor for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPRA), is expressed in cancer cells, and natriuretic peptides have been implicated in cancers. However, the direct role of NPRA signaling in prostate cancer remains unclear. Results NPRA expression was examined by western blotting, RT-PCR and immunohistochemistry. NPRA was downregulated by transfection of siRNA, shRNA and NPRA inhibitor (iNPRA). Antitumor efficacy of iNPRA was tested in mice using a TRAMP-C1 xenograft. Here, we demonstrated that NPRA is abundantly expressed on tumorigenic mouse and human prostate cells, but not in nontumorigenic prostate epithelial cells. NPRA expression showed positive correlation with clinical staging in a human PCa tissue microarray. Down-regulation of NPRA by siNPRA or iNPRA induced apoptosis in PCa cells. The mechanism of iNPRA-induced anti-PCa effects was linked to NPRA-induced expression of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine over-expressed in PCa and significantly reduced by siNPRA. Prostate tumor cells implanted in mice deficient in atrial natriuretic peptide receptor A (NPRA-KO) failed to grow, and treatment of TRAMP-C1 xenografts with iNPRA reduced tumor burden and MIF expression. Using the TRAMP spontaneous PCa model, we found that NPRA expression correlated with MIF expression during PCa progression. Conclusions Collectively, these results suggest that NPRA promotes PCa development in part by regulating MIF. Our findings also suggest that NPRA is a potential prognostic marker and a target for PCa therapy. PMID:21586128

  7. Natriuretic peptides in water-deprived and in salt-loaded rats.

    PubMed

    Makino, Y; Minamino, N; Kakishita, E; Kangawa, K; Matsuo, H

    1996-01-01

    To elucidate the differences of physiological function of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), we measured tissue concentration and mRNA level in cardiac atrium, ventricle, and brain as well as plasma concentration of these three peptides in water-deprived (WD) and in salt-loaded (SI.) rats. WD rats were given no water for 5 days, whereas SL rats had free access to 2% saline for 14 days. Plasma ANP and BNP concentration of the WD group decreased to 21% and < 10%, and the concentration of the SL group to 36% and 47% of the control (CON) group. Atrial and ventricular BNP concentration of the WD group decreased to 36% and 23% of the CON group, and atrial BNP concentration of the SL group decreased to a lesser extent. BNP mRNA level in atrium and ventricle decreased in both the WD and SL groups, with the WD group showing larger decreases to 11% and 20% of the CON group. ANP mRNA level in atrium and ventricle of the WD group decreased to 40% and 61% of the CON group, but increased to 147% in ventricle of the SL group. In the brain, no significant change was observed in ANP and CNP concentration in both the WD and SL group. Under these conditions. BNP generally showed larger changes than ANP in both peptide concentration and mRNA level. Gene transcription and peptide production of ANP and BNP in atrium and in ventricle were not always found to be in concert, especially in the case of salt loading. Taken as a whole, our results demonstrate differences among the systems regulating biosynthesis and secretion of ANP and BNP in atrium and ventricle.

  8. 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

  9. Changes of adrenomedullin and natriuretic peptides in patients with adrenal medullary hyperplasia prior to and following pharmacological therapy and adrenalectomy

    PubMed Central

    Zhou, Pang-Hu; Shi, Lei; Hu, Wei; Zhang, Xiao-Bin; Wang, Wei; Zhang, Li-Jun

    2016-01-01

    The aim of the present study was to investigate the pathophysiological functions of adrenomedullin (ADM), atrial and brain natriuretic peptides (ANP and BNP) in patients with adrenal medullary hyperplasia (AMH). Plasma ADM, ANP and BNP concentrations were measured in 20 patients with AMH, 35 patients with essential hypertension (EH), and 40 healthy control subjects. Following effective antihypertensive therapy, the values in AMH and EH patients were measured again and laparoscopic adrenalectomy was performed for AMH patients. At 2 weeks after surgery, the three peptides were measured again. The AMH patients had higher plasma concentrations of ADM, ANP and BNP compared with the EH and control subjects. There were significant differences in the values of ADM, ANP and BNP between adrenal vein and inferior vena cava and between AMH and contralateral adrenal vein. Plasma ADM concentration was correlated with serum epinephrine and norepinephrine and urine vanillylmandelic acid, in addition to systolic and diastolic blood pressure, left ventricular ejection fraction, left ventricular mass index and ANP and BNP values in the AMH group. Following antihypertensive treatment, ADM, ANP and BNP were significantly decreased in EH patients, but remained unchanged in AMH subjects. However, these concentrations significantly decreased following surgery. Therefore, the present results suggest that ADM, ANP and BNP may be involved in regulating adrenal medulla functions. PMID:27446289

  10. Late atypical atrial flutter after ablation of atrial fibrillation.

    PubMed

    Ferreira, Raquel; Primo, João; Adão, Luís; Gonzaga, Anabela; Gonçalves, Helena; Santos, Rui; Fonseca, Paulo; Santos, José; Gama, Vasco

    2016-10-01

    Cardiac surgery for structural heart disease (often involving the left atrium) and radiofrequency catheter ablation of atrial fibrillation have led to an increased incidence of regular atrial tachycardias, often presenting as atypical flutters. This type of flutter is particularly common after pulmonary vein isolation, especially after extensive atrial ablation including linear lesions and/or defragmentation. The authors describe the case of a 51-year-old man, with no relevant medical history, referred for a cardiology consultation in 2009 for paroxysmal atrial fibrillation. After failure of antiarrhythmic therapy, he underwent catheter ablation, with criteria of acute success. Three years later he again suffered palpitations and atypical atrial flutter was documented. The electrophysiology study confirmed the diagnosis of atypical left flutter and reappearance of electrical activity in the right inferior pulmonary vein. This vein was again ablated successfully and there has been no arrhythmia recurrence to date. In an era of frequent catheter ablation it is essential to understand the mechanism of this arrhythmia and to recognize such atypical flutters.

  11. Molecular Basis of Gene-Gene Interaction: Cyclic Cross-Regulation of Gene Expression and Post-GWAS Gene-Gene Interaction Involved in Atrial Fibrillation.

    PubMed

    Huang, Yufeng; Wang, Chuchu; Yao, Yufeng; Zuo, Xiaoyu; Chen, Shanshan; Xu, Chengqi; Zhang, Hongfu; Lu, Qiulun; Chang, Le; Wang, Fan; Wang, Pengxia; Zhang, Rongfeng; Hu, Zhenkun; Song, Qixue; Yang, Xiaowei; Li, Cong; Li, Sisi; Zhao, Yuanyuan; Yang, Qin; Yin, Dan; Wang, Xiaojing; Si, Wenxia; Li, Xiuchun; Xiong, Xin; Wang, Dan; Huang, Yuan; Luo, Chunyan; Li, Jia; Wang, Jingjing; Chen, Jing; Wang, Longfei; Wang, Li; Han, Meng; Ye, Jian; Chen, Feifei; Liu, Jingqiu; Liu, Ying; Wu, Gang; Yang, Bo; Cheng, Xiang; Liao, Yuhua; Wu, Yanxia; Ke, Tie; Chen, Qiuyun; Tu, Xin; Elston, Robert; Rao, Shaoqi; Yang, Yanzong; Xia, Yunlong; Wang, Qing K

    2015-08-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia at the clinic. Recent GWAS identified several variants associated with AF, but they account for <10% of heritability. Gene-gene interaction is assumed to account for a significant portion of missing heritability. Among GWAS loci for AF, only three were replicated in the Chinese Han population, including SNP rs2106261 (G/A substitution) in ZFHX3, rs2200733 (C/T substitution) near PITX2c, and rs3807989 (A/G substitution) in CAV1. Thus, we analyzed the interaction among these three AF loci. We demonstrated significant interaction between rs2106261 and rs2200733 in three independent populations and combined population with 2,020 cases/5,315 controls. Compared to non-risk genotype GGCC, two-locus risk genotype AATT showed the highest odds ratio in three independent populations and the combined population (OR=5.36 (95% CI 3.87-7.43), P=8.00×10-24). The OR of 5.36 for AATT was significantly higher than the combined OR of 3.31 for both GGTT and AACC, suggesting a synergistic interaction between rs2106261 and rs2200733. Relative excess risk due to interaction (RERI) analysis also revealed significant interaction between rs2106261 and rs2200733 when exposed two copies of risk alleles (RERI=2.87, P<1.00×10-4) or exposed to one additional copy of risk allele (RERI=1.29, P<1.00×10-4). The INTERSNP program identified significant genotypic interaction between rs2106261 and rs2200733 under an additive by additive model (OR=0.85, 95% CI: 0.74-0.97, P=0.02). Mechanistically, PITX2c negatively regulates expression of miR-1, which negatively regulates expression of ZFHX3, resulting in a positive regulation of ZFHX3 by PITX2c; ZFHX3 positively regulates expression of PITX2C, resulting in a cyclic loop of cross-regulation between ZFHX3 and PITX2c. Both ZFHX3 and PITX2c regulate expression of NPPA, TBX5 and NKX2.5. These results suggest that cyclic cross-regulation of gene expression is a molecular basis for gene

  12. Plasma proatrial natriuretic factor (1-98) concentration after myocardial infarction: relation to indices of cardiac and renal function.

    PubMed Central

    Bonarjee, V. V.; Omland, T.; Nilsen, D. W.; Caidahl, K.; Sundsfjord, J. A.; Dickstein, K.

    1995-01-01

    OBJECTIVES--(a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN--Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING--Norwegian central hospital. PATIENTS--Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES--Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS--Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection

  13. What Is Atrial Fibrillation?

    MedlinePlus

    ANSWERS by heart Cardiovascular Conditions What Is Atrial Fibrillation? Your heart has a natural pacemaker, called the “ ... if the electric signals are normal. In atrial fibrillation (AFib), the heart’s two small upper chambers (atria) ...

  14. Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

    SciTech Connect

    Misono, K. S.; Philo, J. S.; Arakawa, T.; Ogata, C. M.; Qiu, Y.; Ogawa, H.; Young, H. S.

    2011-06-01

    Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.

  15. Natriuretic peptide receptor B signaling in the cardiovascular system: protection from cardiac hypertrophy.

    PubMed

    Pagel-Langenickel, Ines; Buttgereit, Jens; Bader, Michael; Langenickel, Thomas H

    2007-08-01

    Natriuretic peptides (NP) represent a family of structurally homologous but genetically distinct peptide hormones involved in regulation of fluid and electrolyte balance, blood pressure, fat metabolism, cell proliferation, and long bone growth. Recent work suggests a role for natriuretic peptide receptor B (NPR-B) signaling in regulation of cardiac growth by either a direct effect on cardiomyocytes or by modulation of other signaling pathways including the autonomic nervous system. The research links NPR-B for the first time to a cardiac phenotype in vivo and underlines the importance of the NP in the cardiovascular system. This manuscript will focus on the role of NPR-B and its ligand C-type natriuretic peptide in cardiovascular physiology and disease and will evaluate these new findings in the context of the known function of this receptor, with a perspective on how future research might further elucidate NPR-B function.

  16. Brain natriuretic peptide predicts mortality in the elderly.

    PubMed Central

    Wallén, T.; Landahl, S.; Hedner, T.; Nakao, K.; Saito, Y.

    1997-01-01

    OBJECTIVE: To study whether prospective measurements of circulating concentrations of brain natriuretic peptide (BNP) could predict mortality in the general elderly population. DESIGN AND SETTING: Circulating BNP was measured in a cohort of 85 year olds from the general population who were followed up prospectively for five years as part of a longitudinal population study, "70 year old people in Gothenburg, Sweden". PATIENTS: 541 subjects from the 85 year old population in Gothenburg. All subjects were investigated for the presence or absence of cardiovascular disorder such as congestive heart failure, ischaemic heart disease, hypertension, and atrial fibrillation. Venous plasma samples were obtained for BNP analysis. MAIN OUTCOME MEASURE: Overall mortality during the prospective follow up period. RESULTS: Circulating concentrations of BNP predicted five-year mortality in the total population (P < 0.001). In subjects with a known cardiovascular disorder, five-year mortality was correlated with increased BNP concentrations (P < 0.01). Increased BNP concentrations predicted five-year mortality in subjects without a defined cardiovascular disorder (P < 0.05). CONCLUSIONS: In an elderly population, measurements of BNP may add valuable prognostic information and may be used to predict mortality in the total population as well as in patients with known cardiovascular disorders. In subjects without any known cardiovascular disorder, BNP was a strong and independent predictor of total mortality. PMID:9093047

  17. Water deprivation enhances the inhibitory effect of natriuretic peptides on cAMP synthesis in rat renal glomeruli.

    PubMed

    Woodard, Geoffrey E; Li, Xiaohong; Rosado, Juan A

    2004-09-01

    This study investigates the effect of water deprivation on the expression of atrial natiruretic peptide (ANP)(1-28) binding sites in rat kidney. Water deprivation increased the B(max) of glomerular binding sites for ANP(1-28) and C-type natriuretic peptide (CNP)(1-22) without modifying their affinity, an effect that was prevented in the presence of C-atrial natriuretic factor (C-ANF), suggesting that natriuretic peptide receptor-C (NPR-C) binding sites might be enhanced. Our results indicate that ANP(1-28), CNP(1-22), and C-ANF inhibit cAMP synthesis directly stimulated by forskolin or by the physiological agonists histamine and 5-hydroxytryptamine. The inhibitory effect was found to be significantly greater in water-deprived rats than in controls. Our observations suggest that this effect must be attributed to the 67-kDa NPR-C-like protein, because the 67- and 77-kDa NPR-C-like proteins show high and low affinities for CNP(1-22), respectively, and the enhanced inhibitory effect of CNP on cAMP generation in water-deprived rats was detected at subnanomolar concentrations. In addition, using affinity cross-linking studies we have observed that water deprivation increases the expression of the 67-kDa NPR-C-like protein, and HS-142, which binds to NPR-A and the 77-kDa NPR-C-like but not the 67-kDa protein, reduced ligand internalization without affecting cAMP inhibition by ANP(1-28). Finally, we have found that ligand binding to the 67-kDa NPR-C-like protein is reduced by GTPgammaS, suggesting that this receptor is associated with a G protein in renal glomeruli. The enhanced inhibitory role of natriuretic peptides on cAMP synthesis induced by water deprivation may influence glomerular function in the rat kidney.

  18. How Is Atrial Fibrillation Treated?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Atrial Fibrillation Treated? Treatment for atrial fibrillation (AF) depends on ... much thyroid hormone). Who Needs Treatment for Atrial Fibrillation? People who have AF but don't have ...

  19. Organized Atrial Tachycardias after Atrial Fibrillation Ablation

    PubMed Central

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

    2011-01-01

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

  20. Atrial fibrillation - discharge

    MedlinePlus

    Auricular fibrillation - discharge; A-fib - discharge; AF - discharge; Afib - discharge ... been in the hospital because you have atrial fibrillation . This condition occurs when your heart beats faster ...

  1. Natriuretic peptides modify Pseudomonas fluorescens cytotoxicity by regulating cyclic nucleotides and modifying LPS structure

    PubMed Central

    Veron, Wilfried; Orange, Nicole; Feuilloley, Marc GJ; Lesouhaitier, Olivier

    2008-01-01

    Background Nervous tissues express various communication molecules including natriuretic peptides, i.e. Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP). These molecules share structural similarities with cyclic antibacterial peptides. CNP and to a lesser extent BNP can modify the cytotoxicity of the opportunistic pathogen Pseudomonas aeruginosa. The psychrotrophic environmental species Pseudomonas fluorescens also binds to and kills neurons and glial cells, cell types that both produce natriuretic peptides. In the present study, we investigated the sensitivity of Pseudomonas fluorescens to natriuretic peptides and evaluated the distribution and variability of putative natriuretic peptide-dependent sensor systems in the Pseudomonas genus. Results Neither BNP nor CNP modified P. fluorescens MF37 growth or cultivability. However, pre-treatment of P. fluorescens MF37 with BNP or CNP provoked a decrease of the apoptotic effect of the bacterium on glial cells and an increase of its necrotic activity. By homology with eukaryotes, where natriuretic peptides act through receptors coupled to cyclases, we observed that cell-permeable stable analogues of cyclic AMP (dbcAMP) and cyclic GMP (8BcGMP) mimicked the effect of BNP and CNP on bacteria. Intra-bacterial concentrations of cAMP and cGMP were measured to study the involvement of bacterial cyclases in the regulation of P. fluorescens cytotoxicity by BNP or CNP. BNP provoked an increase (+49%) of the cAMP concentration in P. fluorescens, and CNP increased the intra-bacterial concentrations of cGMP (+136%). The effect of BNP and CNP on the virulence of P. fluorescens was independent of the potential of the bacteria to bind to glial cells. Conversely, LPS extracted from MF37 pre-treated with dbcAMP showed a higher necrotic activity than the LPS from untreated or 8BcGMP-pre-treated bacteria. Capillary electrophoresis analysis suggests that these different effects of the LPS may be due, at least in part, to

  2. Morphological and morphometric study of atrial specific granules and other secretory components in dogs experimentally infected with Trypanosoma cruzi.

    PubMed Central

    Caliari, M. V.; Lana, M.; Leite, V. H.; Tafuri, W. L.

    1995-01-01

    Changes in blood volume can induce morphometric and morphological alterations in the secretory complex of the myoendocrine cells due to the stretching of atrial walls. These alterations were studied by electron microscopy, using dogs infected intraperitonially with Trypanosoma cruzi and necropsied during the acute phase of the infection when congestive heart failure was present. Several changes were observed in the myoendocrine cells of the heart: hypertrophy and hyperplasia of rough endoplasmic reticulum and Golgi complex, increase in telenuclear secretory complex, increase in fusion of type B atrial specific granules (ASG), decrease of the total number of ASG, enlargement of the maximum diameter of type A ASG and a relative increase in the number of type B ASG. These alterations suggest a larger secretory activity of the atrial myoendocrine cells with a larger secretion of atrial natriuretic peptide (ANP). Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7547444

  3. Molecular cloning of natriuretic peptides from the heart of reptiles: loss of ANP in diapsid reptiles and birds.

    PubMed

    Trajanovska, Sofie; Donald, John A

    2008-04-01

    Atrial natriuretic peptide (ANP) and B-type NP (BNP) are hormones involved in homeostatic control of body fluid and cardiovascular regulation. Both ANP and BNP have been cloned from the heart of mammals, amphibians, and teleost fishes, while an additional cardiac peptide, ventricular NP, has been found in selected species of teleost fish. However, in chicken, BNP is the primary cardiac peptide identified thus far. In contrast, the types of NP/s present in the reptilian heart are unknown, representing a considerable gap in our understanding of NP evolution. In the present study, we cloned and sequenced a BNP cDNA from the atria of representative species of reptile, including crocodile, lizard, snake, and tortoise. In addition, we cloned BNP from the pigeon atria. The reptilian and pigeon BNP cDNAs had ATTTA repeats in the 3' untranslated region, as observed in all vertebrate BNP mRNAs. A high sequence homology was evident when comparing reptile and pigeon preproBNP with the previously identified chicken preproBNP. In particular, the predicted mature BNP-29 was identical between crocodile, tortoise, and chicken, with pigeon having a single amino acid substitution; lizard and snake BNP had seven and nine substitutions, respectively. Furthermore, an ANP cDNA could only be cloned from the tortoise atria. Since ANP was not isolated from the heart of any non-chelonian reptile and appears to be absent in birds, we propose that the ANP gene has been lost after branching of the turtles in the amniote line. This data provides new avenues for research on NP function in reptiles.

  4. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability.

    PubMed

    Jacob, Matthias; Saller, Thomas; Chappell, Daniel; Rehm, Markus; Welsch, Ulrich; Becker, Bernhard F

    2013-05-01

    Atrial natriuretic peptide (ANP) is a peptide hormone released from the cardiac atria during hypervolemia. Though named for its well-known renal effect, ANP has been demonstrated to acutely increase vascular permeability in vivo. Experimentally, this phenomenon was associated with a marked shedding of the endothelial glycocalyx, at least for supraphysiological intravascular concentrations. This study investigates the impact and mechanism of action of physiological doses of ANP and related peptides on the vascular barrier. In isolated guinea pig hearts, prepared and perfused in a modified Langendorff mode with and without the intravascular presence of the colloid hydroxyethyl starch (HES), we measured functional changes in vascular permeability and glycocalyx shedding related to intracoronary infusion of physiological concentrations of A-, B- and C-type natriuretic peptide (ANP, BNP and CNP). Significant coronary venous washout of glycocalyx constituents (syndecan-1 and heparan sulfate) was observed. As tested for ANP, this effect was positively related to the intracoronary concentration. Intravascular shedding of the glycocalyx was morphologically confirmed by electron microscopy. Also, functional vascular barrier competence decreased, as indicated by significant increases in transudate formation and HES extravasation. Ortho-phenanthroline, a non-specific inhibitor of matrix metalloproteases, was able to reduce ANP-induced glycocalyx shedding. These findings suggest participation of natriuretic peptides in pathophysiological processes like heart failure, inflammation or sepsis. Inhibition of metalloproteases might serve as a basis for future therapeutical options.

  5. Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs

    PubMed Central

    Pandey, Kailash N.

    2015-01-01

    The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed. PMID:26151885

  6. Total plasma proANP increases with atrial dilatation in horses.

    PubMed

    Van Der Vekens, N; Hunter, I; Timm, A; Decloedt, A; De Clercq, D; Deprez, P; Goetze, J P; van Loon, G

    2015-12-19

    Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total proANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration was significantly (P<0.001) higher in horses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; P<0.001) or horses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation was calculated. Sample storage at -80°C did not differ from sample storage at -20°C. The measurement of total proANP in plasma detects atrial dilatation in horses and may be useful for clinical evaluation in equine medicine.

  7. Left Atrial Appendage Exclusion for Atrial Fibrillation

    PubMed Central

    Syed, Faisal F.; DeSimone, Christopher V.; Friedman, Paul A.; Asirvatham, Samuel J.

    2015-01-01

    SYNOPSIS Percutaneous left atrial appendage (LAA) closure is increasingly being used as a treatment strategy to prevent stroke in patients with atrial fibrillation (AF) who have contraindications to anticoagulants. A number of approaches and devices have been developed in the last few years, each with their own unique set of advantages and disadvantages. We review the published studies on surgical and percutaneous approaches to LAA closure; focusing on stroke mechanisms in AF, LAA structure and function relevant to stroke prevention, practical differences in procedural approach, and clinical considerations surrounding management. PMID:25443240

  8. Weight Loss, Saline Loading, and the Natriuretic Peptide System

    PubMed Central

    Arora, Pankaj; Reingold, Jason; Baggish, Aaron; Guanaga, Derek P.; Wu, Connie; Ghorbani, Anahita; Song, Yanna; Chen‐Tournaux, Annabel; Khan, Abigail May; Tainsh, Laurel T.; Buys, Emmanuel S.; Williams, Jonathan S.; Heublein, Denise M.; Burnett, John C.; Semigran, Marc J.; Bloch, Kenneth D.; Scherrer‐Crosbie, Marielle; Newton‐Cheh, Christopher; Kaplan, Lee M.; Wang, Thomas J.

    2015-01-01

    Background In epidemiologic studies, obesity has been associated with reduced natriuretic peptide (NP) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading. Methods and Results We enrolled 15 obese individuals (mean BMI 45±5.4 kg/m2) undergoing gastric bypass surgery. Before and 6 months after surgery, subjects were admitted to the clinical research center and administered a large‐volume intravenous saline challenge. Echocardiography and serial blood sampling were performed. From the pre‐operative visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the 6‐month visit, N‐terminal pro‐atrial NP (Nt‐proANP) levels were 40% higher before, during, and after the saline infusion, compared with levels measured at the same time points during the pre‐operative visit (P<0.001). The rise in Nt‐pro‐ANP induced by the saline infusion (≈50%) was similar both before and after surgery (saline, P<0.001; interaction, P=0.2). Similar results were obtained for BNP and Nt‐proBNP; resting concentrations increased by 50% and 31%, respectively, after gastric bypass surgery. The increase in NP concentrations after surgery was accompanied by significant decreases in mean arterial pressure (P=0.004) and heart rate (P<0.001), and an increase in mitral annular diastolic velocity (P=0.02). Conclusion In obese individuals, weight loss is associated with a substantial increase in the “setpoint” of circulating NP concentrations. Higher NP concentrations could contribute to an enhanced ability to handle salt loads after weight loss. PMID:25595796

  9. Surgery for Atrial Fibrillation.

    PubMed

    Lawrance, Christopher P; Henn, Matthew C; Damiano, Ralph J

    2016-04-01

    Atrial fibrillation is the most common cardiac arrhythmia, and its treatment options include drug therapy or catheter-based or surgical interventions. The surgical treatment of atrial fibrillation has undergone multiple evolutions over the last several decades. The Cox-Maze procedure went on to become the gold standard for the surgical treatment of atrial fibrillation and is currently in its fourth iteration (Cox-Maze IV). This article reviews the indications and preoperative planning for performing a Cox-Maze IV procedure. This article also reviews the literature describing the surgical results for both approaches including comparisons of the Cox-Maze IV to the previous cut-and-sew method.

  10. Surgery for atrial fibrillation.

    PubMed

    Lawrance, Christopher P; Henn, Matthew C; Damiano, Ralph J

    2014-11-01

    Atrial fibrillation is the most common cardiac arrhythmia, and its treatment options include drug therapy or catheter-based or surgical interventions. The surgical treatment of atrial fibrillation has undergone multiple evolutions over the last several decades. The Cox-Maze procedure went on to become the gold standard for the surgical treatment of atrial fibrillation and is currently in its fourth iteration (Cox-Maze IV). This article reviews the indications and preoperative planning for performing a Cox-Maze IV procedure. This article also reviews the literature describing the surgical results for both approaches including comparisons of the Cox-Maze IV to the previous cut-and-sew method.

  11. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients.

    PubMed

    Zoccali, C; Mallamaci, F; Benedetto, F A; Tripepi, G; Parlongo, S; Cataliotti, A; Cutrupi, S; Giacone, G; Bellanuova, I; Cottini, E; Malatino, L S

    2001-07-01

    This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.

  12. Case report and literature review: surgical treatment of a right atrial metastatic melanoma from a previously resected "advanced" primary site with regional lymph nodes involvement.

    PubMed

    Parissis, Haralabos; Al-Alao, Bassel Suffian; Young, Vincent K

    2012-10-01

    Although melanoma of the right atrium is a rare cardiac tumor, melanoma in general has a high propensity to involve the heart. Unfortunately, however, when the tumor is involving the heart, widespread metastasis ensues and hence surgery becomes a questionable option. We report a case of a young female who presented with an advanced skin primary melanoma and regional lymph node involvement and a metastasis into the right atrium. Postoperatively tumor dissemination was controlled with adjuvant chemotherapy. A vigorous attempt aiming at tumor clearance followed by adjuvant multimodality therapy along with a tumor surveillance program may improve survival even in advanced cases.

  13. B-type natriuretic peptide (BNP) and proBNP: role of emerging markers to guide therapy and determine prognosis in cardiovascular disorders.

    PubMed

    Godkar, Darshan; Bachu, Kalyan; Dave, Bijal; Niranjan, Selva; Khanna, Ashok

    2008-01-01

    Over the last decade, one group of neurohormonal markers, including atrial natriuretic peptide (ANP), N-terminal pro-ANP, B-type natriuretic peptide (BNP), and N-terminal proBNP, has generated much interest in the evaluation and management of heart failure and acute coronary syndrome. There has been so much literature on the subject, especially concerning BNP and proBNP, that it leaves us confused at times about what the literature has to say about these markers. In this article, we have made an honest attempt to examine all the available literature in relation to the impact of BNP and proBNP on cardiovascular disease and present it to the reader in an assimilated fashion.

  14. Atrial fibrillation and gastroesophageal reflux disease: From the cardiologist perspective.

    PubMed

    Floria, Mariana; Drug, Vasile Liviu

    2015-03-14

    We have read with interest the paper by Roman C. and colleagues discussing the relationship between gastroesophageal reflux disease and atrial fibrillation. The review is presenting the available evidence for the common pathogenic mechanisms. However, from a cardiologist perspective, some available data were not highlighted in the review, cardiovascular involvement in gastroesophageal reflux is less assessed. Hypertension, obesity or diabetes mellitus are substrate for left atrial remodeling that initiate and sustained atrial fibrillation development. One of the pathophysiologic mechanisms in atrial fibrillation is the presence of a trigger. Gastroesophageal reflux could be only a trigger for this arrhythmia. We believe that atrial fibrillation should be considered as possible extraesophageal syndrome in the gastroesophageal reflux classification.

  15. 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 ...

  16. C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling.

    PubMed

    Rose, R A; Hatano, N; Ohya, S; Imaizumi, Y; Giles, W R

    2007-04-01

    In the heart, fibroblasts play an essential role in the deposition of the extracellular matrix and they also secrete a number of hormonal factors. Although natriuretic peptides, including C-type natriuretic peptide (CNP) and brain natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the effects of CNP on fibroblast electrophysiology have not been examined. In this study, acutely isolated ventricular fibroblasts from the adult rat were used to measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non-selective cation current (NSCC). This current has a reversal potential near 0 mV. Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated NSCC was inhibited by the compounds Gd(3+), SKF 96365 and 2-aminoethoxydiphenyl borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts revealed the expression of several transient receptor potential (TRP) channel transcripts. Additional electrophysiological analysis showed that U73122, a phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are defining characteristics of specific TRPC channels. More detailed molecular analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5 transcripts. These data indicate that CNP, acting via the NPR-C receptor, activates a NSCC that is at least partially carried by TRPC channels in cardiac fibroblasts.

  17. Natriuretic peptides in cetaceans: identification, molecular characterization and changes in plasma concentration after landing.

    PubMed

    Naka, Tadaomi; Katsumata, Etsuko; Sasaki, Kazuki; Minamino, Naoto; Yoshioka, Motoi; Takei, Yoshio

    2007-06-01

    Dolphins are aquatic animals free from gravity, and this may have imposed significant changes in their cardiovascular status and its hormonal regulation compared with terrestrial animals. This study molecularly characterized two major cardiovascular hormones, atrial and B-type natriuretic peptides (ANP and BNP) and measured their changes in dolphin plasma concentrations in relation to the cardiovascular status of the animal. We initially identified ANP and BNP in three species of dolphins (Lagenorhynchus obliquidens, Phocoenoides dalli and Tursiops truncatus). ANP precursors are highly conserved in most mammals, but dolphin BNP precursors were more variable. In molecular phylogenetic analyses, dolphin ANP and BNP precursors grouped with those of artiodactyls, particularly to the camel peptides. The chromatographic characterization of tissue and plasma molecular forms using specific radioimmunoassays showed that the predominant ANP and BNP in the atrium are prohormone and mature peptide, respectively, whereas mature ANP and BNP are circulating in the dolphin blood. A mass spectrometric analysis showed that atrial BNP consists of 26 amino acids, rather than the 32-amino-acid form detected in other mammals. Finally, changes in plasma ANP and BNP concentrations were examined in captive bottlenose dolphins (Tursiops truncatus) after their pool was drained. Plasma ANP and BNP concentrations did not change after landing, unlike terrestrial mammals. Plasma angiotensin II and cortisol concentrations did not change either, showing minor stress after landing. Since landed dolphins show a different cardiovascular status on land than terrestrial mammals, plasma ANP and BNP concentrations seem to reflect the cardiovascular status characteristic of dolphins.

  18. Natriuretic peptide-guided management in heart failure.

    PubMed

    Chioncel, Ovidiu; Collins, Sean P; Greene, Stephen J; Ambrosy, Andrew P; Vaduganathan, Muthiah; Macarie, Cezar; Butler, Javed; Gheorghiade, Mihai

    2016-08-01

    Heart failure is a clinical syndrome that manifests from various cardiac and noncardiac abnormalities. Accordingly, rapid and readily accessible methods for diagnosis and risk stratification are invaluable for providing clinical care, deciding allocation of scare resources, and designing selection criteria for clinical trials. Natriuretic peptides represent one of the most important diagnostic and prognostic tools available for the care of heart failure patients. Natriuretic peptide testing has the distinct advantage of objectivity, reproducibility, and widespread availability.The concept of tailoring heart failure management to achieve a target value of natriuretic peptides has been tested in various clinical trials and may be considered as an effective method for longitudinal biomonitoring and guiding escalation of heart failure therapies with overall favorable results.Although heart failure trials support efficacy and safety of natriuretic peptide-guided therapy as compared with usual care, the relationship between natriuretic peptide trajectory and clinical benefit has not been uniform across the trials, and certain subgroups have not shown robust benefit. Furthermore, the precise natriuretic peptide value ranges and time intervals of testing are still under investigation. If natriuretic peptides fail to decrease following intensification of therapy, further work is needed to clarify the optimal pharmacologic approach. Despite decreasing natriuretic peptide levels, some patients may present with other high-risk features (e.g. elevated troponin). A multimarker panel investigating multiple pathological processes will likely be an optimal alternative, but this will require prospective validation.Future research will be needed to clarify the type and magnitude of the target natriuretic peptide therapeutic response, as well as the duration of natriuretic peptide-guided therapy in heart failure patients.

  19. Atrial fibrillation (acute onset)

    PubMed Central

    2014-01-01

    Introduction Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in more than 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 26 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, atenolol, bisoprolol, carvedilol, digoxin, diltiazem, direct current cardioversion, flecainide, metoprolol, nebivolol, propafenone, sotalol, timolol, and verapamil. PMID:25430048

  20. Atrial Septal Defect (For Kids)

    MedlinePlus

    ... Dictionary of Medical Words En Español What Other Kids Are Reading Taking Care of Your Ears Taking ... an X-ray Atrial Septal Defect KidsHealth > For Kids > Atrial Septal Defect Print A A A What's ...

  1. Can Atrial Fibrillation Be Prevented?

    MedlinePlus

    ... from the NHLBI on Twitter. How Can Atrial Fibrillation Be Prevented? Following a healthy lifestyle and taking ... for heart disease may help you prevent atrial fibrillation (AF). These steps include: Following a heart healthy ...

  2. Stroke Prevention in Atrial Fibrillation

    MedlinePlus

    ... Association Cardiology Patient Page Stroke Prevention in Atrial Fibrillation Christian T. Ruff Download PDF https://doi.org/ ... an irregular and fast heartbeat. What Causes Atrial Fibrillation? Several factors and medical conditions make it more ...

  3. Loss of atrial contractility is primary cause of atrial dilatation during first days of atrial fibrillation.

    PubMed

    Schotten, Ulrich; de Haan, Sunniva; Neuberger, Hans-Ruprecht; Eijsbouts, Sabine; Blaauw, Yuri; Tieleman, Robert; Allessie, Maurits

    2004-11-01

    Atrial fibrillation (AF) induces a progressive dilatation of the atria which in turn might promote the arrhythmia. The mechanism of atrial dilatation during AF is not known. To test the hypothesis that loss of atrial contractile function is a primary cause of atrial dilatation during the first days of AF, eight goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. AF was induced with the use of repetitive burst pacing. Atrial contractility was assessed during sinus rhythm, atrial pacing (160-, 300-, and 400-ms cycle length), and electrically induced AF. The compliance of the fibrillating right atrium was measured during unloading the atria with diuretics and loading with 1 liter of saline. All measurements were repeated after 6, 12, and 24 h of AF and then once a day during the first 5 days of AF. Recovery of the observed changes after spontaneous cardioversion was also studied. After 5 days of AF, atrial contractility during sinus rhythm or slow atrial pacing was greatly reduced. During rapid pacing (160 ms) or AF, the amplitude of the atrial pressure waves had declined to 20% of control. The compliance of the fibrillating atria increased twofold, whereas the right atrial pressure was unchanged. As a result, the mean right atrial diameter increased by approximately 12%. All changes were reversible within 3 days of sinus rhythm. We conclude that atrial dilatation during the first days of AF is due to an increase in atrial compliance caused by loss of atrial contractility during AF. Atrial compliance and size are restored when atrial contractility recovers after cardioversion of AF.

  4. Natriuretic peptide type C induces sperm attraction for fertilization in mouse

    PubMed Central

    Kong, Nana; Xu, Xiaoting; Zhang, Yu; Wang, Yakun; Hao, Xiaoqiong; Zhao, Yu; Qiao, Jie; Xia, Guoliang; Zhang, Meijia

    2017-01-01

    Mammalian spermatozoa undergo selective movement along the isthmus of the oviduct to the ampulla during ovulation, which is a prerequisite for fertilization. The factor(s) that involves in selective spermatozoa movement is still unknown. In this study, we found that the oviductal epithelium in mouse ampulla expressed high levels of natriuretic peptide type C (NPPC) in the presence of ovulated oocyte-cumulus complexes (OCCs). Spermatozoa expressed NPPC receptor natriuretic peptide receptor 2 (NPR2, a guanylyl cyclase) on the midpiece of flagellum. NPPC increased intracellular levels of cGMP and Ca2+ of spermatozoa, and induced sperm accumulation in the capillary by attraction. Importantly, spermatozoa from Npr2 mutant mice were not attracted by NPPC, preventing fertilization in vivo. Oocyte-derived paracrine factors promoted the expression of Nppc mRNA in the ampulla. Therefore, NPPC secreted by oviductal ampulla attracts spermatozoa towards oocytes, which is essential for fertilization. PMID:28054671

  5. Methods for the development and assessment of atrial fibrillation and heart failure dog models

    PubMed Central

    Urban, Jon F; Gerhart, Renee L; Krzeszak, Jason R; Leet, Corey R; Lentz, Linnea R; McClay, Carolyn B

    2011-01-01

    Objective To report Medtronic experiences with the development of animal models for atrial fibrillation (AF) and chronic heart failure (CHF) using high-rate pacing for AF and microemboli for CHF. Methods For the AF model, an atrial lead was attached to a Medtronic Synergy™ neurostimulator, which was programmed to stimulate at 50 Hz in an on-off duty cycle. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and N-terminal pro brain natriuretic peptide (NT-proBNP) were assayed at select time points. For CHF model, a serial injection of 90 µm polystyrene microspheres at 62,400 beads/mL (Polybead, Polysciences, Inc.) was performed to induce global ischemia, either with weekly monitoring and embolization schedule (group 1, n = 25) or with biweekly monitoring and emboliation schedule (group 2, n = 36 ). Echocardiograms were used along with ventriculograms and magnetic resonance imaging scans weekly to assess cardiac function and ANP, BNP and NT-proBNP were monitored. Results For the AF model, the days to sustained AF for four animals following surgery were 7, 25, 21 and 19, respectively; For the CHF model, the days to meet CHF endpoints were 116 in group 1 and 89 in group 2. For both AF and CHF models, NT-proBNP correlated well with the development of disease states. Conclusion Our experience for the development and assessment of AF and CHF dog models may help researchers who are in search for animal model for assessing the safety and efficacy of a device-based therapy. PMID:22783299

  6. Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.

    PubMed

    Oliveira, Marcela Silva; Carmona, Fabio; Vicente, Walter V A; Manso, Paulo H; Mata, Karina M; Celes, Mara Rúbia; Campos, Erica C; Ramos, Simone G

    2017-02-18

    Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β1, β2-adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β1 and β2 receptors and

  7. Endurance sport practice as a risk factor for atrial fibrillation and atrial flutter.

    PubMed

    Mont, Lluís; Elosua, Roberto; Brugada, Josep

    2009-01-01

    Although the benefits of regular exercise in controlling cardiovascular risk factors have been extensively proven, little is known about the long-term cardiovascular effects of regular and extreme endurance sport practice, such as jogging, cycling, rowing, swimming, etc. Recent data from a small series suggest a relationship between regular, long-term endurance sport practice and atrial fibrillation (AF) and flutter. Reported case control studies included less than 300 athletes, with mean age between 40 and 50. Most series recruited only male patients, or more than 70% males, who had been involved in intense training for many years. Endurance sport practice increases between 2 and 10 times the probability of suffering AF, after adjusting for other risk factors. The possible mechanisms explaining the association remain speculative. Atrial ectopic beats, inflammatory changes, and atrial size have been suggested. Some of the published studies found that atrial size was larger in athletes than in controls, and this was a predictor for AF. It has also been shown that the left atrium may be enlarged in as many as 20% of competitive athletes. Other proposed mechanisms are increased vagal tone and bradycardia, affecting the atrial refractory period; however, this may facilitate rather than cause the arrhythmia. In summary, recent data suggest an association between endurance sport practice and atrial fibrillation and flutter. The underlying mechanism explaining this association is unclear, although structural atrial changes (dilatation and fibrosis) are probably present. Larger longitudinal studies and mechanistic studies are needed to further characterize the association to clarify whether a threshold limit for the intensity and duration of physical activity may prevent AF, without limiting the cardiovascular benefits of exercise.

  8. [Differences in atrial remodelling between right and left atria in patients with chronic atrial fibrillation].

    PubMed

    Tamargo Menéndez, Juan

    2011-01-01

    Atrial fibrillation starts in the left atrium and from there the activity invades the atrial tissues and causes an inhomogeneous shortening the duration of atrial action potential duration and refractoriness. The purpose of this study was to compare the voltage-dependent potassium currents in human cells isolated from the right and left atria and to determine whether electrical remodeling produced by chronic atrial fibrillation (CAF) differentially affects voltage-dependent potassium currents involved in atrial repolarization in each atrium as compared to sinus rhythm (SR). The currents were recorded using the whole-cell configuration of the patch-clamp technique. We found that in atrial cardiomyocytes of patients both in SR and in CAF there are three types of cells according to their main voltage-dependent repolarizing potassium current: the Ca(2+)-independent 4-aminopyridine sensitive component of the transient outward current (I(to1)) and the ultrarapid (I(Kur)), rapid (I(Kr)) and slow (I(Ks)) components of the delayed rectifier current. CAF differentially modified the proportion of these 3 types of cells on each atrium: CAF reduced the I(to1) more markedly in the left than in the right atria, while I(Kur) was more markedly reduced in the right than in the left atria. Interestingly, in both atria, CAF markedly increased the I(Ks). This increase was enhanced by isoproterenol and suppressed by atenolol. These changes produce a non-uniform shortening of atrial repolarization that facilitates the reentry of the cardiac impulse and the perpetuation of the arrhythmia.

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

    PubMed

    Matějková, Adéla; Šteiner, Ivo

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

  10. Atrial and ventricular tachyarrhythmias in military personnel.

    PubMed

    Posselt, Bonnie N; Cox, A T; D'Arcy, J; Rooms, M; Saba, M

    2015-09-01

    Although rare, sudden cardiac death does occur in British military personnel. In the majority of cases, the cause is considered to be a malignant ventricular tachyarrhythmia, which can be precipitated by a number of underlying pathologies. Conversely, a tachyarrhythmia may have a more benign and treatable cause, yet the initial clinical symptoms may be similar, making differentiation difficult. This is an overview of the mechanisms underlying the initiation and propagation of arrhythmias and the various pathological conditions that predispose to arrhythmia genesis, classified according to which parts of the heart are involved: atrial tachyarrhythmias, atrial and ventricular, as well as those affecting the ventricles alone. It encompasses atrial tachycardia, atrial flutter, supraventricular tachycardias and ventricular tachycardias, including the more commonly encountered inherited primary electrical diseases, also known as the channelopathies. The clinical features, investigation and management strategies are outlined. The occupational impact-in serving military personnel and potential recruits-is described, with explanations relating to the different conditions and their specific implication on continued military service.

  11. 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.

  12. Surgery for Atrial Fibrillation

    PubMed Central

    Lawrance, Christopher P.; Henn, Matthew C.; Damiano, Ralph J.

    2015-01-01

    Synopsis Atrial fibrillation is the most common cardiac arrhythmia and its treatment options include drug therapy or, catheter-based or surgical interventions. The surgical treatment of atrial fibrillation has undergone multiple evolutions over the last several decades. The Cox-Maze procedure which was developed by James Cox in 1987 is a procedure where multiple surgical incisions are created along the atria to interrupt the electrical pathways thought to allow atrial fibrillation to persist. This procedure went on to become the gold standard for the surgical treatment of atrial fibrillation and is currently in its 4th iteration called the Cox-Maze IV. The Cox-Maze IV replaced the previous “cut-and-sew” method with a combination of cryoablation and bipolar RF ablation. The adaption of ablation technologies allowed the Cox-Maze IV procedure to be performed through a less invasive right minithoracotomy instead of a traditional sternotomy approach. The aim of this article is to review the indications and preoperative planning for performing a Cox-Maze IV procedure. A description of the operative techniques for both a sternotomy and right mini-thoracotomy approach will be discussed in addition to specific postoperative considerations. Finally, this article will review the literature describing the surgical results for both approaches including comparisons of the Cox-Maze IV to the previous “cut-and-sew” method. PMID:25443237

  13. Augmented potassium current is a shared phenotype for two genetic defects associated with familial atrial fibrillation

    PubMed Central

    Abraham, Robert L; Yang, Tao; Blair, Marcia; Roden, Dan M; Darbar, Dawood

    2009-01-01

    Background Mutations in multiple genes have been implicated in familial atrial fibrillation (AF), but the underlying mechanisms, and thus implications for therapy, remain ill-defined. Methods and Results Among 231 participants in the Vanderbilt AF Registry, we found a mutation in KCNQ1 (encoding the α-subunit of slow delayed rectifier potassium current [IKs]) and separately a mutation in natriuretic peptide precursor A (NPPA) gene (encoding atrial natriuretic peptide, ANP), both segregating with early-onset lone AF in different kindreds. The functional effects of these mutations yielded strikingly similar IKs “gain of function.” In Chinese Hamster Ovary (CHO) cells, coexpression of mutant KCNQ1 with its ancillary subunit KCNE1 generated ~3-fold larger currents that activated much faster than wild-type (WT)-IKs. Application of the WT NPPA peptide fragment produced similar changes in WT-IKs, and these were exaggerated with the mutant NPPA S64R peptide fragment. Anantin, a competitive ANP receptor antagonist, completely inhibited the changes in IKs gating observed with NPPA-S64R. Computational simulations identified accelerated transitions into open states as the mechanism for variant IKs gating. Incorporating these IKs changes into computed human atrial action potentials (AP) resulted in 37% shortening (120 vs. 192 ms at 300 ms cycle length), reflecting loss of the phase II dome which is dependent on L-type calcium channel current. Conclusions We found striking functional similarities due to mutations in KCNQ1 and NPPA genes which led to IKs “gain of function”, atrial AP shortening, and consequent altered calcium current as a common mechanism between diverse familial AF syndromes. PMID:19646991

  14. Clinical value of natriuretic peptides in chronic kidney disease.

    PubMed

    Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

    2015-01-01

    According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure.

  15. Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature

    PubMed Central

    Thangam, Manoj; Nathan, Sriram; Kar, Biswajit; Petrovic, Marija; Patel, Manish; Loyalka, Pranav; Buja, L. Maximilian

    2016-01-01

    We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions. PMID:27303240

  16. Posterior left atrial wall hematoma mimicking cystic intracavitary atrial mass.

    PubMed

    Bahnacy, Yasser; Suresh, Cheriyil; Dawoud, Hamed; Zubaid, Mohammad

    2010-10-01

    Atrial myxoma is the most common benign primary tumor of the heart most commonly in the left atrium (LA). Cystic or cavitated intracardiac masses are rare. We report the case of a 43-year-old male patient admitted with chest infection, hemoptysis, and severe respiratory distress, who had to be ventilated. Chest computed tomography showed bilateral lung consolidation with large mass occupying the region of the LA. Transthoracic echocardiography and transesophageal echocardiography showed a large intracavitary left atrial cystic mobile mass. Open-heart surgical exploration did not show any mass inside the LA. A posterior left atrial wall hematoma was found and evacuated. Biopsies confirmed the presence of blood clots. Posterior left atrial wall hematoma may appear as left atrial intracavitary cystic mass and should be included in the differential diagnosis of cystic left atrial mass.

  17. Genetics Home Reference: familial atrial fibrillation

    MedlinePlus

    ... Home Health Conditions familial atrial fibrillation familial atrial fibrillation Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Familial atrial fibrillation is an inherited condition that disrupts the heart's ...

  18. A new atrial septostomy technique.

    PubMed

    Park, S C; Zuberbuhler, J R; Neches, W H; Lenox, C C; Zoltun, R A

    1975-01-01

    Balloon atrial septostomy is usually ineffective if the atrial septum is thickened. A technique for incising the atrial septum is described. A no. 6 French catheter was modified to enclose a tiny surgical blade. The distal end of the blade was pivoted to the catheter tip, and the proximal end was attached to a guide wire in the catheter lumen. Advancing the guide wire protruded the blade through a slit in the long axis of the tip of the catheter. Atrial septostomy was performed in five newborn lambs in vivo and in adult dog hearts and human hearts in vitro by advancing the catheter tip across the atrial septum with the blade retracted and withdrawing it to the right atrium with the blade extended. Eight to 12 mm lacerations of the atrial septum were produced and could be extended by subsequent balloon septostomy. The technique may be useful when balloon septostomy has been ineffective.

  19. Multimodality imaging in the assessment of cardiac lymphoma presented as new-onset atrial fibrillation.

    PubMed

    Trifunovic, Danijela; Vujisic-Tesic, Bosiljka; Vuckovic, Maja; Ostojic, Miodrag; Ristic, Arsen; Bogdanovic, Andrija; Mihaljevic, Biljana; Andjelic, Bosko; Perunicic-Jovanovic, Maja; Antonic, Zelimir

    2010-03-01

    Cardiac involvement by non-Hodgkin's lymphoma is not uncommon, however rarely diagnosed during life due to nonspecific clinical presentation. We report a case of secondary cardiac lymphoma in patient who presented with new-onset atrial fibrillation. Cardiac lymphoma was in a form of bulky right atrial mass, infiltrating the atrial septum and cavo-atrial junction with concomitant mild pericardial effusion. In the present case, we illustrate complementary role of transthoracic, transesophageal echocardiography and multislice CT scan with three-dimensional reconstruction, in detection and evaluation of secondary cardiac tumor. Usefulness of echocardiography to follow up the effects of chemotherapy is also shown.

  20. Chronic treatment with trimetazidine reduces the upregulation of atrial natriuretic peptide in heart failure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trimetazidine (TMZ) is effective for the treatment of ischemic cardiomyopathy; however, little is known about the effect of TMZ in established injury-induced heart failure. When rats with established infarct-induced heart failure were treated for 12 weeks with TMZ there was no effect on left ventric...

  1. Distribution and elimination of intravenously administered atrial natriuretic hormone(ANH) to normal and nephrectomized rats

    SciTech Connect

    Devine, E.; Artman, L.; Budzik, G.; Bush, E.; Holleman, W.

    1986-05-01

    The 24 amino acid peptide, ANH(5-28), was N-terminally labeled with I-125 Bolton-Hunter reagent, iodo-N-succinimidyl 3-(4-hydroxyphenyl)propionate. The I-125 peptide plus 1..mu..g/kg of the I-127 Bolton-Hunter peptide was injected into normal and nephrectomized anesthetized (Nembutal) rats. Blood samples were drawn into a cocktail developed to inhibit plasma induced degradation. Radiolabeled peptides were analyzed by HPLC. A biphasic curve of I-125 ANH(5-28) elimination was obtained, the first phase (t 1/2 = 15 sec) representing in vivo distribution and the second phase (t 1/2 = 7-10 min) a measurement of elimination. This biphasic elimination curve was similar in normal and nephrectomized rats. The apparent volumes of distribution were 15-20 ml for the first phase and > 300 ml for the second phase. In order to examine the tissue distribution of the peptide, animals were sacrificed at 2 minutes and the I-125 tissue contents were quantitated. The majority of the label was located in the liver (50%), kidneys (21%) and the lung (5%). The degradative peptides appearing in the plasma and urine of normal rats were identical. No intact radiolabeled ANH(5-28) was found in the urine. In conclusion, iodinated Bolton-Hunter labeled ANH(5-28) is rapidly removed from the circulation by the liver and to a lesser extent by the kidney, but the rate of elimination is not decreased by nephrectomy.

  2. Atrial natriuretic peptide in the rat brain and plasma during clinical death and after resuscitation.

    PubMed

    Kapuściński, A

    1994-01-01

    By means of the radioimmunologic method changes of ANP content in the rat brain and plasma have been evaluated during 5-min clinical death and up to 2 hr after resuscitation. Ischemia did not produce significant rise of ANP immunoreactivity in the brain, however, in the early postresuscitation period its reversible increase was noted with the peak value at 15th min. The content of peptide in plasma significantly increased at the end of clinical death and 5 min after resuscitation. The obtained results can support the notion of quantitative relationship between concentration of ANP and cGMP content in the brain in vivo.

  3. Atrial fibrillation in the elderly

    PubMed Central

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

    2012-01-01

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

  4. Diuretic and natriuretic activity of two mistletoe species in rats

    PubMed Central

    Jadhav, Namita; Patil, C. R.; Chaudhari, K. B.; Wagh, J. P.; Surana, S. J.; Jadhav, R. B.

    2010-01-01

    In different cultural groups, the hemiparasitic plants of the families Loranthaceae and Viscaceae (mistletoes) are frequently used in the treatment of hypertension and/or as diuretic agents. However, it remains unclear as to what commonality makes them diuretic agents or a remedy for hypertension. In this article, the diuretic activity of methanol extracts of Viscum articulatum (VA) Burm. f. and Helicanthus elastica (HE) (Ders.) Dans. in rats is reported. The extracts were administered orally at doses of 100, 200 and 400 mg/kg to rats that had been fasted and deprived of water for 18 hours. Investigations were carried out for diuretic, saluretic and natriuretic effects. The polyphenolic and triterpenoid contents were determined quantitatively using chemical assays and high performance liquid chromatography (HPLC) analysis, respectively. The extracts of VA and HE demonstrated significant and dose-dependent diuretic activity in rats. It was found that while VA mimics the furosemide pattern, HE demonstrated a dose-dependent increase in diuresis, along with an increase in potassium-sparing effects. Phytochemical analysis revealed that polyphenolics and triterpenoids, such as oleanolic acid and lupeol, are the major phytochemicals involved. It was also found that in different combinations, these phytochemicals differed in the way they influenced the electrolyte excretion. A higher content of polyphenolics in association with lower triterpenoid content was found to favor potassium-sparing effects. PMID:21808540

  5. Reflex effects on the heart of stimulating left atrial receptors

    PubMed Central

    Furnival, C. M.; Linden, R. J.; Snow, H. M.

    1971-01-01

    1. Stimulation of left atrial receptors, by distension of the pulmonary vein/left atrial junctions, is known to cause a reflex increase in heart rate; the efferent pathway is known to be solely in the sympathetic nerves. 2. In expectation of a concomitant positive inotropic response the effect of stimulating the left atrial receptors on the inotropic state of the left ventricle was studied, using as a known sensitive index of inotropic changes the maximal rate of rise of pressure in the left ventricle (dP/dt max). 3. Stimulation of left atrial receptors resulted in an increase in heart rate but there were no significant concomitant changes in dP/dt max. 4. It is concluded that activity in this discrete efferent pathway does not include an inotropic effect on the left ventricle and therefore the reflex involves only those sympathetic nerves which innervate the sinu-atrial node. 5. The possible function of atrial receptors in the regulation of heart volumes is discussed. PMID:5124571

  6. [Atrial fibrillation ablation: application of nurse methodology].

    PubMed

    Ramos-González-Serna, Amelia; Mateos-García, M Dolores

    2011-01-01

    Ablation of pulmonary veins for treatment of atrial fibrillation involves applying radiofrequency energy wave by a catheter that causes a circumferential lesion to achieve electrical isolation and voltage drop in the interior. It is mainly applied when there is resistance to treatment and recurrence of symptoms affecting the quality of life of patients. The nurse is an important part of the multidisciplinary team who care for patients who undergo this procedure. The provision of comprehensive nursing care should include nursing procedures prior to, during, and after treatment to ensure the careful and systematic quality required. The aims of this article are: to provide specialised knowledge on the procedure of atrial fibrillation ablation, to describe the preparation of the electrophysiology laboratory, analyse nursing care and develop a standardized care plan for patients on whom this procedure is performed using the NANDA (North American Nursing Association) taxonomy and NIC (Nursing Intervention Classification).

  7. Atrial fibrillation, progression of coronary atherosclerosis and myocardial infarction.

    PubMed

    Bayturan, Ozgur; Puri, Rishi; Tuzcu, E Murat; Shao, Mingyuan; Wolski, Kathy; Schoenhagen, Paul; Kapadia, Samir; Nissen, Steven E; Sanders, Prashanthan; Nicholls, Stephen J

    2017-03-01

    Background Despite atrial fibrillation representing an established risk factor for stroke, the association between atrial fibrillation and both progression of coronary atherosclerosis and major adverse cardiovascular events is not well characterized. We assessed the serial measures of coronary atheroma burden and cardiovascular outcomes in patients with and without atrial fibrillation. Methods Data were analyzed from nine clinical trials involving 4966 patients with coronary artery disease undergoing serial intravascular ultrasonography at 18-24 month intervals to assess changes in percent atheroma volume (PAV). Using a propensity weighted analysis, and following adjustment for baseline variables, patients with ( n = 190) or without ( n = 4776) atrial fibrillation were compared with regard to coronary plaque volume and major adverse cardiovascular events (death, myocardial infarction, and stroke). Results Atrial fibrillation patients demonstrated lower baseline PAV (36.0 ± 8.9 vs. 38.1 ± 8.9%, p = 0.002) and less PAV progression (-0.07 ± 0.34 vs. + 0.23 ± 0.34%, p = 0.001) compared with the non-atrial fibrillation group. Multivariable analysis revealed atrial fibrillation to independently predict both myocardial infarction [HR, 2.41 (1.74,3.35), p<0.001] 2.41 (1.74, 3.35), p < 0.00) and major adverse cardiovascular events [HR, 2.2, (1.66, 2.92), p<0.001] 2.20 (1.66, 2.92), p < 0.001]. Kaplan-Meier analysis showed that atrial fibrillation compared with non-atrial fibrillation patients had a significantly higher two-year cumulative incidence of overall major adverse cardiovascular events (4.4 vs. 2.0%, log-rank p = 0.02) and myocardial infarction (3.3 vs. 1.5%, log-rank p = 0.05). Conclusions The presence of atrial fibrillation independently associates with a heightened risk of myocardial infarction despite a lower baseline burden and progression rate of coronary atheroma. Further studies are necessary to define

  8. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    PubMed Central

    Abdelalim, Essam M.; Bellier, Jean-Pierre; Tooyama, Ikuo

    2016-01-01

    Brain natriuretic peptide (BNP) exerts its functions through NP receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn (DH) of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and dorsal root ganglion (DRG). BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the DH of the spinal cord and in the neurons of the intermediate column (IC) and ventral horn (VH). Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I–II) labeled with calcitonin gene-related peptide (CGRP), suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase (ChAT) in the motor neurons of the VH. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NP receptor-A (NPR-A) and/or NP receptor-B (NPR-B) at the spinal cord level. PMID:27994541

  9. Atrial metabolism and tissue perfusion as determinants of electrical and structural remodelling in atrial fibrillation.

    PubMed

    Opacic, Dragan; van Bragt, Kelly A; Nasrallah, Hussein M; Schotten, Ulrich; Verheule, Sander

    2016-04-01

    Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice. Over decades of research, a vast amount of knowledge has been gathered about the causes and consequences of AF related to cellular electrophysiology and features of the tissue structure that influence the propagation of fibrillation waves. Far less is known about the role of myocyte metabolism and tissue perfusion in the pathogenesis of AF. However, the rapid rates of electrical activity and contraction during AF must present an enormous challenge to the energy balance of atrial myocytes. This challenge can be met by scaling back energy demand and by increasing energy supply, and there are several indications that both phenomena occur as a result of AF. Still, there is ample evidence that these adaptations fall short of redressing this imbalance, which may represent a driving force for atrial electrical as well as structural remodelling. In addition, several 'metabolic diseases' such as diabetes, obesity, and abnormal thyroid function precipitate some well-known 'culprits' of the AF substrate such as myocyte hypertrophy and fibrosis, while some other AF risk factors, such as heart failure, affect atrial metabolism. This review provides an overview of metabolic and vascular alterations in AF and their involvement in its pathogenesis.

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

    SciTech Connect

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

    2015-08-14

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

  11. 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

  12. Left Atrial Epicardial Adiposity and Atrial Fibrillation

    PubMed Central

    Batal, Omar; Schoenhagen, Paul; Shao, Mingyuan; Ayyad, Ala Eddin; Van Wagoner, David R.; Halliburton, Sandra S.; Tchou, Patrick J.; Chung, Mina K.

    2010-01-01

    Background Atrial fibrillation (AF) has been linked to inflammatory factors and obesity. Epicardial fat is a source of several inflammatory mediators related to the development of coronary artery disease. We hypothesized that periatrial fat may have a similar role in the development of AF. Methods and Results Left atrium (LA) epicardial fat pad thickness was measured in consecutive cardiac CT angiograms performed for coronary artery disease or AF. Patients were grouped by AF burden: no (n=73), paroxysmal (n=60), or persistent (n=36) AF. In a short-axis view at the mid LA, periatrial epicardial fat thickness was measured at the esophagus (LA-ESO), main pulmonary artery, and thoracic aorta; retrosternal fat was measured in axial view (right coronary ostium level). LA area was determined in the 4-chamber view. LA-ESO fat was thicker in patients with persistent AF versus paroxysmal AF (P=0.011) or no AF (P=0.003). LA area was larger in patients with persistent AF than paroxysmal AF (P=0.004) or without AF (P<0.001). LA-ESO was a significant predictor of AF burden even after adjusting for age, body mass index, and LA area (odds ratio, 5.30; 95% confidence interval, 1.39 to 20.24; P=0.015). A propensity score–adjusted multivariable logistic regression that included age, body mass index, LA area, and comorbidities was also performed and the relationship remained statistically significant (P=0.008). Conclusions Increased posterior LA fat thickness appears to be associated with AF burden independent of age, body mass index, or LA area. Further studies are necessary to examine cause and effect, and if inflammatory, paracrine mediators explain this association. PMID:20504944

  13. [Non-pharmacologic treatment of atrial fibrillation].

    PubMed

    Csanádi, Zoltán; Fazekas, Tamás; Varró, András

    2003-06-29

    The authors provide an update on non-pharmacological treatment of atrial fibrillation (AF). They emphasize that although antiarrhythmic drugs continue to be first-line therapy for the arrhythmia considered to be a cardiovascular epidemic, clinical research to develop non-pharmacological means of treatment has been unprecedentally intensified during the last decade. Electrical cardioversion is the most successful non-pharmacological method to restore sinus rhythm, also the efficacy and safety of AV node ablation for palliative ventricular rate-controll is established. "Hybrid" therapeutic procedures, involving combinations of pharmacological and non-pharmacological interventions have gained widespread use. Curative transcatheter ablation for arrhythmia prevention is to be considered in case of clinical suggestions that AF is initiated by a primary regular arrhythmia that is amenable to routine catheter ablation (secondary AF). Despite encouraging results, at this point in time, curative catheter ablation for primary AF may offer significant improvement or even cure only for a small subset of patients, mostly young individuals with normal heart, and paroxysmal AF with frequent, symptomatic episodes refractory to multiple antiarrhythmic drugs. These interventions are to be performed in the settings of a clinical research project in some institutions. Regarding pacemaker therapy in case of bradycardia indication, physiologic pacing (AAI or DDD) is associated with significantly lower incidence of atrial fibrillation than ventricular pacing. Large-scale randomized controlled trials are needed to assess the clinical value of specially designed implantable devices to prevent atrial fibrillation in patients with no conventional bradycardia indication. Also, technical optimization and proper clinical evaluation is needed for implantable atrioverters and implantable cardioverter defibrillators capable of atrial cardioversion therapy.

  14. Uncontrolled ventricular rate in atrial fibrillation. A manifestation of dissimilar atrial rhythms.

    PubMed Central

    Leier, C V; Johnson, T M; Lewis, R P

    1979-01-01

    A patient with coarse atrial fibrillation and a rapid ventricular response developed periods of high grade atrioventricular block interpersed with periods of rapid ventricular conduction after the administration of digitalis and propranolol. Intracardiac atrial recordings showed similar atrial rhythms of high right atrial flutter and left atrial fibrillation. The low right atrial recordings showed flutter during the periods of fast ventricular rates and fibrillation during periods of slower ventricular rates. Images PMID:475927

  15. [Perioperative management of atrial fibrillation].

    PubMed

    Arguis, M J; Navarro, R; Regueiro, A; Arbelo, E; Sierra, P; Sabaté, S; Galán, J; Ruiz, A; Matute, P; Roux, C; Gomar, C; Rovira, I; Mont, L; Fita, G

    2014-05-01

    Atrial fibrillation is a frequent complication in the perioperative period. When it appears there is an increased risk of perioperative morbidity due to stroke, thromboembolism, cardiac arrest, myocardial infarction, anticoagulation haemorrhage, and hospital readmissions. The current article focuses on the recommendations for the management of perioperative atrial fibrillation based on the latest Clinical Practice Guidelines on atrial fibrillation by the European Society of Cardiology and the Spanish Society of Cardiology. This article pays special attention to the preoperative management, as well as to the acute perioperative episode. For this reason, the latest recommendations for the control of cardiac frequency, antiarrhythmic treatment and anticoagulation are included.

  16. Electrophysiologic basis of catheter ablation in atrial flutter.

    PubMed

    Touboul, P; Saoudi, N; Atallah, G; Kirkorian, G

    1989-12-05

    A reentrant mechanism is believed to be responsible for atrial flutter. The recent development of the entrainment criteria further supports this theory, and there is a general consensus that circus movement is the underlying abnormality that supports this arrhythmia. In most clinical studies, abnormal fragmented (or double spike) electrograms, suggesting the presence of areas of localized slowing of conduction or block, have been reported. They are almost always recorded in the lower and posterior portion of the right interatrial septum, but also frequently in the high lateral portion of the right atrium. The determination of their involvement in the reentry pathway is important for designing curative procedures such as surgery or ablation. The low atrial septal area surrounding the mouth of the coronary sinus was suspected as being the critical area of slow conduction in atrial flutter. Rapid pacing at that site can yield a surface electrocardiographic pattern similar to the clinically occurring arrhythmias. Additionally, the flutter circuit can be accelerated during atrial pacing at fixed and slightly faster rates than the intrinsic tachycardia rate--the so-called entrainment phenomenon. When entrainment criteria are fulfilled, tachycardia termination being by definition ruled out, any concomitant recorded local type II block identifies an area that must be outside the circuit. Such local block may be recorded either spontaneously or during entrainment and therefore helps in identifying atrial slow conduction areas that do not belong to the reentrant path. This approach was applied to identify the optimal ablation site in 8 patients with long-standing drug resistant atrial flutter. In 7 of 8 patients, we were able to identify a fragmented potential in the low posteroseptal area during sustained atrial flutter.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Atrial Fibrillation, Neurocognitive Decline and Gene Expression After Cardiopulmonary Bypass

    PubMed Central

    Dalal, Rahul S.; Sabe, Ashraf A.; Elmadhun, Nassrene Y.; Ramlawi, Basel; Sellke, Frank W.

    2015-01-01

    OBJECTIVE Atrial fibrillation and neurocognitive decline are common complications after cardiopulmonary bypass. By utilizing genomic microarrays we investigate whether gene expression is associated with postoperative atrial fibrillation and neurocognitive decline. METHODS Twenty one cardiac surgery patients were prospectively matched and underwent neurocognitive assessments pre-operatively and four days postoperatively. The whole blood collected in the pre-cardiopulmonary bypass, 6 hours after-cardiopulmonary bypass, and on the 4th postoperative day was hybridized to Affymetrix Gene Chip U133 Plus 2.0 Microarrays. Gene expression in patients who developed postoperative atrial fibrillation and neurocognitive decline (n=6; POAF+NCD) was compared with gene expression in patients with postoperative atrial fibrillation and normal cognitive function (n=5; POAF+NORM) and patients with sinus rhythm and normal cognitive function (n=10; SR+NORM). Regulated genes were identified using JMP Genomics 4.0 with a false discovery rate of 0.05 and fold change of >1.5 or <-1.5. RESULTS Eleven patients developed postoperative atrial fibrillation. Six of these also developed neurocognitive decline. Of the 12 patients with sinus rhythm, only 2 developed neurocognitive decline. POAF+NCD patients had unique regulation of 17 named genes preoperatively, 60 named genes six hours after cardiopulmonary bypass, and 34 named genes four days postoperatively (P<0.05) compared with normal patients. Pathway analysis demonstrated that these genes are involved in cell death, inflammation, cardiac remodeling and nervous system function. CONCLUSION Patients who developed postoperative atrial fibrillation and neurocognitive decline after cardiopulmonary bypass may have differential genomic responses compared to normal patients and patients with only postoperative atrial fibrillation, suggesting common pathophysiology for these conditions. Further exploration of these genes may provide insight into the

  18. Atrial fibrillation and heart failure: is atrial fibrillation a disease?

    PubMed

    Tilman, V

    2014-09-01

    Atrial fibrillation in heart failure often occur together. The relationship between atrial fibrillation and heart failure has remained a subject of research. The main manifestation of the violation of hydrodynamics in heart failure is the increased end-diastolic pressure, which is transmitted through the intercommunicated system (left ventricle-left atrium-pulmonary veins-alveolar capillaries) causing increased pulmonary wedge pressure with the danger for pulmonary edema. End-diastolic pressure is the sum of left ventricle diastolic pressure and left atrial systolic pressure. Stopping the mechanical systole of the left atrium can reduce the pressure in the system in heart failure. Atrial fibrillation stops the mechanical systole of the left atrium and decreases the intercommunicating pressure and pulmonary wedge pressure. It is possible that atrial fibrillation is a mechanism for protection from increasing end-diastolic pressure and pulmonary wedge pressure, and prevents the danger of pulmonary edema. This hypothesis may explain the relationship between heart failure and atrial fibrillation and their frequent association.

  19. A new endogenous natriuretic factor: LLU-alpha.

    PubMed Central

    Wechter, W J; Kantoci, D; Murray, E D; D'Amico, D C; Jung, M E; Wang, W H

    1996-01-01

    For over three decades, renal physiology has sought a putative natriuretic hormone (third factor) that might control the body's pool of extracellular fluid, an important determinant in hypertension, congestive heart failure, and cirrhosis. In our search for this hormone, we have isolated several pure natriuretic factors from human uremic urine that would appear, alone or in combination, to mark a cluster of phenomena previously presumed to be that of a single "natriuretic hormone." This paper reports the purification, chemical structure, and total synthesis of the first of these compounds, LLU-alpha, which proved to be 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman, presumably a metabolite of gamma-tocopherol. Both natural LLU-alpha and synthetic material are identical (except for optical activity) with respect to structure and biological activity. It appears that the natriuretic activity of LLU-alpha is mediated by inhibition of the 70 pS K+ channel in the apical membrane of the thick ascending limb of the kidney. Images Fig. 5 PMID:8650209

  20. Novel upstream approaches to prevent atrial fibrillation perpetuation.

    PubMed

    Jalife, José

    2014-11-01

    The mechanisms underlying atrial fibrillation (AF) in humans are poorly understood. In particular, we simply do not understand how atrial AF becomes persistent or permanent. The objective of this brief review is to address the most important factors involved in the mechanism of AF perpetuation, including structural remodeling in the form of fibrosis and electrical remodeling secondary to ion channel expression changes. In addition, I discuss the possibility that both fibrosis and electrical remodeling might be preventable when intervening pharmacologically early enough before the remodeling process reaches a point of no return.

  1. Successful treatment of mobile right atrial thrombus and acute pulmonary embolism with intravenous tissue plasminogen activator

    PubMed Central

    Bajaj, R; Ramanakumar, Ajay; Mamidala, Suresh; Kumar, Deepti

    2013-01-01

    An 89-year-old woman came with symptoms of progressively worsening dyspnoea at rest over the preceding week. She was normotensive, had elevated jugular venous pressure and clear lungs. ECG revealed atrial fibrillation with the rapid ventricular rate. Labs were significant for markedly elevated pro-brain natriuretic peptide of 43 000 pg/mL and troponin-T of 1 ng/mL. An urgent 2D echocardiogram was obtained, which revealed the severely dilated right atrium and a large linear mobile mass in the right atrium consistent with a thrombus. An emergent CT scan revealed multiple bilateral pulmonary emboli. She received intravenous tissue plasminogen activator. Repeat echocardiogram performed 6 h later showed no evidence of the right atrial thrombus. She was subsequently maintained on intravenous heparin and transitioned to Coumadin. Early recognition of this rare but potentially fatal complication is important as prompt treatment measures can help in preventing life-threatening complications of the right atrial thrombus. PMID:23892824

  2. Atrial Septal Defect (For Kids)

    MedlinePlus

    ... wall called the septum that normally separates the blue and red blood. In a person with an atrial septal defect, there's an opening in that wall. This hole in the wall lets oxygen-rich blood from ...

  3. Direct Measurement of Left Atrial Pressure during Routine Transradial Catheterization

    PubMed Central

    Fa'ak, Faisal; Younis, George

    2016-01-01

    Left atrial pressure indicates the left ventricular filling pressure in patients who have systolic or diastolic left ventricular dysfunction or valvular heart disease. The use of indirect surrogate methods to determine left atrial pressure has been essential in the modern evaluation and treatment of cardiovascular disease because of the difficulty and inherent risks associated with direct methods (typically the transseptal approach). One method that has been widely used to determine left atrial pressure indirectly is Swan-Ganz catheterization, in which a balloon-flotation technique is applied to measure pulmonary capillary wedge pressure; however, this approach has been associated with several limitations and potential risks. Measuring left ventricular end-diastolic pressure has also been widely used as a simple means to estimate filling pressures but remains a surrogate for the gold standard of directly measuring left atrial pressure. We describe a simple, low-risk method to directly measure left atrial pressure that involves the use of standard coronary catheterization techniques during a transradial procedure. PMID:28100968

  4. Atrial fibrillation and anabolic steroids.

    PubMed

    Sullivan, M L; Martinez, C M; Gallagher, E J

    1999-01-01

    A young male bodybuilder, consuming large doses of anabolic steroids (AS), presented to the Emergency Department (ED) with symptomatic rapid atrial fibrillation (AF). Echocardiogram revealed significant septal hypokinesis, and posterior and septal wall thickness at the upper limit of normal for highly trained athletes. The atrial fibrillation had not recurred at 10 weeks after discontinuation of AS use. Consumption of these agents in athletes has been associated with hypertension, ischemic heart disease, hypertrophic cardiomyopathy, and sudden death.

  5. Left Atrial Reverse Remodeling: Mechanisms, Evaluation, and Clinical Significance.

    PubMed

    Thomas, Liza; Abhayaratna, Walter P

    2017-01-01

    The left atrium is considered a biomarker for adverse cardiovascular outcomes, particularly in patients with left ventricular diastolic dysfunction and atrial fibrillation in whom left atrial (LA) enlargement is of prognostic importance. LA enlargement with a consequent decrease in LA function represents maladaptive structural and functional "remodeling" that in turn promotes electrical remodeling and a milieu conducive for incident atrial fibrillation. Medical and nonmedical interventions may arrest this pathophysiologic process to the extent that subsequent reverse remodeling results in a reduction in LA size and improvement in LA function. This review examines cellular and basic mechanisms involved in LA remodeling, evaluates the noninvasive techniques that can assess these changes, and examines potential mechanisms that may initiate reverse remodeling.

  6. 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.

  7. Pro-A-type natriuretic peptide and pro-adrenomedullin predict progression of chronic kidney disease: the MMKD Study.

    PubMed

    Dieplinger, Benjamin; Mueller, Thomas; Kollerits, Barbara; Struck, Joachim; Ritz, Eberhard; von Eckardstein, Arnold; Haltmayer, Meinhard; Kronenberg, Florian

    2009-02-01

    A-type natriuretic peptide (ANP) and adrenomedullin (ADM) are potent hypotensive, diuretic, and natriuretic peptides involved in maintaining cardiovascular and renal homeostasis. We conducted a prospective 7-year study of 177 nondiabetic patients with primary chronic kidney disease to see if ANP and ADM plasma concentrations predict the progression of their disease, using novel sandwich immunoassays covering the midregional epitopes of the stable prohormones (MRproANP and MR-proADM). Progression of chronic kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure, which occurred in 65 patients. Analysis of the receiver operating characteristic curve for the prediction of renal endpoints showed similar areas under the curve for the glomerular filtration rate (GFR) (0.838), MR-proANP (0.810), and MRproADM (0.876), respectively, as did the Kaplan-Meier curve analyses of the patients stratified according to the median of the respective markers. In separate multiple Cox-proportional hazard regression analyses, increased plasma concentrations of both peptides were each strongly predictive of the progression of chronic kidney disease after adjustments for age, gender, GFR, proteinuria and amino-terminal pro-B-type natriuretic peptide. Our study suggests that MR-proANP and MR-proADM are useful new markers of progression of primary nondiabetic chronic kidney disease.

  8. Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study).

    PubMed

    Käräjämäki, Aki J; Pätsi, Olli-Pekka; Savolainen, Markku; Kesäniemi, Y Antero; Huikuri, Heikki; Ukkola, Olavi

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are widespread diseases and have multiple common risk factors and comorbidities. No studies of association between ultrasonography-diagnosed NAFLD and AF exist in other than diabetic population. The goal of this prospective study was to study the value of NAFLD as a predictor of atrial fibrillation. This study had 958 subjects from the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort, and the mean follow-up time was 16.3 years. NAFLD was diagnosed if the subject had fatty liver in ultrasonography and no excess alcohol intake. AF was followed in the National Registers. In this study 249 subjects (26.0%) had NAFLD and 37 (14.9%) of these had AF whereas only 56 (7.9%) of those without NAFLD experienced AF during the follow-up time (p = 0.001). In the multiple Cox regression analysis including potential confounders (age, sex, study group, diabetes, body mass index (BMI), waist circumference, alcohol consumption, smoking, serum alanine aminotransferase concentration (ALT), systolic blood pressure, quick index, left ventricular mass index, left atrial diameter, coronary artery disease (CAD), atrial natriuretic peptide (ANP) and high sensitive C-reactive protein (hs-CRP)), NAFLD remained as an independent predictor of AF (Adjusted OR, 1.88 (95% Confidence interval (CI) 1.03-3.45)). In conclusion, our data shows that NAFLD is independently associated with the risk of AF.

  9. The impact of 6 weeks of atrial fibrillation on left atrial and ventricular structure and function

    PubMed Central

    Kazui, Toshinobu; Henn, Mathew C.; Watanabe, Yoshiyuki; Kovács, Sándor J.; Lawrance, Christopher P.; Greenberg, Jason W.; Moon, Marc; Schuessler, Richard B.; Damiano, Ralph J.

    2015-01-01

    Objective The impact of prolonged episodes of atrial fibrillation on atrial and ventricular function has been incompletely characterized. The purpose of this study was to investigate the influence of atrial fibrillation on left atrial and ventricular function in a rapid paced porcine model of atrial fibrillation. Methods A control group of pigs (group 1, n = 8) underwent left atrial and left ventricular conductance catheter studies and fibrosis analysis. A second group (group 2, n = 8) received a baseline cardiac magnetic resonance imaging to characterize left atrial and left ventricular function. The atria were rapidly paced into atrial fibrillation for 6 weeks followed by cardioversion and cardiac magnetic resonance imaging. Results After 6 weeks of atrial fibrillation, left atrial contractility defined by atrial end-systolic pressure-volume relationship slope was significantly lower in group 2 than in group 1 (1.1 ± 0.5 vs 1.7 ± 1.0; P = .041), whereas compliance from the end-diastolic pressure-volume relationship was unchanged (1.5 ± 0.9 vs 1.6 ± 1.3; P = .733). Compared with baseline, atrial fibrillation resulted in a significantly higher contribution of left atrial reservoir volume to stroke volume (32% vs 17%; P = .005) and lower left atrial booster pump volume contribution to stroke volume (19% vs 28%; P = .029). Atrial fibrillation also significantly increased maximum left atrial volume (206 ± 41 mL vs 90 ± 21 mL; P < .001). Left atrial fibrosis in group 2 was significantly higher than in group 1. Atrial fibrillation decreased left ventricular ejection fraction (29% ± 9% vs 58 ± 8%; P < .001), but left ventricular stroke volume was unchanged. Conclusions In a chronic model of atrial fibrillation, the left atrium demonstrated significant structural remodeling and decreased contractility. These data suggest that early intervention in patients with persistent atrial fibrillation might mitigate against adverse atrial and ventricular structural

  10. Right atrial tunnel to the left atrial appendage: a danger during balloon septostomy.

    PubMed

    Waldman, J D; McFeeley, P; Bornikova, L

    2001-01-01

    Right atrial tunnel to the left atrial appendage is a very rare anomaly not previously described. Per se, it has no physiological significance but is a source of potential disaster during balloon atrial septostomy. The precise anatomy is demonstrated and ways are proposed to avoid tearing the atrial wall during therapeutic cardiac catheterization.

  11. Wenxin Keli suppresses atrial substrate remodelling after epicardial ganglionic plexi ablation

    PubMed Central

    Xiao, Jinping; Zhao, Qingyan; Kebbati, A Hafid; Deng, Hongping; Wang, Xule; Dai, Zixuan; Yu, Shengbo; Huang, Congxin

    2013-01-01

    BACKGROUND: The chronic effects of ganglionic plexi (GP) ablation on atrial fibrillation (AF) inducibility have not been elucidated. OBJECTIVE: To investigate the effect of Wenxin Keli (WK) on the inducibility of AF and atrial substrate remodelling after epicardial GP ablation. METHODS: Twenty dogs were randomly divided into a sham-operated group, a GP ablation group and a WK-treated group. All animals underwent a left thoracotomy at the fourth intercostal space. AF inducibility was assessed by burst rapid pacing at the right atrium. Both the GP ablation group and the WK-treated group received four major GP ablations. In the WK-treated group, dogs were treated with oral WK once per day, and all animals were allowed to recover for eight weeks, after which AF inducibility and AF duration were measured again. RESULTS: After eight weeks of WK treatment, AF inducibility was lower than in the GP ablation group, and was similar to that of the sham-operated group. Compared with the sham-operated group, the levels of atrial natriuretic peptide (ANP), tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6 in right atrial tissues were increased in GP ablation group (143.6±33.7 pg/mg versus 206.2±41.4 pg/mg, P=0.02; 75.3±12.1 pg/mg versus 141.3±64 pg/mg, P=0.03; and 175.1±42.5 pg/mg versus 351.7±101 pg/mg, P<0.01, respectively). There were no significant differences in levels of ANP, TNF-α and IL-6 in atrial tissues between the sham-operated group and WK treated group. Expression of connexin 43 in atrial tissues was increased after eight weeks of GP ablation, while WK administration inhibited connexin 43 remodelling. CONCLUSIONS: Epicardial GP ablation can induce atrial substrate remodelling, including Cx43 upregulation and increased levels of ANP, TNF-α and IL-6. These changes may be suppressed by long-term oral WK administration. PMID:23940442

  12. 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

  13. Atrial fibrillation in endurance athletes.

    PubMed

    Wilhelm, Matthias

    2014-08-01

    There is a growing population of veteran endurance athletes, regularly participating in training and competition. Although the graded benefit of exercise on cardiovascular health and mortality is well established, recent studies have raised concern that prolonged and strenuous endurance exercise may predispose to atrial and ventricular arrhythmias. Atrial fibrillation (AF) and atrial flutter are facilitated by atrial remodelling, atrial ectopy, and an imbalance of the autonomic nervous system. Endurance sports practice has an impact on all of these factors and may therefore act as a promoter of these arrhythmias. In an animal model, long-term intensive exercise training induced fibrosis in both atria and increased susceptibility to AF. While the prevalence of AF is low in young competitive athletes, it increases substantially in the aging athlete, which is possibly associated with an accumulation of lifetime training hours and participation in competitions. A recent meta-analysis revealed a 5-fold increased risk of AF in middle-aged endurance athletes with a striking male predominance. Beside physical activity, height and absolute left atrial size are independent risk factors for lone AF and the stature of men per se may explain part of their higher risk of AF. Furthermore, for a comparable amount of training volume and performance, male non-elite athletes exhibit a higher blood pressure at rest and peak exercise, a more concentric type of left ventricular remodelling, and an altered diastolic function, possibly contributing to a more pronounced atrial remodelling. The sports cardiologist should be aware of the distinctive features of AF in athletes. Therapeutic recommendations should be given in close cooperation with an electrophysiologist. Reduction of training volume is often not desired and drug therapy not well tolerated. An early ablation strategy may be appropriate for some athletes with an impaired physical performance, especially when continuation of

  14. Role of Endovascular Closure of the Left Atrial Appendage in Stroke Prevention for Atrial Fibrillation.

    PubMed

    Kiani, Jawad; Holmes, David R

    2015-11-01

    The pathophysiologic mechanism of thromboembolic stroke in the setting of non-valvular atrial fibrillation (AF) resides in the left atrial appendage (LAA). In this setting, approximately 90 % of all strokes originate from this structure. Percutaneous left atrial appendage occlusion (LAAO) therapy has recently emerged as an important strategy for prevention of stroke and systemic embolism in patients with non-valvular AF. Systemic anticoagulation therapy in this AF population, while effective, is associated with a significant bleeding risk, drug compliance issues, and limited reversal strategies. In this manuscript, we will review the percutaneous devices and techniques that allow endovascular closure of the LAA, including their efficacy in stroke prevention, the safety profile of these local site-specific therapies, comparison of the multiple approaches being studied, the index patient populations involved, and long-term follow-up in comparison with systemic anticoagulation therapy. The percutaneous LAAO approach indeed represents an exciting and revolutionary advance in the field of stroke prevention in AF.

  15. Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway.

    PubMed

    Yamamoto, Takashi; Wada, Atsuyuki; Tsutamoto, Takayoshi; Ohnishi, Masato; Horie, Minoru

    2004-11-01

    In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.

  16. Atrial Myxoma: A Case Presentation and Review

    PubMed Central

    Cohen, Ronny; Singh, Gagandeep; Mena, Derrick; Garcia, Christine A.; Loarte, Pablo; Mirrer, Brooks

    2012-01-01

    Myxomas are the most common primary cardiac tumors, most frequently found in the left atrium. We present a case of an atrial myxoma. An in-depth review of atrial myxoma is presented, examining the important clinical symptoms and diagnostic indicators. The treatment of atrial myxoma is then discussed, with an emphasis on current therapies. An extensive literature review has been performed to present a comprehensive review of the causes, pathophysiology of atrial myxoma.

  17. Post-Acceleration Chaotic Atrial Rhythm

    DTIC Science & Technology

    1982-04-01

    atrial flutter or two discrete P-wave morphologies with the rate less fibrillation. than 100 bpm). and sinus bradycardia. An occasional The time...mulhilocal paroxysmal atrial tach.- cardia with cclic Wcnckchach phenomenon under observation examinations. The chaotic atrial rhythm in this case ji r 13...CHAOTIC ATRIAL RHYTHM Final Report 1 July 81 - 30 July 81 6. PERFORMING OIG. REPORT NUMBER 7. AUTHOR(s) 8 CONTRACT OR GRANT NUMBERS) r James E

  18. TGF-β1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease.

    PubMed

    Sun, Yu; Huang, Zi-Yang; Wang, Zhen-Hua; Li, Cui-Ping; Meng, Xian-Liang; Zhang, Yun-Jiao; Su, Feng; Ma, Nan

    2015-08-01

    To investigate the involvement of transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase 4 (TIMP-4) in influencing the severity of atrial fibrosis in rheumatic heart disease (RHD) patients with atrial fibrillation (AF). The degree of myocardial fibrosis was evaluated using Masson staining. The expression levels of TGF-β1, TIMP-4, matrix metalloproteinase-2 (MMP-2), type I collagen, and type III collagen were estimated by Western blot analysis. Additionally, TGF-β1 and TIMP-4 mRNA levels were quantified by qRT-PCR. The effect of TGF-β1 stimulation on TIMP-4 expression was assessed by in vitro stimulation of freshly isolated human atrial fibroblasts with recombinant human TGF-β1, followed by Western blot analysis to detect changes in TIMP-4 levels. Masson stain revealed that the left atrial diameter and collagen volume fraction were obviously increased in AF patients, compared to sinus rhythm (SR) controls (both P < 0.05). Western blot analysis showed significantly elevated levels of the AF markers MMP-2, type I collagen, and type III collagen in the AF group, in comparison to the SR controls (all P < 0.05). In the AF group, TGF-β1 expression was relatively higher, while TIMP-4 expression was apparently lower than the SR group (all P < 0.05). TIMP-4 expression level showed a negative association with TGF-β1 expression level (r = -0.98, P < 0.01) and TGF-β1 stimulation of atrial fibroblasts led to a sharp decrease in TIMP-4 protein level. Increased TGF-β1 expression and decreased TIMP-4 expression correlated with atrial fibrosis and ECM changes in the atria of RHD patients with AF. Notably, TGF-β1 suppressed TIMP-4 expression, suggesting that selective TGF-β1 inhibitors may be useful therapeutic agents.

  19. C-type natriuretic peptide stimulates ovarian follicle development.

    PubMed

    Sato, Yorino; Cheng, Yuan; Kawamura, Kazuhiro; Takae, Seido; Hsueh, Aaron J W

    2012-07-01

    C-type natriuretic peptide (CNP) encoded by the NPPC (Natriuretic Peptide Precursor C) gene expressed in ovarian granulosa cells inhibits oocyte maturation by activating the natriuretic peptide receptor (NPR)B (NPRB) in cumulus cells. RT-PCR analyses indicated increased NPPC and NPRB expression during ovarian development and follicle growth, associated with increases in ovarian CNP peptides in mice. In cultured somatic cells from infantile ovaries and granulosa cells from prepubertal animals, treatment with CNP stimulated cGMP production. Also, treatment of cultured preantral follicles with CNP stimulated follicle growth whereas treatment of cultured ovarian explants from infantile mice with CNP, similar to FSH, increased ovarian weight gain that was associated with the development of primary and early secondary follicles to the late secondary stage. Of interest, treatment with FSH increased levels of NPPC, but not NPRB, transcripts in ovarian explants. In vivo studies further indicated that daily injections of infantile mice with CNP for 4 d promoted ovarian growth, allowing successful ovulation induction by gonadotropins. In prepubertal mice, CNP treatment alone also promoted early antral follicle growth to the preovulatory stage, leading to efficient ovulation induction by LH/human chorionic gonadotropin. Mature oocytes retrieved after CNP treatment could be fertilized in vitro and developed into blastocysts, allowing the delivery of viable offspring. Thus, CNP secreted by growing follicles is capable of stimulating preantral and antral follicle growth. In place of FSH, CNP treatment could provide an alternative therapy for female infertility.

  20. The left atrial "Medusa myxoma".

    PubMed

    Williams, Elbert E; Pratt, Jerry W; Martin, David E

    2014-02-01

    Although myxomas are the most commonly seen primary cardiac tumors, encompassing 30% to 50% of all primary tumors of the heart, they remain a rare finding with an annual reported incidence of 0.5 per million. The presenting symptoms of an atrial myxoma are widely varied as are the clinical consequences. Regardless of presentation, once a diagnosis is made prompt surgical excision is recommended to minimize the potential complications of obstruction or embolization. We present the "Medusa myxoma," an arborizing 4-fingered left atrial myxoma extending from the fossa ovalis across the left atrium.

  1. [Panic disorder and atrial fibrillation].

    PubMed

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

    2013-10-01

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

  2. 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.

  3. B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide in pediatric patients with pulmonary arterial hypertension

    PubMed Central

    Takatsuki, Shinichi; Wagner, Brandie D; Ivy, David Dunbar

    2011-01-01

    Objectives B-type natriuretic peptide (BNP) and the amino-terminal fragment (NTproBNP) correlate with clinical variables, but have not been simultaneously studied in a large number of pediatric patients with pulmonary arterial hypertension (PAH). The purpose of our investigation was to compare BNP and NTproBNP with clinical indicators of disease in a pediatric PAH population for which biomarkers are much needed. Design We retrospectively compared BNP and NTproBNP levels with exercise capacity, echocardiographic data, and hemodynamics in PAH patients under 21 years-old. Two hundred sixty three blood samples from 88 pediatric PAH patients were obtained, with BNP and NTproBNP drawn at the same time. Results There was a correlation between BNP and NTproBNP with mean pulmonary arterial pressure/mean arterial pressure (mPAP/mSAP) ratio (r=0.40 p<0.01, r=0.45 p<0.01, respectively), mean right atrial pressure (mRAP) (r=0.48 p<0.01, r=0.48 p<0.01), and tricuspid regurgitant (TR) velocity (r=0.36 p<0.01, r=0.41 p<0.01). BNP and NTproBNP are associated with 6 minute walking distance, mPAP, mPAP/mSAP ratio, mRAP, pulmonary vascular resistance index (PVRI), and TR velocity when investigated longitudinally. On the average, a 1 unit increase in log BNP or NTproBNP was associated with 4.5 unitsxm2 or 3.4 unitsxm2 increase in PVRI, respectively. There was a strong correlation between log BNP and log NTproBNP measurements (r= 0.87, p<0.01). Conclusion In pediatric PAH, BNP and NTProBNP are strongly correlated and predict changes in clinical variables and hemodynamics. In a cross-sectional analysis, NTproBNP correlated with echocardiographic and exercise data better than BNP; NTproBNP showed less within patient variability over time, therefore NTproBNP can add additional information towards predicting these clinical measurements. PMID:22325151

  4. [Chromogranin A: immunocytochemical localization in secretory granules of frog atrial cardiomyocytes].

    PubMed

    Krylova, M I

    2007-01-01

    Chromogranin A (CgA) is a member of the granin family of acidic proteins that present in the secretory granules (SGs) of many endocrine, neuroendocrine and neuronal cells. Atrial natriuretic peptide (ANP)-storing SGs in atrial cardiomyocytes of rat heart also contain CgA. Cardiosuppressive effect of CgA-derived peptides (vasostatins) on in vitro isolated and perfused working frog and rat hearts has been shown under both basal conditions and beta-adrenergic stimulation. More recently it has been revealed that rat heart produces and processes CgA-derived vasostatin-containing peptides. Until now nothing has been known about the presence of CgA in an amphibian heart. We have investigated the subcellular localization of CgA in atrial myocytes of adult frog Rana temporaria heart using ultraimmunocytochemical method. Immunocytochemical staining of the frog atrial tissue for CgA and ANP has shown that out of three morphologically different types (A, B and D) of specific cytoplasmic granules (SCGs) present in myocytes only two (A and B)--large (120-200 nm in diameter) granules with more and with less electron dense core--exhibit immunoreactivity (IR) to these two antigens. The third type (D) of granules (80-100 nm in diameter) are small membrane bound granules characterized by highly electron dense core surrounded with a thin halo. These granules revealed negative reaction on immunostaining for both CgA and ANP. The presence of CgA- and ANP-IR in the same SCGs in frog atrial myocytes is consistent with the endocrine nature of these granules. Taking into account our and literature data we propose that CgA present in frog atrial cardiomyocite SCGs might be a precursor of vasostatin-containing peptides, as it takes place in rat heart. It is possible that these CgA-derived peptides together with ANP exert their regulatory function through the autocrine and/or paracrine mechanisms and play important cardioprotective role in frog heart under stress condition.

  5. Facts about Atrial Septal Defect

    MedlinePlus

    ... Developmental Disabilities) be credited and notified in any public or private usage of this image. Close × Atrial Septal Defect The images are ... Developmental Disabilities) be credited and notified in any public or private usage of this image. Close Information For... ... Makers Language: English ...

  6. 77 FR 4043 - Scientific Information Request on the Use of Natriuretic Peptide Measurement in the Management of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-26

    ... Natriuretic Peptide Measurement in the Management of Heart Failure AGENCY: Agency for Healthcare Research and... manufacturers of natriuretic peptide measurement assays. Scientific information is being solicited to inform our Comparative Effectiveness Review of Use of Natriuretic Peptide Measurement in the Management of Heart...

  7. Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine levels with alterations in arterial stiffness: The Framingham Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experimental studies suggest that the natriuretic peptides influence lipid and fatty acid metabolism. Although it has been shown that obese individuals have reduced natriuretic peptide levels, conflicting data exist on the relation of natriuretic peptide levels to other metabolic risk factors. We ex...

  8. [Atrial fibrillation and cognitive function].

    PubMed

    Duron, Emmanuelle; Hanon, Olivier

    2010-09-01

    Atrial fibrillation (AF), which prevalence increases with age, is a growing public health problem and a well known risk factor for stroke. On the other hand, dementia is one of the most important neurological disorders in the elderly, and with aging of the population in developed countries, the number of demented patients will increase in absence of prevention. In the past decade, several vascular risk factors (hypertension, obesity and metabolic syndrome, hypercholesterolemia) have been found, with various degree of evidence, to be associated with vascular dementia but also, surprisingly, with Alzheimer's disease. This review is devoted to the links between atrial fibrillation, cognitive decline and dementia. Globally, transversal studies showed a significant association between atrial fibrillation, cognitive decline and dementia. However, these studies are particularly sensitive to various biases. In this context, recent longitudinal studies of higher level of evidence have been conducted to assess the link between AF and dementia. One study disclosed a high incidence of dementia among patients suffering from atrial fibrillation during a 4.6 years follow-up. Similarly another study showed that atrial fibrillation was significantly associated with conversion from mild cognitive impairment to dementia during a 3 years follow-up. Nevertheless two other longitudinal studies did not find any significant association between AF and dementia, but this discrepancy should be interpreted taking into account that the comparability of all these studies is moderate because they were using different methodologies (population, cognitive testing, and mean follow-up). Possible explanatory mechanisms for the association between AF and the risk of dementia are proposed, such as thrombo-embolic ischemic damage and cerebral hypo perfusion due to fluctuations in the cardiac output. Thus, there is some evidence that FA could be associated with cognitive decline and dementia but this

  9. The evidence of production or activation of a natriuretic factor in the liver.

    PubMed

    Ivanov, Y I

    1979-01-01

    The natriuretic activity was measured with the aid of bioassay in blood flowing out from the brain, kidney and liver before and after the expansion of extracellular space in dogs. In another experiments in rats the volume natriuresis and the natriuretic activity in blood were measured in controls and in animals with carbon tetrachloride liver dystrophy and pharmacological stimulation (dehydrocholic acid, Ca pantothenate, cyanocobalamin) of liver functions. In dogs, the level of natriuretic activity in blood flowing out of the liver before and after the expansion of extracellular fluid volume was significantly higher than that in arterial blood. In contrast, the natriuretic activity was not found in the blood flowing out of the brain and the kidney. In rats the experimental dystrophy of the liver decreased the content of a natriuretic factor in blood plasma and the expansion of extracellular space did not produce any natriuretic effect as compared to control rats. After pharmacological stimulation of the liver by dehydrocholic acid, Ca pantothenate and cyanocobalamine the volume expansion led to a significant increase of the excretion of sodium by the kidney and to the increase of the content of a natriuretic factor in blood plasma as compared to control rats. These facts are considered to support the view that a natriuretic factor is either synthesized or activated by the liver.

  10. Natriuretic Peptide Receptor B modulates the proliferation of the cardiac cells expressing the Stem Cell Antigen-1

    PubMed Central

    Rignault-Clerc, Stéphanie; Bielmann, Christelle; Liaudet, Lucas; Waeber, Bernard; Feihl, François; Rosenblatt-Velin, Nathalie

    2017-01-01

    Brain Natriuretic Peptide (BNP) injections in adult “healthy” or infarcted mice led to increased number of non-myocyte cells (NMCs) expressing the nuclear transcription factor Nkx2.5. The aim of this study was to identify the nature of the cells able to respond to BNP as well as the signaling pathway involved. BNP treatment of neonatal mouse NMCs stimulated Sca-1+ cell proliferation. The Sca-1+ cells were characterized as being a mixed cell population involving fibroblasts and multipotent precursor cells. Thus, BNP treatment led also to increased number of Sca-1+ cells expressing Nkx2.5, in Sca-1+ cell cultures in vitro and in vivo, in the hearts of neonatal and adult infarcted mice. Whereas BNP induced Sca-1+ cell proliferation via NPR-B receptor and protein kinase G activation, CNP stimulated Sca-1+ cell proliferation via NPR-B and a PKG-independent mechanism. We highlighted here a new role for the natriuretic peptide receptor B which was identified as a target able to modulate the proliferation of the Sca-1+ cells. The involvement of NPR-B signaling in heart regeneration has, however, to be further investigated. PMID:28181511

  11. A Test in Context Critical Evaluation of Natriuretic Peptide Testing in Heart Failure

    PubMed Central

    Francis, Gary S.; Felker, G. Michael; Tang, W.H. Wilson

    2016-01-01

    Circulating natriuretic peptide measurements have been used extensively over the past 15 years to diagnose and monitor patients with heart failure. We are still learning how complex the dynamics of natriuretic peptides can be in the interpretation of test results in individual patients. Although natriuretic peptide measurements are widely used in practice, there are questions regarding why these peptides may not necessarily track with blood volume or invasive hemodynamic measurements in individual patients. Interpretation of natriuretic peptide measurements will depend on many factors, including special patient populations, obesity, renal function, the state of congestion or decongestion, and whether patients are receiving specific therapies. Natriuretic peptide measurements have clearly revolutionized clinical care for patients with heart failure, but further research should provide insights to help use these measurements to individualize patient care beyond the current guidelines. PMID:26796399

  12. Sex Differences of the Natriuretic Peptide Polymorphism Associated With Angiographic Coronary Atherosclerosis

    PubMed Central

    Li, Terry Y.; Tse, M. Yat; Pang, Stephen C.; McLellan, Catherine S.; King, Will D.; Johri, Amer M.

    2017-01-01

    Background Polymorphisms within natriuretic peptide (NP) genes have been associated with clinical outcomes for cardiovascular disease (CVD), but no previous study has compared the effect of these polymorphisms between men and women. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in key genes of the NP system and coronary angiographic outcomes, with the focus on the sexual dimorphism in the effects of these SNPs. Methods Patients undergoing clinically indicated coronary angiography (n = 513, 328 men and 185 women) were consented and genotyped for NPPA rs5065, NPPB rs198389 and NPR2 rs10758325. Patients were stratified into having normal coronaries, non-obstructive coronary artery disease (CAD) or obstructive CAD, based on the highest stenosis in any epicardial artery. Average luminal narrowing across all four arteries was derived to represent the overall atherosclerotic burden. Results The frequency of NPPB rs198389 AA genotype was significantly higher in women with obstructive CAD (P = 0.014). The same association was not observed in males. With respect to atherosclerotic burden, an association was found between the AA genotype and average luminal narrowing in women (P = 0.005), but not in men. Conclusions The current study identified an association between an SNP of the NPPB gene and coronary atherosclerotic burden through angiographic evidence in women but not in men. These results suggest that B-type natriuretic peptide (BNP) may have more important involvement in the development of CAD in women compared to men, and as such, genotyping of the NPPB gene may serve as a potential biomarker to identify women with high risk for CAD. PMID:28275418

  13. What Are the Signs and Symptoms of Atrial Fibrillation?

    MedlinePlus

    ... What Are the Signs and Symptoms of Atrial Fibrillation? Atrial fibrillation (AF) usually causes the heart's lower ... pain Dizziness or fainting Fatigue (tiredness) Confusion Atrial Fibrillation Complications AF has two major complications— stroke and ...

  14. Present treatment options for atrial fibrillation

    PubMed Central

    Lairikyengbam, S; Anderson, M; Davies, A

    2003-01-01

    Atrial fibrillation is the commonest sustained cardiac arrhythmia. It accounts for >35% of all hospital admissions for cardiac arrhythmias in the United States. The presence of atrial fibrillation increases the mortality of a population by up to twofold. The risk of stroke increases from 1.5% in patients with atrial fibrillation from 50–59 years of age to up to 23.5% for such patients aged 80–89 years. Although the diagnosis of atrial fibrillation is usually straightforward, effective treatment is not. This article will discuss how rhythm control of atrial fibrillation can best be achieved, the controversy over the rhythm versus rate control, the maintenance of sinus rhythm with antiarrhythmic drugs after cardioversion, and prevention of thromboembolism. Finally, the recent advances in various non-pharmacological approaches for the treatment of atrial fibrillation will be highlighted. PMID:12612318

  15. [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.

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

    PubMed Central

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

    2015-01-01

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

  17. 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

  18. C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression

    NASA Astrophysics Data System (ADS)

    Scotland, Ramona S.; Cohen, Marc; Foster, Paul; Lovell, Matthew; Mathur, Anthony; Ahluwalia, Amrita; Hobbs, Adrian J.

    2005-10-01

    The multifaceted process of immune cell recruitment to sites of tissue injury is key to the development of an inflammatory response and involved in the pathogenesis of numerous cardiovascular disorders. We recently identified C-type natriuretic peptide (CNP) as an important endothelium-derived mediator that regulates vascular tone and protects against myocardial ischemia/reperfusion injury. Herein, we investigated whether CNP inhibits leukocyte recruitment and platelet aggregation and thereby exerts a potential antiinflammatory influence on the blood vessel wall. We assessed the effects of CNP on leukocyte-endothelial cell interactions in mouse mesenteric postcapillary venules in vivo in animals with high basal leukocyte activation (endothelial nitric oxide synthase knockout mice, eNOS-/-) or under acute inflammatory conditions (induced by interleukin-1 or histamine). CNP suppressed basal leukocyte rolling in eNOS-/- mice in a rapid, reversible, and concentration-dependent manner. These effects of CNP were mimicked by the selective natriuretic peptide receptor-C agonist cANF4-23. CNP also suppressed leukocyte rolling induced by IL-1 or histamine, inhibited platelet-leukocyte interactions, and prevented thrombin-induced platelet aggregation of human blood. Furthermore, analysis of human umbilical vein endothelial cells, leukocytes, and platelets revealed that CNP selectively attenuates expression of P-selectin. Thus, CNP is a modulator of acute inflammation in the blood vessel wall characterized by leukocyte and platelet activation. These antiinflammatory effects appear to be mediated, at least in part, via suppression of P-selectin expression. These observations suggest that endothelial CNP might maintain an anti-atherogenic influence on the blood vessel wall and represent a target for therapeutic intervention in inflammatory cardiovascular disorders. endothelium | natriuretic peptide receptor type C | atherosclerosis | thrombosis

  19. Left Atrial Appendage Closure Devices

    PubMed Central

    Romero, Jorge; Perez, Irving E; Krumerman, Andrew; Garcia, Mario J; Lucariello, Richard J

    2014-01-01

    Atrial fibrillation (AF) increases the risk for thromboembolic stroke five-fold. The left atrial appendage (LAA) has been shown to be the main source of thrombus formation in the majority of strokes associated with AF. Oral anticoagulation with warfarin and novel anticoagulants remains the standard of care; however, it has several limitations, including bleeding and poor compliance. Occlusion of the LAA has been shown to be an alternative therapeutic approach to drug therapy. The purpose of this article is to review the different techniques and devices that have emerged for the purpose of occluding this structure, with a particular emphasis on the efficacy and safety studies published to date in the medical literature. PMID:24963274

  20. Assessment of atrial electromechanical interval using echocardiography after catheter ablation in patients with persistent atrial fibrillation

    PubMed Central

    Chen, Xiaodong; Chen, Minglong; Wang, Yingying; Yang, Bing; Ju, Weizhu; Zhang, Fengxiang; Cao, Kejiang

    2016-01-01

    Abstract We sought to investigate variation of atrial electromechanical interval after catheter ablation procedure in patients with persistent atrial fibrillation using pulse Doppler (PW) and pulse tissue Doppler imaging (PW-TDI). A total of 25 consecutive in-patients with persistent atrial fibrillation, who restored sinus rhythm after ablation procedure, were recruited in our cardiac center. Echocardiography was performed on each patient at 2 hours, 1 day, 5 days, 1 month and 3 months after the ablation therapy, and atrial electromechanical delay was measured simultaneously by PW and PW-TDI. There was no significant difference between PW and TDI in measuring atrial electromechanical delay. However, at postoperative 2 hours, peak A detection rates were mathematically but nonsignificantly greater by PW-TDI than by PW. Second, there was a significant decreasing trend in atrial electromechanical interval from postoperative 2 hours to 3 months, but only postoperative 2-hour atrial electromechanical interval was significantly greater than atrial electromechanical interval at other time. Lastly, patients without postoperative 2-hour atrial electromechanical interval had a significantly longer duration of atrial fibrillation as compared to those with postoperative 2-hour atrial electromechanical interval, by the PW or by PW-TDI, respectively. In patients with persistent atrial fibrillation, atrial electromechanical interval may decrease significantly within the first 24 hours after ablation but remain consistent later, and was significantly related to patients’ duration of atrial fibrillation. Atrial electromechanical interval, as a potential predicted factor, is recommended to be measured by either PW or TDI after 24 hours, when patients had recovered sinus rhythm by radiofrequency ablation. PMID:27924066

  1. Cardiac resynchronization therapy and atrial overdrive pacing for the treatment of central sleep apnoea

    PubMed Central

    Lüthje, Lars; Renner, Bernd; Kessels, Roger; Vollmann, Dirk; Raupach, Tobias; Gerritse, Bart; Tasci, Selcuk; Schwab, Jörg O.; Zabel, Markus; Zenker, Dieter; Schott, Peter; Hasenfuss, Gerd; Unterberg-Buchwald, Christina; Andreas, Stefan

    2009-01-01

    Aims The combined therapeutic impact of atrial overdrive pacing (AOP) and cardiac resynchronization therapy (CRT) on central sleep apnoea (CSA) in chronic heart failure (CHF) so far has not been investigated. We aimed to evaluate the effect of CRT alone and CRT + AOP on CSA in CHF patients and to compare the influence of CRT on CHF between CSA positive and CSA negative patients. Methods and results Thirty patients with CRT indication underwent full night polysomnography, echocardiography, exercise testing, and neurohumoral evaluation before and 3 months after CRT implantation. In CSA positive patients (60%), two additional sleep studies were conducted after 3 months of CRT, with CRT alone or CRT + AOP, in random order. Cardiac resynchronization therapy resulted in significant improvements of NYHA class, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, VO2max, and quality of life irrespective of the presence of CSA. Cardiac resynchronization therapy also reduced the central apnoea–hypopnoea index (AHI) (33.6 ± 14.3 vs. 23.8 ± 16.9 h−1; P < 0.01) and central apnoea index (17.3 ± 14.1 vs. 10.9 ± 13.9 h−1; P < 0.01) without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a small but significant additional decrease of the central AHI (23.8 ± 16.9 vs. 21.5 ± 16.9 h−1; P < 0.01). Conclusion In this study, CRT significantly improved CSA without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a significant but minor additional improvement of CSA. Positive effects of CRT were irrespective of the presence of CSA. PMID:19147446

  2. Endothelial C-type natriuretic peptide maintains vascular homeostasis.

    PubMed

    Moyes, Amie J; Khambata, Rayomand S; Villar, Inmaculada; Bubb, Kristen J; Baliga, Reshma S; Lumsden, Natalie G; Xiao, Fang; Gane, Paul J; Rebstock, Anne-Sophie; Worthington, Roberta J; Simone, Michela I; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F; Djordjevic, Snezana; Caulfield, Mark J; MacAllister, Raymond J; Selwood, David L; Ahluwalia, Amrita; Hobbs, Adrian J

    2014-09-01

    The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor-C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders.

  3. Endothelial C-type natriuretic peptide maintains vascular homeostasis

    PubMed Central

    Moyes, Amie J.; Khambata, Rayomand S.; Villar, Inmaculada; Bubb, Kristen J.; Baliga, Reshma S.; Lumsden, Natalie G.; Xiao, Fang; Gane, Paul J.; Rebstock, Anne-Sophie; Worthington, Roberta J.; Simone, Michela I.; Mota, Filipa; Rivilla, Fernando; Vallejo, Susana; Peiró, Concepción; Sánchez Ferrer, Carlos F.; Djordjevic, Snezana; Caulfield, Mark J.; MacAllister, Raymond J.; Selwood, David L.; Ahluwalia, Amrita; Hobbs, Adrian J.

    2014-01-01

    The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic blood pressure, and the reactivity of leukocytes and platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, and stroke. Herein, we evaluated mice with endothelial-specific deletion of Nppc, which encodes C-type natriuretic peptide (CNP), and determined that this mediator is essential for multiple aspects of vascular regulation. Specifically, disruption of CNP leads to endothelial dysfunction, hypertension, atherogenesis, and aneurysm. Moreover, we identified natriuretic peptide receptor–C (NPR-C) as the cognate receptor that primarily underlies CNP-dependent vasoprotective functions and developed small-molecule NPR-C agonists to target this pathway. Administration of NPR-C agonists promotes a vasorelaxation of isolated resistance arteries and a reduction in blood pressure in wild-type animals that is diminished in mice lacking NPR-C. This work provides a mechanistic explanation for genome-wide association studies that have linked the NPR-C (Npr3) locus with hypertension by demonstrating the importance of CNP/NPR-C signaling in preserving vascular homoeostasis. Furthermore, these results suggest that the CNP/NPR-C pathway has potential as a disease-modifying therapeutic target for cardiovascular disorders. PMID:25105365

  4. To fumble flutter or tackle "tach"? Toward updated classifiers for atrial tachyarrhythmias.

    PubMed

    Lesh, M D; Kalman, J M

    1996-05-01

    Aristotle proposed in his short work, The Categories, that a definition is a statement of a thing's essential nature, and the essence of a thing are those of its properties that cannot change without losing its identity. But Aristotle was not faced with the flux of new information that confronts modern medicine. Nowadays, the argot of a discipline arises organically at the intersection of a given state of empiric knowledge and the exigencies of present scientific discourse. Thus, when the only treatment for a regular, narrow QRS complex tachycardia was digitalis glycosides or vasopressor infusion, the term "PAT" ("paroxysmal atrial tachycardia") seemed adequate, at least to distinguish it from ventricular tachycardia. We now prefer the term "PSVT" (paroxysmal supraventricular tachycardia) because we understand that most such tachycardias are not in truth "atrial" but involve the AV node and/or an accessory AV connection, and because we wish to report on the results of treatment specific to each of the subcategories of "PSVT." Similarly, as our knowledge of atrial arrhythmias has grown and especially as we need to describe the outcome of new interventional approaches to therapy, it may be prudent to use a nomenclature for atrial tachyarrhythmias that is based on the geometry of the tachycardia substrate, the relationship of that substrate to atrial anatomy, and the type of atrial lesions required to abolish that substrate.

  5. Atrial fibrillation management: evaluating rate vs rhythm control.

    PubMed

    Nguyen, Tuan; Jolly, Umjeet; Sidhu, Kiran; Yee, Raymond; Leong-Sit, Peter

    2016-06-01

    Atrial fibrillation (AF) is an increasing global issue leading to increased hospitalizations, adverse health related events and mortality. This review focuses on the management of atrial fibrillation, in particular in the past decade, comparing two major strategies, rate or rhythm control. We evaluate the evidence for each strategy, pharmacological options and the increasing utilization of invasive techniques, in particular catheter ablation and use of implantable cardiac pacing devices. Pharmacological comparative trials evaluating both strategies have shown rate control being non-inferior to rhythm control for clinical outcomes of mortality and other cardiovascular events (including stroke). Catheter ablation techniques, involving radiofrequency ablation and recently cryoablation, have shown promising results in particular with paroxysmal AF. However, persistent AF provides ongoing challenges and will be a particular focus of continued research.

  6. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    PubMed Central

    Fattouh, Aya M; El-Shabrawi, Mortada H; Mahmoud, Enas H; Ahmed, Wafaa O

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue Doppler imaging. Results: Patients’ mean ages were 7.66 ± 4.16 years (vs. 6.88 ± 3.04 years for the controls). The study included 27 males and 25 females (28 and 25 respectively for the controls). Patients had larger left atrium and right ventricle (RV) (P value 0.05) and increased LV posterior wall thickness than controls (P value 0.04). They had higher late atrial diastolic filling velocity (A) of tricuspid valve (TV) inflow (0.59 ± 0.17 vs. 0.5 ± 0.1 m/s, P < 0.001) and lower ratios between the early diastolic filling velocity (E) and A wave velocity (E/A) of both mitral valve and TV inflow (1.7 ± 0.35 vs. 1.87 ± 0.34 and 1.3 ± 0.3 vs. 1.5 ± 0.3, P < 0.005 and 0.0008, respectively). Patients had significantly longer isovolumic relaxation time of LV (45.5 ± 11.1 vs. 40.5 ± 7.7 ms P 0.008), higher late diastolic peak myocardial velocity (A’) (11.8 ± 3.6 vs. 9.5 ± 2.7 ms, P 0.0003) and systolic velocity (S’) of the RV (14.5 ± 2.7 vs. 13.2 ± 2.9, P 0.01) and significantly higher myocardial performance index of both LV and RV (P 0.001 and 0.01). BNP levels were significantly higher in cases than controls (5.25 ng/l vs. 3.75 ng/l, P < 0.04) and was correlated with the E wave velocity of the TV (r 0.004) and the E/E’ ratio of the RV (r 0.001). None of the clinical or laboratory data were correlated with the BNP level. Conclusion Cirrhotic children have cardiac dysfunction mainly in the form of diastolic dysfunction. There is a need that CCM be more accurately

  7. Dynamics of AV coupling during human atrial fibrillation: role of atrial rate.

    PubMed

    Masè, M; Marini, M; Disertori, M; Ravelli, F

    2015-07-01

    The causal relationship between atrial and ventricular activities during human atrial fibrillation (AF) is poorly understood. This study analyzed the effects of an increase in atrial rate on the link between atrial and ventricular activities during AF. Atrial and ventricular time series were determined in 14 patients during the spontaneous acceleration of the atrial rhythm at AF onset. The dynamic relationship between atrial and ventricular activities was quantified in terms of atrioventricular (AV) coupling by AV synchrogram analysis. The technique identified n:m coupling patterns (n atrial beats in m ventricular cycles), quantifying their percentage, maximal length, and conduction ratio (= m/n). Simulations with a difference-equation AV model were performed to correlate the observed dynamics to specific atrial/nodal properties. The atrial rate increase significantly affected AV coupling and ventricular response during AF. The shortening of atrial intervals from 185 ± 32 to 165 ± 24 ms (P < 0.001) determined transitions toward AV patterns with progressively decreasing m/n ratios (from conduction ratio = 0.34 ± 0.09 to 0.29 ± 0.08, P < 0.01), lower occurrence (from percentage of coupled beats = 27.1 ± 8.0 to 21.8 ± 6.9%, P < 0.05), and higher instability (from maximal length = 3.9 ± 1.5 to 2.8 ± 0.7 s, P < 0.01). Advanced levels of AV block and coupling instability at higher atrial rates were associated with increased ventricular interval variability (from 123 ± 52 to 133 ± 55 ms, P < 0.05). AV pattern transitions and coupling instability in patients were predicted, assuming the filtering of high-rate irregular atrial beats by the slow recovery of nodal excitability. These results support the role of atrial rate in determining AV coupling and ventricular response and may have implications for rate control in AF.

  8. 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.

  9. Left atrial myxoma masquerading as viral flu

    PubMed Central

    Chhabra, Lovely; Kiernan, Francis

    2016-01-01

    Atrial myxoma is a rare cardiac tumor that may be diagnosed incidentally on cardiac imaging or may present with life-threatening cardiac symptoms. We present a case of giant left atrial myxoma that presented as a flulike illness. PMID:27695187

  10. 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.

  11. Who Is at Risk for Atrial Fibrillation?

    MedlinePlus

    ... at Risk for Atrial Fibrillation? Atrial fibrillation (AF) affects millions of people, and the number is rising. Men are more ... conditions. It may act as a trigger in people who have other AF risk factors. Genetic factors also may play a role in causing AF. However, their role ... SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA OIG CONTACT ...

  12. Role of atrial receptors in the control of sodium excretion. [pressure breathing and antinatiuretic effects in dogs

    NASA Technical Reports Server (NTRS)

    Meehan, J. R.; Henry, J. P.

    1973-01-01

    Responses of an innervated and a contralateral chronically denervated kidney to mild positive pressure breathing are compared for saline volume expansions in chloralose anesthetized dogs. It is shown that mild pressure breathing significantly reduces sodium excretion, urine flow, free water clearance, and PAH clearance. After 20 minutes of positive pressure breathing, both kidney responses are identical suggesting the release of natriuretic hormone which reduces renal function in addition to the demonstrated change in renal nerve activity. Increase of the left atrial pressure through balloon obstruction of the mitral orifice increases urine flow, sodium excretion and PAH clearance; inflation of the balloon and positive pressure breathing again depresses renal function. Preliminary evidence indicates that receptors in the right atrium are more severely affected by pressure breathing than those in the left atrium.

  13. Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion

    PubMed Central

    Tourki, Bochra; Matéo, Philippe; Morand, Jessica; Elayeb, Mohamed; Godin-Ribuot, Diane; Marrakchi, Naziha; Belaidi, Elise; Messadi, Erij

    2016-01-01

    Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2) is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP). Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR). We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP) opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP) release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP) channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial dysfunction. PMID

  14. Is there a synergic effect of propafenone associated with atrial overdrive pacing for atrial arrhythmia prevention? A randomised crossover study

    PubMed Central

    Garrigue, S; Barold, S; Cazeau, S; Hocini, M; Jais, P; Haissaguerre, M; Clementy, J

    2000-01-01

    OBJECTIVE—To assess the effect of adding propafenone to atrial overdrive for the prevention of atrial arrhythmia episodes in patients with DDD pacemakers.
DESIGN—22 patients (8 female, 14 male, mean (SD) age 67 (9) years, range 48 to 77) with DDD pacemakers and frequent paroxysmal atrial arrhythmia episodes were evaluated in a randomised crossover study.
SETTING—University hospital.
METHODS—Atrial overdrive was defined as a paced rate of 10 paced beats/min above the mean ventricular rate stored for the last 24 hours in the pacemaker memory function. The protocol consisted of two phases of one month each. The first phase consisted of atrial overdrive alone, while in the second phase, propafenone (600 mg/day) was added to atrial overdrive (atrial overdrive + propafenone). All 22 patients underwent the two phases in random order.
RESULTS—Mean ventricular rate was 72 (8) beats/min with atrial overdrive v 73 (6) with atrial overdrive + propafenone (NS). With atrial overdrive, 14 patients (64.6%) had no recorded atrial arrhythmia v 15 (68.2%) with atrial overdrive + propafenone (NS). There was no statistical difference between the atrial overdrive and atrial overdrive + propafenone phases with regard to the number of atrial arrhythmia episodes (14 (27) v 13 (28)), their total duration (30 (78) v 29 (63) h), and their maximum duration (41 (72) v 31 (58) min). However, in the brady-tachy subgroup with persistent atrial arrhythmias, atrial overdrive + propafenone produced a shorter mean cumulative duration of atrial arrhythmia than atrial overdrive (104 (115) v 178 (149) h, p = 0.04), with a significant decrease in the number of atrial arrhythmia episodes (134 (98) v 102 (83), p = 0.05). The proportion of asymptomatic atrial arrhythmia episodes increased only in the AV block group during atrial overdrive + propafenone (p = 0.03). Three patients had atrial arrhythmias during atrial overdrive + propafenone but not

  15. Consensus document and recommendations on the use of natriuretic peptides in clinical practice.

    PubMed

    Pascual-Figal, D A; Casademont, J; Lobos, J M; Piñera, P; Bayés-Genis, A; Ordóñez-Llanos, J; González-Juanatey, J R

    2016-01-01

    Natriuretic peptides are a useful laboratory tool for the diagnosis, prognosis and treatment of patients with heart failure. Natriuretic peptides are used in various healthcare settings (consultations, emergency department, hospitalization, laboratory) and by various primary care and specialised professionals. However, their use in clinical practice is still scare and uneven. Properly using and interpreting natriuretic peptides in clinical practice requires a minimum of prelaboratory (pathophysiology), laboratory (methods) and postlaboratory (interpretation and integration of clinical data) expertise. The objective of this consensus document, developed by several scientific societies, is to update the necessary concepts and expertise on natriuretic peptides that enable its application in the diagnosis, prognosis and treatment of heart failure, in various healthcare environments.

  16. Can Natriuretic Peptides be Used to Guide Therapy?

    PubMed Central

    Lupón, Josep; Jaffe, Allan S.

    2016-01-01

    Over the last 15 years, the hypothesis that intensified treatment directed at reducing natriuretic peptide (NP) concentrations may improve the outcomes of patients with heart failure (HF) has been scrutinized in several prospective clinical trials, with conflicting results. Collectively, however, the data suggest that NP concentrations may be useful in guiding HF management and improving HF-related morbidity and mortality. In this review, we summarize the existing data investigating the use of NPs as targets for outpatient HF therapy. We focus on the information gathered in randomized clinical trials and comprehensive meta-analyses, and also on the recommendations of international guidelines (primarily guidelines from the European Society of Cardiology and the American College of Cardiology/American Heart Association). Although the results for this approach are promising overall, additional well-designed prospective randomized controlled trials (e.g., the GUIDE-IT trial) are necessary to confirm or refute the utility of NP-guided outpatient HF management. PMID:27683534

  17. Agonistic induction of a covalent dimer in a mutant of natriuretic peptide receptor-A documents a juxtamembrane interaction that accompanies receptor activation.

    PubMed

    Labrecque, J; Deschênes, J; McNicoll, N; De Léan, A

    2001-03-16

    The natriuretic peptide receptor-A (NPR-A) is composed of an extracellular domain with a ligand binding site, a transmembrane-spanning domain, a kinase homology domain, and a guanylyl cyclase domain. In response to agonists (atrial natriuretic peptide (ANP) and brain natriuretic peptide), the kinase homology domain-mediated guanylate cyclase repression is removed, which allows the production of cyclic GMP. Previous work from our laboratory strongly indicated that agonists are exerting their effects through the induction of a juxtamembrane dimeric contact. However, a direct demonstration of this mechanism remains to be provided. As a tool, we are now using the properties of a new mutation, D435C. It introduces a cysteine at a position in NPR-A corresponding to a supplementary cysteine found in NPR-C6, another receptor of this family (a disulfide-linked dimer). Although this D435C mutation only leads to trace levels of NPR-A disulfide-linked dimer at basal state, covalent dimerization can be induced by a treatment with rat ANP or with other agonists. The NPR-A(D435C) mutant has not been subjected to significant structural alterations, since it shares with the wild type receptor a similar dose-response pattern of cellular guanylyl cyclase activation. However, a persistent activation accompanies NPR-A(D435C) dimer formation after the removal of the inducer agonist. On the other hand, a construction where the intracellular domain of NPR-A(D435C) has been truncated (DeltaKC(D435C)) displays a spontaneous and complete covalent dimerization. In addition, the elimination of the intracellular domain in wild type DeltaKC and DeltaKC(D435C) is associated with an increase of agonist binding affinity, this effect being more pronounced with the weak agonist pBNP. Also, a D435C secreted extracellular domain remains unlinked even after incubation with rat ANP. In summary, these results demonstrate, in a dynamic fashion, the agonistic induction of a dimeric contact in the

  18. Stimulation of natriuretic peptide receptor C attenuates accumulation of reactive oxygen species and nitric oxide synthesis in ammonia-treated astrocytes.

    PubMed

    Skowrońska, Marta; Zielińska, Magdalena; Albrecht, Jan

    2010-11-01

    Oxidative and nitrosative stress contribute to ammonia-induced astrocytic dysfunction in hepatic encephalopathy. Treatment of cultured astrocytes with 5 mmol/L ammonium chloride ('ammonia') increased the production of reactive oxygen species (ROS), including the toxic NADPH oxidase reaction product, •O(2)(-). Atrial natriuretic peptide (ANP), natriuretic peptide C and a selective natriuretic peptide receptor (NPR)-C ligand, cANP((4-23),) each decreased the total ROS content both in control cells and cells treated with ammonia. However, attenuation of •O(2)(-) accumulation by ANP and cANP((4-23),) was observed in ammonia-treated cells only and the effect of cANP((4-23)) was decreased when the NADPH oxidase-regulatory protein G(iα-2) was blocked with a specific anti-G(iα-2) antibody. Although in contrast to ANP, cANP((4-23)) did not elevate the cGMP content in control astrocytes, it decreased cAMP content and reduced the expression of G(iα-2), the NADPH oxidase-regulatory protein. The results show the presence of functional NPR-C in astrocytes, activation of which (i) attenuates basal ROS production, and (ii) prevents excessive accumulation of the toxic ROS species, •O(2)(-) by ammonia. Ammonia, ANP and cANP((4-23)) added separately, each stimulated formation of NO(x) (nitrates + nitrites) which was associated with up-regulation of the activity [cANP((4-23))] or/and expression (ammonia) of the endothelial isoform of nitric oxide synthase. However, the ammonia-induced increase of NO(x) was not augmented by co-addition of ANP, and was reduced to the control level by co-addition of cANP((4-23)) , indicating that activation of NPR-C may also reduce nitrosative stress. Future hepatic encephalopathy therapy might include the use of cANP((4-23)) or other NPR-C agonists to control oxidative/nitrosative stress induced by ammonia.

  19. In-hospital brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide variations are predictors of short-term and long-term outcome in acute decompensated heart failure

    PubMed Central

    2011-01-01

    Acute decompensated heart failure is one of the most important causes of hospitalisation worldwide. Natriuretic peptides have shown their usefulness in the diagnosis and management of heart failure. Their variations during hospitalisation also appear useful to predict outcomes. In particular, data from the literature demonstrate that reduction from admission to discharge of brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide in these patients is a predictor of future cardiovascular events. PMID:21345261

  20. Four natriuretic peptides (ANP, BNP, VNP and CNP) coexist in the sturgeon: identification of BNP in fish lineage.

    PubMed

    Kawakoshi, A; Hyodo, S; Inoue, K; Kobayashi, Y; Takei, Y

    2004-04-01

    The natriuretic peptide (NP) family is composed of three members: atrial, brain/ventricular and C-type NPs (ANP, BNP/VNP and CNP respectively) in tetrapods and teleostean fish, but only CNP in elasmobranch fish. In order to trace the process of divergence of the NP family in early vertebrate evolution, we attempted to detect NPs in the primitive ray-finned fish, the sturgeon (Acipenser transmontanus). Unexpectedly, we isolated four distinct NP cDNAs from the heart and brain of this chondrostean fish. The single NP from the brain was CNP, as judged from the lack of C-terminal 'tail' sequence extending from the intramolecular ring. Two of the three cardiac NPs were ANP and VNP, as judged by the presence of an amidation signal at its C-terminus (ANP) and a long and conserved C-terminal tail sequence (VNP) respectively. The third cardiac NP was most probably BNP because it possessed all the features characteristic of BNP including: (1) the presence of dibasic amino acids within the intramolecular ring; (2) the presence of AUUUA repeats in the 3'-untranslated region of its mRNA; (3) equivalent expression of its mRNA in the atrium and ventricle and appreciable expression in the brain. Based on the sturgeon BNP sequence, we further isolated BNP cDNA from the heart of tilapia and pufferfish for the first time in teleostean fish. Phylogenetic analysis of the precursors showed that newly identified NPs belong to each group of the four NPs. The current identification of both VNP and BNP in the sturgeon clearly showed that BNP and VNP are coded by distinct genes, and that the NP family consists of at least four members in the ray-finned fish. VNP has not been molecularly identified in mammals but its presence is suggested from physiological studies; heterologous fish VNP exhibited more potent vasorelaxant activity than homologous mammalian ANP in the isolated coronary artery of dogs.

  1. Comparison of B-type natriuretic peptide and left ventricular dysfunction in patients with constrictive pericarditis undergoing pericardiectomy.

    PubMed

    Kapoor, Poonam Malhotra; Aggarwal, Vikram; Chowdhury, Ujjwal; Choudhury, Minati; Singh, Sarvesh Pal; Kiran, Usha

    2010-01-01

    Chronic constrictive pericarditis (CCP) due to tuberculosis has high morbidity and mortality in the periopeartive period following pericardiectomy because of left ventricular (LV) dysfunction. Brain-type natriuretic peptide (BNP) is considered a marker for both LV systolic and diastolic dysfunction. We undertook this prospective study in 24 patients, to measure the BNP levels and to compare it with transmitral Doppler flow velocities, that is, the E/A ratio (E = initial peak velocity during early diastolic filling and A = late peak flow velocity during atrial systole), as a marker of diastolic function and systolic parameters, pre- and post-pericardiectomy, at the time of discharge. The latter parameters have been taken as a flow velocity across the mitral valve on a transthoracic echo. There was a significant decrease in the mean values of log BNP (6.19 +/- 0.33 to 4.65 +/- 0.14) (P = 0.001) and E/A ratio (1.81 +/- 0.21 to 1.01 +/- 0.14) (P = 0.001) post pericardiectomy, with a positive correlation, r = 0.896 and 0.837, respectively, between the two values at both the time periods. There was significant improvement in the systolic parameters of the LV function, that is, stroke volume index, cardiac index, systemic vascular resistance index, and delivered oxygen index. However, no correlation was observed between these values and the BNP levels. We believe that BNP can be used as a marker for LV diastolic dysfunction in place of the E/A ratio in patients with CCP, undergoing pericardiectomy. However, more studies have to be performed for validation of the same.

  2. Onset and Regression of Pregnancy-Induced Cardiac Alterations in Gestationally Hypertensive Mice: The Role of the Natriuretic Peptide System.

    PubMed

    Ventura, Nicole M; Li, Terry Y; Tse, M Yat; Andrew, R David; Tayade, Chandrakant; Jin, Albert Y; Pang, Stephen C

    2015-12-01

    Pregnancy induces cardiovascular adaptations in response to increased volume overload. Aside from the hemodynamic changes that occur during pregnancy, the maternal heart also undergoes structural changes. However, cardiac modulation in pregnancies complicated by gestational hypertension is incompletely understood. The objectives of the current investigation were to determine the role of the natriuretic peptide (NP) system in pregnancy and to assess alterations in pregnancy-induced cardiac hypertrophy between gestationally hypertensive and normotensive dams. Previously we have shown that mice lacking the expression of atrial NP (ANP; ANP(-/-)) exhibit a gestational hypertensive phenotype. In the current study, female ANP(+/+) and ANP(-/-) mice were mated with ANP(+/+) males. Changes in cardiac size and weight were evaluated across pregnancy at Gestational Days 15.5 and 17.5 and Postnatal Days 7, 14, and 28. Nonpregnant mice were used as controls. Physical measurement recordings and histological analyses demonstrated peak cardiac hypertrophy occurring at 14 days postpartum in both ANP(+/+) and ANP(-/-) dams with little to no change during pregnancy. Additionally, left ventricular expression of the renin-angiotensin system (RAS) and NP system was quantified by real-time quantitative polymerase chain reaction. Up-regulation of Agt and AT(1a) genes was observed late in pregnancy, while Nppa and Nppb genes were significantly up-regulated postpartum. Our data suggest that pregnancy-induced cardiac hypertrophy may be influenced by the RAS throughout gestation and by the NP system postpartum. Further investigations are required to gain a complete understanding of the mechanistic aspects of pregnancy-induced cardiac hypertrophy.

  3. A prospective study of brain natriuretic peptide levels in three subgroups: Stroke with hypertension, stroke without hypertension, and hypertension alone

    PubMed Central

    Cakir, Zeynep; Saritas, Ayhan; Emet, Mucahit; Aslan, Sahin; Akoz, Ayhan; Gundogdu, Fuat

    2010-01-01

    Aim: To study brain natriuretic peptide (BNP) levels in three subgroups: patients having stroke with hypertension (HT), those having stroke without HT, and those with HT alone. We also tried to identify whether BNP levels predict the length of stay in hospital and mortality. Materials and Methods: The groups were formed by patients who had been admitted to the emergency department in the first 4–12 h after the onset of symptoms. There were 30 stroke patients with a history of HT (group I), 30 stroke patients without a history of HT (group II), and 20 HT patients without stroke (group III). Patients with congestive heart failure, chronic cor pulmonale, severe valvular heart disease, chronic renal failure, liver insufficiency, diabetes mellitus, atrial fibrillation, and those with a history of stroke were excluded from the study since these diseases can affect the plasma BNP levels. Results: The demographic characteristics, except the age distribution, were similar among the groups. The mean BNP levels in the three groups were 168.8 ± 223.9 pg/ml, 85.0 ± 75.1 pg/ml, and 84.8 ± 178.3 pg/ml, respectively. The differences between the groups were statistically significant. Conclusion: The mean BNP levels were affected by HT and/or stroke. The simultaneous presence of HT and stroke results in a more significant increase BNP than the presence of either stroke or HT alone. When diseases that can affect the plasma BNP levels are excluded, the BNP levels in stroke patients without a history of HT are similar to the levels seen in patients with only HT. PMID:20436747

  4. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes

    PubMed Central

    Bordicchia, Marica; Liu, Dianxin; Amri, Ez-Zoubir; Ailhaud, Gerard; Dessì-Fulgheri, Paolo; Zhang, Chaoying; Takahashi, Nobuyuki; Sarzani, Riccardo; Collins, Sheila

    2012-01-01

    The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of “brown adipocytes” within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional “brown-like” adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK–dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C–/– mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote “browning” of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology. PMID:22307324

  5. Human adrenal tumor cell line SW-13 contains a natriuretic peptide receptor system that responds preferentially to ANP among various natriuretic peptides

    SciTech Connect

    Mizuno, T.; Katafuchi, T.; Hagiwara, H.; Ito, T.; Kangawa, K.; Matsuo, H.; Hirose, S. )

    1990-12-31

    A new type of ANP receptor system which clearly distinguishes natriuretic peptides A and B (ANP and BNP) has been identified in the human adrenal tumor cell line SW-13 and characterized. SW-13 cells responded to nanomolar concentrations of ANP with large increases in cGMP levels but in the case of BNP, much higher concentrations were required to produce the same extent of response. This property is unique since the 140-kDa ANP receptors so far characterized do not discriminate between ANP and BNP. For comparison, various natriuretic peptide receptors were also re-characterized using the recently identified CNP.

  6. [Secondary pulmonary embolism to right atrial myxoma].

    PubMed

    Vico Besó, L; Zúñiga Cedó, E

    2013-10-01

    A case of pulmonary thromboembolism secondary to atrial myxoma right. The myxoma is a primary cardiac tumor, namely, has his origin in the cardiac tissue. Primary cardiac tumors are rare, including myxomas, the most common type. Have a predilection for females and the most useful tool for diagnosis is echocardiography. About 75% of myxomas occur in the left atrium of the heart and rest are in the right atrium. Right atrial myxomas in some sometimes associated with tricuspid stenosis and atrial fibrillation. The most common clinical manifestations include symptoms of this neoplasm constitutional, and embolic phenomena resulting from the obstruction to the flow intracavitary. The treatment of this condition is surgical.

  7. Serum Galectin-3 Levels Predict Recurrences after Ablation of Atrial Fibrillation

    PubMed Central

    Clementy, Nicolas; Benhenda, Nazih; Piver, Eric; Pierre, Bertrand; Bernard, Anne; Fauchier, Laurent; Pages, Jean-Christophe; Babuty, Dominique

    2016-01-01

    Galectin-3 is a biomarker of fibrosis and atrial remodeling, involved in the mechanisms of initiation and maintenance of atrial fibrillation (AF). We sought to study the accuracy of galectin-3 level in predicting recurrences of AF after ablation. Serum concentrations of galectin-3 were determined in a consecutive series of patients addressed for AF ablation in our center. After a 3-month blanking period, recurrences of atrial arrhythmias were collected during the first year in all patients, using Holter monitoring at 3, 6 months and 12 months. A total of 160 patients were included, with a mean galectin-3 rate was 14.4 ± 5.6 ng/mL. At 12-month, 55 patients (34%) had reexperienced sustained atrial arrhythmia. Only higher galectin-3 level (HR = 1.07 [1.01–1.12], p = 0.02) and larger left atrial diameter (HR = 1.07 [1.03–1.12], p = 0.001) independently predicted recurrence. Patients with both galectin-3 level <15 ng/mL and left atrial diameter <40 millimeters had a 1-year arrhythmia-free survival rate − after a single procedure without anti-arrhythmic drug − of 91%, as compared with 41% in patients with galectin-3 ≥ 15 and left trial diameter ≥40 (p < 0.0001), whether AF was paroxysmal or persistent. Galectin-3 and left atrial diameters, rather than clinical presentation of AF, predict recurrences after ablation. PMID:27677964

  8. A new algorithm to diagnose atrial ectopic origin from multi lead ECG systems--insights from 3D virtual human atria and torso.

    PubMed

    Alday, Erick A Perez; Colman, Michael A; Langley, Philip; Butters, Timothy D; Higham, Jonathan; Workman, Antony J; Hancox, Jules C; Zhang, Henggui

    2015-01-01

    Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms.

  9. A New Algorithm to Diagnose Atrial Ectopic Origin from Multi Lead ECG Systems - Insights from 3D Virtual Human Atria and Torso

    PubMed Central

    Alday, Erick A. Perez; Colman, Michael A.; Langley, Philip; Butters, Timothy D.; Higham, Jonathan; Workman, Antony J.; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms. PMID

  10. Arterial Remodeling in B-Type Natriuretic Peptide Knock-Out Females

    PubMed Central

    Holditch, Sara J.; Schreiber, Claire A.; Burnett, John C.; Ikeda, Yasuhiro

    2016-01-01

    Sexual dimorphisms are recognized in cardiovascular conditions such as hypertension, stroke, thrombosis and vasculitis. B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. The anti-hypertensive, vasodilatory, anti-fibrotic, and anti-hypertrophic properties of BNP are well established in male animal models. Although circulating BNP levels are higher in women, when compared to age-matched men, the cardiovascular protective propensity of BNP in females is poorly understood. We assessed the cardiovascular consequences of BNP deletion in genetically null (Nppb−/−) female rat lines. Throughout the study, blood pressure (BP) remained uninfluenced by genotype, and cardiorenal consequences of BNP knock out remained minor. Unexpectedly, approximately 60% of Nppb−/− females developed mesenteric polyarteritis-nodosa (PAN)-like vasculitis in their life span, some as early as 4 months of age. Mesenteric lesions involved intense arterial remodeling, progressive inflammation, occluded lumens, and less frequently intestinal necrosis and multiple visceral arterial aneurysms. Cumulative pathologies resulted in a significant decline in survival of the Nppb−/− female. This study highlights BNP’s vasoprotective propensity, bringing to light a possible sex specific difference in the cardiovascular protection provided by BNP. Defects in the BNP/GC-A/cGMP pathway may play a role in arteriopathies in women, while GC-A agonists may provide effective therapy for arteritis. PMID:27162120

  11. Interpretation and Use of Natriuretic Peptides in Non-Congestive Heart Failure Settings

    PubMed Central

    Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

    2010-01-01

    Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article. PMID:20191004

  12. Towards Low Energy Atrial Defibrillation.

    PubMed

    Walsh, Philip; Kodoth, Vivek; McEneaney, David; Rodrigues, Paola; Velasquez, Jose; Waterman, Niall; Escalona, Omar

    2015-09-03

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

  13. Towards Low Energy Atrial Defibrillation

    PubMed Central

    Walsh, Philip; Kodoth, Vivek; McEneaney, David; Rodrigues, Paola; Velasquez, Jose; Waterman, Niall; Escalona, Omar

    2015-01-01

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

  14. Managing atrial fibrillation in the very elderly patient: challenges and solutions

    PubMed Central

    Karamichalakis, Nikolaos; Letsas, Konstantinos P; Vlachos, Konstantinos; Georgopoulos, Stamatis; Bakalakos, Athanasios; Efremidis, Michael; Sideris, Antonios

    2015-01-01

    Atrial fibrillation (AF) is the most common arrhythmia affecting elderly patients. Management and treatment of AF in this rapidly growing population of older patients involve a comprehensive assessment that includes comorbidities, functional, and social status. The cornerstone in therapy of AF is thromboembolic protection. Anticoagulation therapy has evolved, using conventional or newer medications. Percutaneous left atrial appendage closure is a new invasive procedure evolving as an alternative to systematic anticoagulation therapy. Rate or rhythm control leads to relief in symptoms, fewer hospitalizations, and an improvement in quality of life. Invasive methods, such as catheter ablation, are the new frontier of treatment in maintaining an even sinus rhythm in this particular population. PMID:26604772

  15. Atrial flutter a manifestation of cardiac tamponade.

    PubMed

    Pabón, Guillermo Mora; Ramírez, John A

    2012-04-01

    Atrial flutter (AFL) is a common arrhythmia that is associated with postpericardiotomy and pericarditis. The relationship of AFL with tamponade has rarely been reported. A case of AFL with acute pericarditis and cardiac tamponade is thus presented here.

  16. Atrial fibrillation in elderly: particularities of management.

    PubMed

    Alexa, Ioana Dana; Bucur, Ionela Mirela; Rusu, R I; Ungureanu, G

    2009-01-01

    Atrial fibrillation (AF), a common and serious cardiac rhythm disturbance, is responsible for substantial morbidity and mortality in the population. Currently about 2.3 million people in the US are diagnosed with AF and, based of the US census, this number is expected to rise to 5.6 million by 2050. It doubles in prevalence with each decade of age, reaching almost 9% at age 80-89 years. It has increased in prevalence over the calendar decades, reaching 'epidemic' proportions. The risk of stroke increases from 1.5% in patients with atrial fibrillation from 50-59 years of age to up to 23.5% for such patients aged 80-89 years. Although the diagnosis of atrial fibrillation is usually straightforward, effective treatment is not. We aimed to discuss how rhythm control of atrial fibrillation can best be achieved in elderly patients, the controversy over the rhythm versus rate control, and prevention of thromboembolism.

  17. Atrial Fibrillation During an Exploration Class Mission

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  18. Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers

    PubMed Central

    Levin, Mark D.; Lu, Min Min; Petrenko, Nataliya B.; Hawkins, Brian J.; Gupta, Tara H.; Lang, Deborah; Buckley, Peter T.; Jochems, Jeanine; Liu, Fang; Spurney, Christopher F.; Yuan, Li J.; Jacobson, Jason T.; Brown, Christopher B.; Huang, Li; Beermann, Friedrich; Margulies, Kenneth B.; Madesh, Muniswamy; Eberwine, James H.; Epstein, Jonathan A.; Patel, Vickas V.

    2009-01-01

    Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atrium, but the source and mechanism of these beats remains unclear. The melanin synthesis enzyme dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive species regulation in melanocytes. Given that dysregulation of intracellular calcium and reactive species has been described in patients with atrial fibrillation, we investigated the role of DCT in this process. Here, we characterize a unique DCT-expressing cell population within murine and human hearts that populated the pulmonary veins, atria, and atrioventricular canal. Expression profiling demonstrated that this population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes. Adult mice lacking DCT displayed normal cardiac development but an increased susceptibility to atrial arrhythmias. Cultured primary cardiac melanocyte-like cells were excitable, and those lacking DCT displayed prolonged repolarization with early afterdepolarizations. Furthermore, mice with mutations in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did not develop atrial arrhythmias in the absence of DCT. These data suggest that dysfunction of melanocyte-like cells in the atrium and pulmonary veins may contribute to atrial arrhythmias. PMID:19855129

  19. Atrial development in the human heart: an immunohistochemical study with emphasis on the role of mesenchymal tissues

    NASA Technical Reports Server (NTRS)

    Wessels, A.; Anderson, R. H.; Markwald, R. R.; Webb, S.; Brown, N. A.; Viragh, S.; Moorman, A. F.; Lamers, W. H.

    2000-01-01

    The development of the atrial chambers in the human heart was investigated immunohistochemically using a set of previously described antibodies. This set included the monoclonal antibody 249-9G9, which enabled us to discriminate the endocardial cushion-derived mesenchymal tissues from those derived from extracardiac splanchnic mesoderm, and a monoclonal antibody recognizing the B isoform of creatine kinase, which allowed us to distinguish the right atrial myocardium from the left. The expression patterns obtained with these antibodies, combined with additional histological information derived from the serial sections, permitted us to describe in detail the morphogenetic events involved in the development of the primary atrial septum (septum primum) and the pulmonary vein in human embryos from Carnegie stage 14 onward. The level of expression of creatine kinase B (CK-B) was found to be consistently higher in the left atrial myocardium than in the right, with a sharp boundary between high and low expression located between the primary septum and the left venous valve indicating that the primary septum is part of the left atrial gene-expression domain. This expression pattern of CK-B is reminiscent of that of the homeobox gene Pitx2, which has recently been shown to be important for atrial septation in the mouse. This study also demonstrates a poorly appreciated role of the dorsal mesocardium in cardiac development. From the earliest stage investigated onward, the mesenchyme of the dorsal mesocardium protrudes into the dorsal wall of the primary atrial segment. This dorsal mesenchymal protrusion is continuous with a mesenchymal cap on the leading edge of the primary atrial septum. Neither the mesenchymal tissues of the dorsal protrusion nor the mesenchymal cap on the edge of the primary septum expressed the endocardial tissue antigen recognized by 249-9G9 at any of the stages investigated. The developing pulmonary vein uses the dorsal mesocardium as a conduit to reach

  20. Atrial conduction delay predicts atrial fibrillation in paroxysmal supraventricular tachycardia patients after radiofrequency catheter ablation.

    PubMed

    Xu, Zhen-Xing; Zhong, Jing-Quan; Zhang, Wei; Yue, Xin; Rong, Bing; Zhu, Qing; Zheng, Zhaotong; Zhang, Yun

    2014-06-01

    This study aimed to assess whether intra- and inter-atrial conduction delay could predict atrial fibrillation (AF) for paroxysmal supraventricular tachycardia (PSVT) patients after successful treatment by radiofrequency catheter ablation (RFCA). Echocardiography examination was performed on 524 consecutive PSVT patients (15 patients were excluded). Left atrial dimension, right atrial diameter and intra- and inter-atrial conduction delay were measured before ablation. Patients were divided into group A (n = 32): occurrence of AF after the ablation and group B (n = 477): remained in sinus rhythm during follow-up. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive value of intra- and inter-atrial conduction delay. Both intra- and inter-atrial conduction delay were higher in group A than in group B (4.79 ± 0.30 msec vs. 4.56 ± 0.32 msec; 21.98 ± 1.32 msec vs. 20.01 ± 1.33; p < 0.05). Binary logistic regression analysis showed that intra- and inter-atrial conduction were significant influential factors for the occurrence of AF (odds ratio [OR] = 13.577, 95% confidence interval [CI], 3.469-48.914; OR = 2.569, 95% CI, 1.909-3.459, p < 0.05). The ROC cure analysis revealed that intra-atrial conduction delay ≥ 4.45 msec and inter-atrial conduction delay ≥ 20.65 were the most optimal cut-off value for predicting AF in PSVT patients after RFCA. In conclusion, this is the first study to show that the intra- and inter-atrial conduction delay could effectively predict AF in post-ablation PSVT patients.

  1. Presence of accessory left atrial appendage/diverticula in a population with atrial fibrillation compared with those in sinus rhythm: a retrospective review.

    PubMed

    Troupis, John; Crossett, Marcus; Scneider-Kolsky, Michal; Nandurkar, Dee

    2012-02-01

    Accessory left atrial appendages and atrial diverticula have an incidence of 10-27%. Their association with atrial fibrillation needs to be confirmed. This study determined the prevalence, number, size, location and morphology of accessory left atrial appendages/atrial diverticula in patients with atrial fibrillation compared with those in sinus rhythm. A retrospective analysis of 47 consecutive patients with atrial fibrillation who underwent 320 multidetector Coronary CT angiography (CCTA) was performed. A random group of 47 CCTA patients with sinus rhythm formed the control group. The presence, number, size, location and morphology of accessory left atrial appendages and atrial diverticula in each group were analysed. Twenty one patients had a total of 25 accessory left atrial appendages and atrial diverticula in the atrial fibrillation group and 22 patients had a total of 24 accessory left atrial appendages and atrial diverticula in the sinus rhythm group. Twenty-one atrial diverticula were identified in 19 patients in the atrial fibrillation group and 19 atrial diverticula in 17 patients in the sinus rhythm group. The mean length and width of accessory left atrial appendage was 6.9 and 4.7 mm, respectively in the atrial fibrillation group and 12 and 4.6 mm, respectively, in the sinus rhythm group, P = ns (not significant). The mean length and width of atrial diverticulum was 4.7 and 3.6 mm, respectively in the atrial fibrillation group and 6.2 and 5 mm, respectively in the sinus rhythm group (P = ns). Eighty-four % and 96% of the accessory left atrial appendages/atrial diverticula in the atrial fibrillation and sinus rhythm groups were located along the right anterosuperior left atrial wall. Accessory left atrial appendages and atrial diverticula are common structures with similar prevalence in patients with atrial fibrillation and sinus rhythm.

  2. [Anticoagulation in atrial fibrillation - an update].

    PubMed

    Antz, Matthias; Hullmann, Bettina; Neufert, Christian; Vocke, Wolfgang

    2008-12-01

    The correct anticoagulation regimen for prevention of thromboembolic events is essential in patients with atrial fibrillation. However, only a minority of patients receives anticoagulation according to the guidelines. The current guidelines are intended to make the indication for anticoagulation more simple and are summarized in the present article. This includes recommendations for chronic anticoagulation, prevention of thromboembolic events after cardioversion and in ablation of atrial fibrillation.

  3. Arterial embolism in thyrotoxicosis with atrial fibrillation.

    PubMed Central

    Staffurth, J S; Gibberd, M C; Fui, S N

    1977-01-01

    In 262 patients with thyrotoxicosis and atrial fibrillation there were 26 episodes of arterial embolism (17 cerebral and nine elsewhere) in 21 patients. Twelve incidents occurred with active thyrotoxicosis, three on reversion to sinus rhythm, and 11 after the patients were euthyroid. This important complication is more common than is realised, and most patients should be put on prophylactic anticoagulants when first seen with atrial fibrillation. PMID:902055

  4. Atrial fibrillation cardioversion following acupuncture

    PubMed Central

    Dilber, Dario; Čerkez-Habek, Jasna; Barić, Hrvoje; Gradišer, Marina

    2015-01-01

    Atrial fibrillation (AF) is the most common arrhythmia and it is an independent risk for serious events. Acupuncture has been growing in popularity in the West, and there are reports of its benefits in treating AF. We report a 57-year-old man who was admitted after having an allergic reaction to amiodarone administered to treat paroxysmal AF with fast ventricular response. Cardioversion with intravenous propafenone was uneventful. Before an attempt of electric cardioversion, he was treated with acupuncture as additional therapy to peroral propafenone. After acupuncture treatment consisting of 10 treatments during 30 days period, both immediate cardioversion to sinus rhythm and no paroxysmal AF during 30 days period were recorded. PMID:26593171

  5. Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα

    PubMed Central

    Aschar-Sobbi, Roozbeh; Izaddoustdar, Farzad; Korogyi, Adam S.; Wang, Qiongling; Farman, Gerrie P.; Yang, FengHua; Yang, Wallace; Dorian, David; Simpson, Jeremy A.; Tuomi, Jari M.; Jones, Douglas L.; Nanthakumar, Kumaraswamy; Cox, Brian; Wehrens, Xander H.T.; Dorian, Paul; Backx, Peter H.

    2015-01-01

    Atrial fibrillation (AF) is the most common supraventricular arrhythmia that, for unknown reasons, is linked to intense endurance exercise. Our studies reveal that 6 weeks of swimming or treadmill exercise improves heart pump function and reduces heart-rates. Exercise also increases vulnerability to AF in association with inflammation, fibrosis, increased vagal tone, slowed conduction velocity, prolonged cardiomyocyte action potentials and RyR2 phosphorylation (CamKII-dependent S2814) in the atria, without corresponding alterations in the ventricles. Microarray results suggest the involvement of the inflammatory cytokine, TNFα, in exercised-induced atrial remodelling. Accordingly, exercise induces TNFα-dependent activation of both NFκB and p38MAPK, while TNFα inhibition (with etanercept), TNFα gene ablation, or p38 inhibition, prevents atrial structural remodelling and AF vulnerability in response to exercise, without affecting the beneficial physiological changes. Our results identify TNFα as a key factor in the pathology of intense exercise-induced AF. PMID:25598495

  6. Triggers and Anatomical Substrates in the Genesis and Perpetuation of Atrial Fibrillation

    PubMed Central

    Sánchez-Quintana, Damián; López-Mínguez, José Ramón; Pizarro, Gonzalo; Murillo, Margarita; Cabrera, José Angel

    2012-01-01

    The definition of atrial fibrillation (AF) as a functional electrical disorder does not reflect the significant underlying structural abnormalities. Atrial and Pulmonary Vein (PV) muscle sleeve microstructural remodeling is present, and establishes a vulnerable substrate for AF maintenance. In spite of an incomplete understanding of the anatomo-functional basis for AF, current evidence demonstrates that this arrhythmia usually requires a trigger for initiation and a vulnerable electrophysiological and/or anatomical substrate for maintenance. It is still unclear whether the trigger mechanisms include focal enhanced automaticity, triggered activity and/or micro re-entry from myocardial tissue. Initiation of AF can be favored by both parasympathetic and sympathetic stimulation, which also seem to play a role in maintaining AF. Finally, evolving clinical evidence demonstrates that inflammation is associated with new-onset and recurrent AF through a mechanism that possibly involves cellular degeneration, apoptosis, and subsequent atrial fibrosis. PMID:22920484

  7. Atrial fibrillation: review of current treatment strategies.

    PubMed

    Xu, Joshua; Luc, Jessica G Y; Phan, Kevin

    2016-09-01

    Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in modern clinical practice, with an estimated prevalence of 1.5-2%. The prevalence of AF is expected to double in the next decades, progressing with age and increasingly becoming a global medical challenge. The first-line treatment for AF is often medical treatment with either rate control or anti-arrhythmic agents for rhythm control, in addition to anti-coagulants such as warfarin for stroke prevention in patient at risk. Catheter ablation has emerged as an alternative for AF treatment, which involves myocardial tissue lesions to disrupt the underlying triggers and substrates for AF. Surgical approaches have also been developed for treatment of AF, particularly for patients requiring concomitant cardiac surgery or those refractory to medical and catheter ablation treatments. Since the introduction of the Cox-Maze III, this procedure has evolved into several modern variations, including the use of alternative energy sources (Cox-Maze IV) such as radiofrequency, cryo-energy and microwave, as well as minimally invasive thoracoscopic epicardial approaches. Another recently introduced technique is the hybrid ablation approach, where in a single setting both epicardial thoracoscopic ablation lesions and endocardial catheter ablation lesions are performed by the cardiothoracic surgeon and cardiologist. There remains controversy surrounding the optimal approach for AF ablation, energy sources, and lesion sets employed. The goal of this article is review the history, classifications, pathophysiology and current treatment options for AF.

  8. Atrial fibrillation: review of current treatment strategies

    PubMed Central

    Xu, Joshua; Luc, Jessica G. Y.

    2016-01-01

    Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in modern clinical practice, with an estimated prevalence of 1.5–2%. The prevalence of AF is expected to double in the next decades, progressing with age and increasingly becoming a global medical challenge. The first-line treatment for AF is often medical treatment with either rate control or anti-arrhythmic agents for rhythm control, in addition to anti-coagulants such as warfarin for stroke prevention in patient at risk. Catheter ablation has emerged as an alternative for AF treatment, which involves myocardial tissue lesions to disrupt the underlying triggers and substrates for AF. Surgical approaches have also been developed for treatment of AF, particularly for patients requiring concomitant cardiac surgery or those refractory to medical and catheter ablation treatments. Since the introduction of the Cox-Maze III, this procedure has evolved into several modern variations, including the use of alternative energy sources (Cox-Maze IV) such as radiofrequency, cryo-energy and microwave, as well as minimally invasive thoracoscopic epicardial approaches. Another recently introduced technique is the hybrid ablation approach, where in a single setting both epicardial thoracoscopic ablation lesions and endocardial catheter ablation lesions are performed by the cardiothoracic surgeon and cardiologist. There remains controversy surrounding the optimal approach for AF ablation, energy sources, and lesion sets employed. The goal of this article is review the history, classifications, pathophysiology and current treatment options for AF. PMID:27747025

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  10. Antithrombotic treatment of atrial fibrillation: new insights.

    PubMed

    Le Heuzey, J Y

    2012-10-01

    The incidence and prevalence of atrial fibrillation are quickly increasing, mainly due to the ageing of the population. Atrial fibrillation is, to date, a problem of public health. Atrial fibrillation is associated to a five-fold risk of stroke, which may be identified by score risks, such as CHADS(2) score. The classical antithrombotic treatment of atrial fibrillation is based on vitamin K antagonists. Trials made in the 90's have clearly shown that vitamin K antagonists were able to decrease stroke risk by about 60%. New oral anticoagulants are now available on the market to treat patients with atrial fibrillation. These drugs are dabigatran which has demonstrated an interest in the RE-LY trial. Two doses may be prescribed, 110 mg bid and 150 mg bid. Anti Xa have also demonstrated an interest : rivaroxaban in the ROCKET AF trial and apixaban in the AVERROES (versus aspirin) and ARISTOTLE trials. In the future these drugs will have a major place in the armamentarium used to treat patients with atrial fibrillation. In all these trials a decrease in intra cranial haemorrhages has been demonstrated. In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys.

  11. H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation.

    PubMed

    Lu, Guihua; Xu, Chenggui; Tang, Kaiyu; Zhang, Juhong; Li, Qinglang; Peng, Longyun; Wang, Yesong; Huang, Zhibin; Gao, Xiuren

    2017-01-29

    Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT1R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H2O2) incubation, and these H2O2-induced alterations were reversed by diphenyleneiodonium, apocynin and H2S supplementation. Flow cytometry and Western blotting revealed that blockade of H2S biosynthesis using dl-propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H2S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H2S supplementation and losartan (an AT1R blocker) pretreatment. In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1

  12. Effect of Omega-3 Polyunsaturated Fatty Acids on Inflammation, Oxidative Stress and Recurrence of Atrial Fibrillation

    PubMed Central

    Darghosian, Leon; Free, Marcia; Li, Jie; Gebretsadik, Tebeb; Bian, Aihua; Shintani, Ayumi; McBride, Brian F.; Solus, Joseph; Milne, Ginger; Crossley, George H.; Thompson, David; Vidaillet, Humberto; Okafor, Henry; Darbar, Dawood; Murray, Katherine T.; Stein, C. Michael

    2014-01-01

    The efficacy of n-3 PUFAs in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine omega-3 polyunsaturated fatty acids (n-3 PUFAs) added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4g/d) (n=126) or placebo (n=64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin (IL)-6, IL-8, IL-10, tissue necrosis factor alpha (TNFα), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF)), N-terminal-pro-brain type natriuretic peptide (NTpBNP), and oxidative stress (urinary F2–isoprostanes (IsoPs)). Atrial fibrillation recurred in 74 (58.7%) patients randomized to n3-PUFAs and in 30 (46.9%) who received placebo; time to recurrence of AF did not differ significantly in the two groups (hazard ratio 1.20; 95% CI 0.76 - 1.90, adjusted P=0.438). Compared to placebo, n3-PUFAs did not result in clinically meaningful changes in concentrations of inflammatory markers, NTpBNP or F2-Isops. In conclusion, in patients with paroxysmal or persistent AF treatment with n3-PUFAs 4g/day did not reduce the recurrence of AF, nor was it associated with clinically important effects on concentrations of markers of inflammation and oxidative stress. PMID:25465932

  13. Effects of hypertonic saline infusion and water drinking on atrial peptide.

    PubMed

    Salazar, F J; Granger, J P; Joyce, M L; Burnett, J C; Bove, A A; Romero, J C

    1986-12-01

    This study was undertaken to define the changes in plasma levels of atrial natriuretic peptide (ANP) induced by hypertonic saline infusion followed by spontaneous water drinking and to determine whether these changes in ANP are correlated with changes in right atrial pressure (RAP) and plasma levels of vasopressin (AVP). Conscious dogs (n = 5) were infused with hypertonic saline (6%) at a rate of 1.4 ml/min for 4 h. Water was withheld for the first 2 h and administered ad libitum for the final 2 h. Hypertonic saline infusion induced increases (P less than 0.05) in plasma osmolality (posM), pAVP, mean arterial pressure (MAP), and RAP (1.9 +/- 0.6 to 3.1 +/- 0.7 mmHg). These changes were accompanied by an increase of pANP (68 +/- 14 to 120 +/- 33 pg/ml, P less than 0.05). Spontaneous water drinking (1,410 +/- 127 ml) returned posM and pAVP to control levels and produced a further and significant increment in RAP (150%) and pANP (100%). During the water-drinking phase MAP was not further altered, and hematocrit decreased by 11.1% (P less than 0.05). A positive linear correlation (P less than 0.001) was found between increases in RAP and pANP. The administration of an AVP vasopressor antagonist in a similar protocol, and before hypertonic saline infusion, inhibited the increase of MAP, but it did not alter the changes of posM, hematocrit, RAP, nor pANP. These results suggest that changes in the release of ANP during increases in posM and after spontaneous water drinking are predominantly controlled by changes in RAP.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. C-Type Natriuretic Peptide Analog as Therapy for Achondroplasia.

    PubMed

    Legeai-Mallet, Laurence

    2016-01-01

    Fibroblast growth factor receptor 3 (FGFR3) is an important regulator of bone formation. Gain-of-function mutations in the FGFR3 gene result in chondrodysplasias which include achondroplasia (ACH), the most common form of dwarfism, in which skull, appendicular and axial skeletons are affected. The skeletal phenotype of patients with ACH showed defective proliferation and differentiation of the chondrocytes in the growth plate cartilage. Both endochondral and membranous ossification processes are disrupted during development. At cellular level, Fgfr3 mutations induce increased phosphorylation of the tyrosine kinase receptor FGFR3, which correlate with an enhanced activation of its downstream signaling pathways. Potential therapeutic strategies have emerged for ACH. Several preclinical studies have been conducted such as the C-type natriuretic peptide (CNP) analog (BMN111), intermittent parathyroid hormone injections, soluble FGFR3 therapy, and meclozine and statin treatments. Among the putative targets to antagonize FGFR3 signaling, CNP (or BMN111) is one of the most promising strategies. BMN111 acts as a key regulator of longitudinal bone growth by downregulating the mitogen-activated protein kinase pathway, which is activated as a result of a FGFR3 gain-of-function mutation. Preclinical studies showed that BMN111 treatment led to a large improvement in skeletal parameters in Fgfr3Y367C/+ mice mimicking ACH. In 2014, a clinical trial (phase 2) of BMN111 in pediatric patients with ACH has started. This first clinical trial marks the first big step towards real treatment for these patients.

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

    SciTech Connect

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

    1996-06-01

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

  16. Predictors of new-onset atrial fibrillation in elderly patients with coronary artery disease after coronary artery bypass graft

    PubMed Central

    Anatoĺevna, Rubanenko O; Veniaminovich, Fatenkov O; Mikhaylovich, Khokhlunov S

    2016-01-01

    Objective To identify the factors associated with the development of postoperative atrial fibrillation (POAF) after coronary artery bypass graft (CABG) in elderly patients with coronary artery disease (CAD). Methods A total of 81 patients with CAD who underwent CABG were enrolled in the study. Patients were divided into two groups: Group 1, without postoperative atrial fibrillation (59 patients, 74.6% men, mean age 65.8 ± 4.0 years); Group 2, with early new-onset atrial fibrillation after CABG (22 patients, 90.9% men, mean age 67.7 ± 5.4 years). Interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), fibrinogen, superoxide dismutase (SOD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin I were studied. Results During the observation period, atrial fibrillation occurred in 27.2% cases, an average of 4.9 ± 3.8 days after surgery. In group 2, the left atrium (LA) dimension was larger than in group 1 (43.9 ± 3.4 mm vs. 37.6 ± 3.9 mm, P < 0.001). Patients with POAF had significantly higher IL-6 (72.7 ± 60.8 pg/mL vs. 38.0 ± 34.6 pg/mL, P = 0.04), IL-8 (11.9 ± 6.0 pg/mL vs. 7.7 ± 5.4 pg/mL, P = 0.01) and SOD (2462.0 ± 2029.3 units/g vs. 1515.0 ± 1292.9 units/g, P = 0.04) compared with group without POAF. The multivariate analysis showed that the odds ratio (OR) for POAF development in patients with left atrium more than 39 mm was 2.1 [95% confidence interval (CI): 1.2−3.8, P = 0.0004], IL-6 levels more than 65.18 pg/mL—1.4 (95% CI: 1.1−2.7, P = 0.009), IL-8 levels more than 9.67 pg/mL—1.2 (95% CI: 1.1−3.7, P = 0.009), SOD more than 2948 units/g—1.1 (95% CI: 1.01−2.9, P = 0.04). Conclusions In our study, the independent predictors of postoperative atrial fibrillation after CABG in elderly patients were left atrium dimension and the increased postoperative concentration of IL-6, IL-8 and superoxide dismutase. PMID:27594874

  17. Association of genetic variants with atrial fibrillation.

    PubMed

    Yamase, Yuichiro; Kato, Kimihiko; Horibe, Hideki; Ueyama, Chikara; Fujimaki, Tetsuo; Oguri, Mitsutoshi; Arai, Masazumi; Watanabe, Sachiro; Murohara, Toyoaki; Yamada, Yoshiji

    2016-02-01

    Recent genome-wide association studies (GWASs) identified various genes and loci that confer susceptibility to coronary artery disease or myocardial infarction among Caucasian populations. As myocardial ischemia is an important risk factor for atrial fibrillation, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to atrial fibrillation through affecting the susceptibility to coronary artery disease. The aim of the present study was to examine the possible association of atrial fibrillation in Japanese individuals with 29 polymorphisms identified as susceptibility loci for coronary artery disease or myocardial infarction in the meta-analyses of GWASs in Caucasian populations. The study subjects comprised 5,470 Japanese individuals (305 subjects with atrial fibrillation and 5,165 controls). Genotypes for 29 polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ(2) test revealed that rs599839 (G→A) of the proline/serine-rich coiled-coil 1 gene (PSRC1, P=0.0084) and rs11556924 (C→T, Arg363His) of the zinc finger, C3HC-type containing 1 gene (ZC3HC1, P=0.0076) were significantly (P<0.01) associated with atrial fibrillation. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, estimated glomerular filtration rate, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidemia revealed that rs599839 (P=0.0043; odds ratio, 1.56; dominant model) and rs11556924 (P=0.0043; odds ratio, 1.93; dominant model) were significantly associated with atrial fibrillation, with the minor G and T alleles, respectively, representing risk factors for this condition. PSRC1 and ZC3HC1 may thus be susceptibility loci for atrial fibrillation in Japanese individuals.

  18. Effect of phenylephrine infusion on atrial electrophysiological properties.

    PubMed Central

    Leitch, J. W.; Basta, M.; Fletcher, P. J.

    1997-01-01

    OBJECTIVE: To determine the effect of changes in autonomic tone induced by phenylephrine infusion on atrial refractoriness and conduction. DESIGN: Left and right atrial electrophysiological properties were measured before and after a constant phenylephrine infusion designed to increase sinus cycle length by 25%. SUBJECTS: 20 patients, aged 53 (SD 6) years, undergoing electrophysiological study for investigation of idiopathic paroxysmal atrial fibrillation (seven patients) or for routine follow up after successful catheter ablation of supraventricular tachycardia (13 patients). MAIN OUTCOME MEASURES: Changes in left and right atrial effective refractory periods, atrial activation times, and frequency of induction of atrial fibrillation. RESULTS: Phenylephrine (mean dose 69 (SD 18) mg/min) increased mean blood pressure by 22 (12) mm Hg (range 7 to 44) and lengthened sinus cycle length by 223 (94) ms (20 to 430). Left atrial effective refractory period lengthened following phenylephrine infusion from 250 (25) to 264 (21) ms (P < 0.001) but there was no significant change in right atrial effective refractory period: 200 (20) v 206 (29), P = 0.11. There was a significant relation between the effect of phenylephrine on sinus cycle length and on right atrial refractoriness (r = 0.6, P = 0.005) with shortening of right atrial refractoriness in patients with the greatest prolongation in sinus cycle length. During phenylephrine infusion, the right atrial stimulus to left atrial activation time at the basic pacing cycle length of 600 ms was unchanged, at 130 (18) v 131 (17) ms, but activation delay with a premature extrastimulus increased: 212 (28) v 227 (38) ms, P = 0.002. Atrial fibrillation was induced by two of 58 refractory period measurements at baseline and by 12 of 61 measurements during phenylephrine infusion (P < 0.01). Phenylephrine increased the difference between left and right atrial refractory periods by 22.8 (19.4) ms in the five patients with induced atrial

  19. [No Hodgkin Linfoma diagnosis with intra-atrial infiltration].

    PubMed

    Alcocer Gamba, Marco Antonio; León González, Salvador; Castro Montes, Eliodoro; Loarca Piña, Luis Martín; Lugo Gavidia, Leslie Marisol; García Hernández, Enrique; González Galindo, Ulises; Paredes Serrano, Miguel Isaías

    2012-09-01

    Cardiac tumors are rare entities in clinical practice, with an incidence of 0.05%. Approximately 75% are benign and 25% malignant. Among these, Lymphomas are uncommon, representing about 0.25%. The non-Hodgkin lymphomas can occur in extranodal tissues in 20% of the cases and 80% of these non-Hodgkin lymphomas are composed of diffuse B cells. The extranodal presentation is most frequent in young adults, with a high degree of malignancy and rapid growth. It can present with primary infiltration of various organs; cardiac involvement occurs in 20 to 28% of cases, usually located in the right chambers and with nonspecific symptoms, depending on the location and extent of the tumor. The diagnostic test in these cases is undoubtedly the biopsy of the lymph node or the affected tissue. We present the case of non-Hodgkin disease of diffuse large cells, with right intra-atrial involvement in a 23-year-old-female patient, who presented with progressive dyspnea. A transesophageal echocardiography was performed and an intra-atrial tumor mass was detected. A biopsy was performed, by femoral venous catheterization, allowing the establishment of the histopathological diagnosis and treatment. At a one year follow up, the patient shows complete remission.

  20. Formycin triphosphate as a probe for the ATP binding site involved in the activation of guanylate cyclase.

    PubMed

    Chang, C H; Yu, Z N; Song, D L

    1992-10-01

    Formycin A triphosphate (FTP), a fluorescent analog of ATP, slightly increased basal guanylate cyclase activity, but significantly potentiated guanylate cyclase activity stimulated by atrial natriuretic factor (ANF) in rat lung membranes. FTP potentiated ANF-stimulated guanylate cyclase activity with an EC50 at about 90 microM and inhibited ATP-stimulated guanylate cyclase activity with an IC50 at about 100 microM. These results indicate that FTP binds more tightly than ATP for the same binding site. Therefore, FTP would be an excellent tool for studying the ATP binding site.

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

    PubMed Central

    Zhang, Daoliang; Chen, Xiaoqing; Wang, Qian; Wu, Shaohui; Zheng, Yue; Liu, Xu

    2017-01-01

    Objectives To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD) and its role in atrial fibrillation (AF) after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis. Methods A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF), respectively. Western blot was also used to measure the protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1). Serum angiotensin II (Ang II) levels were assayed using enzyme-linked immunosorbent assay (ELISA). Results Eighteen patients developed AF, whereas 39 remained in sinus rhythm (SR). The severity of atrial fibrosis was significantly higher in patients who developed AF versus those who remained in SR; the mRNA and protein expression of TGF-β1, TRAF6 and CTGF were significantly higher in patients with AF. The protein expression of phosphorylated MAPKs and TAK1 was significantly increased in patients who developed AF compared with the patients who remained in SR. Serum Ang II levels were significantly higher in patients who developed AF versus those who remained in SR. Conclusion The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis in patients with RHD, which results in the occurrence of AF after cardiac surgery. PMID:28323847

  2. A KCNQ1 Mutation Causes a High Penetrance for Familial Atrial Fibrillation

    PubMed Central

    Bartos, Daniel C.; Anderson, Jeffrey B.; Bastiaenen, Rachel; Johnson, Jonathan N.; Gollob, Michael H; Tester, David J.; Burgess, Don E.; Homfray, Tessa; Behr, Elijah R.; Ackerman, Michael J.; Guicheney, Pascale; Delisle, Brian P.

    2012-01-01

    Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease. Method and Results Candidate gene sequencing in five unrelated families with familial AF identified the KCNQ1 missense mutation p.Arg231His (R231H). In addition to AF, several of the family members have abnormal QTc intervals, syncope, or experienced sudden cardiac arrest or death. KCNQ1 encodes the voltage-gated K+ channel that conducts the slowly activating delayed rectifier K+ current in the heart. Functional and computational analyses suggested that R231H increases KCNQ1 current (IKCNQ1) to shorten the atrial action potential (AP) duration. R231H is predicted to minimally affect ventricular excitability, but it prevented the increase in IKCNQ1 following PKA activation. The unique properties of R231H appeared to be caused by a loss in voltage-dependent gating. Conclusions The R231H variant causes a high penetrance for interfamilial early-onset AF. Our study indicates R231H likely shortens atrial refractoriness to promote a substrate for reentry. Additionally, R231H might cause abnormal ventricular repolarization by disrupting PKA activation of IKCNQ1. We conclude genetic variants, which increase IKs during the atrial AP, decrease the atrial AP duration, and/or shorten atrial refractoriness, present a high risk for interfamilial AF. PMID:23350853

  3. Echocardiographic evaluation of patent foramen ovale and atrial septal defect.

    PubMed

    Hari, Pawan; Pai, Ramdas G; Varadarajan, Padmini

    2015-01-01

    Patent foramen ovale (PFO) is a common variant present in up to 25% of the population. Atrial septal defect (ASD) is a direct communication between the 2 atrial chambers, of which the ostium secundum variety is the most common. This manuscript is an in depth review of the complex atrial septation, the diagnosis of PFO and ASD and its clinical and therapeutic implications.

  4. [Atrial defibrillators or implantable atrioverters. Initial results].

    PubMed

    Lévy, S; Taramasco, V; Corbelli, J L; Mistretta, R; Dolla, E; Ricard, P

    1998-07-01

    The atrial defibrillator is a new non-pharmacological treatment of atrial fibrillation (AF) for restoration of sinus rhythm. This device has two programmable modes: automatic or activated by the physician or patient. In the automatic mode, the device delivers a shock synchronous with the R wave to restore sinus rhythm when AF is detected. Two patients with paroxysmal AF resistant to pharmacological therapy were included in a study to assess the efficacy and safety of the atrial defibrillator in the mode activated by the physician. The device implanted in the pectoral region is connected to 3 electrodes, two for atrial defibrillation and sensing positioned in the coronary sinus and right atrium respectively and a sensing and pacing electrode in the right ventricle. The right ventricle is paced if a post-shock pause is detected. It is possible to interrogate the device with a programmer using its Holter function and so determine the number of episodes of AF sensed and treated. The number, intensity and energy of the shocks and the parameters of ventricular stimulation are programmable. In these two patients, the atrial defibrillator effectively reduced prolonged episodes of AF with a follow-up of 12 and 7 months. No pro-arrhythmic effects were observed. Further clinical evaluation is under way to assess this new mode of treatment, including the mode activated by the patient, safety and tolerance of the shocks. In our two patients, the treatment of prolonged episodes of AF was followed by reduction of many short or asymptomatic episodes.

  5. Restoration of Atrial Mechanical Function after Successful Radio-Frequency Catheter Ablation of Atrial Flutter

    PubMed Central

    Rhee, Kyoung-Suk; Kang, Duk-Hyun; Song, Jae-Kwan; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, You-Ho

    2001-01-01

    Background: Atrial mechanical dysfunction and its recovery time course after successful radiofrequency ablation of chronic atrial flutter (AFL) has been largely unknown. We serially evaluated left atrial function by echocardiography after successful ablation of chronic atrial flutter. Methods: In 13 patients with chronic AFL, mitral E wave A wave, and the ratio of A/E velocity were measured at 1 day, 1 month, 3 months and 6–12 months after successful radiofrequency (RF) ablation. Doppler tissue imaging (DTI) technique was also used to avoid load-dependent variation in the flow velocity pattern. Results: Left atrial mechanical function, assessed by A wave velocity and the annular motion, was depressed at 1 day, but improved significantly at 1 month and maintained through 6–12 months after the ablation. Left atrial size did not change significantly. Conclusion: Left atrial mechanical function was depressed immediately after successful RF ablation of chronic AFL, but it improved significantly after 1 month and was maintained over one year. PMID:11590904

  6. Aorta-Right Atrial Tunnel

    PubMed Central

    Krishna, Cheemalapati Sai; Baruah, Dibya Kumar; Reddy, Gangireddy Venkateswara; Panigrahi, Nanda Kishore; Suman, Kalagara; Kumar, Palli Venkata Naresh

    2010-01-01

    Aorta–right atrial tunnel is a vascular channel that originates from one of the sinuses of Valsalva and terminates in either the superior vena cava or the right atrium. The tunnel is classified as anterior or posterior, depending upon its course in relation to the ascending aorta. An origin above the sinotubular ridge differentiates the tunnel from an aneurysm of the sinus of Valsalva, and the absence of myocardial branches differentiates it from a coronary–cameral fistula. Clinical presentation ranges from an asymptomatic precordial murmur to congestive heart failure. The embryologic background and pathogenesis of this lesion are attributable either to an aneurysmal dilation of the sinus nodal artery or to a congenital weakness of the aortic media. In either circumstance, progressive enlargement of the tunnel and ultimate rupture into the low-pressure right atrium could occur under the influence of the systemic pressure. The lesion is diagnosed by use of 2-dimensional echocardiography and cardiac catheterization. Computed tomographic angiography is an additional noninvasive diagnostic tool. The possibility of complications necessitates early therapy, even in asymptomatic patients or those with a hemodynamically insignificant shunt. Available treatments are catheter-based intervention, external ligation under controlled hypotension, or surgical closure with the patient under cardiopulmonary bypass. Herein, we discuss the cases of 2 patients who had this unusual anomaly. We highlight the outcome on follow-up imaging (patient 1) and the identification and safe reimplantation of the coronary artery (patient 2). PMID:20844628

  7. [Antithrombotic therapy in atrial arrhythmia].

    PubMed

    Cohen, Ariel

    2004-02-15

    The principal complication of the atrial arrythmias is the thrombo-embolic accident, notably the cerebro-vascular accident. The efficacity of the oral anticoagulants in reducing cerebro-vascular accidents has been demonstrated in numerous studies. This is significantly superior to that obtained with the anti-platelet drugs. However, the anti-vitamin K drugs (warfarin) carry a risk of serious haemorrhage of around 5% per year. This restricts the proposal of this treatment to patients with an elevated risk of vascular accidents: age, diabetes, previous cerebro-vascular accidents, and cardiac failure are the risk factors. Nevertheless, the risk of haemorrhage is responsible for an under prescription of the anticoagulants in the elderly. This explains the interest aroused by alternative therapeutics: the results of trials on ximelagatran, a direct anti-thrombin, are promising. In patients with an arrythmia, cardioversion carries a thrombo-embolic risk of around 1%. This risk is reduced by prior anticoagulant treatment. The procedure for this treatment is orientated by a trans-oesophageal echocardiogram. The incertitude of the duration of anticoagulant therapy without cardioversion calls for respect of the arrythmia. The treatment of this is limited to control of the cardiac rhythm and anticoagulant treatment.

  8. Aorta-right atrial tunnel.

    PubMed

    Sai Krishna, Cheemalapati; Baruah, Dibya Kumar; Reddy, Gangireddy Venkateswara; Panigrahi, Nanda Kishore; Suman, Kalagara; Kumar, Palli Venkata Naresh

    2010-01-01

    Aorta-right atrial tunnel is a vascular channel that originates from one of the sinuses of Valsalva and terminates in either the superior vena cava or the right atrium. The tunnel is classified as anterior or posterior, depending upon its course in relation to the ascending aorta. An origin above the sinotubular ridge differentiates the tunnel from an aneurysm of the sinus of Valsalva, and the absence of myocardial branches differentiates it from a coronary-cameral fistula. Clinical presentation ranges from an asymptomatic precordial murmur to congestive heart failure. The embryologic background and pathogenesis of this lesion are attributable either to an aneurysmal dilation of the sinus nodal artery or to a congenital weakness of the aortic media. In either circumstance, progressive enlargement of the tunnel and ultimate rupture into the low-pressure right atrium could occur under the influence of the systemic pressure.The lesion is diagnosed by use of 2-dimensional echocardiography and cardiac catheterization. Computed tomographic angiography is an additional noninvasive diagnostic tool. The possibility of complications necessitates early therapy, even in asymptomatic patients or those with a hemodynamically insignificant shunt. Available treatments are catheter-based intervention, external ligation under controlled hypotension, or surgical closure with the patient under cardiopulmonary bypass.Herein, we discuss the cases of 2 patients who had this unusual anomaly. We highlight the outcome on follow-up imaging (patient 1) and the identification and safe reimplantation of the coronary artery (patient 2).

  9. Cardiovascular Disease Update: Atrial Fibrillation.

    PubMed

    McDivitt, Johnathan D; Barstow, Craig

    2017-03-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The prevalence increases with age, especially in the seventh and eighth decades of life. AF also is associated with multiple risk factors and conditions that are managed commonly in family medicine settings, such as hypertension and diabetes. Rhythm control and rate control are primarily equivalent for mortality rate, but patients treated for rhythm control have more hospitalizations; however, rhythm control may be a viable option for select patients. Beta blockers and nondihydropyridine calcium channel blockers can be used to achieve rate control. Pharmacotherapy or electrical cardioversion can be used to achieve rhythm control, and antiarrhythmic drugs are used to maintain sinus rhythm. Catheter ablation is an option for symptomatic patients whose AF is refractory to standard treatment. The CHA2DS2-VASc score should be used to predict the risk of stroke for patients with AF. Patients with nonvalvular AF and a history of stroke or transient ischemic attack or CHA2DS2-VASc scores of 2 or greater should be treated with warfarin or novel oral anticoagulants. Patients with valvular AF should be treated with warfarin.

  10. Left atrial remodelling in competitive adolescent soccer players.

    PubMed

    D'Ascenzi, F; Cameli, M; Lisi, M; Zacà, V; Natali, B; Malandrino, A; Benincasa, S; Catanese, S; Causarano, A; Mondillo, S

    2012-10-01

    Left atrial (LA) enlargement and improved myocardial diastolic properties are a component of athlete's heart. We performed a longitudinal study involving adolescent athletes to investigate the impact of training on LA remodelling and diastolic function. 21 competitive adolescent soccer players were enrolled and engaged in an 8-month training program. Echocardiographic analysis was performed at baseline, after 4 and 8 months. We assessed diastolic function by Doppler tissue imaging and we analyzed LA adaptations by 2D speckle-tracking echocardiography. After 4 months, LA mean volume index significantly increased (Δ=5.47 ± 4.38 mL/m2, p ≤ 0.0001). After 8 months, a further increase occurred (Δ=8.95 ± 4.47 mL/m2, p ≤ 0.0001). A higher E velocity (p=0.001; p=0.001), a greater E/A ratio (p=0.002; p=0.0009), a higher e' peak (p= 0.005; p=0.001), and a greater e'/a' ratio (p=0.01; p=0.0006) were observed at 4 and at 8 months, respectively. E/e' ratio significantly decreased after 8 months (p ≤ 0.005). Global peak atrial longitudinal strain and global peak atrial contraction strain values significantly decreased after 8 months (p=0.0004, p=0.01, respectively). An 8-month training program is associated with LA dimensional and functional training-specific adaptations in competitive adolescent soccer players. Myocardial diastolic properties can improve after training also in subjects already presenting with features of athlete's heart.

  11. Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease.

    PubMed

    Sharma, Abhishek; Ahmed, Vaseem; Garg, Aakash; Aggarwal, Chirag

    2015-01-01

    Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD.

  12. Natriuretic peptides and the heart: current and future implications for clinical biochemistry.

    PubMed

    Penney, M D

    2005-11-01

    The measurement of B-type natriuretic peptides in plasma is under intense promotion as a method of screening for heart failure. This article provides a historical context for this contention, and attempts to highlight what practical problems may be encountered in establishing a screening service from a clinical biochemistry standpoint. B-type natriuretic peptide measurements may also prove, in future, to have a significant role in the objective monitoring of treatment for heart failure, and to be a valuable prognostic indicator in patients suffering from acute coronary syndrome.

  13. Natriuretic peptides stimulate oocyte meiotic resumption in bovine.

    PubMed

    De Cesaro, Matheus P; Macedo, Mariana P; Santos, Joabel T; Rosa, Paulo R A; Ludke, Charles A; Rissi, Vitor B; Gasperin, Bernardo G; Gonçalves, Paulo B D

    2015-08-01

    The aim of the present study was to evaluate the expression of mRNA encoding natriuretic peptides (NPs) and their receptors in the cumulus-oocyte complex in cattle, a monovular mammalian species, and also to investigate the role of NPs in oocyte meiotic resumption in vitro. mRNA was observed for the NP precursor type-A (NPPA), type-C (NPPC), NP receptor-1 (NPR-1), receptor-2 (NPR-2) and receptor-3 (NPR-3) in bovine cumulus cells, and NPR-2 mRNA was observed in oocytes. These results are different from those obtained in mouse and pig models. The effects of NPPA, NP precursor type-B (NPPB) and NPPC on the resumption of arrested meiosis maintained by forskolin were studied at three different doses (10, 100 and 1000nM) with a 12h culture system. The germinal vesicle breakdown rates were greater (P≤0.05) in oocytes that were cultured in the presence of one or a combination of NPs (from 44% to 73%) than the negative control (from 24% to 27%). Additionally, it was demonstrated that the concentration of cyclic guanosine 3',5'-monophosphate (cGMP) is increased by NPPA and NPPC in oocytes and cumulus cells after 3h of in vitro maturation. However, in both groups, the concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in the oocyte did not increase between 3 and 6h of culture, even when forskolin was used. In summary, we observed the presence of mRNA for NPs and their receptors in the bovine cumulus-oocyte complex and demonstrated that, in vitro, NPPA, NPPB and NPPC stimulate oocyte meiotic resumption in a monovular species.

  14. Ammonia inhibits the C-type natriuretic peptide-dependent cyclic GMP synthesis and calcium accumulation in a rat brain endothelial cell line.

    PubMed

    Konopacka, Agnieszka; Zielińska, Magdalena; Albrecht, Jan

    2008-05-01

    Recently we reported a decrease of C-type natriuretic peptide (CNP)-dependent, natriuretic peptide receptor 2 (NPR2)-mediated cyclic GMP (cGMP) synthesis in a non-neuronal compartment of cerebral cortical slices of hyperammonemic rats [Zielińska, M., Fresko, I., Konopacka, A., Felipo, V., Albrecht, J., 2007. Hyperammonemia inhibits the natriuretic peptide receptor 2 (NPR2)-mediated cyclic GMP synthesis in the astrocytic compartment of rat cerebral cortex slices. Neurotoxicology 28, 1260-1263]. Here we accounted for the possible involvement of cerebral capillary endothelial cells in this response by measuring the effect of ammonia on the CNP-mediated cGMP formation and intracellular calcium ([Ca2+]i) accumulation in a rat cerebral endothelial cell line (RBE-4). We first established that stimulation of cGMP synthesis in RBE-4 cells was coupled to protein kinase G (PKG)-mediated Ca2+ influx from the medium which was inhibited by an L-type channel blocker nimodipine. Ammonia treatment (1h, 5mM NH4Cl) evoked a substantial decrease of CNP-stimulated cGMP synthesis which was related to a decreased binding of CNP to NPR2 receptors, and depressed the CNP-dependent [Ca2+]i accumulation in these cells. Ammonia also abolished the CNP-dependent Ca2+ accumulation in the absence of Na+. In cells incubated with ammonia in the absence of Ca2+ a slight CNP-dependent increase of [Ca2+]i was observed, most likely representing Ca2+ release from intracellular stores. Depression of CNP-dependent cGMP-mediated [Ca2+]i accumulation may contribute to cerebral vascular endothelial dysfunction associated with hyperammonemia or hepatic encephalopathy.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. Nitric Oxide Synthases and Atrial Fibrillation

    PubMed Central

    Bonilla, Ingrid M.; Sridhar, Arun; Györke, Sandor; Cardounel, Arturo J.; Carnes, Cynthia A.

    2012-01-01

    Oxidative stress has been implicated in the pathogenesis of atrial fibrillation. There are multiple systems in the myocardium which contribute to redox homeostasis, and loss of homeostasis can result in oxidative stress. Potential sources of oxidants include nitric oxide synthases (NOS), which normally produce nitric oxide in the heart. Two NOS isoforms (1 and 3) are normally expressed in the heart. During pathologies such as heart failure, there is induction of NOS 2 in multiple cell types in the myocardium. In certain conditions, the NOS enzymes may become uncoupled, shifting from production of nitric oxide to superoxide anion, a potent free radical and oxidant. Multiple lines of evidence suggest a role for NOS in the pathogenesis of atrial fibrillation. Therapeutic approaches to reduce atrial fibrillation by modulation of NOS activity may be beneficial, although further investigation of this strategy is needed. PMID:22536189

  17. Practice implications of the Atrial Fibrillation Guidelines.

    PubMed

    Curtis, Anne B

    2013-06-01

    Atrial fibrillation is one of the most common and complex cardiac arrhythmias. Using currently available evidence, leading medical societies have established recommendations for the optimal management of atrial fibrillation. These guidelines have recently been updated by 4 consensus groups: the European Society of Cardiology, the American College of Chest Physicians, the Canadian Cardiovascular Society, and a task force of 3 societies from the United States: the American College of Cardiology Foundation, the American Heart Association, and the Heart Rhythm Society. The present review focused on the similarities and differences among these recently updated guidelines. Key revisions included updated information on newer treatments for rhythm control, treatment options to reduce atrial fibrillation complications, and updated anticoagulant management for thromboprophylaxis.

  18. Aneurysm of the Left Atrial Appendage

    PubMed Central

    Victor, Solomon; Nayak, Vijaya M.

    2001-01-01

    A 43-year-old woman underwent excision of an aneurysm of the left atrial appendage, which had been causing cerebrovascular embolic episodes. We attribute the aneurysm to congenital dysplasia of the musculi pectinati in the left atrial appendage and of the bands of atrial muscle from which they arise. In Appendix I, we draw attention to the morphologically similar arrangements of inner and outer bands that emanate from a common transverse interatrial band and yield morphologically similar medial, descending, and ascending palm-leaf arrangements of musculi pectinati. In addition, we observe that the strap-like arrangements of musculi in both atria connect the outer band with the para-annular segment of the inner band. In Appendix II, we briefly review the literature concerning musculi pectinati and related bands. PMID:11453121

  19. [Operative management of trigono-atrial lesions].

    PubMed

    Hussein, S

    1998-01-01

    Trigono-atrial-Lesions are microsurgically serios accessible, the results of transcortical aproaches are difficult and frequently unsatisfactory. The microsurgical anatomy of the trigono-atrial region will be studied on 100 brain hemispheres (the posterior cerebral arteries were injected selective on 70 hemispheres). According to the anatomical findings, an interhemispheric microsurgical approach has been developed. The operative results of 25 patients with different atrial lesions are presented. There was no operative mortality, the postoperative morbidity was 12%, in 24% (n = 6) the preoperative state was still unchanged, in 12 cases (48%) we note a normal neurological and neuropsychological postoperative status. In 4 patients (16%) the neurological symptoms are postoperatively improved. According to these first results, the described transatrial approach seems to be a real alternative for careful selected meanly leftsided lesions of the trigone.

  20. Randomised trial of two approaches to screening for atrial fibrillation in UK general practice.

    PubMed Central

    Morgan, Stephen; Mant, David

    2002-01-01

    majority (53/65 [82%]) atrial fibrillation had been previously recorded somewhere on their medical record. If the nurse used any irregularity of the pulse as the screening criterion, the sensitivity of screening was 91% and the specificity was 74%; sensitivity fell to 54% but specificity increased to 98% if the criterion used was continuous irregularity. CONCLUSIONS: Nurse-led screening for atrial fibrillation in UK general practice is both feasible and effective and will identify a substantial number of patients who could benefit from antithrombotic therapy. Although the majority of patients detected at first screening could be identified by careful scrutiny of medical records, review of record summaries was insufficient in the practices involved in this study and screening may be a more cost-effective option. PMID:12014534

  1. Vasotocin analogues with selective natriuretic, kaliuretic and antidiuretic effects in rats.

    PubMed

    Kutina, Anna V; Marina, Anna S; Shakhmatova, Elena I; Natochin, Yury V

    2013-08-10

    The aim of the present study was an investigation of mechanisms mediating selective effect of vasotocin analogues on water, sodium, and potassium excretion. We tested vasotocin analogues: Mpa(1)-vasotocin (dAVT), Mpa(1)-Arg(4)-vasotocin (dAAVT) and Mpa(1)-DArg(8)-vasotocin (dDAVT). The effects on water, sodium, and potassium transport were evaluated in experiments using normal and water-loaded Wistar rats. It was shown that all tested peptides exerted antidiuretic activity. Vasotocin and dAVT induced natriuresis and kaliuresis in rats. V1a agonist (Phe(2)-Ile(3)-Orn(8)-vasopressin) reproduced the renal effects of dAVT on sodium and potassium excretion but not on water reabsorption. dAAVT, dDAVT and V2 agonist (desmopressin) induced kaliuresis without any effect on sodium excretion. Natriuresis was associated with increase in cGMP excretion, whereas kaliuresis was correlated with rise of cAMP excretion. V1a antagonist (Pmp(1)-Tyr(Me)(2)-vasopressin) significantly reduced the dAVT-stimulated natriuresis and did not influence on urinary potassium excretion. V2 antagonist (Pmp(1)-DIle(2)-Ile(4)-vasopressin) significantly reduced the dAVT- and dAAVT-induced kaliuresis. It is assumed that effects of the nonapeptides on sodium and potassium transport are independent of their antidiuretic activity and mediated by different subtypes of V receptors (the V1a or V1a-like receptor for natriuretic effect and V2 or V2-like one for kaliuretic). In accordance to the data obtained, there is a possibility of selective regulation of renal water reabsorption and urinary sodium and potassium excretion with involvement of neurohypophysial hormones.

  2. A Novel Bioassay for the Activity Determination of Therapeutic Human Brain Natriuretic Peptide (BNP)

    PubMed Central

    Yu, Lei; Rao, Chunming; Shi, Xinchang; Li, Yonghong; Gao, Kai; Li, Xuguang; Wang, Junzhi

    2012-01-01

    Background Recombinant human brain natriuretic peptide (rhBNP) is an important peptide-based therapeutic drug indicated for the treatment of acute heart failure. Accurate determination of the potency of therapeutic rhBNP is crucial for the safety and efficacy of the drug. The current bioassay involves use of rabbit aortic strips, with experiments being complicated and time-consuming and markedly variable in results. Animal-less methods with better precision and accuracy should be explored. We have therefore developed an alternative cell-based assay, which relies on the ability of BNP to induce cGMP production in HEK293 cells expressing BNP receptor guanylyl cyclase-A. Methodology/Principal Findings An alternative assay based on the measurement of BNP-induced cGMP production was developed. Specifically, the bioassay employs cells engineered to express BNP receptor guanylyl cyclase-A (GCA). Upon rhBNP stimulation, the levels of the second messager cGMP in these cells drastically increased and subsequently secreted into culture supernatants. The quantity of cGMP, which corresponds to the rhBNP activity, was determined using a competitive ELISA developed by us. Compared with the traditional assay, the novel cell-based assay demonstrated better reproducibility and precision. Conclusion/Significance The optimized cell-based assay is much simpler, more rapid and precise compared with the traditional assay using animal tissues. To our knowledge, this is the first report on a novel and viable alternative assay for rhBNP potency analysis. PMID:23185490

  3. [The concise history of atrial fibrillation].

    PubMed

    Fazekas, Tamás

    2007-01-01

    The author reviews the history of atrial fibrillation, the most common sustained cardiac arrhythmia. The chaotic irregularity of arterial pulse was clearly acknowledged by most of physicians of the ancient China, Egypt and Greece. William Harvey (1578-1657), who first described the circulatory system appropriately, was probably the first to describe fibrillation of the auricles in animals in 1628. The French "clinical pathologist", Jean Baptist de Sénac (1693-1770) was the first who assumed a correlation between "rebellious palpitation" and stenosis of the mitral valve. Robert Adams (1791-1875) also reported in 1827 the association of irregular pulses and mitral stenosis. The discovery of digitalis leaf in 1785 by William Withering (1741-1799) brought relief to patients with atrial fibrillation and congestive heart failure by reducing the ventricular rate. From an analysis of simultaneously recorded arterial and venous pressure curves, the Scottish Sir James Mackenzie (1853-11925) demonstrated that a presystolic wave cannot be seen during "pulsus irregularis perpetuus", a term very first used by Heinrich Ewald Hering (1866-1948). Arthur Cushny (1866-1926) noted the similarity between pulse curves in clinical "delirium cordis" and those in dogs with atrial fibrillation. The first human ECG depicting atrial fibrillation was published by Willem Einthoven (1860-1927) in 1906. The proof of a direct connection between absolute arrhythmia and atrial fibrillation was established by two Viennese physicians, Carl Julius Rothberger and Heinrich Winterberg in 1909. Sir Thomas Lewis (1881-1945), the father of modem electrocardiography, studied electrophysiological characteristics of atrial fibrillation and has shown that its basic perpetuating mechanism is circus movement of electrical impulse (re-entry). After him, the major discoveries relating to the pathophysiology and clinical features of atrial fibrillation in the 20th century stemmed from Karel Frederick Wenckebach

  4. Antithrombotic Therapy for Atrial Fibrillation

    PubMed Central

    You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

    2012-01-01

    Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized

  5. Lunar influence on atrial fibrillation?

    PubMed

    Mikulecky, M; Valachova, A

    1996-08-01

    The most popular periodicities in biology and medicine-the circadians and circannuals-stem undoubtedly from the Earth's rotation and its revolution around the sun. The problem is how to explain the existence of circaseptan, i.e. 5-9-day, and other infradian rhythms. They may correspond to the lunar cycles and their 2nd to 6th harmonics. To test such hypothesis, the calendar dates of 127 attacks of atrial fibrillation in one male subject (M.M.) between 1980 and 1994 were transformed into the days numbered 0-29 for the synodic, and 0-26 for tropic lunar cycle. The daily frequencies obtained in this way were smoothed by moving averages of three successive days each. Considerable fluctuations of frequencies of attacks during both cycles were visible by inspection of the corresponding graphs, called lunar plexograms. Thus, a conspicuous nadir is found under the full moon in the synodic cycle, and a marked peak shortly after the extreme southern position of the moon in the tropic cycle. Halberg's cosinor analysis testing the presence of the 1st to 6th harmonic of either lunar cycle rejected the null hypothesis at the alpha = 0.05 level for all harmonics. Accordingly, the occurrence of attacks was cycling with the period lengths of synodic and tropic lunar cycles, and with those of their 1/2-1/6 period lengths, i.e. with a cluster of approximately circa(di)-septan rhythms. This conclusion is supported by similar findings obtained earlier for various medical and biological events.

  6. Dabigatran etexilate in atrial fibrillation.

    PubMed

    Vora, Amit

    2013-12-01

    Atrial fibrillation (AF) affects millions worldwide. Stroke is the most devastating complication of AF and is associated with a huge disease burden. As a preventive measure, anticoagulant therapy is recommended for most AF patients based on presence of stroke risk factors. For the past six decades warfarin remained the gold standard for stroke prevention in AF (SPAF). However, it is associated with numerous limitations such as a high risk of drug-drug, drug-food interactions and need for frequent INR (2-3) monitoring. Novel oral anticoagulant (NOAC) dabigatran etexilate is a selective, specific, reversible direct thrombin inhibitor that has been approved in India for SPAF and primary venous thromboembolism prevention. The efficacy and safety of dabigatran in AF has been established the "Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY)", a randomized clinical trial. RE-LY (n = 18,113) demonstrated that the efficacy of dabigatran 110 mg BID was as good as well controlled warfarin and dabigatran 150 mg BID reduced the risk of ischaemic stroke by 25% (P = 0.03). Till date, 150mg dabigatran is the only NOAC offering a superior reduction in most commonly seen ischemic strokes due to AF compared to warfarin. Additionally, both doses of dabigatran significantly reduced the risk of total bleeds, intracranial, and life threatening bleeds versus warfarin (p < 0.05). Dabigatran has advantages over warfarin including predictable pharmacokinetic/pharmacodynamic profile, minimal drug-drug and no drug-food interactions while no monitoring is needed.The 150 mg dose of dabigatran should be considered in younger patients with a low risk of bleeding and good renal function to achieve a superior ischemic stroke reduction, whereas, the 110 mg dose should be considered in elderly patients, those with mild to moderate renal function or those with high risk of bleeding.

  7. Endogenous natriuretic factors 3: Isolation and characterization of human natriuretic factors LLU-{alpha}, LLU-{beta}{sub 1}, and LLU-{gamma}

    SciTech Connect

    Murray, E.D. Jr.; Kantoci, D.; DeWind, S.A.

    1995-12-31

    A low molecular weight endogenous substance believed to be responsible for extracellular fluid homeostasis in mammals has been sought for many years. Our goal is to isolate and structurally characterize this putative {open_quotes}natriuretic hormone{close_quotes}. We have developed an assay using the conscious rat to measure prolonged natriuresis, the activity originally described for this putative substance. Using this assay we have identified a number of natriuretic compounds isolated from human uremic urine. The collected urine is processed by ultrafiltration ({le} 3 kDa), gel filtration chromatography (G-25) and extraction with isopropanol and diethyl ether. The organic soluble material is then subjected to sequential high-performance liquid chromatography. We report here the initial characterization of two pure isolates (LLU-{alpha} and LLU-{gamma}) obtained by this method, and the structural elucidation of a third pure compound, LLU-{beta}{sub 1}, a natriuretic and previously unreported metabolite of the drug diltiazem. 33 refs., 7 figs., 4 tabs.

  8. Evidence that Asn542 of neprilysin (EC 3.4.24.11) is involved in binding of the P2' residue of substrates and inhibitors.

    PubMed Central

    Dion, N; Le Moual, H; Fournié-Zaluski, M C; Roques, B P; Crine, P; Boileau, G

    1995-01-01

    Neprilysin (EC 3.4.24.11) is a Zn2+ metallopeptidase involved in the degradation of biologically active peptides, e.g. enkephalins and atrial natriuretic peptide. The substrate specificity and catalytic activity of neprilysin resemble those of thermolysin, a crystallized bacterial Zn2+ metalloprotease. Despite little overall homology between the primary structures of thermolysin and neprilysin, many of the amino acid residues involved in catalysis, as well as Zn2+ and substrate binding, are highly conserved. Most of the active-site residues of neprilysin have their homologues in thermolysin and have been characterized by site-directed mutagenesis. Furthermore, hydrophobic cluster analysis has revealed some other analogies between the neprilysin and thermolysin sequences [Benchetrit, Bissery, Mornon, Devault, Crine and Roques (1988) Biochemistry 27, 592-596]. According to this analysis the role of Asn542 in the neprilysin active site is analogous to that of Asn112 of thermolysin, which is to bind the substrate. Site-directed mutagenesis was used to change Asn542 to Gly or Gln residues. The effect of these mutations on substrate catalysis and inhibitor binding was examined with a series of thiorphan-like compounds containing various degrees of methylation at the P2' residue. For both mutated enzymes, determination of kinetic parameters with [D-Ala2,Leu5]enkephalin as substrate showed that the large decrease in activity was attributable to an increase in Km (14-16-fold) whereas kcat values were only slightly affected (2-3-fold decrease). This is in agreement with Asn542 being involved in substrate binding rather than directly in catalysis. Finally, the IC50 values for thiorphan and substituted thiorphans strongly suggest that Asn542 of neprilysin binds the substrate on the amino side of the P2' residue by formation of a unique hydrogen bond. Images Figure 2 Figure 3 PMID:7487905

  9. A rare large right atrial myxoma with rapid growth rate.

    PubMed

    Kelly, Shawn C; Steffen, Kelly; Stys, Adam T

    2014-10-01

    Atrial myxomas are the most common benign intracavitary cardiac neoplasms. They most frequently occur in the left atrium. Right atrial tumors are rare, comprising 20 percent of myxomas achieving an incidence of 0.02 percent. Due to their rarity, right atrial tumor development and associated clinical symptoms has not been well described. The classical clinical triad for the presentation of left atrial myxomas--heart failure, embolic events, and constitutional symptoms--may not be applicable to right sided tumors. Also, natural development of myxoma is not well described, as surgical resection is the common practice. Previously ascribed growth rates of myxomas refer mostly to left atrial ones, as right atrial tumors are rare. We present a case of right atrial myxoma with growth rates exceeding those previously described.

  10. An improved method for echographic detection of left atrial enlargement

    NASA Technical Reports Server (NTRS)

    Brown, O. R.; Harrison, D. C.; Popp, R. L.

    1974-01-01

    Echographic dimensions of the aortic root and left atrium were compared in 170 patients in order to assess dilation of the left atrium with reference to the relatively nondistensible fibrous aortic root. In 50 patients without cause for left atrial or aortic enlargement, the ratio of left atrial/aortic root dimensions was 0.87 to 1.11. In 80 patients with known cause for left atrial enlargement, the left atrial/aortic root ratio was greater than or equal to 1.17. In 40 patients with isolated valve disease, dilation of both the aortic root and the left atrium resulted in a left atrial/aortic root dimension ratio less than 1.17 in some patients. Despite this consideration, the comparison of left atrial and aortic root dimension appears to be as specific as, and more sensitive than, previously proposed methods for the evaluation of left atrial enlargement.

  11. Fiber photo-catheters for laser treatment of atrial fibrillation

    PubMed Central

    Peshko, Igor; Rubtsov, Vladimir; Vesselov, Leonid; Sigal, Gennady; Laks, Hillel

    2009-01-01

    A fiber photo-catheter has been developed for surgical treatment of atrial fibrillation with laser radiation. Atrial fibrillation (AF) is a heart rhythm abnormality that involves irregular and rapid heartbeats. Recent studies demonstrate the superiority of treating AF disease with optical radiation of the near infrared region. To produce long continuous transmural lesions, solid-state lasers and laser diodes, along with end-emitting fiber catheters, have been used experimentally. The absence of side-emitting flexible catheters with the ability to produce long continuous lesions limits the further development of this technology. In this research, a prototype of an optical catheter, consisting of a flexible 10-cm fiber diffuser has been used to make continuous photocoagulation lesions for effective maze procedure treatments. The system also includes: a flexible optical reflector; a series of openings for rapid self-attachment to the tissue; and an optional closed-loop irrigating chamber with circulating saline to cool the optical diffuser and irrigate the tissue. PMID:19587838

  12. Application of Traditional Chinese Medicine in Treatment of Atrial Fibrillation

    PubMed Central

    Dong, Yan; Yao, Kuiwu; Jiang, Wenrui

    2017-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, which is related to many cardiac and cerebral vascular diseases, especially stroke. It can therefore increase cardiovascular mortality and all-cause death. The current treatments of AF remain to be western drugs and radiofrequency ablation which are limited by the tolerance of patients, adverse side effects, and high recurrence rate, especially for the elderly. On the contrary, traditional Chinese medicine (TCM) with long history of use involves various treatment methods, including Chinese herbal medicines (CHMs) or bioactive ingredients, Chinese patent medicines, acupuncture, Qigong, and Tai Chi Chuan. With more and more researches reported, the active roles of TCM in AF management have been discovered. Then it is likely that TCM would be effective preventive means and valuable additional remedy for AF. The potential mechanisms further found by numerous experimental studies showed the distinct characteristics of TCM. Some CHMs or bioactive ingredients are atrial-selective, while others are multichannel and multifunctional. Therefore, in this review we summarized the treatment strategies reported in TCM, with the purpose of providing novel ideas and directions for AF management. PMID:28243308

  13. Digitalis does not improve left atrial mechanical dysfunction after successful electrical cardioversion of chronic atrial fibrillation.

    PubMed

    Yujing, Wang; Congxin, Huang; Shaning, Yang; Lijun, Jin; Xiaojun, Hu; Gang, Wu; Qiang, Xie

    2010-05-01

    This study was designed to investigate whether administration of digitalis could improve mechanical function of left atrial appendage (LAA) and left atrium prospectively in patients with atrial stunning. Fifty-four consecutive patients in whom atrial stunning was observed immediately after cardioversion of chronic atrial fibrillation (AF) were randomized into digitalis or control group for 1 week following cardioversion. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were performed prior to, immediately following, 1 day after and 1 week after cardioversion to measure transmitral flow velocity and LAA flow velocity. Electrical cardioversion of AF elicited significantly slower left atrial appendage peak emptying velocity (LAA-PEV) and peak filling velocity (LAA-PFV) immediately following cardioversion in both groups. 1 day post cardioversion, there were no significant differences in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or left atrial appendage ejection fraction (LAA-EF) between digitalis and control groups. 1 week post cardioversion, no significant differences were found in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or LAA-EF between the two groups. The occurrence rates of spontaneous echo contrast were not significantly different between digitalis and control groups one day and one week post cardioversion. In conclusion, digitalis did not improve left atrial and appendage mechanical dysfunction following cardioversion of chronic AF. Digitalis did not prevent the development of spontaneous echo contrast in left atrial chamber and appendage. This may be due to the fact that digitalis aggravates intracellular calcium overload induced by chronic AF and has a negative effect on ventricular rate.

  14. Computational models of atrial cellular electrophysiology and calcium handling, and their role in atrial fibrillation.

    PubMed

    Heijman, Jordi; Erfanian Abdoust, Pegah; Voigt, Niels; Nattel, Stanley; Dobrev, Dobromir

    2016-02-01

    The complexity of the heart makes an intuitive understanding of the relative contribution of ion channels, transporters and signalling pathways to cardiac electrophysiology challenging. Computational modelling of cardiac cellular electrophysiology has proven useful to integrate experimental findings, extrapolate results obtained in expression systems or animal models to other systems, test quantitatively ideas based on experimental data and provide novel hypotheses that are experimentally testable. While the bulk of computational modelling has traditionally been directed towards ventricular bioelectricity, increasing recognition of the clinical importance of atrial arrhythmias, particularly atrial fibrillation, has led to widespread efforts to apply computational approaches to understanding atrial electrical function. The increasing availability of detailed, atrial-specific experimental data has stimulated the development of novel computational models of atrial-cellular electrophysiology and Ca(2+) handling. To date, more than 300 studies have employed mathematical simulations to enhance our understanding of atrial electrophysiology, arrhythmogenesis and therapeutic responses. Future modelling studies are likely to move beyond current whole-cell models by incorporating new data on subcellular architecture, macromolecular protein complexes, and localized ion-channel regulation by signalling pathways. At the same time, more integrative multicellular models that take into account regional electrophysiological and Ca(2+) handling properties, mechano-electrical feedback and/or autonomic regulation will be needed to investigate the mechanisms governing atrial arrhythmias. A combined experimental and computational approach is expected to provide the more comprehensive understanding of atrial arrhythmogenesis that is required to develop improved diagnostic and therapeutic options. Here, we review this rapidly expanding area, with a particular focus on Ca(2+) handling, and

  15. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  16. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  17. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  18. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  19. 21 CFR 862.1117 - B-type natriuretic peptide test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false B-type natriuretic peptide test system. 862.1117 Section 862.1117 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  20. Diminished natriuretic response to dopamine D1 receptor agonist, SKF-38393 in obese Zucker rats.

    PubMed

    Marwaha, Aditi; Lokhandwala, Mustafa F

    2003-11-01

    Dopamine causes natriuresis and diuresis via activation of D1 receptors located on the renal proximal tubules and subsequent inhibition of the sodium transporters, Na-H exchanger and Na+/K+ ATPase. We have reported that dopamine fails to inhibit the activities of these two transporters in the obese Zucker rats (OZR). The present study was designed to examine the functional consequence of this phenomenon by determining the natriuretic and diuretic response to D1 receptor activation in lean Zucker rats (LZR) and OZR. In 11-12 week-old OZR and LZR, natriuretic and diuretic responses to intravenously administered D1 receptor agonist, SKF 38393 (3 microg/kg/min for 30 min) were measured under Inactin anesthesia. Plasma insulin and glucose levels were significantly higher in the obese rats as compared to the lean rats. Intravenous infusion of SKF 38393 caused significant increases in urine flow, urinary sodium excretion (U(Na)V), fractional excretion of sodium (FE(Na)), and glomerular filtration rate (GFR) in the lean rats. However, the natriuretic and diuretic response to SKF 38393 was markedly blunted in OZR. Infusion of SKF 38393 did not cause significant changes in the mean blood pressure and heart rate in either of the two groups. We suggest that the diminished natriuretic response to D1 receptor activation in OZR is the consequence of the previously reported defect in the D1 receptor-G-protein coupling and the failure of dopamine to inhibit the sodium transporters in these animals.

  1. B-type natriuretic peptides and mortality after stroke

    PubMed Central

    García-Berrocoso, Teresa; Giralt, Dolors; Bustamante, Alejandro; Etgen, Thorleif; Jensen, Jesper K.; Sharma, Jagdish C.; Shibazaki, Kensaku; Saritas, Ayhan; Chen, Xingyong; Whiteley, William N.

    2013-01-01

    Objective: To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information. Methods: Suitable studies for meta-analysis were found by searching MEDLINE and EMBASE databases until October 26, 2012. Weighted mean differences measured effect size; meta-regression and publication bias were assessed. Individual participant data were used to estimate effects by logistic regression and to evaluate BNP/NT-proBNP additional predictive value by area under the receiver operating characteristic curves, and integrated discrimination improvement and categorical net reclassification improvement indexes. Results: Literature-based meta-analysis included 3,498 stroke patients from 16 studies and revealed that BNP/NT-proBNP levels were 255.78 pg/mL (95% confidence interval [CI] 105.10–406.47, p = 0.001) higher in patients who died; publication bias entailed the loss of this association. Individual participant data analysis comprised 2,258 stroke patients. After normalization of the data, patients in the highest quartile had double the risk of death after adjustment for clinical variables (NIH Stroke Scale score, age, sex) (odds ratio 2.30, 95% CI 1.32–4.01 for BNP; and odds ratio 2.63, 95% CI 1.75–3.94 for NT-proBNP). Only NT-proBNP showed a slight added value to clinical prognostic variables, increasing discrimination by 0.028 points (integrated discrimination improvement index; p < 0.001) and reclassifying 8.1% of patients into correct risk mortality categories (net reclassification improvement index; p = 0.003). Neither etiology nor time from onset to death affected the association of BNP/NT-proBNP with mortality. Conclusion: BNPs are associated with poststroke mortality independent of NIH Stroke Scale score, age, and sex. However, their translation to clinical practice seems difficult because BNP

  2. Effect of years of endurance exercise on risk of atrial fibrillation and atrial flutter.

    PubMed

    Myrstad, Marius; Nystad, Wenche; Graff-Iversen, Sidsel; Thelle, Dag S; Stigum, Hein; Aarønæs, Marit; Ranhoff, Anette H

    2014-10-15

    Emerging evidence suggests that endurance exercise increases the risk for atrial fibrillation (AF) in men, but few studies have investigated the dose-response relation between exercise and risk for atrial arrhythmias. Both exposure to exercise and reference points vary among studies, and previous studies have not differentiated between AF and atrial flutter. The aim of this study was to assess the risk for atrial arrhythmias by cumulative years of regular endurance exercise in men. To cover the range from physical inactivity to long-term endurance exercise, the study sample in this retrospective cohort study was based on 2 distinct cohorts: male participants in a long-distance cross-country ski race and men from the general population, in total 3,545 men aged ≥ 53 years. Arrhythmia diagnoses were validated by electrocardiograms during review of medical records. Regular endurance exercise was self-reported by questionnaire. A broad range of confounding factors was available for adjustment. The adjusted odds ratios per 10 years of regular endurance exercise were 1.16 (95% confidence interval 1.06 to 1.29) for AF and 1.42 (95% confidence interval 1.20 to 1.69) for atrial flutter. In stratified analyses, the associations were significant in cross-country skiers and in men from the general population. In conclusion, cumulative years of regular endurance exercise were associated with a gradually increased risk for AF and atrial flutter.

  3. Relationship between body mass index and left atrial appendage thrombus in nonvalvular atrial fibrillation.

    PubMed

    Cohoon, Kevin P; McBane, Robert D; Ammash, Naser; Slusser, Joshua P; Grill, Diane E; Wysokinski, Waldemar E

    2016-05-01

    Atrial fibrillation and obesity are two major growing epidemics in the United States and globally. Obese people are at the increased risk of developing atrial fibrillation. The contribution of obesity as an independent risk factor for stroke in the setting of atrial fibrillation remains unclear. We tested the hypothesis that non-valvular atrial fibrillation (NVAF) patients with increased body mass index (BMI) would be at increased risk for the development of left atrial appendage thrombus (LAAT). Consecutive, anticoagulation naïve patients with NVAF referred for a transesophageal echocardiogram (TEE) between January 1, 2007 and October 21, 2009 were approached for study participation. All clinical, laboratory, and TEE measurement data were collected prospectively. Within a group of 400 anticoagulation naïve NVAF patients (mean age 63 ± 15 years, 28 % women; 17 % with LAAT) the prevalence of LAAT was similar across all BMI categories (normal 13 %, overweight 19 %, obese 16 %, morbidly obese 16 %; p = 0.71). Despite a higher CHADS2 score and a higher prevalence of both hypertension and diabetes mellitus, elevated BMI was not an independent predictor of LAAT when analyzed as either a continuous variable, across BMI WHO categories, a dichotomous variable stratified at values above versus below 27 kg/m(2), or BMI stratified on atrial fibrillation duration. Despite a higher prevalence of major risk factors for thromboembolism, the prevalence of LAAT was not increased in overweight, obese, and morbidly obese patients.

  4. The effect of asanguinous cardioplegic arrest on atrial preservation using atrial ATP as a marker.

    PubMed

    Hines, G L; Scheaffer, P; Williams, L; Mantell, P; Cheifitz, P

    1990-01-01

    Changes in atrial adenosine triphosphate (ATP) and the presence of postoperative arrhythmias were studied in 14 patients during routine coronary artery bypass grafting to 1) attempt to evaluate atrial preservation, and 2) determine if a relationship exists between changes in ATP and the development of postoperative arrhythmias. Atrial biopsies were obtained at the time of cannulation (preischemic sample) and after the removal of the aortic crossclamp (postischemic sample). Methods of myocardial protection included systemic hypothermia (28 degrees C), periodic reinfusion of crystalloid cardioplegia into the aortic root and completed vein grafts, and iced slush in the pericardial well. Atrial temperature was monitored. Preischemic ATP was 0.412 +/- 0.32 mu mol/gm, and the postischemic value was 0.220 +/- 0.13 mu mol/gm (p less than .02). Atrial temperature routinely decreased to 13-18 degrees C after cardioplegic infusion but rose to 24 degrees C between infusions. There was no correlation between postoperative supraventricular arrhythmias (4 patients) and changes in ATP. In conclusion, routine coronary artery bypass grafting with standard methods of cardiac preservation does not appear to satisfactorily preserve atrial tissue. The clinical correlation and significance of this remains to be elucidated.

  5. Ultrasound guidance for distal insertion of ventriculo-atrial shunt catheters: technical note.

    PubMed

    Sheth, Sameer A; McGirt, Matthew; Woodworth, Graeme; Wang, Paul; Rigamonti, Daniele

    2009-04-01

    Ventriculo-atrial (VA) shunts are often used for CSF diversion in situations involving abdominal pathology that preclude the use of ventriculo-peritoneal shunts. Distal (venous) catheters of VA shunts have historically been inserted using a cut-down on the internal jugular vein (IJV). Less invasive placement of atrial catheters may minimize operative times and attenuate post-operative incisional discomfort. We describe a method for atrial catheter placement using ultrasound guidance to visualize the IJV and facilitate percutaneous venous puncture in 17 adult patients (23 total insertions) undergoing treatment for hydrocephalus or pseudotumor cerebri. The IJV and carotid artery were visualized by ultrasound in 23 (100%) cases. Venous penetration and successful atrial catheter placement was achieved on the first attempt in 23 (100%) cases. Pneumothorax, carotid artery puncture or need for venous cut-down occurred in no cases. The utilization of ultrasound guidance for distal VA shunt catheter insertion may increase comfort with this procedure and ultimately decrease complication rate and operative time.

  6. Quantification of fiber orientation in the canine atrial pacemaker complex using optical coherence tomography

    PubMed Central

    Ambrosi, Christina M.; Fedorov, Vadim V.; Schuessler, Richard B.; Rollins, Andrew M.

    2012-01-01

    Abstract The atrial pacemaker complex is responsible for the initiation and early propagation of cardiac impulses. Optical coherence tomography (OCT), a nondestructive imaging modality with spatial resolutions of ∼1 to 15 μm, can be used to identify unique fiber orientation patterns in this region of the heart. Functionally characterized canine sinoatrial nodes (SAN) (n=7) were imaged using OCT up to ∼1  mm below the endocardial tissue surface. OCT images were directly compared to their corresponding histological sections. Fiber orientation patterns unique to the crista terminalis (CT), SAN, and surrounding atrial myocardium were identified with dominant average fiber angles of 89±12  deg, 110±16  deg, and 95±35  deg, respectively. Both the CT and surrounding atrial myocardium displayed predominantly unidirectionally based fiber orientation patterns within each specimen, whereas the SAN displayed an increased amount of fiber disarray manifested quantitatively as a significantly greater standard deviation in fiber angle distribution within specimens [33±7  deg versus 23±5  deg, atrium (p=0.02); 18±3  deg, CT (p=0.0003)]. We also identified unique, local patterns of fiber orientation specific to the functionally characterized block zone. We demonstrate the ability of OCT in detecting components of the atrial pacemaker complex which are intimately involved in both normal and abnormal cardiac conduction. PMID:22894470

  7. An unusual presentation of atrial myxoma

    PubMed Central

    Anpalakhan, Shaemala; Ramasamy, Dewi; Fan, Kin Sing

    2014-01-01

    Myxomas are uncommon primary cardiac tumours that usually affect the left atrium. We herein report the case of a patient who presented with right heart failure and proteinuria, leading to the diagnosis of atrial myxoma. Surgical resection resulted in resolution of the patient’s symptoms. PMID:25631903

  8. Spinal cord ischemia and left atrial myxoma.

    PubMed

    Hirose, G; Kosoegawa, H; Takado, M; Shimazaki, K; Murakami, E

    1979-07-01

    A 62-year-old man had an acute, transient, flaccid paraplegia. Examination showed a primary cardiac tumor with emboli to major branches of the aorta. A myxoma was removed from the left atrium, and normal function returned. Left atrial myxoma should be suspected as a cause for embolism to the CNS.

  9. Obstructive Sleep Apnea and Atrial Arrhythmogenesis

    PubMed Central

    Hohl, Mathias; Linz, Benedikt; Böhm, Michael; Linz, Dominik

    2014-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with relevant morbidity and mortality. Besides hypertension, valvular disease and cardiomyopathy, mainly ischemic and dilated, also other conditions like obesity, alcohol abusus, genetic factors and obstructive sleep apnea (OSA) are discussed to contribute to the progression from paroxysmal to persistent AF. The prevalence of OSA among patients with AF is 40-50%. OSA is characterized by periodic or complete cessation of effective breathing during sleep due to obstruction of the upper airways. Obstructive respiratory events result in acute intrathoracic pressure swings and profound changes in blood gases together leading to atrial stretch and acute sympatho-vagal dysbalance resulting in acute apnea related to electrophysiological and hemodynamic alterations. Additionally, repetitive obstructive events in patients with OSA may lead to sympathetic and neurohumoral activation and subsequent structural and functional changes in the atrium creating an arrhythmogenic substrate for AF in the long run. This review focuses on the acute and chronic effects of negative thoracic pressure swings, changes in blood pressure and sympatho-vagal dysbalance induced by obstructive respiratory events on atrial electrophysiology and atrial structure in patients with obstructive sleep apnea. PMID:25004989

  10. Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure

    PubMed Central

    Testani, Jeffrey M.; Hanberg, Jennifer S.; Cheng, Susan; Rao, Veena; Onyebeke, Chukwuma; Laur, Olga; Kula, Alexander; Chen, Michael; Wilson, F. Perry; Darlington, Andrew; Bellumkonda, Lavanya; Jacoby, Daniel; Tang, W. H. Wilson; Parikh, Chirag R.

    2015-01-01

    Background Removal of excess sodium and fluid is a primary therapeutic objective in acute decompensated heart failure (ADHF) and commonly monitored with fluid balance and weight loss. However, these parameters are frequently inaccurate or not collected and require a delay of several hours after diuretic administration before they are available. Accessible tools for rapid and accurate prediction of diuretic response are needed. Methods and Results Based on well-established renal physiologic principles an equation was derived to predict net sodium output using a spot urine sample obtained one or two hours following loop diuretic administration. This equation was then prospectively validated in 50 ADHF patients using meticulously obtained timed 6-hour urine collections to quantitate loop diuretic induced cumulative sodium output. Poor natriuretic response was defined as a cumulative sodium output of <50 mmol, a threshold that would result in a positive sodium balance with twice-daily diuretic dosing. Following a median dose of 3 mg (2–4 mg) of intravenous bumetanide, 40% of the population had a poor natriuretic response. The correlation between measured and predicted sodium output was excellent (r=0.91, p<0.0001). Poor natriuretic response could be accurately predicted with the sodium prediction equation (AUC=0.95, 95% CI 0.89–1.0, p<0.0001). Clinically recorded net fluid output had a weaker correlation (r=0.66, p<0.001) and lesser ability to predict poor natriuretic response (AUC=0.76, 95% CI 0.63–0.89, p=0.002). Conclusions In patients being treated for ADHF, poor natriuretic response can be predicted soon after diuretic administration with excellent accuracy using a spot urine sample. PMID:26721915

  11. Stroke as the First Manifestation of Atrial Fibrillation

    PubMed Central

    Jaakkola, Jussi; Mustonen, Pirjo; Kiviniemi, Tuomas; Hartikainen, Juha E. K.; Palomäki, Antti; Hartikainen, Päivi; Nuotio, Ilpo; Ylitalo, Antti; Airaksinen, K. E. Juhani

    2016-01-01

    Atrial fibrillation may remain undiagnosed until an ischemic stroke occurs. In this retrospective cohort study we assessed the prevalence of ischemic stroke or transient ischemic attack as the first manifestation of atrial fibrillation in 3,623 patients treated for their first ever stroke or transient ischemic attack during 2003–2012. Two groups were formed: patients with a history of atrial fibrillation and patients with new atrial fibrillation diagnosed during hospitalization for stroke or transient ischemic attack. A control group of 781 patients with intracranial hemorrhage was compiled similarly to explore causality between new atrial fibrillation and stroke. The median age of the patients was 78.3 [13.0] years and 2,009 (55.5%) were women. New atrial fibrillation was diagnosed in 753 (20.8%) patients with stroke or transient ischemic attack, compared to 15 (1.9%) with intracranial hemorrhage. Younger age and no history of coronary artery disease or other vascular diseases, heart failure, or hypertension were the independent predictors of new atrial fibrillation detected concomitantly with an ischemic event. Thus, ischemic stroke was the first clinical manifestation of atrial fibrillation in 37% of younger (<75 years) patients with no history of cardiovascular diseases. In conclusion, atrial fibrillation is too often diagnosed only after an ischemic stroke has occurred, especially in middle-aged healthy individuals. New atrial fibrillation seems to be predominantly the cause of the ischemic stroke and not triggered by the acute cerebrovascular event. PMID:27936187

  12. Effectiveness of Early Invasive Therapy for Atrial Tachycardia in Adult Atrial-Baffle Survivors

    PubMed Central

    Zaidi, Ali N.; Morrison, Justin; Daniels, Curt J.; Kalbfleisch, Steven; Kertesz, Naomi J.

    2017-01-01

    Adults who underwent complex atrial baffling as children via Mustard or Senning procedures are at heightened risk for atrial arrhythmias. Antiarrhythmic therapies are typically ineffective in this population. Accordingly, our team of pediatric and adult electrophysiologists investigated the effectiveness of early invasive transbaffle-access techniques to perform early radiofrequency ablation at the source of these clinically significant arrhythmias. For this retrospective study, we selected 11 adult survivors of atrial baffling (mean age, 34 ± 9 yr) who underwent clinically indicated electrophysiologic study after no more than one trial of antiarrhythmic therapy. Using transbaffle-access techniques and 3-dimensional mapping of the venous atria, we found 12 inducible arrhythmias in 10 patients: intra-atrial reentrant tachycardia (n=6), atrioventricular nodal reentrant tachycardia (n=3), focal atrial tachycardia (n=2), and repetitive double firing of the atrioventricular node (n=1). Defining success as short- and midterm freedom from arrhythmia, we analyzed outcomes of radiofrequency ablation at 1 and 6 months. At 1 month, ablation was 100% successful. At 6 months, after 11 ablations in 9 patients, 5 patients had no clinical recurrence, 2 had improved arrhythmia control from minimal medical therapy, and 2 were to undergo repeat study for recurrent tachycardia. In the recurrence-free patients, arrhythmias during electrophysiology study matched the types found clinically before the study. To our knowledge, this is the largest one-year cohort of adult survivors of atrial baffling to have undergone study by a combined pediatric–adult electrophysiology team. We conclude that early invasive transbaffle access for ablating diverse atrial tachyarrhythmias was effective in these patients. PMID:28265208

  13. Successful anesthetic management of a child with blepharophimosis syndrome and atrial septal defect for reconstructive ocular surgery

    PubMed Central

    Baidya, Dalim Kumar; Khanna, Puneet; Kumar, Anil; Shende, Dilip

    2011-01-01

    Blepharophimosis syndrome is an autosomal dominant disorder characterized by eyelid malformation, involvement of reproductive system and abnormal facial morphology leading to difficult airway. We report a rare association of blepharophimosis syndrome and atrial septal defect in a 10-year-old girl who came for reconstruction surgery of eyelid. The child had dyspnea on exertion. Atrial septal defect was identified preoperatively by clinical examination and echocardiography. Anesthesia management was complicated by failure in laryngeal mask airway placement and Cobra perilaryngeal airway was subsequently used. PMID:22096296

  14. A Review of the Relevant Embryology, Pathohistology, and Anatomy of the Left Atrial Appendage for the Invasive Cardiac Electrophysiologist

    PubMed Central

    DeSimone, Christopher V.; Gaba, Prakriti; Tri, Jason; Syed, Faisal; Noheria, Amit; Asirvatham, Samuel J.

    2016-01-01

    The three-dimensional morphology of the left atrial appendage provides the substrate for thrombus generation, and is a harbinger for embolic material due to its direct connection to the left-sided circulation. Appreciating the development of the appendage from mesodermal layer to its adult form provides the basis to improve exclusion from the atrial circulation, and thereby can lead to a significant reduction in stroke risk. This process also provides insight into the role of the left atrial appendage as an endocrine organ, its involvement in fluid homeostasis, and its connection to the autonomic nervous system. Knowledge of the surrounding structural arrangement is critical to identify landmarks from both an endocardial and epicardial perspective to improve targeted device placement. Furthermore, correlation of the left atrial appendage body, neck, and ostium to the surrounding anatomy can also improve both procedural efficacy and safety. In addition, a working knowledge of the regional anatomy adds a prudent degree of awareness for procedural complications, and allows for early identification and timely intervention as these situations arise. A detailed understanding of the left atrial appendage embryology, histology, and gross anatomy is imperative to identify the correct device and approach for each individual patient. In addition, this increased awareness can identify areas that are in need of further innovation, and thus provide the ability to adapt and refine existing technologies to overcome pitfalls currently facing catheter-based approaches. PMID:27087889

  15. 78 FR 11207 - Clinical Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... Treatment of Atrial Fibrillation; Guidance for Industry and Food and Drug Administration Staff; Availability... Ablation Devices for Treatment of Atrial Fibrillation.'' This guidance provides FDA's recommendations on clinical trial designs for surgical ablation devices intended for the treatment of atrial...

  16. Staged transthoracic approach to persistent atrial fibrillation (TOP-AF): study protocol for a randomized trial

    PubMed Central

    2014-01-01

    Background Persistent atrial fibrillation frequently shows multiple different electrophysiological mechanisms of induction. This heterogeneity causes a low success rate of single procedures of ablation and a high incidence of recurrence. Surgical ablation through bilateral thoracotomy demonstrates better results after a single procedure. Prospective observational studies in inhomogeneous populations without control groups report a remarkable 90% of success with hybrid or staged procedures of surgical ablation coupled with catheter ablation. In this trial, we will examine the hypothesis that a staged approach involving initial minimally invasive surgical ablation of persistent atrial fibrillation, followed by a second percutaneous procedure in case of recurrence, has a higher success rate than repeated percutaneous procedures. Methods/Design This is a controlled (2:1) randomized trial comparing use of a percutaneous catheter with minimally invasive transthoracic surgical ablation of persistent atrial fibrillation. The inclusion and exclusion criteria, definitions, and treatment protocols are those reported by the 2012 Expert Consensus Statement on catheter and surgical ablation of atrial fibrillation. Patients will be randomized to either percutaneous catheter (n = 100) or surgical (n = 50) ablation as the first procedure. After 3 months, they are re-evaluated, according to the same guidelines, and receive a second procedure if necessary. Crossover will be allowed and data analyzed on an “intention-to-treat” basis. Primary outcomes are the incidence of sinus rhythm at 6 and 12 months and the proportions of patients requiring a second procedure. Discussion The use of a staged strategy combining surgical and percutaneous approaches might be more favorable in treatment of persistent atrial fibrillation than the controversial single percutaneous ablation. Trial registration ISRCTN08035058 Reg 06.20.2013 PMID:24885377

  17. Intraoperative device closure of atrial septal defects in the Older Population

    PubMed Central

    2011-01-01

    Objective This study sought to prove the safety and feasibility of intraoperative device closure of atrial septal defect (ASD) with transthoracic minimal invasion in the older patients. Methods From January 2006 to December 2009, 47 patients aged 50 years or more and suffered from atrial septal defect were enrolled in our institution. Patients were divided into two groups, 27 of which in group I with intraoperative device closure and the other 20 in group II with surgical closure. In group I, the method involved a minimal intercostal incision, which was performed after full evaluation of the atrial septal defect by transthoracic echocardiography, and the insertion of the device through the delivery sheath to occlude the atrial septal defect. Results In group I, implantation was ultimately successful in all patients. The complete closure rate at 24 hours and 1 year were 81.5% and 100% respectively. In 6 of 27 patients, minor complications occurred: transient arrhythmia (n = 5) and blood transfusion (n = 3). In group II, all patients were closured successfully; almost all of them needed blood transfusion and suffered from various minor complications though. During a follow-up period of 1 to 5 years, no residual shunt, noticeable mitral regurgitation, significant arrhythmias, thrombosis, or device failure were found. In our comparative studies, group II had significantly longer ICU stay and hospital stay than group I (p < 0.05). The cost of group I was less than that of group II(p < 0.05). Conclusions Minimally invasive transthoracic device closure of the atrial septal defect at advanced age with a domestically made device without cardiopulmonary bypass is safe and feasible under transthoracic echocardiographic guidance. It was cost-savings, yielding better cosmetic results and leaving fewer traumas than surgical closure. Early and mid-term results are encouraging. However, it is necessary to evaluate the long-term results. PMID:21958758

  18. Perspectives and challenges of antioxidant therapy for atrial fibrillation.

    PubMed

    Gasparova, Iveta; Kubatka, Peter; Opatrilova, Radka; Caprnda, Martin; Filipova, Slavomira; Rodrigo, Luis; Malan, Leone; Mozos, Ioana; Rabajdova, Miroslava; Nosal, Vladimir; Kobyliak, Nazarii; Valentova, Vanda; Petrovic, Daniel; Adamek, Mariusz; Kruzliak, Peter

    2017-01-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia associated with significant morbidity and mortality. The mechanisms underlying the pathogenesis of AF are poorly understood, although electrophysiological remodeling has been described as an important initiating step. There is growing evidence that oxidative stress is involved in the pathogenesis of AF. Many known triggers of oxidative stress, such as age, diabetes, smoking, and inflammation, are linked with an increased risk of arrhythmia. Numerous preclinical studies and clinical trials reported the importance of antioxidant therapy in the prevention of AF, using vitamins C and E, polyunsaturated fatty acids, statins, or nitric oxide donors. The aim of our work is to give a current overview and analysis of opportunities, challenges, and benefits of antioxidant therapy in AF.

  19. [Atrial fibrillation as consequence and cause of structural changes of atria].

    PubMed

    Aparina, O P; Chikhireva, L N; Stukalova, O V; Mironova, N A; Kashtanova, S Iu; Ternovoĭ, S K; Golitsyn, S P

    2014-01-01

    Changes of atrial structure and function are the contributors of atrial fibrillation clinical course, complications and treatment effectiveness. Effects of inflammation and mechanical stretch on atrial structural remodeling leading to atrial fibrillation are reviewed in the article. Contemporary invasive and non-invasive methods of evaluation (including late gadolinium enhancement magnetic resonance imaging) of patients with atrial structural remodeling in atrial fibrillation are also described.

  20. Atrial Myxoma in a Patient with Hypertrophic Cardiomyopathy

    PubMed Central

    Abdou, Mahmoud; Hayek, Salim; Williams, Byron R.

    2013-01-01

    Atrial myxoma is the most common primary cardiac tumor. Patients with atrial myxoma typically present with obstructive, embolic, or systemic symptoms; asymptomatic presentation is very rare. To our knowledge, isolated association of atrial myxoma with hypertrophic cardiomyopathy has been reported only once in the English-language medical literature. We report the case of an asymptomatic 71-year-old woman with known hypertrophic cardiomyopathy in whom a left atrial mass was incidentally identified on cardiac magnetic resonance images. After surgical excision of the mass and partial excision of the left atrial septum, histopathologic analysis confirmed the diagnosis of atrial myxoma. The patient was placed on preventive implantable cardioverter-defibrillator therapy and remained asymptomatic. The management of asymptomatic cardiac myxoma is a topic of debate, because no reports definitively favor either conservative or surgical measures. PMID:24082380

  1. Left atrial appendage mass: is it always a thrombus?

    PubMed Central

    Guler, Adem; Kurkluoglu, Mustafa; Yesil, Fahri Gurkan; Tavlasoglu, Murat; Cingoz, Faruk

    2016-01-01

    Myxoma is the most common benign tumor of the heart, but it is very rare for it to originate from the left atrial appendage. Distinguishing between a mass, a thrombus, and a tumor in the body of the left atrium with preoperative transthoracic or transesophageal echocardiography is very difficult, even more so in patients with mitral valve disease and chronic atrial fibrillation. A 50-year-old male patient was admitted for surgery with the diagnosis of mitral stenosis and chronic atrial fibrillation. Transesophageal echocardiography demonstrated a mass attached to the wall of the left atrial appendage. Histopathological examination of the mass showed an image compatible with a myxoma. We hereby describe a case of a left atrial appendage myxoma mimicking a left atrial appendage thrombus. PMID:28096835

  2. Unusual case of right atrial reinfarction.

    PubMed

    Radojevic, Nemanja; Savic, Slobodan; Aleksic, Vuk; Cukic, Dragana

    2012-02-01

    It is well known that atrial infarctions are rare comparing to the ventricular. They cannot easily be verified on ECG and the standard autopsy technique does not include a detailed review of the atrial wall, so the atrial infarction often remains undiagnosed. A 63-year-old male was treated and died in an intensive care unit due to decompensated liver insufficiency and cardiac disease following long-lasting alcohol abuse. At autopsy, the extreme cardiomegaly was found, severe atherosclerosis of the anterior descending branch of left coronary artery. The posterior wall of the right atrium was thickened (cca 9 mm) in diameter of cca 3 × 3 cm, and this area was yellowish in the luminal part, while the central part was filled with dark red blood. A detailed dissection of the coronary arteries showed the complete occlusion of the atrial branch of the right coronary artery wreath as far as the place of sinoatrial artery branching, which corresponded anatomically to the described area of infarction on the posterior wall of the right atrium. Histopathological examination of the previously described area of the posterior wall of the right atrium, showed four zones of heart muscle changes: 1. zone of partially preserved structure of the heart muscle, 2. zone of cellular (immature) connective tissue, 3. areas of bleeding in cellular connective tissue, and 4. zone of acellular (old) connective tissue. These histopathological changes indicated that the posterior wall of the right atrium was affected by myocardial necrosis in at least two and possibly more times. It is reasonable to think that bleeding in the third zone of the posterior wall of the right atrium contributed greatly to the death due to the anatomical proximity to the sinoatrial node. It was confirmed by the existence of bradycardia with a prolonged PR interval, PR segment elevation in D1 and aVL lead and PR depression in the D3 lead on the ECG. These ECG changes appeared immediately before asystolia and the

  3. Atrial septal defects in Florida panthers.

    PubMed

    Cunningham, M W; Dunbar, M R; Buergelt, C D; Homer, B L; Roelke-Parker, M E; Taylor, S K; King, R; Citino, S B; Glass, C

    1999-07-01

    Ostium secundum atrial septal defects (ASDs) were observed in six (3 M, 3 F) of 33 (20 M, 13 F) (18%) Florida panthers (Puma concolor coryi) necropsied by veterinary pathologists between 1985 and 1998. A seventh ASD was found in a female panther necropsied in the field and is included in the pathological description but not the prevalence of ASDs in Florida panthers. One panther (FP205) with severe ASD also had tricuspid valve dysplasia (TVD). Atrial septal defects and/or TVD are believed to have caused or contributed to the deaths of three (9%) Florida panthers in this study. Mean diameter +/- SD of ASDs was 9.0 +/- 4.7 mm (range 3 to 15 mm). Gross pathological changes attributed to ASDs/TVD in severely affected panthers (ASD > or = 10 mm) (n = 4) included mild right ventricular dilatation (n = 3) and hypertrophy (n = 2), mild to severe right atrial dilatation (n = 2), and acute pulmonary edema (n = 3). Panthers with mild ASDs (ASD < or = 5 mm) (n = 3) had no other detectable gross pathological changes associated with the ASDs. Histological examination of lungs of three panthers with severe ASDs revealed mild to moderate dilatation with fibrosis and smooth muscle atrophy of the tunica media of medium to large caliber arteries (n = 2), interstitial and/or pleural fibrosis (n = 2), perivascular fibrosis (n = 1), and acute to chronic edema (n = 3). Twenty-six necropsied panthers were examined one or more times while living; medical records were retrospectively evaluated. Antemortem radiographic, electrocardiographic, and echocardiographic examinations were performed on two panthers with severe ASDs (FP20 and FP205). Thoracic radiographic abnormalities in both included right heart enlargement, and in FP205 (severe ASD and TVD), mild pulmonary overperfusion. Electrocardiographic examination of FP205 revealed a right ventricular hypertrophy pattern, while FP205 had a normal electrocardiogram. Echocardiographic examination of FP20 revealed marked right atrial dilatation

  4. Inter-Subject Variability in Human Atrial Action Potential in Sinus Rhythm versus Chronic Atrial Fibrillation

    PubMed Central

    Sánchez, Carlos; Bueno-Orovio, Alfonso; Wettwer, Erich; Loose, Simone; Simon, Jana; Ravens, Ursula; Pueyo, Esther; Rodriguez, Blanca

    2014-01-01

    Aims Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR) and chronic atrial fibrillation (cAF) patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP) recorded in 363 patients both under SR and cAF conditions. Methods and Results Human AP recordings in atrial trabeculae (n = 469) from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in GK1, GKur and Gto, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in IK1 and INaK underlies variability in APD90, variability in IKur, ICaL and INaK modulates variability in APD50 and combined variability in Ito and IKur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by IK1 and either INaK or INaCa depending on the model. Conclusion Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in

  5. Hemoglobin and B-type natriuretic peptide preoperative values but not inflammatory markers, are associated with postoperative morbidity in cardiac surgery: a prospective cohort analytic study

    PubMed Central

    2013-01-01

    Introduction Risk stratification in cardiac surgery significantly impacts outcome. This study seeks to define whether there is an independent association between the preoperative serum level of hemoglobin (Hb), leukocyte count (LEUCO), high sensitivity C-reactive protein (hsCRP), or B-type natriuretic peptide (BNP) and postoperative morbidity and mortality in cardiac surgery. Methods Prospective, analytic cohort study, with 554 adult patients undergoing cardiac surgery in a tertiary cardiovascular hospital and followed up for 12 months. The cohort was distributed according to preoperative values of Hb, LEUCO, hsCRP, and BNP in independent quintiles for each of these variables. Results After adjustment for all covariates, a significant association was found between elevated preoperative BNP and the occurrence of low postoperative cardiac output (OR 3.46, 95% CI 1.53–7.80, p = 0.003) or postoperative atrial fibrillation (OR 3.8, 95% CI 1.45–10.38). For the combined outcome (death/acute coronary syndrome/rehospitalization within 12 months), we observed an OR of 1.93 (95% CI 1.00–3.74). An interaction was found between BNP level and the presence or absence of diabetes mellitus. The OR for non-diabetics was 1.26 (95% CI 0.61–2.60) and for diabetics was 18.82 (95% CI 16.2–20.5). Preoperative Hb was also significantly and independently associated with the occurrence of postoperative low cardiac output (OR 0.33, 95% CI 0.13–0.81, p = 0.016). Both Hb and BNP were significantly associated with the lengths of intensive care unit and hospital stays and the number of transfused red blood cells (p < 0.002). Inflammatory markers, although associated with adverse outcomes, lost statistical significance when adjusted for covariates. Conclusions High preoperative BNP or low Hb shows an association of independent risk with postoperative outcomes, and their measurement could help to stratify surgical risk. The ability to predict the onset of atrial fibrillation or

  6. A prospective randomized study to assess the efficacy of rate and site of atrial pacing on long-term development of atrial fibrillation.

    PubMed

    Lau, Chu-Pak; Wang, Chun-Chieh; Ngarmukos, Tachapong; Kim, You-Ho; Kong, Chi-Woon; Omar, Razali; Sriratanasathavorn, Charn; Munawar, Muhammad; Kam, Ruth; Lee, Kathy Lf; Lau, Elizabeth Oi-Yan; Tse, Hung-Fat

    2009-09-01

    The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is a single-blinded, parallel randomized designed multicenter study in pacemaker indicated patients with paroxysmal atrial fibrillation (AF). The objective is to evaluate whether the site of atrial pacing--conventional right atrial appendage versus low atrial septal--with or without atrial overdrive pacing will influence the development of persistent AF. The study will provide a definitive answer to whether a different atrial pacing site or the use of AF suppression pacing or both can give incremental antiarrhythmic benefit when one is implanting a device for a patient with a history of paroxysmal AF.

  7. The role of left atrial receptors in the diuretic response to left atrial distension

    PubMed Central

    Ledsome, J. R.; Linden, R. J.

    1968-01-01

    1. The diuretic response to distension of the whole left atrium caused by obstruction of the mitral orifice has been compared with the effects of distension (by means of small balloons) of the left pulmonary vein/left atrial junctions. 2. Distension of the pulmonary vein/atrial junctions caused an increase in heart rate and a diuresis similar to but smaller than that caused by mitral obstruction. 3. Section of both ansae subclaviae prevented the increase in heart rate produced by distension of the pulmonary vein/left atrial junctions but had little effect on the diuretic response either to pulmonary vein distension or to mitral obstruction. 4. A diuretic response to mitral obstruction could be demonstrated after all nerves from the lungs had been cut but not after the vagus nerves had been cut at levels likely to interrupt the majority of afferent fibres from left atrial receptors. 5. The results support the view that stimulation of left atrial receptors is a major factor in the production of a diuretic response to mitral obstruction. PMID:5698283

  8. Energetic metabolism during acute stretch-related atrial fibrillation Shortened title: atrial fibrillation and metabolism

    PubMed Central

    Kalifa, J; Maixent, JM; Chalvidan, T; Dalmasso, C; Colin, D; Cozma, D; Laurent, P; Deharo, JC; Djiane, P; Cozzone, P; Bernard, M

    2010-01-01

    Background and methods Perturbations in energetic metabolism and impaired atrial contractility may play an important role in the pathogenesis of atrial fibrillation (AF). Besides, atrial stretch is commonly associated with AF. However, the atrial energetics of stretch-related AF are poorly understood. Here, we measured indicators of energy metabolism during acute-stretch related AF. PCr, adenine nucleotides and derivatives concentrations as well as the activity of the F0F1-ATPase and Na,K-ATPase were obtained after one hour of stretch and/or AF in isolated rabbit hearts and compared to control hearts without stretch and AF. Results After one hour of stretch-related AF, the total adenine nucleotides pool was significantly lower (42.2±2.6 versus 63.7±8.3 µmol/g protein in control group, p<0.05) and the PCr/ATP ratio significantly higher (2.3±0.3 vs 1.1± 0.1 in control group p<0.05), because of ATP, ADP and AMP decrease and PCr increase. The sum of high energy phosphate compounds did not change. There were no significant differences in F0F1-ATPase nor Na,K-ATPase activity between the groups. Conclusions Results show that in this experimental model, acute-stretch related AF induces specific modifications of atrial myocytes energetics that may play a pivotal role in the perpetuation of the arrhythmia. PMID:18553177

  9. Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation.

    PubMed

    Greiser, Maura; Neuberger, Hans-Ruprecht; Harks, Erik; El-Armouche, Ali; Boknik, Peter; de Haan, Sunniva; Verheyen, Fons; Verheule, Sander; Schmitz, Wilhelm; Ravens, Ursula; Nattel, Stanley; Allessie, Maurits A; Dobrev, Dobromir; Schotten, Ulrich

    2009-03-01

    Atrial dilatation is an independent risk factor for thromboembolism in patients with and without atrial fibrillation (AF). In many patients, atrial dilatation goes along with depressed contractile function of the dilated atria. While some mechanisms causing atrial contractile dysfunction in fibrillating atria have been addressed previously, the cellular and molecular mechanisms of atrial contractile remodeling in dilated atria are unknown. This study characterized in vivo atrial contractile function in a goat model of atrial dilatation and compared it to a goat model of AF. Differences in the underlying mechanisms were elucidated by studying contractile function, electrophysiology and sarcoplasmic reticulum (SR) Ca2+ load in atrial muscle bundles and by analyzing expression and phosphorylation levels of key Ca2+-handling proteins, myofilaments and the expression and activity of their upstream regulators. In 7 chronically instrumented, awake goats atrial contractile dysfunction was monitored during 3 weeks of progressive atrial dilatation after AV-node ablation (AV block goats (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC), transmembrane action potentials (APs) and rapid cooling contractures (RCC, a measure of SR Ca2+ load) were studied in right atrial muscle bundles. Total and phosphorylated Ca2+-handling and myofilament protein levels were quantified by Western blot. In AVB goats, atrial size increased by 18% (from 26.6+/-4.4 to 31.6+/-5.5 mm, n=7 p<0.01) while atrial fractional shortening (AFS) decreased (from 18.4+/-1.7 to 12.8+/-4.0% at 400 ms, n=7, p<0.01). In open chest experiments, AWI was reduced in AVB and in AF goats compared to controls (at 400 ms: 8.4+/-0.9, n=7, and 3.2+/-1.8, n=5, vs 18.9+/-5.3 mmxmmHg, n=7, respectively, p<0.05 vs control). FC of isolated right

  10. Extreme variation in the atrial septation of caecilians (Amphibia: Gymnophiona)

    PubMed Central

    de Bakker, Desiderius M; Wilkinson, Mark; Jensen, Bjarke

    2015-01-01

    Caecilians (order Gymnophiona) are elongate, limbless, snake-like amphibians that are the sister-group (closest relatives) of all other recent amphibians (frogs and salamanders). Little is known of their cardiovascular anatomy and physiology, but one nearly century old study suggests that Hypogeophis (family Indotyphlidae), commonly relied upon as a representative caecilian species, has atrial septation in the frontal plane and more than one septum. In contrast, in other vertebrates there generally is one atrial septum in the sagittal plane. We studied the adult heart of Idiocranium (also Indotyphlidae) using immunohistochemistry and confirm that the interatrial septum is close to the frontal plane. Additionally, a parallel right atrial septum divides three-fourths of the right atrial cavity of this species. Idiocranium embryos in the Hill collection reveal that atrial septation initiates in the sagittal plane as in other tetrapods. Late developmental stages, however, see a left-ward shift of visceral organs and a concordant rotation of the atria that reorients the atrial septa towards the frontal plane. The gross anatomies of species from six other caecilian families reveal that (i) the right atrial septum developed early in caecilian evolution (only absent in Rhinatrematidae) and that (ii) rotation of the atria evolved later and its degree varies between families. In most vertebrates a prominent atrial trabeculation associates with the sinuatrial valve, the so-called septum spurium, and the right atrial septum seems homologous to this trabeculation but much more developed. The right atrial septum does not appear to be a consequence of body elongation because it is absent in some caecilians and in snakes. The interatrial septum of caecilians shares multiple characters with the atrial septum of lungfishes, salamanders and the embryonic septum primum of amniotes. In conclusion, atrial septation in caecilians is based on evolutionarily conserved structures but

  11. Atrial fibrillation in hypertrophic cardiomyopathy: mechanisms, embolic risk and prognosis.

    PubMed

    Nair, Ajith G; Fischer, Avi G

    2006-12-01

    Hypertrophic cardiomyopathy (HCM) is associated with an increased incidence of supraventricular and ventricular arrhythmias. Atrial fibrillation (AF) is the most common arrhythmia in HCM with a prevalence of 20% and an annual incidence of two percent per year. Increased left atrial size and volume along with impaired left atrial function confer an increased likelihood of AF. The onset of AF is often accompanied by a decrease in functional status in conjunction with an increased risk of stroke and overall mortality.

  12. Juxtaposed atrial appendages: A curiosity with some clinical relevance

    PubMed Central

    Singhi, Anil Kumar; Pradhan, Priya; Agarwal, Ravi; Sivakumar, Kothandum

    2016-01-01

    If the atrial appendages lie adjacent to each other on same side of the great arteries, instead of encircling their roots, they are referred as juxtaposed. Right juxtaposition of atrial appendages is less common than left juxtaposition. The images demonstrate the classical radiological, echocardiographic, and surgical images of juxtaposed atrial appendages. Their clinical incidence, associations, and relevance during interventional and surgical procedures are discussed. PMID:27212860

  13. Aorto-left atrial tunnel: a rare entity.

    PubMed

    Paul, Sajiv K; Gajjar, Trushar P; Desai, Neelam B

    2013-05-01

    Aorto-left atrial tunnel (ALAT) is a vascular channel that originates from 1 of the sinuses of Valsalva and terminates in the left atrium. The aorto-left atrial tunnel is an extremely rare anomaly. We describe here a case of congenital aorto-left atrial tunnel in a 4-year-old child who underwent successful surgical ligation with good immediate and early results.

  14. Extreme variation in the atrial septation of caecilians (Amphibia: Gymnophiona).

    PubMed

    de Bakker, Desiderius M; Wilkinson, Mark; Jensen, Bjarke

    2015-01-01

    Caecilians (order Gymnophiona) are elongate, limbless, snake-like amphibians that are the sister-group (closest relatives) of all other recent amphibians (frogs and salamanders). Little is known of their cardiovascular anatomy and physiology, but one nearly century old study suggests that Hypogeophis (family Indotyphlidae), commonly relied upon as a representative caecilian species, has atrial septation in the frontal plane and more than one septum. In contrast, in other vertebrates there generally is one atrial septum in the sagittal plane. We studied the adult heart of Idiocranium (also Indotyphlidae) using immunohistochemistry and confirm that the interatrial septum is close to the frontal plane. Additionally, a parallel right atrial septum divides three-fourths of the right atrial cavity of this species. Idiocranium embryos in the Hill collection reveal that atrial septation initiates in the sagittal plane as in other tetrapods. Late developmental stages, however, see a left-ward shift of visceral organs and a concordant rotation of the atria that reorients the atrial septa towards the frontal plane. The gross anatomies of species from six other caecilian families reveal that (i) the right atrial septum developed early in caecilian evolution (only absent in Rhinatrematidae) and that (ii) rotation of the atria evolved later and its degree varies between families. In most vertebrates a prominent atrial trabeculation associates with the sinuatrial valve, the so-called septum spurium, and the right atrial septum seems homologous to this trabeculation but much more developed. The right atrial septum does not appear to be a consequence of body elongation because it is absent in some caecilians and in snakes. The interatrial septum of caecilians shares multiple characters with the atrial septum of lungfishes, salamanders and the embryonic septum primum of amniotes. In conclusion, atrial septation in caecilians is based on evolutionarily conserved structures but

  15. Left atrial mass 16 years after radiation therapy for mediastinal neuroblastoma

    SciTech Connect

    Ensing, G.J.; Driscoll, D.J.; Smithson, W.A.

    1987-01-01

    Tumors involving the heart during childhood are rare. However, neuroblastoma, a common pediatric malignancy, has been described to involve the cardiovascular system in 3%-12% of patients dying with this tumor. Rarely is such involvement diagnosed ante mortem and never, to our knowledge, has a benign cardiac tumor been reported to present in childhood after successful eradication of neuroblastoma. We describe the identification and surgical resection of a nodular, hypertrophied, calcified, pedunculated left atrial mass in a 16-year-old boy who was complaining of exercise-associated presyncope and headaches 16 years after irradiation and chemotherapy for mediastinal neuroblastoma.

  16. Coherex WAVECREST I Left Atrial Appendage Occlusion Study

    ClinicalTrials.gov

    2015-01-13

    Non-valvular Paroxysmal, Persistent, or Permanent Atrial Fibrillation; LAA Anatomy Amenable to Treatment by Percutaneous Technique; Anticoagulation Indication for Potential Thrombus Formation in the Left Atrium

  17. Hemodynamic forces regulate developmental patterning of atrial conduction.

    PubMed

    Bressan, Michael C; Louie, Jonathan D; Mikawa, Takashi

    2014-01-01

    Anomalous action potential conduction through the atrial chambers of the heart can lead to severe cardiac arrhythmia. To date, however, little is known regarding the mechanisms that pattern proper atrial conduction during development. Here we demonstrate that atrial muscle functionally diversifies into at least two heterogeneous subtypes, thin-walled myocardium and rapidly conducting muscle bundles, during a developmental window just following cardiac looping. During this process, atrial muscle bundles become enriched for the fast conduction markers Cx40 and Nav1.5, similar to the precursors of the fast conduction Purkinje fiber network located within the trabeculae of the ventricles. In contrast to the ventricular trabeculae, however, atrial muscle bundles display an increased proliferation rate when compared to the surrounding myocardium. Interestingly, mechanical loading of the embryonic atrial muscle resulted in an induction of Cx40, Nav1.5 and the cell cycle marker Cyclin D1, while decreasing atrial pressure via in vivo ligation of the vitelline blood vessels results in decreased atrial conduction velocity. Taken together, these data establish a novel model for atrial conduction patterning, whereby hemodynamic stretch coordinately induces proliferation and fast conduction marker expression, which in turn promotes the formation of large diameter muscle bundles to serve as preferential routes of conduction.

  18. The role of myocardial wall thickness in atrial arrhythmogenesis.

    PubMed

    Whitaker, John; Rajani, Ronak; Chubb, Henry; Gabrawi, Mark; Varela, Marta; Wright, Matthew; Niederer, Steven; O'Neill, Mark D

    2016-12-01

    Changes in the structure and electrical behaviour of the left atrium are known to occur with conditions that predispose to atrial fibrillation (AF) and in response to prolonged periods of AF. We review the evidence that changes in myocardial thickness in the left atrium are an important part of this pathological remodelling process. Autopsy studies have demonstrated changes in the thickness of the atrial wall between patients with different clinical histories. Comparison of the reported tissue dimensions from pathological studies provides an indication of normal ranges for atrial wall thickness. Imaging studies, most commonly done using cardiac computed tomography, have demonstrated that these changes may be identified non-invasively. Experimental evidence using isolated tissue preparations, animal models of AF, and computer simulations proves that the three-dimensional tissue structure will be an important determinant of the electrical behaviour of atrial tissue. Accurately identifying the thickness of the atrial may have an important role in the non-invasive assessment of atrial structure. In combination with atrial tissue characterization, a comprehensive assessment of the atrial dimensions may allow prediction of atrial electrophysiological behaviour and in the future, guide radiofrequency delivery in regions based on their tissue thickness.

  19. Ebstein Anomaly With Right Atrial Clot

    PubMed Central

    Kumar, Prakash; Singhal, Gaurav; Sinha, Santosh Kumar; Pandey, Umeshwar; Thakur, Ramesh; Varma, Chandra Mohan

    2015-01-01

    Ebstein anomaly (EA) is a rare congenital malformation of the tricuspid valve (TV), often associated with other cardiac malformations, especially atrial septal defect/patent foramen ovale (PFO) which is present in 80-90% of patients and predisposes to paradoxical embolization. We describe the case of a 17-year-old female, who presented with worsening exertional dyspnea, fatigue and pedal edema and atrial fibrillation (AF). Transthoracic echocardiography showed EA with severely dilated right atrium (RA), small functional right ventricle (RV), low velocity flow across TV with spontaneous echo contrast and giant clot in RA. Fortunately for the patient, contrast and transesophageal echocardiography revealed an intact interatrial septum with no PFO preventing any paradoxical embolism from large clot in RA, more so in the background of AF. Important differential diagnosis of congenitally unguarded TV orifice was ruled out due to presence of septal and anterior leaflets of TV and associated chordae. PMID:28197250

  20. [Atrial fibrillation concomitant with valvular heart disease].

    PubMed

    Ishii, Yosuke

    2013-01-01

    Patients with valvular heart disease frequently have atrial fibrillation(AF) due to elevated pressure and dilatation of the left and right atria and pulmonary veins. Guidelines for valvular heart disease and AF recommend that surgical treatment for the valvular heart disease should be performed concomitantly with AF surgery. The Full-Maze procedure has evolved into the gold standard of treatment for medically refractory AF. In addition to the pulmonary vein isolation, the right and left atrial incisions of the Full-Maze procedure are designed to block potential macroreentrant pathways. According to the mechanisms of AF with valvular heart disease, the Full-Maze procedure is more effective for the patients than the pulmonary vein isolation alone.

  1. Effects of APD Dispersion on Atrial Reentry

    NASA Astrophysics Data System (ADS)

    Vigmond, Edward; Kuo, Samuel; Trayanova, Natalia

    2002-03-01

    Atrial fibrillation is the most common cardiac arrhythmia with dispersion of refractoriness being postulated as a mechanism promoting its formation. The distribution of action potential duration (APD) over the atria, however, remains unmapped under both normal and pathological conditions. The purpose of this computer study was to investigate how APD heterogenity interacts with morphological barriers to produce reentry. Reentries were first initiated in a 2D sheet of atrial tissue. The effects of incorporating APD heterogeneity and periodic boundary conditions, to better mimic physiological conditions, on reentry were ascertained. Analysis was extended to a morphologically realistic 3D model wherein several APD distributions were simulated. Comparisons between the 2D and 3D models demonstrated that the sheet behaviour was insufficient to capture the complex behaviour. Regional differences in APD, aided by anatomical barriers, were found to affect the formation and stabilization of reentrant circuits, as well as lead to the fractionation of wavefronts.

  2. [Progress of anticoagulation therapy in atrial fibrillation].

    PubMed

    Hernández Olmedo, Miguel; Suárez Fernández, Carmen

    2015-08-07

    Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization.

  3. Ebstein Anomaly With Right Atrial Clot.

    PubMed

    Kumar, Prakash; Singhal, Gaurav; Sinha, Santosh Kumar; Pandey, Umeshwar; Thakur, Ramesh; Varma, Chandra Mohan

    2015-10-01

    Ebstein anomaly (EA) is a rare congenital malformation of the tricuspid valve (TV), often associated with other cardiac malformations, especially atrial septal defect/patent foramen ovale (PFO) which is present in 80-90% of patients and predisposes to paradoxical embolization. We describe the case of a 17-year-old female, who presented with worsening exertional dyspnea, fatigue and pedal edema and atrial fibrillation (AF). Transthoracic echocardiography showed EA with severely dilated right atrium (RA), small functional right ventricle (RV), low velocity flow across TV with spontaneous echo contrast and giant clot in RA. Fortunately for the patient, contrast and transesophageal echocardiography revealed an intact interatrial septum with no PFO preventing any paradoxical embolism from large clot in RA, more so in the background of AF. Important differential diagnosis of congenitally unguarded TV orifice was ruled out due to presence of septal and anterior leaflets of TV and associated chordae.

  4. Lipid-altering therapy and atrial fibrillation.

    PubMed

    Bachmann, Justin M; Majmudar, Maulik; Tompkins, Christine; Blumenthal, Roger S; Marine, Joseph E

    2008-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia with significant morbidity and public health cost. Because of limitations of efficacy and safety of conventional antiarrhythmic agents, alternative therapies for AF are needed. The potential antiarrhythmic properties of lipid-altering therapy, including the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and fish oils, are increasingly recognized, particularly in light of their potential anti-inflammatory properties. This review examines the known effects of lipid-altering therapy on atrial arrhythmias in both experimental and clinical settings. Inflammatory states, such as post-cardiac surgery and AF of recent onset, show promise as targets. In contrast, lipid-lowering therapy is less likely to affect longstanding persistent AF. Current recommendations for the use of lipid-altering therapy for prevention and treatment of AF are summarized.

  5. Sequential Hybrid Procedure for Persistent Atrial Fibrillation

    PubMed Central

    Bulava, Alan; Mokracek, Ales; Hanis, Jiri; Kurfirst, Vojtech; Eisenberger, Martin; Pesl, Ladislav

    2015-01-01

    Background Catheter ablation of persistent atrial fibrillation yields an unsatisfactorily high number of failures. The hybrid approach has recently emerged as a technique that overcomes the limitations of both surgical and catheter procedures alone. Methods and Results We investigated the sequential (staged) hybrid method, which consists of a surgical thoracoscopic radiofrequency ablation procedure followed by radiofrequency catheter ablation 6 to 8 weeks later using the CARTO 3 mapping system. Fifty consecutive patients (mean age 62±7 years, 32 males) with long‐standing persistent atrial fibrillation (41±34 months) and a dilated left atrium (>45 mm) were included and prospectively followed in an unblinded registry. During the electrophysiological part of the study, all 4 pulmonary veins were found to be isolated in 36 (72%) patients and a complete box‐lesion was confirmed in 14 (28%) patients. All gaps were successfully re‐ablated. Twelve months after the completed hybrid ablation, 47 patients (94%) were in normal sinus rhythm (4 patients with paroxysmal atrial fibrillation required propafenone and 1 patient underwent a redo catheter procedure). The majority of arrhythmias recurred during the first 3 months. Beyond 12 months, there were no arrhythmia recurrences detected. The surgical part of the procedure was complicated by 7 (13.7%) major complications, while no serious adverse events were recorded during the radiofrequency catheter part of the procedure. Conclusions The staged hybrid epicardial–endocardial treatment of long‐standing persistent atrial fibrillation seems to be extremely effective in maintenance of normal sinus rhythm compared to radiofrequency catheter or surgical ablation alone. Epicardial ablation alone cannot guarantee durable transmural lesions. Clinical Trial Registration URL: www.ablace.cz Unique identifier: cz‐060520121617 PMID:25809548

  6. Atrial Fibrillation During an Exploration Class Mission

    NASA Technical Reports Server (NTRS)

    Lipset, Mark A.; Lemery, Jay; Polk, J. D.; Hamilton, Douglas R.

    2010-01-01

    Background: A long-duration exploration class mission is fraught with numerous medical contingency plans. Herein, we explore the challenges of symptomatic atrial fibrillation (AF) occurring during an exploration class mission. The actions and resources required to ameliorate the situation, including the availability of appropriate pharmaceuticals, monitoring devices, treatment modalities, and communication protocols will be investigated. Challenges of Atrial Fibrillation during an Exploration Mission: Numerous etiologies are responsible for the initiation of AF. On Earth, we have the time and medical resources to evaluate and determine the causative situation for most cases of AF and initiate therapy accordingly. During a long-duration exploration class mission resources will be severely restricted. How is one to determine if new onset AF is due to recent myocardial infarction, pulmonary embolism, fluid overload, thyrotoxicosis, cardiac structural abnormalities, or CO poisoning? Which pharmaceutical therapy should be initiated and what potential side effects can be expected? Should anti-coagulation therapy be initiated? How would one monitor the therapeutic treatment of AF in microgravity? What training would medical officers require, and which communication strategies should be developed to enable the best, safest therapeutic options for treatment of AF during a long-duration exploration class mission? Summary: These questions will be investigated with expert opinion on disease elucidation, efficient pharmacology, therapeutic monitoring, telecommunication strategies, and mission cost parameters with emphasis on atrial fibrillation being just one illustration of the tremendous challenges that face a long-duration exploration mission. The limited crew training time, medical hardware, and drugs manifested to deal with such an event predicate that aggressive primary and secondary prevention strategies be developed to protect a multibillion-dollar asset like the

  7. Atrial Fibrillation - Multiple Languages: MedlinePlus

    MedlinePlus

    ... sharing features on this page, please enable JavaScript. Arabic (العربية) Chinese - Simplified (简体中文) Chinese - Traditional (繁體中文) French ( ... Somali (af Soomaali) Spanish (español) Vietnamese (Tiếng Việt) Arabic (العربية) Atrial Fibrillation (Arabic) العربية Bilingual PDF Health ...

  8. Predictive value of various Doppler-derived parameters of atrial conduction time for successful atrial fibrillation ablation

    PubMed Central

    Valtuille, Lucas; Choy, Jonathan B; Becher, Harald

    2015-01-01

    Various Doppler-derived parameters of left atrial electrical remodeling have been demonstrated to predict recurrence of atrial fibrillation (AF) after AF ablation. The aim of this study was to compare three Doppler-derived measures of atrial conduction time in patients undergoing AF ablation, and to investigate their predictive value for successful procedure. In 32 prospectively enrolled patients undergoing the first AF ablation, atrial conduction time was estimated by measuring the time delay between the onset of P-wave on the surface ECG to the peak of the a′-wave on the pulsed-wave Doppler and color-coded tissue Doppler imaging of the left atrial lateral wall, and to the peak of the A-wave on the pulsed-wave Doppler of the mitral inflow. There was a significant difference in the baseline atrial conduction time measured by different echocardiographic techniques. Most (88%) patients had normal or only mildly dilated left atrium. At 6 months, 12 patients (38%) had recurrent AF/atrial tachycardia. The duration of history of AF was the only predictor of AF/atrial tachycardia recurrence following the first AF ablation (P=0.024; OR 1.023, CI 1.003–1.044). A combination of normal left atrial volume and history of paroxysmal AF of ≤48 months was associated with the best outcome. Predictive value of the Doppler derived parameters of atrial conduction time may be reduced in the early stages of left atrial remodeling. Future studies may determine which echocardiographic parameter correlates best with the extent of left atrial remodeling and is most predictive of successful AF ablation. PMID:26795694

  9. Is percutaneous closure of the left atrial appendage comparable to anticoagulants for atrial fibrillation?

    PubMed

    Uslar, Thomas; Anabalón, Jaime

    2015-08-17

    For most atrial fibrillation patients oral anticoagulation constitutes the standard treatment to prevent stroke. However, they carry a risk of bleeding, which is why alternative treatments have been put into practice, such as percutaneous closure of the left atrial appendage. It is not clear whether this is as effective as the conventional treatment with anticoagulants. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including only one pertinent randomized controlled trial. We combined the evidence and generated a summary of findings following the GRADE approach. We concluded that percutaneous left atrial appendage occlusion may decrease stroke and mortality, but the certainty of the evidence is low. The effect on other outcomes is not clear because the certainty of the evidence is very low.

  10. Percutaneous epicardial ablation of incessant atrial tachycardia originating from the left atrial appendage

    PubMed Central

    Ban, Ji-Eun; Park, Tae Young

    2016-01-01

    A 38-year-old woman presented with antiarrhythmic drug-refractory atrial tachycardia (AT). Holter recording demonstrated incessant episodes of AT followed by a long sinus pause. Electrophysiologic study revealed that the earliest endocardial activation was observed at the neck of the left atrial appendage (LAA). After unsuccessful endocardial ablation, epicardial access via a percutaneous subxiphoid approach demonstrated that the earliest epicardial atrial activation was observed on the opposite site to the endocardial LAA neck suggestive of ligament of Marshall (LOM) muscle sleeve as regarding the epicardial sharp potentials under guidance of a circular mapping catheter. Application of radiofrequency (RF) energy at this site terminated the tachycardia. After tachycardia ablation, the sinus pause also resolved. PMID:28066659

  11. B-type natriuretic peptide rapid assay: a diagnostic test for heart failure.

    PubMed

    Ancheta, Irma B

    2006-01-01

    Hospitals are constantly besieged with congestive heart failure admissions. Current studies show that the advent of the B-type natriuretic peptide (BNP) rapid assay as a quick and easy blood test is beneficial to nurses in confirming the diagnosis of heart failure. B-type natriuretic peptide is a neurohormone produced by the failing heart in response to increased volume and cardiac overload. The BNP rapid assay measures the presence of BNP levels present in the circulating bloodstream to confirm the diagnosis of congestive heart failure. It is a simple blood test that can be done at the bedside or at the clinic so it is a valid point-of-care modality. Elevated levels suggest severity of heart failure and possibility of sudden death. This article focuses on the description of the diagnostic performance of the BNP rapid assay, its clinical dimensions, and its implications to nursing practice and collaborative practice models.

  12. Maintaining the Phenotype Stability of Chondrocytes Derived from MSCs by C-Type Natriuretic Peptide

    PubMed Central

    Shi, Quan; Qian, Zhiyong; Liu, Donghua; Sun, Jie; Xu, Juan; Guo, Ximin

    2017-01-01

    Mesenchymal stem cells (MSCs) play a critical role in cartilage tissue engineering. However, MSCs-derived chondrocytes or cartilage tissues are not stable and easily lose the cellular and cartilage phenotype during long-term culture in vitro or implantation in vivo. As a result, chondrocytes phenotypic instability can contribute to accelerated ossification. Thus, it is a big challenge to maintain their correct phenotype for engineering hyaline cartilage. As one member of the natriuretic peptide family, C-type natriuretic peptide (CNP) is found to correlate with the development of the cartilage, affect the chondrocytes proliferation and differentiation. Besides, based on its biological effects on protection of extracellular matrix of cartilage and inhibition of mineralization, we hypothesize that CNP may contribute to the stability of chondrocyte phenotype of MSCs-derived chondrocytes. PMID:28337152

  13. [Assessment of natriuretic peptide indices and oxidative stress in patients with chronic heart failure].

    PubMed

    Abezov, D K; Kamilova, U K; Shukurdzhanova, S M; Rakhmonov, R R; Alieva, T A

    2010-01-01

    The authors have studied indices of natriuretic peptide and oxidative stress in patients with chronic heart failure (CHF). 52 male patients with postinfarction cardiosclerosis (PICS) who have developed CHF have been observed. The age of the patients varied from 38 till 60. It was established that CHF patients with progression of the disease had worsening of their clinical condition together with an increase of oxidative stress which was characterized through decrease of NO metabolites, NADPH--diaphorase (eNOS), increase of nitrite reductase (iNOS) and peroxinitrite (ONOO), correlative increase the level of brain natriuretic peptide in blood plazma. Reliable connection between considerable increase of oxidative stress and the level of NT-pro BNP was noted in CHF patients, which demands necessity of correction of observed disorders.

  14. Atrial fibrillation in obstructive sleep apnea

    PubMed Central

    Goyal, Sandeep K; Sharma, Abhishek

    2013-01-01

    Atrial fibrillation (AF) is a common arrhythmia with rising incidence. Obstructive sleep apnea (OSA) is prevalent among patients with AF. This observation has prompted significant research in understanding the relationship between OSA and AF. Multiple studies support a role of OSA in the initiation and progression of AF. This association has been independent of obesity, body mass index and hypertension. Instability of autonomic tone and wide swings in intrathoracic pressure are seen in OSA. These have been mechanistically linked to initiation of AF in OSA patients by lowering atrial effective refractory period, promoting pulmonary vein discharges and atrial dilation. OSA not only promotes initiation of AF but also makes management of AF difficult. Drug therapy and electrical cardioversion for AF are less successful in presence of OSA. There has been higher rate of early and overall recurrence after catheter ablation of AF in patients with OSA. Treatment of OSA with continuous positive airway pressure has been shown to improve control of AF. However, additional studies are needed to establish a stronger relationship between OSA treatment and success of AF therapies. There should be heightened suspicion of OSA in patients with AF. There is a need for guidelines to screen for OSA as a part of AF management. PMID:23802045

  15. Right atrial thrombi: Percutaneous mechanical thrombectomy

    SciTech Connect

    Beregi, Jean-Paul; Aumegeat, Valerie; Loubeyre, Christophe; Coullet, Jean-Michel; Asseman, Philippe; Debacker-Steckelorom, Caroline; Bauchart, Jean-Jacques; Liu Pengcheng; Thery, Claude

    1997-03-15

    The current therapeutic options for right atrial thrombi-surgical embolectomy and thrombolysis- are associated with high mortality and such patients often have contraindications to these therapeutic options. the purpose of this study was to evaluate the feasibility of endovascular right atrial embolectomy. Two patients with contraindications to thrombolysis and surgery were treated by a femoral approach. A catheter was placed in the right atrium, under fluoroscopic control, and a basket device was used to trap the thrombus. The location and extent of the thrombus was established before the procedure by transesophageal echocardiography (TEE) and the procedure was performed with TEE and fluoroscopy. Thrombi were withdrawn in the basket into the inferior vena cava (IVC) and a filter was inserted by a jugular approach and positioned in the IVC, just above the thrombi. The basket was removed leaving the thrombus below the filter. One patient died immediately after the procedure. In conclusion, endovascular extraction of right atrial thrombi may represent a potential therapeutic alternative, particularly in patients with contraindications to thrombolysis and surgery.

  16. Atrial fibrillation: effects beyond the atrium?

    PubMed

    Wijesurendra, Rohan S; Casadei, Barbara

    2015-03-01

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

  17. Dronedarone in the management of atrial fibrillation

    PubMed Central

    Saleem, TS Mohamed; Bharani, K; Chetty, C Madhusudhana; Gauthaman, K

    2010-01-01

    Atrial fibrillation is the most common type of tachyarrhythmia caused by multiple re-entrant wave forms within the atria and bombarding the atrioventricular node several times making it beat in a rapid, disorganized fashion termed “fibrillation”. In atrial fibrillation, atria beat more than 300 times per minute. The arrhythmatous condition needs to be controlled, as humans cannot withstand this rapid and chaotic beating of the heart. New investigational drugs like Dronedarone® are being used. Dronedarone is the most recent antiarrhythmic drugs. It was approved by US-FDA on July 2nd 2009 and is available in the USA as Multaq tablets (400 mg). Dronedarone falls under the category of multiple ion channel blocker. It mainly targets the repolarization currents, making them less active and hence prolonging the action potential duration (APD). Dronedarone also exhibits antiadrenergic activity, thus reducing the pace of the pacemaker. Dronedarone has been proven to be a safer and efficacious AAD, evidenced by both animal and human studies. These studies showed that there was prolongation of the APD and absence of QT interval prolongation with long term administration of the drug. Also there was reduced thyroid hormone receptor expression. Dronedarone is significantly safer and effective in maintaining the sinus rhythm and reducing the ventricular proarrhythmias, justifying it for the long term treatment of atrial fibrillation compared to other antiarrhythmic drugs. PMID:27147833

  18. Benchmarking electrophysiological models of human atrial myocytes

    PubMed Central

    Wilhelms, Mathias; Hettmann, Hanne; Maleckar, Mary M.; Koivumäki, Jussi T.; Dössel, Olaf; Seemann, Gunnar

    2013-01-01

    Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation (AF). In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential (AP) alternans. To assess the models' ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation (cAF) was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate AP and restitution properties, as well as the initiation of reentrant circuits. PMID:23316167

  19. [Pharmacological rate control therapy for atrial fibrillation].

    PubMed

    Ishikawa, Toshiyuki

    2013-01-01

    Many studies have reported that there is no significant difference in survival rate between rhythm control and rate control strategies in combination of with anticoagulation in patients with atrial fibrillation. Even in patients with atrial fibrillation and with heart failure there is no significant difference in survival rate between both strategies. There is no need of strict rate control. In patients with permanent atrial fibrillation, lemient rate control(resting heart rate of below 110 beats per minute) is as effective as strict rate control (< 70 beats per minute) and easier to achieve. Digitalis, beta-blockers and Ca channel blockers are used for rate control treatments. Digitalis is the only drug that has both decreasing ventricular response by suppressing atrioventricular conduction and inotropic effects. However, digitalis can not suppress heart rates during exercise. Beta-blockers and Ca channel blockers can suppress heart rates not only at rest but also during exercise. Ca channel blockers can not be used for patients with heart failure due to reduction in contractility of heart muscle. It has been reported that cardiac function and survival rate can be improved by beta-blockers in patients with heart failure if starting low dose and increasing gradually.

  20. Atrial Fibrillation: The Science behind Its Defiance

    PubMed Central

    Czick, Maureen E.; Shapter, Christine L.; Silverman, David I.

    2016-01-01

    Atrial fibrillation (AF) is the most prevalent arrhythmia in the world, due both to its tenacious treatment resistance, and to the tremendous number of risk factors that set the stage for the atria to fibrillate. Cardiopulmonary, behavioral, and psychological risk factors generate electrical and structural alterations of the atria that promote reentry and wavebreak. These culminate in fibrillation once atrial ectopic beats set the arrhythmia process in motion. There is growing evidence that chronic stress can physically alter the emotion centers of the limbic system, changing their input to the hypothalamic-limbic-autonomic network that regulates autonomic outflow. This leads to imbalance of the parasympathetic and sympathetic nervous systems, most often in favor of sympathetic overactivation. Autonomic imbalance acts as a driving force behind the atrial ectopy and reentry that promote AF. Careful study of AF pathophysiology can illuminate the means that enable AF to elude both pharmacological control and surgical cure, by revealing ways in which antiarrhythmic drugs and surgical and ablation procedures may paradoxically promote fibrillation. Understanding AF pathophysiology can also help clarify the mechanisms by which emerging modalities aiming to correct autonomic imbalance, such as renal sympathetic denervation, may offer potential to better control this arrhythmia. Finally, growing evidence supports lifestyle modification approaches as adjuncts to improve AF control. PMID:27699086

  1. Animal studies of epicardial atrial ablation.

    PubMed

    Schuessler, Richard B; Lee, Anson M; Melby, Spencer J; Voeller, Rochus K; Gaynor, Sydney L; Sakamoto, Shun-Ichiro; Damiano, Ralph J

    2009-12-01

    The Cox maze procedure is an effective treatment of atrial fibrillation, with a long-term freedom from recurrence greater than 90%. The original procedure was highly invasive and required cardiopulmonary bypass. Modifications of the procedure that eliminate the need for cardiopulmonary bypass have been proposed, including use of alternative energy sources to replace cut-and-sew lesions with lines of ablation made from the epicardium on the beating heart. This has been challenging because atrial wall muscle thickness is extremely variable, and the muscle can be covered with an epicardial layer of fat. Moreover, the circulating intracavitary blood acts as a potential heat sink, making transmural lesions difficult to obtain. In this report, we summarize the use of nine different unidirectional devices (four radiofrequency, two microwave, two lasers, one cryothermic) for creating continuous transmural lines of ablation from the atrial epicardium in a porcine model. We define a unidirectional device as one in which all the energy is applied by a single transducer on a single heart surface. The maximum penetration of any device was 8.3 mm. All devices except one, the AtriCure Isolator pen, failed to penetrate 2 mm in some nontransmural sections. Future development of unidirectional energy sources should be directed at increasing the maximum depth and the consistency of penetration.

  2. Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm

    PubMed Central

    Smorodinova, Natalia; Bláha, Martin; Melenovský, Vojtěch; Rozsívalová, Karolína; Přidal, Jaromír; Ďurišová, Mária; Pirk, Jan; Kautzner, Josef; Kučera, Tomáš

    2017-01-01

    Background Atrial fibrillation (AF) is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients. Objective The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR). Methods We examined 46 subjects (19 with AF, and 27 in SR) undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry. Results The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample. Conclusions An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence. PMID:28225836

  3. Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation

    PubMed Central

    Xi, Yutao; Chao, Zhi-Yang James; Yan, Wen; Abbasi, Shahrzad; Yin, Xiaomeng; Mathuria, Nilesh; Patel, Mehul; Fan, Christopher; Sun, Junping; Wu, Geru; Wang, Suwei; Elayda, MacArthur; Gao, Lianjun; Wehrens, Xander H.T.; Lin, Shien-Fong; Cheng, Jie

    2015-01-01

    BACKGROUND Vagal hyperactivity promotes atrial fibrillation (AF), which has been almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide (VIP) and acetylcholine are neurotransmitters co-released during vagal stimulation. Exogenous VIP has been shown to promote AF by shortening action potential duration (APD), increasing APD spatial heterogeneity, and causing intra-atrial conduction block. OBJECTIVE The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation. METHODS We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts. RESULTS H9935 significantly attenuated (1) the vagally induced shortening of atrial effective refractory period and widening of atrial vulnerability window during stimulation of cervical vagosym-pathetic trunks (VCNS) and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS. In contrast, VGPS-induced slowing of local conduction velocity was completely abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS, maximal dominant frequencies and their spatial gradients were reduced significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP release in the atria during vagal stimulation was inhibited by atropine, which may account for the concealment of VIP effects with muscarinic blockade. CONCLUSION Neuronally released VIP contributes to vagal effects on atrial electrophysiologic properties and affects the pathophysiology of vagally induced AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a novel mechanism by which VIP effects are concealed by atropine during vagal stimulation. PMID:25748673

  4. Atrial Tachycardias after Atrial Fibrillation Ablation Manifest Different Waveform Characteristics: Implications for Characterizing Tachycardias

    PubMed Central

    Biviano, Angelo B.; Ciaccio, Edward J.; Fleitman, Jessica; Knotts, Robert; Lawrence, John; Haynes, Norrisa; Cyrille, Nicole; Hickey, Kathleen; Iyer, Vivek; Wan, Elaine; Whang, William; Garan, Hasan

    2015-01-01

    INTRODUCTON Atrial fibrillation (AF) ablation patients often manifest atrial tachycardias (AT) with atypical ECG morphologies that preclude accurate localization and mechanism. Diagnostic maneuvers used to define ATs during electrophysiology studies can be limited by tachycardia termination or transformation. Additional methods of characterizing post-AF ablation ATs are required. METHODS AND RESULTS We evaluated the utility of noninvasive ECG signal analytics in post-ablation AF patients for the following features: 1) Localization of ATs (i.e., right versus left atrium), and 2) Identification of common left AT mechanisms (i.e., focal vs. macroreentrant). Atrial waveforms from the surface ECG were used to analyze: 1) Spectral organization, including dominant amplitude (DA) and mean spectral profile (MP), and 2) Temporospatial variability, using temporospatial correlation coefficients. We studied 94 ATs in 71 patients who had undergone prior pulmonary vein isolation for AF and returned for a second ablation: 1) right atrial cavotricuspid-isthmus dependent (CTI) ATs (n=21); 2) left atrial macroreentrant ATs (n=41) and focal ATs (n=32). Right CTI ATs manifested higher DAs and lower MPs than left ATs, indicative of greater stability and less complexity in the frequency spectrum. Left macroreentrant ATs possessed higher temporospatial organization than left focal ATs. CONCLUSIONS Noninvasively recorded atrial waveform signal analyses show that right ATs possess more stable activation properties than left ATs, and left macroreentrant ATs manifest higher temporospatial organization than left focal ATs. Further prospective analyses evaluating the role these novel ECG-derived tools can play to help localize and identify mechanisms of common ATs in AF ablation patients are warranted. PMID:26228873

  5. Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study

    NASA Technical Reports Server (NTRS)

    Jaber, W. A.; Prior, D. L.; Thamilarasan, M.; Grimm, R. A.; Thomas, J. D.; Klein, A. L.; Asher, C. R.

    2000-01-01

    BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard for evaluation of the left atrium and the left atrial appendage (LAA) for the presence of thrombi. Anticoagulation is conventionally used for patients with atrial fibrillation to prevent embolization of atrial thrombi. The mechanism of benefit and effectiveness of thrombi resolution with anticoagulation is not well defined. METHODS AND RESULTS: We used a TEE database of 9058 consecutive studies performed between January 1996 and November 1998 to identify all patients with thrombi reported in the left atrium and/or LAA. One hundred seventy-four patients with thrombi in the left atrial cavity (LAC) and LAA were identified (1.9% of transesophageal studies performed). The incidence of LAA thrombi was 6.6 times higher than LAC thrombi (151 vs 23, respectively). Almost all LAC thrombi were visualized on transthoracic echocardiography (90.5%). Mitral valve pathology was associated with LAC location of thrombi (P <.0001), whereas atrial fibrillation or flutter was present in most patients with LAA location of thrombi. Anticoagulation of 47 +/- 18 days was associated with thrombus resolution in 80.1% of the patients on follow-up TEE. Further anticoagulation resulted in limited additional benefit. CONCLUSIONS: LAC thrombi are rare and are usually associated with mitral valve pathology. Transthoracic echocardiography is effective in identifying these thrombi. LAA thrombi occur predominantly in patients with atrial fibrillation or flutter. Short-term anticoagulation achieves a high rate of resolution of LAA and LAC thrombi but does not obviate the need for follow-up TEE.

  6. Cytochrome P4504A inhibitors attenuate the exaggerated natriuretic response to volume expansion in thyroidectomized rats

    PubMed Central

    Colombero, Cecilia; Venara, Marcela; Gonzalez, Daniel; Roman, Richard J.; Nowicki, Susana

    2014-01-01

    Abstract Thyroidectomy augments the natriuretic response to volume expansion; however, the mechanism remains unknown. This study assessed the role of 20‐hydroxyeicosatetraenoic acid (20‐HETE) in the natriuretic response to an acute volume expansion in hypothyroid rats. Urine flow (1.9‐fold), sodium excretion (2.4‐fold), fractional sodium excretion (3.8‐fold), and distal delivery of sodium (4.1‐fold) increased to a greater extent in thyroidectomized rats (TX) than in sham‐operated controls (SHAM) following i.v. infusion of isotonic saline (5% body weight) over 60 min. This was associated with inhibition of both proximal and distal tubular reabsorption of sodium. Administration of two mechanistic and chemical dissimilar inhibitors of the synthesis of 20‐HETE, 1‐aminobenzotriazole (ABT), and N‐hydroxy‐N’‐(‐4‐butyl‐2‐methylphenyl)formamidine (HET0016) decreased the natriuretic response in TX rats. Glomerular filtration rate was lower in TX than in SHAM rats and was not altered by the CYP4A inhibitors. The expression, intrarenal distribution, and the formation of 20‐HETE and expoxygenase metabolites of arachidonic acid were similar in the cortex and medulla of SHAM and TX rats. These results suggest that CYP4A‐derived metabolites of arachidonic acid play an important role in the enhanced natriuretic response to volume expansion in hypothyroid rats even though TX did not alter the expression or activity of these enzymes. PMID:24920124

  7. Natriuretic hormone—its possible role in fluid and electrolyte disturbances in chronic liver disease

    PubMed Central

    Kramer, Herbert J.

    1975-01-01

    Besides intrarenal physical factors and aldosterone, a natriuretic hormone has been postulated to modulate renal tubular sodium resorption in order to maintain body fluid homeostasis. To investigate the possible role of a natriuretic activity in sodium retention of chronic liver disease, the effects of plasma and plasma fraction IV from patients with cirrhosis of the liver and ascites on sodium transport of the isolated frog skin and on renal sodium excretion in the rat were compared to the antinatriferic and natriuretic effects of plasma from healthy subjects. While plasma from healthy individuals obtained following acute expansion of the extracellular fluid volume (ECV) significantly inhibited potential difference (PD) by -43·8 ± 5·5% and short circuit current (SCC) by -41·3 ± 1·7% when applied to the inner skin surface, control plasma and plasma from patients with liver cirrhosis and ascites affected PD by -3·8 ± 4·7% and -5·2 ± 3·7% and SCC by -7·3 ± 4·6% and -11·7 ± 2·5% respectively. Similar effects on PD and SCC were observed with plasma fractions IV. In contrast to fraction IV from ECV-expanded individuals, which caused marked diuresis and natriuresis when injected in the rat, fraction IV of plasma from cirrhotic patients failed to affect urinary flow rate, free-water clearance or renal sodium excretion. The results suggest that at least some patients with cirrhosis of the liver and sodium retention may lack an adequate humoral natriuretic activity sufficiently to promote renal sodium excretion. PMID:1234337

  8. B-type natriuretic peptide level in a patient with constrictive pericarditis.

    PubMed

    Brown, Todd; Hollman, Jay

    2006-12-01

    We report the case of a 35-year-old man with constrictive pericarditis who had a B-type natriuretic peptide (BNP) level of 129 pg/dl despite a left ventricular end diastolic pressure of 35 mmHg. We discuss a possible explanation for the relatively low BNP level given this patient's markedly elevated intracavitary pressures in the setting of constrictive pericarditis.

  9. Discovery and dimeric approach of novel Natriuretic Peptide Receptor A (NPR-A) agonists.

    PubMed

    Iwaki, Takehiko; Oyama, Yoshiaki; Tomoo, Toshiyuki; Tanaka, Taisaku; Okamura, Yoshihiko; Sugiyama, Masako; Yamaki, Akira; Furuya, Mayumi

    2017-03-15

    Novel agonists of the Natriuretic Peptide Receptor A (NPR-A) were obtained through random screening and subsequent structural modification of triazine derivatives. The key structural feature to improve in vitro activity was the dimerization of triazine monomer derivatives. The non peptide derivative 7c and 13a showed highly potent NPR-A agonistic activity in vitro and diuretic activity in vivo. These results implied that non-peptidic small molecules open the possibility of new therapy for congestive heart failure.

  10. Angiotensin Receptor Blockers and Statins Could Alleviate Atrial Fibrosis via Regulating Platelet-Derived Growth Factor/Rac1 /Nuclear Factor-Kappa B Axis

    PubMed Central

    Yang, Dongfang; Yuan, Jia; Liu, Gan; Ling, Zhiyu; Zeng, Haiyan; Chen, Yunqing; Zhang, Yue; She, Qiang; Zhou, Xue

    2013-01-01

    Aims: To investigate whether the administration of renin-angiotensin system (RAS) inhibitors and statins could alleviate atrial fibrosis via platelet-derived growth factor (PDGF)/Rac1 /nuclear factor-kappa B (NF-κB) axis. Methods and Results: In human left atrium, the degree of atrial fibrosis, as well as the expression levels of PDGF, Rac1 and NF-κB increased 1.5 to 2.9 folds in patients with atrial fibrillation compared to that with sinus rhythm, (P<0.0001). There were strongly positive correlations between angiotensin II (Ang II) or procollagen type III-alpha-1 (COL3A1) with PDGF, Rac1, NF-κB, and among PDGF, Rac1 and NF-κB (all P<0.05). At 3 weeks after the transverse aorta constriction (TAC) operation in rat model and with intervention of irbesartan or/and simvastatin, the collagen volume fraction (CVF) and atrial natriuretic peptide (ANP) values respectively increased 6-folds and 3.5-folds in the TAC group compared to SHAM group (P<0.0001), but these levels decreased by 16% to 63% with following drug intervention (all P<0.0001), the combined treatment was the lowest. Accordingly, the expression leve