[Plasma cardiac natriuretic peptide as a biological marker of recurrence of atrial fibrillation in elderly people].

PubMed

Mabuchi, N; Tsutamoto, T; Maeda, K; Masahiko, K

2000-07-01

We designed this study to evaluate the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and recurrence of atrial fibrillation (AF) after direct current cardioversion (DC) and the differences with aging. Fifty patients with mild congestive heart failure (CHF) undergoing elective DC of AF were included in this study (New York Heart Association (NYHA) functional class II: n = 42, III = 8). Patients who failed to show restoration of sinus rhythm or those with mitral valve stenosis were excluded. Before successful DC, we measured plasma levels of ANP and BNP and evaluated left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (EF) by echocardiography. Twenty-one patients had recurrence of AF within 2 months after DC (average 9.05 days). We followed up the other 29 patients for 580.5 days. By Cox stepwise multivariate analysis, history of AF (p = 0.007), low plasma levels of ANP (p = 0.003), and high plasma levels of BNP (p = 0.0003) were found to be independent predictors of recurrent AF. High plasma BNP levels indicating ventricular dysfunction and low plasma ANP levels may be due to atrial histological change such as fibrosis. In these patients, plasma ratios of ANP and BNP (ANP/BNP) less than 0.43 were predictive factors for AF recurrence (sensitivity 70%, specificity 62%), especially in patients who were older than 70 years (sensitivity 100%, specificity 80%). Relatively low plasma ANP level compared to BNP is an independent risk factor of AF recurrence in patients with CHF, especially in elderly patients, suggesting that plasma cardiac natriuretic peptides are important biochemical markers of AF recurrence in elderly patients with CHF.

Apelin-APJ system is responsible for stress-induced increase in atrial natriuretic peptide expression in rat heart.

PubMed

Izgut-Uysal, Vecihe Nimet; Acar, Nuray; Birsen, Ilknur; Ozcan, Filiz; Ozbey, Ozlem; Soylu, Hakan; Avci, Sema; Tepekoy, Filiz; Akkoyunlu, Gokhan; Yucel, Gultekin; Ustunel, Ismail

2018-04-01

The cardiovascular system is a primary target of stress and stress is the most important etiologic factor in cardiovascular diseases. Stressors increase expressions of atrial natriuretic peptide (ANP) and apelin in cardiac tissue. The aim of the present study was to investigate whether stress-induced apelin has an effect on the expression of ANP in the right atrium of rat heart. The rats were divided into the control, stress and F13A+stress groups. In the stress and F13A+stress groups, the rats were subjected to water immersion and restraint stress (WIRS) for 6h. In the F13A+stress group, apelin receptor antagonist F13A, was injected intravenously immediately before application of WIRS. The plasma samples were obtained for the measurement of corticosterone and atrial natriuretic peptide. The atrial samples were used for immunohistochemistry and western blot analysis. F13A administration prevented the rise of plasma corticosterone and ANP levels induced by WIRS. While WIRS application increased the expressions of apelin, HIF-1α and ANP in atrial tissue, while F13A prevented the stress-induced increase in the expression of HIF-1α and ANP. Stress-induced apelin induces ANP expression in atrial tissue and may play a role in cardiovascular homeostasis by increasing ANP expression under WIRS conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ultrastructural characterization of atrial natriuretic peptide receptors (ANP-R) mRNA expression in rat kidney cortex.

PubMed

Grandclément, B; Morel, G

1998-06-01

Atrial natriuretic peptide (ANP) and two complementary peptides named brain natriuretic peptide and C-type natriuretic peptide are involved in diuresis, natriuresis, hypotension and vasorelaxation. Their actions are mediated by highly selective and specific ANP receptors. Three subtypes have been characterized and cloned: ANP receptor A, -B and -C. In the present study, the mRNA for each subtype was detected by ultrastructural in situ hybridization on ultrathin sections of Lowicryl-embedded tissue and frozen tissue. The distribution of mRNA (visualized by gold particles) for each subtype was found to differ in different cells of the nephron. The three subtypes of this receptor family were expressed in all the parts of the nephron, but their expression levels were different. The ANPR-A mRNA was the most abundant in cells of glomerulus, proximal and distal tubules. The subtype C was the least expressed mRNA in glomerulus. In contrast, the subcellular localization of the three mRNAs was similar; they were found in the cytoplasmic matrix and the euchromatin of the nucleus. In conclusion, the differential expression of these mRNAs in kidney cortex indicates that these three peptides act directly in differing parts of nephron regions which are the glomerulus, the proximal and distal tubules.

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.

Obese Hypertensive Men Have Lower Circulating Proatrial Natriuretic Peptide Concentrations Despite Greater Left Atrial Size.

PubMed

Asferg, Camilla L; Andersen, Ulrik B; Linneberg, Allan; Goetze, Jens P; Jeppesen, Jørgen L

2018-05-07

Obese persons have lower circulating natriuretic peptide (NP) concentrations. It has been proposed that this natriuretic handicap plays a role in obesity-related hypertension. In contrast, hypertensive patients with left atrial enlargement have higher circulating NP concentrations. On this background, we investigated whether obese hypertensive men could have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size. We examined 98 obese men (body mass index [BMI] ≥ 30.0 kg/m2) and 27 lean normotensive men (BMI 20.0-24.9 kg/m2). All men were healthy, medication free, with normal left ventricular ejection fraction. We measured blood pressure using 24-hour ambulatory blood pressure (ABP) recordings. Hypertension was defined as 24-hour ABP ≥ 130/80 mm Hg, and normotension was defined as 24-hour ABP < 130/80 mm Hg. We determined left atrial size using echocardiography, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP). Of the 98 obese men, 62 had hypertension and 36 were normotensive. The obese hypertensive men had greater left atrial size (mean ± SD: 28.7 ± 6.0 ml/m2) compared with the lean normotensive men (23.5 ± 4.5 ml/m2) and the obese normotensive men (22.7 ± 5.1 ml/m2), P < 0.01. Nevertheless, despite evidence of pressure-induced greater left atrial size, the obese hypertensive men had lower serum MR-proANP concentrations (median [interquartile range]: 48.5 [37.0-64.7] pmol/l) compared with the lean normotensive men (69.3 [54.3-82.9] pmol/l), P < 0.01, whereas the obese normotensive men had serum MR-proANP concentrations in between the 2 other groups (54.1 [43.6-62.9] pmol/l). Despite greater left atrial size, obese hypertensive men have lower circulating MR-proANP concentrations compared with lean normotensive men.

Atrial natriuretic peptide induces acrosomal exocytosis of human spermatozoa.

PubMed

Rotem, R; Zamir, N; Keynan, N; Barkan, D; Breitbart, H; Naor, Z

1998-02-01

Acrosomal exocytosis in mammalian spermatozoa is a process essential for fertilization. We report here that atrial natriuretic peptide (ANP) markedly stimulates acrosomal exocytosis of capacitated human spermatozoa. Typically, ANP exerts some of its actions via activation of the ANP receptor (ANPR-A), a particulate guanylyl cyclase-linked receptor, and subsequent formation of guanosine 3',5'-cyclic monophosphate (cGMP). We found that ANP-stimulated acrosome reaction was inhibited by the competitive ANPR-A antagonist anantin, indicating a receptor-mediated process. A linear fragment of ANP, ANP-(13-28), and another ANP-like compound, brain natriuretic peptide, were inactive. The stimulatory effect of ANP on acrosome reaction was mimicked by the permeable cGMP analog, 8-bromo-cGMP (8-BrcGMP). Addition of the protein kinase C (PKC) inhibitors, staurosporine and GF-109203X, resulted in a dose-related inhibition of ANP-induced acrosome reaction. Also, downregulation of endogeneous PKC activity resulted in inhibition of ANP- but not 8-BrcGMP-induced acrosome reaction. Removal of extracellular Ca2+ abolished ANP-induced acrosome reaction. Thus ANP via Ca2+ influx, PKC activation, and stimulation of particulate guanylyl cyclase may play a role in the induction of acrosome reaction of human spermatozoa.

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.

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.

Atrial natriuretic-like peptide and its prohormone within metasequoia.

PubMed

Yang, Q; Gower, W R; Li, C; Chen, P; Vesely, D L

1999-07-01

Metasequoia glyptostroboides was one of the dominant conifers in North America, Asia, and Europe for more than 100 million years since the late Cretaceous Albian Age, but Quaternary glaciations drove the Metasequoia population to apparent extinction. A small pocket of Metasequoia, however, was found in central China in the 1940s representing the only surviving population of this "living fossil" species. Atrial natriuretic peptide, a 28-amino-acid peptide hormone that causes sodium and water excretion in animals, has been found to be part of the first peptide hormonal system in lower plants. The existence of this hormonal system has never been examined within trees of any genus. High-performance gel permeation chromatography of the leaves and stems (i.e., branches) of Metasequoia followed by atrial natriuretic peptide radioimmunoassay revealed an ANP-like peptide and its prohormone (i.e., approximately 13,000 mol wt) were present in both leaves and stems of this conifer. The elution profile of ANP-like peptide in stems of Metasequoia had a shoulder to the left of where pure synthetic ANP elutes suggesting the possibility of a slightly larger peptide eluting within this shoulder secondary to alternate processing of the ANP-like prohormone and similar to what occurs with the kidney of animals. The elution profile of ANP-like peptide in the leaves of Metasequoia revealed two peaks; one where ANP elutes and a second peak suggesting a smaller peptide that has been metabolically processed. The presence of the ANP-like prohormone strongly suggests that ANP-like gene expression is occurring in both leaves and stems of Metasequoia since this prohormone is the gene product of this hormonal system. The presence of the ANP-like hormonal system in trees implies that this hormonal system may have been present early in land plant evolution to allow trees to reach heights of greater than 30 feet where a water flow-enhancing substance is absolutely necessary for water flow to occur

Expression of receptors for atrial natriuretic peptide on the murine bone marrow-derived stromal cells.

PubMed

Agui, T; Yamada, T; Legros, G; Nakajima, T; Clark, M; Peschel, C; Matsumoto, K

1992-05-01

Atrial natriuretic peptide (ANP) receptors were identified on both murine bone marrow-derived stromal cell lines A-3 and ALC and primary cultured cells using [125I]ANP binding assays and Northern blot analyses. The binding of [125I] ANP to the stromal cells was rapid, saturable, and of high affinity. The dissociation constants between ANP and its receptors on these cells showed no difference among cell types, while maximal binding capacity values were different among cell types. Competitive inhibition of [125I]ANP binding with C-atrial natriuretic factor, specific for ANP clearance receptor (ANPR-C), revealed that most of [125I]ANP-binding sites corresponded to ANPR-C. Northern blotting data corroborated that bone marrow-derived stromal cells expressed ANPR-C. However, in ALC cells, ANP biological receptors (either ANPR-A or ANPR-B), the mol wt of which is approximately 130K, were detected, and cGMP was accumulated after stimulation with ANP. On the other hand, in another stromal cell clone, A-3 cells, the expression of biological receptor was not detected in the affinity cross-linking and competitive inhibition experiments using [125I]ANP. However, A-3 cells accumulated cGMP by responding to ANPR-B-specific ligand, C-type natriuretic peptide. These results suggest that ALC cells equally express ANPR-A and ANPR-B, while A-3 cells express ANPR-B dominantly. Although the physiological roles of these receptors in the bone marrow is still not resolved, ANP is expected to play a role in the regulation of stromal cell functions in bone marrow.

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.

Alteration of lung atrial natriuretic peptide receptors in genetic cardiomyopathy.

PubMed

Mukaddam-Daher, S; Tremblay, J; Fujio, N; Koch, C; Jankowski, M; Quillen, E W; Gutkowska, J

1996-07-01

These studies were designed to characterize the atrial natriuretic peptide (ANF) receptor subtypes [guanylyl cyclase natriuretic peptide receptors (NPR-A, NPR-B) and NPR-C] in lungs of normal hamsters and to evaluate alterations in receptor kinetics in genetic cardiomyopathy (CMO), a model of human congestive heart failure. Lung membranes were obtained from normal and CMO 200-to 230-day-old hamsters. Cross-linking and competitive binding receptor assays using 125I-labeled human ANF showed that lung membranes exhibit NPR, mainly guanylyl cyclase NPR-A and clearance NPR-C receptors. Stimulation of guanylyl cyclase by ANF and C-type natriuretic peptide (CNP) confirmed the presence of NPR-A and NPR-B. The maximum binding capacity of total ANF binding sites (442 +/- 68 vs. 271 +/- 57 fmol/mg protein, P < 0.05) was reduced, but dissociation constant (0.26 +/- 0.04 vs. 0.41 +/- 0.08 nM) was not altered in CMO animals. Similar reductions were observed in the binding sites for brain natriuretic peptide (BNP; 438 +/- 83 vs. 236 +/- 53 fmol/mg protein) and CNP (321 +/- 80 vs. 165 +/- 56 fmol/mg protein, P < 0.05) which may reflect a decline in NPR-A and NPR-B and/or NPR-C. Acid wash improved binding of 125I-labeled rat ANF to lung membranes of both normal and CMO hamsters, but the tendency towards reduced binding in CMO hamsters did not reach statistical significance, implying that downregulation may not have been due only to prior occupancy of the receptors. Transcripts of NPR-A, NPR-B, and NPR-C receptors in hamster lungs were detected by quantitative polymerase chain reaction. Compared with normal controls, the CMO hamster lung NPR-A mRNA was reduced by 50%, but NPR-B mRNA and NPR-C mRNA were not altered. Moreover, CMO hamster lungs showed less activation of guanylyl cyclase by ANF. These studies demonstrate that lung NPR are downregulated in hamster CMO.

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

Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system.

PubMed

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.

Atrial natriuretic factor increases vascular permeability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lockette, W.; Brennaman, B.

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 determinationsmore » 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.« less

Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

PubMed

Ishikura, Fuminobu; Beppu, Shintaro; Asanuma, Toshihiko; Seward, James B; Khandheria, Bijoy K

2007-12-01

Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

Natriuretic peptides: Diagnostic and therapeutic use

PubMed Central

Pandit, Kaushik; Mukhopadhyay, Pradip; Ghosh, Sujoy; Chowdhury, Subhankar

2011-01-01

Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and have important natriuretic and kaliuretic properties. There are four different groups NPs identified till date [atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own characteristic functions. The N-terminal part of the prohormone of BNP, NT-proBNP, is secreted alongside BNP and has been documented to have important diagnostic value in heart failure. NPs or their fragments have been subjected to scientific observation for their diagnostic value and this has yielded important epidemiological data for interpretation. However, little progress has been made in harnessing the therapeutic potential of these cardiac hormones. PMID:22145138

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

PubMed Central

Lara-Castillo, Nuria; Zandi, Souska; Nakao, Shintaro; Ito, Yasuhiro; Noda, Kousuke; She, Haicheng; Ahmed, Muna; Frimmel, Sonja; Ablonczy, Zsolt; Hafezi-Moghadam, Ali

2009-01-01

Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 μmol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP’s effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP’s TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy. PMID:19910509

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.

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 bindingmore » 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.« less

Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal pro B-type natriuretic peptide in the diagnosis of patients with atrial fibrillation and dyspnoea.

PubMed

Eckstein, Jens; Potocki, Mihael; Murray, Karsten; Breidthardt, Tobias; Ziller, Ronny; Mosimann, Tamina; Klima, Theresia; Hoeller, Rebeca; Moehring, Berit; Sou, Seoung Mann; Rubini Gimenez, Maria; Morgenthaler, Nils G; Mueller, Christian

2012-10-01

Due to different release mechanisms, mid-regional pro-atrial natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for their diagnostic value in patients with AF and sinus rhythm (SR). Prospective cohort study. University hospital, emergency department. 632 consecutive patients presenting with acute dyspnoea. MR proANP and NT proBNP plasma levels were determined. The diagnosis of AHF was adjudicated by two independent cardiologists using all available data. Patients received long-term follow-up. AF was present in 151 patients (24%). MR proANP and NT proBNP levels were significantly higher in the AF group compared with the SR group (385 (258-598) versus 201 (89-375) pmol/l for MR proANP, p<0.001 and 4916 (2169-10285) versus 1177 (258-5166) pg/ml, p<0.001 for NT proBNP). Diagnostic accuracy in AF patients was similar for MR proANP (0.90, 95% CI 0.84 to 0.95) and NT proBNP (0.89, 95% CI 0.81 to 0.96). Optimal cut-off levels in AF patients were significantly higher compared with the optimal cut-off levels for patients in SR (MR proANP 240 vs 200 pmol/l; NT proBNP 2670 vs 1500 pg/ml respectively). After adjustment in multivariable Cox proportional hazard analysis, MR proANP strongly predicted one-year all-cause mortality (HR=1.13 (1.09-1.17), per 100 pmol/l increase, p<0.001). In AF patients, NT proBNP and MR proANP have similar diagnostic value for the diagnosis of AHF. The rhythm at presentation has to be taken into account because plasma levels of both peptides are significantly higher in patients with AF compared with SR.

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. © 2013.

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

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations.

PubMed

Oyama, Mark A; Sisson, D David; Solter, Phil F

2007-01-01

To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). 118 client-owned dogs. Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.

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

Atrial natriuretic peptide: a magic bullet for cancer therapy targeting Wnt signaling and cellular pH regulators.

PubMed

Serafino, A; Pierimarchi, P

2014-01-01

Atrial natriuretic peptide (ANP) is a cardiac hormone playing a crucial role in cardiovascular homeostasis mainly through blood volume and pressure regulation. In the last years, the new property ascribed to ANP of inhibiting tumor growth both in vitro and in vivo has made this peptide an attractive candidate for anticancer therapy. The molecular mechanism underlying the anti-proliferative effect of ANP has been mainly related to its interaction with the specific receptors NPRs, through which this natriuretic hormone inhibits some metabolic targets critical for cancer development, including the Ras-MEK1⁄2-ERK1⁄2 kinase cascade, functioning as a multikinase inhibitor. In this review we summarize the current knowledge on this topic, focusing on our recent data demonstrating that the antitumor activity of this natriuretic hormone is also mediated by a concomitant effect on the Wnt/β-catenin pathway and on the pH regulation ability of cancer cells, through a Frizzled-related mechanism. This peculiarity of simultaneously targeting two processes crucial for neoplastic transformation and solid tumor survival reinforces the utility of ANP for the development of both preventive and therapeutic strategies.

Interactive effect of body posture on exercise-induced atrial natriuretic peptide release.

PubMed

Ray, C A; Delp, M D; Hartle, D K

1990-05-01

The purpose of this investigation was to test the hypothesis that supine exercise elicits a greater atrial natriuretic peptide (ANP) response than upright exercise because of higher atrial filling pressure attained in the supine posture. Plasma ANP concentration ([ANP]) was measured during continuous graded supine and upright exercise in eight healthy men at rest after 4 min of cycling exercise at 31, 51, and 79% of posture-specific peak oxygen uptake (VO2 peak), after 2 min of cycling at posture-specific VO2 peak, and 5 and 15 min postexercise. [ANP] was significantly increased (P less than 0.05) above rest by 64, 140, and 228% during supine cycling at 51 and 79% and VO2 peak, respectively. During upright cycling, [ANP] was significantly increased (P less than 0.05) at 79% (60%) and VO2 peak (125%). After 15 min of postexercise rest, [ANP] remained elevated (P less than 0.05) only in the supine subjects. [ANP] was 63, 79, and 75% higher (P less than 0.05) in the supine than in the upright position during cycling at 51 and 79% and VO2 peak. Systolic, diastolic, and mean blood pressures were not significantly (P greater than 0.05) different between positions in all measurement periods. Heart rates were lower (P less than 0.05) in the supine position compared with the upright position. In conclusion, these results suggest that supine exercise elicits greater ANP release independent of blood pressure and heart rate but presumably caused by greater venous return, central blood volume, and concomitant atrial filling pressure and stretch.

Effect of pericardiocentesis on circulating concentrations of atrial natriuretic hormone and arginine vasopressin in dogs with spontaneous pericardial effusion.

PubMed

Stokhof, A A; Overduin, L M; Mol, J A; Rijnberk, A

1994-04-01

Factors regulating the secretion of atrial natriuretic hormone (ANH) and arginine vasopressin (AVP) have not been elucidated fully. In several studies the release of these peptides has been studied by inducing both increased atrial pressure and atrial distension. A few studies employ cardiac tamponade, allowing the effect of atrial pressure and atrial stretch to be studied separately. In eleven dogs with spontaneous cardiac tamponade the effect of pericardiocentesis on circulating concentrations of ANP and AVP was studied. Pericardiocentesis was followed by a prompt rise in (non-elevated) plasma ANH concentrations from 21.6 +/- 7.3 to 65.4 +/- 17.1 pmol/l (mean +/- SEM). The initially slightly elevated AVP concentration of 5.5 +/- 1.5 pmol/l declined following pericardiocentesis to 2.1 +/- 0.5 pmol/l. In three dogs the systolic arterial pressure was measured indirectly and the central venous pressure was measured with a fluid-filled catheter. Before and after pericardiocentesis arterial pressure readings did not change significantly. Central venous pressure values showed an immediate very steep significant decrease after centesis. It is concluded that ANH release is primarily regulated by stretch and not by atrial pressure, that plasma AVP concentrations are moderately elevated in cardiac tamponade and that in cardiac tamponade pericardiocentesis causes a rapid decline in plasma AVP concentration.

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

PubMed

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

2018-05-26

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

Atrial natriuretic factor receptor heterogeneity in rat tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andresen, J.W.; Kuno, T.; Kamisaki, Y.

1986-03-01

Rat /sup 125/I-atrial natriuretic factor (ANF, 8-33) was used to identify ANF receptors in membrane preparations from rat adrenal gland and lung. When solubilized with Lubrol-PX, the receptors retained a binding profile and properties that correspond to the high affinity and specificity found in crude membranes. Single peaks of binding activity were observed in gel permeation HPLC and density gradient centrifugation analysis of the solubilized preparations. However, when membranes and solubilized preparations were labeled with /sup 125/I-ANF, treated with crosslinking reagent (disuccinimidyl suberate), and analyzed by SDS gel electrophoresis several specifically labeled bands (120,000, 70,000, and 60,000 daltons) were identifiedmore » by autoradiography. The relative distribution of the specifically labeled proteins varied significantly between rat adrenal gland and lung. In adrenal glands the 120K dalton band was the most prominent specifically labeled protein, while the 60K and 70K dalton proteins were labeled to a lesser degree. In lung membranes the lower molecular weight proteins were more prominent. These results suggest the presence of multiple ANF receptor subtypes, the distribution of which varies among tissues. Chromatographic separation and further characterization of these receptors are currently in progress, and preliminary purification studies support this hypothesis.« less

Atrial natriuretic peptide induces acrosomal exocytosis in bovine spermatozoa.

PubMed

Zamir, N; Barkan, D; Keynan, N; Naor, Z; Breitbart, H

1995-08-01

The induction of acrosomal exocytosis in capacitated bull spermatozoa by atrial natriuretic peptide (ANP) was studied in vitro. ANP markedly stimulated acrosomal exocytosis in a calcium-dependent manner. Typically, ANP exerts its action via activation of the ANP receptor (ANPR-A), a particulate guanylyl cyclase-linked receptor, and subsequent formation of guanosine 3',5'-cyclic monophosphate (cGMP). We found that the ANP-induced acrosome reaction was inhibited by the competitive ANPR-A receptor antagonist-anantin, indicating a receptor-mediated effect. We could mimic the effect of ANP on the acrosome reaction by using 8-bromo-cGMP, suggesting that cGMP may serve as a signal transducer mediating the acrosome reaction. Indeed, the ANP-induced acrosome reaction was associated with elevation of cGMP levels. cGMP can also be formed by activation of the soluble form of guanylyl cyclase. Sodium nitroprusside (SNP) stimulated cGMP accumulation and acrosome reaction of capacitated spermatozoa. Thus ANP and the nitric oxide-releasing compound SNP, via activation of guanylyl cyclase (the former activating the particulate and the latter activating the soluble form of the enzyme), may play a significant role in the induction of the acrosome reaction.

Severe tricuspid regurgitation in the aged: atrial remodeling associated with long-standing atrial fibrillation.

PubMed

Yamasaki, Naohito; Kondo, Fumiaki; Kubo, Toru; Okawa, Makoto; Matsumura, Yoshihisa; Kitaoka, Hiroaki; Yabe, Toshikazu; Furuno, Takashi; Doi, Yoshinori

2006-12-01

Severe idiopathic tricuspid regurgitation (TR) occurs in the aged, but the mechanism of TR is unclear and there is little information on atrial abnormalities associated with this condition. This study retrospectively analyzed patients with severe functional TR presenting with common clinical features suggesting a distinct syndrome. Eleven patients with severe functional TR were identified by reviewing the records of 16,235 consecutive patients. All patients had undergone clinical evaluation including echocardiography, electrocardiography and laboratory data. The median age of patients with severe functional TR was 78 years. All had a long-standing history of atrial fibrillation (median duration, 23 years). Clinical features are characterized by severe functional TR due to annular dilation, markedly dilated right atrium, episodes of right-sided heart failure, absent or diminished fibrillation waves on electrocardiogram, bradycardia probably due to partial atrial standstill, and decreased atrial natriuretic peptide secretion. During long-term follow up, right atrial size progressively increased in association with worsening TR. Severe functional TR occurs with long-standing atrial fibrillation and causes right-sided heart failure. The TR is caused by tricuspid valve systolic coaptation loss due to tricuspid annular dilation associated with atrial dilation. This condition is associated with atrial abnormalities, such as atrial standstill and impaired atrial natriuretic peptide secretion. We propose that atrial remodeling associated with atrial fibrillation is central to the occurrence of the syndrome.

Involvement of atrial natriuretic peptide in abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart.

PubMed

Vishwakarma, V K; Goyal, A; Gupta, J K; Upadhyay, P K; Yadav, H N

2018-07-01

Nitric oxide (NO) is an effective mediator of ischemic preconditioning (IPC)-induced cardioprotection. Atrial natriuretic peptide (ANP) is downregulated after ovariectomy, which results in reduction in the level of NO. The present study deals with the investigation of the role of ANP in abrogated cardioprotective effect of IPC in the ovariectomized rat heart. Heart was isolated from ovariectomized rat and mounted on Langendorff's apparatus, subjected to 30 min of ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Krebs-Henseleit solution. The myocardial infract size was estimated employing triphenyltetrazolium chloride stain, and coronary effluent was analyzed for creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release to consider the degree of myocardial injury. The cardiac release of NO was estimated by measuring the level of nitrite in coronary effluent. IPC-mediated cardioprotection was significantly attenuated in ovariectomized rat as compared to normal rat, which was restored by perfusion with ANP. However, this observed cardioprotection was significantly attenuated by perfusion with L-NAME, an endothelial nitric oxide synthase inhibitor, and Glibenclamide, a K ATP channel blocker, alone or in combination noted in terms of increase in myocardial infract size, release of CK-MB and LDH, and also decrease in release of NO. Thus, it is suggested that ANP restores the attenuated cardioprotective effect of IPC in the ovariectomized rat heart which may be due to increase in the availability of NO and consequent increase activation of mitochondrial K ATP channels.

Atrial natriuretic peptide decreases blood volume in intact and anephric rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trippodo, N.C.; Chien, Y.W.; Pegram, B.L.

1986-03-05

Atrial natriuretic peptide (ANP) reportedly lowers atrial pressure and increases hematocrit, suggesting venodilation and/or decreased blood volume (BV). To examine these possibilities, rat ANP (99-126) was administered to Inactinanesthetized rats (313 +/- 9 g, +/- SE) at 0.5 ..mu..g/kg/min for 30 minutes. Urine flow increased by 0.05 ml/min (p < 0.001) during the last 15 minutes of infusion. Mean arterial pressure (MAP) and thoracic central venous pressure (CVP) decreased (p < 0.001) by 12 and 0.5 mmHg, respectively; hematocrit increased by 4.1 units (p < 0.001) and BV (/sup 51/Cr-RBC) decreased by 3.4 ml/kg (p < 0.001). Mean circulatory fillingmore » pressure, measured by inflating an intracardiac balloon to briefly stop the circulation, did not change. Distribution of BV between the thoracic and spanchnic organs (whole-animal freezing in liquid nitrogen) was not measurably altered. The results suggest that the decrease in CVP was related more to decreased BV than to venodilation. To investigate possible mechanisms for the decreased BV, the same dose of ANP was administered to anephric rats. MAP decreased by 8 mmHg (p < 0.001); hematocrit increased by 2.4 units (p < 0.001) and BV decreased by 1.7 ml/kg (p < 0.05). The results indicate that short-term administration of ANP decreases blood volume by causing intravascular fluid to shift into the interstitium as well as by inducing diuresis.« less

Natriuretic Peptides as Biomarkers in Heart Failure

PubMed Central

Januzzi, James L.

2014-01-01

Following the initial discovery of a natriuretic and diuretic peptide factor present in atrial myocardial tissue homogenates, subsequent elucidation of the natriuretic peptide family has led to substantial advances in the understanding of the autocrine, paracrine, and endocrine regulation of the cardiovascular system. Furthermore, with the development of assays for the measurement of the natriuretic peptides, these important biomarkers have gone from being regarded as biological mediators of the cardiovascular system to now represent important clinical tools for the diagnostic and prognostic evaluation of patients with heart failure, and may have potential as a therapeutic target in this setting as well. An historical perspective on the natriuretic peptides from bench to bedside translation will be discussed. PMID:23661103

Renal atrial natriuretic factor receptors in hamster cardiomyopathy.

PubMed

Mukaddam-Daher, S; Jankowski, M; Dam, T V; Quillen, E W; Gutkowska, J

1995-12-01

Hamsters with cardiomyopathy (CMO), an experimental model of congestive heart failure, display stimulated renin-angiotensin-aldosterone and enhanced sympathetic nervous activity, all factors that lead to sodium retention, volume expansion and subsequent elevation of plasma atrial natriuretic factor (ANF) by the cardiac atria. However, sodium and water retention persist in CMO, indicating hyporesponsiveness to endogenous ANF. These studies were undertaken to fully characterize renal ANF receptor subtypes in normal hamsters and to evaluate whether alterations in renal ANF receptors may contribute to renal resistance to ANF in cardiomyopathy. Transcripts of the guanylyl cyclase-A (GC-A) and guanylyl cyclase B (GC-B) receptors were detected by quantitative polymerase chain reaction (PCR) in renal cortex, and outer and inner medullas. Compared to normal controls, the cardiomyopathic hamster's GC-A mRNA was similar in cortex but significantly increased in outer and inner medulla. Levels of GC-B mRNA were not altered by the disease. On the other hand, competitive binding studies, autoradiography, and affinity cross-linking demonstrated the absence of functional GC-B receptors in the kidney glomeruli and inner medulla. Also, C-type natriuretic peptide (CNP), the natural ligand for the GC-B receptors, failed to stimulate glomerular production of its second messenger cGMP. In CMO, sodium and water excretion were significantly reduced despite elevated plasma ANF (50.5 +/- 11.1 vs. 309.4 +/- 32.6 pg/ml, P < 0.001). Competitive binding studies of renal glomerular ANF receptors revealed no change in total receptor density, Bmax (369.6 +/- 27.4 vs. 282.8 +/- 26.2 fmol/mg protein), nor in dissociation constant, Kd (647.4 +/- 79.4 vs. 648.5 +/- 22.9 pM). Also, ANF-C receptor density (254.3 +/- 24.8 vs. 233.8 +/- 23.5 fmol/mg protein), nor affinity were affected by heart failure. Inner medullary receptors were exclusively of the GC-A subtype with Bmax (153.2 +/- 26.4 vs. 134

Serum N-terminal-pro-brain natriuretic peptide level and its clinical implications in patients with atrial fibrillation.

PubMed

Bai, Mei; Yang, Jiefu; Li, Yingying

2009-12-01

Brain natriuretic peptide (BNP) is increasingly being used for screening and monitoring of congestive heart failure. However, the role of BNP in patients with atrial fibrillation (AF) and normal left ventricular function has not been determined. This study investigates serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and its clinical implications in patients with AF. Serum NT-proBNP levels were measured by enzyme-linked immunosorbent assay (ELISA) and transthoracic echocardiography was performed in 136 subjects (90 cases with AF and 46 cases with sinus rhythm [SR]). Subjects were excluded if they had a history of myocardial infarction, cardiomyopathy, rheumatic heart disease, or hyperthyroidism that preceded the onset of AF. Controls (n = 30) were from a healthy outpatient primary care population. Potential determinants of serum NT-proBNP levels were identified by univariate and multivariate analyses. Individuals with AF had higher serum NT-proBNP levels (689.56 +/- 251.87 fmol/ml) than those with SR (456.11 +/- 148.14 fmol/ml, P < 0.01) and control subjects (415.83 +/- 62.02 fmol/ml, P < 0.01). Individuals with SR and control subjects did not show significant difference at serum NT-proBNP levels (P > 0.05). The regression model of serum NT-proBNP levels and clinical predictors showed that presence of AF, older age, and larger right atrial diameter were independently predictive of higher serum NT-proBNP values. Patients with AF were associated with increased serum NT-proBNP levels. Examining the change of serum NT-proBNP levels is helpful to evaluate the cardiac function in patients with AF. Copyright 2009 Wiley Periodicals, Inc.

Atrial natriuretic factor increases splenic microvascular pressure and fluid extravasation in the rat.

PubMed

Sultanian, R; Deng, Y; Kaufman, S

2001-05-15

The spleen is an important site of atrial natriuretic factor (ANF)-induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood-perfused (1 ml min(-1)) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1-28), infused into the splenic artery of anaesthetized male rats, caused a dose-dependent (0.3-59 pmol min(-1)) increase in microvascular pressure from 11.3 +/- 0.7 to 14.9 +/- 0.5 mmHg and in post-capillary resistance from 7.2 +/- 0.6 to 10.1 +/- 1.1 mmHg ml(-1). ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min(-1)) caused a sustained increase in intrasplenic fluid efflux from 0.1 +/- 0.1 to 0.3 +/- 0.1 ml min(-1), and in capillary filtration coefficient (Kf) from 1.2 +/- 0.5 to 2.4 +/- 0.6 ml mmHg-1 min-1 (100 g tissue)-1. Mechanical elevation of splenic intravascular pressure (from 11.3 +/- 0.7 to 22.4 +/- 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 +/- 0.3 to 1.4 +/- 0.3 ml min(-1)). The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol min(-1)) did not alter splenic intravascular pressure or pre-/post-capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min-1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), inhibited the ANF-induced changes in splenic microvascular pressure and post-capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post-capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA.

ATRIAL NATRIURETIC FACTOR RECEPTOR GUANYLATE CYCLASE SIGNALING: NEW ATP- REGULATED TRANSDUCTION MOTIF

PubMed Central

Duda, Teresa; Bharill, Shashank; Wojtas, Ireneusz; Yadav, Prem; Gryczynski, Ignacy; Gryczynski, Zygmunt; Sharma, Rameshwar K.

2010-01-01

ANF-RGC$ membrane guanylate cyclase is the receptor for the hypotensive peptide hormones, atrial natriuretic factor (ANF) and type B natriuretic peptide (BNP). It is a single transmembrane spanning protein. Binding the hormone to the extracellular domain activates its intracellular catalytic domain. This results in accelerated production of cyclic GMP, a second messenger in controlling blood pressure, cardiac vasculature and fluid secretion. ATP is the obligatory transducer of the ANF signal. It works through its ATP regulated module, ARM, which is juxtaposed to the C-terminal side of the transmembrane domain. Upon interaction, ATP induces a cascade of temporal and spatial changes in the ARM, which, finally, result in activation of the catalytic module. Although the exact nature and the details of these changes are not known, some of these have been stereographed in the simulated three-dimensional model of the ARM and validated biochemically. Through comprehensive techniques ofsteady-state, time-resolved tryptophan fluorescence and Forster Resonance Energy Transfer (FRET), site-directed and deletion-mutagenesis, and reconstitution, the present study validates and explains themechanism of the model-based predicted transduction role of the ARM’s structural motif, 669WTAPELL675. This motif is critical in the ATP-dependent ANF signaling. Molecular modeling shows that ATP binding exposes the 669WTAPELL675 motif, the exposure, in turn, facilitates its interaction and activation of the catalytic module. These principles of the model have been experimentally validated. This knowledge brings us a step closer to our understanding of the mechanism by which the ATP-dependent spatial changes within the ARM cause ANF signaling of ANF-RGC. PMID:19137266

Renal receptors for atrial and C-type natriuretic peptides in the rat.

PubMed

Brown, J; Zuo, Z

1992-07-01

Receptors for alpha-atrial natriuretic peptide (alpha-ANP) and C-type natriuretic peptide [CNP-(1-22)] were quantified in kidneys from adult Wistar rats by in vitro autoradiography. 125I-labeled alpha-ANP (100 pM) bound reversibly to glomeruli, outer medullary vasa recta, and inner medulla with an apparent dissociation constant (Kd) of 3-6 nM. The presence of 10 microM des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23) (C-ANP), a specific ligand of the ANPR-C subtype of alpha-ANP receptor, inhibited approximately 50% of the glomerular binding of 125I-alpha-ANP, and this moiety of glomerular binding was also inhibited by CNP-(1-22) with an apparent inhibitory constant (Ki) of 10.47 +/- 7.59 nM. C-ANP and CNP-(1-22) showed little affinity for the medullary binding sites of alpha-ANP. 125I-[Tyr0]CNP-(1-22) (110 pM) bound solely to glomeruli and was competitively displaced by increasing concentrations of [Tyr0]CNP-(1-22) with an apparent Kd of 1.42 +/- 0.48 nM. Binding of increasing concentrations (25 pM to 1 nM) of 125I-[Tyr0]CNP-(1-22) in the presence or absence of 1 microM [Tyr0]CNP-(1-22) also demonstrated a high affinity (Kd of 0.41 +/- 0.07 nM) for the glomerular binding of 125I-[Tyr0]CNP-(1-22). Bound 125I-[Tyr0]CNP-(1-22) could be displaced by excess alpha-ANP and excess CNP-(1-22), both with high affinities. The glomerular binding of 125I-[Tyr0]CNP-(1-22) was also prevented by 10 microM C-ANP. Guanosine 3',5'-cyclic monophosphate produced by isolated glomeruli was measured by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator.

PubMed

Elesgaray, Rosana; Caniffi, Carolina; Savignano, Lucía; Romero, Mariana; Mac Laughlin, Myriam; Arranz, Cristina; Costa, María A

2012-06-01

Atrial natriuretic peptide (ANP) is an important regulator of blood pressure (BP). One of the mechanisms whereby ANP impacts BP is by stimulation of nitric oxide (NO) production in different tissues involved in BP control. We hypothesized that ANP-stimulated NO is impaired in the kidneys of spontaneously hypertensive rats (SHR) and this contributes to the development and/or maintenance of high levels of BP. We investigated the effects of ANP on the NO system in SHR, studying the changes in renal nitric oxide synthase (NOS) activity and expression in response to peptide infusion, the signaling pathways implicated in the signaling cascade that activates NOS, and identifying the natriuretic peptide receptors (NPR), guanylyl cyclase receptors (NPR-A and NPR-B) and/or NPR-C, and NOS isoforms involved. In vivo, SHR and Wistar-Kyoto rats (WKY) were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg(-1)·min(-1)). NOS activity and endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) NOS expression were measured in the renal cortex and medulla. In vitro, ANP-induced renal NOS activity was determined in the presence of iNOS and nNOS inhibitors, NPR-A/B blockers, guanine nucleotide-regulatory (G(i)) protein, and calmodulin inhibitors. Renal NOS activity was higher in SHR than in WKY. ANP increased NOS activity, but activation was lower in SHR than in WKY. ANP had no effect on expression of NOS isoforms. ANP-induced NOS activity was not modified by iNOS and nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in kidney. The renal NOS response to ANP was reduced by G(i) protein and calmodulin inhibitors. We conclude that ANP interacts with NPR-C, activating Ca-calmodulin eNOS through G(i) protein. NOS activation also involves NPR-A/B. The NOS response to ANP was diminished in kidneys of SHR. The impaired NO system response to ANP in SHR participates in the maintenance of high blood pressure.

Crystallization and preliminary X-ray analysis of the atrial natriuretic peptide (ANP) receptor extracellular domain complex with ANP: use of ammonium sulfate as the cryosalt.

PubMed

Ogawa, Haruo; Zhang, Xiaolun; Qiu, Yue; Ogata, Craig M; Misono, Kunio S

2003-10-01

Atrial natriuretic peptide (ANP) plays a major role in blood pressure and volume regulation owing to its natriuretic and vasodilatory activities. The ANP receptor is a single-span transmembrane receptor coupled to its intrinsic guanylyl cyclase activity. The extracellular hormone-binding domain of rat ANP receptor (ANPR) was overexpressed by permanent transfection in CHO cells and purified. ANPR complexed with ANP was crystallized at 301 K by the hanging-drop vapor-diffusion method. The crystals were frozen in 3.4 M ammonium sulfate used as a cryoprotectant. The crystals diffracted to 3.1 A resolution using synchrotron radiation and belonged to the hexagonal space group P6(1), with unit-cell parameters a = b = 100.3, c = 258.6 A.

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.

Beta-adrenergic and atrial natriuretic peptide interactions on human cardiovascular and metabolic regulation

PubMed Central

Birkenfeld, Andreas L.; Boschmann, Michael; Moro, Cedric; Adams, Frauke; Heusser, Karsten; Tank, Jens; Diedrich, André; Schroeder, Christoph; Franke, Gabi; Berlan, Michel; Luft, Friedrich C.; Lafontan, Max; Jordan, Jens

2006-01-01

Context Atrial natriuretic peptide (ANP) has well known cardiovascular effects and modifies lipid and carbohydrate metabolism in humans. Objective To determine the metabolic and cardiovascular interaction of beta-adrenergic receptors and ANP. Design Cross over study, conducted 2004–2005 Setting Academic clinical research center Patients Ten healthy, young, male subjects (BMI 24±1 kg/m2) Intervention We infused intravenously incremental ANP doses (6.25, 12.5, and 25 ng/kg/min) with and without propranolol (0.20 mg/kg in divided doses followed by 0.033 mg/kg/h infusion). Metabolism was monitored through venous blood sampling, intramuscular and subcutaneous microdialysis and indirect calorimetry. Cardiovascular changes where monitored by continuous ECG and beat-by-beat blood pressure recordings. Main outcome measures Venous NEFA, glycerol, glucose, insulin; microdialysate glucose, glycerol, lactate, pyruvate. Results ANP increased heart rate dose dependently. Beta-adrenergic receptor blockade abolished the response. ANP elicited a dose-dependent increase in serum non-esterified fatty acid and glycerol concentrations. The response was not suppressed with propranolol. Venous glucose and insulin concentrations increased with ANP, both, without or with propranolol. ANP induced lipid mobilization in subcutaneous adipose tissue. In skeletal muscle, microdialysate lactate increased while the lactate to pyruvate ratio decreased, both, with and without propranolol. Higher ANP doses increased lipid oxidation while energy expenditure remained unchanged. Propranolol tended to attenuate the increase in lipid oxidation. Conclusions Selected cardiovascular ANP effects are at least partly mediated by beta-adrenergic receptor stimulation. ANP induced changes in lipid mobilization and glycolysis are mediated by another mechanism, presumably stimulation of natriuretic peptide receptors whereas substrate oxidation might be modulated through adrenergic mechanisms. PMID:16984990

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.

Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

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,more » 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.« less

Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

PubMed Central

Wei, C M; Kim, C H; Miller, V M; Burnett, J C

1993-01-01

This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. Images PMID:8408658

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, P.; Stoff, J.S.; Solomon, R.J.

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 parallelmore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing

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:more » 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

Arterial stiffness, physical activity, and atrial natriuretic Peptide gene polymorphism in older subjects.

PubMed

Iemitsu, Motoyuki; Maeda, Seiji; Otsuki, Takeshi; Sugawara, Jun; Kuno, Shinya; Ajisaka, Ryuichi; Matsuda, Mitsuo

2008-04-01

An increase in arterial stiffness with advancing age is associated with several pathological states, including hypertension and arteriosclerosis. Regular exercise improves the aging-induced increase in arterial stiffness and has a protective effect against these diseases. However, not all individuals respond to exercise to the same extent. Atrial natriuretic peptide (ANP) is involved in the regulation of basal blood pressure, blood flow, and vascular tone. The present study was designed to clarify whether gene polymorphisms in ANP-related genes affect exercise-induced improvements in arterial stiffness. We performed a cross-sectional study of 291 healthy middle-aged and older Japanese subjects (63+/-1 years), examining the relationship between daily physical activity-induced improvements in arterial stiffness, estimated by brachial-ankle arterial pulse wave velocity (baPWV), and the gene polymorphisms of valine32methionine (V32M: 664G>A) in exon 1 of ANP and asparagine521aspartic acid (N521D: 1780A>G) in exon 8 of the ANP clearance receptor (NPR-C). The baseline baPWV was significantly lower in the active group, but no differences were seen in blood pressure. Active subjects with the ANP-VV genotype had significantly lower baPWV and higher plasma ANP levels compared with inactive subjects, but there were no variations related to the VM+MM genotype. Additionally, baPWV and plasma ANP levels were negatively correlated in ANP-VV genotype subjects, but were not correlated in VM+MM individuals. Our results suggest that ANP polymorphism in older Japanese subjects may affect the cardiovascular response to regular exercise.

The interaction of cadmium with atrial natriuretic factor: A study in in vivo and in vitro models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giridhar, J.

1990-01-01

The involvement of atrial natriuretic factor (ANF) and its receptor in cadmium(Cd)-induced cardiovascular alterations and neurotoxicity is not known. This study examines the mechanisms underlying Cd-induced changes in the ANF peptide and its receptor in cardiovascular toxicity. In rats on short term Cd exposure (0.01, 0.1, 0.5 and 1.0 mg/kg, i.p., twice a day for 7 days and a maintenance period of 30 days), atrial ANF levels decreased significantly in the Cd 1 mg/kg group; plasma ANF levels were unchanged. Hypothalamic ANF content decreased significantly in 0.1-1.0 mg/kg Cd groups. Plasma renin activity and concentration were unchanged by Cd treatment.more » However, plasma aldosterone was significantly decreased in Cd 1.0 mg/kg group. Binding of [sup 125]I-ANF to its receptors in kidney, adrenals and aorta was not significantly altered. Cd treatment decreased urine volume indicating nephrotoxicity. Neuromodulation by ANF involved significant decrease in K[sup +] stimulated [[sup 3]H]NE release in rat hypothalamic slices. This action is proposed to be mediated by ANF-B receptors. 8Br-cGMP mimicked this action. In Cd treated animals (0.5 mg/kg twice a day for 7 days and maintained for 30 days), ANF neuromodulation in the hypothalmus was blocked, even though Cd content was undetectable. Cd preincubated (0.5 mM) slices showed a 49.1% block in neurotransmitter release indicating that Cd may block calcium channels leading to decreased K[sup +]-stimulated release of [[sup 3]H]NE. Hence, Cd-induced cardiovascular toxicity and neurotoxicity may be partly mediated by alteration in the release and possibly the synthesis of ANF peptide, disruption of ANF function through alterations in receptor dynamics and possibly alteration in cellular calcium homeostasis and membrane integrity. Central ANF function is sensitive to Cd and this effect may be partly resposible for the cardiovascular and neurotoxic responses to CD.« less

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.

B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

PubMed Central

Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

2014-01-01

Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats.

PubMed

Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas A; Leighton, Emma V; Greenwood, Iain A

2015-03-01

The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations. © 2014 American Heart Association, Inc.

The secretions of oviduct epithelial cells increase the equine in vitro fertilization rate: are osteopontin, atrial natriuretic peptide A and oviductin involved?

PubMed

Mugnier, Sylvie; Kervella, Morgane; Douet, Cécile; Canepa, Sylvie; Pascal, Géraldine; Deleuze, Stefan; Duchamp, Guy; Monget, Philippe; Goudet, Ghylène

2009-11-19

Oviduct epithelial cells (OEC) co-culture promotes in vitro fertilization (IVF) in human, bovine and porcine species, but no data are available from equine species. Yet, despite numerous attempts, equine IVF rates remain low. Our first aim was to verify a beneficial effect of the OEC on equine IVF. In mammals, oviductal proteins have been shown to interact with gametes and play a role in fertilization. Thus, our second aim was to identify the proteins involved in fertilization in the horse. In the first experiment, we co-incubated fresh equine spermatozoa treated with calcium ionophore and in vitro matured equine oocytes with or without porcine OEC. We showed that the presence of OEC increases the IVF rates. In the subsequent experiments, we co-incubated equine gametes with OEC and we showed that the IVF rates were not significantly different between 1) gametes co-incubated with equine vs porcine OEC, 2) intact cumulus-oocyte complexes vs denuded oocytes, 3) OEC previously stimulated with human Chorionic Gonadotropin, Luteinizing Hormone and/or oestradiol vs non stimulated OEC, 4) in vivo vs in vitro matured oocytes. In order to identify the proteins responsible for the positive effect of OEC, we first searched for the presence of the genes encoding oviductin, osteopontin and atrial natriuretic peptide A (ANP A) in the equine genome. We showed that the genes coding for osteopontin and ANP A are present. But the one for oviductin either has become a pseudogene during evolution of horse genome or has been not well annotated in horse genome sequence. We then showed that osteopontin and ANP A proteins are present in the equine oviduct using a surface plasmon resonance biosensor, and we analyzed their expression during oestrus cycle by Western blot. Finally, we co-incubated equine gametes with or without purified osteopontin or synthesized ANP A. No significant effect of osteopontin or ANP A was observed, though osteopontin slightly increased the IVF rates. Our study

The secretions of oviduct epithelial cells increase the equine in vitro fertilization rate: are osteopontin, atrial natriuretic peptide A and oviductin involved?

PubMed Central

2009-01-01

Background Oviduct epithelial cells (OEC) co-culture promotes in vitro fertilization (IVF) in human, bovine and porcine species, but no data are available from equine species. Yet, despite numerous attempts, equine IVF rates remain low. Our first aim was to verify a beneficial effect of the OEC on equine IVF. In mammals, oviductal proteins have been shown to interact with gametes and play a role in fertilization. Thus, our second aim was to identify the proteins involved in fertilization in the horse. Methods & results In the first experiment, we co-incubated fresh equine spermatozoa treated with calcium ionophore and in vitro matured equine oocytes with or without porcine OEC. We showed that the presence of OEC increases the IVF rates. In the subsequent experiments, we co-incubated equine gametes with OEC and we showed that the IVF rates were not significantly different between 1) gametes co-incubated with equine vs porcine OEC, 2) intact cumulus-oocyte complexes vs denuded oocytes, 3) OEC previously stimulated with human Chorionic Gonadotropin, Luteinizing Hormone and/or oestradiol vs non stimulated OEC, 4) in vivo vs in vitro matured oocytes. In order to identify the proteins responsible for the positive effect of OEC, we first searched for the presence of the genes encoding oviductin, osteopontin and atrial natriuretic peptide A (ANP A) in the equine genome. We showed that the genes coding for osteopontin and ANP A are present. But the one for oviductin either has become a pseudogene during evolution of horse genome or has been not well annotated in horse genome sequence. We then showed that osteopontin and ANP A proteins are present in the equine oviduct using a surface plasmon resonance biosensor, and we analyzed their expression during oestrus cycle by Western blot. Finally, we co-incubated equine gametes with or without purified osteopontin or synthesized ANP A. No significant effect of osteopontin or ANP A was observed, though osteopontin slightly

Atrial natriuretic peptide for management of acute kidney injury: a systematic review and meta-analysis.

PubMed

Nigwekar, Sagar U; Navaneethan, Sankar D; Parikh, Chirag R; Hix, John K

2009-02-01

Randomized controlled trials (RCTs) with atrial natriuretic peptide (ANP) have shown inconsistent effects for renal end-points. The authors aimed to systematically review these trials to ascertain the benefit of ANP in prevention and treatment of acute kidney injury (AKI). The authors searched MEDLINE, EMBASE, and Cochrane Renal Health Library that investigated ANP in adult patients considered with or at risk for AKI. Outcomes were analyzed separately for prevention and treatment of AKI. Nineteen RCTs (11 prevention, 8 treatment) involving 1861 participants were included. Pooled analysis of prevention trials showed a trend toward reduction in renal replacement therapy in the ANP group (OR = 0.45, 95% CI, 0.21 to 0.99) and good safety profile, but no improvement in mortality. For the treatment of established AKI, ANP, particularly in high doses, was associated with a trend toward increased mortality and more adverse events. Subgroup analysis of AKI after a major surgery (14 RCTs, 817 participants) showed a significant reduction in renal replacement therapy requirement in the ANP group (OR = 0.49, 95% CI, 0.27 to 0.88). Included RCTs were mostly low- or moderate-quality, underpowered studies. There are an insufficient number of high-quality studies to make any definite statement about the role of ANP in AKI. Analysis of the existing literature suggests ANP might be associated with beneficial clinical effects when administered in patients undergoing major surgery such as cardiovascular surgery. Its use, in low doses, should be explored further in this setting.

Does atrial natriuretic factor protect against right ventricular overload II. Tissue binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ou, L.C.; Yen, S.; Sardella, G.L.

1989-10-01

Previous studies have led us to hypothesize that the physiological significance of the diuretic and pulmonary vaso-relaxant effects of atrial natriuretic factor (ANF) is to protect the right heart. This study was designed to evaluate the relative importance of various peripheral tissues as sites of ANF action by tracing the temporal pattern of distribution of {sup 125}I-ANF and quantitating the specific binding sites. An in vivo approach, utilizing trace amount of {sup 125}I-ANF was adopted to simulate physiological conditions. {sup 125}I-ANF injected either intravenously or intra-arterially was quickly bound to peripheral tissues with less than 5% remaining in the circulationmore » after 1 min. The relative binding capacity was greatest in the lung, followed by the kidney, right ventricle, adrenal gland, and left ventricle. The magnitude of specific ANF binding sites per gram of tissue weight followed a similar order. The data demonstrate that ANF released under all circumstances is quickly bound to the target organs, particularly the lung and the kidney, and suggest that these two organs could be the most important target organs of ANF. This evidence provides further support for the proposed hypothesis that a major evolutionary role of ANF is the protection of the right ventricle from mechanical loads.« less

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.

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Absence of C-type natriuretic peptide receptors in hamster glomeruli.

PubMed

Luk, J K; Wong, E F; Wong, N L

1994-01-01

The distribution of atrial natriuretic peptide receptor B (ANPR-B) varies between tissues and species. The aim of this study is to determine whether ANPR-B is present in the hamster glomeruli. In vitro C-type natriuretic peptide (CNP)- and atrial natriuretic factor (ANF)-stimulated cGMP accumulation studies were performed in hamster glomeruli. Elevated cGMP accumulations were observed upon ANF addition. No cGMP response was seen with CNP. Competitive receptor-binding experiments were performed with 125I-CNP and 125I-ANF against their respective cold peptides in hamster glomeruli. Although no CNP binding was detected, positive ANF binding was found and two types of ANF receptor were demonstrated. The affinity (Kdl) and maximum binding capacity (Bmaxl) of the high-affinity ANF receptor were 0.014 +/- 0.001 nM and 60.4 +/- 10.2 fmol/mg protein, respectively. Those of the low-affinity receptor (Kd2 and Bmax2) were 45.7 +/- 6.2 nM and 28.3 +/- 6.3 pmol/mg protein, respectively. Similarly, saturation binding experiments also failed to show any CNP receptor binding in hamster glomeruli. This finding suggests that ANPR-B is not present in hamster glomeruli and CNP is not a direct physiological regulator of hamster renal function.

Atrial natriuretic peptide administered just prior to reperfusion limits infarction in rabbit hearts.

PubMed

Yang, Xi-Ming; Philipp, Sebastian; Downey, James M; Cohen, Michael V

2006-07-01

We investigated whether atrial natriuretic peptide (ANP) given just prior to reperfusion reduces infarction in rabbit hearts and whether protection is related to activation of protein kinase G (PKG). Isolated rabbit hearts were subjected to a 30-min period of regional ischemia; treated hearts received a 20-min infusion of ANP (0.1 microM) starting 5 min before 2 h of reperfusion. ANP infusion decreased infarction from 31.5+/-2.4% of the risk zone in untreated hearts to 12.5+/-2.0% (P<0.001). To explore mechanisms of protection ischemic hearts were treated simultaneously with ANP and isatin, a blocker of the natriuretic peptide receptor, shortly before reperfusion. ANP's protective effect was aborted (36.8+/-2.9% infarction). There is no acceptable blocker of protein kinase G that can be used in intact organs. However, 8-(4-chlorophenylthio)-guanosine 3', 5'-cyclic monophosphate (10 microM), a cell-permeable cGMP analog that directly activates PKG, was infused from 5 min before to 15 min after reperfusion. The PKG activator mimicked ANP's protection with only 18.2+/-3.6% infarction (P<0.001). 5-Hydroxyde-canoate (5-HD), a putative mitochondrial KATP channel (mKATP) inhibitor, abrogated ANP's protection (34.4+/-2.6% infarction). Unexpectedly, 1H-[1,2,4]oxadiazole- [4,3-a]quinoxalin-1-one (ODQ), a blocker of soluble guanylyl cyclase also prevented ANP's infarct-sparing effect. It is unclear whether this observation implicated participation of soluble guanylyl cyclase in the mechanism or simply a lack of selectivity of ODQ. Finally the reperfusion injury salvage kinases (RISK), phosphatidylinositol 3-kinase and extracellular signal-regulated kinase, were implicated in ANP's mechanism since either wortmannin or PD98059 infused at reperfusion prevented ANP's infarct-sparing effect. ANP administered just prior to reperfusion protects hearts against infarction, likely by activation of PKG, opening of mKATP, and stimulation of downstream kinases.

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.

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.

N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

PubMed

Adjagba, Philippe M; Desjardins, Laurent; Fournier, Anne; Spigelblatt, Linda; Montigny, Martine; Dahdah, Nagib

2015-10-01

We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP

PubMed Central

Lisy, Ondrej; Huntley, Brenda K.; McCormick, Daniel J.; Kurlansky, Paul A.; Burnett, John C.

2008-01-01

Objectives Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Background Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Methods Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Results Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. Conclusions The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides. PMID:18582636

Design, synthesis, and actions of a novel chimeric natriuretic peptide: CD-NP.

PubMed

Lisy, Ondrej; Huntley, Brenda K; McCormick, Daniel J; Kurlansky, Paul A; Burnett, John C

2008-07-01

Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides.

Gene regulation of atrial natriuretic peptide A, B, and C receptors in rat glomeruli.

PubMed

Itoh, K; Nonoguchi, H; Shiraishi, N; Tomita, K

1999-01-01

Atrial natriuretic peptide (ANP) has three types of receptor. We investigated the gene regulation of three types of ANP receptors (ANPR-A, B, and C) in rat glomeruli using reverse transcription coupled with competitive polymerase chain reaction (PCR). Competitive PCR revealed that ANPR-C mRNA expression was most abundant (ANPR-C > A > B) in glomeruli from control rats among mRNA expressions of three receptors, which were 20- to 15,000-fold higher than those in inner medullary collecting ducts. Two days' dehydration caused reversible decreases of ANPR-A, B, and C mRNAs by 50-80%. To determine the mechanisms of down-regulation of mRNA expression, isolated glomeruli were incubated in isotonic or hypertonic solution. Hyperosmolality induced by NaCl, mannitol or raffinose caused significant increases of ANPR-A, B, and C mRNA expression. Hypertonicity by urea showed smaller effects. ANP stimulated the expression of ANPR-A, B, and C mRNA in vitro. These results indicate that dehydration caused reversible decreases of ANPR-A, B, and C mRNA expression in glomeruli, and these decreases were not caused by increased plasma osmolality but probably by lower circulating levels of ANP.

Regulation of atrial natriuretic peptide clearance receptors in mesangial cells by growth factors.

PubMed

Paul, R V; Wackym, P S; Budisavljevic, M; Everett, E; Norris, J S

1993-08-25

Rat mesangial cells can express both 130-kDa guanylyl cyclase-coupled and 66-kDa non-coupled atrial natriuretic peptide (ANP) receptors (ANPR-A and ANPR-C, respectively). Exposure of mesangial cells, grown in 20% fetal calf serum, to 0.1% serum for 24 h increased total ANP receptor density more than 2-fold (Bmax = 87 versus 37 fmol/mg of cell protein) without changing binding affinity (Kd = 94 versus 88 pM). Radioligand binding and cross-linking studies demonstrated that up-regulation of ANP binding after serum deprivation was entirely due to an increase in ANPR-C, with little or no change in ANPR-A. Inhibition of protein synthesis with cycloheximide blocked up-regulation after serum deprivation. Steady-state ANPR-C mRNA level was increased 15-fold by serum deprivation, as judged by Northern blotting. There was no change in ANPR-A mRNA. Platelet-derived growth factor and phorbol myristate acetate, when added to low serum medium, blocked or reversed the effect of serum deprivation on ANPR-C. We conclude that synthesis and expression of ANPR-C but not ANPR-A is suppressed by serum, platelet-derived growth factor, and phorbol myristate acetate. Suppression of ANPR-C in vivo could contribute to mesangial cell proliferative responses to growth factors.

Comparison of Pulmonary Venous and Left Atrial Remodeling in Patients With Atrial Fibrillation With Hypertrophic Cardiomyopathy Versus With Hypertensive Heart Disease.

PubMed

Yoshida, Kentaro; Hasebe, Hideyuki; Tsumagari, Yasuaki; Tsuneoka, Hidekazu; Ebine, Mari; Uehara, Yoshiko; Seo, Yoshihiro; Aonuma, Kazutaka; Takeyasu, Noriyuki

2017-04-15

Left ventricular diastolic dysfunction in hypertrophic cardiomyopathy (HC) increases susceptibility to atrial fibrillation. Although phenotypical characteristics of the hypertrophied left ventricle are clear, left atrial (LA) and pulmonary venous (PV) remodeling has rarely been investigated. This study aimed to identify differences in LA and PV remodeling between HC and hypertensive heart disease (HHD) using 3-dimensional computed tomography. Included were 33 consecutive patients with HC, 25 with HHD, and 29 without any co-morbidities who were referred for catheter ablation of atrial fibrillation. Pre-ablation plasma atrial and brain natriuretic peptide levels, post-ablation troponin T level, and LA pressure were measured, and LA and PV diameters were determined 3 dimensionally. LA transverse diameter in the control group was smaller than that in the HHD or HC group (55 ± 6 vs 63 ± 9 vs 65 ± 12 mm, p = 0.0003). PV diameter in all 4 PVs was greatest in the HC group and second greatest in the HHD group (21.0 ± 3.1 vs 23.8 ± 2.8 vs 26.8 ± 4.1 mm, p <0.0001 for left superior PV). Differences in PV size between the HHD and HC groups were enhanced by indexing to the body surface area (12.4 ± 1.9 vs 13.1 ± 1.4 vs 16.1 ± 3.3 mm/m 2 , p <0.0001). The PV/LA diameter ratio was greater in the HC than in the other groups (0.38 ± 0.06 vs 0.38 ± 0.05 vs 0.42 ± 0.07, p = 0.01). Atrial natriuretic peptide, brain natriuretic peptide, troponin T levels, and LA pressure were highest in the HC group (all p <0.05). In conclusion, the stiff LA caused from atrial hypertrophy may account for higher levels of biomarkers, higher LA pressure, and PV-dominant remodeling in HC. Copyright © 2017 Elsevier Inc. All rights reserved.

[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.

Carperitide and atrial fibrillation after coronary bypass grafting: the Nihon University working group study of low-dose HANP infusion therapy during cardiac surgery trial for postoperative atrial fibrillation.

PubMed

Sezai, Akira; Iida, Mitsuru; Yoshitake, Isamu; Wakui, Shinji; Osaka, Shunji; Kimura, Haruka; Yaoita, Hiroko; Hata, Hiroaki; Shiono, Motomi; Nakai, Toshiko; Takayama, Tadateru; Kunimoto, Satoshi; Kasamaki, Yuji; Hirayama, Atsushi

2015-06-01

Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group (P<0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid-binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of β-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. -Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing postoperative atrial fibrillation. -URL: http://www.umin.ac.jp. Unique Identifier: UMIN000003958. © 2015 American Heart Association, Inc.

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

PubMed Central

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

2011-01-01

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

Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

PubMed Central

Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

1990-01-01

1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

Cardiac distribution of the binding sites for natriuretic peptides in vertebrates.

PubMed

Cerra, M C

1994-12-01

Natriuretic peptides are hormones that play an important role in the cardiovascular control of mammalian and non-mammalian vertebrates. They have been classified into four groups. Of these, ANP (atrial natriuretic peptide), BNP (brain atriuretic peptides), CNP (C-type natriuretic peptide) are detected in cardiac and non cardiac tissues of all vertebrates; while VNP (ventricular natriuretic peptide) has been isolated only from the fish ventricle. All peptides have shown a high degree of sequence homology. The expression of the three principal types of natriuretic peptide (ANP, BNP and CNP) in cardiac tissues is developmentally and functionally regulated in a highly tissue-specific manner. Three types of natriuretic peptide receptors have been identified in numerous target tissues. Two receptors are transmembrane guanylyl cyclases (ANPR-A and ANPR-B) that mediate biological effects of natriuretic peptides; the third one (ANPR-C) has no guanylyl cyclase and is called "clearance receptor." The presence of natriuretic peptide binding sites in the heart suggests new aspects of paracrine control of cardiac function. A relevant localization of natriuretic peptide receptors was found in those cardiac regions particularly suitable for monitoring blood volume and pressure oscillations such as the inflow tract and the outflow tract. For example, in birds (quail) the highest levels of natriuretic peptide receptors were detected in the inflow tract represented by the vena cava. In both fish and birds, the outflow chamber, the bulbus cordis, had a high number of natriuretic peptide binding sites. In mammals, a remarkable concentration of natriuretic peptide receptors was also observed in the coronary vessels. This zoning of cardiac natriuretic peptide receptors indicates an intracardiac action of the hormones and adds a humoral dimension to the morphofunctional design of the vertebrate heart.

Atrial natriuretic factor in two kidney--two clip renovascular hypertension in the rat.

PubMed

Puyo, A M; Vega, G W; Pellegrino de Iraldi, A; Albornoz, L E; Rosón, M I; Scaglia, P; Celentano, M M; Corazza, J P; Palumbo, E L; Fernández, B E; de la Riva, I J

1998-01-01

Hig levels of circulating atrial natriuretic factor (ANF) have been reported in several physiopathologic conditions like hypertension, heart and renal failure, pregnancy and high sodium intake. Nevertheless, neither relationships with water-sodium space regulation nor the role of an ANF vascular relaxant effect have been yet defined. The aim of present experiments was to characterize the contribution of circulating ANF and its vascular relaxing effects in the two kidney-two clip (2K2C) experimental model of renovascular hypertension. Complementary, plasma metabolites nitrite/nitrate of nitric oxide (NO) was examined because of mediation for both (NO an ANF) through cGMP. Three results showed (two-four weeks after surgery): indirect systolic blood pressure (mmHg), 186 +/- 4 in HT and 122 +/- 1 in SH (p < 0.001); a significant increase of plasma ANF (fmol/ml) in HT (n = 7, 1221 +/- 253) vs. SH (n = 9, 476 +/- 82; p < 0.02). Nitrate/nitrite plasma concentrations (mumol/l) were mpt different between SH and. The relaxant effect of ANF (10(-9), 10(-8) and 10(-7) M) on phenylephrine (3,5 x 10(-6) M) contracted rings from HT rats was smaller than SH rats (10(-8) M, p < 0.05). Contractions to phorbol 12, 13-dibutyrate (seven weeks after surgery) were significantly higher in rings from HT rats (p < 0.001). We conclude: 1) in addition to decreased granularity in atrial myocardiocytes, high circulating values of ANF here described suggest an increased turnover of the peptide in 2K2C hypertensive rats; 2) lower significant vascular relaxant effects in HT rats would indicate down regulation of ANF receptors in this model; the latter would derive from high plasma ANF concentration and, tentatively, because of greater activity of protein kinase C in the vascular wall; 39 similar values of plasma nitrite/nitrate in SH and HT rats would indicate a comparable NO circulating availability in both groups.

Dwarfism and early death in mice lacking C-type natriuretic peptide

PubMed Central

Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

2001-01-01

Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 levelsmore » 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.« less

Identification and quantification of human kidney atrial natriuretic peptide receptors.

PubMed

Kahana, L; Yechiely, H; Mecz, Y; Lurie, A

1995-04-01

The present study determined 125I-label atrial natriuretic peptide (ANP) binding sites in human kidney glomerular and papillary membranes. The membranes were prepared from non-malignant renal tissue obtained at nephrectomy of patients with renal carcinoma. To evaluate the proportion of ANP receptor classes ANP-R1 (ANPR-A, -B) versus ANP-R2 (ANPR-C), competitive binding studies were performed using [125I]-ANP in the presence of increasing concentrations of ANP or an internally ring-deleted analog, des(Gln116, Ser117, Gly118, Leu119, Gly120)ANP(102-121), called C-ANP, which binds selectively to ANPR-C receptors. Analysis of the competitive binding curve with ANP in glomerular membranes suggested the presence of one group of high-affinity receptors with dissociation constant Kd = 26 +/- 12 pmol/l and density Bmax = 101 +/- 47 nmol/kg protein. A decrease of 10-30% in Bmax with no change in Kd was obtained in the presence of excess (10(-6) mol/l) C-ANP, suggesting the existence of a small amount of a second class of receptors, the ANPR-C class. The densities of ANPR-A, -B versus ANPR-C receptors in human glomeruli, calculated from competitive inhibition experiments, were 75 +/- 42 and 22 +/- 16 nmol/kg protein (N = 8). Autoradiography of the sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions showed two bands: a highly labeled 130kD band and a weakly labeled 66 kD band, both displaced by ANP. Only the 66-kD band was displaced by the C-ANP analog. Human papilla membrane, as shown by competition binding studies and SDS gel electrophoresis, presented only one class of receptors with Kd = 40 +/- 23 pmol/l (mean +/- SD, N = 3) and Bmax = 17 +/- 6.3 nmol/kg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).

PubMed

Hijazi, Ziad; Wallentin, Lars; Siegbahn, Agneta; Andersson, Ulrika; Christersson, Christina; Ezekowitz, Justin; Gersh, Bernard J; Hanna, Michael; Hohnloser, Stefan; Horowitz, John; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Granger, Christopher B

2013-06-04

This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984). Copyright �

Brain Natriuretic Peptide Is a Powerful Predictor of Outcome in Stroke Patients with Atrial Fibrillation

PubMed Central

Maruyama, Kenji; Uchiyama, Shinichiro; Shiga, Tsuyoshi; Iijima, Mutsumi; Ishizuka, Kentaro; Hoshino, Takao; Kitagawa, Kazuo

2017-01-01

Background Since stroke patients with nonvalvular atrial fibrillation (NVAF) have poor outcomes in general, the prediction of outcomes following discharge is of utmost concern for these patients. We previously reported that brain natriuretic peptide (BNP) levels were significantly higher in NVAF patients with larger infarcts, higher modified Rankin Scale (mRS) score, and higher CHADS2 score. In the present study, we evaluated an array of variables, including BNP, in order to determine significant predictors for functional outcome in patients with NVAF after acute ischemic stroke (AIS). Methods A total of 615 consecutive patients with AIS within 48 h of symptom onset, admitted to our hospital between April 2010 and October 2015, were retrospectively searched. Among these patients, we enrolled consecutive patients with NVAF. We evaluated the mRS score 3 months after onset of stroke and investigated associations between mRS score and the following clinical and echocardiographic variables. Categorical variables included male sex, current smoking, alcohol intake, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease, peripheral artery disease, use of antiplatelet drugs, anticoagulants, or tissue plasminogen activator (tPA), and infarct size. Continuous variables included age, systolic blood pressure (SBP), diastolic blood pressure, hemoglobin, creatinine, D-dimer, brain natriuretic peptide (BNP), left atrial diameter, left ventricular ejection fraction (EF), and early mitral inflow velocity/diastolic mitral annular velocity (E/e’). We also analyzed the association of prestroke CHADS2, CHA2DS2-VASc, and R2CHADS2 scores, and National Institutes of Health Stroke Scale (NIHSS) score on admission with mRS score 3 months after the onset of stroke. Patients were classified into 2 groups according to mRS score: an mRS score ≤2 was defined as good outcome, an mRS score ≥3 was defined as poor outcome. To clarify the correlations between categorical or

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. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

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

PubMed

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

2012-01-01

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

Culture on electrospun polyurethane scaffolds decreases atrial natriuretic peptide expression by cardiomyocytes in vitro.

PubMed

Rockwood, Danielle N; Akins, Robert E; Parrag, Ian C; Woodhouse, Kimberly A; Rabolt, John F

2008-12-01

The function of the mammalian heart depends on the functional alignment of cardiomyocytes, and controlling cell alignment is an important consideration in biomaterial design for cardiac tissue engineering and research. The physical cues that guide functional cell alignment in vitro and the impact of substrate-imposed alignment on cell phenotype, however, are only partially understood. In this report, primary cardiac ventricular cells were grown on electrospun, biodegradable polyurethane (ES-PU) with either aligned or unaligned microfibers. ES-PU scaffolds supported high-density cultures and cell subpopulations remained intact over two weeks in culture. ES-PU cultures contained electrically-coupled cardiomyocytes with connexin-43 localized to points of cell:cell contact. Multi-cellular organization correlated with microfiber orientation and aligned materials yielded highly oriented cardiomyocyte groupings. Atrial natriuretic peptide, a molecular marker that shows decreasing expression during ventricular cell maturation, was significantly lower in cultures grown on ES-PU scaffolds than in those grown on tissue culture polystyrene. Cells grown on aligned ES-PU had significantly lower steady state levels of ANP and constitutively released less ANP over time indicating that scaffold-imposed cell organization resulted in a shift in cell phenotype to a more mature state. We conclude that the physical organization of microfibers in ES-PU scaffolds impacts both multi-cellular architecture and cardiac cell phenotype in vitro.

Physiologic regulation of atrial natriuretic peptide receptors in rat renal glomeruli.

PubMed Central

Ballermann, B J; Hoover, R L; Karnovsky, M J; Brenner, B M

1985-01-01

Isolated rat renal glomeruli and cultured glomerular mesangial and epithelial cells were examined for atrial natriuretic peptide (ANP) receptors, and for ANP-stimulated cyclic guanosine monophosphate (cGMP) generation. In glomeruli from normal rats, human (1-28) 125I-ANP bound to a single population of high affinity receptors with a mean equilibrium dissociation constant of 0.46 nM. Human (1-28) ANP markedly stimulated cGMP generation, but not cAMP generation in normal rat glomeruli. Analogues of ANP that bound to the glomerular ANP receptor with high affinity stimulated cGMP accumulation, whereas the (13-28) ANP fragment, which failed to bind to the receptor, was devoid of functional activity. Cell surface receptors for ANP were expressed on cultured glomerular mesangial but not epithelial cells, and appreciable ANP-stimulated cGMP accumulation was elicited only in mesangial cells. Approximately 12,000 ANP receptor sites were present per mesangial cell, with an average value for the equilibrium dissociation constant of 0.22 nM. Feeding of a low-salt diet to rats for 2 wk resulted in marked up regulation of the glomerular ANP receptor density to a mean of 426 fmol/mg protein, compared with 116 fmol/mg in rats given a high-salt diet. A modest reduction in the affinity of glomerular ANP receptors was also observed in rats fed the low-salt diet. ANP-stimulated cGMP generation in glomeruli did not change with alterations in salt intake. We conclude that high salt feeding in the rat results in reduced glomerular ANP receptor density relative to values in salt restricted rats. Furthermore, the mesangial cell is a principal target for ANP binding in the glomerulus. Images PMID:3001139

Global left atrial failure in heart failure.

PubMed

Triposkiadis, Filippos; Pieske, Burkert; Butler, Javed; Parissis, John; Giamouzis, Gregory; Skoularigis, John; Brutsaert, Dirk; Boudoulas, Harisios

2016-11-01

The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure [deficient atrial natriuretic peptide (ANP) processing-synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

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. Copyright © 2014 the American Physiological Society.

Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides.

PubMed

Nishikimi, Toshio; Kuwahara, Koichiro; Nakao, Kazuwa

2011-03-01

The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Characterization and distribution of natriuretic peptide receptors in the rat uterus.

PubMed

Dos Reis, A M; Fujio, N; Dam, T V; Mukaddam-Daher, S; Jankowski, M; Tremblay, J; Gutkowska, J

1995-10-01

Atrial natriuretic peptide (ANP) receptors were characterized in rat uterus. The binding of [125I]ANP to uterine membranes was completely competed for by increasing concentrations of unlabeled ANP (Kd = 0.39 nM) and brain natriuretic peptide (Kd = 1.24 nM) and partially by C-type natriuretic peptide (CNP; Kd = 80.4 nM), but not by C-ANF. Also, [125I]Tyr-CNP bound to uterine membranes was completely competed by unlabeled CNP (Kd = 1.12 nM). Cross-linking of [125I]ANP to uterine membranes revealed the presence of one band of 130 kilodaltons, corresponding to the guanylyl cyclase (GC-A and/or GC-B) subtypes of natriuretic peptide receptors. The presence of messenger RNA coding for genes of both GC-A and GC-B receptors was shown by quantitative reverse transcriptase polymerase chain reaction. Furthermore, ANP and, to a lesser degree, CNP stimulated the production of cGMP in rat uterus. Autoradiographic studies localized the highest binding of [125I]ANP in the endometrium, whereas [125I]Tyr-CNP binding was distributed in the endometrium as well as in the myometrium. These results demonstrate that rat uterine ANP receptors are of the guanylyl cyclase-coupled subtypes. The uterus is a target of natriuretic peptides where ANP induces its biological effects through the production of cGMP.

Mechanisms underlying chemoreceptor inhibition induced by atrial natriuretic peptide in rabbit carotid body.

PubMed Central

Wang, W J; He, L; Chen, J; Dinger, B; Fidone, S

1993-01-01

1. Previous studies in our laboratory revealed the presence of atrial natriuretic peptide (ANP) in preneural chemosensory type I cells of the cat carotid body, and demonstrated that submicromolar concentrations of the peptide inhibited carotid sinus nerve (CSN) activity evoked by hypoxia. In the present study, we have evaluated the role of the cyclic nucleotide second messenger, cyclic GMP (cGMP), and the involvement of type I cells in rabbit chemosensory inhibition. 2. Submicromolar concentrations of the potent ANP analogue, APIII, greatly elevated both the content and release of cGMP from the carotid body. Denervation experiments confirmed earlier immunocytochemical studies which suggested that APIII-induced cGMP production occurs almost exclusively in type I cells; these experiments also indicate that both the sympathetic and sensory innervation to the carotid body exert a trophic influence on the metabolism of this second messenger. 3. Submicromolar concentrations of APIII inhibited the CSN activity evoked by hypoxia (79.8 +/- 3.2% (mean +/- S.E.M.) inhibition with 100 nM APIII) and nicotine (74.5 +/- 3.6% inhibition with 100 nM APIII), but did not affect basal CSN activity established in 100% O2-equilibrated superfusion solutions. 4. The biologically inactive analogue of ANP, C-ANP, failed to produce CSN inhibition; however, the inhibitory effects of APIII were mimicked by cell-permeant analogues of cGMP (dibutyryl-cGMP and 8-bromo-cGMP, 2 mM), which likewise did not alter basal CSN activity. Because we found that unmodified cGMP was an ineffective inhibitor of CSN activity, our data suggest that APIII inhibition is mediated intracellularly by cGMP produced within the type I cells. 5. APIII does not inhibit the CSN activity produced by 20 mM K+ (in zero Ca2+ media), which very probably results from direct depolarization of the sensory nerve terminals. 6. Catecholamine release from the carotid body evoked by hypoxia is likewise not altered by APIII (100 nM). 7

[Changes of right atrial myoendocrine cells during hypertension and after arterial pressure decrease].

PubMed

Maksimov, V F; Korostyshevskaia, I M; Kurganov, S A; Markel', A L; Rudenko, N S; Iakobson, G S

2014-01-01

It is well known now that atrial cardiomyocytes carry out both contractile and endocrine activities--they synthesize, accumulate in specific secretory granules and release the natriuretic peptides. The main physiological effects of natriuretic peptides are antagonistic to the renin-angiotensin-aldostrol system, but their role in the development of hypertension is still disputable. The aim of this investigation is to estimate using electron microscopy the secretory activities of atrial myoendocrine cells in rats with inherited stress-induced arterial hypertension (ISIAH stain). It has been shown that myoendocrine cells in the ISIAH rats with arterial pressure about 180 mm Hg reveal morphological features of increased synthesis, extra accumulation and release of natriuretic peptides compared with normotensive control rats. In the ISIAH rats treated with losartan (angiotensin II receptor blocker) and therefore having a sustained decrease in arterial pressure to 140 mm Hg, changes in granular pool composition, reduction of the number and diameter of the secretory granules, reduction of Golgi complexes, and increased intracellular degradation of secretory stores were found in the myoendocrine cells. At the same time the marked capillary hyperemia and interstitial edema in the myocardium were observed. Thus, in rats with severe inherited hypertension, the secretory activity of heart myoendocrine cells is sharply increased and directly depends on the arterial blood pressure level. This proves that natriuretic peptides actively participate in the regulation of hemodynamics during with cardiovascular pathology.

Serum levels of natriuretic peptides in children with various types of loading conditions.

PubMed

Eerola, Anneli; Jokinen, Eero; Pihkala, Jaana I

2009-06-01

To evaluate the influence of volume overload of the left (LV) and right ventricle (RV) and pressure overload of LV and restrictive physiology on levels of N-terminal proatriopeptide (ANPN) and N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied 41 children with atrial septal defect (ASD), 35 with patent ductus arteriosus (PDA), 27 with coarctation of the aorta (CoA), 25 with restrictive physiology caused by Mulibrey nanism, and 64 control children. We measured serum concentrations of natriuretic peptides and evaluated ventricular size and function with echocardiography. In patients with ASD, PDA, and Mulibrey nanism, levels of both ANPN and NT-proBNP were higher than in controls but in children with CoA, only ANPN levels were higher. ANPN levels correlated with RV size in ASD and NT-proBNP levels with LV size in PDA. In patients with restriction, NT-proBNP levels correlated negatively with LV size. Correlation between echo measurements and levels of natriuretic peptides varied according to loading condition. Measurement of natriuretic peptide levels provides a supplemental method for non-invasive haemodynamic evaluation of children's heart disease.

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

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

PubMed

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

1992-11-23

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% of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41% 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.

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.

Atrial natriuretic peptide regulation of noradrenaline release in the anterior hypothalamic area of spontaneously hypertensive rats.

PubMed Central

Peng, N; Oparil, S; Meng, Q C; Wyss, J M

1996-01-01

In spontaneously hypertensive rats (SHR), high NaCl diets increase arterial pressure and sympathetic nervous system activity by decreasing noradrenaline release in the anterior hypothalamic area (AHA), thereby reducing the activation of sympathoinhibitory neurons in AHA. Atrial natriuretic peptide (ANP) can inhibit the release of noradrenaline, and ANP concentration is elevated in the AHA of SHR. The present study tests the hypothesis that in SHR, local ANP inhibits noradrenaline release from nerve terminals in AHA. Male SHR fed a basal or high NaCl diet for 2 wk and normotensive Wistar Kyoto rats (WKY) fed a basal NaCl diet were studied. In SHR on the basal diet, microperfusion of exogenous ANP into the AHA elicited a dose-related decrease in the concentration of the major noradrenaline metabolite 3-methoxy-4-hydroxy-phenylglycol (MOPEG) in the AHA; this effect was attenuated in the other two groups. In a subsequent study, the ANP-C (clearance) receptor agonist c-ANP was microperfused into the AHA to increase extracellular concentration of endogenous ANP in AHA. c-ANP reduced AHA MOPEG concentration in SHR on the basal NaCl diet but not in the other two groups. These data support the hypothesis that local ANP inhibits noradrenaline release in the AHA and thereby contributes to NaCl-sensitive hypertension in SHR. PMID:8903325

Comparison of Plasma Levels of Renin, Vasopressin and Atrial Natriuretic Peptide in Hypertensive Amlodipine Induced Pedal Oedema, Non-Oedema and Cilnidipine Treated Patients

PubMed Central

Shetty, Kiran; Rao, Pragna; Ballal, Mamatha; Kiran, Amruth; Reddy, Sravan; Pai, Umesh; Samanth, Jyothi

2017-01-01

Introduction Amlodipine is a third generation dihydropyridine group of calcium channel blocker and having an excellent antihypertensive profile. Pedal Oedema (PE) is the major drawback of amlodipine therapy and the incidence of Amlodipine Induced Pedal Oedema (AIPE) has been found significantly high. Several neurohumoral factors influence the incidence of oedema. Aim We aimed to compare the plasma levels of renin, vasopressin and atrial natriuretic peptide in hypertensive AIPE, non-oedema and cilnidipine treated patients. Materials and Methods The present prospective, interventional study was conducted on 104 mild to moderate hypertensive patients (52 patients in each group), after due consideration of eligibility criteria. Plasma Renin (PR), Vasopressin (VAS), and the Atrial Natriuretic Peptide (ANP) was estimated by ELISA test and compared between the AIPE, Amlodipine Treated Non-Oedema (ATNE) in Phase I, and AIPE and Cilnidipine Treated (CT) Groups in Phase II. Results The clinical and demographic parameters were matched. PR was significantly high in AIPE group than the ATNE, and it was significantly reduced after one month follow up with the substitution of cilnidipine. The median (IQR) value of PR was 4.87 (3.58, 6.63), 3.50 (1.44, 5.47) and 2.66 (1.02, 5.66) ng/ml in AIPE, ATNE, CT group respectively. VAS was significantly high in AIPE group than ATNE, and it significantly reduced after one month follow up with CT group. The median (IQR) value of vasopressin was 6.78 (2.55, 9.16), 2.58 (1.61, 5.73) and 2.50 (1.23, 5.00) ng/ml in AIPE, ATNE and CT groups respectively. There was no significant difference seen in plasma ANP levels between the groups. The p-value was <0.05 which is statistically significant. Conclusion The AIPE may not be volume overload or fluid retention; it may be due to persistent raise in adrenergic activity followed chronic amlodipine therapy. Cilnidipine relatively suppresses the sympathetic activity, and completely resolves the AIPE by

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)). Copyright © 2012 Elsevier Ltd. All rights reserved.

Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary.

PubMed

Pereira, Virginia M; Honorato-Sampaio, Kinulpe; Martins, Almir S; Reis, Fernando M; Reis, Adelina M

2014-10-01

Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries. Copyright © 2014 Elsevier Inc. All rights reserved.

Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness.

PubMed

Ge, R L; Shai, H R; Takeoka, M; Hanaoka, M; Koizumi, T; Matsuzawa, Y; Kubo, K; Kobayashi, T

2001-01-01

Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood. We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years. A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P < .01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects. These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

The three subtypes of atrial natriuretic peptide (ANP) receptors are expressed in the rat adrenal gland.

PubMed

Grandclément, B; Ronsin, B; Morel, G

1997-03-01

Atrial natriuretic peptide (ANP) actions are mediated by highly selective and specific receptors. Three subtypes have been characterized and cloned: ANP receptor-A (or GC-A), -B (or GC-B) and -C (the so-called clearance receptor). In rat adrenal gland, the mRNA for each subtype was detected using 35S-dUTP or digoxigenin-11-dUTP specific labeled probes, and in situ hybridization at light and electron microscopic levels respectively. The three subtypes were expressed the most abundantly in the zona glomerulosa. The amount of GC-A mRNA expression, quantified using macro-autoradiography and densitometry, was higher than the amounts of GC-B mRNA and ANPR-C mRNA both in zona glomerulosa and medullary of adrenal gland. At electron microscopic level, the three subtypes of ANPR were revealed in glomerulosa cells. A noticeable signal was also present in the medullary area, especially for GC-A mRNA, in adrenaline-containing chromaffin cells. No signal was detected in noradrenaline-containing chromaffin cells. The subcellular localization of the three mRNAs is similar: in the cytoplasmic matrix and in the euchromatin of the nucleus in each cell of glomerulosa, and in the same compartments of the adrenaline-containing chromaffin cells. These data indicate that the adrenal gland is an important target tissue for ANP action both in glomerulosa cells and adrenaline-containing chromaffin cells. The mRNA expression levels were different for each ANPR subtype.

Increased cyclic guanosine monophosphate production and overexpression of atrial natriuretic peptide A-receptor mRNA in spontaneously hypertensive rats.

PubMed

Tremblay, J; Huot, C; Willenbrock, R C; Bayard, F; Gossard, F; Fujio, N; Koch, C; Kuchel, O; Debinski, W; Hamet, P

1993-11-01

Atrial natriuretic peptide (ANP) specifically stimulates particulate guanylate cyclase, and cyclic guanosine monophosphate (cGMP) has been recognized as its second messenger. Spontaneously hypertensive rats (SHR) have elevated plasma ANP levels, but manifest an exaggerated natriuretic and diuretic response to exogenous ANP when compared to normotensive strains. In isolated glomeruli, the maximal cGMP response to ANP corresponds to a 12- to 14-fold increase over basal levels in normotensive strains (Wistar 13 +/- 2; Wistar-Kyoto 12 +/- 2; Sprague-Dawley 14 +/- 2) while a maximal 33 +/- 3-fold elevation occurs in SHR (P < 0.001). This hyperresponsiveness of cGMP is reproducible in intact glomeruli from SHR from various commercial sources. Furthermore, this abnormality develops early in life, even before hypertension is clearly established, and persists despite pharmacological modulation of blood pressure, indicating that it is a primary event in hypertension. In vitro studies have revealed a higher particulate guanylate cyclase activity in membranes from glomeruli and other tissues from SHR. This increase is not accounted for by different patterns of ANP binding to its receptor subtypes between normotensive and hypertensive strains, as assessed by competitive displacement with C-ANP102-121, an analog which selectively binds to one ANP receptor subtype. The hyperactivity of particulate guanylate cyclase in SHR and its behavior under basal, ligand (ANP), and detergent-enhanced conditions could be attributed either to increased expression or augmented sensitivity of the enzyme. Radiation-inactivation analysis does not evoke a disturbance in the size of regulatory elements normally repressing enzymatic activity, while the expression of particulate guanylate cyclase gene using mutated standard of A- and B-receptors partial cDNAs, quantified by polymerase chain reaction (PCR) transcript titration assay, manifests a selective increase of one guanylate cyclase subtype. Our

Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

PubMed

Wallentin, Lars; Hijazi, Ziad; Andersson, Ulrika; Alexander, John H; De Caterina, Raffaele; Hanna, Michael; Horowitz, John D; Hylek, Elaine M; Lopes, Renato D; Asberg, Signild; Granger, Christopher B; Siegbahn, Agneta

2014-11-18

Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients. Efficacy and safety outcomes during 1.9 years of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977-2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P<0.001); of major bleeding, from 1.22% to 4.53% (P<0.001); and of mortality, from 1.34% to 7.19% (P<0.001) in the lowest compared with the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, whereas the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality, and bleeding, regardless of GDF-15 levels. GDF-15 is a risk factor for major bleeding, mortality, and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of N-terminal pro-brain natriuretic peptide and high-sensitivity troponin I. http://www.clinicaltrials.gov. Unique identifier

Left atrial appendage resection can be performed minimally invasively with good clinical and echocardiographic outcomes without any severe risk.

PubMed

Inoue, Takafumi; Suematsu, Yoshihiro

2018-01-22

The adverse effects of left atrial appendage (LAA) closure have not yet been evaluated. This study aimed to prove the safety and low invasiveness of LAA resection through our thoracoscopic stand-alone left atrial appendectomy experience. Eighty-seven patients [mean age 68 ± 9 years, 68 men (78%), mean congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack to thromboembolism, vascular disease, age 65-74 years and sex category (CHA2DS2-VASc) score 2.9 ± 1.6 points] who had undergone thoracoscopic left atrial appendectomy were selected. The operative and clinical data (left atrial diameter, left ventricular diameter of systole/diastole, ejection fraction, brain natriuretic peptide and human atrial natriuretic peptide) were evaluated. All procedures were performed without cardiopulmonary bypass or cardiac arrest. The LAA was resected with an endoscopic linear cutter device. Except for 1 case with severe pleural adhesion, all operations were performed thoracoscopically. The preoperative and postoperative data are as follows: left atrial diameter 43 ± 5 mm and 43 ± 5 mm (P = 0.8); left ventricular diameter of systole/diastole 50 ± 5/35 ± 6 mm and 48 ± 5/34 ± 6 mm (P < 0.01); ejection fraction 57 ± 10% and 56 ± 10% (P = 0.11); brain natriuretic peptide 97 ± 77 pg/ml and 72 ± 65 pg/ml (P < 0.01) and human atrial natriuretic peptide 73 ± 64 pg/ml and 96 ± 67 pg/ml (P = 0.03), respectively. The mean volume of bleeding in the operation was very small (<10 ml). The mean length of postoperative in-hospital stay was 3.8 ± 1.8 days. All the patients were discharged while maintaining their preoperative activities of daily living without major complications. No thrombus or residual stumps were detected during the 3-month postoperative computed tomography follow-up. The perioperative heart

Comparison of the clinical utility of atrial and B type natriuretic peptide measurement for the diagnosis of systolic dysfunction in a low‐risk population

PubMed Central

Galasko, Gavin; Collinson, Paul O; Barnes, Sophie C; Gaze, David; Lahiri, Arjivit; Senior, Roxy

2007-01-01

Background Measurement of B type natriuretic peptide and its N terminal prohormone (NTproBNP) can now be performed routinely by automated high‐throughput immunoassays. The study compared measurement of NTproBNP with measurement of N terminal pro‐atrial natriuretic peptide (NTproANP) for detection of ventricular systolic dysfunction in primary care. Methods 734 subjects aged >45 years (349 men and 385 women, median age 58 years, range 45–89, interquartile range 51–67 years) from seven representative general practices attended for echocardiography with determination of ejection fraction and completed a questionnaire. Blood samples were collected into gel serum separation tubes (Becton–Dickinson, Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen at −70°C until analyses. Samples were analysed for NTproBNP (Roche Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2–2.4%) and for NTproANP (Biomedica, Vienna, Austria; CV 5.6–10.1%). Echocardiography was used as the diagnostic “gold standard”, with ventricular systolic dysfunction defined as abnormal when there was an ejection fraction of ⩽40%. Patients were dichotomised by ejection fraction from 50% to 30%, and receiver operating characteristic curves constructed and the area under the curve (AUC) compared. Results At 40% ejection fraction, NTproANP and NTproBNP showed AUCs of, respectively, 0.738 (0.601–0.875) and 0.973 (0.958–0.989), p<0.004. Conclusion NTproBNP is superior to NTproANP for detection of systolic dysfunction. PMID:17513518

A randomized study of the effects of exercise training on patients with atrial fibrillation.

PubMed

Osbak, Philip Samuel; Mourier, Malene; Kjaer, Andreas; Henriksen, Jens Henrik; Kofoed, Klaus Fuglsang; Jensen, Gorm Boje

2011-12-01

Exercise training is beneficial in ischemic and congestive heart disease. However, the effect on atrial fibrillation (AF) is unknown. Forty-nine patients with permanent AF (age [mean ± SD], 70.2 ± 7.8 years; male-to-female ratio, 0.75; body mass index [mean ± SD], 29.7 ± 4.3 kg/m(2)) were randomized to 12-week aerobic exercise training or a control group. Exercise capacity, 6-minute walk test (6MWT), cardiac output, quality of life, and natriuretic peptides were measured. Cardiac output was measured at rest and during ergometer testing, and atrial natriuretic peptide and N-terminal pro-B-type natriuretic peptide were measured before and after the training period. Quality of life was evaluated using the Short-Form 36 and Minnesota Living With Heart Failure (MLHF-Q) questionnaires. Improved exercise capacity and 6MWT were observed in the active patients (P < .001), and at study end, there was a significant difference between the active patients and the controls (P = .002). Resting pulse decreased in the active patients (94.8 ± 22.4 to 86.3 ± 22.5 beats/min, P = .049) but remained unchanged in the controls. Cardiac output was unchanged from baseline to end-of-study period. The MLHF-Q score improved in the active group (21.1 ± 18.0 vs 15.4 ± 17.5, P = .03). Active patients showed progress in 3 of the 8 Short-Form 36 subscales: physical functioning (P = .02), general health perceptions (P = .001), and vitality (P = .02). Natriuretic peptides were unchanged. Twelve weeks of exercise training increased exercise capacity and 6MWT and decreased resting pulse rate significantly in patients with AF. Overall quality of life increased significantly as measured by the cardiology-related MLHF-Q. Cardiac output and natriuretic peptides were unchanged in both groups. Copyright © 2011 Mosby, Inc. All rights reserved.

Dabigatran exhibits low intensity of left atrial spontaneous echo contrast in patients with nonvalvular atrial fibrillation as compared with warfarin.

PubMed

Watanabe, Tetsuya; Shinoda, Yukinori; Ikeoka, Kuniyasu; Inui, Hirooki; Fukuoka, Hidetada; Sunaga, Akihiro; Kanda, Takashi; Uematsu, Masaaki; Hoshida, Shiro

2017-03-01

The presence of spontaneous echo contrast (SEC) in the left atrium has been reported to be an independent predictor of thromboembolic risk in patients with atrial fibrillation (AF). Dabigatran was associated with lower rates of stroke and systemic embolism as compared with warfarin when administered at a higher dose. Between July 2011 and October 2015, nonvalvular AF patients treated with warfarin or dabigatran who had transesophageal echocardiography prior to ablation therapy for AF were enrolled. The intensity of SEC was classified into four grades, from 0 to 3. Univariate and multivariate analysis was performed to analyze factors associated with SEC. Sixty-five patients were on dabigatran and 65 were on warfarin, with the prothrombin time in therapeutic range. There were no significant differences in the age, CHADS2 score, left atrial dimension, and left atrial appendage flow between the two groups. However, there were more grade 2 or higher patients with left atrial SEC in the warfarin group (n = 20) than in the dabigatran group (n = 2) (p < 0.001). When multivariate regression analysis was performed, grade 2 or higher left atrial SEC was independently associated with no dabigatran usage in addition to high brain natriuretic peptide level and high incidence of diabetes mellitus or persistent AF. Thus, dabigatran exhibited low intensity of left atrial SEC in nonvalvular AF patients as compared with warfarin.

Refractoriness of the gravid rat uterus to tocolytic and biochemical effects of atrial natriuretic peptide.

PubMed Central

Potvin, W.; Varma, D. R.

1990-01-01

1. Effects of atrial natriuretic peptide (ANP) on tension development, particulate guanylate cyclase activity and guanosine 3':5'-cyclic monophosphate (cyclic GMP) concentrations of uteri from oestrogen-treated, progesterone-treated, ovariectomized and pregnant rats were determined in vitro. 2. ANP inhibited the tension development by myometrial tissues from oestrogen-treated virgin rats and the sterile horn of 10 to 14 day pregnant rats but not of the uterus from pregnant and progesterone-treated rats. 3. Inhibition of cyclo-oxygenase and lipoxygenase activities did not restore the tocolytic activity of ANP on gravid uterus. ANP exerted a tocolytic effect on nongravid uterus submaximally stimulated by prostaglandin F2 alpha (PGF2 alpha), oxytocin, vasopressin, angiotensin II or 5-hydroxytryptamine (5-HT). 4. Ovariectomy decreased the tocolytic effects of ANP, which could be restored by oestrogen treatment. 5. The refractoriness to the tocolytic effect of ANP in pregnant rats was not accompanied by a decrease in its relaxant effects on isolated aortic strips. 6. Tocolytic effects of isoprenaline, isobutylmethyl xanthine and hydroxylamine were not influenced by pregnancy or progesterone treatment. Up to a concentration of 3 mM, sodium nitroprusside did not affect myometrial tension development. 7. Pregnancy and progesterone treatment markedly inhibited ANP-induced increases in myometrial particulate guanylate cyclase activity and cyclic GMP concentrations but did not influence the effects of ANP on aortic cyclic GMP concentrations. 8. It is concluded that exposure of the myometrium to circulating and placentally-produced progesterone is responsible for the pregnancy-induced decrease in the effects of ANP on myometrial particulate guanylate cyclase activity and cyclic GMP concentrations and in turn on myometrial tension development. PMID:1974161

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

PubMed Central

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

2013-01-01

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. PMID:23897233

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.

[Expression of A-type atrial natriuretic peptide receptor in the kidneys of renovascular hypertension rats and its implication].

PubMed

Liu, Rong-Tao; Xiao, Jing; Guo, Hui-Ling; Qiu, Dun-Guo; Yin, Hua-Hu; Wang, Zheng-Rong

2005-11-01

To investigate the expression of A-type atrial natriuretic peptide receptor (ANPR-A) in the kidneys of renovascular hypertension rats and evaluate the significance of the expression. The rat model of renovascular hypertension was produced by constricting one lateral renal artery. After the renal artery being constricted for 4 weeks and 8 weeks, the systolic BP of rats was measured with a manometer using the tail-cuff method. Then, the expression of ANPR-A was respectively detected by immunohistochemical technique in the kidneys of the two-kidney, one-clip (2K1C) rats, and the expression level of ANPR-A was semi-quantitatively measured by Mias-2000 computer image analyzer. At 4 weeks after the artery-constricted operation,the expression of ANPR-A increased significantly in 2K1C hypertensive rat glomeruli and decreased significantly in renal tubules, compared with control (P<0.01), but there was no marked change in medullar collecting tubules. At 8 weeks after the artery-constricted operation, the expression of ANPR-A decreased significantly in 2K1C hypertensive rat renal tubules and medullar collecting tubules, compared with control (P<0.01); however, there was weak expression in glomeruli, and no statistically significant difference was seen when compared with control (P>0.05). The expression of ANPR-A decreased significantly in kidney tissues of renovascular

Factors associated with the development of atrial fibrillation in patients with rheumatic mitral stenosis.

PubMed

Ozaydin, Mehmet; Turker, Yasin; Varol, Ercan; Alaca, Sule; Erdogan, Dogan; Yilmaz, Nigar; Dogan, Abdullah

2010-06-01

The aim of this study was to evaluate the factors associated with the development of atrial fibrillation (AF) in patients with rheumatic mitral stenosis (MS). A total of 146 consecutive patients with rheumatic MS were screened. They were accepted to be in AF group and sinus rhythm group according to their rhythm in the baseline ECG. After screening, 38 patients were excluded due to hyperthyroidism (n = 13), chronic obstructive pulmonary disease (n = 22), malignancy (n = 2) and rheumatoid arthritis (n = 1). Therefore, remaining 108 patients, 74 of whom in sinus rhythm (MS-SR) and 34 of whom in AF (MS-AF) constituted study population. Fourty age- and gender-matched patients constituted control group. Factors associated with development of AF in multivariable analysis included High sensitivity C reactive protein (P = 0.005; odds ratio, 3.44; 95% confidence interval, 1.44-8.22), N-terminal of brain natriuretic peptide precursor (P < 0.0001; odds ratio, 1.03; 95% confidence interval, 1.02-1.06) and left atrial diameter (P < 0.0001; odds ratio, 1.68; 95% confidence interval, 1.32-2.14). Present study suggests that High sensitivity C reactive protein, N-terminal of brain natriuretic peptide precursor and left atrial diameter are associated with development AF in patients with MS.

Chronic treatment with atrial natriuretic peptide in spontaneously hypertensive rats: beneficial renal effects and sex differences.

PubMed

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

2015-01-01

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. 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. 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. 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.

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

Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS.

PubMed

Frøssing, Signe; Nylander, Malin; Kistorp, Caroline; Skouby, Sven O; Faber, Jens

2018-01-01

Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP. To investigate if treatment with liraglutide in women with PCOS reduces levels of the cardiovascular biomarkers MR-proADM, MR-proANP and copeptin. Seventy-two overweight women with PCOS were treated with 1.8 mg/day liraglutide or placebo for 26 weeks in a placebo-controlled RCT. Biomarkers, anthropometrics, insulin resistance, body composition (DXA) and visceral fat (MRI) were examined. Baseline median (IQR) levels were as follows: MR-proADM 0.52 (0.45-0.56) nmol/L, MR-proANP 44.8 (34.6-56.7) pmol/L and copeptin 4.95 (3.50-6.50) pmol/L. Mean percentage differences (95% CI) between liraglutide and placebo group after treatment were as follows: MR-proADM -6% (-11 to 2, P  = 0.058), MR-proANP -25% (-37 to -11, P  = 0.001) and copeptin +4% (-13 to 25, P  = 0.64). Reduction in MR-proANP concentration correlated with both increased heart rate and diastolic blood pressure in the liraglutide group. Multiple regression analyses with adjustment for BMI, free testosterone, insulin resistance, visceral fat, heart rate and eGFR showed reductions in MR-proANP to be independently correlated with an increase in the heart rate. In an RCT, liraglutide treatment in women with PCOS reduced levels of the cardiovascular risk biomarkers MR-proANP with 25% and MR-proADM with 6% (borderline significance) compared with placebo. The decrease in MR-proANP was independently

Atrial natriuretic peptide provokes a dramatic increase in cyclic GMP formation and markedly inhibits muscarinic-stimulated Ca2+ mobilisation in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells.

PubMed

Ding, K H; Ali, N; Abdel-Latif, A A

1999-02-01

We investigated the effects of cGMP-elevating agents, including atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and sodium nitroprusside (SNP), on cGMP accumulation and on carbachol (CCh)-stimulated intracellular calcium ([Ca2+]i) mobilisation in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells and in primary cultured cat iris sphincter smooth muscle (CISM) cells. The stimulatory effects of the natriuretic peptides on cGMP production correlated well with their inhibitory effects on CCh-induced [Ca+1]i mobilisation, and these effects were significantly more pronounced in the SV-CISM-2 cells than in the CISM cells. Thus, ANP (1 microM) increased cGMP production in the SV-CISM-2 cells and CISM cells by 487- and 1.7-fold, respectively, and inhibited CCh-induced [Ca2+]i mobilisation by 95 and 3%, respectively. In the SV-CISM-2 cells, ANP and CNP dose dependently inhibited CCh-induced [Ca2+]i mobilisation with IC50 values of 156 and 412 nM, respectively, and dose dependently stimulated cGMP formation with EC50 values of 24 and 88 nM, respectively, suggesting that the inhibitory actions of the peptides are mediated through cGMP. Both ANP and CNP stimulated cGMP accumulation in a time-dependent manner. The potency of the cGMP-elevating agents were in the following order: ANP>CNP>SNP; these agents had no effect on cAMP accumulation. The inhibitory effects of the natriuretic peptides were mimicked by 8-Br-cGMP, a selective activator of cGMP-dependent protein kinase. LY83583, a soluble guanylyl cyclase inhibitor, significantly inhibited SNP-induced cGMP formation but had no effect on those of ANP and CNP. The basal activities of the guanylyl cyclase and the dissociation constant (Kd) and total receptor density (Bmax) values of the natriuretic peptide receptor for [125I]ANP binding were not significantly different between the two cell types. The cGMP system, as with the cAMP system, has a major inhibitory influence on the muscarinic

Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: plasma soluble Fas as a prognostic predictor in patients with congestive heart failure.

PubMed

Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M

2001-12-01

Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.

Effects of ANP receptor antagonists on ANP secretion from adult rat cultured atrial myocytes.

PubMed

Nachshon, S; Zamir, O; Matsuda, Y; Zamir, N

1995-03-01

Atrial natriuretic peptide (ANP) is a hormone-secreted predominantly by atrial myocytes. ANP exerts many of its actions via activation of the particulate guanylyl cyclase receptor ANPR-A and the formation of guanosine 3',5'-cyclic monophosphate (cGMP), which serves as a second messenger in the target cells. Using membrane-permeable cGMP analogues (8-bromo-cGMP and dibutyryl- cGMP), we first tested the hypothesis that ANP secretion by adult rat cultured atrial myocytes can be modulated through the second messenger cGMP. Second, we examined the effects of two competitive ANPR-A receptor antagonists, namely HS-142-1 and anantin, on cGMP formation and ANP secretion from cultured atrial myocytes. Cultured atrial myocytes secreted large quantities of immunoreactive (ir) ANP under basal conditions. We found that cGMP analogues inhibited basal irANP secretion from cultured atrial myocytes, whereas HS-142-1 and anantin had stimulating effects. HS-142-1 and anantin reduced cGMP formation in cultured atrial myocytes at basal conditions. These results suggest an autoregulatory mechanism of ANP secretion by atrial myocytes in an autocrine/paracrine fashion.

Receptors for atrial natriuretic peptide are decreased in the kidney of rats with streptozotocin-induced diabetes mellitus.

PubMed Central

Sechi, L A; Valentin, J P; Griffin, C A; Lee, E; Bartoli, E; Humphreys, M H; Schambelan, M

1995-01-01

To determine whether decreased renal responsiveness to atrial natriuretic peptide (ANP) in diabetes is mediated by alterations in the renal ANP receptor, ANP receptor density and affinity were measured 17-20 d after streptozotocin injection and compared with values in vehicle-treated controls and streptozotocin-treated rats made euglycemic with insulin. Plasma ANP concentration was significantly greater in hyperglycemic diabetic rats than in control or euglycemic diabetic rats. Both in glomeruli and inner medulla, ANP receptor dissociation constant did not differ among the three study groups, whereas the maximum binding capacity was decreased significantly in hyperglycemic diabetics in comparison with controls and euglycemic diabetics. Glomerular clearance receptors were also decreased significantly in hyperglycemic diabetic rats in comparison with control and euglycemic diabetic rats. To determine whether the decreased number of renal ANP receptors in diabetic rats was associated with a decreased biological response, we measured ANP-dependent cyclic GMP (cGMP) accumulation by isolated glomeruli and inner medullary collecting duct cells in vitro. cGMP accumulation was significantly less in hyperglycemic diabetic rats than in controls or euglycemic diabetic rats both in the presence or absence of the phosphodiesterase inhibitor zaprinast. cGMP phosphodiesterase activity in inner medullary collecting duct cells obtained from control and hyperglycemic diabetic rats did not differ. Thus, the decreased number of biologically active ANP receptors in the kidneys of diabetic rats is accompanied by decreased biological responsiveness in vitro and provides a potential explanation for the reduction in renal sensitivity to ANP in this condition. Images PMID:7769090

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. British Veterinary Association.

B-type natriuretic peptide and echocardiography reflect volume changes during pregnancy

PubMed Central

Burlingame, Janet M.; Yamasato, Kelly; Ahn, Hyeong Jun; Seto, Todd; Tang, W. H. Wilson

2017-01-01

Objective To evaluate B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac structure and function in normal women through pregnancy and the postpartum. Methods In this prospective observational study, we obtained serial transthoracic echocardiograms, BNP, and NT-proBNP at seven intervals from 6 weeks’ gestation through 12 months postpartum. Women with hypertension or cardiac disease were excluded. Using 6–12 months postpartum as reference for non-pregnant levels, echocardiogram measurements and BNP/NT-proBNP were compared over time using linear mixed models with Tukey-Kramer adjustment for multiple comparisons. Results Of 116 patients, data was available for 78–114 healthy pregnant or postpartum women within each time interval, and 102 patients provided data for ≥ 4 intervals. Compared to 6–12 months postpartum, BNP and NT-proBNP remained stable through pregnancy and delivery, increased within 48 h postpartum (P < 0.0001), then returned to baseline. Left ventricular volume increased within 48 h postpartum (P = 0.021) while left atrial volume increased at 18–24 weeks (P = 0.0002), 30–36 weeks (P < 0.0001) and within 48 h postpartum (P = 0.002). The transmittal early/late diastolic velocity (E/A) ratio, transmittal early/peak mitral annulus diastolic velocity (E/E′) ratio, isovolumic relaxation times, and mitral valve deceleration times were similar within 48 h and 6–12 months postpartum. Conclusion In normal women, BNP/NT-proBNP, left atrial, and left ventricular volumes increase within 48 h postpartum without indications of altered diastolic function. PMID:28195551

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Misono, K. S.; Philo, J. S.; Arakawa, T.

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 ofmore » 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.« less

Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development

PubMed Central

Becker, Jason R.; Chatterjee, Sneha; Robinson, Tamara Y.; Bennett, Jeffrey S.; Panáková, Daniela; Galindo, Cristi L.; Zhong, Lin; Shin, Jordan T.; Coy, Shannon M.; Kelly, Amy E.; Roden, Dan M.; Lim, Chee Chew; MacRae, Calum A.

2014-01-01

Organ development is a highly regulated process involving the coordinated proliferation and differentiation of diverse cellular populations. The pathways regulating cell proliferation and their effects on organ growth are complex and for many organs incompletely understood. In all vertebrate species, the cardiac natriuretic peptides (ANP and BNP) are produced by cardiomyocytes in the developing heart. However, their role during cardiogenesis is not defined. Using the embryonic zebrafish and neonatal mammalian cardiomyocytes we explored the natriuretic peptide signaling network during myocardial development. We observed that the cardiac natriuretic peptides ANP and BNP and the guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2 are functionally redundant during early cardiovascular development. In addition, we demonstrate that low levels of the natriuretic peptides preferentially activate Npr3, a receptor with Gi activator sequences, and increase cardiomyocyte proliferation through inhibition of adenylate cyclase. Conversely, high concentrations of natriuretic peptides reduce cardiomyocyte proliferation through activation of the particulate guanylate cyclase-linked natriuretic peptide receptors Npr1 and Npr2, and activation of protein kinase G. These data link the cardiac natriuretic peptides in a complex hierarchy modulating cardiomyocyte numbers during development through opposing effects on cardiomyocyte proliferation mediated through distinct cyclic nucleotide signaling pathways. PMID:24353062

Natriuretic factor, a lasting enigma.

PubMed

Licht, A; Fine, L G; Bourgoignie, J J

1978-01-01

A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.

Right heart overload contributes to cardiac natriuretic hormone elevation in patients with heart failure.

PubMed

Passino, Claudio; Maria Sironi, Anna; Favilli, Brunella; Poletti, Roberta; Prontera, Concetta; Ripoli, Andrea; Lombardi, Massimo; Emdin, Michele

2005-09-15

Atrial and brain natriuretic peptides (ANP and BNP) plasma concentration increases and holds a prognostic significance in patients with left ventricular dysfunction. We assessed the hypothesis that right ventricular (RV) overload might significantly contribute to plasma elevation of cardiac natriuretic hormones in patients with heart failure. Forty-one patients with cardiomyopathy and depressed left ventricular (LV) function (ejection fraction, EF, <40%), underwent cardiac magnetic resonance imaging (MRI) and resting plasma determination of ANP and BNP. Nineteen healthy subjects were also studied as control group. Ventricular volumes and function were assessed by MRI. In the group of patients, LVEF was 22.6+/-1.2% (controls: 61.2+/-1.3%, P<0.001, mean+/-S.E.M.), while RVEF was 48.2+/-2.5% (controls: 66.7+/-1.6%, P<0.001); LV and RV end diastolic/systolic volumes, corrected by body surface area, were 143+/-7/114+/-7 ml/m2 (controls 70+/-3/27+/-2 ml/m2, both P<0.001) and 66+/-3/37+/-4 ml/m2 (controls: 63+/-4/21+/-2 ml/m2, P<0.01 only for end-systolic volume). BNP plasma value was on average 324+/-39 pg/ml (range: 23-1280, controls 10+/-2 pg/ml), ANP value was 144+/-17 pg/ml (range: 26-534, controls 15+/-1 pg/ml). BNP positively correlated with either end-diastolic or end-systolic RV volume in patients, less with LV systolic, and not with LV diastolic volume. Moreover, a significant negative correlation was observed between BNP and either LVEF or RVEF. Conversely, ANP showed a significant correlation only with end-systolic RV volume and with both RVEF and LVEF. When multivariate stepwise linear regression analysis was applied LVEF resulted the only independent predictor for ANP plasma values (R=0.591, P<0.001), while LVEF and RV end-diastolic volume for BNP (R=0.881, P<0.001, and R=0.881, P=0.035, respectively). Right heart overload contributes independently to plasma elevation of natriuretic peptides. RV involvement, which is known to independently worsen prognosis

Atrial natriuretic peptide therapy and in-hospital mortality in acute myocardial infarction patients undergoing percutaneous coronary intervention.

PubMed

Isogai, Toshiaki; Matsui, Hiroki; Tanaka, Hiroyuki; Fushimi, Kiyohide; Yasunaga, Hideo

2016-11-01

Atrial natriuretic peptide (ANP) therapy has been reported to have beneficial effects in patients with acute myocardial infarction (AMI); however, its impact on in-hospital mortality remains unclear. This study aimed to investigate the effects of ANP therapy on in-hospital mortality in AMI patients undergoing percutaneous coronary intervention (PCI). This was a retrospective cohort study using the Diagnosis Procedure Combination inpatient database in Japan. We identified AMI patients who underwent PCI with stent implantation on the day of admission, between 2010 and 2014. We compared 30-day in-hospital mortality between patients who started ANP therapy on the day of admission (ANP group) and those who received no ANP therapy during hospitalization (control group), using propensity score and instrumental variable methods. Of 60,592 eligible patients (8189 ANP group, 52,403 control group) from 850 hospitals, 1:1 propensity score matching created 8027 pairs. There was no significant difference in 30-day in-hospital mortality between the ANP and control groups (3.4% vs. 3.8%, respectively; p=0.162; risk difference, -0.42%; 95% confidence interval [CI], -1.00% to 0.15%) in the propensity score-matched cohort. Logistic regression analysis with adjustment for propensity score deciles found no significant association between ANP therapy and 30-day in-hospital mortality (odds ratio, 0.99; 95% CI, 0.82 to 1.19). Instrumental variable analysis also showed no significant association between ANP therapy and 30-day in-hospital mortality (risk difference, -0.59%; 95% CI, -1.24% to 0.05%). This study found no significant association between ANP therapy and in-hospital mortality in AMI patients undergoing PCI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prediction about severity and outcome of sepsis by pro-atrial natriuretic peptide and pro-adrenomedullin.

PubMed

Wang, Rui-lan; Kang, Fu-xin

2010-06-01

Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores. Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay. On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores. Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients.

The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation.

PubMed

Kawabata, Mihoko; Goya, Masahiko; Takagi, Takamitsu; Yamashita, Shu; Iwai, Shinsuke; Suzuki, Masahito; Takamiya, Tomomasa; Nakamura, Tomofumi; Hayashi, Tatsuya; Yagishita, Atsuhiko; Sasaki, Takeshi; Takahashi, Yoshihide; Ono, Yuhichi; Hachiya, Hitoshi; Yamauchi, Yasuteru; Otomo, Kenichiro; Nitta, Junichi; Okishige, Kaoru; Nishizaki, Mitsuhiro; Iesaka, Yoshito; Isobe, Mitsuaki; Hirao, Kenzo

2016-12-01

Atrial fibrillation (AF) often coexists with Wolff-Parkinson-White (WPW) syndrome. We compared the efficacy of Kent bundle ablation alone and additional AF ablation on accompanying AF, and examined which patients would still have a risk of AF after successful Kent bundle ablation. This retrospective multicenter study included 96 patients (56±15 years, 72 male) with WPW syndrome and AF undergoing Kent bundle ablation. Some patients underwent simultaneous pulmonary vein isolation (PVI) for AF. The incidence of post-procedural AF was examined. Sixty-four patients underwent only Kent bundle ablation (Kent-only group) and 32 also underwent PVI (+PVI group). There was no significant difference in the basic patient characteristics between the groups. Additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p=0.53). In the Kent-only group, AF episodes remained in 25.0% during the follow-up (709 days). A univariate analysis showed that age ≥60 years, left atrial dimension ≥38mm, B-type natriuretic peptide (BNP) ≥40pg/ml, and concomitant hypertension were predictive factors for residual AF. However, in the multivariate analysis, only BNP ≥40pg/ml remained as an independent predictive factor (HR=17.1 and CI: 2.3-128.2; p=0.006). Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact of preventing recurrence of AF in select patients. Screening the BNP level would help decide the strategy to manage those patients. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Atrial Cardiopathy and Cryptogenic Stroke: A Cross-sectional Pilot Study.

PubMed

Yaghi, Shadi; Boehme, Amelia K; Hazan, Rebecca; Hod, Eldad A; Canaan, Alberto; Andrews, Howard F; Kamel, Hooman; Marshall, Randolph S; Elkind, Mitchell S V

2016-01-01

There is increasing evidence that left atrial dysfunction or cardiopathy is associated with ischemic stroke risk independently of atrial fibrillation. We aimed to determine the prevalence of atrial cardiopathy biomarkers in patients with cryptogenic stroke. We included consecutive patients with ischemic stroke enrolled in the New York Columbia Collaborative Specialized Program of Translational Research in Acute Stroke registry between December 1, 2008, and April 30, 2012. Medical records were reviewed and patients with a diagnosis of cryptogenic stroke were identified. Atrial cardiopathy was defined as at least one of the following: serum N-terminal probrain natriuretic peptide (NT-proBNP) level greater than 250 pg/mL, P-wave terminal force velocity in lead V1 (PTFV1) on electrocardiogram (ECG) greater than 5000 µV⋅ms, or severe left atrial enlargement (LAE) on echocardiogram. We compared clinical, echocardiographic, and radiological characteristics between patients with and without atrial cardiopathy. Among 40 patients with cryptogenic stroke, 63% had at least one of the biomarkers of atrial cardiopathy; 49% had elevated NT-proBNP levels, 20% had evidence of increased PTFV1 on ECG, and 5% had severe LAE. Patients with atrial cardiopathy were more likely to be older (76 versus 62 years, P = .012); have hypertension (96% versus 33%, P < .001), hyperlipidemia (60% versus 27%, P = .05), or coronary heart disease (28% versus 0%, P = .033); and less likely to have a patent foramen ovale (4% versus 40%, P = .007). There is a high prevalence of biomarkers indicative of atrial cardiopathy in patients with cryptogenic stroke. Clinical trials are needed to determine whether these patients may benefit from anticoagulation to prevent stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The Role of Natriuretic Agents In the Mechanism of Hypertension in the Dahl Strain of Salt-Sensitive and Salt-Resistant Rats

DTIC Science & Technology

1986-07-02

the pathogenesis of volume-dependent hypertension. OLHF, by inhibiting Na+ I - K+ pump activity in cardiovascular muscle cells , stimulates the...role of OLHF in hypertension •••••••••••••••••••• 18 Atrial Natriuretic Factor (ANF) ••.•••••••••••••••••••••• 19 Renal effects of atrial extracts...20 Vascular effects of ANF.... • . • • • • • • • • • • • • • • • • • • • • • • • 25 Primary structure and biological actions of

Expansion of extracellular volume and suppression of atrial natriuretic peptide after growth hormone administration in normal man.

PubMed

Møller, J; Jørgensen, J O; Møller, N; Hansen, K W; Pedersen, E B; Christiansen, J S

1991-04-01

Sodium retention and symptoms and signs of fluid retention are commonly recorded during GH administration in both GH-deficient patients and normal subjects. Most reports have however, been casuistic or uncontrolled. In a randomized double blind placebo-controlled cross-over study we therefore examined the effect of 14-day GH administration (12 IU sc at 2000 h) on plasma volume, extracellular volume (ECV), atrial natriuretic peptide (ANP), arginine vasopressin, and the renin angiotensin system in eight healthy adult men. A significant GH induced increase in serum insulin growth factor I was observed. GH caused a significant increase in ECV (L): 20.45 +/- 0.45 (GH), 19.53 +/- 0.48 (placebo) (P less than 0.01), whereas plasma volume (L) remained unchanged 3.92 +/- 0.16 (GH), 4.02 +/- 0.13 (placebo). A significant decrease in plasma ANP (pmol/L) after GH administration was observed: 2.28 +/- 0.54 (GH), 3.16 +/- 0.53 (placebo) P less than 0.01. Plasma aldosterone (pmol/L): 129 +/- 14 (GH), 89 +/- 17 (placebo), P = 0.08, and plasma angiotensin II (pmol/L) levels: 18 +/- 12 (GH), 14 +/- 7 (placebo), P = 0.21, were not significantly elevated. No changes in plasma arginine vasopressin occurred (1.86 +/- 0.05 pmol/L vs. 1.90 +/- 0.05, P = 0.33). Serum sodium and blood pressure remained unaffected. Moderate complaints, which could be ascribed to water retention, were recorded in four subjects [periorbital edema (n = 3), acral paraesthesia (n = 2) and light articular pain (n = 1)]. The symptoms were most pronounced after 2-3 days of treatment and diminished at the end of the period. In summary, 14 days of high dose GH administration caused a significant increase in ECV and a significant suppression of ANP.

Relation of Natriuretic Peptide Concentrations to Central Sleep Apnea in Patients With Heart Failure

PubMed Central

Calvin, Andrew D.; Somers, Virend K.; van der Walt, Christelle; Scott, Christopher G.

2011-01-01

Background: Central sleep apnea (CSA) is frequent among patients with heart failure (HF) and associated with increased morbidity and mortality. Elevated cardiac filling pressures promote CSA and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) secretion. We hypothesized that circulating natriuretic peptide concentrations predict CSA. Methods: Consecutive patients with HF (n = 44) with left ventricular ejection fraction (LVEF) ≤ 35% underwent polysomnography for detection of CSA. CSA was defined as an apnea-hypopnea index ≥ 15 with ≥ 50% central apneic events. The relation of natriuretic peptide concentrations to CSA was evaluated by estimation of ORs and receiver operator characteristics (ROCs). Results: Twenty-seven subjects (61%) had CSA, with men more frequently affected than women (73% vs 27%; OR, 7.1; P = .01); given that only three women had CSA, further analysis was restricted to men. Subjects with CSA had higher mean ANP (4,336 pg/mL vs 2,510 pg/mL, P = .03) and BNP concentrations (746 pg/mL vs 379 pg/mL, P = .05). ANP and BNP concentrations were significantly related to CSA (OR, 3.7 per 3,000 pg/mL, P = .03 and OR, 1.5 per 200 pg/mL, P = .04, respectively), whereas age, LVEF, and New York Heart Association functional class were not. Concentrations of ANP and BNP were predictive of CSA as ROC demonstrated areas under the curve of 0.75 and 0.73, respectively. Conclusions: Risk of CSA is related to severity of HF. ANP and BNP concentrations performed similarly for detection of CSA; low concentrations appear associated with low risk for CSA in men. PMID:21636668

Inhibition of epithelial Na sup + transport by atriopeptin, protein kinase c, and pertussis toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohrmann, M.; Cantiello, H.F.; Ausiello, D.A.

1987-08-01

The authors have recently shown the selective inhibition of an amiloride-sensitive, conductive pathway for Na{sup +} by atrial natriuretic peptide and 8-bromoguanosine 3{prime},5{prime}-cyclic monophosphate (8-BrcGMP) in the renal epithelial cell line, LLC-PK{sub i}. Using {sup 22}Na{sup +} fluxes, they further investigated the modulation of Na{sup +} transport by atrial natriuretic peptide and by agents that increase cGMP production, activate protein kinase c, or modulate guanine nucleotide regulatory protein function. Sodium nitroprusside increases intracellular cGMP concentrations without affecting cAMP concentrations and completely inhibits amiloride-sensitive Na{sup +} uptake in a time- and concentration-dependent manner. Oleoyl 2-acetylglycerol and phorbol 12-myristate 13-acetate, activators ofmore » protein kinase c, inhibit Na{sup +} uptake by 93 {plus minus} 13 and 51 {plus minus} 10%, respectively. Prolonged incubation with phorbol ester results in the downregulation of protein kinase c activity and reduces the inhibitory effect of atrial natriuretic peptide, suggesting that the action of this peptide involves stimulation of protein kinase c. Pertussis toxin, which induces the ADP-ribosylation of a 41-kDa guanine nucleotide regulatory protein in LLC-PK{sub i} cells, inhibits {sup 22}Na{sup +} influx to the same extent as amiloride. Thus, increasing cGMP, activating protein kinase c, and ADP-ribosylating a guanine nucleotide regulatory protein all inhibit Na{sup +} uptake. These events may be sequentially involved in the action of atrial natriuretic peptide.« less

The effect of water deprivation on the expression of atrial natriuretic peptide and its receptors in the spinifex hopping mouse, Notomys alexis.

PubMed

Heimeier, Rachel A; Davis, Belinda J; Donald, John A

2002-08-01

This study investigated the mRNA expression of the atrial natriuretic peptide (ANP) system (peptide and receptors) during water deprivation in the spinifex hopping mouse, Notomys alexis, a native of central and western Australia that is well adapted to survive in arid environments. Initially, ANP, NPR-A and NPR-C cDNAs (partial for receptors) were cloned and sequenced, and were shown to have high homology with those of rat and mouse. Using a semi-quantitative multiplex PCR technique, the expression of cardiac ANP mRNA and renal ANP, NPR-A, and NPR-C mRNA was determined in 7- and 14-day water-deprived hopping mice, in parallel with control mice (access to water). The levels of ANP mRNA expression in the heart remained unchanged, but in the kidney ANP mRNA levels were increased in the 7-day water-deprived mice, and were significantly decreased in the 14-day water-deprived mice. NPR-A mRNA levels were significantly higher in 7-day water-deprived mice while no change for NPR-A mRNA expression was observed in 14-day water-deprived mice. No variation in NPR-C mRNA levels was observed. This study shows that water deprivation differentially affects the expression of the ANP system, and that renal ANP expression is more important than cardiac ANP in the physiological adjustment to water deprivation.

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

PubMed

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

2011-04-01

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

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic value of brain natriuretic peptide and β-endorphin plasma concentration changes in patients with acute left heart failure and atrial fibrillation.

PubMed

Feng, Shao-Dan; Jiang, Yong; Lin, Zhi-Hong; Lin, Pei-Hong; Lin, Si-Ming; Liu, Qi-Cai

2017-08-01

This study aims to evaluate the diagnostic value of beta-endorphin (β-EP) and brain natriuretic peptid (BNP) plasma concentrations for the early diagnosis of acute left heart failure and atrial fibrillation. A total of 45 patients were included. These patients comprised 23 male and 22 female patients,and 20 healthy subjects who underwent physical examinations in the Outpatient Department during the same periodwere included and assigned to the control group. The diagnos stand was that of the Chinese guidelines for the diagnosis and treatment of heart failure. Enzyme-linked immunosorbent assay was performed to detect the plasma concentration of β-EP and BNP in the treatment and control groups, and electrocardiogram targeting was performed to determine the left ventricular ejection fraction (LVEF). BNP, β-EP, and LVEF levels were higher in the treatment group (688.01 ± 305.78 ng/L, 394.06 ± 180.97 ng/L, and 70.48 ± 16.62%) compared with the control group (33.90 ± 8.50 ng/L, 76.87 ± 57.21 ng/L, and 32.11 ± 5.25%). The P-values were .015, .019, and .026, respectively, which were <.05. The difference was statistically significant. The BNP and β-EP's 4 correlations (r = 0.895, P <.001), BNP, β-EP, and the combination of BNP and β-EP for acute left heart failure diagnosis in maximizing Youden index sensitivity, specific degree, area under the ROC curve (AUC), and 95% confidence interval (CI) were respectively 93.5%, 81.3%, 0.921, 0.841, 0.921; 80.5%, 78.6%, 0.697, 0.505, 0.697; 94.1%, 83.5%, 0.604 to 0.979, and 0.604. Acute left heart failure in patients with LVEF acuity plasma BNP and β-EP 50% group was obviously lower than that in the LVEF <50% group (P <.01). BNP, β-EP, and LVEF were negatively correlated (r = -0.741, -0.635, P = .013, .018). β-EP and BNP have high specificity and sensitivity for detecting early acute left heart failure and atrial fibrillation in patients, which is convenient, easy to

Characterization of C-type natriuretic peptide receptors in human mesangial cells.

PubMed

Zhao, J; Ardaillou, N; Lu, C Y; Placier, S; Pham, P; Badre, L; Cambar, J; Ardaillou, R

1994-09-01

Our aim was to examine whether the human glomerulus was a target for C-type natriuretic peptide (CNP) and how A, B and C receptors of natriuretic peptides (ANPR-A, ANPR-B, ANPR-C) were distributed in glomerular mesangial and epithelial cells. CNP stimulated cyclic GMP production in cultured human mesangial and epithelial cells with similar threshold concentrations (1 nM) and maximum effects (basal value x 30 at 1 microM). In contrast, atrial natriuretic peptide (ANP) was only stimulatory in epithelial cells. [125I] CNP bound specifically to mesangial cells with a Kd of 0.47 nM and Bmax of 42 fmol/mg. Equilibrium of binding was obtained after four to five hours at +4 degrees C and nonspecific binding represented 10 to 20% of total binding. HS142-1 (100 micrograms/ml), a specific inhibitor of ANPR-A and ANPR-B, suppressed 90% of CNP-dependent cyclic GMP production whereas it had little effect on [125I]-CNP binding, suggesting that C receptors were largely predominant in mesangial cells. No biological effect of CNP on mesangial cells, including change in basal or angiotensin II-induced contractility and inhibition of basal or serum-dependent proliferation, could be demonstrated. Similar results were obtained with 8-bromo-cyclic GMP and sodium nitroprusside. Intraglomerular localization of ANPR-A, ANPR-B and ANPR-C mRNA was studied using reverse transcriptase-polymerase chain reaction with amplification of their corresponding cDNA by different primers. Amplification products were identified on gel electrophoresis by their predicted sizes and sequencing. ANPR-A, ANPR-B and ANPR-C mRNA were present in epithelial cells whereas only ANPR-B and ANPR-C mRNA were detected in mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of plasma N-terminal pro-brain natriuretic peptide in patients with severe sepsis.

PubMed

Brueckmann, Martina; Huhle, Guenter; Lang, Siegfried; Haase, Karl K; Bertsch, Thomas; Weiss, Christel; Kaden, Jens J; Putensen, Christian; Borggrefe, Martin; Hoffmann, Ursula

2005-07-26

Increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been identified as predictors of cardiac dysfunction and prognosis in congestive heart failure and ischemic heart disease. In severe sepsis patients, however, no information is available yet about the prognostic value of natriuretic peptides. Therefore, the aim of the present study was to determine the role of the N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C [drotrecogin alfa (activated)] on plasma levels of natriuretic peptides in severe sepsis was evaluated. Fifty-seven patients with severe sepsis were included. Levels of NT-proANP and NT-proBNP were measured on the second day of sepsis by ELISA. Septic patients with NT-proBNP levels >1400 pmol/L were 3.9 times more likely (relative risk [RR], 3.9; 95% CI, 1.6 to 9.7) to die from sepsis than patients with lower NT-proBNP values (P<0.01). NT-proANP levels, however, were not predictive of survival in our patient population. A highly significant correlation was found between troponin I levels and plasma concentrations of NT-proBNP in septic patients (r=0.68, P<0.0001). In addition, troponin I significantly accounted for the variation in NT-proBNP levels (P<0.0001), suggesting an important role for NT-proBNP in the context of cardiac injury and dysfunction in septic patients. Twenty-three septic patients who received treatment with drotrecogin alfa (activated) presented with significantly lower concentrations of NT-proANP, NT-proBNP, and troponin I compared with patients not receiving drotrecogin alfa (activated). NT-proBNP may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.

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.

Rapid increase in plasma levels of atrial natriuretic peptide after common bile duct ligation in the rabbit.

PubMed

Valverde, J; Martínez-Ródenas, F; Pereira, J A; Carulla, X; Jiménez, W; Gubern, J M; Sitges-Serra, A

1992-11-01

Previous studies have shown that common bile duct ligation in the rabbit is followed by a reduction of the extracellular water compartment. To further elucidate the mechanisms leading to volume depletion in this model, water and sodium balances and changes in plasma concentrations of atrial natriuretic peptide (ANP), vasopressin (ADH), plasma renin activity (PRA) and aldosterone (Ald) were investigated during the first 4 days after common bile duct ligation (group OJ,) or sham operation (group SO). Water and chow intakes were lower in group OJ (148 +/- 30 versus 226 +/- 40 mL/4 days; p = 0.004 and 12 +/- 9 versus 171 +/- 40 g/4 days; p = 0.0001). There were no differences in urine output. Sodium urinary losses were marginally higher in group OJ (12.4 +/- 7 versus 6.7 +/- 5 mEq/4 days; p = 0.06). Water balance was lower in group OJ (-50 +/- 56 versus 101 +/- 71 mL/4 days; p = 0.0001). At 24 hours, plasma ANP (41 +/- 7 versus 10.7 +/- 1 fmol/mL, p = 0.0001), ADH (21.8 +/- 7 versus 12.3 +/- 6 pg/mL, p = 0.008) and Ald (14.5 +/- 5 versus 3.7 +/- 3 ng/dL, p = 0.001) were higher in group OJ. These alterations persisted 72 hours after bile duct ligation, when a concomitant increase in PRA (10.7 +/- 5 versus 3 +/- 1.6 ng/dL, p = 0.006) was also observed. A group of pair-fed pair-watered sham-operated controls (group SO2, n = 13) showed a metabolic profile similar to group OJ but a low ANP concentration. Multiple venous sampling in five rabbits 24 hours after bile duct ligation showed the highest plasma levels of ANP in the aorta and infrarenal vena cava. These results suggest that common bile duct ligation in the rabbit is followed by marked hypodipsia and hypophagia, possibly mediated by ANP, leading to isotonic volume depletion and secondary activation of the water and sodium retaining hormones.

Augmented Renal Clearance in Traumatic Brain Injury: A Single-Center Observational Study of Atrial Natriuretic Peptide, Cardiac Output, and Creatinine Clearance.

PubMed

Udy, Andrew A; Jarrett, Paul; Lassig-Smith, Melissa; Stuart, Janine; Starr, Therese; Dunlop, Rachel; Deans, Renae; Roberts, Jason A; Senthuran, Siva; Boots, Robert; Bisht, Kavita; Bulmer, Andrew C; Lipman, Jeffrey

2017-01-01

Augmented renal clearance (ARC) is being increasingly described in neurocritical care practice. The mechanisms driving this phenomenon are largely unknown. The aim of this project was therefore to explore changes in renal function, cardiac output (CO), and atrial natriuretic peptide (ANP) concentrations in patients with isolated traumatic brain injury (TBI). This prospective observational cohort study was conducted in a tertiary-level, university-affiliated intensive care unit (ICU). Patients with normal plasma creatinine concentrations (<120 μmol/L) at admission and no history of chronic kidney disease, admitted with isolated TBI, were eligible for enrollment. Continuous CO measures were obtained using arterial pulse waveform analysis. Eight-hour urinary creatinine clearances (CL CR ) were used to quantify renal function. ANP concentrations in plasma were measured on alternate days. Data were collected from study enrollment until ICU discharge, death, or day 15, which ever came first. Eleven patients, contributing 100 ICU days of physiological data, were enrolled into the study. Most participants were young men, requiring mechanical ventilation. Median ICU length of stay was 9.6 [7.8-13.0] days. Elevated CL CR measures (>150 mL/min) were frequent and appeared to parallel changes in CO. Plasma ANP concentrations were also significantly elevated over the study period (minimum value = 243 pg/mL). These data suggest that ARC is likely to complicate the care of TBI patients with normal plasma creatinine concentrations, and may be driven by associated cardiovascular changes and/or elevated plasma ANP concentrations. However, significant additional research is required to further understand these findings.

Comparison of aldosterone synthesis in adrenal cells, effect of various AT1 receptor blockers with or without atrial natriuretic peptide.

PubMed

Miura, Shin-Ichiro; Nakayama, Asuka; Tomita, Sayo; Matsuo, Yoshino; Suematsu, Yasunori; Saku, Keijiro

2015-01-01

Bifunctional angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) that can block the activation of not only AT1 receptor, but also neprilysin, which metabolizes vasoactive peptides including atrial natriuretic peptide (ANP), are currently being developed. However, the usefulness of the inactivation of ANP in addition to the AT1 receptor with regard to aldosterone (Ald) synthesis is not yet clear. We evaluated the inhibitory effects of various ARBs combined with or without ANP on Ang II-induced adrenal Ald synthesis using a human adrenocortical cell line (NCI-H295R). Ang II increased Ald synthesis in a dose- and time-dependent manner. Ald synthesis induced by Ang II was completely blocked by azilsartan, but not PD123319 (AT2 receptor antagonist). CGP42112 AT2 receptor agonist did not affect Ald synthesis. While most ARBs block Ang II-induced Ald synthesis to different extents, azilsartan and olmesartan have similar blocking effects on Ald synthesis. The different effects of ARBs were particularly observed at 10(-7) and 10(-8 )M. ANP attenuated Ang II-induced Ald synthesis, and ANP-mediated attenuation of Ang II-induced Ald synthesis were blocked by inhibitors of G-protein signaling subtype 4 and protein kinase G. ANP (10(-8) and 10(-7 )M) without ARBs inhibited Ald synthesis, and the combination of ANP (10(-7 )M) and ARB (10(-8 )M) had an additive effect with respect to the inhibition of Ald synthesis. In conclusions, ARBs had differential effects on Ang II-induced Ald synthesis, and ANP may help to block Ald synthesis when the dose of ARB is not sufficient to block its secretion.

Decrease in B-Type Natriuretic Peptide Levels and Successful Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure.

PubMed

Yanagisawa, Satoshi; Inden, Yasuya; Kato, Hiroyuki; Fujii, Aya; Mizutani, Yoshiaki; Ito, Tadahiro; Kamikubo, Yosuke; Kanzaki, Yasunori; Hirai, Makoto; Murohara, Toyoaki

2016-03-01

Little is known about the association between B-type natriuretic peptide (BNP) levels and catheter ablation of atrial fibrillation (AF) in patients with heart failure. This study aimed to examine the impact of elimination of AF by catheter ablation on BNP levels in patients with left ventricular systolic dysfunction. Fifty-four AF patients with left ventricular ejection fraction (LVEF) ≤ 50%, who underwent radiofrequency catheter ablation therapy of AF, were included. BNP sampling was performed at baseline, 3 days, and 1 month after ablation. After a follow-up period of 6 months, the BNP levels decreased significantly in the nonrecurrence group (n = 35; median 126.3 [interquartile 57.2-206.5] pg/mL, 63.5 [23.9-180.2] pg/mL, and 45.9 [21.9-160.3] pg/mL, P < 0.001, respectively), but not in the recurrence group (n = 19; 144.7 [87.1-217.3] pg/mL, 88.8 [12.9-213.2] pg/mL, and 118.5 [51.6-298.2] pg/mL, P = 0.368, respectively). The patients in the nonrecurrence group had a higher percentage relative reduction in BNP levels from baseline to 1 month after ablation than those in the recurrence group (56.5 [-9.0-77.4]% vs -2.4 [-47.1-60.9]%, P = 0.027). Additionally, a relative reduction in BNP levels significantly correlated with an increase in LVEF after ablation (r = 0.486, P < 0.001). Plasma BNP levels decreased significantly with successful catheter ablation of AF in patients with impaired LVEF. The decrease in BNP levels might be associated with early recovery of cardiac function and subsequent maintenance of sinus rhythm at follow-up. ©2015 Wiley Periodicals, Inc.

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study.

PubMed

Morgenthaler, Nils G; Struck, Joachim; Christ-Crain, Mirjam; Bergmann, Andreas; Müller, Beat

2005-02-01

Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores. Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay. On admission, 53 patients had sepsis, severe sepsis, or septic shock, and 68 had systemic inflammatory response syndrome. The median pro-ANP value in the survivors was 194 pmol/l (range 20-2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100-2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in non-surviving [corrected] than in surviving [corrected] sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score. Pro-ANP appears to be a valuable tool for individual risk assessment in sepsis patients and for stratification of high-risk patients in future intervention trials. Further studies are needed to validate our results.

[The effect of atrial pacing on left ventricular diastolic function and BNP levels in patients with DDD pacemaker].

PubMed

Apali, Zeynep; Bayata, Serdar; Yeşil, Murat; Arikan, Erdinç; Postaci, Nursen

2010-08-01

We aimed to investigate the effect of atrial pacing on left ventricular diastolic function and brain natriuretic peptide (BNP) levels in patients with DDD pacemaker. Thirty patients with complete atrio-ventricular (AV) block and DDD pacemaker were included. All patients had normal left ventricular systolic function. Echocardiographic diastolic function parameters (transmitral and tissue Doppler velocities during early (E and E') and late (A and A') filling) and NT-pro-BNP levels were evaluated prospectively during atrial sensing and pacing periods. Echocardiographic data were compared with paired sample t test and NT-pro-BNP levels were compared with Wilcoxon test. Echocardiographic E/A, E'/A', E/E' ratios were calculated as 0.72+/-0.34, 0.61+/-0.21 and 8.76+/-2.58 during atrial sensing period. Same parameters were found as 0.71+/-0.23, 0.64+/-0.16 and 8.93+/-3.16 respectively during atrial pacing period. Echocardiographic left ventricular diastolic function parameters were not significantly different during atrial pacing and atrial sensing periods. Median plasma NT-pro-BNP levels were measured as 142 pg/ml (min-max 47-563 pg/ml) and 147 pg/ml (min-max 33-1035 pg/ml) during atrial sensing and pacing periods respectively. These levels were not significantly different (p=0.86). The result of this study has shown that, atrial pacing has not any additional detrimental effect on left ventricular diastolic function parameters in paced patients with normal left ventricular systolic function.

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

PubMed

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

2017-11-01

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

Sacubitril/valsartan: beyond natriuretic peptides.

PubMed

Singh, Jagdeep S S; Burrell, Louise M; Cherif, Myriam; Squire, Iain B; Clark, Andrew L; Lang, Chim C

2017-10-01

Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation

Impact of Body Mass Index on Plasma N-Terminal ProB-Type Natriuretic Peptides in Chinese Atrial Fibrillation Patients without Heart Failure

PubMed Central

Zheng, Li-hui; Wu, Ling-min; Yao, Yan; Chen, Wen-sheng; Bao, Jing-ru; Huang, Wen; Shi, Rui; Zhang, Kui-jun; Zhang, Shu

2014-01-01

Background An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure. Methods A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m2) and normal weight (BMI<25 kg/m2) patients. Results Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level. Conclusions An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients. PMID:25144363

Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

PubMed

Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

2007-10-01

In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

Early identification of acute heart failure at the time of presentation: do natriuretic peptides make the difference?

PubMed

Möckel, Martin; von Haehling, Stephan; Vollert, Jörn O; Wiemer, Jan C; Anker, Stefan D; Maisel, Alan

2018-06-01

The early identification of patients with acute heart failure (AHF) is challenging as many other diseases lead to a clinical presentation with dyspnea. The aim of the study was to evaluate the impact of natriuretic peptides at common HF study cut-offs on the diagnosis of patients with dyspnea at admission. For this post hoc analysis, we analysed n = 726 European Union (EU) patients from the prospective BACH (Biomarkers in Acute Heart Failure) study. Cut-offs were 350 ng/L (BNP), 300 pmol/L [pro-atrial natriuretic peptide (proANP)], and 1800 ng/L (NT-proBNP). These cut-offs had equivalent 90 days' mortality in the EU cohort of BACH. We analysed the effect of selection using these cut-offs on the prevalence of the gold standard diagnoses made in the BACH study and the respective mortality. The prevalence of AHF is increased from 47.5 to 75.6% (NT-proBNP criteria) up to 79.7% (BNP criteria). With the use of the proANP criteria, 90 days' mortality of patients with AHF rose from 14 to 17% (P = 0.029). In the group with no-AHF diagnoses, mortality rose from 10 to 25% (P < 0.001). The prevalence of patients with the gold standard diagnoses of AHF among those presenting with dyspnea to the emergency department is significantly increased by the use of natriuretic peptides with common cut-offs used in prospective HF studies. Nevertheless, in the selected groups, patients with no AHF diagnosis have the highest mortality, and therefore, the addition of a natriuretic peptide alone is insufficient to start specific therapies. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Neonatal oxytocin treatment modulates oxytocin receptor, atrial natriuretic peptide, nitric oxide synthase and estrogen receptor mRNAs expression in rat heart

PubMed Central

Pournajafi-Nazarloo, Hossein; Perry, Adam; Partoo, Leila; Papademeteriou, Eros; Azizi, Feridoun; Carter, C. Sue; Cushing, Bruce S.

2007-01-01

Oxytocin (OT) has been implicated in reproductive functions, induction of maternal behavior as well as endocrine and neuroendocrine regulation of the cardiovascular system. Here we demonstrate that neonatal manipulation of OT can modulate the mRNAs expression for OT receptor (OTR), atrial natriuretic peptide (ANP), endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERα) in the heart. On the first day of postnatal life, female and male rats were randomly assigned to receive one of following treatments; (a) 50 µl i.p. injection of 7 µg OT, (b) 0.7 µg of OT antagonist (OTA), or (c) isotonic saline (SAL). Hearts were collected either on postnatal day 1 or day 21 (D1 or D21) and the mRNAs expression of OTR, ANP, inducible NOS (iNOS), eNOS, ERα and estrogen receptor beta (ERβ) were compared by age, treatment, and sex utilizing Real Time PCR. OT treatment significantly increased heart OTR, ANP and eNOS mRNAs expression on D1 in both males and females, ERα increased only in females. While there were significant changes in the relative expression of all types of mRNA between D1 and D21 there were no significant treatment effects observed in D21 animals. OTA treatment significantly decreased basal ANP and eNOS mRNAs expression on D1 in both sexes. The results indicate that during the early postnatal period OT can have an immediate effect on the expression OTR, ANP, eNOS, and ERα mRNAs and that these effects are mitigated by D21. Also with the exception of ERα mRNA, the effects are the same in both sexes. PMID:17537544

Plant natriuretic peptides: systemic regulators of plant homeostasis and defense that can affect cardiomyoblasts.

PubMed

Gehring, Chris; Irving, Helen

2013-06-01

Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3',5'-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apoptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs.

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

Opposite actions of transforming growth factor-beta 1 on the gene expression of atrial natriuretic peptide biological and clearance receptors in a murine thymic stromal cell line.

PubMed

Agui, T; Xin, X; Cai, Y; Shim, G; Muramatsu, Y; Yamada, T; Fujiwara, H; Matsumoto, K

1995-09-01

The regulation of the gene expression of the atrial natriuretic peptide receptor (ANPR) subtypes, ANPR-A, ANPR-B, and ANPR-C, was investigated in a murine thymic stromal cell line, MRL 104.8a. When MRL 104.8a cells were cultured with transforming growth factor (TGF)-beta1, [125I]ANP binding sites increased with increasing dose of TGF-beta1. These binding sites were identified as ANPR-C by a displacement experiment with ANPR-C-specific ligand, C-ANF, and by the affinity cross-linking of the [125I]ANP binding sites with a chemical cross-linker to determine the molecular weight of the ANPR. This augmentation of the ANPR-C expression was elucidated to occur at the transcriptional level by Northern blot experiment, comparison of the relative amounts of mRNA by reverse transcription (RT)-PCR, and in vitro nuclear transcription assay. Conversely, the expression of the ANP biological receptors, ANPR-A and ANPR-B, was shown to be down-regulated by TGF-beta1. These data suggest that TGF-beta1 regulates the gene expression of ANPRs in the thymic stromal cells and that ANP and TGF-beta1 might affect the thymic stromal cell functions.

Excessive Adiposity and Metabolic Dysfunction Relate to Reduced Natriuretic Peptide During RAAS Activation in HIV.

PubMed

Murphy, Caitlin A; Fitch, Kathleen V; Feldpausch, Meghan; Maehler, Patrick; Wong, Kimberly; Torriani, Martin; Adler, Gail K; Grinspoon, Steven K; Srinivasa, Suman

2018-02-01

Natriuretic peptides (NPs) negatively feedback on the renin-angiotensin-aldosterone system (RAAS) and play a critical role in preserving cardiac structure and maintaining metabolic homeostasis. Well-treated HIV-infected individuals are at risk for fat redistribution and demonstrate evidence of RAAS dysregulation, which relates to metabolic dysfunction. We investigated circulating NPs in relation to RAAS physiology and metrics of body composition for the first time in HIV. We assessed atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and amino terminal pro B-type natriuretic peptide (NT-proBNP) during acute activation of the RAAS using a low sodium controlled diet among 20 HIV-infected and 10 non-HIV-infected individuals well-phenotyped for body composition. BNP(60[44,152] vs. 196[91,251], P=.04) was significantly lower and serum aldosterone higher among HIV-infected vs. non-HIV-infected individuals. BNP was significantly and inversely associated with body composition [waist circumference(r=-0.46, P=.04), BMI(r=-0.55, P=.01), body adiposity index (r=-0.49, P=.03)], metabolic indices [total cholesterol(r=-0.44, P=.05), HOMA-IR(r=-0.44, P=.05), MAP (r=-0.44, P=.05)], and serum aldosterone(r=-0.49,P=.03) among the HIV group. These relationships were not demonstrated in the non-HIV group. In a four-group comparison stratifying by HIV serostatus and above/below BMI 25 kg/m2, BNP decreased significantly across groups, being highest in non-HIV with BMI<25 kg/m2 and lowest in HIV with BMI >25 kg/m2 (overall P=.01). Relatively reduced NP, particularly BNP, among HIV-infected individuals with excess adiposity may contribute to reduced suppression of aldosterone and potentially drive aldosterone-mediated metabolic complications. Novel strategies which target RAAS blockade and/or augment NPs may be potentially useful to reduce cardiometabolic disease among HIV-infected individuals in whom these systems are perturbed. Copyright © 2018 Endocrine Society

Evaluation of atrial electromechanical delay and left atrial mechanical function in patients with obstructive sleep apnea : Cardiac involvement in patients with OSA.

PubMed

Karabag, Turgut; Aydin, Mustafa; Altin, Remzi; Dogan, Sait M; Cil, Cem; Buyukuysal, Cagatay; Sayin, Muhammet R

2012-07-01

The aim of this study was to evaluate atrial electromechanical delay measured by tissue Doppler imaging and left atrial mechanical function in patients with obstructive sleep apnea (OSA). Fourty-seven moderate-to-severe OSA patients who were newly diagnosed by polysomnography (Apnea-hypopnea index ≥ 15 events/h, 32 males, mean age 49.4 ± 11.5) and 30 patients who had no OSA in polysomnography (Apnea-hypopnea index < 5 events/h, 21 males, mean age 45.4 ± 9.1) were included in the study. Using tissue Doppler, diastolic functions, atrial electromechanical coupling were measured from the lateral mitral, septal, and tricuspid annulus. Inter, intra, and left atrial electromechanical delay were calculated (lateral-tricuspid, septum-tricuspid, lateral-septal). Left atrial volumes (maximal, minimal, and presystolic) were measured by the method of discs in the apical four-chamber view and were indexed to body surface area. Mechanical function parameters of the left atrium were also calculated. Interatrial, intraatrial, and left atrial electromechanical delays were significantly higher in the OSA group compared to the control group. Passive emptying fraction was significantly decreased, volume at the beginning of atrial systole and active emptying volume were significantly increased in OSA patients compared to the controls. The apnea-hypopnea index was significantly associated with interatrial and intraatrial electromechanical delay, passive emptying fraction, and conduit volume. Electromechanical delay was markedly prolonged and left atrial electromechanical function was impaired in untreated OSA patients. These impairments worsen with increasing severity of OSA.

Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?

PubMed

Sidorova, Tatiana N; Mace, Lisa C; Wells, K Sam; Yermalitskaya, Liudmila V; Su, Pei-Fang; Shyr, Yu; Atkinson, James B; Fogo, Agnes B; Prinsen, Joseph K; Byrne, John G; Petracek, Michael R; Greelish, James P; Hoff, Steven J; Ball, Stephen K; Glabe, Charles G; Brown, Nancy J; Barnett, Joey V; Murray, Katherine T

2014-12-02

Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ-specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (PAOs) in atrial tissue has not been previously investigated. Atrial samples were collected during elective cardiac surgery in patients without a history of atrial arrhythmias, congestive heart failure, cardiomyopathy, or amyloidosis. Immunohistochemistry was performed for PAOs using a conformation-specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium-specific marker, the fraction of myocardium colocalizing with PAOs (PAO burden) was quantified (green/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7±13.8 years. Most patients (62%) were male, 23% had diabetes, 72% had hypertension, and 42% had coronary artery disease. A majority (n=62) underwent aortic valve replacement, with fewer undergoing coronary artery bypass grafting (n=34) or mitral valve replacement/repair (n=24). Immunostaining detected intracellular PAOs in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green/red ratio value for the samples was 0.11±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAOs in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates, PAO burden was independently associated with the presence of hypertension. PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Effects of atorvastatin on atrial remodeling in a rabbit model of atrial fibrillation produced by rapid atrial pacing.

PubMed

Yang, Qian; Qi, Xiaoyong; Dang, Yi; Li, Yingxiao; Song, Xuelian; Hao, Xiao

2016-06-24

Accumulating evidence suggests that myeloperoxidase (MPO) is involved in atrial remodeling of atrial fibrillation (AF). Statins could reduce the MPO levels in patients with cardiovascular diseases. This study evaluated the effects of atorvastatin on MPO level and atrial remodeling in a rabbit model of pacing-induced AF. Eighteen rabbits were randomly divided into sham, control and atorvastatin groups. Rabbits in the control and atorvastatin groups were subjected to rapid atrial pacing (RAP) at 600 bpm for 3 weeks, and treated with placebo or atorvastatin (2.5 mg/kg/d), respectively. Rabbits in the sham group did not receive RAP. After 3 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, atrial effective refractory period (AERP) and AF inducibility were measured by atrial electrophysiological examination, and histological changes were evaluated by Masson trichrome-staining. The L-type calcium channel α1c (Cav1.2), collagen I and III, MPO, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by real time polymerase chain reaction and/or western blot. All rabbits were found to have maintained sinus rhythm after 3 weeks of RAP. Atrial burst stimulation induced sustained AF (>30 min) in 5, 4, and no rabbits in the control, atorvastatin, and sham groups, respectively. The AERP shortened and Cav1.2 mRNA level decreased in the control group, but these changes were suppressed in the atorvastatin group. Obvious left atrial enlargement and dysfunction was found in both control and atorvastatin groups. Compared with the control group, these echocardiograhic indices of left atrium did not differ in the atorvastatin group. Prominent atrial fibrosis and increased levels of collagen I and III were observed in the control group but not in the atorvastatin group. The mRNA and protein levels of MPO, MMP-2 and MMP-9 significantly increased in the control group, but these changes were prevented in the atorvastatin group. Treatment

Constitutive activation and uncoupling of the atrial natriuretic peptide receptor by mutations at the dimer interface. Role of the dimer structure in signalling.

PubMed

Qiu, Yue; Ogawa, Haruo; Miyagi, Masaru; Misono, Kunio S

2004-02-13

The crystal packing of the extracellular hormone binding domain of the atrial natriuretic peptide (ANP) receptor contains two possible dimer pairs, the head-to-head (hh) and tail-to-tail (tt) dimer pairs associated through the membrane-distal and membrane-proximal subdomains, respectively. The tt-dimer structure has been proposed previously (van den Akker, F., Zhang, X., Miyagi, M., Huo, X., Misono, K. S., and Yee, V. C. (2000) Nature 406, 101-104). However, no direct evidence is available to identify the physiological dimer form. Here we report site-directed mutagenesis studies of residues at the two alternative dimer interfaces in the full-length receptor expressed on COS cells. The Trp74 to Arg mutation (W74R) or D71R at the hh-dimer interface caused partial constitutive guanylate cyclase activation, whereas mutation F96D or H99D caused receptor uncoupling. In contrast, mutation Y196D or L225D at the tt-interface had no such effect. His99 modification at the hh-dimer interface by ethoxyformic anhydride abolished ANP binding. These results suggest that the hh-dimer represents the physiological structure. Recently, we determined the crystal structure of ANPR complexed with ANP and proposed a hormone-induced rotation mechanism mediating transmembrane signaling (H. Ogawa, Y. Qiu, C. M. Ogata, and K. S. Misono, submitted for publication). The observed effects of mutations are consistent with the ANP-induced structural change identified from the crystal structures with and without ANP and support the proposed rotation mechanism for ANP receptor signaling.

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

PubMed

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

2018-08-15

Idiopathic isolated fibrotic atrial cardiomyopathy (IIF-ACM) is a novel subtype of cardiomyopathy characterized by atrial fibrosis that does not involve the ventricular myocardium and is associated with significant atrial tachyarrhythmia. The mechanisms underlying its pathogenesis are unknown. Atrium samples were obtained from 3 patients with IIF-ACM via surgical intervention. Control samples were consisted of 3 atrium biopsies from patients with congenital heart disease and normal sinus rhythm, matched for gender, age and basic clinical characteristics. Comparative histology, immunofluorescence staining, electron microscopy and proteomics analyses were carried out to explore the unique pathogenesis of IIF-ACM. IIF-ACM atria displayed disordered myofibrils, profound fibrosis and mitochondrial damages compared to the control atria. Proteomics profiling identified metabolic pathways as the most profound changes in IIF-ACM. Our study suggested that metabolic changes in the atrial myocardium caused mitochondrial oxidative stress and potential cell damage, which further led to atrial fibrosis and myofibril disorganization, the characteristic phenotype of IIF-ACM. Copyright © 2018 Elsevier B.V. All rights reserved.

Mid-regional pro-atrial natriuretic peptide as a prognostic marker for all-cause mortality in patients with symptomatic coronary artery disease.

PubMed

von Haehling, Stephan; Papassotiriou, Jana; Hartmann, Oliver; Doehner, Wolfram; Stellos, Konstantinos; Geisler, Tobias; Wurster, Thomas; Schuster, Andreas; Botnar, Rene M; Gawaz, Meinrad; Bigalke, Boris

2012-11-01

In the present study, we investigated the prognostic value of MR-proANP (mid-regional pro-atrial natriuretic peptide). We consecutively evaluated a catheterization laboratory cohort of 2700 patients with symptomatic CAD (coronary artery disease) [74.1% male; ACS (acute coronary syndrome), n=1316; SAP (stable angina pectoris), n=1384] presenting to the Cardiology Department of a large primary care hospital, all of whom underwent coronary angiography. Serum MR-proANP and other laboratory markers were sampled at the time of presentation or in the catheterization laboratory. Clinical outcome was assessed by hospital chart analysis and telephone interviews. The primary end point was all-cause death at 3 months after enrolment. Follow-up data were complete in 2621 patients (97.1%). Using ROC (receiver operating characteristic) curves, the AUC (area under the curve) of 0.73 [95% CI (confidence interval), 0.67-0.79] for MR-proANP was significantly higher compared with 0.58 (95% CI, 0.55-0.62) for Tn-I (troponin-I; DeLong test, P=0.0024). According to ROC analysis, the optimal cut-off value of MR-proANP was at 236 pmol/l for all-cause death, which helped to find a significantly increased rate of all-cause death (n=76) at 3 months in patients with elevated baseline concentrations (≥236 pmol/l) compared with patients with a lower concentration level in Kaplan-Meier survival analysis (log rank, P<0.001). The predictive performance of MR-proANP was independent of other clinical variables or cardiovascular risk factors, and superior to that of Tn-I or other cardiac biomarkers (all: P<0.0001). MR-proANP may help in the prediction of all-cause death in patients with symptomatic CAD. Further studies should verify its prognostic value and confirm the appropriate cut-off value.

Surgery for atrial fibrillation.

PubMed

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

1996-01-01

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

Diverse molecular forms of plasma B-type natriuretic peptide in heart failure.

PubMed

Nishikimi, Toshio; Minamino, Naoto; Nakao, Kazuwa

2011-06-01

Recent studies have shown that not only plasma B-type natriuretic peptide (BNP)-32, but also plasma proBNP-108 is increased in heart failure (HF), and that the current BNP-32 assay kit crossreacts with proBNP-108. It also was shown that both BNP-32 and proBNP-108 were higher in HF than in normal. The proBNP-108/total BNP (BNP-32 + proBNP-108) ratio was widely distributed and patients with HF with ventricular overload had higher proBNP-108/total BNP ratio than HF patients with atrial overload. Consistent with this finding, proBNP-108 was the major molecular form in ventricular tissue, and BNP-32 was the major molecular form in atrial tissue. In addition, proBNP-108 was the major molecular form of BNP in pericardial fluid. The proBNP-108/total BNP ratio increased with deterioration of HF and decreased with improvement of HF. Thus, not only BNP-32, but also proBNP-108 is increased in HF and the proBNP-108/total BNP ratio also rises in association with pathophysiological conditions such as ventricular overload. A new hypothesis that O-glycosylation at Thr71 in a region close to the cleavage site impairs proBNP-108 processing was proposed. In the future, the precise mechanism of increased proBNP-108 in HF should be elucidated.

The Left Atrial Appendage Revised

PubMed Central

Evora, Paulo Roberto Barbosa; Menardi, Antonio Carlos; Celotto, Andrea Carla; Albuquerque, Agnes Afrodite S.; Chagas, Hannah Miranda Araujo; Rodrigues, Alfredo José

2017-01-01

Nonvalvular atrial fibrillation is associated with a 4- to 5-fold strokes increase and may be responsible for 15% to 20% of all strokes in the elderly. In this scenario, the left atrial appendage thrombus would be the associated with 90% of cases. The use of anticoagulants, percutaneous devices, and the left atrial appendage surgical exclusion is still an open discussion. For left atrial appendage procedures, relevant anatomic spatial relationships have to be emphasized, besides the chance of the normal physiological functioning would be eliminated with the proceedings. There are evidences that the left atrial appendage closure during routine cardiac surgery is significantly associated with an increased risk of early postoperative atrial fibrillation. Therefore, the purpose of this review is to focus basic aspects for continuous medical education. In summary, the rationale of this text is to emphasize anatomical and pharmacological aspects involved in the simple surgical exclusion of left atrial appendage under cardiopulmonary bypass. There are several operative techniques, but to conclude this revision it will present one of them based on the discussed basic sciences. PMID:29267615

Regulation of natriuretic peptide receptor A and B expression by transforming growth factor-beta 1 in cultured aortic smooth muscle cells.

PubMed

Fujio, N; Gossard, F; Bayard, F; Tremblay, J

1994-06-01

Two types of natriuretic peptide receptors (NPR-A and NPR-B) are membrane guanylate cyclases whose relative expression varies in different tissues. Because natriuretic peptides have been shown to inhibit aortic smooth muscle proliferation, we investigated the regulation of NPR-A and NPR-B in these cells under different proliferative conditions. NPR subtype mRNA levels were measured by our newly developed quantitative reverse transcription-polymerase chain reaction assay using mutated NPR-A and NPR-B cRNA as internal standards. The functional impact of their expression was determined by atrial natriuretic peptide (ANP)- and C-type natriuretic peptide (CNP)-induced stimulation of cyclic GMP production. In the intact aorta, NPR-B mRNA levels were found to be 10-fold higher than those of NPR-A. This dominance was further amplified (1000-fold) in long-term cultures (10 to 15 passages) of aortic smooth muscle cells (ASMC). Higher cyclic GMP production with CNP than with ANP was observed in cultured ASMC from Wistar-Kyoto (WKY) rats. Similar stimulation by the two agonists was noted in spontaneously hypertensive rat (SHR) cells, paralleled by a 10-fold increase in NPR-A mRNA levels and ANP stimulation of cyclic GMP in hypertensive cells. The present study also evaluated NPR-A and NPR-B mRNA control by transforming growth factor-beta 1 (TGF-beta 1), an important regulator of cell proliferation that is overexpressed in SHR ASMC. TGF-beta 1 decreased both NPR-A and NPR-B mRNA levels with a predominant effect in SHR cells at high cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

[The role of natriuretic peptides in heart failure].

PubMed

Ancona, R; Limongelli, G; Pacileo, G; Miele, T; Rea, A; Roselli, T; Masarone, D; Messina, S; Palmieri, R; Golia, E; Iacomino, M; Gala, S; Calabrò, P; Di Salvo, G; Calabrò, R

2007-10-01

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Relation of Obesity to New-Onset Atrial Fibrillation and Atrial Flutter in Adults.

PubMed

Foy, Andrew J; Mandrola, John; Liu, Guodong; Naccarelli, Gerald V

2018-05-01

Prospective cohort studies involving older adults report an association of obesity and new-onset atrial fibrillation and atrial flutter. To assess this relation, we performed a longitudinal cohort study from January 1, 2006 to December 31, 2013, using a national claims database that tracks all inpatient, outpatient, and pharmacy claims data. The primary end point of new-onset atrial fibrillation was compared between obese and nonobese cohorts. We used logistic regression to determine the strength of association between obesity and new-onset atrial fibrillation controlling for age, gender, hypertension, and diabetes. Overall, 67,278 subjects were included in the cohort, divided evenly between those with and without a diagnosis of obesity. Obese subjects were significantly more likely to have hypertension (29.5% vs 14.6%) and diabetes (12.7% vs 5.2%) at study onset. Over 8 years of follow-up, we recorded a new diagnosis of atrial fibrillation in 1,511 (2.2%) subjects. Obesity was strongly associated with a new diagnosis of atrial fibrillation after controlling for age, gender, hypertension, and diabetes (odds ratio 1.4, 95% confidence interval 1.3 to 1.6). In conclusion, this information contributes to the growing evidence supporting the causal relation between obesity and atrial fibrillation, and emphasizes the need of addressing obesity as part of our therapeutic strategy to prevent atrial fibrillation. Copyright © 2018 Elsevier Inc. All rights reserved.

Associates of an elevated natriuretic peptide level in stable heart failure patients: implications for targeted management.

PubMed

Jan, Aftab; Dawkins, Ian; Murphy, Niamh; Collier, Patrick; Baugh, John; Ledwidge, Mark; McDonald, Kenneth; Watson, Chris J

2013-01-01

Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e') was measured. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e', creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e' and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

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

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

PubMed

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

1993-12-01

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

Amino terminal pro brain natriuretic peptide predicts all-cause mortality in patients with chronic obstructive pulmonary disease: Systematic review and meta-analysis.

PubMed

Pavasini, Rita; Tavazzi, Guido; Biscaglia, Simone; Guerra, Federico; Pecoraro, Alessandro; Zaraket, Fatima; Gallo, Francesco; Spitaleri, Giosafat; Contoli, Marco; Ferrari, Roberto; Campo, Gianluca

2017-05-01

Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF). HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, the prognostic role of NP in COPD patients remains unclear. The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients. We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients. Nine studies were considered for qualitative analysis for a total of 2788 patients. Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis. Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively). The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age). NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD.

Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery.

PubMed

Larifla, Laurent; Déprez, Isabelle; Pham, Isabelle; Rideau, Dominique; Louzier, Vanessa; Adam, Micheline; Eloit, Marc; Foucan, Lydia; Adnot, Serge; Teiger, Emmanuel

2012-07-01

Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury. ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus expressing the RSV-controlled β-galactosidase gene (Ad-RSV-β-gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution. VSMCs transfected by Ad-RSV-ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control group. The present study demonstrates the efficacy of recombinant adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury. Copyright © 2012 John Wiley & Sons, Ltd.

Correlation between plasma N-terminal pro-brain natriuretic peptide levels and changes in New York Heart Association functional class, left atrial size, left ventricular size and function after mitral and/or aortic valve replacement.

PubMed

Elasfar, Abdelfatah

2012-01-01

Elevated plasma brain natriuretic peptide (BNP) levels have been demonstrated in patients with chronic valvular disease. We designed the present study to assess whether changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after mitral, aortic and double mitral and aortic valve replacement reflect changes in heart failure (HF) symptoms including New York Heart Association (NYHA) class and changes in left atrium (LA) size, left ventricle (LV) size and LV function. A prospective observational nonrandomized study among consecutive patients undergoing mitral and/or aortic valve replacement in our center. The study population consisted of 24 patients (mean [SD] age of 55.3 [16.2] years, 58% were males) who underwent surgical mitral valve replacement (12 patients), aortic valve replacement (8 patients) and combined mitral and aortic valve replacement (4 patients). NT-proBNP measurements, transthoracic echocardiography and NYHA class assessments were performed before and 6 months after surgery. The decrease in NT-proBNP was associated with decrease in left atrial dimension (r = 0.73, P < .002), LV end-diastolic dimension (r=0.65, P=.001), LV end-systolic dimension (r=0.53, P=.036), and increase in ejection fraction (r=-0.65, P=.001) after 6 months postoperatively. Furthermore, a decreasing NT-proBNP was associated with improvement in NYHA class. NT-proBNP levels after mitral, aortic and double valve replacement correlates with changes in HF manifestations as well as changes in LA size and LV dimension and function. Thus, we hypothesize that interval measurement of the NT-proBNP level at clinic visits can allow early detection of any clinical deterioration as well as the possibility of assessment of the long-term outcome of those patients.

Influence of Genotype on Structural Atrial Abnormalities and Atrial Fibrillation or Flutter in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

PubMed

Bourfiss, Mimount; Te Riele, Anneline S J M; Mast, Thomas P; Cramer, Maarten J; VAN DER Heijden, Jeroen F; VAN Veen, Toon A B; Loh, Peter; Dooijes, Dennis; Hauer, Richard N W; Velthuis, Birgitta K

2016-12-01

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with desmosomal mutations. Although desmosomal disruption affects both ventricles and atria, little is known about atrial involvement in ARVD/C. To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype. We included 71 patients who met ARVD/C Task Force Criteria and underwent cardiac magnetic resonance (CMR) imaging and molecular genetic analysis. Indexed atrial end-diastolic volume and area-length-ejection-fraction (ALEF) were evaluated on CMR and compared to controls with idiopathic right ventricular outflow tract tachycardia (n = 40). The primary outcome was occurrence of AA (atrial fibrillation or atrial flutter) during follow-up, recorded by 12-lead ECG, Holter monitoring or implantable cardioverter defibrillator (ICD) interrogation. Patients harbored a desmosomal plakophilin-2 (PKP2) (n = 37) or nondesmosomal phospholamban (PLN) (n = 14) mutation. In 20 subjects, no pathogenic mutation was identified. Compared to controls, right atrial (RA) volumes were reduced in PKP2 (P = 0.002) and comparable in PLN (P = 0.441) mutation carriers. In patients with no mutation identified, RA (P = 0.011) and left atrial (P = 0.034) volumes were increased. Bi-atrial ALEF showed no significant difference between the groups. AA were experienced by 27% of patients and occurred equally among PKP2 (30%) and no mutation identified patients (30%), but less among PLN mutation carriers (14%). Genotype influences atrial volume and occurrence of AA in ARVD/C. While the incidence of AA is similar in PKP2 mutation carriers and patients with no mutation identified, PKP2 mutation carriers have significantly smaller atria. This suggests a different arrhythmogenic mechanism. © 2016 Wiley Periodicals, Inc.

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

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.

Impact of B-Type Natriuretic Peptide Level on Risk Stratification of Thromboembolism and Death in Patients With Nonvalvular Atrial Fibrillation　- The Hokuriku-Plus AF Registry.

PubMed

Hayashi, Kenshi; Tsuda, Toyonobu; Nomura, Akihiro; Fujino, Noboru; Nohara, Atsushi; Sakata, Kenji; Konno, Tetsuo; Nakanishi, Chiaki; Tada, Hayato; Nagata, Yoji; Teramoto, Ryota; Tanaka, Yoshihiro; Kawashiri, Masa-Aki; Yamagishi, Masakazu

2018-04-25

B-type natriuretic peptide (BNP) may be a predictor of stroke risk in patients with nonvalvular atrial fibrillation (NVAF); because heart failure is associated with the incidence of stroke in AF patients. However, limited data exist regarding the association between BNP at baseline and risks of thromboembolic events (TE) and death in NVAF patients. We prospectively studied 1,013 NVAF patients (725 men, 72.8±9.7 years old) from the Hokuriku-plus AF Registry to determine the relationship between BNP at baseline and prognosis among Japanese NVAF patients. During the follow-up period (median, 751 days); 31 patients experienced TE and there were 81 cases of TE/all-cause death. For each endpoint we constructed receiver-operating characteristic curves that gave cutoff points of BNP for TE (170 pg/mL) and TE/all-cause death (147 pg/mL). Multivariate analysis with the Cox-proportional hazards model indicated that high BNP was significantly associated with risks of TE (hazard ratio [HR] 3.86; 95% confidence interval [CI] 1.83-8.67; P=0.0003) and TE/all-cause death (HR 2.27; 95% CI 1.45-3.56; P=0.0003). Based on the C-index and net reclassification improvement, the addition of BNP to CHA 2 DS 2 -VASc statistically improved the prediction of TE. In a real-world cohort of Japanese NVAF patients, high BNP was significantly associated with TE and death. Plasma BNP might be a useful biomarker for these adverse clinical events.

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.

PubMed

Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S

2010-03-01

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, H.; Qiu, Y; Philo, J

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. Amore » 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.« less

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

PubMed Central

Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S

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. PMID:20066666

Thyrotoxic atrial fibrillation.

PubMed

Parmar, Malvinder S

2005-01-04

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

Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death.

PubMed

Li, Zheng; Wang, Ji-Wei; Wang, Wei-Zhi; Zhi, Xiao-Fei; Zhang, Qun; Li, Bo-Wen; Wang, Lin-Jun; Xie, Kun-Ling; Tao, Jin-Qiu; Tang, Jie; Wei, Song; Zhu, Yi; Xu, Hao; Zhang, Dian-Cai; Yang, Li; Xu, Ze-Kuan

2016-10-01

Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

PubMed Central

Cheng, Juan-Juan; Zhao, Shi-Di; Gao, Ming-Zhu; Huang, Hong-Yu; Gu, Bing; Ma, Ping; Chen, Yan; Wang, Jun-Hong; Yang, Cheng-Jian; Yan, Zi-He

2015-01-01

Background Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion. Methods PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model. Results In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies. Conclusions BNP, NT-proBNP, and MR-proANP, either in blood

Diadenosine tetraphosphate stimulates atrial ANP release via A(1) receptor: involvement of K(ATP) channel and PKC.

PubMed

Yuan, Kuichang; Cao, Chunhua; Bai, Guang Yi; Kim, Sung Zoo; Kim, Suhn Hee

2007-07-01

Diadenosine polyphosphates (APnAs) are endogenous compounds and exert diverse cardiovascular functions. However, the effects of APnAs on atrial ANP release and contractility have not been studied. In this study, the effects of diadenosine tetraphosphate (AP4A) on atrial ANP release and contractility, and their mechanisms were studied using isolated perfused rat atria. Treatment of atria with AP4A resulted in decreases in atrial contractility and extracellular fluid (ECF) translocation whereas ANP secretion and cAMP levels in perfusate were increased in a dose-dependent manner. These effects of AP4A were attenuated by A(1) receptor antagonist but not by A(2A) or A(3) receptor antagonist. Other purinoceptor antagonists also did not show any effects on AP4A-induced ANF release and contractility. The increment of ANP release and negative inotropy induced by AP4A was similar to those induced by AP3A, AP5A, and AP6A. Protein kinase A inhibitors accentuated AP4A-induced ANP secretion. In contrast, an inhibitor of phospholipase C, protein kinase C or sarcolemma K(ATP) channel completely blocked AP4A-induced ANP secretion. However, an inhibitor of adenylyl cyclase or mitochondria K(ATP) channel had no significant modification of AP4A effects. These results suggest that AP4A regulates atrial inotropy and ANP release mainly through A(1) receptor signaling involving phospholipase C-protein kinase C and sarcolemmal K(ATP) channel and that protein kinase A negatively modulates the effects of AP4A.

Clathrin-dependent internalization, signaling, and metabolic processing of guanylyl cyclase/natriuretic peptide receptor-A.

PubMed

Somanna, Naveen K; Mani, Indra; Tripathi, Satyabha; Pandey, Kailash N

2018-04-01

Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP), have pivotal roles in renal hemodynamics, neuroendocrine signaling, blood pressure regulation, and cardiovascular homeostasis. Binding of ANP and BNP to the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) induces rapid internalization and trafficking of the receptor via endolysosomal compartments, with concurrent generation of cGMP. However, the mechanisms of the endocytotic processes of NPRA are not well understood. The present study, using 125 I-ANP binding assay and confocal microscopy, examined the function of dynamin in the internalization of NPRA in stably transfected human embryonic kidney-293 (HEK-293) cells. Treatment of recombinant HEK-293 cells with ANP time-dependently accelerated the internalization of receptor from the cell surface to the cell interior. However, the internalization of ligand-receptor complexes of NPRA was drastically decreased by the specific inhibitors of clathrin- and dynamin-dependent receptor internalization, almost 85% by monodansylcadaverine, 80% by chlorpromazine, and 90% by mutant dynamin, which are specific blockers of endocytic vesicle formation. Visualizing the internalization of NPRA and enhanced GFP-tagged NPRA in HEK-293 cells by confocal microscopy demonstrated the formation of endocytic vesicles after 5 min of ANP treatment; this effect was blocked by the inhibitors of clathrin and by mutant dynamin construct. Our results suggest that NPRA undergoes internalization via clathrin-mediated endocytosis as part of its normal itinerary, including trafficking, signaling, and metabolic degradation.

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

2017-08-01

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.

Central peptidergic mechanisms controlling reproductive hormone secretion: novel methodology reveals a role for the natriuretic peptides.

PubMed

Samson, W K; Alexander, B D; Skala, K D; Huang, F L; Fulton, R J

1992-05-01

A variety of neural factors can influence reproductive hormone secretion by neuromodulatory actions within the hypothalamus or neuroendocrine actions within the anterior pituitary gland. Passive immunoneutralization and antagonist administration protocols have suggested physiological roles for a number of these factors; however, both experimental approaches have severe technical limitations. We have developed novel methodology utilizing cytotoxin cell targeting with neuropeptides linked to the toxic A chain of the plant cytotoxin ricin. With this methodology we can target and destroy in vivo or in vitro cells bearing receptors for that peptide. Ricin A chain conjugated to atrial natriuretic peptide (ANP), a neuropeptide known to pharmacologically inhibit luteinizing hormone-releasing hormone (LHRH) release, was injected into the cerebroventricular system of intact, cycling rats and ovariectomized rats. Cytotoxin conjugate treatment significantly lengthened the estrous cycle. In ovariectomized rats the luteinizing hormone surge induced by steroid priming was completely inhibited. LHRH content of the median eminences of these rats was not significantly altered. These data suggest that ANP binding to clearance receptors in the hypothalamus displaces the C-type natriuretic peptide (CNP) from the shared clearance receptor, making more CNP available to inhibit LHRH release. In the absence of cells bearing the clearance receptor all available CNP binds to the ANPR-B receptor and exerts its effect via an inhibitory interneuron, since LHRH fibers are spared by this treatment.

Usefulness of bedside tissue Doppler echocardiography and B-type natriuretic peptide (BNP) in differentiating congestive heart failure from noncardiac cause of acute dyspnea in elderly patients with a normal left ventricular ejection fraction and permanent, nonvalvular atrial fibrillation: insights from a prospective, monocenter study.

PubMed

Arques, Stephane; Roux, Emmanuel; Sbragia, Pascal; Pieri, Bertrand; Gelisse, Richard; Luccioni, Roger; Ambrosi, Pierre

2007-05-01

The incremental role of bedside tissue Doppler echocardiography and B-type natriuretic peptide (BNP) over the clinical judgment has been recently reported in the emergency diagnosis of congestive heart failure with a normal left ventricular ejection fraction (HFNEF). However, how well does this diagnostic strategy be applicable in the setting of atrial fibrillation is unknown. To investigate the usefulness of bedside tissue Doppler echocardiography and BNP in the emergency diagnosis of HFNEF in elderly patients with permanent, nonvalvular atrial fibrillation. Forty-one consecutive elderly patients with an ejection fraction > or =50% (mean age 84 years; 22 with HFNEF and 19 with noncardiac cause), hospitalized for acute dyspnea at rest, were prospectively enrolled; bedside septal E/Ea and BNP were obtained at admission. By multivariable logistic regression analysis including the clinical judgment of heart failure, E/Ea and BNP, E/Ea (P = 0.014) and BNP (P = 0.018) provided independent diagnostic information. Optimal cutoffs were 13 for E/Ea (area under the ROC curve of 0.846, P < 0.0001; sensitivity 81.8%, specificity 89.5%) and 253 pg/ml for BNP (area under the ROC curve of 0.928, P < 0.0001; sensitivity 86.4%, specificity 89.5%). The concordance between the clinical judgment and BNP concentration at the cutoff of 253 pg/ml correctly classified 24 of 25 patients; E/Ea at the cutoff of 13 correctly classified 14 of the 16 patients with discrepancy. Bedside tissue Doppler echocardiography and BNP provide useful additional diagnostic information over the clinical judgment for the emergency diagnosis of HFNEF in elderly patients with permanent, nonvalvular atrial fibrillation.

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.

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

PubMed

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

2018-06-01

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

Modulation of natriuretic peptide receptors in human adipose tissue: molecular mechanisms behind the "natriuretic handicap" in morbidly obese patients.

PubMed

Gentili, Alessandra; Frangione, Maria Rosaria; Albini, Elisa; Vacca, Carmine; Ricci, Maria Anastasia; De Vuono, Stefano; Boni, Marcello; Rondelli, Fabio; Rotelli, Luciana; Lupattelli, Graziana; Orabona, Ciriana

2017-08-01

The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as "natriuretic handicap." Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap. The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects. The study enrolled 34 obese and 20 control subjects undergoing bariatric or abdominal surgery, respectively. The main clinical and biochemical parameters, including circulating BNP, were assessed. In visceral (VAT) and subcutaneous AT (SAT) samples, collected during surgery, the adipocytes and stromal vascular fraction (SVF) expression of NPR-A and NPR-C and the SVF secretion of interleukin 6 (IL-6) were determined. Both VAT and SAT from obese patients expressed a lower NPR-A/NPR-C ratio in adipocytes and the SVF secreted a higher level of IL-6, compared with the controls. Moreover, NPR-A/NPR-C ratio expressed by VAT and SAT adipocytes negatively correlated with body mass index, insulin, the Homeostasis Model Assessment of Insulin resistance, and IL-6 secreted by SVF, and the expression of the clearance receptor NPR-C, in both the VAT and SAT adipocytes, showed a negative correlation with circulating BNP. Overall, insulin resistance/hyperinsulinemia and AT inflammation (ie, high level of IL-6) are the major determinants of the lower NPR-A/NPR-C ratio in adipocytes, thus contributing to the natriuretic handicap in obese subjects. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

Atrial therapies reduce atrial arrhythmia burden in defibrillator patients.

PubMed

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

2001-08-28

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

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

PubMed Central

Mesubi, Olurotimi O.; Anderson, Mark E.

2016-01-01

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

α-Adrenoceptor blockade modifies neurally induced atrial arrhythmias

PubMed Central

Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L.; Armour, John Andrew

2008-01-01

Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by α-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (α1-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (α2-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined α-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by α1,2-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal α-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that α-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system. PMID:18716036

Alpha-adrenoceptor blockade modifies neurally induced atrial arrhythmias.

PubMed

Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L; Armour, John Andrew

2008-10-01

Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by alpha-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (alpha(1)-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (alpha(2)-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined alpha-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by alpha(1,2)-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal alpha-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that alpha-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system.

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

PubMed

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

2018-05-01

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

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

Calcineurin Regulates Homologous Desensitization of Natriuretic Peptide Receptor-A and Inhibits ANP-Induced Testosterone Production in MA-10 Cells

PubMed Central

Henesy, Michelle B.; Britain, Andrea L.; Zhu, Bing; Amable, Lauren; Honkanen, Richard E.; Corbin, Jackie D.; Francis, Sharron H.; Rich, Thomas C.

2012-01-01

Receptor desensitization is a ubiquitous regulatory mechanism that defines the activatable pool of receptors, and thus, the ability of cells to respond to environmental stimuli. In recent years, the molecular mechanisms controlling the desensitization of a variety of receptors have been established. However, little is known about the molecular mechanisms that underlie desensitization of natriuretic peptide receptors, including natriuretic peptide receptor-A (NPR-A). Here we report that calcineurin (protein phosphatase 2B, PP2B, PPP3C) regulates homologous desensitization of NPR-A in murine Leydig tumor (MA-10) cells. We demonstrate that both pharmacological inhibition of calcineurin activity and siRNA-mediated suppression of calcineurin expression potentiate atrial natriuretic peptide (ANP)-induced cGMP synthesis. Treatment of MA-10 cells with inhibitors of other phosphoprotein phosphatases had little or no effect on ANP-induced cGMP accumulation. In addition, overexpression of calcineurin blunts ANP-induced cGMP synthesis. We also present data indicating that the inhibition of calcineurin potentiates ANP-induced testosterone production. To better understand the contribution of calcineurin in the regulation of NPR-A activity, we examined the kinetics of ANP-induced cGMP signals. We observed transient ANP-induced cGMP signals, even in the presence of phosphodiesterase inhibitors. Inhibition of both calcineurin and phosphodiesterase dramatically slowed the decay in the response. These observations are consistent with a model in which calcineurin mediated dephosphorylation and desensitization of NPR-A is associated with significant inhibition of cGMP synthesis. PDE activity hydrolyzes cGMP, thus lowering intracellular cGMP toward the basal level. Taken together, these data suggest that calcineurin plays a previously unrecognized role in the desensitization of NPR-A and, thereby, inhibits ANP-mediated increases in testosterone production. PMID:22876290

Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease.

PubMed

Wang, Rui; Yi, Xin; Li, Xiaoyan; Jiang, Xuejun

2015-01-01

Fibroblast growth factor-21 (FGF-21) has been discovered as a strong hormone, plays an important role in lipid metabolism, glucose metabolism, associated with several diseases such as obesity, metabolic syndrome, diabetes mellitus, and cardiovascular events; however, no evidence is available concerning the relationship of FGF-21 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). Twenty-four rheumatic heart disease patients were divided into two groups, 12 cases with AF and 12 cases with sinus rhythm (SR). Clinical characteristics and blood samples were collected before surgery; right atrial appendage samples were taken in the surgery of valve replacement. HE staining was performed to determine cross-sectional area of atrial myocytes; Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to evaluate the degree of cardiac fibrosis; the level of FGF-21 was evaluated via enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and real-time polymerase chain reaction (PCR). Compared with SR group, cross-sectional area of atrial myocytes and collagen volume fraction were significantly increased in the atrial tissue of AF group. The distribution of FGF-21 in the AF group was remarkably higher than SR group. In addition, plasma and mRNA levels of FGF-21 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. Using linear correlation analysis, the expression level of FGF-21 was found to be positively related to the degree of atrial fibrosis. FGF-21 might involve in the development and maintenance of atrial fibrosis in atrial fibrillation with rheumatic heart disease, and FGF-21 could be used as a novel biomarker to evaluate myocardial fibrosis in the future.

Impact of left atrial volume reduction concomitant with atrial fibrillation surgery on left atrial geometry and mechanical function.

PubMed

Marui, Akira; Saji, Yoshiaki; Nishina, Takeshi; Tadamura, Eiji; Kanao, Shotaro; Shimamoto, Takeshi; Sasahashi, Nozomu; Ikeda, Tadashi; Komeda, Masashi

2008-06-01

Left atrial geometry and mechanical functions exert a profound effect on left ventricular filling and overall cardiovascular performance. We sought to investigate the perioperative factors that influence left atrial geometry and mechanical functions after the Maze procedure in patients with refractory atrial fibrillation and left atrial enlargement. Seventy-four patients with atrial fibrillation and left atrial enlargement (diameter > or = 60 mm) underwent the Maze procedure in association with mitral valve surgery. The maximum left atrial volume and left atrial mechanical functions (booster pump, reservoir, and conduit function [%]) were calculated from the left atrial volume-cardiac cycle curves obtained by magnetic resonance imaging. A stepwise multiple regression analysis was performed to determine the independent variables that influenced the postoperative left atrial geometry and function. The multivariate analysis showed that left atrial reduction surgery concomitant with the Maze procedure and the postoperative maintenance of sinus rhythm were predominant independent variables for postoperative left atrial geometry and mechanical functions. Among the 58 patients who recovered sinus rhythm, the postoperative left atrial geometry and function were compared between patients with (VR group) and without (control group) left atrial volume reduction. At a mean follow-up period of 13.8 months, sinus rhythm recovery rate was better (85% vs 68%, P < .05) in the VR group and maximum left atrial volume was less (116 +/- 25 mL vs 287 +/- 73 mL, P < .001) than in the control group. The maximum left atrial volume reduced with time only in the VR group (reverse remodeling). Postoperative booster pump and reservoir function in the VR group were better than in the control group (25% +/- 6% vs 11% +/- 4% and 34% +/- 7% vs 16% +/- 4%, respectively, P < .001), whereas the conduit function in the VR group was lower than in the control group, indicating that the improvement of

Natriuretic peptide system in the rat submaxillary gland.

PubMed

Jankowski, M; Petrone, C; Tremblay, J; Gutkowska, J

1996-04-09

Natriuretic peptides and their receptors were characterized in rat submaxillary glands (SGs). Reverse phase-high performance liquid chromatography (HPLC) of rat SGs extracts revealed the presence of the 28-amino-acid (AA) circulating peptide ANP (Ser99-Tyr126) and the 126-AA prohormone (Asn1-Tyr126). The presence of ANP prohormone indicated that SGs are a site of ANP synthesis. Indeed, ANP mRNAs were demonstrated. ANP mRNA was 10 times lower than in the lung and only about 7 times lower than in the hypothalamus. ANP content in SG was determined as 30 +/- 8 ng/mg of protein (n = 7). In addition the presence of another member of the natriuretic peptide family, C-type natriuretic peptide (CNP), was found in SG. The CNP level of 293 +/- 38 pg/mg protein was significantly higher than in the lungs (44 +/- 6 pg/mg protein, P < 0.001, n = 5), but about 15 times lower than in hypothalamus (4.5 +/- 0.6 ng/mg protein, P < 0.001, n = 6). Both guanylyl cyclase and clearance receptors were expressed in SG. The presence of natriuretic peptide transcripts and their receptors suggests a role in rat SG functions.

Comparison of Brain Natriuretic Peptide Levels to Simultaneously Obtained Right Heart Hemodynamics in Stable Outpatients with Pulmonary Arterial Hypertension.

PubMed

Helgeson, Scott A; Imam, J Saadi; Moss, John E; Hodge, David O; Burger, Charles D

2018-05-01

Pulmonary arterial hypertension (PAH) is a progressive disease that requires validated biomarkers of disease severity. While PAH is defined hemodynamically by right heart catheterization (RHC), brain natriuretic peptide (BNP) is recommended by guidelines to assess disease status. Retrospectively collected data in 138 group 1 PAH patients were examined for the correlation of BNP levels to simultaneously obtained right heart catheterization (RHC). Patients were mostly Caucasian women, with functional class III symptoms, mean BNP of 406 ± 443 pg/mL, and an average right atrial pressure (RAP) of 9.9 ± 5.7 mm Hg and mean pulmonary artery pressure (mPAP) of 47.3 ± 14.7 mm Hg. Significant correlation was demonstrated between BNP and RAP ( p = 0.021) and mPAP ( p = 0.003). Additional correlation was seen with right heart size on echocardiography: right atrial (RAE; p = 0.04) and right ventricular enlargement ( p = 0.03). An increased BNP level was an independent predictor of mortality ( p < 0.0001), along with RAP ( p = 0.039) and RAE ( p = 0.018). Simultaneous collection of BNP at the time of RHC confirmed the correlation of BNP with right heart hemodynamics. The current results reinforce the use of BNP level as a continuous variable to assess disease severity in group 1 PAH.

Genomic analyses and cloning of novel chicken natriuretic peptide genes reveal new insights into natriuretic peptide evolution.

PubMed

Trajanovska, Sofie; Inoue, Koji; Takei, Yoshio; Donald, John A

2007-11-01

The natriuretic peptide (NP) family consists of multiple subtypes in teleosts, including atrial, B-type, ventricular, and C-type NPs (ANP, BNP, VNP, CNP-1-4, respectively), but only ANP, BNP, CNP-3, and CNP-4 have been identified in tetrapods. As part of understanding the molecular evolution of NPs in the tetrapod lineage, we identified NP genes in the chicken genome. Previously, only BNP and CNP-3 have been identified in birds, but we characterized two new chicken NP genes by cDNA cloning, synteny and phylogenetic analyses. One gene is an orthologue of CNP-1, which has only ever been reported in teleostei and bichir. The second gene could not be assigned to a particular NP subtype because of high sequence divergence and was named renal NP (RNP) due to its predominant expression in the kidney. CNP-1 mRNA was only detected in brain, while CNP-3 mRNA was expressed in kidney, heart, and brain. In the developing embryo, BNP and RNP transcripts were most abundant 24h post-fertilization, while CNP mRNA increased in a stage-dependent manner. Synthetic chicken RNP stimulated an increase in cGMP production above basal level in chicken kidney membrane preparations and caused a potent dose-dependent vasodilation of pre-constricted dorsal aortic rings. From conserved chromosomal synteny, we propose that the CNP-4 and ANP genes have been lost in chicken, and that RNP may have evolved from a VNP-like gene. Furthermore, we have demonstrated for the first time that CNP-1 is retained in the tetrapod lineage.

Age, Sex, and Blood Pressure-Related Influences on Reference Values of Left Atrial Deformation and Mechanics From a Large-Scale Asian Population.

PubMed

Liao, Jo-Nan; Chao, Tze-Fan; Kuo, Jen-Yuan; Sung, Kuo-Tzu; Tsai, Jui-Peng; Lo, Chi-In; Lai, Yau-Huei; Su, Cheng-Huang; Hung, Chung-Lieh; Yeh, Hung-I; Chen, Shih-Ann

2017-10-01

Left atrial (LA) function is tightly linked to several cardiovascular diseases and confers key prognostic information. Speckle tracking-based deformation as a feasible and sensitive LA mechanical assessment has proven its clinical significance beyond volume measures; however, the reference values remain largely unknown. We studied 4042 participants undergoing annual cardiovascular survey. Among them, 2812 healthy participants (65% men; mean age, 47.4±9.9 years) were eligible for speckle tracking analysis. Peak atrial longitudinal systolic strain and strain rate (SR) at systolic (SRs), early diastolic (SRe), and late diastolic atrial contraction phases (SRa) were analyzed by dedicated software (EchoPAC, GE) and compared in terms of age, sex, and blood pressure. Overall, women demonstrated higher peak atrial longitudinal systolic strain (39.34±7.99% versus 37.95±7.96%; P<0.001) and showed age-dependent more pronounced peak atrial longitudinal systolic strain functional decay than those of men (P value for interaction, <0.05), with men showing higher SRs and SRa, although lower SRe (all P<0.001). Both increasing age and higher blood pressure were independently associated with deteriorated peak atrial longitudinal systolic strain, SRs, and SRe, although augmented LA SRa, even after accounting for baseline clinical covariates in multivariable models that incorporated LA volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or left ventricular E/e' (all P<0.001). Our findings suggest LA mechanical functional decays in association with increasing age and higher blood pressure, which seem to be compensated for by augmentation of atrial pump function. We have also provided age- and sex-stratified reference values for strain and SR based on a large-scale Asian population. © 2017 American Heart Association, Inc.

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

Assessment of left atrial mechanical functions and atrial electromechanical delay in Juvenile idiopathic arthritis by tissue Doppler echocardiography.

PubMed

El Eraky, Azza Z; Handoka, Nesrin M; Ghaly, Mona Sayed; Nasef, Samah Ismail; Eldahshan, Nahed A; Ibrahim, Ahmed M; Shalaby, Sherein

2016-11-24

Juvenile idiopathic arthritis (JIA) is a systemic chronic inflammatory disease. Studies using tissue Doppler imaging (TDI) for the evaluation of cardiac functions of children with JIA are limited. Thus, this study was conducted to evaluate Left ventricular function, left atrial mechanical functions and atrial electromechanical delay in JIA. This study was carried out as a across sectional study. A total of 34 patients with active JIA and 34 controls were included. Atrial electromechanical delay and left atrial (LA) mechanical functions in addition to systolic and diastolic left ventricular (LV) functions were measured by using conventional echocardiography and TDI. Assessment of disease activity was done using Juvenile arthritis disease activity score (JADAS-27). JIA patients had abnormal atrial electromechanical coupling as established from prolonged lateral mitral annulus (PA lateral), septal mitral annulus (PA septum), inter-atrial and intra-atrial electromechanical delays compared with healthy controls. Left ventricular filling abnormalities were found characterized by a reduced E/A ratio (1.07 ± 0.56 vs. 1.48 ± 0.16, p = 0.01). E/Em was significantly higher in patients with JIA (7.58 ± 1.79 vs. 4.74 ± 1.45, p = 0.003) denoting impaired diastolic function. Left atrial mechanical functions assessment showed significantly decreased LA passive emptying fraction, increased LA active emptying fraction and LA total emptying volume in JIA patients (p = 0.01, p = 0.01, p = 0.03 respectively). Atrial electromechanical coupling intervals, and LA mechanical functions were impaired which can be considered as an early form of subclinical cardiac involvement in JIA patients. Significant diastolic functional abnormalities exist in JIA.

Recovery of atrial function after atrial compartment operation for chronic atrial fibrillation in mitral valve disease.

PubMed

Shyu, K G; Cheng, J J; Chen, J J; Lin, J L; Lin, F Y; Tseng, Y Z; Kuan, P; Lien, W P

1994-08-01

We prospectively studied the recovery of atrial function after atrial compartment operation and mitral valve surgery in patients with chronic atrial fibrillation caused by mitral valve disease. Chronic atrial fibrillation is the most common arrhythmia in mitral valve disease. This arrhythmia is associated with excessive morbidity and mortality. Mitral valve surgery alone rarely eliminates it. Twenty-two patients underwent mitral valve surgery and a new surgical method, atrial compartment operation. Doppler echocardiography was performed in all patients before operation and at 1 week and 2 and 6 months after operation in the successful cardioversion group. Peak early diastolic (E) and atrial (A) filling velocities, peak A/E velocity ratio and A/E integral ratio of the mitral and tricuspid valves were measured. Sinus rhythm was restored immediately after operation in 91% of patients and was maintained for > 1 week in 15 (68%) of 22 patients and > 6 months in 14 (64%) of 22. Eleven of 15 patients had left atrial paralysis (A/E integral ratio 0) at 1 week and 6 of 14 patients at 2 months. Nine of 15 patients had right atrial paralysis (A/E integral ratio 0) at 1 week and 1 of 14 patients at 2 months. Both left and right atrial contractile function (presence of an A wave on Doppler findings) was detected at 6 months in 14 patients. Mean (+/- SD) peak atrial filling velocity of the mitral valve was 15 +/- 26 cm/s at 1 week, 38 +/- 39 cm/s at 2 months and 93 +/- 32 cm/s at 6 months (p < 0.001). Mean peak atrial filling velocity of the tricuspid valve was 14 +/- 19 cm/s at 1 week, 33 +/- 19 cm/s at 2 months and 50 +/- 19 cm/s at 6 months (p < 0.001). Peak early diastolic and atrial filling velocities, peak A/E velocity ratio and A/E integral ratio of the mitral and tricuspid valves increased significantly from 1 week to 6 months. Chronic atrial fibrillation in mitral valve disease can often be eliminated by atrial compartment operation. No surgical mortality or significant

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Baode; Li, Chenxing

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

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.

Atrial myocardial nox2 containing NADPH oxidase activity contribution to oxidative stress in mitral regurgitation: potential mechanism for atrial remodeling.

PubMed

Chang, Jen-Ping; Chen, Mien-Cheng; Liu, Wen-Hao; Yang, Cheng-Hsu; Chen, Chien-Jen; Chen, Yung-Lung; Pan, Kuo-Li; Tsai, Tzu-Hsien; Chang, Hsueh-Wen

2011-01-01

Oxidative stress is linked with several cardiovascular diseases. However, the NADPH oxidase activity in severe mitral regurgitation patients with and without atrial fibrillation has not yet been explored. This study involved 16 adult patients (eight patients with persistent atrial fibrillation and eight with sinus rhythm) with severe mitral and moderate-to-severe tricuspid regurgitation and five control patients without mitral and tricuspid disease. Atrial tissues of the right and left atrial appendages were obtained during surgery. Superoxide anion production was measured by lucigenin-enhanced chemiluminescence, and the expression of nox2 containing NADPH oxidase mRNA was measured by quantitative real-time RT-PCR. Additionally, immunohistochemical study was performed. NADPH-stimulated superoxide release was significantly higher than basal superoxide production from right [5671.9±3498.7 vs. 232.7±70.0 relative light units per second per milligram of protein (RLU s(-1) mg protein(-1)), P=.008) and left atrial homogenates (6475.1±1890.8 vs. 229.0±79.6 RLU s(-1) mg protein(-1), P=.008) in atrial fibrillation patients. The NADPH-stimulated superoxide release from right atrial homogenates was also significantly higher than basal superoxide production in sinus patients (6809.1±1327.1 vs. 244.2±65.5 RLU s(-1) mg protein(-1), P=.008). Additionally, there was a borderline significant correlation between NADPH-stimulated superoxide production from left atrial homogenates and left atrial sizes (r=0.683, P=.062) in atrial fibrillation patients. Membrane-bound nox2 containing NADPH oxidase mRNA expression was increased and was similar in both the atrial fibrillation patients and sinus patients. The NADPH-stimulated superoxide production in right atrial homogenates in control atrial samples was 1863.7±137.2 RLU s(-1) mg protein(-1). Immunohistochemical study demonstrated increased expression of nox2 in myocytes with moderate-to-severe myolysis and hypertrophy. Results of

Atrial Fibrillation: Diagnosis

MedlinePlus

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

Effect of irbesartan on development of atrial fibrosis and atrial fibrillation in a canine atrial tachycardia model with left ventricular dysfunction, association with p53.

PubMed

Kataoka, Naoya; Nishida, Kunihiro; Kinoshita, Koshi; Sakamoto, Tamotsu; Nakatani, Yosuke; Tsujino, Yasushi; Mizumaki, Koichi; Inoue, Hiroshi; Kinugawa, Koichiro

2016-12-01

Effects of an angiotensin II receptor blocker, irbesartan (IRB), on the development of atrial fibrosis and atrial fibrillation (AF) were assessed in a canine model of atrial tachycardia remodeling (ATR) with left ventricular dysfunction, together with its possible association with involvement of p53. Atrial tachypacing (400 bpm for 4 weeks) was used to induce ATR in beagles treated with placebo (ATR-dogs, n = 6) or irbesartan (IRB-dogs, n = 5). Non-paced sham dogs served as control (Control-dogs, n = 4). ATR- and IRB-dogs developed tachycardia-induced left ventricular dysfunction. Atrial effective refractory period (AERP) shortened (83 ± 5 ms, p < 0.05), inter-atrial conduction time prolonged (72 ± 2 ms, p < 0.05), and AF duration increased (29 ± 5 s, p < 0.05 vs. baseline) after 4 weeks in ATR-dogs. ATR-dogs also had a larger area of atrial fibrous tissue (5.2 ± 0.5 %, p < 0.05 vs. Control). All these changes, except for AERP, were attenuated in IRB-dogs (92 ± 3 ms, 56 ± 3 ms, 9 ± 5 s, and 2.5 ± 0.7 %, respectively; p < 0.05 vs. ATR for each). In ATR-dogs, p53 expression in the left atrium decreased by 42 % compared with Control-dogs (p < 0.05); however, it was highly expressed in IRB-dogs (+89 % vs. ATR). Transforming growth factor (TGF)-β1 expression was enhanced in ATR-dogs (p < 0.05 vs. Control) but reduced in IRB-dogs (p < 0.05 vs. ATR). Irbesartan suppresses atrial fibrosis and AF development in a canine ATR model with left ventricular dysfunction in association with p53.

Presumptive partial atrial standstill secondary to atrial cardiomyopathy in a Greyhound.

PubMed

Wesselowski, S; Abbott, J; Borgarelli, M; Tursi, M

2017-06-01

Persistent atrial standstill is a rare arrhythmia in both human and veterinary patients. In recent decades, cases of partial atrial standstill have been recognized in humans. We describe a case of presumptive partial atrial standstill in a Greyhound, in which there was disparate left and right atrial electromechanical function and rapid progression to congestive heart failure over the span of fourteen weeks. An atrial cardiomyopathy characterized by severe, diffuse, fibrofatty replacement of the atrial myocardium was identified histologically. Copyright © 2017 Elsevier B.V. All rights reserved.

M‐Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure: Differential Actions of 2 cGMP Activating Therapeutics

PubMed Central

McKie, Paul M.; Cataliotti, Alessandro; Ichiki, Tomoko; Sangaralingham, S. Jeson; Chen, Horng H.; Burnett, John C.

2014-01-01

Background Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M‐atrial natriuretic peptide (M‐ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator. Methods and Results HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenous M‐ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced by M‐ANP (139±4 to 118±3 mm Hg, P<0.05) and nitroglycerin (137±3 to 116±4 mm Hg, P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) with M‐ANP (12±2 to 6±2 mm Hg, P<0.05) and nitroglycerin (12±1 to 6±1 mm Hg, P<0.05). M‐ANP enhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38±4 to 53±5 mL/min), renal blood flow (132±18 to 236±23 mL/min), and natriuresis (11±4 to 689±37 mEq/min) and also inhibited aldosterone activation (32±3 to 23±2 ng/dL, P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation. Conclusions Our results advance the differential cardiorenal actions of pGC (M‐ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M‐ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal. PMID:24385449

M-atrial natriuretic peptide and nitroglycerin in a canine model of experimental acute hypertensive heart failure: differential actions of 2 cGMP activating therapeutics.

PubMed

McKie, Paul M; Cataliotti, Alessandro; Ichiki, Tomoko; Sangaralingham, S Jeson; Chen, Horng H; Burnett, John C

2014-01-02

Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M-atrial natriuretic peptide (M-ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator. HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenous M-ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced by M-ANP (139 ± 4 to 118 ± 3 mm Hg, P<0.05) and nitroglycerin (137 ± 3 to 116 ± 4 mm Hg, P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) with M-ANP (12 ± 2 to 6 ± 2 mm Hg, P<0.05) and nitroglycerin (12 ± 1 to 6 ± 1 mm Hg, P<0.05). M-ANP enhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38 ± 4 to 53 ± 5 mL/min), renal blood flow (132 ± 18 to 236 ± 23 mL/min), and natriuresis (11 ± 4 to 689 ± 37 mEq/min) and also inhibited aldosterone activation (32 ± 3 to 23 ± 2 ng/dL, P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation. Our results advance the differential cardiorenal actions of pGC (M-ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M-ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal.

Pathophysiology, prognostic significance and clinical utility of B-type natriuretic peptide in acute coronary syndromes.

PubMed

Wiviott, Stephen D; de Lemos, James A; Morrow, David A

2004-08-16

The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.

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

2017-09-01

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.

Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement: mAF App Trial.

PubMed

Guo, Yutao; Chen, Yundai; Lane, Deirdre A; Liu, Lihong; Wang, Yutang; Lip, Gregory Y H

2017-12-01

Mobile Health technology for the management of patients with atrial fibrillation is unknown. The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA 2 DS 2 -VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65-74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT 2 R 2 [Sex, Age <60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial fibrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients' knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAF App were assessed at 1 month. A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF App was easy, user-friendly, helpful, and associated with significant improvements in knowledge compared with the usual care arm (P values for trend <.05). Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care (all P < .05). Quality of life scores were significantly increased in the mAF App arm versus usual care, with anxiety and depression reduced (all P < .05). The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support, education, and patient-involvement

Incremental value of right atrial strain for early diagnosis of hemodynamic deterioration in pulmonary hypertension: a new noninvasive tool for a more comprehensive diagnostic paradigma.

PubMed

Piccinino, Cristina; Giubertoni, Ailia; Zanaboni, Jacopo; Gravellone, Miriam; Sola, Daniele; Rosso, Roberta; Ferrarotti, Lorena; Marino, Paolo Nicola

2017-11-01

Increased right atrial size is related to adverse prognosis in pulmonary hypertension. The potential incremental value of right atrial function assessment is still unclear. We tested the relationship between right atrial two-dimensional speckle-tracking echocardiography impairment and hemodynamic, functional and clinical deterioration in patients with pulmonary hypertension. We prospectively evaluated 36 patients (27 female, 9 male; mean age 68 ± 13 years) with suspected pulmonary hypertension undergoing right heart catheterization and 16 matched controls. All patients underwent baseline evaluation by New York Heart Association functional class, 6-min walking test, brain natriuretic peptide (BNP), and standard two-dimensional echocardiography in less than 48 h of right heart catheterization. Right atrial two-dimensional speckle-tracking echocardiography was assessed by averaging all segments in standard four-chamber apical view. Right atrial global integral strain was significantly lower in patients compared with controls (11.40 ± 5.22% vs. 25.72 ± 5.95 P < 0.001). Moreover, right atrial global strain, but not right atrial area or volume, was correlated with invasively measured cardiac index (CI) (r = 0.72; P < 0.0001) and pulmonary vascular resistances in all patients, even though stronger in subjects with precapillary pulmonary hypertension (r = -0.42, P = 0.018; r = -0.54, P = 0.007 respectively; P = 0.007). It was also correlated with New York Heart Association (P = 0.027), BNP (P = 0.002), and 6-min walking test (P = 0.006). After multivariate analysis including right atrial volume, tricuspid annular plane systolic excursion, left atrial strain, and BNP, right atrial global strain showed the strongest correlation with CI. Area under the curve optimal cutoff for predicting CI at least 2.4 l/min/m was 17% (area under the curve: 0.83, sensitivity: 90%, specificity: 54%). Right atrial global strain can

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

PubMed

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

1998-07-01

The involvement of left atrial (LA) appendage flow velocity in reduced left atrial function was investigated in 24 patients with hypertrophic cardiomyopathy, who retained sinus rhythm at the examination. Patients were divided into 11 with a history of paroxysmal atrial fibrillation [PAf(+)] and 13 without such history [PAf(-)]. Transthoracic echocardiography was performed to evaluate LA fractional shortening (LA%FS) and mean velocity of circumferential LA fiber shortening (LAmVcf), as contractile functions of the left atrium at the phase of active atrial contraction. Transesophageal echocardiographic Doppler examination was performed in all patients to measure the LA appendage velocity. In all patients, significant positive correlations were observed between the LA appendage velocity and LA%FS (r = 0.50, p < 0.05) or LAmVcf (r = 0.82, p < 0.001). LAmVcf and LA appendage velocity in patients with paroxysmal fibrillation were significantly lower than in those without (0.84 +/- 0.15 vs 1.28 +/- 0.37 circ/sec, 44 +/- 12 vs 65 +/- 20 cm/sec, both p < 0.01), whereas LA diameter was greater in the former compared to the latter (45 +/- 5 vs 38 +/- 5 mm, p < 0.01). LAmVcf and LA appendage velocity were low in four patients with cerebral infarction or transient cerebral ischemic attack (LAmVcf < 1.0 circ/sec, LA appendage velocity < or = 40 cm/sec). Importantly, all these patients had a history of paroxysmal fibrillation. These results indicate that there is a close relationship between LA appendage velocity and LA contractile function in patients with hypertrophic cardiomyopathy with paroxysmal atrial fibrilation, and these patients have potential risk of cerebral infarction.

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

2017-05-01

Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (I Kv1.5 ) 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 (I hERG ). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (I Kir2.1 ). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of I Kv1.5 and I hERG , which contributed to preventing the development and duration of AF. Copyright © 2017 Elsevier Inc. All rights reserved.

B-type natriuretic peptide testing for detection of heart failure.

PubMed

Saul, Lauren; Shatzer, Melanie

2003-01-01

The incidence of heart failure (HF) is on the increase with the aging population. Heart failure can manifest as either systolic or diastolic dysfunction. Systolic dysfunction causes impaired ventricular contractility with an ejection fraction of less than 45%. In contrast, diastolic dysfunction is evidenced by impaired ventricular relaxation and an ejection fraction greater than 45%. The diagnosis of HF is challenging with patients who present with acute dyspnea and a history of chronic obstructive pulmonary disease or pneumonia. The pathophysiology of HF and the resulting compensatory mechanisms involve a complex neuroendocrine response that includes a release of natriuretic peptides including B-type natriuretic peptides (BNPs). Elevation of BNP is in response to ventricular wall stress and volume overload from HF. BNP promotes natriuresis, diuresis, and vasodilitation and therefore counteracts some of the deleterious effects of the neuroendocrine response in HF Recently, a new laboratory test for BNP has been developed to assist in rapid identification of patients with HF. Research studies have shown that BNP testing assists in differentiating between cardiac and pulmonary causes of acute dyspnea and could be used to evaluate effectiveness of therapy and as a predictor for length of stay and readmission.

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

PubMed

Ravens, Ursula; Odening, Katja E

2017-08-01

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

Impaired Left Atrial Strain as a Predictor of New-onset Atrial Fibrillation After Aortic Valve Replacement Independently of Left Atrial Size.

PubMed

Pessoa-Amorim, Guilherme; Mancio, Jennifer; Vouga, Luís; Ribeiro, José; Gama, Vasco; Bettencourt, Nuno; Fontes-Carvalho, Ricardo

2018-06-01

Left atrial dysfunction in aortic stenosis may precede atrial enlargement and predict the occurrence of atrial fibrillation (AF). To test this hypothesis, we assessed left atrial function and determined its impact on the incidence of AF after aortic valve replacement. A total of 149 severe aortic stenosis patients (74±8.6 years, 51% men) with no prior AF were assessed using speckle-tracking echocardiography. Left atrial function was evaluated using peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and phasic left atrial volumes. The occurrence of AF was monitored in 114 patients from surgery until hospital discharge. In multiple linear regression, PALS and PACS were inversely correlated with left atrial dilation, left ventricular hypertrophy, and diastolic function. Atrial fibrillation occurred in 36 patients within a median time of 3 days [interquartile range, 1-4] after aortic valve replacement. In multiple Cox regression, PALS and PACS were independently associated with the incidence of AF (HR, 0.946; 95%CI, 0.910-0.983; P=.005 and HR, 0.932; 95%CI, 0.883-0.984; P=.011, respectively), even after further adjustment for left atrial dimensions. Both reduced PALS and PACS were associated with the incidence of AF in patients with nondilated left atria (P value for the interaction of PALS with left atrial dimensions=.013). In severe aortic stenosis, left atrial dysfunction predicted the incidence of postoperative AF independently of left atrial dilation, suggesting that speckle-tracking echocardiography before surgery may help in risk stratification, particularly in patients with nondilated left atria. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

PubMed

Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

2008-05-01

Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Triiodothyronine and brain natriuretic peptide: similar long-term prognostic values for chronic heart failure.

PubMed

Kozdag, Guliz; Ertas, Gokhan; Kilic, Teoman; Acar, Eser; Sahin, Tayfun; Ural, Dilek

2010-01-01

Although low levels of free triiodothyronine and high levels of brain natriuretic peptide have been shown as independent predictors of death in chronic heart failure patients, few studies have compared their prognostic values. The aim of this prospective study was to measure free triiodothyronine and brain natriuretic peptide levels and to compare their prognostic values among such patients.A total of 334 patients (mean age, 62 ± 13 yr; 218 men) with ischemic and nonischemic dilated cardiomyopathy were included in the study. The primary endpoint was a major cardiac event.During the follow-up period, 92 patients (28%) experienced a major cardiac event. Mean free triiodothyronine levels were lower and median brain natriuretic peptide levels were higher in patients with major cardiac events than in those without. A significant negative correlation was found between free triiodothyronine and brain natriuretic peptide levels. Receiver operating characteristic curve analysis showed that the predictive cutoff values were < 2.12 pg/mL for free triiodothyronine and > 686 pg/mL for brain natriuretic peptide. Cumulative survival was significantly lower among patients with free triiodothyronine < 2.12 pg/mL and among patients with brain natriuretic peptide > 686 pg/mL. In multivariate analysis, the significant independent predictors of major cardiac events were age, free triiodothyronine, and brain natriuretic peptide.In the present study, free triiodothyronine and brain natriuretic peptide had similar prognostic values for predicting long-term prognosis in chronic heart failure patients. These results also suggested that combining these biomarkers may provide an important risk indicator for patients with heart failure.

Thyrotoxic Atrial Fibrillation

PubMed Central

Parmar, Malvinder S.

2005-01-01

Abstract and Introduction Abstract Atrial fibrillation is the most common cardiac complication of hyperthyroidism and occurs in 15% of patients with hyperthyroidism. It is associated with a higher risk of thromboembolism that often involves the central nervous system. Oral anticoagulation is important in the majority of these patients to prevent thromboembolic complications. These patients require adjustment in the dose of various rate-controlling agents because of increased clearance associated with hyperthyroidism and a decrease in warfarin dosage because of increased clearance of vitamin K-dependent clotting factors. The management of thyrotoxic atrial fibrillation is summarized in this clinical review. Introduction A 52-year-old woman presents with symptoms of palpitations and mild shortness of breath. She is noted to be in atrial fibrillation with a rapid ventricular response of 157 beats per minute. She gives a 1-year history of increasing fatigue, intermittent palpitations, hot flashes, and weight loss of 15 lb in the past 6 months. She denies chest pain. Examination revealed an apprehensive woman with mild proptosis and diffuse thyroid enlargement. Lungs are clear. Heart sounds are irregular and rapid. Thyroid function studies performed last week at the doctor's office show a suppressed thyroid-stimulating hormone (TSH) level of .01 with elevated free thyroxine (T4) of 60 pmol/L (normal, 9–23 pmol/L). How Should This Patient Be Managed in the Emergency Department? Management of the patient in the emergency department with thyrotoxic atrial fibrillation depends on the presence or absence of associated cardiac symptoms. A conservative management with antithyroid agents is appropriate for patients without associated cardiac complications, such as angina or heart failure. However, if the patient is symptomatic with angina or heart failure, then in addition to control of rapid heart rate, therapy to inhibit thyroid hormone release and synthesis should be

Higher Natriuretic Peptide Levels Associate with a Favorable Adipose Tissue Distribution Profile

PubMed Central

Neeland, Ian J.; Winders, Benjamin R.; Ayers, Colby R.; Das, Sandeep R.; Chang, Alice Y.; Berry, Jarett D.; Khera, Amit; McGuire, Darren K.; Vega, Gloria L.; de Lemos, James A.; Turer, Aslan T.

2013-01-01

Objectives To investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Background Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models but data are lacking in humans. Methods 2619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and NT-proBNP and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Results Median BNP and NT-proBNP levels in the study cohort (mean age 44 years, 56% women, 48% African-Americans, 32% obese) were 3.0 and 28.1 pg/mL, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance including lower visceral fat, liver fat, and HOMA-IR; and more lower body fat and higher adiponectin (p<0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral (β= −0.08, p<0.0001) and liver fat (β= −0.14, p<0.0001) and positively associated with lower body fat (β= 0.07, p<0.0001) independent of age, sex, race, and obesity-status; findings were similar with BNP. Adjustment for body composition, HOMA-IR, circulating androgens, and adipocytokines did not attenuate the associations. Conclusions Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides. PMID:23602771

Rivaroxaban as an effective alternative to warfarin in a patient with atrial fibrillation, thrombophilia, and left atrial appendage thrombus: a case report.

PubMed

Scarano, Michele; Casale, Matteo; Mantini, Cesare; Imbalzano, Egidio; Consorti, Cristiana; Clemente, Daniela; Dattilo, Giuseppe

2017-04-09

Atrial fibrillation is the most common cardiac arrhythmia. It is responsible for up to 20% of all ischemic strokes. Rate control and anticoagulation are crucial for atrial fibrillation management and stroke prevention. We present the case of an 84-year-old Italian woman with a left atrial appendage thrombus that developed despite her use of anticoagulant therapy with warfarin for a previous pulmonary embolism. She had atrial fibrillation and heterozygosity for both factor V Leiden and methylenetetrahydrofolate reductase C677T mutation, thus creating resistance to activated protein C. Anticoagulant therapy was switched to heparin for 1 week and then to rivaroxaban. After 3 months of rivaroxaban use, the thrombus disappeared. This case raises the issue of the ineffectiveness of warfarin therapy in complex cases involving particular thrombophilic conditions and the possibility of using rivaroxaban as a safe and effective alternative.

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

PubMed

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

2008-11-25

To evaluate the effectiveness of radiofrequency modified maze operation for the treatment of atrial fibrillation (AF) and compare the results of the left versus bi-atrial procedures. 305 patients of organic heart disease combined with AF, 117 males and 188 females, aged (53 +/- 10), that underwent cardiac valve operation (n = 293) and/or coronary artery bypass graft surgery (n = 14), received concomitant atrial fibrillation, bi-atrial (n = 160) or left atrial (n = 145) with a mean duration of (36 +/- 43) months. Follow-up was conducted for (28 +/- 5) (3 - 42) months. Thirteen patients (4.3%) died postoperatively: 7 died of multisystem and organ failure, 3 of low cardiac output, 1 of rupture of left ventricle, 1 of arrhythmia, and 1 of sudden death. During the follow-up, 1 patient died of heart failure, 1 of encephalorrhagia and 1 of unknown reason in the bi-atrial group. At the end of the procedure 223 patients (73.1%) had sinus rhythm, with a sinus rhythm rate of 66.9% (107/160) in the bi-atrial group, significant lower than that in the left atrial group (80.0%, 116/145, P < 0.05). At late follow-up, 215 of the 266 patients (80.8%) were in stable sinus rhythm. Sinus rhythm rate of the bi-atrial group was 80.0%, not significantly different from that of the left atrial group (81.9%, P > 0.05). The Kaplan-Meier survival analysis showed there was no significant difference in the AF rhythm rate between these 2 groups (P = 0.33). Logistic regression analysis showed that the left atrial diameter of >/= 80 mm was an independent predictor of AF recurrence. Both the left and bi-atrial procedures are successful in terms of restoring sinus rhythm. Left atrial ablation in severe cases and where the incision of right atrium is not needed is a reasonable choice.

Nephroblastoma with right atrial extension: preoperative diagnosis and management.

PubMed

Vaughan, E D; Crosby, I K; Tegtmeyer, C J

1977-04-01

A 14-year-old black boy, with a large nephroblastoma of the right kidney, had preoperative identification of inferior vena cava and right atrial involvement. Renal arteriography revealed linear arterial channels in the anatomic distribution of the inferior vena cava and venography revealed total caval occlusion and a right atrial mass. Radical excision, using a cardiopulmonary bypass, resulted in a 6-month postoperative survival.

Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal Function.

PubMed

Staffel, Janina; Valletta, Daniela; Federlein, Anna; Ehm, Katharina; Volkmann, Regine; Füchsl, Andrea M; Witzgall, Ralph; Kuhn, Michaela; Schweda, Frank

2017-01-01

The cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels. Copyright © 2016 by the American Society of Nephrology.

Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal Function

PubMed Central

Staffel, Janina; Valletta, Daniela; Federlein, Anna; Ehm, Katharina; Volkmann, Regine; Füchsl, Andrea M.; Witzgall, Ralph; Kuhn, Michaela

2017-01-01

The cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels. PMID:27153922

C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa

PubMed Central

Blier, Anne-Sophie; Veron, Wilfried; Bazire, Alexis; Gerault, Eloïse; Taupin, Laure; Vieillard, Julien; Rehel, Karine; Dufour, Alain; Le Derf, Franck; Orange, Nicole; Hulen, Christian; Feuilloley, Marc G. J.

2011-01-01

Pseudomonas aeruginosa coordinates its virulence expression and establishment in the host in response to modification of its environment. During the infectious process, bacteria are exposed to and can detect eukaryotic products including hormones. It has been shown that P. aeruginosa is sensitive to natriuretic peptides, a family of eukaryotic hormones, through a cyclic nucleotide-dependent sensor system that modulates its cytotoxicity. We observed that pre-treatment of P. aeruginosa PAO1 with C-type natriuretic peptide (CNP) increases the capacity of the bacteria to kill Caenorhabditis elegans through diffusive toxin production. In contrast, brain natriuretic peptide (BNP) did not affect the capacity of the bacteria to kill C. elegans. The bacterial production of hydrogen cyanide (HCN) was enhanced by both BNP and CNP whereas the production of phenazine pyocyanin was strongly inhibited by CNP. The amount of 2-heptyl-4-quinolone (HHQ), a precursor to 2-heptyl-3-hydroxyl-4-quinolone (Pseudomonas quinolone signal; PQS), decreased after CNP treatment. The quantity of 2-nonyl-4-quinolone (HNQ), another quinolone which is synthesized from HHQ, was also reduced after CNP treatment. Conversely, both BNP and CNP significantly enhanced bacterial production of acylhomoserine lactone (AHL) [e.g. 3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and butanoylhomoserine lactone (C4-HSL)]. These results correlate with an induction of lasI transcription 1 h after bacterial exposure to BNP or CNP. Concurrently, pre-treatment of P. aeruginosa PAO1 with either BNP or CNP enhanced PAO1 exotoxin A production, via a higher toxA mRNA level. At the same time, CNP led to elevated amounts of algC mRNA, indicating that algC is involved in C. elegans killing. Finally, we observed that in PAO1, Vfr protein is essential to the pro-virulent effect of CNP whereas the regulator PtxR supports only a part of the CNP pro-virulent activity. Taken together, these data reinforce the hypothesis that during

Increased α-Actinin-2 Expression in the Atrial Myocardium of Patients with Atrial Fibrillation Related to Rheumatic Heart Disease.

PubMed

Zhang, Lei; Zhang, Nan; Tang, Xuejiao; Liu, Fajin; Luo, Suxin; Xiao, Hua

was increased in the atrial tissues of patients with AF secondary to RHD. α-Actinin-2 was upregulated via the TGF-β1/Smad pathway in atrial fibroblasts, which suggests that it may be involved in TGF-β1/Smad pathway-induced atrial fibrosis in patients with AF. © 2016 S. Karger AG, Basel.

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

Atrial Fibrillation: Complications

MedlinePlus

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Will sacubitril-valsartan diminish the clinical utility of B-type natriuretic peptide testing in acute cardiac care?

PubMed

Mair, Johannes; Lindahl, Bertil; Giannitsis, Evangelos; Huber, Kurt; Thygesen, Kristian; Plebani, Mario; Möckel, Martin; Müller, Christian; Jaffe, Allan S

2017-06-01

Since the approval of sacubitril-valsartan for the treatment of chronic heart failure with reduced ejection fraction, a commonly raised suspicion is that a wider clinical use of this new drug may diminish the clinical utility of B-type natriuretic peptide testing as sacubitril may interfere with B-type natriuretic peptide clearance. In this education paper we critically assess this hypothesis based on the pathophysiology of the natriuretic peptide system and the limited published data on the effects of neprilysin inhibition on natriuretic peptide plasma concentrations in humans. As the main clinical application of B-type natriuretic peptide testing in acute cardiac care is and will be the rapid rule-out of suspected acute heart failure there is no significant impairment to be expected for B-type natriuretic peptide testing in the acute setting. However, monitoring of chronic heart failure patients on sacubitril-valsartan treatment with B-type natriuretic peptide testing may be impaired. In contrast to N-terminal-proBNP, the current concept that the lower the B-type natriuretic peptide result in chronic heart failure patients, the better the prognosis during treatment monitoring, may no longer be true.

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

[Right atrial appendage thrombosis during atrial fibrillation: an element to look for].

PubMed

Barbati, Giovanni; De Domenico, Renato; Rossi, Stefania; Vecchiato, Elena; Zeppellini, Roberto

2017-03-01

Oral anticoagulant therapy (OAT) is a mainstay of atrial fibrillation (AF) pharmacological treatment. Left atrial appendage closure is a possible treatment, when feasible, in patients with intracerebral hemorrhage during OAT. We report a case of right atrial appendage thrombosis in a patient with chronic AF admitted for syncope due to diuretic-induced orthostatic hypotension. Two years previously, he had undergone left atrial appendage closure with the Amplatzer Cardiac Plug device because of intracerebral hemorrhage during OAT. After neurological consult, OAT was resumed with apixaban 5 mg twice daily, and transesophageal echocardiography performed two months later showed complete resolution of the right atrial appendage thrombosis. This particular case underlines the importance of searching for a possible right atrial appendage thrombosis in patients affected by AF, and suggests that left atrial appendage closure in AF patients not suitable for OAT does not fully eliminate the risk of thromboembolism.

Heart failure and atrial fibrillation: current concepts and controversies.

PubMed Central

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

1997-01-01

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

Stiff Left Atrial Syndrome: A Complication Undergoing Radiofrequency Catheter Ablation for Atrial Fibrillation.

PubMed

Yang, Yufan; Liu, Qiming; Wu, Zhihong; Li, Xuping; Xiao, Yichao; Tu, Tao; Zhou, Shenghua

2016-07-01

Radiofrequency catheter ablation for atrial fibrillation is an effective approach for treating atrial fibrillation. Its complications have attracted much attention, of which the stiff left atrial syndrome is a recently discovered complication that has not been completely understood. This study aims to investigate the concept, pathologic basis, clinical characteristics, predictors, and treatment protocols of the stiff left atrial syndrome after radiofrequency ablation for atrial fibrillation. © 2016 Wiley Periodicals, Inc.

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

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

PubMed Central

Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A; Low, Siew-Kee; Weeke, Peter E.; Müller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Dörr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurman, Claudia; Kleber, Marcus E.; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Malik, Rainer; Horimoto, Andrea R. V. R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Thériault, Sébastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu-Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Paré, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kähönen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii-Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Völker, Uwe; Jöckel, Karl-Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J. F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; van der Harst, Pim; Lokki, Marja-Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; März, Winfried; Lehtimäki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kääb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.

2017-01-01

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups.3–7 To further define the genetic basis of atrial fibrillation, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with atrial fibrillation and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate new potential targets for drug discovery.8 PMID:28416818

The prognostic value of midregional proatrial natriuretic peptide in patients with hemorrhagic stroke.

PubMed

Fischer, Marlene; Katan, Mira; Morgenthaler, Nils G; Seiler, Marleen; Müller, Beat; Lackner, Peter; Errath, Mario; Helbok, Raimund; Pfausler, Bettina; Beer, Ronny; Schmutzhard, Erich; Broessner, Gregor

2014-01-01

Atrial natriuretic peptide (ANP) is a well-known prognostic marker of outcome and mortality in patients with cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP) is a stable fragment of the ANP precursor hormone. As a prognostic marker after ischemic stroke, it reliably predicts poststroke mortality and functional outcome. This study aimed to analyze the prognostic value of MR-proANP in patients with hemorrhagic stroke, i.e. subarachnoid (SAH) and intracerebral hemorrhage (ICH). MR-proANP was analyzed in patients with spontaneous SAH or spontaneous ICH. All patients were prospectively randomized into two treatment arms: (1) a prophylactic normothermia group with a target core temperature 36.5°C using endovascular cooling, and (2) a control group with conventional stepwise predefined fever management using antipyretic medication and surface cooling. Blood samples were obtained on admission and on days 4 and 7. Measurement of MR-proANP was performed in serum using sandwich immunoassay. The primary endpoint was functional outcome [assessed by the Glasgow Outcome Score (GOS)] and the secondary endpoints were mortality within 180 days after hemorrhagic stroke and influence of temperature on MR-proANP. A favorable outcome was defined as GOS 4-5, and the patients were considered to have a poor outcome with a 180-day GOS score between 1 and 3. Analysis of MR-proANP was performed in 24 patients with spontaneous SAH and 22 patients with spontaneous ICH. MR-proANP was elevated on days 4 and 7 as compared to baseline levels (p < 0.05 and p < 0.001, respectively). High MR-proANP levels (>120 pmol/l) were associated with increased mortality and poor outcome (after 180 days; p < 0.05, respectively). There was no significant difference regarding MR-proANP serum concentrations between the endovascular and the control groups. Increased levels of MR-proANP are independently associated with poor functional outcome and increased mortality after 180 days in

Surgical treatment of atrial fibrillation.

PubMed

Pagé, Pierre; Skanes, Allan C

2005-09-01

Surgery aims to eliminate atrial fibrillation (AF) through direct modification of the arrhythmogenic substratum. The Maze procedure, developed two decades ago, has proven to be clearly effective in restoring sinus rhythm in AF patients with or without associated organic cardiac disorders. Indications for surgery may be tailored to the clinical situation involved. In patients with continuous AF associated with structural heart disease (eg, valvular, congenital or coronary artery disease), the performance of a concomitant AF ablation procedure proven to add minimal morbidity to the operation may be highly beneficial to patient outcome. It is likely, although not entirely proven, that the restoration and maintenance of sinus rhythm after mitral valve surgery promotes survival by preventing tachycardia-induced cardiomyopathy and stroke. Novel strategies for AF surgery involve the use of alternate energy sources to create the lines of block in the atria and the simplification of the lesion pattern compared with the earlier Cox-Maze procedure. Published clinical data support the contention that left atrial ablation techniques performed concomitantly with valvular and/or coronary artery bypass surgery are likely to result in a 70% to 90% cure rate of AF in patients with preoperatively documented AF. Despite the lack of evidence for long-term outcome benefit, intraoperative pulmonary vein ablation, feasible with minimal morbidity, clearly appears to be an improvement over simply ignoring AF in patients undergoing cardiac surgery. Left atrial appendectomy appears warranted in patients with chronic persistent AF.

Measurement of funny current (I(f)) channel mRNA in human atrial tissue: correlation with left atrial filling pressure and atrial fibrillation.

PubMed

Lai, L P; Su, M J; Lin, J L; Tsai, C H; Lin, F Y; Chen, Y S; Hwang, J J; Huang, S K; Tseng, Y Z; Lien, W P

1999-07-01

The funny current (I(f)) contributes to phase IV spontaneous depolarization in cardiac pacemaker tissue. Enhanced I(f) activity in myocardial tissue may lead to increased automaticity and therefore tachyarrhythmia. We measured the amount of I(f) activity in the messenger ribonucleic acid (mRNA) in human atrial tissue and correlated the mRNA amount to left atrial filling pressure and atrial fibrillation (AF). A total of 34 patients undergoing open heart surgery were included (15 men and 19 women, aged 55+/-10 years). Atrial tissue was obtained from the right atrial free wall, the right atrial appendage, the left atrial free wall, and the left atrial appendage, respectively. The mRNA amount of the I(f) channel was measured by reverse transcription polymerase chain reaction and was normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. We found that the I(f) channel mRNA was present at all the atrial sampling sites. A higher left atrial filling pressure, an indicator of congestive heart failure, was associated with a higher I(f) mRNA level (r2 = 0.446, P < 0.01 by linear regression). We also found that the mRNA amount was significantly higher in patients with AF than in patients without AF (1.68+/-0.49 vs 1.27+/-0.43; P < 0.05). Age, sex, right atrial filling pressure, left atrial dimension, and left ventricular ejection fraction had no significant effect on the mRNA level. The mRNA of the I(f) channel is present in the free-wall area and appendage area from both atria. Increased left atrial filling pressure and clinical AF are associated with increased I(f) mRNA level.

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.

Neurohumoral mechanism in the natriuretic action of intracerebroventricular administration of renin.

PubMed

Zavala, Lida; Barbella, Yarisma; Israel, Anita

2004-03-01

Intracerebroventricular (i.v.t.) administration of renin (R) decreases urinary volume and increases urinary sodium excretion. We investigated whether i.v.t.-R-induced natriuresis could be associated with the release of atrial natriuretic peptide (ANP), its interaction with renal ANP-A receptors (ANPR-A) and the subsequent increase of urinary cyclic 3-5 guanosine monophosphate (cGMP). In i.v.t. cannulated rats, the left carotid artery was catheterised with PE-50 tubing for blood collection, renin was injected i.v.t. and arterial blood samples were collected at 0, 2, 5, 10 and 15 minutes of injection, and urinary sodium and cGMP excretion at 1-, 3- and 6-hour periods of urine collection. Plasma ANP levels and urinary cGMP were determined by radioimmunoassay, and each urine sample was analysed for sodium concentration using a flame photometer. Our results demonstrate that i.v.t.-R administration increases plasma ANP levels after two minutes of injection and urinary cGMP concentration at 1-, 3- and 6 hour period of urine collection. The natriuretic action induced by i.v.t.-R was blunted by peripheral administration of anantin, an ANPR-A antagonist. We assessed the role of brain angiotensin II (Ang II) AT1-receptors on the i.v.t.-induced antidiuresis, natriuresis and cGMP urinary excretion, the last as an indirect index of ANP secretion. Blockade of brain Ang II AT1-receptors with losartan (LOS; 120 microg/3 microl, i.v.t.), inhibited the antidiuretic action and blocked the increased urinary sodium and cGMP excretion induced by i.v.t.-R (7.14 mGU/5 microl). The increase in urinary cGMP was independent of nitric oxide synthase stimulation, since L-NAME pre-treatment did not alter the renal actions induced by i.v.t.-R. Our results suggest that there is a link between the brain and the kidney. The activation of brain angiotensinergic neurons and stimulation of AT1- receptors may stimulate the release of ANP to the circulation. The released ANP circulates to the kidneys

Antiarrhythmic properties of atrial pacing.

PubMed

Kliś, Magdalena; Sławuta, Agnieszka; Gajek, Jacek

2017-01-01

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

Simulation of Atrial Fibrosis Using Coupled Myocyte-Fibroblast Cellular and Human Atrial Models

PubMed Central

Gao, Yuan

2017-01-01

Atrial fibrosis is characterized by expansion of extracellular matrix and increase in the number of fibroblasts which has been associated with the development and maintenance of atrial arrhythmias. However, the mechanisms how the fibrosis contributes to atrial arrhythmia remain incompletely understood. In this study, we used a proposed fibroblast model coupled with the human atrial myocyte to investigate the effects of fibrosis on atrial excitability and repolarization at both cellular and macroscopic levels. The 12-lead electrocardiogram (ECG) was also simulated to explore the index of clinical diagnosis for fibrosis. The simulation results showed that the fibrosis can modify action potential morphology of human atrial myocyte, slow down wave propagation, and have rate adaptation, thus causing the atrial electrical heterogeneity. The fibrosis alone was sufficient to cause arrhythmia, induce reentry wave, and result in low amplitude and wide P waves at normal heart rate and significant prolonged and inverse P waves at high heart rate. All these symptoms aggravated when the level of fibrosis increased. Our simulations demonstrated that fibrosis is the substrate of atrial arrhythmia and thereby may be a potential target in the treatment of atrial arrhythmias. PMID:29441121

Natriuretic peptides and their therapeutic potential in heart failure treatment: An updated review.

PubMed

Namdari, M; Eatemadi, A; Negahdari, B

2016-09-30

Brain natriuretic peptide (BNP), also known as a B-type natriuretic peptide, is one of the important biomarkers with a proven role in the diagnosis of congestive heart failure (CHF). Researchers from the different clinical field have researched into the performance features of BNP testing in the acute care set-up to assist and improve in diagnosing CHF and in predicting future morbidity and mortality rates. The potency of BNP has also been researched into in cases like myocardial ischemia and infarction, cor pulmonale, and acute pulmonary embolism (PE). Based on their vaso-dilatory and diuretic properties and ability to inhibit renin-angiotensin-aldosterone system, natriuretic peptides are able to provide an efficient technique and mechanism of action in the pathophysiologic framework for CHF treatment and management. Recent clinical studies reported that ularitide, a synthetic form of urodilatin, secreted by kidney may be effective in managing and treatment of decompensated heart failure. It has also been reported that Nesiritide, a recombinant natriuretic peptide has been proven to improve dyspnea and hemodynamic parameters in heart failure patients. This review provides an update on natriuretic peptides and their therapeutic potential in CHF treatment.

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

PubMed

Sticherling, Christian; Müller, Dirk; Schaer, Beat A; Krüger, Silke; Kolb, Christof

2018-03-27

Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF. Seventeen patients (16 males, mean age 73 ± 6 years, mean EF 25 ± 5%) with permanent AF and an indication for CRT-defibrillator placement were implanted with a designated CRT-D system comprising a single pass defibrillator lead with a atrial floating bipole. They were followed-up for 103 ± 22 days using remote monitoring for AEGM transmission. All patients had at last one AEGM suitable for atrial rhythm diagnosis and of 100 AEGM 99% were suitable for visual atrial rhythm assessment. Four patients were discharged in sinus rhythm and one reverted to AF during follow-up. Atrial electrograms retrieved from a single-pass defibrillator lead with a floating atrial bipole can be reliably used for atrial rhythm diagnosis in CRT recipients with permanent AF. Hence, a single pass ventricular defibrillator lead with a floating bipole can be considered in this population. Copyright © 2018 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

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

PubMed

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

2017-01-01

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

C-type natriuretic peptide: a link between hyperandrogenism and anovulation in a mouse model of polycystic ovary syndrome.

PubMed

Reis, Adelina M; Honorato-Sampaio, Kinulpe

2018-05-16

The polycystic ovary (PCO) syndrome (PCOS) is the most common cause of anovulatory infertility in women and is associated with several clinical disorders. Despite the great amount of research in the area, mechanisms involved in the genesis of this syndrome remain poorly understood. In a recent issue of Clinical Science (vol. 132, issue 7, 759-776), Wang and colleagues, highlight the important role of overactivated C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (CNP/NPR2) system in preventing oocyte maturation and ovulation in PCOS mice model induced by androgen. Dehydroepiandrosterone (DHEA) treatment caused anovulation, high levels of androgen and estrogen receptors (AR and ER) in the ovary, high expression of CNP and natriuretic peptide receptor 2 (NPR2) in granulosa cells (GC), and an increase in testosterone and estradiol (E 2 ) levels in sera. The high level of CNP/NPR2 was associated with oocyte meiotic arrest and very low ovulation rate. Treatment with human chorionic gonadotropin (hCG) or inhibitors of AR or ER reduced the level of CNP/NPR2, which resulted in meiotic resumption and ovulation. The article provided important information for understanding the effect of ovarian steroids on control of oocyte maturation and fertility and highlighted CNP/NPR2 as a specific pathway that is potentially involved in the ovulatory disruption in PCOS. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Atrial and ventricular function after cardioversion of atrial fibrillation.

PubMed Central

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

1995-01-01

OBJECTIVE--Previous studies on atrial recovery after cardioversion of atrial fibrillation have not taken into account new knowledge about the pathophysiology of transmitral and transtricuspid flow velocity patterns. It is possible to shed further light on this problem if atrioventricular inflow velocity, venous filling pattern, and atrioventricular annulus motion are recorded and interpreted together. DESIGN--Prospective examinations of mitral and tricuspid transvalvar flow velocities, superior caval and pulmonary venous filling, and mitral and tricuspid annulus motion were recorded using Doppler echocardiography. Examinations were performed before and 24 hours, 1 month, and 20 months after cardioversion. SETTING--Tertiary referral centre for cardiac disease with facilities for invasive and non-invasive investigation. PATIENTS--16 patients undergoing cardioversion of atrial fibrillation in whom sinus rhythm had persisted for 24 hours or more. RESULTS--Before conversion there was no identifiable A wave in transvalvar flow recordings. The total motion of the tricuspid and mitral annulus was subnormal and there was no identifiable atrial component. Venous flow patterns in general showed a low systolic velocity. After conversion, A waves and atrial components were seen in all patients and increased significantly (P < 0.01) with time. There was a similar time course for the amplitude of annulus atrial components, an increased systolic component of venous inflow, an increased A wave velocity, and a decreased E/A ratio of the transvalvar velocity curves. The ventricular component of annulus motion was unchanged. Changes in general occurred earlier on the right side than the left. CONCLUSIONS--This study indicates that, in addition to the previously known electromechanical dissociation of atrial recovery that exists after cardioversion of atrial fibrillation, there may also be a transient deterioration of ventricular function modulating the transvalvar inflow velocity

Summary of a symposium on natriuretic and digitalis-like factors.

PubMed

Buckalew, V M; Gonick, H C

1998-01-01

An international symposium on natriuretic and digitalis-like factors was convened for the first time since 1992. Topics discussed included structures and biosynthesis of endogenous digitalis-like factors (EDLF), biologic activities, physiology function and role of EDLF in hypertension, and novel natriuretic factors. Progress was reported in determining the exact structure of an isomer of ouabain isolated from bovine hypothalamus. Evidence was presented supporting the existence of a second mammalian EDLF that resembles steroids found in toads (bufodienolides). Support for endogenous synthesis of mammalian EDLF was also presented. Mammalian EDLF were reported to have effects which are different from those possessed by digitalis like steroids derived from plants. New evidence was presented implicating EDLF in various forms of hypertension in humans and animal models. Finally, several unique natriuretic factors that do not inhibit Na, K ATPase and that appear to play a role in mammalian volume regulation were discussed.

Structural studies of the natriuretic peptide receptor: a novel hormone-induced rotation mechanism for transmembrane signal transduction.

PubMed

Misono, Kunio S; Ogawa, Haruo; Qiu, Yue; Ogata, Craig M

2005-06-01

The atrial natriuretic peptide (ANP) receptor is a single-span transmembrane receptor that is coupled to its intrinsic intracellular guanylate cyclase (GCase) catalytic activity. To investigate the mechanisms of hormone binding and signal transduction, we have expressed the extracellular hormone-binding domain of the ANP receptor (ANPR) and characterized its structure and function. The disulfide-bond structure, state of glycosylation, binding-site residues, chloride-dependence of ANP binding, dimerization, and binding stoichiometry have been determined. More recently, the crystal structures of both the apoANPR dimer and ANP-bound complex have been determined. The structural comparison between the two has shown that, upon ANP binding, two ANPR molecules in the dimer undergo an inter-molecular twist with little intra-molecular conformational change. This motion produces a Ferris wheel-like translocation of two juxtamembrane domains with essentially no change in the inter-domain distance. This movement alters the relative orientation of the two domains equivalent to counter-clockwise rotation of each by 24 degrees . These results suggest that transmembrane signaling by the ANP receptor is mediated by a novel hormone-induced rotation mechanism.

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation.

PubMed

Kristensen, Søren Lund; Jhund, Pardeep S; Mogensen, Ulrik M; Rørth, Rasmus; Abraham, William T; Desai, Akshay; Dickstein, Kenneth; Rouleau, Jean L; Zile, Michael R; Swedberg, Karl; Packer, Milton; Solomon, Scott D; Køber, Lars; McMurray, John J V

2017-10-01

Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without ( P <0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P <0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and ≥3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; ≥3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found

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

2017-04-01

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 β 1 , β 2 -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 β 1 and β 2

Ablation for Atrial Fibrillation

PubMed Central

2006-01-01

Executive Summary Objective To review the effectiveness, safety, and costing of ablation methods to manage atrial fibrillation (AF). The ablation methods reviewed were catheter ablation and surgical ablation. Clinical Need Atrial fibrillation is characterized by an irregular, usually rapid, heart rate that limits the ability of the atria to pump blood effectively to the ventricles. Atrial fibrillation can be a primary diagnosis or it may be associated with other diseases, such as high blood pressure, abnormal heart muscle function, chronic lung diseases, and coronary heart disease. The most common symptom of AF is palpitations. Symptoms caused by decreased blood flow include dizziness, fatigue, and shortness of breath. Some patients with AF do not experience any symptoms. According to United States data, the incidence of AF increases with age, with a prevalence of 1 per 200 people aged between 50 and 60 years, and 1 per 10 people aged over 80 years. In 2004, the Institute for Clinical Evaluative Sciences (ICES) estimated that the rate of hospitalization for AF in Canada was 582.7 per 100,000 population. They also reported that of the patients discharged alive, 2.7% were readmitted within 1 year for stroke. One United States prevalence study of AF indicated that the overall prevalence of AF was 0.95%. When the results of this study were extrapolated to the population of Ontario, the prevalence of AF in Ontario is 98,758 for residents aged over 20 years. Currently, the first-line therapy for AF is medical therapy with antiarrhythmic drugs (AADs). There are several AADs available, because there is no one AAD that is effective for all patients. The AADs have critical adverse effects that can aggravate existing arrhythmias. The drug selection process frequently involves trial and error until the patient’s symptoms subside. The Technology Ablation has been frequently described as a “cure” for AF, compared with drug therapy, which controls AF but does not cure it

Brain natriuretic peptide predicts functional outcome in ischemic stroke

PubMed Central

Rost, Natalia S; Biffi, Alessandro; Cloonan, Lisa; Chorba, John; Kelly, Peter; Greer, David; Ellinor, Patrick; Furie, Karen L

2011-01-01

Background Elevated serum levels of brain natriuretic peptide (BNP) have been associated with cardioembolic (CE) stroke and increased post-stroke mortality. We sought to determine whether BNP levels were associated with functional outcome after ischemic stroke. Methods We measured BNP in consecutive patients aged ≥18 years admitted to our Stroke Unit between 2002–2005. BNP quintiles were used for analysis. Stroke subtypes were assigned using TOAST criteria. Outcomes were measured as 6-month modified Rankin Scale score (“good outcome” = 0–2 vs. “poor”) as well as mortality. Multivariate logistic regression was used to assess association between the quintiles of BNP and outcomes. Predictive performance of BNP as compared to clinical model alone was assessed by comparing ROC curves. Results Of 569 ischemic stroke patients, 46% were female; mean age was 67.9 ± 15 years. In age- and gender-adjusted analysis, elevated BNP was associated with lower ejection fraction (p<0.0001) and left atrial dilatation (p<0.001). In multivariate analysis, elevated BNP decreased the odds of good functional outcome (OR 0.64, 95%CI 0.41–0.98) and increased the odds of death (OR 1.75, 95%CI 1.36–2.24) in these patients. Addition of BNP to multivariate models increased their predictive performance for functional outcome (p=0.013) and mortality (p<0.03) after CE stroke. Conclusions Serum BNP levels are strongly associated with CE stroke and functional outcome at 6 months after ischemic stroke. Inclusion of BNP improved prediction of mortality in patients with CE stroke. PMID:22116811

Cardiac Cycle Dependent Left Atrial Dynamics: Implications for Catheter Ablation of Atrial Fibrillation

PubMed Central

Patel, Amit R.; Fatemi, Omid; Norton, Patrick T.; West, J. Jason; Helms, Adam S.; Kramer, Christopher M.; Ferguson, John D.

2008-01-01

Background Left atrial volume (LAV) determines prognosis and response to therapy in atrial fibrillation. Integration of electro-anatomical maps with 3D-images rendered from CT and MRI is used to facilitate atrial fibrillation ablation. Objectives We measured LAV changes and regional motion during the cardiac cycle that might affect the accuracy of image integration and determined their relationship to standard LAV measurements. Methods MRI was performed in thirty patients with paroxysmal atrial fibrillation. Left atrial time-volume curves were generated and used to divide the left atrial function (LAEF) into pumping (PEF) and conduit (CEF) fractions and to determine the maximum LAV (LAMAX) and the pre-atrial contraction volume (PACV). LAV was measured using an MRI angiogram and traditional geometric models from echocardiography (area-length and ellipsoid). The in-plane displacement of the pulmonary veins, anterior left atrium, mitral annulus, and left atrial appendage was measured. Results LAMAX was 107±36ml and occurred at 42±5% of the RR interval. PACV was 86 ±34ml and occurred at 81±4% of the RR interval. LAEF was 45±10% and PEF was 31±10%. LAV measurements made from the MRI angiogram, area-length and ellipsoid models underestimated LAMAX by 21±25ml, 16±26ml, and 35±22ml, respectively. The anterior LA, mitral annulus, and left atrial appendage were significantly displaced during the cardiac cycle (8.8±2.0mm, 13.2±3.8mm, and 10.2±3.4mm, respectively); the pulmonary veins were not. Conclusions LAV changes significantly during the cardiac cycle and substantial regional variation in left atrial motion exists. Standard measurements of left atrial volume significantly underestimate LAMAX when compared to the gold standard measure of 3D-volumetrics. PMID:18486563

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

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

PubMed

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

2017-08-15

Atrial arrhythmias are the most common complication encountered in the growing and aging population with congenital heart disease. This study sought to assess the types and patterns of atrial arrhythmias, associated factors, and age-related trends. A multicenter cohort study enrolled 482 patients with congenital heart disease and atrial arrhythmias, age 32.0 ± 18.0 years, 45.2% female, from 12 North American centers. Qualifying arrhythmias were classified by a blinded adjudicating committee. The most common presenting arrhythmia was intra-atrial re-entrant tachycardia (IART) (61.6%), followed by atrial fibrillation (28.8%), and focal atrial tachycardia (9.5%). The proportion of arrhythmias due to IART increased with congenital heart disease complexity from 47.2% to 62.1% to 67.0% in patients with simple, moderate, and complex defects, respectively (p = 0.0013). Atrial fibrillation increased with age to surpass IART as the most common arrhythmia in those ≥50 years of age (51.2% vs. 44.2%; p < 0.0001). Older age (odds ratio [OR]: 1.024 per year; 95% confidence interval [CI]: 1.010 to 1.039; p = 0.001) and hypertension (OR: 2.00; 95% CI: 1.08 to 3.71; p = 0.029) were independently associated with atrial fibrillation. During a mean follow-up of 11.3 ± 9.4 years, the predominant arrhythmia pattern was paroxysmal in 62.3%, persistent in 28.2%, and permanent in 9.5%. Permanent atrial arrhythmias increased with age from 3.1% to 22.6% in patients <20 years to ≥50 years, respectively (p < 0.0001). IART is the most common presenting atrial arrhythmia in patients with congenital heart disease, with a predominantly paroxysmal pattern. However, atrial fibrillation increases in prevalence and atrial arrhythmias progressively become permanent as the population ages. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Atrial Tachycardias Following Atrial Fibrillation Ablation

PubMed Central

Sághy, László; Tutuianu, Cristina; Szilágyi, Judith

2015-01-01

One of the most important proarrhythmic complications after left atrial (LA) ablation is regular atrial tachycardia (AT) or flutter. Those tachycardias that occur after atrial fibrillation (AF) ablation can cause even more severe symptoms than those from the original arrhythmia prior to the index ablation procedure since they are often incessant and associated with rapid ventricular response. Depending on the method and extent of LA ablation and on the electrophysiological properties of underlying LA substrate, the reported incidence of late ATs is variable. To establish the exact mechanism of these tachycardias can be difficult and controversial but correlates with the ablation technique and in the vast majority of cases the mechanism is reentry related to gaps in prior ablation lines. When tachycardias occur, conservative therapy usually is not effective, radiofrequency ablation procedure is mostly successful, but can be challenging, and requires a complex approach. PMID:25308808

Limited left atrial surgical ablation effectively treats atrial fibrillation but decreases left atrial function.

PubMed

Compier, Marieke G; Tops, Laurens F; Braun, Jerry; Zeppenfeld, Katja; Klautz, Robert J; Schalij, Martin J; Trines, Serge A

2017-04-01

Limited left atrial (LA) surgical ablation with bipolar radiofrequency is considered to be an effective procedure for treatment of atrial fibrillation (AF). We studied whether limited LA surgical ablation concomitant to cardiac surgery is able to maintain LA function. Thirty-six consecutive patients (age 66 ± 12 years, 53% male, 78% persistent AF) scheduled for valve surgery and/or coronary revascularization and concomitant LA surgical ablation were included. Epicardial pulmonary vein isolation (PVI) and additional endo-epicardial lines were performed using bipolar radiofrequency. An age- and gender-matched control group (n = 36, age 66 ± 9 years, 69% male, 81% paroxysmal AF) was selected from patients undergoing concomitant epicardial PVI only. Left atrial dimensions and function were assessed on two-dimensional echocardiography preoperatively and at 3- and 12-month follow-up. Sinus rhythm (SR) maintenance was 67% for limited LA ablation and 81% for PVI at 1-year follow-up (P = 0.18). Left atrial volume decreased from 72 ± 21 to 50 ± 14 mL (31%, P < 0.01) after limited LA ablation and from 65 ± 23 to 56 ± 20 mL (14%, P < 0.01) after PVI. Atrial transport function was restored in 54% of patients in SR after limited LA ablation compared with 100% of patients in SR after PVI. Atrial strain and contraction parameters (LA ejection fraction, A-wave velocity, reservoir function, and strain rate) significantly decreased after limited LA ablation. After PVI, strain and contraction parameters remained unchanged. Even limited LA ablation decreased LA volume, contraction, transport function, and compliance, indicating both reverse remodelling combined with significant functional deterioration. In contrast, surgical PVI decreased LA volume while function remained unchanged. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Effects of the ECE/NEP inhibitor CGS 34225 on the big ET-1-induced pressor response and plasma atrial natriuretic peptide concentration in conscious rats.

PubMed

Trapani, Angelo J; Beil, Michael E; Bruseo, Charles W; Fink, Cynthia A; Hoyer, Denton; Savage, Paula; Jeng, Arco Y

2002-08-01

CGS 34226 is a thiol-containing, potent dual inhibitor of endothelin converting enzyme-1 (ECE-1) and neutral endopeptidase 24.11 (NEP) with IC(50) values of 11 and 5 nM respectively. The purpose of the present study was to characterize the inhibitory effects of CGS 34225, an orally active prodrug of CGS 34226, on ECE-1 and NEP in vivo. The effects on ECE-1 and NEP were assessed by determining the inhibition of big endothelin-1 (big ET-1)-induced increases in mean arterial pressure (MAP) and increases in plasma atrial natriuretic peptide (ANP) concentrations respectively, in conscious rats. Thirty and 120 min after the administration of vehicle, big ET-1 (0.3 nmol/kg, intravenously; i.v.) produced pressor responses of approximately 800 mmHg.min (area under the curve for change in MAPxtime). Treatment with CGS 34225 at 1 mgEq/kg, per os (p.o.), decreased the pressor effect of big ET-1 by 39 and 53% at 30 and 120 min respectively (P<0.05, both times). Increasing the dose of CGS 34255 to 30 mgEq/kg, p.o., resulted in greater inhibition, 84 and 92% (P<0.05) at 30 and 120 min respectively. Furthermore, at this higher dose, the inhibitory effect on ECE-1 was long-lasting, averaging 86, 75 and 30% (P<0.05, all times) at 4, 8 and 24 h respectively. In rats treated with vehicle, the infusion of ANP at 450 ng/kg per min i.v. resulted in plasma ANP concentrations of 3.9-4.8 ng/ml that remained relatively constant for 4 h. Treatment with CGS 34225 at 10 mgEq/kg, p.o., increased the ANP level to 7.7+/-1.0 and 10.6+/-1.8 ng/ml at 1 and 4 h after dosing (P<0.05, both times). These data demonstrate that CGS 34225 is a potent, orally active and long-acting inhibitor of ECE-1 and NEP in vivo. It is anticipated that compounds with this dual function may be useful in the treatment of cardiovascular diseases where the ET system plays a pathogenic role and the potentiation of ANP elicits therapeutic benefits.

Expert opinion paper on atrial fibrillation detection after ischemic stroke.

PubMed

Haeusler, Karl Georg; Gröschel, Klaus; Köhrmann, Martin; Anker, Stefan D; Brachmann, Johannes; Böhm, Michael; Diener, Hans-Christoph; Doehner, Wolfram; Endres, Matthias; Gerloff, Christian; Huttner, Hagen B; Kaps, Manfred; Kirchhof, Paulus; Nabavi, Darius Günther; Nolte, Christian H; Pfeilschifter, Waltraud; Pieske, Burkert; Poli, Sven; Schäbitz, Wolf Rüdiger; Thomalla, Götz; Veltkamp, Roland; Steiner, Thorsten; Laufs, Ulrich; Röther, Joachim; Wachter, Rolf; Schnabel, Renate

2018-04-27

This expert opinion paper on atrial fibrillation detection after ischemic stroke includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. This paper was endorsed by the Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork. In patients with ischemic stroke, detection of atrial fibrillation should usually lead to a change in secondary stroke prevention, since oral anticoagulation is superior to antiplatelet drugs. The detection of previously undiagnosed atrial fibrillation can be improved in patients with ischemic stroke to optimize stroke prevention. This paper summarizes the present knowledge on atrial fibrillation detection after ischemic stroke. We propose an interdisciplinary standard for a "structured analysis of ECG monitoring" on the stroke unit as well as a staged diagnostic scheme for the detection of atrial fibrillation. Since the optimal duration and mode of ECG monitoring has not yet been finally established, this paper is intended to give advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on the expert opinion, reported case series and clinical experience. Therefore, this paper is not intended as a guideline.

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

PubMed

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

2016-11-01

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. © 2016 by the Journal of Biomedical Research. All rights reserved.

Dynamic and dual-site atrial pacing in the prevention of atrial fibrillation: The STimolazione Atrial DInamica Multisito (STADIM) Study.

PubMed

De Simone, Antonio; Senatore, Gaetano; Donnici, Giovanni; Turco, Pietro; Romano, Enrico; Gazzola, Carlo; Stabile, G

2007-01-01

The impact of new algorithms to consistently pace the atrium on the prevention of atrial fibrillation (AF) remains unclear. Our randomized, crossover study compared the efficacy of single- and dual-site atrial pacing, with versus without dynamic atrial overdrive pacing in preventing AF. We studied 72 patients (mean age = 69.6 +/- 6.5 years, 34 men) with sick sinus syndrome (SSS) and paroxysmal or persistent AF, who received dual-chamber pacemakers (PM) equipped with an AF prevention algorithm and two atrial leads placed in the right atrial appendage (RAA), by passive fixation, and in the coronary sinus ostium (CS), by active fixation, respectively. At implant, the patients were randomly assigned to unipolar CS versus RAA pacing. The PM was programmed in DDDR mode 1 month after implant. Each patient underwent four study phases of equal duration: (1) unipolar, single site (CS or RAA) pacing with the AF algorithm ON (atrial lower rate = 0 ppm); (2) unipolar, single site pacing with the AF algorithm OFF (atrial lower rate = 70 bpm); (3) bipolar, dual-site pacing with AF algorithm ON; (4) bipolar, dual-site pacing with the AF algorithm OFF. Among 40 patients (56%), who completed the follow-up (15 +/- 4 months) no difference was observed in the mean number of automatic mode switch (AMS) corrected for the duration of follow-up, in unipolar (5.6 +/- 22.8 vs 2.6 +/- 5.5) or bipolar mode (3.3 +/- 12.7 vs 2.1 +/- 4.9) with, respectively, the algorithm OFF or ON. With the AF prevention algorithm ON, the percentage of atrial pacing increased significantly from 78.7 +/- 22.1% to 92.4 +/- 4.9% (P < 0.001), while the average ventricular heart rate was significantly lower with the algorithm ON (62.4 +/- 17.5 vs 79.9 +/- 3 bpm (P < 0.001). The AF prevention algorithm increased the percentage of atrial pacing significantly, regardless of the atrial pulse configuration and pacing site, while maintaining a slower ventricular heart rate. It had no impact on the number of AMS in the

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

PubMed

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

2017-09-01

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

Left atrial ejection force predicts the outcome after catheter ablation for paroxysmal atrial fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2018-02-01

Left atrium (LA) systolic dysfunction is observed in the early stages of atrial fibrillation (AF) prior to LA anatomical change. We investigated whether LA systolic dysfunction predicts recurrent AF after catheter ablation (CA) in patients with paroxysmal AF. We studied 106 patients who underwent CA for paroxysmal AF. LA systolic function was assessed with the LA emptying volume = Maximum LA volume (LAV max ) - Minimum LA volume (LAV min ), LA emptying fraction = [(LAV max - LAV min )/LAV max ] × 100, and LA ejection force calculated with Manning's method [LA ejection force = (0.5 × ρ × mitral valve area × A 2 )], where ρ is the blood density and A is the late-diastolic mitral inflow velocity. Recurrent AF was detected in 35/106 (33%) during 14.6 ± 9.1 months. Univariate analysis revealed reduced LA ejection force, decreased LA emptying fraction, larger LA diameter, and elevated brain natriuretic peptide as significant variables. On multivariate analysis, reduced LA ejection force and larger LA diameter were independently associated with recurrent AF. Moreover, patients with reduced LA ejection force and larger LA diameter had a higher risk of recurrent AF than preserved LA ejection force (log-rank P = 0.0004). Reduced LA ejection force and larger LA diameter were associated with poor outcome after CA for paroxysmal AF, and could be a new index to predict recurrent AF. © 2017 Wiley Periodicals, Inc.

A comparative study of plasma renin activity, aldosterone and atrial natriuretic hormone between normotensive and hypertensive people living at below sea level altitude (Jordan Valley) and those residing at moderate altitude above.

PubMed

El-Migdadi, Fayig

2007-08-01

A cross-sectional study was designed to investigate the association of the levels of plasma renin activity (PRA) and aldosterone (ALDO) and atrial natriuretic hormone (ANH) with the rates of hypertension prevalence in people living at 340 meters below sea level, the Jordan Valley (JV) and those residing at 620 meters above sea level, Irbid City. 1072 natives from the JV and 1402 natives from Irbid City were covered by a questionnaire to estimate hypertension prevalence in the JV and Irbid city (population age: 35-65 years). Male subjects were selected from the JV (24 hypertensives, 46+/-15 years old, and 93 normotensives, 33+/-13 years old) and from Irbid City (31 hypertensives, 47+/-12 years old, and 89 normotensives, 40+/-13 years old) to evaluate the levels of PRA, ALDO and ANH. Hypertension was less common in the JV than in Irbid City (9.9% vs. 13.6%). The levels of PRA in the hypertensive subjects compared to the normotensive subjects were lower in the JV (1.7+/-1.0 vs. 2.6+/-1.4 ng/ml/hr) but were similar in Irbid City (2.9+/-2.7 vs. 3.2+/-2.7). The levels of ALDO in the hypertensive subjects compared to the normotensive subjects were similar in the JV (119+/-58 vs. 139+/-66 pg/ml) but were higher in Irbid City (199+/-112 vs. 146+/-84). The levels of ANH in the hypertensive subjects compared to the normotensive subjects were lower in the JV (13.9+/-9.3 vs. 28.0+/-12.7 ng/ml) and were also lower in Irbid City (21.0+/-12.2 vs. 26.7+/-11.6).

Effects of oral contraceptives on natriuretic peptide levels in women with hypothalamic amenorrhea: a pilot study.

PubMed

Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K

2011-06-30

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60%-75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives (OC) increases natriuretic peptide levels and that end-of-study free T levels are inversely associated with amino-terminal pro-B-type natriuretic peptide levels, consistent with the hypothesis that natriuretic peptide levels may be mediated by differences in gonadal steroid concentrations-estrogens (E) or androgens. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

2016-01-01

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are

Lone atrial fibrillation: where are we now?

PubMed

Potpara, Tatjana S; Lip, Gregory Y

2011-10-01

There is a growing pandemic of atrial fibrillation (AF), affecting nearly 2% of the general adult population. Atrial fibrillation is commonly associated with structural heart disease, and AF itself causes a sequence of complex processes of electrical, contractile, and structural remodeling of the atrial myocardium, which facilitate further AF progression. Nonetheless, AF may also affect individuals aged ≤ 65 years who have no evidence of associated cardiopulmonary or other disease, including hypertension; this is otherwise referred to as "lone" AF and is considered to have a generally favorable prognosis. The true prevalence of lone AF is unknown. Growing insights into the diversity of numerous mechanisms involved in the pathogenesis of AF, including acute atrial stretch, structural and electrophysiological alterations, systemic inflammation, oxidative stress, autonomic imbalance, genetic predisposition, and many others, and increasing recognition of novel risk factors for AF, including obesity, metabolic syndrome, subclinical atherosclerosis, sleep apnea, alcohol consumption, and endurance sports, suggest that apparently lone AF might not be so "lone" in many patients, which could have important prognostic and therapeutic implications. In this article, we summarize the current knowledge of epidemiology, etiopathogenesis, and pathophysiology of so-called lone AF and discuss the issues of long-term prognosis and management of patients who have an apparently lone AF.

Clinical implications of atrial isomerism.

PubMed Central

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

1988-01-01

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

Atrial fibrillation and hyperthyroidism: A literature review.

PubMed

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

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

Familial pulmonary arterial hypertension, leucopenia, and atrial septal defect: a probable new familial syndrome with multisystem involvement.

PubMed

Dursun, Ali; Ozgul, R Koksal; Soydas, Asli; Tugrul, Tugba; Gurgey, Aytemiz; Celiker, Alpay; Barst, Robyn J; Knowles, James A; Mahesh, Mansukhani; Morse, Jane H

2009-01-01

We present two siblings with identical clinical findings that seem to represent a previously unreported familial syndrome. Major findings involve three systems: pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, and the hematopoietic system with intermittent neutropenia, lymphopenia, monocytosis, and anemia. The siblings also shared several minor abnormalities: pectus carinatum, long fingers, proximally placed thumb, broad nasal bridge, and high-arched palate. The male proband also had bilateral inguinal hernias and undescended testes. The same findings in two siblings suggest a genetic cause--either an autosomal recessive disorder or germline mosaicism in one parent for a dominant mutation. Investigations revealed a bone morphogenetic protein receptor 2 polymorphism in intron 4 in only one sibling, which was also present in unaffected maternal relatives.

Elevated admission N-terminal pro-brain natriuretic peptide level predicts the development of atrial fibrillation in general surgical intensive care unit patients.

PubMed

Chokengarmwong, Nalin; Yeh, Daniel Dante; Chang, Yuchiao; Ortiz, Luis Alfonso; Kaafarani, Haytham M A; Fagenholz, Peter; King, David R; DeMoya, Marc; Butler, Kathryn; Lee, Jarone; Velmahos, George; Januzzi, James Louis; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent

2017-09-01

New onset atrial fibrillation (AF) in critically ill surgical patients is associated with significant morbidity and increased mortality. N-terminal pro-B type natriuretic peptide (NT-proBNP) is released by cardiomyocytes in response to stress and may predict AF development after surgery. We hypothesized that elevated NT-proBNP level at surgical intensive care unit (ICU) admission predicts AF development in a general surgical and trauma population. From July to October 2015, NT-proBNP concentrations were measured at ICU admission. Abnormal NT-proBNP concentrations were defined by age-adjusted cut-offs. We examined the relationship between the development of AF and demographics, clinical variables, and NT-proBNP level using univariate analysis and a multivariable logistic regression model. Three hundred eighty-seven subjects were included in the cohort, none of whom were in AF at ICU admission. The median age was 63 years (52-73 years), and 40.3% were women. The risk of developing AF was higher for abnormal versus normal NT-proBNP (22% vs. 4%; p < 0.0001). Using optimal derived cutoffs (regardless of age), the risk of developing AF was 2% for NT-proBNP less than 600 ng/L, 15% for NT-proBNP of 600 ng/L to 1,999 ng/L, and 27% for NT-proBNP of 2,000 ng/L or greater. Multiple logistic regression analysis identified three independent predictors for new-onset AF: age, older than 70 years (odds ratio [OR], 3.7, 95% confidence interval [CI], 1.5-9.3), history of AF (OR, 25.3; 95% CI, 9.6-67.0), and NT-proBNP of 600 or greater (OR, 4.3; 95% CI, 1.3-14.2). When none or only one predictor was present, AF incidence was less than 1%. When all three predictors were present, AF incidence was 66%. For subjects 70 years or older but no history of AF, AF incidence was 12.8% when NT-proBNP was 600 or greater compared with 0% when NT-proBNP was less than 600. For subjects younger than 70 years with a history of AF, AF incidence was 44.4% when NT-proBNP was 600 or higher compared to 0

Atrial Fibrillation - Multiple Languages

MedlinePlus

... Atrial Fibrillation - العربية (Arabic) Bilingual PDF Health Information Translations Chinese, Simplified (Mandarin dialect) (简体中文) Expand Section Atrial ... Chinese, Simplified (Mandarin dialect)) Bilingual PDF ... Health Information Translations Chinese, Traditional (Cantonese dialect) (繁體中文) Expand Section Atrial ...

B-type natriuretic peptides. A diagnostic breakthrough in heart failure.

PubMed

McCullough, P A

2003-04-01

B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac ventricles, which is released as N-terminal pro-brain natriuretic peptide (NT-proBNP) and then enzymatically cleaved in to the NT fragment and the immunoreactive BNP. Both tests have been used to identify patients with congestive heart failure (CHF). Important considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, and the interpretation of their units of measure. In general, a BNP level below 100 pg/mL has strong negative predictive value in the assessment of patients with dyspnea caused by a disorder other than CHF. In addition, BNP levels can be used to gauge the effect of short-term treatment of acutely decompensated heart failure, and the peptide has been shown to be a reliable independent predictor of sudden cardiac death. In the absence of renal dysfunction NT-proBNP has also been shown to be an independent predictor of sudden death in CHF patients. Because both a large area of myonecrosis or concomitant left ventricular failure are related to prognosis in acute coronary syndromes, B-type natriuretic peptides have also been linked to outcomes in this condition. This article describes the physiology and timing of release of B-type natriuretic peptides and the rationale for their use in the following settings: 1) evaluation of decompensated CHF, 2) screening for chronic CHF, 3) prognosis of CHF and sudden death, and 4) prognosis in acute coronary syndromes with inferred left ventricular dysfunction.

Atrial arrhythmias and autonomic dysfunction in rats exposed to chronic intermittent hypoxia.

PubMed

Bober, Sara L; Ciriello, John; Jones, Douglas L

2018-06-01

Obstructive sleep apnea, which involves chronic intermittent hypoxia (CIH), is a major risk factor for developing atrial fibrillation (AF). Whether or not CIH alone alters cardiac mechanisms to support AF is unknown. This study investigated the effects of CIH on atrial electrophysiology and arrhythmia vulnerability and evaluated the role of autonomics in CIH promotion of AF. Adult male Sprague-Dawley rats were exposed to 8 h/day of CIH or normoxia for 7 days. After exposure, rats were anesthetized for intracardiac electrophysiological experiments. Atrial effective refractory periods (AERPs) and AF inducibility were determined using programmed electrical stimulation and burst pacing in the absence and presence of autonomic receptor agonists and antagonists. Western blot analysis measured atrial protein expression of muscarinic M2, M3, and β 1 -adrenergic receptors. Compared with normoxia-exposed control rats, CIH-exposed rats had enhanced AF vulnerability using both programmed electrical stimulation and burst pacing, accompanied by greater AERP responses to carbachol and propranolol, lesser responses to isoproterenol, and higher atrial M2 receptor protein levels. Enhanced atrial vulnerability was accentuated by carbachol and abolished by atropine, indicating that the AF-promoting effects of CIH depended principally on parasympathetic activation. Enhancement of atrial vulnerability and AERP shortening with cholinergic agonists in CIH-exposed rats is consistent with sensitivity to parasympathetic activation. Higher responses to adrenergic receptor blockade in CIH-exposed rats is consistent with sympathetic potentiation. These findings implicate CIH as an important mediator of enhanced AF susceptibility in obstructive sleep apnea and provide novel insights into the underlying mechanisms. NEW & NOTEWORTHY Our study demonstrates, for the first time, that chronic intermittent hypoxia alone enhances vulnerability to atrial arrhythmia induction, which depends principally

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.

Atrial fibrillation.

PubMed

Medi, Caroline; Hankey, Graeme J; Freedman, Saul B

2007-02-19

The incidence and prevalence of atrial fibrillation are increasing because of both population ageing and an age-adjusted increase in incidence of atrial fibrillation. Deciding between a rate control or rhythm control approach depends on patient age and comorbidities, symptoms and haemodynamic consequences of the arrhythmia, but either approach is acceptable. Digoxin is no longer a first-line drug for rate control: beta-blockers and verapamil and diltiazem control heart rate better during exercise. Anti-arrhythmic drugs have only a 40%-60% success rate of maintaining sinus rhythm at 1 year, and have significant side effects. The selection of optimal antithrombotic prophylaxis depends on the patient's risk of ischaemic stroke and the benefits and risks of long-term warfarin versus aspirin, but is independent of rate or rhythm control strategy. Ischaemic stroke risk is best estimated with the CHADS2 score (Congestive heart failure, Hypertension, Age > or = 75 years, Diabetes, 1 point each; prior Stroke or transient ischaemic attack, 2 points). For patients with valvular atrial fibrillation or a CHADS(2) score > or = 2, anticoagulation with warfarin is recommended (INR 2-3, higher for mechanical valves) unless contraindicated or annual major bleeding risk > 3%. Aspirin or warfarin may be used when the CHADS(2) score = 1. Aspirin, 81-325 mg daily, is recommended in patients with a CHADS(2) score of 0 or if warfarin is contraindicated. Stroke rate is similar for paroxysmal, persistent, and permanent atrial fibrillation, and probably for atrial flutter.

Value of Combining Left Atrial Diameter and Amino-terminal Pro-brain Natriuretic Peptide to the CHA2DS2-VASc Score for Predicting Stroke and Death in Patients with Sick Sinus Syndrome after Pacemaker Implantation.

PubMed

Mo, Bin-Feng; Lu, Qiu-Fen; Lu, Shang-Biao; Xie, Yu-Quan; Feng, Xiang-Fei; Li, Yi-Gang

2017-08-20

The CHA2DS2-VASc score is used clinically for stroke risk stratification in patients with atrial fibrillation (AF). We sought to investigate whether the CHA2DS2-VASc score predicts stroke and death in Chinese patients with sick sinus syndrome (SSS) after pacemaker implantation and to evaluate whether the predictive power of the CHA2DS2-VASc score could be improved by combining it with left atrial diameter (LAD) and amino-terminal pro-brain natriuretic peptide (NT-proBNP). A total of 481 consecutive patients with SSS who underwent pacemaker implantation from January 2004 to December 2014 in our department were included. The CHA2DS2-VASc scores were retrospectively calculated according to the hospital medical records before pacemaker implantation. The outcome data (stroke and death) were collected by pacemaker follow-up visits and telephonic follow-up until December 31, 2015. During 2151 person-years of follow-up, 46 patients (9.6%) suffered stroke and 52 (10.8%) died. The CHA2DS2-VASc score showed a significant association with the development of stroke (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.20-1.75, P< 0.001) and death (HR 1.45, 95% CI 1.22-1.71, P< 0.001). The combination of increased LAD and the CHA2DS2-VASc score improved the predictive power for stroke (C-stat 0.69, 95% CI 0.61-0.77 vs. C-stat 0.66, 95% CI 0.57-0.74, P= 0.013), and the combination of increased NT-proBNP and the CHA2DS2-VASc score improved the predictive power for death (C-stat 0.70, 95% CI 0.64-0.77 vs. C-stat 0.67, 95% CI 0.60--0.75, P= 0.023). CHA2DS2-VASc score is valuable for predicting stroke and death risk in patients with SSS after pacemaker implantation. The addition of LAD and NT-proBNP to the CHA2DS2-VASc score improved its predictive power for stroke and death, respectively, in this patient cohort. Future prospective studies are warranted to validate the benefit of adding LAD and NT-proBNP to the CHA2DS2-VASc score for predicting stroke and death risk in non

Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers.

PubMed

Feola, Iolanda; Volkers, Linda; Majumder, Rupamanjari; Teplenin, Alexander; Schalij, Martin J; Panfilov, Alexander V; de Vries, Antoine A F; Pijnappels, Daniël A

2017-11-01

Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers. Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca 2+ -translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting). Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation. © 2017 American Heart Association, Inc.

F-amplitude, left atrial appendage velocity, and thromboembolic risk in nonrheumatic atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators.

PubMed

Blackshear, J L; Safford, R E; Pearce, L A

1996-04-01

Reduced left atrial appendage velocity (LAAV) has been identified as a marker for thromboembolism in patients with atrial fibrillation. It was postulated that electrocardiographic (ECG) F-wave amplitude would correlate with LAAV, and inversely with the risk of thromboembolism in patients with atrial fibrillation. In all, 53 patients with nonrheumatic (NRAF) and 7 patients with rheumatic (RAF) atrial fibrillation underwent assessment of maximum LAAV, which was correlated to the maximum ECG F-wave voltage from lead V1 (F(max)). In 450 NRAF patients on neither aspirin nor warfarin, the relationship between F(max) and thromboembolic risk was assessed over an average follow-up of 1.3 years. F(max) did not correlate with LAAV (r = 0.2, p = 0.07). Patients with intermittent atrial fibrillation (n = 123) had smaller F(max) amplitude than patients with constant atrial fibrillation (n = 327) (mean 0.73 vs. 0.88 mV-1, p = 0.001). F(max) amplitude was not related to a history of hypertension, systolic blood pressure, duration of NRAF, abnormal transthoracic echocardiographic left ventricular (LV) systolic function or left atrial (LA) diameter. There was a strong trend for increased LV mass being related to smaller F(max) amplitude after adjusting for body surface area (p = 0.06). F(max) amplitude was not correlated with risk of embolic events, including only those events presumed by a panel of case-blinded neurologists to be cardioembolic. F(max) amplitude in NRAF is smaller in patients with intermittent versus constant AF. It does not correlate with LAAV, LA size, increased LV mass, or systolic dysfunction, hypertension, or risk of embolism. Therefore, F(max) amplitude may not be used as a surrogate for LAAV, or as a measure of thromboembolic risk in NRAF.

Temporary atrial epicardial pacing as prophylaxis against atrial fibrillation after heart surgery: a meta-analysis.

PubMed

Daoud, Emile G; Snow, Rick; Hummel, John D; Kalbfleisch, Steven J; Weiss, Raul; Augostini, Ralph

2003-02-01

Recent studies have reported the use of temporary epicardial atrial pacing as prophylaxis for postoperative atrial fibrillation (AF). The aim of this study was to assess the effect of pacing therapies for prevention of postoperative AF using meta-analysis. Using a computerized MEDLINE search, eight pacing prophylaxis trials with 776 patients were included in the meta-analysis. Trials compared control patients to patients randomized to right atrial, left atrial, or biatrial pacing used in conjunction with either fixed high-rate pacing or overdrive pacing. Overdrive biatrial pacing (OR 2.6, CI 1.4-4.8), overdrive right atrial pacing (OR 1.8, CI 1.1-2.7), and fixed high-rate biatrial pacing (OR 2.5, CI 1.3-5.1) demonstrated a significant antiarrhythmic effect for prevention of AF after open heart surgery. Furthermore, studies investigating overdrive left atrial pacing and fixed high-rate right atrial pacing have been underpowered to assess efficacy. Biatrial overdrive and fixed high-rate pacing and right atrial fixed high-rate pacing reduced the risk of new-onset AF after open heart surgery, and the relative risk reduction is approximately 2.5-fold. These results imply that various pacing algorithms are useful as a nonpharmacologic method to prevent postoperative AF.

Cardiac telocytes. From basic science to cardiac diseases. I. Atrial fibrillation.

PubMed

Hostiuc, Sorin; Negoi, Ionuț; Dogaroiu, Catalin; Drima, Eduard; Iancu, Cristian Bogdan

2018-04-12

Atrial fibrillation (AF) is nowadays considered to be one of the most important causes of heart failure, stroke, cognitive decline, vascular dementia, sudden death and overall cardiovascular morbidity. Recently were published a few articles suggesting a possible involvement of telocytes in the development of atrial fibrillation. The purpose of this article is to analyze the results obtained in the field systematically, and to see if there is enough data to support a possible involvement of telocytes in arrhythmogenesis. To this end, we performed a systematic review of the relevant scientific literature, indexed in PubMed, Web of Science, and Scopus. Our systematic review of the published data identified five articles containing original data, based on which the association between telocytes and atrial fibrillation was inferred in later studies. We analyzed the usefulness of the information contained in the original articles to support this association, showing a lack of definite proofs correlating telocytes with atrial fibrillation. Even if a few articles implied a potential association between AF and telocytes, the current data is not enough to support it. Moreover, even an association between the morphology, characteristics, or density of the telocytes in the atrium/pulmonary veins and AF is potentially speculative, and more studies should be performed before implying it with a reasonable degree of certainty. Copyright © 2018 Elsevier GmbH. All rights reserved.

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

[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. © Georg Thieme Verlag KG Stuttgart · New York.

Circulating osteocrin stimulates bone growth by limiting C-type natriuretic peptide clearance.

PubMed

Kanai, Yugo; Yasoda, Akihiro; Mori, Keita P; Watanabe-Takano, Haruko; Nagai-Okatani, Chiaki; Yamashita, Yui; Hirota, Keisho; Ueda, Yohei; Yamauchi, Ichiro; Kondo, Eri; Yamanaka, Shigeki; Sakane, Yoriko; Nakao, Kazumasa; Fujii, Toshihito; Yokoi, Hideki; Minamino, Naoto; Mukoyama, Masashi; Mochizuki, Naoki; Inagaki, Nobuya

2017-11-01

Although peptides are safe and useful as therapeutics, they are often easily degraded or metabolized. Dampening the clearance system for peptide ligands is a promising strategy for increasing the efficacy of peptide therapies. Natriuretic peptide receptor B (NPR-B) and its naturally occurring ligand, C-type natriuretic peptide (CNP), are potent stimulators of endochondral bone growth, and activating the CNP/NPR-B system is expected to be a powerful strategy for treating impaired skeletal growth. CNP is cleared by natriuretic peptide clearance receptor (NPR-C); therefore, we investigated the effect of reducing the rate of CNP clearance on skeletal growth by limiting the interaction between CNP and NPR-C. Specifically, we generated transgenic mice with increased circulating levels of osteocrin (OSTN) protein, a natural NPR-C ligand without natriuretic activity, and observed a dose-dependent skeletal overgrowth phenotype in these animals. Skeletal overgrowth in OSTN-transgenic mice was diminished in either CNP- or NPR-C-depleted backgrounds, confirming that CNP and NPR-C are indispensable for the bone growth-stimulating effect of OSTN. Interestingly, double-transgenic mice of CNP and OSTN had even higher levels of circulating CNP and additional increases in bone length, as compared with mice with elevated CNP alone. Together, these results support OSTN administration as an adjuvant agent for CNP therapy and provide a potential therapeutic approach for diseases with impaired skeletal growth.

Virtual screening of commercial cyclic peptides as NS2B-NS3 protease inhibitor of dengue virus serotype 2 through molecular docking simulation

NASA Astrophysics Data System (ADS)

Nasution, M. A. F.; Aini, R. N.; Tambunan, U. S. F.

2017-04-01

A disease caused by dengue virus infection has become one of the major health problems in the world, particularly in Asia, Africa, and South America. This disease has become endemic in more than 100 countries, and approximately 100 million cases occur each year with 2.5 billion people or 40% of the world population at risk of having this virus infection. Therefore, we need an antiviral drug that can inhibit the activity of the enzymes that involved in the virus replication in the body. Lately, the peptide-based drug design has been developed and proved to have interesting pharmacological properties. This study uses commercially cyclic peptides that have already marketed. The purpose of this study is to screen the commercial cyclic peptides that can be used as an inhibitor of the NS2B-NS3 protease of dengue virus serotype 2 (DENV-2) through molecular docking simulations. Inhibition of NS3 protease enzyme can lead to enzymatic inhibition activity so the formed polyprotein from the translation of RNA cannot be cut into pieces and remain in the long strand form. Consequently, proteins that are vital for the sustainability of dengue virus replication cannot be formed. This research resulted in [alpha]-ANF (1-28), rat, Brain Natriuretic Peptide, porcine, Atrial Natriuretic Factor (3-28) (human) and Atrial Natriuretic Peptide (126-150) (rat) as the best drug candidate for inhibiting the NS2B-NS3 protease of DENV-2.

Effects of Oral Contraceptives on Natriuretic Peptide Levels in Women with Hypothalamic Amenorrhea: A Pilot Study

PubMed Central

Lin, Eleanor; Grinspoon, Steven; Wang, Thomas; Miller, Karen K.

2011-01-01

Natriuretic peptides, which are important regulators of salt handling and blood pressure, are 60 – 75% higher in healthy young women than in men, consistent with a gender dimorphism. In this randomized, placebo-controlled study in women with functional hypothalamic amenorrhea, we show that administration of oral contraceptives increases natriuretic peptide levels and that end-of-study free testosterone levels are inversely associated with NT-proBNP levels, consistent with the hypothesis that natriuretic peptide levels may be mediated by differences in gonadal steroid concentrations – estrogens or androgens. PMID:21620395

Cardiac natriuretic peptide response to water restriction in the hormonal adaptation of two semidesert rodents from West Africa (Steatomys caurinus, Taterillus gracilis).

PubMed

Lacas, S; Allevard, A M; Ag'Atteinine, S; Gallo-Bona, N; Gauquelin-Koch, G; Hardin-Pouzet, H; Gharib, C; Sicard, B; Maurel, D

2000-11-01

Two African rodents, Taterillus gracilis and Steatomys caurinus, native to regions of alternate dry and wet seasons, were studied under laboratory conditions. These species differ in estivation behavior, one undergoing pseudoestivation and the other strong estivation. One group of animals of each species was provided with unlimited access to seed and vegetables rich in water, mimicking the food availability of the wet season (control group). A second group of animals of each species was subjected to water restriction for 8 days, mimicking the natural drought that occurs during the dry-hot season. The effects of water restriction on osmoregulation and body water content were assessed from hematocrit, and plasma and urinary osmolalities (PO, UO). Whether the natriuretic peptide system was modified by the osmoregulator adaptation to aridity of these semidesert rodents was examined from measurements of atrial natriuretic peptide (ANP) levels in plasma, atria, and ventricles, in parallel with morphological studies. In both species, UO was increased by water restriction. In water-deprived T. gracilis, ANP levels were about twice (right atria: 1.08 +/- 0.16 microg/mg protein vs control: 0.40 +/- 0.06 microg/mg protein) and plasma concentrations half (0.28 +/- 0.06 ng/ml vs control: 0.64 +/- 0.07 ng/ml) those in control animals. In S. caurinus these variables were not affected by water availability (right atria water restricted: 2. 20 +/- 0.15 microg/mg protein vs control: 2.86 +/- 0.37 microg/mg protein; plasma ANP water restricted: 0.80 +/- 0.12 ng/ml vs control: 0.90 +/- 0.16 ng/ml). Consistent with these quantitative results, immunohistochemical and ultrastructural observations showed an increase in immunostaining for both the N- and the C-terminal ANP and a larger number of granules in the atria of T. gracilis following water restriction, whereas there was no visible change in S. caurinus. Thus, water restriction induced a decrease in ANP secretion in T. gracilis

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

PubMed

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

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

Mathematical Approaches to Understanding and Imaging Atrial Fibrillation: Significance for Mechanisms and Management

PubMed Central

Trayanova, Natalia A

2014-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia in humans. The mechanisms that govern AF initiation and persistence are highly complex, of dynamic nature, and involve interactions across multiple temporal and spatial scales in the atria. This articles aims to review the mathematical modeling and computer simulation approaches to understanding AF mechanisms and aiding in its management. Various atrial modeling approaches are presented, with descriptions of the methodological basis and advancements in both lower-dimensional and realistic geometry models. A review of the most significant mechanistic insights made by atrial simulations is provided. The article showcases the contributions that atrial modeling and simulation have made not only to our understanding of the pathophysiology of atrial arrhythmias, but also to the development of AF management approaches. A summary of the future developments envisioned for the field of atrial simulation and modeling is also presented. The review contends that computational models of the atria assembled with data from clinical imaging modalities that incorporate electrophysiological and structural remodeling could become a first line of screening for new AF therapies and approaches, new diagnostic developments, and new methods for arrhythmia prevention. PMID:24763468

[Echocardiographic diagnosis of atrial thrombosis].

PubMed

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

1982-01-01

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

Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.

PubMed

Gibbons, David D; Southerland, E Marie; Hoover, Donald B; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

2012-02-01

Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential.

Natriuretic Peptide Receptor Guanylyl Cyclase-A Protects Podocytes from Aldosterone-Induced Glomerular Injury

PubMed Central

Ogawa, Yoshihisa; Yokoi, Hideki; Kasahara, Masato; Mori, Kiyoshi; Kato, Yukiko; Kuwabara, Takashige; Imamaki, Hirotaka; Kawanishi, Tomoko; Koga, Kenichi; Ishii, Akira; Tokudome, Takeshi; Kishimoto, Ichiro; Sugawara, Akira; Nakao, Kazuwa

2012-01-01

Natriuretic peptides produced by the heart in response to cardiac overload exert cardioprotective and renoprotective effects by eliciting natriuresis, reducing BP, and inhibiting cell proliferation and fibrosis. These peptides also antagonize the renin-angiotensin-aldosterone system, but whether this mechanism contributes to their renoprotective effect is unknown. Here, we examined the kidneys of mice lacking the guanylyl cyclase-A (GC-A) receptor for natriuretic peptides under conditions of high aldosterone and high dietary salt. After 4 weeks of administering aldosterone and a high-salt diet, GC-A knockout mice, but not wild-type mice, exhibited accelerated hypertension with massive proteinuria. Aldosterone-infused GC-A knockout mice had marked mesangial expansion, segmental sclerosis, severe podocyte injury, and increased oxidative stress. Reducing the BP with hydralazine failed to lessen such changes; in contrast, blockade of the renin-angiotensin-aldosterone system markedly reduced albuminuria, ameliorated podocyte injury, and reduced oxidative stress. Furthermore, treatment with the antioxidant tempol significantly reduced albuminuria and abrogated the histologic changes. In cultured podocytes, natriuretic peptides inhibited aldosterone-induced mitogen-activated protein kinase phosphorylation. Taken together, these results suggest that renoprotective properties of the endogenous natriuretic peptide/GC-A system may result from the local inhibition of the renin-angiotensin-aldosterone system and oxidative stress in podocytes. PMID:22652704

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

[Typical atrial flutter: Diagnosis and therapy].

PubMed

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

2016-03-01

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

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

PubMed

Liu, Lei; Geng, Jianqiang; Zhao, Hongwei; Yun, Fengxiang; Wang, Xiaoyu; Yan, Sen; Ding, Xue; Li, Wenpeng; Wang, Dingyu; Li, Jianqiang; Pan, Zhenwei; Gong, Yongtai; Tan, Xiangyang; Li, Yue

2015-01-01

Angiotensin II receptor blockers (ARBs) have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF). Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II) and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT) antibody. Western blot was used to analysis the protein expression of neurturin. Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway. © 2015 S. Karger AG, Basel.

Novel ion channel targets in atrial fibrillation.

PubMed

Hancox, Jules C; James, Andrew F; Marrion, Neil V; Zhang, Henggui; Thomas, Dierk

2016-08-01

Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the development of electrical and structural remodeling makes early intervention desirable. Existing antiarrhythmic pharmacological approaches are not always effective and can produce unwanted side effects. Additional atrial-selective antiarrhythmic strategies are therefore desirable. Evidence for three novel ion channel atrial-selective therapeutic targets is evaluated: atrial-selective fast sodium channel current (INa) inhibition; small conductance calcium-activated potassium (SK) channels; and two-pore (K2P) potassium channels. Data from animal models support atrial-ventricular differences in INa kinetics and also suggest atrial-ventricular differences in sodium channel β subunit expression. Further work is required to determine whether intrinsic atrial-ventricular differences in human INa exist or whether functional differences occur due to distinct atrial and ventricular action and resting potentials. SK and K2P channels (particularly K2P 3.1) offer potentially attractive atrial-selective targets. Work is needed to identify the underlying basis of SK current that contributes to (patho)physiological atrial repolarization and settings in which SK inhibition is anti- versus pro-arrhythmic. Although K2P3.1 appears to be a promising target with comparatively selective drugs for experimental use, a lack of selective pharmacology hinders evaluation of other K2P channels as potential atrial-selective targets.

Effects of novel oral anticoagulants on left atrial and left atrial appendage thrombi: an appraisal.

PubMed

Marsico, Fabio; Cecere, Milena; Parente, Antonio; Paolillo, Stefania; de Martino, Fabiana; Dellegrottaglie, Santo; Trimarco, Bruno; Perrone Filardi, Pasquale

2017-02-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and predisposes to an increased risk of thromboembolic events. Patients affected by AF exhibit an increased risk of stroke compared with those in sinus rhythm, with the most common location of thrombi in the left atrial appendage. Until 2009, warfarin and other vitamin K antagonists were the only class of oral anticoagulants available. More recently, dabigatran, rivaroxaban, apixaban, and edoxaban have been approved by regulatory authorities for prevention of stroke in patients with non-valvular AF. Few data are available about the efficacy of novel oral anticoagulants for the treatment of left atrial and left atrial appendage thrombosis. Aim of this review is to summarize available evidence regarding the effectiveness of novel oral anticoagulants on left atrial appendage thrombosis.

[Electrophysiological findings and ablation strategies in patients with atrial tachyarrhythmias after left atrial circumferential ablation in the treatment of atrial fibrillation].

PubMed

Chen, Ming-long; Yang, Bing; Xu, Dong-jie; Zou, Jian-gang; Shan, Qi-jun; Chen, Chun; Chen, Hong-wu; Li, Wen-qi; Cao, Ke-jiang

2007-02-01

To report the electrophysiological findings and the ablation strategies in patients with atrial tachyarrhythmias (ATAs) or atrial fibrillation (AF) recurrence after left atrial circumferential ablation (LACA) in the treatment of AF. 91 patients with AF had LACA procedure from April 2004 to May 2006, 19 of which accepted the second ablation procedure due to ATAs or AF recurrence. In all the 19 patients [17 male, 2 female, age 25 - 65 (53 +/- 12) years], 11 presented with paroxysmal AF before the first ablation procedure, 2 with persistent AF and 6 with permanent AF. Pulmonary vein potentials (PVP) were investigated in both sides in all the patients. Delayed PVP was identified inside the left circular line in 5 patients, in the right in 1 and both in 2 during sinus rhythm. "Gap" conduction was found and successfully closed guided by circular mapping catheter. In 3 cases, irregular left atrial tachycardia was caused by fibrillation rhythm inside the left ring via decremental "gap" conduction. Reisolation was done successfully again guided by 3-D mapping and made the left atrium in sinus rhythm but the fibrillation rhythm was still inside the left ring. Pulmonary vein tachycardia with 1:1 conduction to the left atrium presented in one case and reisolation stopped the tachycardia. No PVP was discovered in both sides in 4 patients but other tachycardias could be induced, including two right atrial scar related tachycardias, two supraventricular tachycardias mediated by concealed accessory pathway, one cavo-tricuspid isthmus dependent atrial flutter and one focal atrial tachycardia near the coronary sinus ostium. All the tachycardias in these 4 patients were successfully ablated with the help of routine and 3-D mapping techniques. In the rest 3, which were in AF rhythm, LACA was successfully done again. After a mean follow-up of 4 - 26 (11.5 +/- 8.5) months, 16 patients were symptom free without anti-arrhythmic drug therapy; 1 of them had frequent palpitation attack with

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

PubMed

Gudul, Naile Eris; Karabag, Turgut; Sayin, Muhammet Rasit; Bayraktaroglu, Taner; Aydin, Mustafa

2017-03-01

The aim of this study was to investigate atrial conduction times and left atrial mechanical functions, the noninvasive predictors of atrial fibrillation, in prediabetic patients with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Study included 59 patients (23 males, 36 females; mean age 52.5 ± 10.6 years) diagnosed with IFG or IGT by the American Diabetes Association criteria, and 43 healthy adults (22 males, 21 females; mean age 48.5 ± 12.1 years). Conventional and tissue Doppler echocardiography were performed. The electromechanical delay parameters were measured from the onset of the P wave on the surface electrocardiogram to the onset of the atrial systolic wave on tissue Doppler imaging from septum, lateral, and right ventricular annuli. The left atrial volumes were calculated by the disk method. Left atrial mechanical functions were calculated. The mitral E/A and E'/A' ratios measured from the lateral and septal annuli were significantly lower in the prediabetics compared to the controls. The interatrial and left atrial electromechanical delay were significantly longer in prediabetic group compared to the controls. Left atrial active emptying volume (LAAEV) and fraction (LAAEF) were significantly higher in the prediabetics than the controls. LAAEV and LAAEF were significantly correlated with E/A, lateral and septal E'/A'. In the prediabetic patients, the atrial conduction times and P wave dispersion on surface electrocardiographic were longer before the development of overt diabetes. In addition, the left atrial mechanical functions were impaired secondary to a deterioration in the diastolic functions in the prediabetic patients.

Effects of Transdermal Testosterone on Natriuretic Peptide Levels in Women: A Randomized Placebo-Controlled Pilot Study

PubMed Central

Lin, Eleanor; McCabe, Elizabeth; Newton-Cheh, Christopher; Bloch, Kenneth; Buys, Emmanuel; Wang, Thomas; Miller, Karen K.

2011-01-01

Objective To investigate whether testosterone administration alters natriuretic peptide levels in women. Design Three-month, double-blind, randomized, placebo-controlled study. Setting Clinical research center. Patients 51 women with hypoandrogenemia due to hypopituitarism. Intervention Transdermal testosterone (300 mcg daily) or placebo patch. Main Outcome Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Results NT-proBNP levels decreased in the transdermal testosterone group compared with placebo over three months (p = 0.009). The difference between groups remained significant after controlling for baseline age, systolic blood pressure, body mass index, and homeostasis model of assessment-insulin resistance (p = 0.008). Change in NT-proBNP over three months was inversely associated with change in free testosterone levels (ρ = −0.41, p = 0.01). Conclusions Testosterone administration to women results in decreased natriuretic peptide levels, suggesting that testosterone may be an inverse regulator of the natriuretic peptide system. Clinical Trials Registration Number NCT00027430 PMID:22137497

Echocardiographic estimation of left atrial pressure in beagle dogs with experimentally-induced mitral valve regurgitation.

PubMed

Ishikawa, Taisuke; Fukushima, Ryuji; Suzuki, Shuji; Miyaishi, Yuka; Nishimura, Taiki; Hira, Satoshi; Hamabe, Lina; Tanaka, Ryou

2011-08-01

Non-invasive and immediate estimation of left atrial pressure (LAP) is very useful for the management of mitral regurgitation (MR), and many reports have assessed echocardiographic estimations of LAP to date. However, it has been unclear of which examination and evaluate article possess the best accuracy for the MR severity. The present research aims to establish the echocardiographic estimation equation of LAP that is well applicable for clinical MR dogs. After the chordae tendineae rupture was experimentally induced via left atriotomy in six healthy beagle dogs (three males and three females, two years old, weighing between 9.8 to 12.8 kg), a radio telemetry transmitter catheter was inserted, which allows the continuous recordings of LAP without the use of sedation. Approximately 5 weeks after the surgery, echocardiographic examination, indirect blood pressure measurement, measurement of plasma atrial natriuretic peptide (ANP) and LAP measurement by way of the radio telemetry system was performed simultaneously. Subsequently, simple linear regression equations between LAP and each variable were obtained, and the equations were evaluated whether to be applicable for clinical MR dogs. As a result, the ratio of early diastolic mitral flow to early diastolic lateral mitral annulus velocity (E/Ea) had the strongest correlation as maximum LAP=7.03*(E/Ea)-54.86 (r=0.74), and as mean LAP=4.94*(E/Ea)-40.37 (r=0.70) among the all variables. Therefore, these two equations associated with E/Ea should bring more precise and instant estimations of maximum and mean LAP in clinical MR dogs.

Limitations of N-Terminal Pro-B-Type Natriuretic Peptide in the Diagnosis of Heart Disease among Cancer Patients Who Present with Cardiac or Pulmonary Symptoms.

PubMed

Wieshammer, Siegfried; Dreyhaupt, Jens; Müller, Dirk; Momm, Felix; Jakob, Andreas

2016-01-01

Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml. A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy. Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity. The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

Subclinical atrial fibrillation and the risk of stroke.

PubMed

Healey, Jeff S; Connolly, Stuart J; Gold, Michael R; Israel, Carsten W; Van Gelder, Isabelle C; Capucci, Alessandro; Lau, C P; Fain, Eric; Yang, Sean; Bailleul, Christophe; Morillo, Carlos A; Carlson, Mark; Themeles, Ellison; Kaufman, Elizabeth S; Hohnloser, Stefan H

2012-01-12

One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. Subclinical atrial

The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting.

PubMed

Roberts, Emmert; Ludman, Andrew J; Dworzynski, Katharina; Al-Mohammad, Abdallah; Cowie, Martin R; McMurray, John J V; Mant, Jonathan

2015-03-04

To determine and compare the diagnostic accuracy of serum natriuretic peptide levels (B type natriuretic peptide, N terminal probrain natriuretic peptide (NTproBNP), and mid-regional proatrial natriuretic peptide (MRproANP)) in people presenting with acute heart failure to acute care settings using thresholds recommended in the 2012 European Society of Cardiology guidelines for heart failure. Systematic review and diagnostic meta-analysis. Medline, Embase, Cochrane central register of controlled trials, Cochrane database of systematic reviews, database of abstracts of reviews of effects, NHS economic evaluation database, and Health Technology Assessment up to 28 January 2014, using combinations of subject headings and terms relating to heart failure and natriuretic peptides. Eligible studies evaluated one or more natriuretic peptides (B type natriuretic peptide, NTproBNP, or MRproANP) in the diagnosis of acute heart failure against an acceptable reference standard in consecutive or randomly selected adults in an acute care setting. Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or report age independent natriuretic peptide thresholds. Studies not available in English were also excluded. 37 unique study cohorts described in 42 study reports were included, with a total of 48 test evaluations reporting 15 263 test results. At the lower recommended thresholds of 100 ng/L for B type natriuretic peptide and 300 ng/L for NTproBNP, the natriuretic peptides have sensitivities of 0.95 (95% confidence interval 0.93 to 0.96) and 0.99 (0.97 to 1.00) and negative predictive values of 0.94 (0.90 to 0.96) and 0.98 (0.89 to 1.0), respectively, for a diagnosis of acute heart failure. At the lower recommended threshold of 120 pmol/L, MRproANP has a sensitivity ranging from 0.95 (range 0.90-0.98) to 0.97 (0.95-0.98) and a negative predictive value ranging from 0.90 (0

Racial Differences in Circulating Natriuretic Peptide Levels: The Atherosclerosis Risk in Communities Study

PubMed Central

Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

2015-01-01

Background Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. Methods and Results We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996–1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], −43, −36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. Conclusions African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in

Racial differences in circulating natriuretic peptide levels: the atherosclerosis risk in communities study.

PubMed

Gupta, Deepak K; Claggett, Brian; Wells, Quinn; Cheng, Susan; Li, Man; Maruthur, Nisa; Selvin, Elizabeth; Coresh, Josef; Konety, Suma; Butler, Kenneth R; Mosley, Thomas; Boerwinkle, Eric; Hoogeveen, Ron; Ballantyne, Christie M; Solomon, Scott D

2015-05-21

Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996-1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], -43, -36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population. © 2015 The Authors. Published on

[Atrial fibrillation].

PubMed

Spinar, J; Vítovec, J

2003-09-01

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

Frequency of and Prognostic Significance of Cardiac Involvement at Presentation in Hereditary Transthyretin-Derived Amyloidosis and the Value of N-Terminal Pro-B-Type Natriuretic Peptide.

PubMed

Klaassen, Sebastiaan H C; Tromp, Jasper; Nienhuis, Hans L A; van der Meer, Peter; van den Berg, Maarten P; Blokzijl, Hans; van Veldhuisen, Dirk J; Hazenberg, Bouke P C

2018-01-01

The aim of this study is to assess the prevalence of cardiac involvement in hereditary transthyretin-derived (ATTRm) amyloidosis at the time of diagnosis and to determine the diagnostic and clinical value of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The University Medical Center Groningen is the national center of expertise for amyloidosis. All consecutive patients between 1994 and 2016 with ATTRm amyloidosis were followed prospectively. Baseline was set at the time of the first positive biopsy. All patients underwent a standard cardiac and neurologic work-up. Cardiac involvement was defined by otherwise unexplained left and/or right ventricular wall hypertrophy on cardiac ultrasound and/or advanced conduction disturbances. Seventy-seven patients had ATTRm amyloidosis and were included in the study. The TTR V30M mutation was present in 30 patients (39%). In both the V30M and the non-V30M groups, the neurologic presentation dominated (77% vs 51%), whereas cardiac presentation was infrequent (7% vs 15%). Clinical work-up showed that cardiac involvement was present at baseline in 51% of all patients irrespective of genotype and was associated with increased overall mortality (hazard ratio 5.95, 95% confidence interval 2.12 to 16.7), independent from clinical confounders. At a cutoff level of 125 ng/L, NT-proBNP had a sensitivity of 92% for establishing cardiac involvement. In conclusion, irrespective of the frequent noncardiac presentation of ATTRm amyloidosis, cardiac involvement is already present at diagnosis in half of the patients and is associated with increased mortality. NT-proBNP is a useful marker to determine cardiac involvement in this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Left Atrial Anatomy in Patients Undergoing Ablation for Atrial Fibrillation.

PubMed

Krum, David; Hare, John; Gilbert, Carol; Choudhuri, Indrajit; Mori, Naoyo; Sra, Jasbir

2013-01-01

Background: Left atrial anatomy is highly variable, asymmetric, irregular and three-dimensionally unique. This variability can affect the outcome of atrial ablation. A catalog of anatomic varieties may aid patient selection and ablation approach and provide better tools for left atrial ablation. Methods: We analyzed computed tomography scans from 514 patients undergoing left atrial ablation. Images were processed on Advantage Windows with CardEP™ software (GE Healthcare, Waukesha, WI). Measurements of pulmonary vein (PV) ostial size along the long and short axes were made using double oblique cuts, and area of the ostia was calculated. Results: Patients with 2 left (LPV) and 2 right PVs (RPV) (62.6%), 2 LPVs and 3 RPVs (17.3%) and 1 LPV and 2 RPVs (14.2%) made up the three most common variants. In the 2-LPV/2-RPV anatomy, the ostial size and area of the RPVs were larger than their corresponding LPVs (p<0.001), and the ostial size and area of the superior PVs were larger than their corresponding inferior PVs (p<0.001). In the 2-LPV/3-RPV anatomy, the total area of the RPVs was larger than the total area of the LPVs (p<0.001). In the 1-LPV/2-RPV anatomy, the ostial size of the left common PV was larger than either right PV (p<0.007). However, the total area of the RPVs was larger than the area of the left common PV (p<0.002). The left common PV was also larger than any of the left veins in any of the other anatomies. The total PV area between the three most common anatomies was not significantly different. Conclusions: More than 37% of patients have a left atrial anatomy other than 2 left and 2 right PVs. This data may help in designing approaches for left atrial ablation, tailoring the procedure to individual patients and improving ablation tools.

Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion.

PubMed

Gaddam, Krishna K; Nishizaka, Mari K; Pratt-Ubunama, Monique N; Pimenta, Eduardo; Aban, Inmaculada; Oparil, Suzanne; Calhoun, David A

2008-06-09

Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage. We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using natriuretic peptide, atrial natriuretic peptide, and 24-hour urinary aldosterone (UAldo), cortisol, sodium, and potassium values while adhering to a routine diet. Plasma aldosterone (P < .001), aldosterone to renin ratio (P < .001), 24-hour UAldo (P = .02), brain-type natriuretic peptide (P = .007), and atrial natriuretic peptide (P = .001) values were higher and plasma renin activity (P = .02) and serum potassium (P < .001) values were lower in patients with resistant hypertension vs controls. Of patients with resistant hypertension, men had significantly higher plasma aldosterone (P = .003), aldosterone to renin ratio (P = .02), 24-hour UAldo (P < .001), and urinary cortisol (P < .001) values than women. In univariate linear regression analysis, body mass index (P = .01), serum potassium (P < .001), urinary cortisol (P < .001), urinary sodium (P = .02), and urinary potassium (P < .001) values were correlated with 24-hour UAldo levels. Serum potassium (P = .001), urinary potassium (P < .001), and urinary sodium (P = .03) levels were predictors of 24-hour UAldo levels in multivariate modeling. Aldosterone levels are higher and there is evidence of intravascular volume expansion (higher brain-type and atrial natriuretic peptide levels) in patients with resistant hypertension vs controls. These differences are most pronounced in men. A significant correlation between 24-hour urinary aldosterone levels and cortisol excretion suggests that a common stimulus, such as

Left atrial function measured by cardiac magnetic resonance imaging in patients with heart failure: clinical associations and prognostic value.

PubMed

Pellicori, Pierpaolo; Zhang, Jufen; Lukaschuk, Elena; Joseph, Anil C; Bourantas, Christos V; Loh, Huan; Bragadeesh, Thanjavur; Clark, Andrew L; Cleland, John G F

2015-03-21

Left atrial (LA) volume is an important marker of cardiac dysfunction and cardiovascular outcome in heart failure (HF), but LA function is rarely measured. Left atrial emptying function (LAEF), its clinical associations and prognostic value was studied in outpatients referred with suspected HF who were in sinus rhythm and had cardiac magnetic resonance imaging (CMRI). Heart failure was defined as relevant symptoms and signs with either a left ventricular ejection fraction (LVEF) <50% or amino-terminal pro-B-type natriuretic peptide (NTproBNP) >400 pg/mL (or >125 pg/mL if taking loop diuretics). Of 982 patients, 664 fulfilled the HF criteria and were in sinus rhythm. The median (interquartile range, IQR) LAEF was 42 (31-51)% and 55 (48-61)% in patients with and without HF (P < 0.001). Patients with HF in the lowest quartile of LAEF (23%; IQR: 17-28%) had lower LV and right ventricular (RV) EF, and greater LV and RV mass and higher plasma NTproBNP than those in the highest quartile of LAEF (56%; IQR: 53-61%). Log[LAEF] and log[NTproBNP] were inversely correlated (r = -0.410, P < 0.001). During a median follow-up of 883 (IQR: 469-1626) days, 394 (59%) patients with HF died or were admitted with HF and 101 (15%) developed atrial fibrillation (AF). In a multivariable Cox model, increasing LAEF, but not LVEF, was independently associated with survival (HR for 10% change: 0.81 (95%CI: 0.73-0.90), P = <0.001). Increasing age and decreasing LAEF predicted incident AF. In patients with HF, LAEF predicts adverse outcome independently of other measures of cardiac dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Fall in readmission rate for heart failure after implementation of B-type natriuretic peptide testing for discharge decision: a retrospective study.

PubMed

Valle, Roberto; Aspromonte, Nadia; Carbonieri, Emanuele; D'Eri, Alessandra; Feola, Mauro; Giovinazzo, Prospero; Noventa, Federica; Prevaldi, Carolina; Barro, Sabrina; Milani, Loredano

2008-06-06

B-type natriuretic peptide is the most powerful predictor of long term prognosis in patients hospitalised with heart failure. On an outsetting basis, a decrease in B-type natriuretic peptide levels is associated to a decrease in event rate for outpatients managed using the neuro-hormone levels as the target in heart failure therapy. We have retrospectively checked whether the addition of pre-discharge B-type natriuretic peptide levels to a clinical-instrumental decisional score for discharge decision in patients admitted for heart failure reduced readmission rate for heart failure and related cost. We studied two series of consecutive patients admitted to the Heart Failure Unit due to acute heart failure as a main diagnosis. One-hundred and forty-nine patients discharged on the basis of the sole clinical acumen were compared to one hundred and sixty-six subjects discharged adding B-type natriuretic peptide levels to the decisional score. During a six-month follow-up period, there were 52 readmissions (35%) among the clinical group (n=149) compared with 38 (23%) readmissions in the B-type natriuretic peptide group (n=166) (chi(2)=5.5; P=0.02). Survival did not differ between groups (87%). Changes in B-type natriuretic peptide values were correlated to clinical events: a B-type natriuretic peptide value on discharge of < or =250 pg/ml or a reduction of > or =30% in B-type natriuretic peptide values predicted a 23% event rate (death, plus readmission for heart failure), whereas a far higher percentage (71%) were observed in the remaining patients (chi(2)=32.7; P=0.001). Likewise, the overall costs of care were lower (-7%) in the B-type natriuretic peptide group: 2.781+/-923 vs 2.978+/-1.057 euros per patient respectively. our study suggest that the addition of pre-discharge B-type natriuretic peptide levels to a clinical-instrumental decisional score for discharge decision in patients admitted for heart failure may contribute to reduce the number of readmissions and

Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?

PubMed

Ravens, Ursula

2017-11-01

In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K + ) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two-pore domain K + (K2P) channels (tandem of P domains, weak inward-rectifying K + channels (TWIK-1), TWIK-related acid-sensitive K + channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.

Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet

PubMed Central

Goncalves, Gleisy Kelly; de Oliveira, Thiago Henrique Caldeira; de Oliveira Belo, Najara

2017-01-01

Background Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. Material/Methods Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. Results A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. Conclusions The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model. PMID:29249795

Left ventricular stiffness estimated by diastolic wall strain is associated with paroxysmal atrial fibrillation in structurally normal hearts.

PubMed

Uetake, Shunsuke; Maruyama, Mitsunori; Yamamoto, Teppei; Kato, Katsuhito; Miyauchi, Yasushi; Seino, Yoshihiko; Shimizu, Wataru

2016-12-01

Left ventricular (LV) diastolic dysfunction depends on an impaired relaxation and stiffness. Abnormal LV relaxation contributes to the development of atrial fibrillation (AF), but the role of LV stiffness in AF remains unclear. Diastolic wall strain (DWS), a load-independent, noninvasive direct measure of LV stiffness, correlates with prevalent AF. This study included 328 consecutive subjects with structurally normal hearts: 164 paroxysmal AF patients and 164 age- and sex-matched (1:1) controls. We calculated the DWS from the M-mode echocardiographic measurements of the LV posterior wall thickness at end-systole and end-diastole during sinus rhythm. The DWS was lower in the AF patients (0.35 ± 0.07) than in the controls (0.41 ± 0.06; P < 0.001). After adjusting for the risk factors of AF using a conditional logistic regression analysis, a history of hypertension, plasma brain-type natriuretic peptide level, and DWS were independently associated with AF prevalence, whereas body mass index, LV mass index, left atrial volume, and any conventional indices of the diastolic function were not. A low DWS (<0.380) was the strongest indicator of AF (odds ratio: 6.22, 95% confidence interval: 3.08-14.2, P < 0.001). Increased LV stiffness estimated by DWS was a strong determinant of the prevalence of AF. LV stiffness may play a role in the pathogenesis of paroxysmal AF in structurally normal hearts. © 2016 Wiley Periodicals, Inc.

Primary prevention of atrial fibrillation: does the atrial lead position influence the incidence of atrial arrhythmias in patients with sinus node dysfunction? Results from the PASTA Trial.

PubMed

Spitzer, Stefan G; Wacker, Petra; Gazarek, Steffen; Malinowski, Klaus; Schibgilla, Volker

2009-12-01

PASTA (pacing of the atria in sinus node disease) is a prospective and randomized trial, assessing the effect of different atrial lead positions on the atrial fibrillation (AF) incidence in patients with sinus node disease (SND). The atrial lead position is randomized to: (a) free right atrial wall, (b) right atrial appendage (RAA), (c) coronary sinus ostium (CS-Os), or (d) dual site right atrial pacing (CS-Os + RAA). The pacemakers (Vitatron Selection 9000 or Prevent AF, Vitatron B.V., Arnhem, The Netherlands) are programmed in DDDR 70 mode and the total follow-up duration is 24 months. To describe the atrial rhythm state, pacemaker-derived data (arrhythmia counter) were assessed for AF episodes. AF was considered as evident, if the AF burden (time in AF related to follow-up interval) was >1% (i.e., 15 min/d). Follow-up data after 24 months were evaluated. The analysis evaluates 142 patients (77 male, 74.5 +/- 7.8 years). There was no statistical significant difference with respect to the occurrence of AF between the four groups after 24 months (A: 36%; B: 38%, C: 32%, D: 48%). The percentage of atrial/ventricular pacing was in A: 78/76%, in B: 84/81%, in C: 70/65%, and in D: 79/69%. These differences were not significant. The evaluation of the AF burden >1% and the total AF burden after 24 months did not show differences in the incidence of AF in patients with dual chamber pacemaker therapy for SND. We were not able to demonstrate a significant influence of right atrial lead position on the incidence of AF recurrence.

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

PubMed

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

2014-05-01

We aimed to investigate effects of left ventricular diastolic dysfunction on left atrial appendage functions, spontaneous echo contrast and thrombus formation in patients with nonvalvular atrial fibrillation. In 58 patients with chronic nonvalvular atrial fibrilation and preserved left ventricular systolic function, left atrial appendage functions, left atrial spontaneous echo contrast grading and left ventricular diastolic functions were evaluated using transthoracic and transoesophageal echocardiogram. Patients divided in two groups: Group D (n=30): Patients with diastolic dysfunction, Group N (n=28): Patients without diastolic dysfunction. Categorical variables in two groups were evaluated with Pearson's chi-square or Fisher's exact test. The significance of the lineer correlation between the degree of spontaneous echo contrast (SEC) and clinical measurements was evaluated with Spearman's correlation analysis. Peak pulmonary vein D velocity of the Group D was significantly higher than the Group N (p=0.006). However, left atrial appendage emptying velocity, left atrial appendage lateral wall velocity, peak pulmonary vein S, pulmonary vein S/D ratio were found to be significantly lower in Group D (p=0.028, p<0.001, p<0.001; p<0.001). Statistically significant negative correlation was found between SEC in left atrium and left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities respectively (r=-0.438, r=-0.328, r=-0.233, r=-0.447). Left atrial appendage emptying, filling, pulmonary vein S/D levels and lateral wall velocities were significantly lower in SEC 2-3-4 than SEC 1 (p=0.003, p=0.029, p<0.001, p=0.002). In patients with nonvalvular atrial fibrillation and preserved left ventricular ejection fraction, left atrial appendage functions are decreased in patients with left ventricular diastolic dysfunction. Left ventricular diastolic dysfunction may constitute a potential risk for formation of thrombus and stroke.

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

PubMed

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

2004-09-01

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

Greater nighttime blood pressure variability is associated with left atrial enlargement in atrial fibrillation patients with preserved ejection fraction.

PubMed

Norioka, Naoki; Iwata, Shinichi; Ito, Asahiro; Tamura, Soichiro; Kawai, Yu; Nonin, Shinichi; Ishikawa, Sera; Doi, Atsushi; Hanatani, Akihisa; Yoshiyama, Minoru

2018-06-13

Left atrial enlargement is an independent risk factor for ischemic stroke in patients with atrial fibrillation. Little is known regarding the association between nighttime blood pressure variability and left atrial enlargement in patients with atrial fibrillation and preserved ejection fraction. The study population consisted of 140 consecutive patients with atrial fibrillation (mean age 64 ± 10 years) with preserved ejection fraction (≥50%). Nighttime blood pressure was measured at hourly intervals, using a home blood pressure monitoring device. Nighttime blood pressure variability was expressed as the standard deviation of all readings. Left atrial volume index was measured using the modified Simpson's biplane method with transthoracic echocardiography. Multiple regression analysis indicated that nighttime mean systolic/diastolic blood pressure and its variability remained independently associated with left atrial enlargement after adjustment for age, sex, anti-hypertensive medication class, and left ventricular mass index (P < 0.01). When patients were divided into four groups according to nighttime blood pressure and its variability, the group with higher nighttime blood pressure and its variability had significantly larger left atrial volume than the group with lower nighttime blood pressure and its variability (46.6 ml/m 2 vs. 35.0 ml/m 2 , P < 0.0001). Higher nighttime blood pressure and its variability are associated with left atrial enlargement. The combination of nighttime blood pressure and its variability has additional predictive value for left atrial enlargement. Intensive intervention for these high-risk patients may avoid or delay progression of left atrial enlargement and reduce the risk of stroke.

Sleep disordered breathing in cardiac surgery patients: The NU-SLEEP trial.

PubMed

Sezai, Akira; Akahoshi, Toshiki; Osaka, Shunji; Yaoita, Hiroko; Arimoto, Munehito; Hata, Hiroaki; Tanaka, Masashi; Sekino, Hisakuni; Akashiba, Tsuneto

2017-01-15

Sleep disordered breathing (SDB) is associated with lifestyle-related diseases and its treatment influence the prognosis of cardiac disease, but little investigation of SDB has been conducted in cardiac surgery patients. A prospective study was performed in 1005 patients undergoing cardiac surgery. The primary endpoint was the severity of SDB determined from the apnea/hypopnea index. The secondary endpoints were patient background factors, cardiovascular risk factors, ejection fraction, atrial and brain natriuretic peptides, oxidative stress and inflammatory markers, and postoperative atrial fibrillation. While 227 patients (22.6%) did not have SDB, there were 361 patients (35.9%) with mild SDB, 260 patients (25.9%) with moderate SDB, and 157 patients (15.6%) with severe SDB. Patients with severe SDB had a lower ejection fraction and higher levels of atrial and brain natriuretic peptides than the other groups. Postoperative atrial fibrillation occurred in 28 patients without SDB (13.6%), 43 patients with mild SDB (13.5%), 74 patients with moderate SDB (31.9%), and 73 patients with severe SDB (52.5%), being significantly more frequent in the severe group than the other groups. SDB was frequent in cardiac surgery patients. Activation of the renin-angiotensin-aldosterone system, postoperative atrial fibrillation atrial, and cardiac dysfunction were associated with severe SDB. Markers of inflammation and oxidative stress also increased as SDB became more severe. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Surgical treatment for ectopic atrial tachycardia.

PubMed

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

1992-08-01

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

Histopathologic analysis of atrial tissue in patients with atrial fibrillation: comparison between patients with atrial septal defect and patients with mitral valvular heart disease.

PubMed

Kwak, Jae Gun; Seo, Jeong-Wook; Oh, Sam Se; Lee, Sang Yun; Ham, Eui Keun; Kim, Woong-Han; Kim, Soo-Jin; Bae, Eun Jung; Lim, Cheoung; Lee, Chang-Ha; Lee, Cheul

2014-01-01

Atrial fibrillation (AF) in adult patients with atrial septal defect (ASD) accompanies an enlarged right atrium (RA) with a less enlarged left atrium (LA), which is the opposite situation in patients with AF and mitral valvular disease. This study was to compare the histopathological change in the atrium of patients with AF of two different etiologies: ASD and mitral disease. Twenty-four patients were enrolled. Group 1 included patients with ASD (8), Group 2 included patients with ASD with AF (6), and Group 3 included patients with mitral disease with AF (10). Preoperative atrial volumes were measured. Atrial tissues were obtained during surgical procedures and stained with periodic acid-Schiff, smooth muscle actin, Sirius red, and Masson's trichrome to detect histopathologic changes compatible with AF. The severity of histopathological changes was represented with "positivity" and "strong positivity" after analyzing digitalized images of the staining. We investigated the relationship between the degree of atrial dilatation and severity of histopathological changes according to the groups and tissues. Group 2 and Group 3 patients showed a tendency toward an enlarged RA volume and enlarged LA volume, respectively, compared with each others. However, in the histopathologic analysis, "positivity" and "strong positivity" showed no significant positive correlations with the degree of atrial volume in special staining. A similar degree of histopathologic changes was observed in both atria in patients with AF (Group 2 and 3) regardless of the degree of dilatation of atrial volume and disease entities. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2018-01-01

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

Patients' experiences of communication and involvement in decision-making about atrial fibrillation treatment in consultations with nurses and physicians.

PubMed

Siouta, Eleni; Hellström Muhli, Ulla; Hedberg, Berith; Broström, Anders; Fossum, Bjöörn; Karlgren, Klas

2016-09-01

Insights in consultations across patient interactions with physicians and nurses are of vital importance for strengthening the patients' involvement in the treatment decision-making process. The experience of involvement and communication in decision-making from the patients' perspective has been sparsely explored. To examine how patients describe involvement in and communication about decision-making regarding treatment in consultations with nurses and physicians. Twenty-two patients with atrial fibrillation (AF), aged 37-90 years, were interviewed directly after their consultations with nurses and physicians in outpatient AF clinics in six Swedish hospitals. In consultations with nurses, the patients felt involved when obtaining clarifications about AF as a disease and its treatment and when preparing for and building up confidence in decision-making. In consultations with physicians, the patients felt involved when they could cooperate in decision-making, when acquiring knowledge, and when they felt that they were being understood. One shared category was found in consultations with both nurses and physicians, and the patients felt involved when they had a sense of trust and felt secure during and between consultations. Patients with AF stated that they would need to acquire knowledge and build up confidence and ability in order to be effectively involved in the decision-making about treatment. Despite not being actively involved in decision-making, patients felt involved through experiencing supportive and confirming communication. Attention must be given to the relationship with the patient to create the conditions for patient involvement in the consultation. This can be achieved through supportive communication attempting to create a feeling of clarity and building confidence. This will support involvement in decision-making concerning AF treatment and feelings of being understood and of trust in physicians and/or nurses. © 2015 Nordic College of Caring

Contemporary Diagnosis and Management of Atrial Flutter: A Continuum of Atrial Fibrillation and Vice Versa?

PubMed

Manolis, Antonis S

Atrial flutter (AFlu) is usually a fast (>240 bpm) and regular right atrial macroreentrant tachycardia, with a constrained critical region of the reentry circuit located at the cavotricuspid isthmus (CTI; typical CTI-dependent AFlu). However, a variety of right and left atrial tachycardias, resulting from different mechanisms, can also present as AFlu (atypical non-CTI-dependent AFlu). The electrocardiogram can provide clues to its origin and location; however, additional entrainment and more sophisticated electroanatomical mapping techniques may be required to identify its mechanism, location, and target area for a successful ablation. Although atrial fibrillation and AFlu are 2 separate arrhythmias, they often coexist before and after drug and/or ablation therapies. Indeed, there appears to be a close interrelationship between these 2 arrhythmias, and one may "transform" into the other. These issues are discussed in this overview, and practical algorithms are proposed to guide AFlu localization and illustrate the AFlu and atrial fibrillation continuum.

The clinical significance of the atrial subendocardial smooth muscle layer and cardiac myofibroblasts in human atrial tissue with valvular atrial fibrillation.

PubMed

Park, Jae Hyung; Pak, Hui-Nam; Lee, Sak; Park, Han Ki; Seo, Jeong-Wook; Chang, Byung-Chul

2013-01-01

The existence of myofibroblasts (MFBs) and the role of subendocardial smooth muscle (SSM) layer of human atrial tissue in atrial fibrillation (AF) have not yet been elucidated. We hypothesized that the SSM layer and MFB play some roles in atrial structural remodeling and maintenance of valvular AF in patients who undergo cardiac surgery. We analyzed immunohistochemical staining of left atrial (LA) appendage tissues taken from 17 patients with AF and 15 patients remaining in sinus rhythm (SR) who underwent cardiac surgery (male 50.0%, 54.1 ± 14.2 years old, valve surgery 87.5%). SSM was quantified by α-smooth muscle actin (α-SMA) stain excluding vascular structure. MFB was defined as α-SMA+ cells with disorganized Connexin 43-positive gap junctions in Sirius red-positive fibrotic area. The SSM layer of atrium was significantly thicker in patients with AF than in those with SR (P=.0091). Patients with SSM layer ≥ 14 μm had a larger LA size (P=.0006) and greater fibrotic area (P=.0094) than those patients whose SSM layer <14 μm. MFBs were found in 7 of 17 (41.2%) patients with AF and 2 of 15 (13.3%) in SR group (P=.0456) in SSM area, colocalized with Periodic Acid-Schiff (PAS) stain-positive glycogen storage cells (95.5%). SSM layer was closely related to the existence of AF, degrees of atrial remodeling, and fibrosis in patients who underwent open heart surgery. We found that MFB does exist in SSM layer of human atrial tissue co-localized with PAS-positive cells. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2015-01-01

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

Urodilatin, a natriuretic peptide with clinical implications.

PubMed

Meyer, M; Richter, R; Forssmann, W G

1998-02-21

Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also

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

PubMed Central

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

2009-01-01

Background Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. Methods We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and paediatric cardiology. This has permitted the preparation of three-dimensional (3-D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. Results We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. Conclusion We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning. PMID:19363807

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

PubMed

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

2009-01-01

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

New-Onset Atrial Fibrillation in the Critically Ill*

PubMed Central

Moss, Travis J.; Calland, James Forrest; Enfield, Kyle B.; Gomez-Manjarres, Diana C.; Ruminski, Caroline; DiMarco, John P.; Lake, Douglas E.

2017-01-01

Objective: To determine the association of new-onset atrial fibrillation with outcomes, including ICU length of stay and survival. Design: Retrospective cohort of ICU admissions. We found atrial fibrillation using automated detection (≥ 90 s in 30 min) and classed as new-onset if there was no prior diagnosis of atrial fibrillation. We identified determinants of new-onset atrial fibrillation and, using propensity matching, characterized its impact on outcomes. Setting: Tertiary care academic center. Patients: A total of 8,356 consecutive adult admissions to either the medical or surgical/trauma/burn ICU with available continuous electrocardiogram data. Interventions: None. Measurements and Main Results: From 74 patient-years of every 15-minute observations, we detected atrial fibrillation in 1,610 admissions (19%), with median burden less than 2%. Most atrial fibrillation was paroxysmal; less than 2% of admissions were always in atrial fibrillation. New-onset atrial fibrillation was subclinical or went undocumented in 626, or 8% of all ICU admissions. Advanced age, acute respiratory failure, and sepsis were the strongest predictors of new-onset atrial fibrillation. In propensity-adjusted regression analyses, clinical new-onset atrial fibrillation was associated with increased hospital mortality (odds ratio, 1.63; 95% CI, 1.01–2.63) and longer length of stay (2.25 d; CI, 0.58–3.92). New-onset atrial fibrillation was not associated with survival after hospital discharge (hazard ratio, 0.99; 95% CI, 0.76–1.28 and hazard ratio, 1.11; 95% CI, 0.67–1.83, respectively, for subclinical and clinical new-onset atrial fibrillation). Conclusions: Automated analysis of continuous electrocardiogram heart rate dynamics detects new-onset atrial fibrillation in many ICU patients. Though often transient and frequently unrecognized, new-onset atrial fibrillation is associated with poor hospital outcomes. PMID:28296811

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

PubMed

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Matsuda, Yasuhiro; Okuno, Shota; Ohashi, Takuya; Tsuji, Aki; Mano, Toshiaki

2018-04-15

Association between the presence of left atrial low-voltage areas and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been shown mainly in persistent AF patients. We sought to compare the AF recurrence rate in paroxysmal AF patients with and without left atrial low-voltage areas. This prospective observational study included 147 consecutive patients undergoing initial ablation for paroxysmal AF. Voltage mapping was performed after PVI during sinus rhythm, and low-voltage areas were defined as regions where bipolar peak-to-peak voltage was <0.50mV. Left atrial low-voltage areas after PVI were observed in 22 (15%) patients. Patients with low-voltage areas were significantly older (72±6 vs. 66±10, p<0.0001), more likely to be female (68% vs. 32%, p=0.002), and had higher CHA 2 DS 2 -VASc score (2.5±1.5 vs. 1.8±1.3, p=0.028). During a mean follow-up of 22 (18, 26) months, AF recurrence was observed in 24 (16%) and 16 (11%) patients after the single and multiple ablation procedures, respectively. AF recurrence rate after multiple ablations was higher in patients with low-voltage areas than without (36% vs. 6%, p<0.001). Low-voltage areas were independently associated with AF recurrence even after adjustment for the other related factors (Hazard ratio, 5.89; 95% confidence interval, 2.16 to 16.0, p=0.001). The presence of left atrial low-voltage areas after PVI predicts AF recurrence in patients with paroxysmal AF as well as in patients with persistent AF. Copyright © 2017 Elsevier B.V. All rights reserved.

Atrial cardiopathy: a mechanism of cryptogenic stroke.

PubMed

Yaghi, Shadi; Kamel, Hooman; Elkind, Mitchell S V

2017-08-01

Cryptogenic stroke accounts for approximately 30% of all ischemic strokes. Recently, atrial cardiopathy diagnosed by the presence of one of its serum, imaging, or electrocardiogram biomarkers has been shown to be associated with ischemic stroke, particularly of embolic subtypes. Areas covered: This paper aims to summarize data on occult atrial fibrillation and stroke, provide an overview on mechanisms, such as inflammation and fibrosis, of stroke in atrial cardiopathy, critically review data on biomarkers of atrial cardiopathy and their association with stroke, and suggest therapeutic implications, including directions for future research. Expert commentary: Atrial cardiopathy may constitute one of the mechanisms in cryptogenic stroke, and patients with evidence of atrial cardiopathy constitute a group of patients in whom clinical trials are warranted to test anticoagulation versus antiplatelet therapy to reduce stroke recurrence risk. In addition, more studies are needed to determine the degree of overlap between these atrial cardiopathy biomarkers and which one is more useful in predicting the risk of stroke and response to anticoagulation therapy.

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

PubMed

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

2015-04-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia, causing substantial cardiovascular morbidity and mortality. The renin-angiotensin system (RAS) has been shown to be involved in the pathophysiology of AF. The (pro)renin receptor [(p)RR] is the last identified member of RAS. However, the role of (p)RR in AF is still unknown. Circulating levels of (p)RR were determined using an immunosorbent assay in 22 patients with AF (paroxysmal or persistent) and 22 healthy individuals. The plasma levels of (p)RR increased 3.6-fold in AF patients (P<0.001), indicating a relationship between (p)RR and AF. To investigate the role of (p)RR in the regulation of cardiac arrhythmia, we generated a transgenic mouse with overexpression of human (p)RR gene specifically in the heart. Electrocardiograms from (p)RR transgenic mice showed typical atrial flutter since 2 months, then spontaneously converted to atrial fibrillation by 10 months. The atria of the transgenic mice demonstrated significant dilation and fibrosis, and exhibited a high incidence of sudden death. Additionally, the genes of SERCA and HCN4, which are involved in the electrophysiology of AF, were significantly down-regulated and up-regulated respectively in transgenic mice atria. The phosphorylation of Erk1/2 significantly increased in the atria of the transgenic mice, and the activated Erk1/2 was found predominantly in cardiac fibroblasts, suggesting that the transgenic (p)RR gene may induce atrial fibrillation by activation of Erk1/2 in the cardiac fibroblasts of the atria. (p)RR promotes atrial structural and electrical remodeling in vivo, which indicates that (p)RR plays an important role in the pathological development of AF. Copyright © 2015. Published by Elsevier Ireland Ltd.

Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: reversal of tachycardia-mediated atrial cardiomyopathy with fish oils.

PubMed

Kumar, Saurabh; Sutherland, Fiona; Wheeler, Miriam; Heck, Patrick M; Lee, Geoffrey; Teh, Andrew W; Garg, Manohar L; Morgan, John G; Sparks, Paul B

2011-05-01

Atrial mechanical stunning is a form of tachycardia-mediated atrial cardiomyopathy that manifests after reversion of persistent atrial arrhythmias to sinus rhythm. This study sought to examine whether chronic omega-3 polyunsaturated fatty acid supplementation with fish oils can reverse atrial mechanical stunning. Patients undergoing reversion of persistent atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm were randomized to a control group (n = 26) or an omega-3 group (n = 23). The latter were prescribed 6 g/day of fish oil for ≥1 month prior to the procedure. Parameters of left atrial appendage function were compared immediately before and immediately after reversion. After fish oil intake for a mean of 70 days, the following were noted favoring the omega-3 group among both AF and AFL patients: (1) 2-fold higher serum omega-3 levels (P < .001), (2) less mean decrease in emptying velocity (e.g., AF: 8% vs. 32%, P = .02), (3) less mean decrease in appendage emptying fraction (e.g., AFL: 7% vs. 60%, P = .002), (4) lower incidence of new or increased spontaneous echocardiographic contrast (e.g., AF: 11% vs. 62.5%, P = .003), and (5) lower incidence of atrial mechanical stunning (e.g., AFL: 20% vs. 100%, P = .001). Omega-3 intake conferred protection against stunning in a multivariable analysis (odds ratio 0.18, P = .02). Chronic fish oil ingestion in humans attenuates atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm. This suggests that fish oils may target or even reverse underlying cellular and/or structural remodeling that occurs in response to persistent atrial arrhythmias. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2009-01-01

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

Pulmonary vein stenosis following catheter ablation of atrial fibrillation.

PubMed

Pürerfellner, Helmut; Martinek, Martin

2005-11-01

This review provides an update on the mechanisms, incidence, and current management of significant pulmonary vein stenosis following catheter ablation of atrial fibrillation. Catheter ablation involving the pulmonary veins and the surrounding left atrial tissue is increasingly used to treat atrial fibrillation. In parallel with the fact that these procedures may cure a substantial proportion of patients, severe complications have been observed. Pulmonary vein stenosis is a new clinical entity produced by radiofrequency energy delivery mainly within or at the orifice of the pulmonary veins. The exact incidence is currently unknown because the diagnosis is dependent on the imaging modality and on the rigor with which patients are followed up. The optimal method for screening patients has not been determined. Stenosis of a pulmonary vein may be assessed by combining anatomic and functional imaging using computed tomographic or magnetic resonance imaging, transesophageal echocardiography, and lung scanning. Symptoms vary considerably and may be misdiagnosed, leading to severe clinical consequences. Current treatment strategies involve pulmonary vein dilatation or stenting; however, the restenosis rate remains high. The long-term outcome in patients with pulmonary vein stenosis is unclear. Strategies under development to prevent pulmonary vein stenosis include alternate energy sources and modified ablation techniques. Pulmonary vein stenosis following catheter ablation is a new clinical entity that has been described in various reports recently. There is much uncertainty with respect to causative factors, incidence, diagnosis, and treatment, and long-term sequelae are unclear.

Isolation of the posterior left atrium for patients with persistent atrial fibrillation: routine adenosine challenge for dormant posterior left atrial conduction improves long-term outcome.

PubMed

McLellan, Alex J A; Prabhu, Sandeep; Voskoboinik, Alex; Wong, Michael C G; Walters, Tomos E; Pathik, Bhupesh; Morris, Gwilym M; Nisbet, Ashley; Lee, Geoffrey; Morton, Joseph B; Kalman, Jonathan M; Kistler, Peter M

2017-12-01

Catheter ablation to achieve posterior left atrial wall (PW) isolation may be performed as an adjunct to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). We aimed to determine whether routine adenosine challenge for dormant posterior wall conduction improved long-term outcome. A total of 161 patients with persistent AF (mean age 59 ± 9 years, AF duration 6 ± 5 years) underwent catheter ablation involving circumferential PVI followed by PW isolation. Posterior left atrial wall isolation was performed with a roof and inferior wall line with the endpoint of bidirectional block. In 54 patients, adenosine 15 mg was sequentially administered to assess reconnection of the pulmonary veins and PW. Sites of transient reconnection were ablated and adenosine was repeated until no further reconnection was present. Holter monitoring was performed at 6 and 12 months to assess for arrhythmia recurrence. Posterior left atrial wall isolation was successfully achieved in 91% of 161 patients (procedure duration 191 ± 49 min, mean RF time 40 ± 19 min). Adenosine-induced reconnection of the PW was demonstrated in 17%. The single procedure freedom from recurrent atrial arrhythmia was superior in the adenosine challenge group (65%) vs. no adenosine challenge (40%, P < 0.01) at a mean follow-up of 19 ± 8 months. After multiple procedures, there was significantly improved freedom from AF between patients with vs. without adenosine PW challenge (85 vs. 65%, P = 0.01). Posterior left atrial wall isolation in addition to PVI is a readily achievable ablation strategy in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with an improvement in the success of catheter ablation for persistent AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes.

PubMed

Iida, Masato; Yamamoto, Mitsuru; Ishiguro, Yuko S; Yamazaki, Masatoshi; Ueda, Norihiro; Honjo, Haruo; Kamiya, Kaichirou

2014-01-01

Urinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions. We studied hypertensive patients with early prediabetes (HbA1c <5.7% and fasting glucose >110, n=18), those with prediabetes (HbA1c 5.7-6.4, n=98), and those with diabetes (HbA1c>6.5 or on diabetes medications, n=92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e'). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e'≥15, or E/e'=9-14 accompanied by left atrial volume/BSA≥32ml/mm(2). Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c. Urinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes. In hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP. Copyright © 2014 Elsevier Inc. All rights reserved.

Early cardioversion of atrial fibrillation and atrial flutter guided by transoesophageal echocardiography: a single centre 8.5-year experience.

PubMed

Corrado, G; Santarone, M; Beretta, S; Tadeo, G; Tagliagambe, L M; Foglia-Manzillo, G; Spata, M; Miglierina, E; Acquati, F; Santarone, M

2000-04-01

To analyse the safety and impact on maintenance of sinus rhythm of transoesophageal echocardiographically guided early cardioversion associated with short-term anticoagulation in a large series of patients with atrial fibrillation and atrial flutter. Patients who were candidates for cardioversion were eligible for inclusion if they had atrial fibrillation or atrial flutter lasting longer than 2 days or of unknown duration. Patients received short-term anticoagulation with warfarin or heparin and underwent transthoracic echocardiography followed by transoesophageal echocardiography. Early cardioversion was performed if no thrombus was seen on the transoesophageal study. Warfarin was maintained for 1 month after cardioversion. In patients with atrial thrombi, cardioversion was deferred and prolonged anticoagulation was prescribed. The study population included 183 patients. One hundred and sixty nine patients without atrial thrombi underwent early cardioversion. Fourteen patients with atrial thrombi (7.6%) underwent a second transoesophageal echocardiogram after a median of 4 weeks of oral warfarin, and cardioversion was performed if clot regression was documented. No patient in our study population had a clinical thromboembolic event at 1 month follow-up (95% C.I. 0-0.016). The immediate success rate of cardioversion was better among patients with atrial fibrillation < 4 weeks duration compared with patients with atrial fibrillation of longer or of unknown duration: 96.6% vs 85%, respectively (P = 0.014). At 1 month follow-up, the percentage of arrhythmia relapses in patients with initially successful cardioversion was similar in the two groups (29% vs 26%, P = ns); thus the initial better outcome in patients with recent-onset arrhythmia was not lost. Transoesophageal echocardiography-guided early cardioversion in concert with short-term anticoagulation is safe. This approach permits abbreviation of the overall duration of atrial fibrillation and has a better impact

Initial clinical experience with ambulatory use of an implantable atrial defibrillator for conversion of atrial fibrillation. Metrix Investigators.

PubMed

Daoud, E G; Timmermans, C; Fellows, C; Hoyt, R; Lemery, R; Dawson, K; Ayers, G M

2000-09-19

A recent study has shown that the implantable atrial defibrillator can restore sinus rhythm in patients with recurrent atrial fibrillation when therapy was delivered under physician observation. The objective of this study was to evaluate the safety and efficacy of ambulatory use of the implantable atrial defibrillator. An atrial defibrillator was implanted in 105 patients (75 men; mean age, 59+/-12 years) with recurrent, symptomatic, drug-refractory atrial fibrillation. After successful 3-month testing, patients could transition to ambulatory delivery of shock therapy. Patients completed questionnaires regarding shock therapy discomfort and therapy satisfaction using a 10-point visual-analog scale (1 represented "not at all," 10 represented "extremely") after each treated episode of atrial fibrillation. During a mean follow-up of 11.7 months, 48 of 105 patients satisfied criteria for transition and received therapy for 275 episodes of atrial fibrillation. Overall shock therapy efficacy was 90% with 1.6+/-1.2 shocks delivered per episode (median, 1). Patients rated shock discomfort as 5.2+/-2.4 for successful therapy and 4.2+/-2.2 for unsuccessful therapy (P:>0.05). The satisfaction score was higher for successful versus unsuccessful therapy (3.4+/-3. 3 versus 8.7+/-1.3, P:<0.05). There was no ventricular proarrhythmia observed throughout the course of this study. Ambulatory use of an implantable atrial defibrillator can safely and successfully convert most episodes of atrial fibrillation, often requiring only a single shock. Successful therapy is associated with high satisfaction and only moderate discomfort.

Randomized, double-blind trial of simultaneous right and left atrial epicardial pacing for prevention of post-open heart surgery atrial fibrillation.

PubMed

Daoud, E G; Dabir, R; Archambeau, M; Morady, F; Strickberger, S A

2000-08-15

The purpose of this study was to assess simultaneous right and left atrial pacing as prophylaxis for postoperative atrial fibrillation. In a double-blind, randomized fashion, 118 patients who underwent open heart surgery were assigned to right atrial pacing at 45 bpm (RA-AAI; n=39), right atrial triggered pacing at a rate of >/=85 bpm (RA-AAT; n=38), or simultaneous right and left atrial triggered pacing at a rate of >/=85 bpm (Bi-AAT; n=41). Holter monitoring was performed for 4. 8+/-1.4 days after surgery to assess for episodes of atrial fibrillation lasting >5 minutes. The prevalence of postoperative atrial fibrillation was significantly less in the patients randomized to biatrial AAT pacing when compared with the other 2 pacing regimens (P=0.02). An episode of atrial fibrillation occurred in 4 (10%) of 41 patients in the Bi-AAT group compared with 11 (28%) of 39 patients in the RA-AAI group (P=0.03 versus Bi-AAT) and 12 (32%) of 38 patients in the RA-AAT group (P=0.01 versus Bi-AAT). There was no difference in the occurrence of atrial fibrillation between the right atrial AAI and AAT groups (P=0.8). There was no significant difference among the 3 groups with regard to the number of postoperative hospital days (7.3+/-4.2 days), morbidity (5.1%), or mortality rate (2.5%). Simultaneous right and left atrial triggered pacing is well tolerated and significantly reduces the prevalence of post-open heart surgery atrial fibrillation.

Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study.

PubMed

Go, Alan S; Reynolds, Kristi; Yang, Jingrong; Gupta, Nigel; Lenane, Judith; Sung, Sue Hee; Harrison, Teresa N; Liu, Taylor I; Solomon, Matthew D

2018-05-16

Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial. To determine if the burden of atrial fibrillation characterized using noninvasive, continuous ambulatory monitoring is associated with the risk of ischemic stroke or arterial thromboembolism in adults with paroxysmal atrial fibrillation. This retrospective cohort study conducted from October 2011 and October 2016 at 2 large integrated health care delivery systems used an extended continuous cardiac monitoring system to identify adults who were found to have paroxysmal atrial fibrillation on 14-day continuous ambulatory electrocardiographic monitoring. The burden of atrial fibrillation was defined as the percentage of analyzable wear time in atrial fibrillation or flutter during the up to 14-day monitoring period. Ischemic stroke and other arterial thromboembolic events occurring while patients were not taking anticoagulation were identified through November 2016 using electronic medical records and were validated by manual review. We evaluated the association of the burden of atrial fibrillation with thromboembolism while not taking anticoagulation after adjusting for the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) or CHA2DS2-VASc stroke risk scores. Among 1965 adults with paroxysmal atrial fibrillation, the mean (SD) age was 69 (11.8) years, 880 (45%) were women, 496 (25%) were persons of color, the median ATRIA stroke risk score was 4 (interquartile range [IQR], 2-7), and the median CHA2DS2-VASc score was 3 (IQR, 1-4). The median burden of atrial fibrillation was 4.4% (IQR ,1.1%-17.23%). Patients with a higher burden of atrial fibrillation were less likely to be women or of Hispanic ethnicity, but had more prior cardioversion attempts compared with those who had a lower burden. After adjusting for either ATRIA or CHA2DS2

Atriocaval Rupture After Right Atrial Isthmus Ablation for Atrial Flutter.

PubMed

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

2016-06-01

A patient with symptomatic typical atrial flutter (AFL) underwent right atrial isthmus ablation with an 8-mm catheter. Eight months later, his typical AFL recurred. Ten months later, he underwent a repeat right atrial isthmus ablation with an irrigated tip catheter and an 8-mm tip catheter. Six weeks after his second procedure, while performing intense sprint intervals on a treadmill, he developed an abrupt onset of chest pain, hypotension, and cardiac tamponade. He underwent emergency surgery to repair an atriocaval rupture and has done well since. Our report suggests that an association of multiple radiofrequency ablations with increased risk for delayed atriocaval rupture occurring 1 to 3 months after ablation. In conclusion, although patients generally were advised to limit exercise for 1 to 2 weeks after AFL ablation procedures in the past, it may be prudent to avoid intense exercise for at least 3 months after procedure. Copyright © 2016 Elsevier Inc. All rights reserved.

Ambulatory ECG monitoring in atrial fibrillation management.

PubMed

Rosero, Spencer Z; Kutyifa, Valentina; Olshansky, Brian; Zareba, Wojciech

2013-01-01

Ambulatory ECG monitoring technology has rapidly evolved over the last few decades and has been shown to identify life-threatening and non-life threatening arrhythmias and provide actionable data to guide clinical decision making. Atrial fibrillation episodes can often be asymptomatic, even after catheter ablation for atrial fibrillation, creating a disconnect between symptoms and actual arrhythmia burden which may alter clinical management. In this review, we aim to provide a comprehensive overview of invasive and non-invasive ECG monitoring strategies in patients with atrial fibrillation, with a special focus on the diagnosis of atrial fibrillation, and on follow-up of patients after catheter ablation for atrial fibrillation ablation. © 2013.

Interpretation of B-type natriuretic peptides in the era of angiotensin receptor-neprilysin inhibitors.

PubMed

Bettencourt, Paulo; Fonseca, Cândida; Franco, Fátima; Andrade, Aurora; Brito, Dulce

2017-12-01

Assessment of serum levels of natriuretic peptides, especially the amino-terminal portion (NT-proBNP) and the carboxy-terminal portion (BNP) of pro-B-type natriuretic peptide, has had a highly significant clinical impact on the diagnosis and prognostic stratification of patients with heart failure (HF). They are now an instrument with recognized value in this context and several studies have demonstrated their value in tailoring therapy for these patients. Following the recent advent of angiotensin receptor-neprilysin inhibitors (ARNIs), there is a need to review how these two biomarkers are interpreted in HF. The use of ARNIs is associated with a reduction in NT-proBNP but an increase in BNP levels. The authors of this concise article review the interpretation of natriuretic peptide levels in the light of the most recent evidence. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Is There a Role for Genes in Exercise-Induced Atrial Cardiomyopathy?

PubMed

Fatkin, Diane; Cox, Charles D; Huttner, Inken G; Martinac, Boris

2018-04-09

In endurance athletes, prolonged high intensity exercise participation can have deleterious effects on the myocardium with subsequent structural and electrical remodelling. In a subset of athletes, there is a predilection for atrial involvement and the risk of atrial fibrillation (AF) is increased. The mechanisms underpinning exercise-induced atrial cardiomyopathy have yet to be fully elucidated and the contribution of an individual's genetic makeup is unknown. Some athletes may have rare genetic variants that are sufficient to cause AF irrespective of exercise exposure. In AF-causing variant carriers, the additional haemodynamic stress of exercise on atrial structure and function might accelerate or increase the severity of disease. Variants in genes that lack known links to AF may indirectly promote an arrhythmogenic substrate by affecting threshold levels for exercise-induced myocardial damage and remodelling responses, or by effects on AF-associated co-morbidities, sinus node function, and autonomic nervous system tone. Given the exquisite stress-sensitivity of the atria, mechanosensitive ion channels could plausibly have a key role in mediating exercise effects on atrial structure and function. Knowing an athlete's profile of genetic variants may be useful for AF risk stratification and have implications for clinical management. Pre-participation genetic testing may influence sports choices and facilitate AF prevention. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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...

B-type natriuretic peptide measurement for early diagnosis of acute pulmonary edema during pregnancy.

PubMed

Seror, Jeremy; Lefevre, Guillaume; Berkane, Nathalie; Richard, Frederic; Bornes, Marie; Uzan, Serge; Berkane, Nadia

2014-12-01

Calcium-channel blockers administered to pregnant women as tocolytic agents can cause acute pulmonary edema. The first signs of this severe complication can be atypical and so delay introduction of appropriate therapy. We describe three cases in whom B-type natriuretic peptide measurements proved to be relevant in early diagnosis and monitoring of pregnant women with acute pulmonary edema. B-type natriuretic peptide measurement in this setting could contribute to timely diagnosis and improve follow-up. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Atrial electromechanical coupling intervals in pregnant subjects.

PubMed

Altun, Burak; Tasolar, Hakan; Gazï, Emïne; Gungor, Aysenur Cakir; Uysal, Ahmet; Temïz, Ahmet; Barutcu, Ahmet; Acar, Gurkan; Colkesen, Yucel; Ozturk, Ufuk; Akkoy, Murat

2014-01-01

The aim of this study was to evaluate atrial conduction abnormalities obtained by tissue Doppler imaging (TDI) and electrocardiogram analysis in pregnant subjects. A total of 30 pregnant subjects (28 ± 4 years) and 30 controls (28 ± 3 years) were included. Systolic and diastolic left ventricular (LV) function was measured using conventional echocardiography and TDI. Inter-atrial, intraatrial and intra-left atrial electromechanical coupling (PA) intervals were measured with TDI. P-wave dispersion (PD) was calculated from a 12-lead electrocardiogram. Atrial electromechanical coupling at the septal and left lateral mitral annulus (PA septal, PA lateral) was significantly prolonged in pregnant subjects (62.1 ± 2.7 vs 55.3 ±3.2 ms, p < 0.001; 45.7 ± 2.5 vs 43.1 ± 2.7 ms, p < 0.001, respectively). Inter-atrial (PA lateral - PA tricuspid), intra-atrial (PA septum - PA tricuspid) and intra-left atrial (PA lateral - PA septum) electromechanical coupling intervals, maximum P-wave (Pmax) duration and PD were significantly longer in the pregnant subjects (26.4 ± 4.0 vs 20.2 ± 3.6 ms, p < 0.001; 10.0 ± 2.0 vs 8.0 ± 2.6 ms, p = 0.002; 16.4 ± 3.3 vs 12.2 ± 3.0 ms, p < 0.001; 103.1 ± 5.4 vs 96.8 ± 7.4 ms, p ± 0.001; 50.7 ± 6.8 vs 41.6 ± 5.5 ms, p < 0.001, respectively). We found a significant positive correlation between inter-atrial and intraleft atrial electromechanical coupling intervals and Pmax (r = 0.282, p = 0.029, r = 0.378, p = 0.003, respectively). This study showed that atrial electromechanical coupling intervals and PD, which are predictors of AF, were longer in pregnant subjects and this may cause an increased risk of AF in pregnancy.

Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation and contraindication for anticoagulation.

PubMed

Grosset-Janin, D; Barth, E; Bertrand, B; Detante, O

2015-05-01

Stroke, as the third cause of death in developed countries, is a public health issue. Atrial fibrillation is an important cause of ischemic stroke and its prevention is efficient with oral anticoagulation. However, oral anticoagulation can be contraindicated because of hemorrhagic risk related to these treatments. Percutaneous left atrial appendage occlusion is a new alternative of oral anticoagulation for patients with atrial fibrillation and high risk of cardio-embolic stroke but contraindicated for oral anticoagulation. We describe in this paper the procedure of left atrial appendage occlusion with the Amplatzer cardiac plug device, used in our center in Grenoble university hospital, for the first three patients who have been treated with this device. These three patients (one man and two women) have all atrial fibrillation with neurological complication of this arrhythmia, as ischemic stroke. Oral anticoagulation is indicated to prevent another ischemic stroke. However, they all have a high risk of cerebral bleeding for different reasons (cavernomatosis, history of intracerebral hemorrhage and aneurysm of the polygon of Willis). Consequently, they have a high risk of cardio-embolic complication but contraindication for oral anticoagulation. They have been treated by left atrial appendage occlusion with Amplatzer cardiac plug device by percutaneous and trans-septal access. Then, they have been followed by neurologist and cardiologist, with clinical and paraclinical evaluation by echocardiography. Our three first patients have been successfully implanted, without periprocedural complication. No latest adverse event was observed, and particularly no cardiac or neurologic adverse event. The technique of left atrial appendage occlusion is a very interesting and promising technique for ischemic stroke prevention in patient with high risk of cardio-embolic complication because of atrial fibrillation, but high risk of bleeding and contraindication for oral

[Recurrent right atrial thrombus in a patient with atrial fibrillation and heart failure].

PubMed

Elikowski, Waldemar; Wróblewski, Dariusz; Małek-Elikowska, Małgorzata; Mazurek, Andrzej; Foremska-Iciek, Joanna; Łazowski, Stanisław

2015-11-01

Atrial fibrillation and heart failure are factors predisposing to locally formed intracardiac thrombosis, which is usually localized in left-sided chambers. A case report. The authors present a case of a 50-year-old male with permanent atrial fibrillation and dilated cardiomyopathy in whom recurrent right atrial thrombus was observed. Initially, the lesion was detected in echocardiography while he was hospitalized due to extensive right-sided pneumonia. The thrombus was successfully treated with heparin, followed by warfarin. Even though the patient continued warfarin use properly, there was recurrence of the thrombus two years later during a new episode of heart failure exacerbation. Because the thrombus was resistant to intensified anticoagulation, cardiac surgery was needed. A large (30 x 25 mm) pedunculated thrombus, as well as two smaller ones (each of 10 x 10 mm) attached closely to the atrial wall and previously not detected either by echocardiography or by magnetic resonance imaging, were excited. A partially organized pattern of the thrombi in histological examination can explain lack of anticoagulation effectiveness. © 2015 MEDPRESS.

Predicting functional capacity in patients with a systemic right ventricle: subjective patient self-assessment is better than B-type natriuretic peptide levels and right ventricular systolic function.

PubMed

Book, Wendy; McConnell, Michael; Oster, Matthew; Lyle, Teresa; Kogon, Brian

2013-01-01

Many adults with transposition of the great arteries have an anatomic right ventricle functioning as the systemic ventricle and are known to develop congestive heart failure, premature cardiac death, and need for cardiac transplantation. Predictors of poor clinical outcome and functional status in patients with left ventricular failure do not always apply to these patients. We aimed to identify predictors of poor functional status in those patients with a systemic right ventricle. We performed a prospective study of 51 adults with transposition of the great arteries and systemic right ventricles. Demographic, clinical, laboratory, and imaging data were collected, and patients completed a Minnesota Living with Heart Failure Questionnaire (MLHFQ). Comparisons were made between those patients with d-type transposition of the great arteries (dTGA) who have undergone prior atrial switch and those with congenitally corrected transposition (ccTGA). A correlation analysis was performed to identify predictors of poor functional status, as determined by a 6-minute walk distance test. Median age was 30 years (range 19-65). Median B-type natriuretic peptide was 48 pg/mL (range 16-406). There were 27 patients (53%) with moderate-severe right ventricular dysfunction and 10 (20%) with moderate-severe tricuspid valve regurgitation. The median MLHFQ score was 9 (range 0-78) and 6-minute walk test was 510 m (range 231-703). Forty-one patients had a diagnosis of dTGA atrial switch and 11 patients had ccTGA. Patients with ccTGA were significantly older (40 vs. 28 years, P =.004) and had more tricuspid valve regurgitation (P =.02). Despite this, their MLHFQ scores were significantly lower (2.5 vs. 17, P =.04) and they walked further (635 vs. 504 m, P =.02). Predictors of a short 6-minute walk distance included short stature (P =.009) and dTGA (P =.002). The patient's self-assessment of poor health, as measured by an increased New York Heart Association class (P =.003) and a decreased

Spectral of electrocardiographic RR intervals to indicate atrial fibrillation

NASA Astrophysics Data System (ADS)

Nuryani, Nuryani; Satrio Nugroho, Anto

2017-11-01

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

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition

PubMed Central

Fabiansen, Christian; Lykke, Mikkel; Hother, Anne-Louise; Koch, Jørgen; Nielsen, Ole Bækgaard; Hunter, Ingrid; Goetze, Jens P.; Friis, Henrik; Thymann, Thomas

2015-01-01

Background Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. Objective To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. Methods and Results Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5–7 (p≤0.001). There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2–19.7; p = 0.03). However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0–15.9; p<0.001) in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p<0.001), whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p<0.001) and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025). Conclusions Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from

Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

2010-01-01

To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

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

PubMed

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

2015-01-01

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

Determination of inadvertent atrial capture during para-Hisian pacing.

PubMed

Obeyesekere, Manoj; Leong-Sit, Peter; Skanes, Allan; Krahn, Andrew; Yee, Raymond; Gula, Lorne J; Bennett, Matthew; Klein, George J

2011-08-01

Inadvertent capture of the atrium will lead to spurious results during para-Hisian pacing. We sought to establish whether the stimulation-to-atrial electrogram interval at the proximal coronary sinus (stim-PCS) or high right atrium (stim-HRA) could signal inadvertent atrial capture. Para-Hisian pacing with and without intentional atrial capture was performed in 31 patients. Stim-HRA and stim-PCS intervals were measured with atrial capture, His plus para-Hisian ventricular (H+V) capture, and para-Hisian ventricular (V) capture alone. The mean stim-HRA interval was significantly shorter with atrial capture (66 ± 18 ms) than with H+V (121 ± 27 ms, P < 0.001) or V capture alone (174 ± 38 ms, P < 0.001). The mean stim-PCS interval was significantly shorter with atrial capture (51 ± 16 ms) than with H+V (92 ± 22 ms, P<0.001) or V capture alone (146 ± 33 ms, P < 0.001). A stim-PCS < 60 ms (stim-HRA < 70 ms) was observed only with atrial capture. A stim-PCS >90 ms (stim-HRA >100 ms) was observed only in the absence of atrial capture. A stim-HRA of < 85 ms was highly specific and stim-PCS of < 85 ms highly sensitive at identifying atrial capture. Stim-HRA intervals of 75 to 97 ms and stim-PCS intervals of 65 to 88 ms were observed with either atrial, His, or para-Hisian ventricular capture without atrial capture. In this overlap zone, all patients demonstrated a stim-PCS or stim-HRA interval prolongation of at least 20 ms when the catheter was advanced to avoid deliberate atrial pacing. The QRS morphology was of limited value in distinguishing atrial capture due to concurrent ventricular or H+V capture, as observed in 20 of 31 (65%) patients. Stim-PCS and stim-HRA intervals can be used to monitor for inadvertent atrial capture during para-Hisian pacing. A stim-PCS < 60 ms (or stim-HRA < 70 ms) and stim-PCS > 90 ms (or stim-HRA > 100 ms) were observed only with and without atrial capture, respectively, but there was significant overlap between these values. Deliberate

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

Low Energy Multi-Stage Atrial Defibrillation Therapy Terminates Atrial Fibrillation with Less Energy than a Single Shock

PubMed Central

Li, Wenwen; Janardhan, Ajit H.; Fedorov, Vadim V.; Sha, Qun; Schuessler, Richard B.; Efimov, Igor R.

2011-01-01

Background Implantable device therapy of atrial fibrillation (AF) is limited by pain from high-energy shocks. We developed a low-energy multi-stage defibrillation therapy and tested it in a canine model of AF. Methods and Results AF was induced by burst pacing during vagus nerve stimulation. Our novel defibrillation therapy consisted of three stages: ST1 (1-4 low energy biphasic shocks), ST2 (6-10 ultra-low energy monophasic shocks), and ST3 (anti-tachycardia pacing). Firstly, ST1 testing compared single or multiple monophasic (MP) and biphasic (BP) shocks. Secondly, several multi-stage therapies were tested: ST1 versus ST1+ST3 versus ST1+ST2+ST3. Thirdly, three shock vectors were compared: superior vena cava to distal coronary sinus (SVC>CSd), proximal coronary sinus to left atrial appendage (CSp>LAA) and right atrial appendage to left atrial appendage (RAA>LAA). The atrial defibrillation threshold (DFT) of 1BP shock was less than 1MP shock (0.55 ± 0.1 versus 1.38 ± 0.31 J; p =0.003). 2-3 BP shocks terminated AF with lower peak voltage than 1BP or 1MP shock and with lower atrial DFT than 4 BP shocks. Compared to ST1 therapy alone, ST1+ST3 lowered the atrial DFT moderately (0.51 ± 0.46 versus 0.95 ± 0.32 J; p = 0.036) while a three-stage therapy, ST1+ST2+ST3, dramatically lowered the atrial DFT (0.19 ± 0.12 J versus 0.95 ± 0.32 J for ST1 alone, p=0.0012). Finally, the three-stage therapy ST1+ST2+ST3 was equally effective for all studied vectors. Conclusions Three-stage electrotherapy significantly reduces the AF defibrillation threshold and opens the door to low energy atrial defibrillation at or below the pain threshold. PMID:21980076

Approaches to catheter ablation for persistent atrial fibrillation.

PubMed

Verma, Atul; Jiang, Chen-yang; Betts, Timothy R; Chen, Jian; Deisenhofer, Isabel; Mantovan, Roberto; Macle, Laurent; Morillo, Carlos A; Haverkamp, Wilhelm; Weerasooriya, Rukshen; Albenque, Jean-Paul; Nardi, Stefano; Menardi, Endrj; Novak, Paul; Sanders, Prashanthan

2015-05-07

Catheter ablation is less successful for persistent atrial fibrillation than for paroxysmal atrial fibrillation. Guidelines suggest that adjuvant substrate modification in addition to pulmonary-vein isolation is required in persistent atrial fibrillation. We randomly assigned 589 patients with persistent atrial fibrillation in a 1:4:4 ratio to ablation with pulmonary-vein isolation alone (67 patients), pulmonary-vein isolation plus ablation of electrograms showing complex fractionated activity (263 patients), or pulmonary-vein isolation plus additional linear ablation across the left atrial roof and mitral valve isthmus (259 patients). The duration of follow-up was 18 months. The primary end point was freedom from any documented recurrence of atrial fibrillation lasting longer than 30 seconds after a single ablation procedure. Procedure time was significantly shorter for pulmonary-vein isolation alone than for the other two procedures (P<0.001). After 18 months, 59% of patients assigned to pulmonary-vein isolation alone were free from recurrent atrial fibrillation, as compared with 49% of patients assigned to pulmonary-vein isolation plus complex electrogram ablation and 46% of patients assigned to pulmonary-vein isolation plus linear ablation (P=0.15). There were also no significant differences among the three groups for the secondary end points, including freedom from atrial fibrillation after two ablation procedures and freedom from any atrial arrhythmia. Complications included tamponade (three patients), stroke or transient ischemic attack (three patients), and atrioesophageal fistula (one patient). Among patients with persistent atrial fibrillation, we found no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01203748.).

Coronary sinus signal amplitude predicts left atrial scarring.

PubMed

Attanasio, Philipp; Qaiyumi, Daniel; Röhle, Robert; Wutzler, Alexander; Safak, Erdal; Muntean, Bogdan; Boldt, Leif-Hendrik; Pieske, Burkert; Haverkamp, Wilhelm; Huemer, Martin

2017-12-22

Left atrial scarring is recognised as a critical component in the maintenance of atrial fibrillation and is associated with the failure of interventional treatment. Diminished bipolar voltage (LV) has been proposed as a useful tool for left atrial scar quantification. We hypothesised that, due to its anatomic location, signals on the coronary sinus catheter might be used to predict the amount of left atrial low voltage. A total of 124 patients (42% women, average age 66 ± 9 years) were included. Forty-one with paroxysmal and 83 with persistent atrial fibrillation. Left atrial low-voltage (<0.5 mV, measured during sinus rhythm) area size and distribution varied considerably among the included patients (mean: 34.9%; maximum: 94.6%; minimum: 0.4%). Spearman correlation revealed a strong negative correlation between bipolar voltage of the signals on the coronary sinus catheter and the amount of left atrial scarring (R = -0.778, p < .0001). The optimal CS voltage cut off for prediction of left atrial low-voltage size of ≥50% was 1.9 mV with an area-under-the receiver-operating-characteristic (ROC) curve of 0.982, a sensitivity of 97% and a specificity of 98%. There is a strong negative correlation between the size of left atrial low-voltage areas (LVA) and coronary sinus signal amplitude. With increasing left atrial LVA size, CS signal amplitudes decrease, and vice versa. On the basis of these findings, average CS signal amplitudes of ≤1.9 mV can be used as a predictor for a left atrial low-voltage size of ≥50%.

Benefits of Atrial Substrate Modification Guided by Electrogram Similarity and Phase Mapping Techniques to Eliminate Rotors and Focal Sources Versus Conventional Defragmentation in Persistent Atrial Fibrillation.

PubMed

Lin, Yenn-Jiang; Lo, Men-Tzung; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chao, Tze-Fan; Chung, Fa-Po; Liao, Jo-Nan; Lin, Chin-Yu; Kuo, Huan-Yu; Chang, Yi-Chung; Lin, Chen; Tuan, Ta-Chuan; Vincent Young, Hsu-Wen; Suenari, Kazuyoshi; Dan Do, Van Buu; Raharjo, Suunu Budhi; Huang, Norden E; Chen, Shih-Ann

2016-11-01

This prospective study compared the efficacy of atrial substrate modification guided by a nonlinear phase mapping technique with that of conventional substrate ablation. The optimal ablation strategy for persistent atrial fibrillation (AF) was unknown. In phase 1 study, we applied a cellular automation technique to simulate the electrical wave propagation to improve the phase mapping algorithm, involving analysis of high-similarity electrogram regions. In addition, we defined rotors and focal AF sources, using the physical parameters of the divergence and curvature forces. In phase 2 study, we enrolled 68 patients with persistent AF undergoing substrate modification into 2 groups, group-1 (n = 34) underwent similarity index (SI) and phase mapping techniques; group-2 (n = 34) received complex fractionated atrial electrogram ablation with commercially available software. Group-1 received real-time waveform similarity measurements in which a phase mapping algorithm was applied to localize the sources. We evaluated the single-procedure freedom from AF. In group-1, we identified an average of 2.6 ± 0.89 SI regions per chamber. These regions involved rotors and focal sources in 65% and 77% of patients in group-1, respectively. Group-1 patients had shorter ablation procedure times, higher termination rates, and significant reduction in AF recurrence compared to group-2 and a trend toward benefit for all atrial arrhythmias. Multivariate analysis showed that substrate mapping using nonlinear similarity and phase mapping was the independent predictor of freedom from AF recurrence (hazard ratio: 0.26; 95% confidence interval: 0.09 to 0.74; p = 0.01). Our study showed that for persistent AF ablation, a specified substrate modification guided by nonlinear phase mapping could eliminate localized re-entry and non-pulmonary focal sources after pulmonary vein isolation. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Clinical Features and Surgical Results of Right Atrial Myxoma.

PubMed

Li, Han; Guo, Hongwei; Xiong, Hui; Xu, Jianping; Wang, Wei; Hu, Shengshou

2016-01-01

We retrospectively analyzed 367 patients receiving surgical resection of cardiac myxomas in our center over six years, and analyzed the incidence and surgical results of 28 cases of right atrial myxomas. We also compared the age, gender, and attached sites between left atrial myxoma and right atrial myxoma. Between January 2007 and December 2012, 28 patients with right atrial myxomas underwent surgical resection. There were 16 males and 12 females. The mean age was 47.77 ± 13.20 years (range: 8.00-79.00 years). Associated cardiac lesions included moderate and severe tricuspid regurgitation in four, coronary atherosclerotic heart disease in five, and pulmonary embolism in one. Twenty-seven patients (96.43%) were followed from 26 to 94 months (mean 55.78 ± 21.10 months). There was no early death after operation. The incidence of right atrial myxomas among sporadic cardiac myxomas was 7.89%. One patient died of lung cancer 34 months after myxoma resection. Two patients underwent coronary artery stent implantation due to coronary atherosclerotic heart disease during the follow-up period. One patient underwent myxoma resection due to recurrence in the left atrium four years after the first operation. There was no significant difference in the age between left atrial myxoma and right atrial myxoma (p > 0.05). There was a significant difference in the gender between left atrial myxomas and right atrial myxomas (p < 0.05). The most common attached sites of left atrial myxomas and right atrial myxomas are the atrial septum. Surgical resection of the right atrial myxoma results in good clinical outcomes and a decreased incidence of recurrence. © 2015 Wiley Periodicals, Inc.

Factors associated with atrial fibrillation in rheumatic mitral stenosis.

PubMed

Pourafkari, Leili; Ghaffari, Samad; Bancroft, George R; Tajlil, Arezou; Nader, Nader D

2015-01-01

Atrial fibrillation is a complication of mitral valve stenosis that causes several adverse neurologic outcomes. Our objective was to establish a mathematical model to predict the risk of atrial fibrillation in patients with mitral stenosis. Of 819 patients with mitral stenosis who were screened, 603 were enrolled in the study and grouped according to whether they were in sinus rhythm or atrial fibrillation. Demographic, echocardiographic, and hemodynamic data were recorded. Logistic regression models were constructed to identify the relative risks for each contributing factor and calculate the probability of developing atrial fibrillation. Receiver operating characteristic curves were plotted. Two hundred (33%) patients had atrial fibrillation; this group was older, in a higher functional class, more likely to have suffered previous thromboembolic events, and had significantly larger left atrial diameters, lower ejection fractions, and lower left atrial appendage emptying flow velocity. The factors independently associated with atrial fibrillation were left atrial strain (odds ratio = 7.53 [4.47-12.69], p < 0.001), right atrial pressure (odds ratio = 1.09 [1.02-1.17], p = 0.01), age (odds ratio = 1.14 [1.05-1.25], p = 0.002), and ejection fraction (odds ratio = 0.92 [0.87-0.97], p = 0.003). The area under the curve for the combined receiver operating characteristic for this model was 0.90 ± 0.12. Age, right atrial pressure, ejection fraction, and left atrial strain can be used to construct a mathematical model to predict the development of atrial fibrillation in rheumatic mitral stenosis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Percutaneous closure of atrial septal defects leads to normalisation of atrial and ventricular volumes

PubMed Central

Teo, Karen SL; Dundon, Benjamin K; Molaee, Payman; Williams, Kerry F; Carbone, Angelo; Brown, Michael A; Worthley, Matthew I; Disney, Patrick J; Sanders, Prashanthan; Worthley, Stephen G

2008-01-01

Background Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing left-to-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function. Furthermore, atrial changes post-ASD closure have been poorly understood and may be important for understanding risk of atrial arrhythmia post-ASD closure. Cardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using CMR. Methods Consecutive patients (n = 23) underwent CMR pre- and 6 months post-ASD closure. Steady state free precession cine CMR was performed using contiguous slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial, ventricular end diastolic volumes (EDV) and end systolic volumes (ESV). Data is presented as mean ± SD, volumes as mL, and paired t-testing performed between groups. Statistical significance was taken as p < 0.05. Results There was a significant reduction in right ventricular volumes at 6 months post-ASD closure (RVEDV: 208.7 ± 76.7 vs. 140.6 ± 60.4 mL, p < 0.0001) and RVEF was significantly increased (RVEF 35.5 ± 15.5 vs. 42.0 ± 15.2%, p = 0.025). There was a significant increase in the left ventricular volumes (LVEDV 84.8 ± 32.3 vs. 106.3 ± 38.1 mL, p = 0.003 and LVESV 37.4 ± 20.9 vs. 46.8 ± 18.5 mL, p = 0.016). However, there was no significant difference in LVEF and LV mass post-ASD closure. There was a significant reduction in right atrial volumes at 6 months post-ASD closure (pre-closure 110.5 ± 55.7 vs. post-closure 90.7 ± 69.3 mL, p = 0.019). Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant (84.5 ± 34.8 mL to 81.8 ± 44.2 mL, p = NS). Conclusion ASD closure leads to

Acute effects of unilateral temporary stellate ganglion block on human atrial electrophysiological properties and atrial fibrillation inducibility.

PubMed

Leftheriotis, Dionyssios; Flevari, Panayota; Kossyvakis, Charalampos; Katsaras, Dimitrios; Batistaki, Chrysanthi; Arvaniti, Chrysa; Giannopoulos, Georgios; Deftereos, Spyridon; Kostopanagiotou, Georgia; Lekakis, John

2016-11-01

In experimental models, stellate ganglion block (SGB) reduces the induction of atrial fibrillation (AF), while data in humans are limited. The aim of this study was to assess the effect of unilateral SGB on atrial electrophysiological properties and AF induction in patients with paroxysmal AF. Thirty-six patients with paroxysmal AF were randomized in a 2:1 order to temporary, transcutaneous, pharmaceutical SGB with lidocaine or placebo before pulmonary vein isolation. Lidocaine was 1:1 randomly infused to the right or left ganglion. Before and after randomization, atrial effective refractory period (ERP) of each atrium, difference between right and left atrial ERP, intra- and interatrial conduction time, AF inducibility, and AF duration were assessed. After SGB, right atrial ERP was prolonged from a median (1st-3rd quartile) of 240 (220-268) ms to 260 (240-300) ms (P < .01) and left atrial ERP from 235 (220-260) ms to 245 (240-280) ms (P < .01). AF was induced by atrial pacing in all 24 patients before SGB, but only in 13 patients (54%) after the intervention (P < .01). AF duration was shorter after SGB: 1.5 (0.0-5.8) minutes from 5.5 (3.0-12.0) minutes (P < .01). Intra- and interatrial conduction time was not significantly prolonged. No significant differences were observed between right and left SGB. No changes were observed in the placebo group. Unilateral temporary SGB prolonged atrial ERP, reduced AF inducibility, and decreased AF duration. An equivalent effect of right and left SGB on both atria was observed. These findings may have a clinical implication in the prevention of drug refractory and postsurgery AF and deserve further clinical investigation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Intermittent atrial tachycardia promotes repolarization alternans and conduction slowing during rapid rates, and increases susceptibility to atrial fibrillation in a free-behaving sheep model.

PubMed

Monigatti-Tenkorang, Joanna; Jousset, Florian; Pascale, Patrizio; Vesin, Jean-Marc; Ruchat, Patrick; Fromer, Martin; Narayan, Sanjiv M; Pruvot, Etienne

2014-04-01

Paroxysmal atrial fibrillation (AF) may be triggered by intermittent atrial tachycardia, and ultimately lead to persistent AF. However, the mechanisms by which intermittent atrial tachycardia promotes sustained AF are not well understood. Eight sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms, and for the delivery of electrophysiological stimulation protocols and intermittent right atrial tachycardia. Right atrial kinetics of activation recovery interval (ARI) as a surrogate for action potential duration, of conduction time and velocity, and of repolarization alternans were analyzed at incremental pacing rates during the remodeling process induced by weeks of intermittent atrial tachycardia until the development of sustained AF. Intermittent atrial tachycardia decreased ARI and blunted its rate adaptation, facilitated atrial capture, and slowed conduction at high rates, and increased susceptibility to pacing-induced AF. In spite of blunted ARI rate adaptation, right atrial repolarization alternans was maintained during remodeling, and further increased in magnitude just before rapid pacing-induced AF. This study suggests that weeks of intermittent right atrial tachycardia result in a gradual electrical remodeling favorable for wavebreaks and reentry that may facilitate fibrillation. © 2014 Wiley Periodicals, Inc.

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

Recurrent atrial myxoma.

PubMed

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

2004-01-01

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

Left atrial booster function in valvular heart disease.

PubMed

Heidenreich, F P; Shaver, J A; Thompson, M E; Leonard, J J

1970-09-01

This study was designed to assess atrial booster pump action in valvular heart disease and to dissect booster pump from reservoir-conduit functions. In five patients with aortic stenosis and six with mitral stenosis, sequential atrioventricular (A-V) pacing was instituted during the course of diagnostic cardiac catheterization. Continuous recording of valvular gradient allowed estimation of flow for each cardiac cycle by transposition of the Gorlin formula. Left ventricular ejection time and left ventricular stroke work in aortic stenosis or left ventricular mean systolic pressure in mitral stenosis were also determined. Control observations were recorded during sequential A-V pacing with well-timed atrial systole. Cardiac cycles were then produced with no atrial contraction but undisturbed atrial reservoir function by intermittently interrupting the atrial pacing stimulus during sequential A-V pacing. This intervention significantly reduced valvular gradient, flow, left ventricular ejection time, and left ventricular mean systolic pressure or stroke work. Cardiac cycles were then produced with atrial booster action eliminated by instituting synchronous A-V pacing. The resultant simultaneous contraction of the atrium and ventricle not only eliminated effective atrial systole but also placed atrial systole during the normal period of atrial reservoir function. This also significantly reduced all the hemodynamic measurements. However, comparison of the magnitude of change from these two different pacing interventions showed no greater impairment of hemodynamic state when both booster pump action and reservoir function were impaired than when booster pump action alone was impaired. The study confirms the potential benefit of well placed atrial booster pump action in valvular heart disease in man.

Atrial contribution to ventricular filling in mitral stenosis.

PubMed

Meisner, J S; Keren, G; Pajaro, O E; Mani, A; Strom, J A; Frater, R W; Laniado, S; Yellin, E L

1991-10-01

The importance of the contribution of atrial systole to ventricular filling in mitral stenosis is controversial. The cause of reduced cardiac output following the onset of atrial fibrillation may be due to an increased heart rate, a loss of booster pump function, or both. We studied the atrial contribution to filling under a variety of conditions by combining noninvasive studies of patients with computer modeling. Thirty patients in sinus rhythm with mild-to-severe stenosis were studied with two-dimensional and Doppler echocardiography for measurement of mitral flow velocity and mitral valve area (MVA). The mean +/- SD atrial contribution to left ventricular filling volume was 18 +/- 10% and varied inversely with mitral resistance. Patients with mild mitral stenosis (MVA, 1.8 +/- 0.7 cm2) and severe mitral stenosis (MVA, 0.9 +/- 0.2 cm2) had atrial contributions of 29 +/- 4% and 9 +/- 5%, respectively. The pathophysiological mechanisms responsible for these trends were further investigated by the computer model. In modeled severe mitral stenosis, increasing heart rate from 75 to 150 beats/min caused an increase of 5.2 mm Hg in mean left atrial pressure, whereas loss of atrial contraction at a heart rate of 150 beats/min caused only a 1.3 mm Hg increase. The atrial booster pump contributes less to ventricular filling in mitral stenosis than in the normal heart, and the loss of atrial pump function is less important than the effect of increasing heart rate as the cause of decompensation during atrial fibrillation.

The usefulness of left atrial volume index and left ventricular mass index in determining subclinical cardiac involvement in patients with early-stage sarcoidosis.

PubMed

Kasapkara, H A; Şentürk, A; Bilen, E; Duran Karaduman, B; Ayhan, H; Özen, M B; Durmaz, T; Keleş, T; Bozkurt, E

2016-08-01

Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. The present study has been designed to evaluate the importance of diastolic dysfunction with left atrial volume index (LAVi) and left ventricular mass index (LVMi) in determining subclinical cardiac involvement in subjects with stage I-II pulmonary sarcoidosis. A total of 54 patients under follow-up for sarcoidosis without cardiac involvement and 56 healthy subjects were included in the study. The echocardiographic assessment of the patients revealed no significant difference between the two groups regarding left ventricular end-systolic and end-diastolic diameters, ejection fraction (LVEF) and annular velocity determined by tissue Doppler evaluation. The LVEF calculated was 61.8 ± 7.8 % in the sarcoidosis group versus 64.1 ± 2.7 % in the control group (p = 0.04). Left ventricular interventricular septum thickness, posterior wall thickness, and relative wall thickness were significantly higher in the sarcoidosis group compared to the control group (p < 0.001). The sarcoidosis group had higher LVM and LVMi values compared to the control group (145 ± 18.1 and 79 ± 14 g/m(2), 135 ± 27.7 and 74 ± 14.2 g/m(2); p = 0.020 and p = 0.021, respectively). Left atrial end-systolic volume and LAVi were higher in the sarcoidosis group (28.7 ± 18.5; 15.6 ± 10.2) compared to the control group (16.6 ± 10.9; 8.9 ± 5.5) with a statistically significant difference (p < 0.001). The present study indicates diastolic dysfunction and increased LVMi despite normal systolic function in patients with early-stage sarcoidosis without cardiac involvement. Also, the diastolic parameters were normal without showing any significant difference compared to the control group while there was a statistically significant increase in LAVi. This finding suggests that LAVi may be the earliest marker of diastolic dysfunction in patients with early-stage sarcoidosis without cardiac

Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation.

PubMed

Verheule, Sander; Wilson, Emily; Everett, Thomas; Shanbhag, Sujata; Golden, Catherine; Olgin, Jeffrey

2003-05-27

Clinically, chronic atrial dilatation is associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism is not clear. We have investigated atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation (MR). Thirteen control and 19 MR dogs (1 month after partial mitral valve avulsion) were studied. Dogs in the MR group were monitored using echocardiography and Holter recording. In open-chest follow-up experiments, electrode arrays were placed on the atria to investigate conduction patterns, effective refractory periods, and inducibility of AF. Alterations in tissue structure and ultrastructure were assessed in atrial tissue samples. At follow-up, left atrial length in MR dogs was 4.09+/-0.45 cm, compared with 3.25+/-0.28 at baseline (P<0.01), corresponding to a volume of 205+/-61% of baseline. At follow-up, no differences in atrial conduction pattern and conduction velocities were noted between control and MR dogs. Effective refractory periods were increased homogeneously throughout the left and right atrium. Sustained AF (>1 hour) was inducible in 10 of 19 MR dogs and none of 13 control dogs (P<0.01). In the dilated MR left atrium, areas of increased interstitial fibrosis and chronic inflammation were accompanied by increased glycogen ultrastructurally. Chronic atrial dilatation in the absence of overt heart failure leads to an increased vulnerability to AF that is not based on a decrease in wavelength.

Association Between Left Atrial Compression And Atrial Fibrillation: A Case Presentation And A Short Review Of Literature.

PubMed

Ahmed, Niloy; Carlos, Morales-Mangual; Moshe, Gunsburg; Yitzhak, Rosen

2016-01-01

This case report describes a patient who developed palpitations and chest pain and was found to be in atrial fibrillation, which was likely due to the presence of an extra-cardiac mass. This was compressing the left atrium. The mass was related to small cell carcinoma, which decreased significantly in size after chemotherapy. Resolution of the atrial fibrillation correlated temporally with reduction in the size of the mass and alleviation of the left atrial compression.

Recurrent patterns of atrial depolarization during atrial fibrillation assessed by recurrence plot quantification.

PubMed

Censi, F; Barbaro, V; Bartolini, P; Calcagnini, G; Michelucci, A; Gensini, G F; Cerutti, S

2000-01-01

The aim of this study was to determine the presence of organization of atrial activation processes during atrial fibrillation (AF) by assessing whether the activation sequences are wholly random or are governed by deterministic mechanisms. We performed both linear and nonlinear analyses based on the cross correlation function (CCF) and recurrence plot quantification (RPQ), respectively. Recurrence plots were quantified by three variables: percent recurrence (PR), percent determinism (PD), and entropy of recurrences (ER). We recorded bipolar intra-atrial electrograms in two atrial sites during chronic AF in 19 informed subjects, following two protocols. In one, both recording sites were in the right atrium; in the other protocol, one site was in the right atrium, the other one in the left atrium. We extracted 19 episodes of type I AF (Wells' classification). RPQ detected transient recurrent patterns in all the episodes, while CCF was significant only in ten episodes. Surrogate data analysis, based on a cross-phase randomization procedure, decreased PR, PD, and ER values. The detection of spatiotemporal recurrent patterns together with the surrogate data results indicate that during AF a certain degree of local organization exists, likely caused by deterministic mechanisms of activation.

History of surgery for atrial fibrillation.

PubMed

Edgerton, Zachary J; Edgerton, James R

2009-12-01

There is a rich history of surgery for atrial fibrillation. Initial procedures were aimed at controlling the ventricular response rate. Later procedures were directed at converting atrial fibrillation to normal sinus rhythm. These culminated in the Cox Maze III procedure. While highly effective, the complexity and morbidity of the cut and sew Maze III limited its adoption. Enabling technology has developed alternate energy sources designed to produce a transmural atrial scar without cutting and sewing. Termed the Maze IV, this lessened the morbidity of the procedure and widened the applicability. Further advances in minimal access techniques are now being developed to allow totally thorascopic placement of all the left atrial lesions on the full, beating heart, using alternate energy sources.

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

PubMed Central

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

2015-01-01

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

Effect of renal sympathetic denervation on the progression of paroxysmal atrial fibrillation in canines with long-term intermittent atrial pacing.

PubMed

Wang, Xule; Huang, Congxin; Zhao, Qingyan; Huang, He; Tang, Yanhong; Dai, Zixuan; Wang, Xiaozhan; Guo, Zongwen; Xiao, Jinping

2015-04-01

The aim of the present study was to explore the effect of renal sympathetic denervation (RSD) on the progression of paroxysmal atrial fibrillation (AF) in canines with long-term intermittent atrial pacing. Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (six dogs), and RSD group (seven dogs). Sham-operated group were implanted with pacemakers without pacing; control group were implanted with pacemakers with long-term intermittent atrial pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Atrial pacing was maintained for 8 h a day and a total of 12 weeks in the control group and RSD group. Echocardiography showed that the left atrial structure and function were significantly improved in the RSD group compared with the control group (P < 0.05). Compared with the control group, the RSD group had fewer incidences of AF and a shorter duration of AF (P < 0.05) after long-term intermittent atrial pacing. In addition to increased atrial effective refractory period (AERP) and AF cycle length, AERP dispersion and P-wave duration and dispersion were significantly decreased in the RSD group compared with the control group (P < 0.05). Atrial morphological evaluation suggested that fibrosis and ultrastructural changes induced by long-term intermittent atrial pacing were markedly suppressed in the RSD dogs compared with controls (P < 0.05). Immunohistochemistry results showed that connexin 43 distribution in RSD mid-myocardial was significantly fewer heterogeneous than that in control mid-myocardial (P < 0.05). Renal denervation inhibits the progression of paroxysmal AF, which might be related to the suppression of atrial electrophysiology and structural heterogeneity. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Prevalence of atrial arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

PubMed

Camm, Christian F; James, Cynthia A; Tichnell, Crystal; Murray, Brittney; Bhonsale, Aditya; te Riele, Anneline S J M; Judge, Daniel P; Tandri, Harikrishna; Calkins, Hugh

2013-11-01

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy, characterized by right ventricular dysfunction and ventricular arrhythmias. Limited information is available concerning atrial arrhythmias in ARVD/C. The purpose of this study was to characterize spontaneous atrial arrhythmias in a large registry population of ARVD/C patients. Patients (n = 248) from the Johns Hopkins ARVD/C registry who met the diagnostic criteria and had undertaken genotype analysis were included. Medical records of each were reviewed to ascertain incidence and characteristics of atrial arrhythmia episodes. Detailed demographic, phenotypic, and structural information was obtained from registry data. Thirty-five patients with ARVD/C (14%) experienced one or more types of atrial arrhythmia during median follow-up of 5.78 (interquartile range 8.52) years. Atrial fibrillation was the most common atrial arrhythmia, occurring in 80% of ARVD/C patients with atrial arrhythmias. Patients developed atrial arrhythmias at a mean age of 43.0 ± 14.0 years. Atrial arrhythmia patients obtained a total of 22 inappropriate implantable cardioverter-defibrillator shocks during follow-up. Older age at last follow-up (P <.001) and male gender (P = .044) were associated with atrial arrhythmia development. Patients with atrial arrhythmias had a higher occurrence of death (P = .028), heart failure (P <.001), and left atrial enlargement on echocardiography (P = .004). Atrial arrhythmias are common in ARVD/C and present at a younger age than in the general population. They are associated with male gender, increasing age, and left atrial enlargement. Atrial arrhythmias are clinically important as they are associated with inappropriate implantable cardioverter-defibrillator shocks and increased risk of both death and heart failure. © 2013 Heart Rhythm Society. All rights reserved.

Linagliptin prevents atrial electrical and structural remodeling in a canine model of atrial fibrillation.

PubMed

Igarashi, Tazuru; Niwano, Shinichi; Niwano, Hiroe; Yoshizawa, Tomoharu; Nakamura, Hironori; Fukaya, Hidehira; Fujiishi, Tamami; Ishizue, Naruya; Satoh, Akira; Kishihara, Jun; Murakami, Masami; Ako, Junya

2018-05-02

Dipeptidyl peptidase 4 (DPP-4) inhibitors have recently been reported to exhibit additional cardioprotective effects; however, their effect in atrial remodeling, such as in atrial fibrillation (AF), remains unclear. In this study, the effect of linagliptin on atrial electrical and structural remodeling was evaluated in a canine AF model. Sixteen beagle dogs with 3-week atrial rapid stimulation were divided into the linagliptin group (9 mg/kg/day, n = 8) and pacing control group (n = 8). Three additional dogs without rapid pacing were assigned into non-pacing group, which was used as sham in this study. In the dogs with rapid pacing, the atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated and blood was sampled every week. After the entire protocol, atrial tissue was sampled for histological examinations using HE, Azan, and dihydroethidium (DHE) staining to evaluate any tissue damage or oxidative stress. The pacing control group exhibited a gradual AERP shortening and CV decrease along the time course as previously reported. In the linagliptin group, the AERP shortening was not affected, but the CV decrease was suppressed in comparison to the control group (p < 0.05). The AF inducibility was increased in the control group and suppressed in the linagliptin group (p < 0.05). The control group exhibited tissue fibrosis, the degree of which was suppressed in the linagliptin group. DHE staining exhibited suppression of the reactive oxygen species expression in the linagliptin group in comparison to the pacing control group. Linagliptin, a DPP-4-inhibitor, suppressed the AF inducibility, CV decrease, and overexpression of oxidative stress in the canine AF model. Such suppressive effects of linagliptin on AF in the canine model may possibly be related to the anti-oxidative effect.

Atrial Function after the Atrial Switch Operation for Transposition of the Great Arteries: Comparison with Arterial Switch and Normals by Cardiovascular Magnetic Resonance.

PubMed

Franzoso, Francesca D; Wohlmuth, Christoph; Greutmann, Matthias; Kellenberger, Christian J; Oxenius, Angela; Voser, Eva M; Valsangiacomo Buechel, Emanuela R

2016-09-01

The atria serve as reservoir, conduit, and active pump for ventricular filling. The performance of the atrial baffles after atrial switch repair for transposition of the great arteries may be abnormal and impact the function of the systemic right ventricle. We sought to assess atrial function in patients after atrial repair in comparison to patients after arterial switch repair (ASO) and to controls. Using magnetic resonance imaging, atrial volumes and functional parameters were measured in 17 patients after atrial switch repair, 9 patients after ASO and 10 healthy subjects. After the atrial switch operation, the maximum volume of the pulmonary venous atrium was significantly enlarged, but not of the systemic venous atrium. In both patients groups, independently from the surgical technique used, the minimum atrial volumes were elevated, which resulted in a decreased total empting fraction compared with controls (P < .01). The passive empting volume was diminished for right atrium, but elevated for left atrium after atrial switch and normal for left atrium after ASO; however, the passive empting fraction was diminished for both right atrium and left atrium after both operations (P < .01). The active empting volume was the most affected parameter in both atria and both groups and active empting fractions were highly significantly reduced compared with controls. Atrial function is abnormal in all patients, after atrial switch and ASO repair. The cyclic volume changes, that is, atrial filling and empting, are reduced when compared with normal subjects. Thus, the atria have lost part of their capacity to convert continuous venous flow into a pulsatile ventricular filling. The function of the pulmonary venous atrium, acting as preload for the systemic right ventricle, after atrial switch is altered the most. © 2015 Wiley Periodicals, Inc.

Assessment of electrocardiographic criteria of left atrial enlargement.

PubMed

Batra, Mahesh Kumar; Khan, Atif; Farooq, Fawad; Masood, Tariq; Karim, Musa

2018-05-01

Background Left atrial enlargement is considered to be a robust, strong, and widely acceptable indicator of cardiovascular outcomes. Echocardiography is the gold standard for measurement of left atrial size, but electrocardiography can be simple, cost-effective, and noninvasive in clinical practice. This study was undertaken to assess the diagnostic accuracy of an established electrocardiographic criterion for left atrial enlargement, taking 2-dimensional echocardiography as the gold-standard technique. Methods A cross-sectional study was conducted on 146 consecutively selected patients with the complaints of dyspnea and palpitation and with a murmur detected on clinical examination, from September 10, 2016 to February 10, 2017. Electrocardiography and echocardiography were performed in all patients. Patients with a negative P wave terminal force in lead V 1  > 40 ms·mm on electrocardiography or left atrial dimension > 40 mm on echocardiography were classified as having left atrial enlargement. Sensitivity and specificity were calculated to assess the diagnostic accuracy. Results Taking 2-dimensional echocardiography as the gold-standard technique, electrocardiography correctly diagnosed 68 patients as positive for left atrial enlargement and 12 as negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of electrocardiography for left atrial enlargement were 54.4%, 57.1%, 88.3%, 17.4%, and 54.8%, respectively. Conclusion The electrocardiogram appears to be a reasonable indicator of left atrial enlargement. In case of nonavailability of echocardiography, electrocardiography can be used for diagnosis of left atrial enlargement.

Rotor mapping and ablation to treat atrial fibrillation

PubMed Central

Zaman, Junaid A.B.; Peters, Nicholas S.; Narayan, Sanjiv M.

2015-01-01

Purpose of review Rotors have long been postulated to drive atrial fibrillation, but evidence has been limited to animal models. This changed recently with the demonstration using focal impulse and rotor modulation (FIRM) mapping that rotors act as human atrial fibrillation sources. This mechanistic approach to diagnosing the causes of atrial fibrillation in individual patients has been supported by substantially improved outcomes from FIRM-guided ablation, resulting in increased attention to rotors as therapeutic targets. Recent findings In this review, we outline the pathophysiology of rotors in animal and in-silico studies of fibrillation, and how this motivated FIRM mapping in humans. We highlight the characteristics of rotors in human atrial fibrillation, now validated by several techniques, with discussion on similar and discrepant findings between techniques. The interventional approaches to eliminate atrial fibrillation rotors are explained and the ablation results in latest studies using FIRM are discussed. Summary We propose that mapping localized sources for human atrial fibrillation, specifically rotors, is moving the field towards a unifying hypothesis that explains several otherwise contradictory observations in atrial fibrillation management. We conclude by suggesting areas of potential research that may reveal more about these critical sites and how these may lead to better and novel treatments for atrial fibrillation. PMID:25389649

Involvement of neutral endopeptidase in neoplastic progression.

PubMed

Sumitomo, Makoto; Shen, Ruoqian; Nanus, David M

2005-08-01

Neutral endopeptidase 24.11 (NEP) is a 90-110 kDa cell surface cell surface peptidase that is normally expressed by numerous tissues, including prostate, kidney, intestine, endometrium, adrenal glands and lung. This enzyme cleaves peptide bonds on the amino side of hydrophobic amino acids and inactivates a variety of physiologically active peptides, including atrial natriuretic factor, substance P, bradykinin, oxytocin, Leu- and Met-enkephalins, neurotensin, bombesin, endothelin-1, and bombesin-like peptides. NEP reduces the local concentration of peptide available for receptor binding and signal transduction. Loss or decreases in NEP expression have been reported in a variety of malignancies. Reduced NEP may promote peptide-mediated proliferation by allowing accumulation of higher peptide concentrations at the cell surface, and facilitate the development or progression of neoplasia. We have used prostate cancer as model in which to study the involvement of NEP in malignancy. Using a variety of experimental approaches, including recombinant NEP, cell lines expressing wild-type and mutant NEP protein, and cell lines expressing NEP protein with a mutated cytoplasmic domain, we have examined the effects of NEP on cell migration and cell survival. We have shown that the effects of NEP are mediated by its ability to catalytically inactivate substrates such as bombesin and endothelin-1, but also through direct protein-protein interaction with other protein such as Lyn kinase [which associates with the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in NEP-Lyn-PI3-K protein complex], ezrin/radixin/moesin (ERM) proteins, and the PTEN tumor suppressor protein. We review the mechanisms of NEP's tumor suppressive action and how NEP loss contributes to tumor progression.

Left atrial size and function: role in prognosis.

PubMed

Hoit, Brian D

2014-02-18

The author examines the ability of left atrial size and function to predict cardiovascular outcomes. Data are sufficient to recommend evaluation of left atrial volume in certain populations, and although analysis of atrial reservoir, conduit, and booster pump function trails in that regard, the gap is rapidly closing. In this state-of-the-art paper, the author reviews the methods used to assess left atrial size and function and discusses their role in predicting cardiovascular events in general and referral populations and in patients with atrial fibrillation, cardiomyopathy, ischemic heart disease, and valvular heart disease. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

Renal sympathetic denervation suppresses atrial fibrillation induced by acute atrial ischemia/infarction through inhibition of cardiac sympathetic activity.

PubMed

Zhou, Qina; Zhou, Xianhui; TuEr-Hong, ZuKe-la; Wang, Hongli; Yin, Tingting; Li, Yaodong; Zhang, Ling; Lu, Yanmei; Xing, Qiang; Zhang, Jianghua; Yang, Yining; Tang, Baopeng

2016-01-15

This study aims to explore the effects of renal sympathetic denervation (RSD) on atrial fibrillation (AF) inducibility and sympathetic activity induced by acute atrial ischemia/infarction. Acute ischemia/infarction was induced in 12 beagle dogs by ligating coronary arteries that supply the atria. Six dogs in the sham-RSD group did not undergo RSD, and six dogs without coronary artery ligation served as controls. AF induction rate, sympathetic discharge, catecholamine concentration and densities of tyrosine hydroxylase-positive nerves were measured. Acute atrial ischemia/infarction resulted in a significant increase of AF induction rate, which was decreased by RSD compared to controls (P<0.05). The root-mean-square peak value, peak area and number of sympathetic discharges were significantly augmented by atrial ischemia relative to the baseline and control (P<0.05). The number of sympathetic discharges was significantly reduced in the RSD group, compared to the control and sham-RSD groups (P<0.05). Norepinephrine and epinephrine concentrations in the atria, ventricle and kidney were elevated by atrial ischemia/infarction, but were reduced by RSD (P<0.05). Sympathetic hyperactivity was associated with pacing-induced AF after acute atrial ischemia/infarction. RSD has the potential to reduce the incidence of new-onset AF after acute atrial ischemia/infarction. The inhibition of cardiac sympathetic activity by RSD may be one of the major underlying mechanisms for the marked reduction of AF inducibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Right versus left atrial pacing in patients with sick sinus syndrome and paroxysmal atrial fibrillation (Riverleft study): study protocol for randomized controlled trial.

PubMed

Ramdjan, Tanwier T T K; van der Does, Lisette J M E; Knops, Paul; Res, Jan C J; de Groot, Natasja M S

2014-11-17

The incidence of sick sinus syndrome will increase due to population ageing. Consequently, this will result in an increase in the number of pacemaker implantations. The atrial lead is usually implanted in the right atrial appendage, but this position may be ineffective for prevention of atrial fibrillation. It has been suggested that pacing distally in the coronary sinus might be more successful in preventing atrial fibrillation episodes. The aim of this trial is to study the efficacy of distal coronary sinus versus right atrial appendage pacing in preventing atrial fibrillation episodes in patients with sick sinus syndrome. This study is designed as a multicenter, randomized controlled trial. Patients with sick sinus syndrome and at least one atrial fibrillation episode of 30 seconds or more in the six months before recruitment will be eligible for participation in this study.All participants will be randomized between pacing distally in the coronary sinus and right atrial appendage. Randomization is stratified for all participating centers. Conventional dual-chamber pacemakers with advanced home monitoring functionality will be implanted. The ventricular lead will be implanted in the right ventricular apex. The first three months of the 36-month follow-up period are considered as run-in time. During the pre-randomization visit and follow-up, an interview, electrocardiogram and pacemaker assessment will be performed, prescribed antiarrhythmic medication will be reviewed and patients will be asked to complete an SF-36 questionnaire. An echocardiographic examination will be conducted in the pre-randomization phase and at the end of each follow-up year. Home monitoring will be used to send daily reports in case of atrial fibrillation episodes. This randomized controlled trial is the first in which home monitoring will be used to compare atrial fibrillation recurrences between pacing in the distal coronary sinus or right atrial appendage. Home monitoring gives the

[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

Prospective randomized study to assess the efficacy of site and rate of atrial pacing on long-term progression of atrial fibrillation in sick sinus syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study.

PubMed

Lau, Chu-Pak; Tachapong, Ngarmukos; Wang, Chun-Chieh; Wang, Jing-Feng; Abe, Haruhiko; Kong, Chi-Woon; Liew, Reginald; Shin, Dong-Gu; Padeletti, Luigi; Kim, You-Ho; Omar, Razali; Jirarojanakorn, Kreingkrai; Kim, Yoon-Nyun; Chen, Mien-Cheng; Sriratanasathavorn, Charn; Munawar, Muhammad; Kam, Ruth; Chen, Jan-Yow; Cho, Yong-Keun; Li, Yi-Gang; Wu, Shu-Lin; Bailleul, Christophe; Tse, Hung-Fat

2013-08-13

Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79-1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79-1.74; P=0.69) did not prevent the development of persistent AF. In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00419640.

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 Test...

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 Test...

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 Test...

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 Test...

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 Test...

Delayed right atrial lateral electromechanical coupling relative to the septal one can be associated with paroxysmal atrial fibrillation.

PubMed

Karapinar, H; Acar, G; Kirma, C; Kaya, Z; Karavelioglu, Y; Kucukdurmaz, Z; Esen, O; Alizade, E; Dasli, T; Sirma, D; Esen, A M

2013-08-01

Non-invasive prediction of paroxysmal atrial fibrillation (PAF) is one of the most recent interests of cardiology. The current study investigates the relationship between the atrial electromechanical coupling time (EMCT) and PAF. A group of 35 patients with PAF was compared with a group of 37 subjects without PAF. Pulsed wave tissue Doppler evaluations of atrial walls were performed from apical four chambers view under ECG monitoring. The time intervals from the onset of P wave to the onset of late diastolic wave (A') at right atrial wall (P-RA), interatrial septum (P-IAS), and left atrial wall (P-LA, maximum EMCT) were measured. The right atrial EMCT (P-RA minus P-IAS), left atrial EMCT (P-LA minus P-IAS) and interatrial EMCT (P-LA minus P-RA) were computed. A' wave velocities were measured from each atrial wall. RA (16.0±13.1 vs. -8.7±18.6 ms, p < 0.001) and maximum (91.5±32.6 vs. 72.0±23.1 ms, p = 0.001) EMCT were longer, RA A' velocity was higher in the patient group. There were no differences between the groups in LA and interatrial EMCT, and septal and LA A' velocities. Regression analysis revealed that only RA [OR: 1.148 (1.041-1.267), p = 0.006] and maximum [OR: 1.099 (1.009-1.197), p = 0.031] EMCT were independent variables for PAF. In order to predict patients with PAF, we have chosen +7.5 msn for the RA EMCT which yielded 69% sensitivity and 71.4% specificity to predict patients. Delayed RA lateral EMCT relative to septal one and delayed maximum EMCT detected by tissue Doppler could be a valuable method for identifying patients with PAF.

[The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery].

PubMed

Baysal, Ayse; Saşmazel, Ahmet; Yildirim, Ayse; Ozyaprak, Buket; Gundogus, Narin; Kocak, Tuncer

2014-01-01

In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48h after operation. The patients enrolled into the study were divided into two groups depending on: (1) Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2) Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1) duration of mechanical ventilation ≥72h, (2) intensive care unit stay >7days, and (3) mortality. The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n=35, n=16, respectively) showed significant differences in repeated measurement time points (p=0.0001). The preoperative brain natriuretic peptide cut-off value of 125.5pgmL-1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r=0.67, p=0.0001). In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5pgmL-1 are at risk of developing low cardiac output syndrome which is an important postoperative outcome. Copyright © 2013 Sociedade

Association of serum chemerin concentrations with the presence of atrial fibrillation.

PubMed

Zhang, Guowei; Xiao, Mochao; Zhang, Lili; Zhao, Yue; Yang, Qinghui

2017-05-01

Objective Chemerin, a newly discovered adipokine, is correlated with hypertension, diabetes and coronary heart disease. The aim of this study is to investigate the association of serum chemerin concentrations with the presence of atrial fibrillation. Methods Serum chemerin concentrations were determined in 256 patients with atrial fibrillation and 146 healthy subjects. Atrial fibrillation patients were then divided into paroxysmal, persistent and permanent atrial fibrillation. Results Serum chemerin concentrations were significantly higher in atrial fibrillation patients compared with healthy controls. In subgroup studies, patients with permanent atrial fibrillation had higher serum chemerin concentrations than those with persistent and paroxysmal atrial fibrillation. Furthermore, significant higher serum chemerin concentrations were observed in persistent atrial fibrillation patients compared with paroxysmal atrial fibrillation subjects. Serum chemerin concentrations were associated with the presence of atrial fibrillation after logistic regression analysis. Pearson correlation analysis revealed a positive relation of serum chemerin concentrations with body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine, C-reactive protein and left atrial diameter. Conclusion Serum chemerin concentrations are associated with the presence of atrial fibrillation and atrial remodelling.