Sparse spectral analysis of atrial fibrillation electrograms

Atrial fibrillation (AF) is a common heart disorder. One of the most prominent hypothesis about its initiation and maintenance considers multiple uncoordinated activation foci inside the atrium. However, the implicit assumption behind all the signal processing techniques used for AF, such as dominant frequency and organization analysis, is the existence of a single regular component in the observed signals. In this paper we take into account the existence of multiple foci, performing a spectral analysis to detect their number and frequencies. In order to obtain a cleaner signal on which the spectral analysis can be performed, we introduce sparsity-aware learning techniques to infer the spike trains corresponding to the activations. The good performance of the proposed algorithm is demonstrated both on synthetic and real data. RESUMEN. Algoritmo basado en técnicas de regresión dispersa para la extracción de las señales cardiacas en pacientes con fibrilación atrial (AF).

Proyecto de remodelación de la Calle Serrano y construcción de tres aparcamientos. Metodología de trabajos topográficos.

El 8 de Agosto de 2008 el Ayuntamiento de Madrid adjudicó a un consorcio formado por Cintra Infraestructuras e Iridium Concesiones el proyecto de Remodelación de la calle Serrano y la redacción del proyecto, construcción y explotación de tres aparcamientos con un total de 3.297 plazas repartidas entre parte pública y de residentes. El proyecto supuso una transformación total de la calle más exclusiva de Madrid invitando al paseo y el disfrute de su parte comercial con un aumento de hasta el 64% de superficie de aceras mientras se potencio la calidad ambiental de todo el entorno plantando 813 nuevos árboles y creando más de 2,1 Km de carril bici, a la vez que se doto a la calle del más moderno mobiliario urbano facilitando puntos de encuentro y descanso. La reordenación urbana se completó con la creación de dos carriles destinados a vehículos públicos, uno para autobuses y otro para taxis y motos, mientras se reservan tres carriles para vehículos privados. Todas las entradas y salidas a los aparcamientos se han realizado desde las calles transversales a Serrano, que también se transformaron en esta actuación. La actuación en superficie abarcó el tramo de la calle Serrano que discurre desde la calle María de Molina hasta la Plaza de la Independencia. Incluyó la reurbanización del cruce de maría de Molina- Serrano, de las calles aledañas a Serrano, así como la reordenación como glorieta convencional de la Plaza de la Independencia. Para hacerse una idea de la magnitud del proyecto basta citar algunos de los consumos durante la fase de obra: • Más de 9.000 toneladas de acero. • Más de 125.000 m3 de hormigón in situ. • Más de 65.000 m2 de forjados prefabricados. • Más de 87.800 ml de pilote y pantallas desde 450 a 850mm de diámetro. • Más de 65.000 m2 de granito. • Más de 11.000 ml de bordillo. • Más de 56.000 m2 de aglomerado. En los trabajos, más de 350 operarios trabajaron simultáneamente con más de 80n técnicos y personal de administración dedicados directamente al proyecto. En esta presentación vamos a ver una visión general de este proyecto y de los trabajosde índole topográfica que se tuvieron que llevar a cabo, tanto en la definición del proyecto como en su replanteo y control.

Plan de remodelación del sistema de transporte colectivo de Logroño

El proyecto tenía como objeto resolver ciertas ineficiencias del sistema actual así como la adaptación a cambios de la estructura urbana de la ciudad de Logroño. Para ello se siguieron las distintas fases de un proceso de planificación (descripción y diagnóstico del territorio y el sistema actual, formulación de fines y objetivos, generación de alternativas, selección de alternativas). Además, se incluyó un análisis económico así como unas directrices para la puesta en marcha del plan.

Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart

Previous studies indicated that the central nervous system induces release of the cardiac hormone atrial natriuretic peptide (ANP) by release of oxytocin from the neurohypophysis. The presence of specific transcripts for the oxytocin receptor was demonstrated in all chambers of the heart by amplification of cDNA by the PCR using specific oligonucleotide primers. Oxytocin receptor mRNA content in the heart is 10 times lower than in the uterus of female rats. Oxytocin receptor transcripts were demonstrated by in situ hybridization in atrial and ventricular sections and confirmed by competitive binding assay using frozen heart sections. Perfusion of female rat hearts for 25 min with Krebs–Henseleit buffer resulted in nearly constant release of ANP. Addition of oxytocin (10−6 M) significantly stimulated ANP release, and an oxytocin receptor antagonist (10−7 and 10−6 M) caused dose-related inhibition of oxytocin-induced ANP release and in the last few minutes of perfusion decreased ANP release below that in control hearts, suggesting that intracardiac oxytocin stimulates ANP release. In contrast, brain natriuretic peptide release was unaltered by oxytocin. During perfusion, heart rate decreased gradually and it was further decreased significantly by oxytocin (10−6 M). This decrease was totally reversed by the oxytocin antagonist (10−6 M) indicating that oxytocin released ANP that directly slowed the heart, probably by release of cyclic GMP. The results indicate that oxytocin receptors mediate the action of oxytocin to release ANP, which slows the heart and reduces its force of contraction to produce a rapid reduction in circulating blood volume.

Antisense oligonucleotides against rat brain α1E DNA and its atrial homologue decrease T-type calcium current in atrial myocytes

Low voltage-activated, or T-type, calcium currents are important regulators of neuronal and muscle excitability, secretion, and possibly cell growth and differentiation. The gene (or genes) coding for the pore-forming subunit of low voltage-activated channel proteins has not been unequivocally identified. We have used reverse transcription–PCR to identify partial clones from rat atrial myocytes that share high homology with a member of the E class of calcium channel genes. Antisense oligonucleotides targeting one of these partial clones (raE1) specifically block the increase in T-current density that normally results when atrial myocytes are treated with insulin-like growth factor 1 (IGF-1). Antisense oligonucleotides targeting portions of the neuronal rat α1E sequence, which are not part of the clones detected in atrial tissue, also block the IGF-1-induced increase in T-current, suggesting that the high homology to α1E seen in the partial clone may be present in the complete atrial sequence. The basal T-current expressed in these cells is also blocked by antisense oligonucleotides, which is consistent with the notion that IGF-1 up-regulates the same gene that encodes the basal current. These results support the hypothesis that a member of the E class of calcium channel genes encodes a low voltage-activated calcium channel in atrial myocytes.

A Constitutively “Phosphorylated” Guanylyl Cyclase-linked Atrial Natriuretic Peptide Receptor Mutant Is Resistant to Desensitization

Dephosphorylation of the natriuretic peptide receptor-A (NPR-A) is hypothesized to mediate its desensitization in response to atrial natriuretic peptide (ANP) binding. Recently, we identified six phosphorylation sites within the kinase homology domain of NPR-A and determined that the conversion of these residues to alanine abolished the ability of the receptor to be phosphorylated or to be activated by ANP and ATP. In an attempt to generate a form of NPR-A that mimics a fully phosphorylated receptor but that is resistant to dephosphorylation, we engineered a receptor variant (NPR-A-6E) containing glutamate substitutions at all six phosphorylation sites. Consistent with the known ability of negatively charged glutamate residues to substitute functionally, in some cases, for phosphorylated residues, we found that NPR-A-6E was activated 10-fold by ANP and ATP. As determined by guanylyl cyclase assays, the hormone-stimulated activity of the wild-type receptor declined over time in membrane preparations in vitro, and this loss was blocked by the serine/threonine protein phosphatase inhibitor microcystin. In contrast, the activity of NPR-A-6E was more linear with time and was unaffected by microcystin. The nonhydrolyzable ATP analogue adenosine 5′-(β,γ-imino)-triphosphate was half as effective as ATP in stimulating the wild-type receptor but was equally as potent in stimulating NPR-A-6E, suggesting that ATP is required to keep the wild-type but not 6E variant phosphorylated. Finally, the desensitization of NPR-A-6E in whole cells was markedly blunted compared with that of the wild-type receptor, consistent with its inability to shed the negative charge from its kinase homology domain via dephosphorylation. These data provide the first direct test of the requirement for dephosphorylation in guanylyl cyclase desensitization and they indicate that it is an essential component of this process.

Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats

In both normally hydrated and volume-expanded rats, there was a biphasic effect of corticotropin-releasing hormone (CRH) (1–10 μg, i.v.) on renal function. Within the first hour, CRH caused antidiuresis, antinatriuresis, and antikaliuresis together with reduction in urinary cGMP output that, in the fourth hour, were replaced by diuresis, natriuresis, and kaliuresis accompanied by increased cGMP output. Plasma arginine vasopressin (AVP) concentrations increased significantly within 5 min, reached a peak at 15 min, and declined by 30 min to still-elevated values maintained for 180 min. Changes in plasma atrial natriuretic peptide (ANP) were the mirror image of those of AVP. Plasma ANP levels were correlated with decreased ANP in the left ventricle at 30 min and increased ANP mRNA in the right atrium at 180 min. All urinary changes were reversed by a potent AVP type 2 receptor (V2R) antagonist. Control 0.9% NaCl injections evoked an immediate increase in blood pressure and heart rate measured by telemetry within 3–5 min. This elevation of blood pressure was markedly inhibited by CRH (5 μg). We hypothesize that the effects are mediated by rapid, direct vasodilation induced by CRH that decreases baroreceptor input to the brain stem, leading to a rapid release of AVP that induces the antidiuresis by direct action on the V2Rs in the kidney. Simultaneously, acting on V2Rs in the heart, AVP inhibits ANP release and synthesis, resulting in a decrease in renal cGMP output that is responsible for the antinatriuretic and antikaliuretic effects.

Atrial natriuretic peptide-stimulated Ca2+ reabsorption in rabbit kidney requires membrane-targeted, cGMP-dependent protein kinase type II

Atrial natriuretic peptide (ANP) and nitric oxide (NO) are key regulators of ion and water transport in the kidney. Here, we report that these cGMP-elevating hormones stimulate Ca2+ reabsorption via a novel mechanism specifically involving type II cGMP-dependent protein kinase (cGK II). ANP and the NO donor, sodium nitroprusside (SNP), markedly increased Ca2+ uptake in freshly immunodissected rabbit connecting tubules (CNT) and cortical collecting ducts (CCD). Although readily increasing cGMP, ANP and SNP did not affect Ca2+ and Na+ reabsorption in primary cultures of these segments. Immunoblot analysis demonstrated that cGK II, and not cGK I, was present in freshly isolated CNT and CCD but underwent a complete down-regulation during the primary cell culture. However, upon adenoviral reexpression of cGK II in primary cultures, ANP, SNP, and 8-Br-cGMP readily increased Ca2+ reabsorption. In contrast, no cGMP-dependent effect on electrogenic Na+ transport was observed. The membrane localization of cGK II proved to be crucial for its action, because a nonmyristoylated cGK II mutant that was shown to be localized in the cytosol failed to mediate ANP-stimulated Ca2+ transport. The Ca2+-regulatory function of cGK II appeared isotype-specific because no cGMP-mediated increase in Ca2+ transport was observed after expression of the cytosolic cGK Iβ or a membrane-bound cGK II/Iβ chimer. These results demonstrate that ANP- and NO-stimulated Ca2+ reabsorption requires membrane-targeted cGK II.

Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme

Atrial natriuretic peptide (ANP) is a cardiac hormone essential for the regulation of blood pressure. In cardiac myocytes, ANP is synthesized as a precursor, pro-ANP, that is converted to biologically active ANP by an unknown membrane-associated protease. Recently, we cloned a transmembrane serine protease, corin, that is highly expressed in the heart. In this study, we examine effects of corin on pro-ANP processing. Our results show that recombinant human corin converts pro-ANP to ANP and that the cleavage in pro-ANP by corin is highly sequence specific. Our findings suggest that corin is the long-sought pro-ANP-converting enzyme and that the corin-mediated pro-ANP activation may play a role in regulating blood pressure.