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).

Caracterización geométrica y lumínica de los atrios incorporados en los edificios de Santiago de Chile

El atrio incorporado en los edificios ha sido un recurso espacial que tempranamente se difundió a nivel global, siendo adoptado por las distintas arquitecturas locales en gran parte del mundo. Su masificación estuvo favorecida primero por la rápida evolución de la tecnología del acero y el vidrio, a partir del siglo XIX, y en segundo termino por el posterior desarrollo del hormigón armado. Otro aspecto que explica tal aceptación en la arquitectura contemporánea, es de orden social y radica en la llamativa cavidad del espacio describiendo grandes dimensiones y favoreciendo con ello, el desarrollo de una multiplicidad de usos en su interior que antes eran impensados. Al interior del atrio, la luz natural es clave en las múltiples vivencias que alberga y sea tal vez la condición ambiental más valorada, ya que entrega una sensación de bienestar al conectarnos visualmente con el ambiente natural. Por esta razón de acuerdo al método hipotético deductivo, se evaluaron los efectos de la configuración geométrica, la cubierta y la orientación en el desempeño de la iluminación natural en la planta baja, a partir un modelo extraído desde el inventario de los edificios atrio construidos en Santiago de Chile, en los últimos 30 años que fue desarrollado en el capitulo 2. El análisis cuantitativo de los edificios inventariados se elaboró en el capítulo 3, considerando las dimensiones de los atrios. Simultáneamente fueron clasificados los aspectos constructivos, los materiales y las características del ambiente interior de cada edificio. En esta etapa además, fueron identificadas las variables de estudio de las proporciones geométricas de la cavidad del atrio con los coeficientes de aspecto de las proporciones, en planta (PAR), en corte (SAR) y de la cavidad según (WI), (AR) y (RI). Del análisis de todos estos parámetros se extrajo el modelo de prueba. El enfoque del estudio del capítulo 4 fue la iluminación natural, se revisaron los conceptos y el comportamiento en el atrio, a partir de un modelo físico construido a escala para registro de la iluminancia bajo cielo soleado de la ciudad. Más adelante se construyó el modelo en ambiente virtual, relacionando las variables determinadas por la geometría de la cavidad y el cerramiento superior; examinándose de esta manera distintas transparencias, proporciones de apertura, en definitiva se evaluó un progresivo cerramiento de las aberturas, verificando el ingreso de la luz y disponibilidad a nivel de piso con la finalidad, de proveer lineamientos útiles en una primera etapa del diseño arquitectónico. Para el análisis de la iluminación natural se revisaron diferentes métodos de cálculo con el propósito de evaluar los niveles de iluminancia en un plano horizontal al interior del atrio. El primero de ellos fue el Factor de Luz Día (FLD) que corresponde, a la proporción de la iluminancia en un punto de evaluación interior respecto, la cantidad proveniente del exterior bajo cielo nublado, a partir de la cual se obtuvo resultados que revelaron la alta luminosidad del cielo nublado de la ciudad. Además fueron evaluadas las recientes métricas dinámicas que dan cuenta, de la cantidad de horas en las cuales de acuerdo a los extensos registros meteorológico de la ciudad, permitieron obtener el porcentajes de horas dentro de las cuales se cumplió el estándar de iluminancia requerido, llamado autonomía lumínica (DA) o mejor aún se permanece dentro de un rango de comodidad visual en el interior del atrio referido a la iluminancia diurna útil (UDI). En el Capítulo 5 se exponen los criterios aplicados al modelo de estudio y cada una de las variantes de análisis, además se profundizó en los antecedentes y procedencia de las fuentes de los registros climáticos utilizados en las simulaciones llevadas a cabo en el programa Daysim operado por Radiance. Que permitieron evaluar el desempeño lumínico y la precisión, de cada uno de los resultados para comprobar la disponibilidad de iluminación natural a través de una matriz. En una etapa posterior se discutieron los resultados, mediante la comparación de los datos logrados según cada una de las metodologías de simulación aplicada. Finalmente se expusieron las conclusiones y futuras lineas de trabajo, las primeras respecto el dominio del atrio de cuatro caras, la incidencia del control de cerramiento de la cubierta y la relación establecida con la altura; indicando en lo específico que las mediciones de iluminancia bajo el cielo soleado de verano, permitieron aclarar, el uso de la herramienta de simulación y método basado en el clima local, que debido a su reciente desarrollo, orienta a futuras líneas de trabajo profundizando en la evaluación dinámica de la iluminancia contrastado con monitorización de casos. ABSTRACT Atriums incorporated into buildings have been a spatial resource that quickly spread throughout the globe, being adopted by several local architecture methods in several places. Their widespread increase was highly favored, in the first place, with the rapid evolution of steel and glass technologies since the nineteen century, and, in second place, by the following development of reinforced concrete. Another issue that explains this success into contemporary architecture is associated with the social approach, and it resides in the impressive cavity that describes vast dimensions, allowing the development of multiple uses in its interior that had never been considered before. Inside the atrium, daylight it is a key element in the many experiences that involves and it is possibly the most relevant environmental factor, since it radiates a feeling of well-being by uniting us visually with the natural environment. It is because of this reason that, following the hypothetical deductive method, the effects in the performance of daylight on the floor plan were evaluated considering the geometric configuration, the deck and orientation factors. This study was based in a model withdrawn from the inventory of atrium buildings that were constructed in Santiago de Chile during the past thirty years, which will be explained later in chapter 2. The quantitative analysis of the inventory of those buildings was elaborated in chapter 3, considering the dimensions of the atriums. Simultaneously, several features such as construction aspects, materials and environmental qualities were identified inside of each building. At this stage, it were identified the variables of the geometric proportions of the atrium’s cavity with the plan aspect ratio of proportions in first plan (PAR), in section (SAR) and cavity according to well index (WI), aspect ratio (AR) and room index (RI). An experimental model was obtained from the analysis of all the mentioned parameters. The main focus of the study developed in chapter 4 is daylight. The atrium’s concept and behavior were analyzed from a physical model built under scale to register the illuminances under clear, sunny sky of the city. Later on, this physical model was built in a virtual environment, connecting the variables determined by the geometry of the cavity and the superior enclosure, allowing the examination of transparencies and opening proportions. To summarize, this stage consisted on evaluating a progressive enclosure of the openings, checking the access of natural light and its availability at the atrium floor, in an effort to provide useful guidelines during the first stage of the architectural design. For the analysis of natural lighting, several calculations methods were used in order to determine the levels of illuminances in a horizontal plane inside of the atrium. The first of these methods is the Daylight Factor (DF), which consists in the proportion of light in an evaluation interior place with the amount of light coming from the outside in a cloudy day. Results determined that the cloudy sky of the city has high levels of luminosity. In addition, the recent dynamic metrics were evaluated which reflects the hours quantity. According to the meteorological records of the city’s climate, the standard of illuminance- a standard measure called Daylight Autonomy (DA) – was met. This is even better when the results stay in the line of visual convenience within the atrium, which is referred to as Useful Daylight Illuminance (UDI). In chapter 5, it was presented the criteria applied to the study model and on each of the variants of the analysis. Moreover, the information of the climate records used for the simulations - carried out in the Daysim program managed by Radiance – are detailed. These simulations allowed the observation of the daylight performance and the accuracy of each of the results to confirm the availability of natural light through a matrix. In a later stage, the results were discussed comparing the collected data in each of the methods of simulation used. Finally, conclusions and further discussion are presented. Overall, the four side atrium’s domain and the effect of the control of the cover’s enclosure. Specifically, the measurements of the daylight under summer’s clear, sunny sky allowing clarifying the use of the simulation tool and the method based on the local climate. This method allows defining new and future lines of work deepening on the dynamic of the light in contrast with the monitoring of the cases.

Rat heart: A site of oxytocin production and action

We report here that the rat heart is a site of oxytocin (OT) synthesis and release. Oxytocin was detected in all four chambers of the heart. The highest OT concentration was in the right atrium (2128 ± 114 pg/mg protein), which was 19-fold higher than in rat uterus but 3.3-fold lower than in the hypothalamus. OT concentrations were significantly greater in the right and left atria than in the corresponding ventricles. Furthermore, OT was released into the effluent of isolated, perfused rat heart (34.5 ± 4.7 pg/min) and into the medium of cultured atrial myocytes. Reverse-phase HPLC purification of the heart extracts and heart perfusates revealed a main peak identical with the retention time of synthetic OT. Southern blots of reverse transcription–PCR products from rat heart revealed gene expression of specific OT mRNA. OT immunostaining likewise was found in atrial myocytes and fibroblasts, and the intensity of positive stains from OT receptors paralleled the atrial natriuretic peptide stores. Our findings suggest that heart OT is structurally identical, and therefore derived from, the same gene as the OT that is primarily found in the hypothalamus. Thus, the heart synthesizes and processes a biologically active form of OT. The presence of OT and OT receptor in all of the heart’s chambers suggests an autocrine and/or paracrine role for the peptide. Our finding of abundant OT receptor in atrial myocytes supports our hypothesis that OT, directly and/or via atrial natriuretic peptide release, can regulate the force of cardiac contraction.

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.

The heart communicates with the kidney exclusively through the guanylyl cyclase-A receptor: acute handling of sodium and water in response to volume expansion.

Disruption of guanylyl cyclase-A (GC-A) results in mice displaying an elevated blood pressure, which is not altered by high or low dietary salt. However, atrial natriuretic peptide (ANP), a proposed ligand for GC-A, has been suggested as critical for the maintenance of normal blood pressure during high salt intake. In this report, we show that infusion of ANP results in substantial natriuresis and diuresis in wild-type mice but fails to cause significant changes in sodium excretion or urine output in GC-A-deficient mice. ANP, therefore, appears to signal through GC-A in the kidney. Other natriuretic/diuretic factors could be released from the heart. Therefore, acute volume expansion was used as a means to cause release of granules from the atrium of the heart. That granule release occurred was confirmed by measurements of plasma ANP concentrations, which were markedly elevated in both wild-type and GC-A-null mice. After volume expansion, urine output as well as urinary sodium and cyclic GMP excretion increased rapidly and markedly in wild-type mice, but the rapid increases were abolished in GC-A-deficient animals. These results strongly suggest that natriuretic/diuretic factors released from the heart function exclusively through GC-A.

Oxytocin mediates atrial natriuretic peptide release and natriuresis after volume expansion in the rat.

Our previous studies have shown that stimulation of the anterior ventral third ventricular region increases atrial natriuretic peptide (ANP) release, whereas lesions of this structure, the median eminence, or removal of the neural lobe of the pituitary block ANP release induced by blood volume expansion (BVE). These results indicate that participation of the central nervous system is crucial in these responses, possibly through mediation by neurohypophysial hormones. In the present research we investigated the possible role of oxytocin, one of the two principal neurohypophysial hormones, in the mediation of ANP release. Oxytocin (1-10 nmol) injected i.p. caused significant, dose-dependent increases in urinary osmolality, natriuresis, and kaliuresis. A delayed antidiuretic effect was also observed. Plasma ANP concentrations increased nearly 4-fold (P < 0.01) 20 min after i.p. oxytocin (10 nmol), but there was no change in plasma ANP values in control rats. When oxytocin (1 or 10 nmol) was injected i.v., it also induced a dose-related increase in plasma ANP at 5 min (P < 0.001). BVE by intra-atrial injection of isotonic saline induced a rapid (5 min postinjection) increase in plasma oxytocin and ANP concentrations and a concomitant decrease in plasma arginine vasopressin concentration. Results were similar with hypertonic volume expansion, except that this induced a transient (5 min) increase in plasma arginine vasopressin. The findings are consistent with the hypothesis that baroreceptor activation of the central nervous system by BVE stimulates the release of oxytocin from the neurohypophysis. This oxytocin then circulates to the right atrium to induce release of ANP, which circulates to the kidney and induces natriuresis and diuresis, which restore body fluid volume to normal levels.

Characterization of a voltage-gated K+ channel beta subunit expressed in human heart.

Voltage-gated K+ channels are important modulators of the cardiac action potential. However, the correlation of endogenous myocyte currents with K+ channels cloned from human heart is complicated by the possibility that heterotetrameric alpha-subunit combinations and function-altering beta subunits exist in native tissue. Therefore, a variety of subunit interactions may generate cardiac K+ channel diversity. We report here the cloning of a voltage-gated K+ channel beta subunit, hKv beta 3, from adult human left ventricle that shows 84% and 74% amino acid sequence identity with the previously cloned rat Kv beta 1 and Kv beta 2 subunits, respectively. Together these three Kv beta subunits share > 82% identity in the carboxyl-terminal 329 aa and show low identity in the amino-terminal 79 aa. RNA analysis indicated that hKv beta 3 message is 2-fold more abundant in human ventricle than in atrium and is expressed in both healthy and diseased human hearts. Coinjection of hKv beta 3 with a human cardiac delayed rectifier, hKv1.5, in Xenopus oocytes increased inactivation, induced an 18-mV hyperpolarizing shift in the activation curve, and slowed deactivation (tau = 8.0 msec vs. 35.4 msec at -50 mV). hKv beta 3 was localized to human chromosome 3 by using a human/rodent cell hybrid mapping panel. These data confirm the presence of functionally important K+ channel beta subunits in human heart and indicate that beta-subunit composition must be accounted for when comparing cloned channels with endogenous cardiac currents.

Avaliação da função ventricular direita por meio da ecocardiografia em cães com doença valvar crônica de mitral

A doença valvar crônica de mitral (DVCM) é a principal cardiopatia adquirida dos cães e uma das suas complicações é a hipertensão arterial pulmonar (HAP), o que pode induzir a disfunção do ventriculo direito (VD). Assim, constituíram-se em objetivos do presente estudo identificar e descrever alterações de tamanho do VD, padrão de fluxo na artéria pulmonar (AP) e função sistólica ventricular direita nas diferentes fases da DVCM, além de correlacionar estas variáveis com índices de tamanho, volume, funções sistólica e diastólica do lado esquerdo do coração, bem como com a velocidade da insuficiência tricúspide (IT) e gradiente de pressão entre o ventrículo e átrio direitos nos cães que apresentavam regurgitação da valva tricúspide. Para tanto, foram incluídos 96 cães de diversas raças no estudo, que foram separados em quatro grupos de acordo com o estágio da DVCM: grupos ou estágios A, B1, B2 e C. Os cães com DVCM sintomáticos ou em estágio C apresentaram alterações no fluxo da artéria pulmonar (AP), bem evidenciadas pela redução das suas velocidades máxima e média, além da redução dos tempos de aceleração (TAC) e ejeção (TEJ) do fluxo sistólico da AP e correlação negativa com as variáveis de tamanho e funções sistólica e diastólica do coração esquerdo. O tamanho do VD foi estatisticamente maior nos animais do estágio C em comparação aos do estágio B1 e associou-se, negativamente, com os índices de função sistólica ventricular esquerda (VE). Os índices de função sistólica do VD como índice de excursão sistólica do plano anular tricúspide (iTAPSE) e variação fracional de área (FAC) foram maiores nos estágios mais avançados da DVCM e, juntamente com a velocidade de movimentação miocárdica sistólica do anel valvar tricúspide (onda Sm), correlacionou-se com índices de funções sistólica e diastólica do VE, seguindo o mesmo padrão de aumento de movimentação e estado hipercinético das variáveis do lado esquerdo do coração na evolução da DVCM. O padrão de fluxo sistólico da AP, bem caracterizado pelo TAC e TEJ, e o índice de área doVD foram os índices que mais alteraram com a evolução da hipertensão pulmonar na DVCM, enquanto que os índices de função do VD não apresentaram alterações significativas neste modelo de hipertensão arterial pulmonar em cão

Habilidades funcionais de autocuidado, mobilidade e função social em crianças com fissura labiopalatina e Espectro Óculo-Aurículo-Vertebral (EOAV)

As anomalias craniofaciais ocasionam comprometimentos estéticos e funcionais com grande impacto na saúde e na integração social da criança, com interferência no desenvolvimento global e social. Das anomalias craniofaciais este estudo abordou as Fissuras Labiopalatinas (FLP) e o Espectro Óculo Aurículo Vertebral (EOAV). As FLP constituem malformações resultantes de falta do fechamento completo dos tecidos que compõe o lábio e o palato. O EOAV, também conhecido como Síndrome de Goldenhar, é uma anomalia congênita de etiologia desconhecida, com manifestação genética variável e de causa bastante heterogênea. Conhecer as habilidades funcionais e o impacto destas no desenvolvimento global de crianças com EOAV e FLP pode otimizar o desenvolvimento de programas de prevenção e intervenção para promover a saúde e a integração social destes indivíduos. Este estudo foi delineado com objetivo de verificar e comparar o desempenho em habilidades funcionais quanto ao desempenho nas áreas de autocuidado, mobilidade, função social e nível de independência entre crianças com EOAV, crianças com FLP e um grupo comparativo, de crianças sem anomalias. O modelo de pesquisa foi observacional descritivo transversal com uma casuística de 39 pais/responsáveis de crianças na faixa etária entre três anos e sete anos e seis meses, de ambos os gêneros. Foram convidados para participar pais/responsáveis de crianças em tratamento no Hospital de Reabilitação de Anomalias Craniofaciais da Universidade e São Paulo (HRAC-USP) os quais foram divididos em três grupos: dois experimentais e um grupo comparativo. O instrumento para coleta dos dados das habilidades funcionais foi o Pediatric Evaluation of Disability Inventory (PEDI), em sua versão adaptada para o português. A avaliação é realizada por meio de entrevista com o cuidador, o qual deve saber informar sobre o desempenho da criança em atividades e tarefas típicas da rotina diária. Os dados foram apresentados por análise descritiva com medidas de tendência central (média aritmética), dispersão (desvio-padrão) e distribuição de frequência, nas variáveis: idades, gênero e nível socioeconômico da família e caracterização da casuística. Para as análises das pontuações bruta e normativa do questionário PEDI no que se refere às habilidades funcionais e a assistência do cuidador nas três áreas de função autocuidado, mobilidade e função social, foi utilizado o teste de variância One Way, e para o teste de normalidade foi utilizado Shapiro Wilk para variável dependente. A análise comparativa foi realizada pelo teste de Kruskal-Wallis, adotando-se o valor de significância de p< 0,05. Os resultados deste estudo na análise comparativa nas habilidades funcionais na mobilidade, houve diferença estatisticamente significante na comparação entre os grupos GC vs GEEOAV, no escore bruto, e entre os grupos GC vs GEEOAV e GC vs GEFLP, no escore normativo.Na assistência do cuidador no autocuidado, houve diferença estatisticamente significante na comparação entre os grupos GC vs GEEOAV, no escore normativo. Na assistência do cuidador na mobilidade, houve diferença estatisticamente significante na comparação entre os grupos GC vs GEEOAV nos escores bruto e normativo.Na assistência do cuidador na função social houve diferença estatisticamente significante na comparação entre os grupos GC vs GEFLP.

Introduction des sonorités du Mexique préhispanique dans l'orchestration moderne

Les compositions musicales de l’étudiante qui accompagne cette thèse sous la forme d’un disque audio est disponible au comptoir de la Bibliothèque de musique sous le titre : Cristina García Islas (http://atrium.umontreal.ca/notice/UM-ALEPH002385786)

Operum mathematico-physicorum, tomus primus [-tertius]

t.1. Continens Elementa matheseos, in progressionem harmonicam mathemata, clavem astronomiae altero tanto auctiorem.--t.2 Continens Historiam reformationis calendarii inter evangelicos. Annotationes in monumenta paschalia antiquorum patrum. M.C.H. Vindicias aerae Donysianae. Methodum paschalem, et secundum hanc computum ecclesiasticum.--t.3. Continens Basin astronomiae cum triduo Roemeriano. Copernicum triumphantem cum vindiciis. Atrium astronomiae. Artem interpolandi.

Kemper Museum of Contemporary Art & Design, Kansas City Art Institute, Kansas City, Missouri, 1991-1994

Competition Drawing of Grand Atrium Hall. Ink drawing on tracing paper, initialed, 11x17 inches [from photographic copy by Lance Burgharrdt]

Kemper Museum of Contemporary Art & Design, Kansas City Art Institute, Kansas City, Missouri, 1991-1994

Competition Drawing of Grand Atrium Hall, Permanent Collection Gallery and Changing Exhibition Gallery. Ink drawing on tracing paper, initialed, 11x17 inches [from photographic copy by Lance Burgharrdt]

Emerging roles of urotensin-II in cardiovascular disease

Urotensin-II (UII) is a highly potent endogenous peptide within the cardiovascular system. Through stimulation of Galphaq-coupled UT receptors, UII mediates contraction of vascular smooth muscle and endothelial-dependent vasorelaxation, and positive inotropy in human right atrium and ventricle. A pathogenic role of the UT receptor system is emerging in cardiovascular disease states, with evidence for upregulation of the UT receptor system in patients with congestive heart failure (CHF), pulmonary hypertension, cirrhosis and portal hypertension, and chronic renal failure. In vitro and in vivo studies show that under pathophysiological conditions, UII might contribute to cardiomyocyte hypertrophy, extracellular matrix production, enhanced vasoconstriction, vascular smooth muscle cell hyperplasia, and endothelial cell hyper-permeability. Single nucleotide polymorphisms of the UII gene may also impart a genetic predisposition of patients to diabetes. Therefore, the UT receptor system is a potential therapeutic target in the treatment of cardiac, pulmonary, and renal diseases. UT receptor antagonists are currently being developed to prevent and/or reverse the effects of over-activated UT receptors by the endogenous ligand. This review describes UII peptide and converting enzymes, and UT receptors in the cardiovascular system, focusing on pathophysiological roles of UII in the heart and blood vessels. (C) 2004 Elsevier Inc. All rights reserved,

Functional serotonin 5-HT4 receptors in porcine and human ventricular myocardium with increased 5-HT4 mRNA in heart failure

Serotonin (5-hydroxytryptamine, 5-HT) increases contractile force and elicits arrhythmias through 5-HT4 receptors in porcine and human atrium, but its ventricular effects are unknown. We now report functional 5-HT4 receptors in porcine and human ventricle. 5-HT4 mRNA levels were determined in porcine and human ventricles and contractility studied in ventricular trabeculae. Cyclic AMP-dependent protein kinase (PKA) activity was measured in porcine ventricle. Porcine and human ventricles expressed 5-HT4 receptor mRNA. Ventricular 5-HT4(b) mRNA was increased by four times in 20 failing human hearts compared with five donor hearts. 5-HT increased contractile force maximally by 16% (EC50=890 nM) and PKA activity by 20% of the effects of (-)-isoproterenol (200 muM) in ventricular trabeculae from new-born piglets in the presence of the phosphodiesterase-inhibitor 3-isobutyl-1-methylxanthine. In ventricular trabeculae from adult pigs (3-isobutyl-1-methylxanthine present) 5-HT increased force by 32% (EC50=60 nM) and PKA activity by 39% of (-)-iso-proterenol. In right and left ventricular trabeculae from failing hearts, exposed to modified Krebs solution, 5-HT produced variable increases in contractile force in right ventricular trabeculae from 4 out of 6 hearts and in left ventricular trabeculae from 3 out of 3 hearts- range 1-39% of (-)-isoproterenol, average 8%. In 11 left ventricular trabeculae from the failing hearts of four beta-blocker-treated patients, pre-exposed to a relaxant solution with 0.5 mM Ca2+ and 1.2 mM Mg2+ followed by a switch to 2.5 mM Ca2+ and 1 mM Mg2+, 5-HT (1-100 muM, 3-isobutyl-1-melhylxanthine present) consistently increased contractile force and hastened relaxation by 46% and 25% of (-)-isoproterenol respectively. 5-HT caused arrhythmias in three trabeculae from 3 out of I I patients. In the absence of phosphodiesterase inhibitor, 5-HT increased force in two trabeculae, but not in another six trabeculae from 4 patients. All 5-HT responses were blocked by 5-HT4 receptor antagonists. We conclude that phosphodiesterase inhibition uncovers functional ventricular 5-HT4 receptors, coupled to a PKA pathway, through which 5-HT enhances contractility, hastens relaxation and can potentially cause arrhythmias.