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1.
Geophys Res Lett ; 49(15): e2022GL099655, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-36247517

RESUMEN

Microbursts are impulsive (<1 s) injections of electrons into the atmosphere, thought to be caused by nonlinear scattering by chorus waves. Although attempts have been made to quantify their contribution to outer belt electron loss, the uncertainty in the overall size and duration of the microburst region is typically large, so that their contribution to outer belt loss is uncertain. We combine datasets that measure chorus waves (Van Allen Probes [RBSP], Arase, ground-based VLF stations) and microburst (>30 keV) precipitation (FIREBIRD II and AC6 CubeSats, POES) to determine the size of the microburst-producing chorus source region beginning on 5 December 2017. We estimate that the long-lasting (∼30 hr) microburst-producing chorus region extends from 4 to 8 Δ MLT and 2-5 Δ L. We conclude that microbursts likely represent a major loss source of outer radiation belt electrons for this event.

2.
J Geophys Res Space Phys ; 125(3): e2019JA027651, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32714732

RESUMEN

Microbursts are an impulsive increase of electrons from the radiation belts into the atmosphere and have been directly observed in low Earth orbit and the upper atmosphere. Prior work has estimated that microbursts are capable of rapidly depleting the radiation belt electrons on the order of a day; hence, their role to radiation belt electron losses must be considered. Losses due to microbursts are not well constrained, and more work is necessary to accurately quantify their contribution as a loss process. To address this question, we present a statistical study of > 35 keV microburst sizes using the pair of AeroCube-6 CubeSats. The microburst size distribution in low Earth orbit and the magnetic equator was derived using both spacecraft. In low Earth orbit, the majority of microbursts were observed, while the AeroCube-6 separation was less than a few tens of kilometers, mostly in latitude. To account for the statistical effects of random microburst locations and sizes, Monte Carlo and analytic models were developed to test hypothesized microburst size distributions. A family of microburst size distributions were tested, and a Markov chain Monte Carlo sampler was used to estimate the optimal distribution of model parameters. Finally, a majority of observed microbursts map to sizes less than 200 km at the magnetic equator. Since microbursts are widely believed to be generated by scattering of radiation belt electrons by whistler mode waves, the observed microburst size distribution was compared to whistler mode chorus size distributions derived in prior literature.

3.
Rev Sci Instrum ; 91(3): 034503, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32260014

RESUMEN

FIREBIRD-II is a National Science Foundation funded CubeSat mission designed to study the scale size and energy spectrum of relativistic electron microbursts. The mission consists of two identical 1.5 U CubeSats in a low earth polar orbit, each with two solid state detectors that differ only in the size of their geometric factors and fields of view. Having two spacecraft in close orbit allows the scale size of microbursts to be investigated through the intra-spacecraft separation when microbursts are observed simultaneously on each unit. Each detector returns high cadence (10 s of ms) measurements of the electron population from 200 keV to >1 MeV across six energy channels. The energy channels were selected to fill a gap in the observations of the Heavy Ion Large Telescope instrument on the Solar, Anomalous, and Magnetospheric Particle Explorer. FIREBIRD-II has been in orbit for 5 years and continues to return high quality data. After the first month in orbit, the spacecraft had separated beyond the expected scale size of microbursts, so the focus has shifted toward conjunctions with other magnetospheric missions. FIREBIRD-II has addressed all of its primary science objectives, and its long lifetime and focus on conjunctions has enabled additional science beyond the scope of the original mission. This paper presents a brief history of the FIREBIRD mission's science goals, followed by a description of the instrument and spacecraft. The data products are then discussed along with some caveats necessary for proper use of the data.

4.
J Geophys Res Space Phys ; 125(12): e2020JA028462, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33520562

RESUMEN

Curtain precipitation is a recently discovered stationary, persistent, and latitudinally narrow electron precipitation phenomenon in low Earth orbit. Curtains are observed over consecutive passes of the dual AeroCube-6 CubeSats while their in-track lag varied from a fraction of a second to 65 s, with dosimeters that are sensitive to >35-keV electrons. This study uses the AeroCube-6 mission to quantify the statistical properties of 1,634 curtains observed over 3 years. We found that many curtains are narrower than 10 km in the latitudinal direction with 90% narrower than 20 km. We examined the geographic, magnetic local time, and geomagnetic dependence of curtains. We found that curtains are observed in the late-morning and premidnight magnetic local times, with a higher occurrence rate at premidnight, and curtains are observed more often during times of enhanced Auroral Electrojet. We found a few curtains in the bounce loss cone region above the North Atlantic, whose electrons were continuously scattered for at least 6 s. Such observations suggest that continuous curtain precipitation may be a significant loss of >35-keV electrons from the magnetosphere into the atmosphere. We hypothesize that the curtains observed in the bounce loss cone were accelerated by parallel electric fields, and we show that this mechanism is consistent with the observations.

5.
Space Sci Rev ; 215(1): 9, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30880847

RESUMEN

With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.

6.
Nat Commun ; 7: 12274, 2016 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-27447820

RESUMEN

Methane cold seep systems typically exhibit extensive buildups of authigenic carbonate minerals, resulting from local increases in alkalinity driven by methane oxidation. Here, we demonstrate that modern seep authigenic carbonates exhibit anomalously low clumped isotope values (Δ47), as much as ∼0.2‰ lower than expected values. In modern seeps, this range of disequilibrium translates into apparent temperatures that are always warmer than ambient temperatures, by up to 50 °C. We examine various mechanisms that may induce disequilibrium behaviour in modern seep carbonates, and suggest that the observed values result from several factors including kinetic isotopic effects during methane oxidation, mixing of inorganic carbon pools, pH effects and rapid precipitation. Ancient seep carbonates studied here also exhibit potential disequilibrium signals. Ultimately, these findings indicate the predominance of disequilibrium clumped isotope behaviour in modern cold seep carbonates that must be considered when characterizing environmental conditions in both modern and ancient cold seep settings.

7.
Nature ; 523(7559): 193-5, 2015 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-26123022

RESUMEN

Over 40 years ago it was suggested that electron loss in the region of the radiation belts that overlaps with the region of high plasma density called the plasmasphere, within four to five Earth radii, arises largely from interaction with an electromagnetic plasma wave called plasmaspheric hiss. This interaction strongly influences the evolution of the radiation belts during a geomagnetic storm, and over the course of many hours to days helps to return the radiation-belt structure to its 'quiet' pre-storm configuration. Observations have shown that the long-term electron-loss rate is consistent with this theory but the temporal and spatial dynamics of the loss process remain to be directly verified. Here we report simultaneous measurements of structured radiation-belt electron losses and the hiss phenomenon that causes the losses. Losses were observed in the form of bremsstrahlung X-rays generated by hiss-scattered electrons colliding with the Earth's atmosphere after removal from the radiation belts. Our results show that changes of up to an order of magnitude in the dynamics of electron loss arising from hiss occur on timescales as short as one to twenty minutes, in association with modulations in plasma density and magnetic field. Furthermore, these loss dynamics are coherent with hiss dynamics on spatial scales comparable to the size of the plasmasphere. This nearly global-scale coherence was not predicted and may affect the short-term evolution of the radiation belts during active times.

8.
Geobiology ; 13(6): 562-80, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26081483

RESUMEN

We present data from sediment cores collected from IODP Site C0012 in the Shikoku Basin. Our site lies at the Nankai Trough, just prior to subduction of the 19 Ma Philippine Sea plate. Our data indicate that the sedimentary package is undergoing multiple routes of electron transport and that these differing pathways for oxidant supply generate a complex array of metabolic routes and microbial communities involved in carbon cycling. Numerical simulations matched to pore water data document that Ca(2+) and Cl(1-) are largely supplied via diffusion from a high-salinity (44.5 psu) basement fluid, which supports the presence of halophile Archean communities within the deep sedimentary package that are not observed in shallow sediments. Sulfate supply from basement supports anaerobic oxidation of methane (AOM) at a rate of ~0.2 pmol cm(-3) day(-1) at ~400 mbsf. We also note the disappearance of δ-Proteobacteria at 434 mbsf, coincident with the maximum in methane concentration, and their reappearance at 463 mbsf, coinciding with the observed deeper increase in sulfate concentration toward the basement. We did not, however, find ANME representatives in any of the samples analyzed (from 340 to 463 mbsf). The lack of ANME may be due to an overshadowing effect from the more dominant archaeal phylotypes or may indicate involvement of unknown groups of archaea in AOM (i.e., unclassified Euryarchaeota). In addition to the supply of sulfate from a basement aquifer, the deep biosphere at this site is also influenced by an elevated supply of reactive iron (up to 143 µmol g(-1)) and manganese (up to 20 µmol g(-1)). The effect of these metal oxides on the sulfur cycle is inferred from an accompanying sulfur isotope fractionation much smaller than expected from traditional sulfate-reducing pathways. The detection of the manganese- and iron-reducer γ-Proteobacteria Alteromonas at 367 mbsf is consistent with these geochemical inferences.


Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Biodiversidad , Ambiente , Sedimentos Geológicos/microbiología , Archaea/genética , Archaea/aislamiento & purificación , Bacterias/genética , Bacterias/aislamiento & purificación , ADN de Archaea/genética , ADN Bacteriano/genética , Océano Pacífico , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética
9.
J Geophys Res Space Phys ; 120(6): 4922-4935, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26937330

RESUMEN

BARREL observed electron precipitation over wide range of energy and timescalesPrecipitating electron distribution is determined using spectroscopy for 19 January 2013 eventBARREL timing data has accuracy within sampling interval of 0.05 s.

10.
Blood Cancer J ; 4: e261, 2014 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-25382611

RESUMEN

PRDM1/Blimp-1 is a tumor suppressor gene in the activated B-cell subtype of diffuse large B-cell lymphomas. Its inactivation contributes to pathogenesis in this setting by impairing terminal B-cell differentiation induced by constitutive nuclear factor-κB activation. The role of PRDM1 in Burkitt lymphoma (BL) lymphomagenesis is not known. Here we identified hypermethylation of the promoter region and exon 1 of PRDM1 in all six Epstein-Barr virus (EBV)-positive BL cell lines and 12 of 23 (52%) primary EBV-positive BL or BL-related cases examined, but in none of the EBV-negative BL cell lines or primary tumors that we assessed, implying a tumor suppressor role for PRDM1 specifically in EBV-associated BL. A direct induction of PRDM1 hypermethylation by EBV is unlikely, as PRDM1 hypermethylation was not observed in EBV-immortalized B lymphoblastoid cell lines. Treatment of EBV-positive BL cells with 5' azacytidine resulted in PRDM1 induction associated with PRDM1 demethylation, consistent with transcriptional silencing of PRDM1 as a result of DNA methylation. Overexpression of PRDM1 in EBV-positive BL cell lines resulted in cell cycle arrest. Our results expand the spectrum of lymphoid malignancies in which PRDM1 may have a tumor suppressor role and identify an epigenetic event that likely contributes to the pathogenesis of BL.


Asunto(s)
Linfoma de Burkitt/metabolismo , Metilación de ADN , Herpesvirus Humano 4 , Proteínas Represoras/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/patología , Linfoma de Burkitt/virología , Línea Celular Tumoral , Femenino , Humanos , Masculino , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Proteínas Represoras/genética , Proteínas Supresoras de Tumor/genética
11.
Environ Sci Process Impacts ; 16(7): 1659-75, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24718675

RESUMEN

Across the EU, programmes of measures have been introduced as part of river basin management planning as a means of tackling problems of diffuse pollution from agriculture. Evidence is required to demonstrate the effectiveness of these measures and with this overarching objective, monitoring of an agricultural catchment in Eastern Scotland was initiated in 2007. As a precursor to evaluating the effect of new management measures it is essential to understand how other factors, including hydrology and land use changes, could have influenced water quality. This study undertook an analysis of the trends in concentrations and loads of nitrate, soluble reactive phosphorus (SRP), suspended solids (SS) and turbidity measured at six points in the catchment over a six year period. The results identified both differing trends between determinands and differing trends occurring over varying spatial scales. The only direct relationships between land use and water quality that could be identified based on annual data was a positive link between arable cropping and nitrate concentrations. At the sub-catchment scale some temporal changes in land use and management explained short-term trends in nitrate but not in SRP. Lags in the system were identified due to soil adsorption, in-stream/loch processing and groundwater transport making the identification of cause and effect problematic. The results have implications for the demonstration of effectiveness of measures over the shorter term and the timescales of recovery from diffuse pollution. Longer term monitoring at small scales will be important in this regard.


Asunto(s)
Agricultura , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Contaminación del Agua/estadística & datos numéricos , Hidrología , Nitratos , Fósforo/análisis , Escocia , Calidad del Agua
12.
Rev Sci Instrum ; 85(12): 125117, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25554336

RESUMEN

We report on the design and development of a low resource, dual sensor vector magnetometer for space science applications on very small spacecraft. It is based on a hybrid device combining an orthogonal triad of commercial anisotropic magnetoresistive (AMR) sensors with a totem pole H-Bridge drive on a ceramic substrate. The drive enables AMR operation in the more sensitive flipped mode and this is achieved without the need for current spike transmission down a sensor harness. The magnetometer has sensitivity of better than 3 nT in a 0-10 Hz band and a total mass of 104 g. Three instruments have been launched as part of the TRIO-CINEMA space weather mission, inter-calibration against the International Geomagnetic Reference Field model makes it possible to extract physical signals such as field-aligned current deflections of 20-60 nT within an approximately 45,000 nT ambient field.

13.
Proc Natl Acad Sci U S A ; 99 Suppl 2: 6456-9, 2002 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-11880611

RESUMEN

This perspective examines quantum dot (QD) superlattices as model systems for achieving a general understanding of the electronic structure of solids and devices built from nanoscale components. QD arrays are artificial two-dimensional solids, with novel optical and electric properties, which can be experimentally tuned. The control of the properties is primarily by means of the selection of the composition and size of the individual QDs and secondly, through their packing. The freedom of the architectural design is constrained by nature insisting on diversity. Even the best synthesis and separation methods do not yield dots of exactly the same size nor is the packing in the self-assembled array perfectly regular. A series of experiments, using both spectroscopic and electrical probes, has characterized the effects of disorder for arrays of metallic dots. We review these results and the corresponding theory. In particular, we discuss temperature-dependent transport experiments as the next step in the characterization of these arrays.

14.
Phys Rev E Stat Nonlin Soft Matter Phys ; 64(6 Pt 1): 061303, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11736176

RESUMEN

We study the drag force on discrete objects with circular cross section moving slowly through a spherical granular medium. Variations in the geometry of the dragged object change the drag force only by a small fraction relative to shape effects in fluid drag. The drag force depends quadratically on the object's diameter as expected. We do observe, however, a deviation above the expected linear depth dependence, and the magnitude of the deviation is apparently controlled by geometrical factors.

15.
Phys Rev E Stat Nonlin Soft Matter Phys ; 64(3 Pt 1): 031307, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11580332

RESUMEN

We study fluctuations in the drag force experienced by an object moving through a granular medium. The successive formation and collapse of jammed states give a stick-slip nature to the fluctuations which are periodic at small depths but become "stepped" at large depths, a transition that we interpret as a consequence of the long-range nature of the force chains and the finite size of our experiment. Another important finding is that the mean force and the fluctuations appear to be independent of the properties of the contact surface between the grains and the dragged object. These results imply that the drag force originates in the bulk properties of the granular sample.

16.
J Cardiovasc Pharmacol ; 38(4): 618-24, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11588532

RESUMEN

The adenosine subtype 1 (A1) receptor, which may influence cardiac function and modulate renal function, may have particular relevance in congestive heart failure (CHF). However, the effects of A1 receptor inhibition in the setting of CHF are poorly defined. Systemic hemodynamics and indices of renal function were measured in pigs with pacing-induced CHF at 240 bpm for 3 weeks (n = 10) before and after A1 receptor blockade with 100 microg of BG9719 (1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthene) or in CHF pigs after infusion of vehicle only (n = 10). Heart rate, mean aortic pressure, and left ventricular peak pressure increased following A1 blockade in the CHF group, consistent with an adenosine inhibitory effect. However, cardiac output and global measures of vascular resistance did not significantly change following A1 blockade. Urine output increased twofold and sodium clearance increased threefold following A1 blockade (p < 0.05). Creatinine clearance increased following A1 blockade (127 +/- 17 vs. 62 +/- 7 ml/min, p < 0.05). Selective A1 receptor blockade improved glomerular filtration rate and induced a natriuresis and diuresis in a model of CHF without adverse effects on cardiac function. These unique results suggest that renal A1 receptor activation may contribute to the reduced renal function associated with CHF.


Asunto(s)
Riñón/fisiología , Receptores Purinérgicos P1/fisiología , Función Ventricular Izquierda/fisiología , Animales , Creatinina/metabolismo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/orina , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Riñón/efectos de los fármacos , Riñón/metabolismo , Pruebas de Función Renal , Masculino , Antagonistas de Receptores Purinérgicos P1 , Sodio/metabolismo , Porcinos , Micción/fisiología , Función Ventricular Izquierda/efectos de los fármacos
18.
J Card Fail ; 7(1): 84-91, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11264554

RESUMEN

BACKGROUND: Although reduced pulmonary clearance of endothelin-1 (ET-1) has been suggested to contribute to increased circulating levels in congestive heart failure (CHF), the regulation of the pulmonary ET system with CHF remains to be defined. Accordingly, the aim of the present study is to investigate the expression and activity of the ET system with the development of CHF. METHODS AND RESULTS: Pulmonary tissue samples were collected from pigs with pacing CHF (240 bpm, 3 wks, n = 10) and controls (n = 10). The pulmonary messenger RNA (mRNA) and protein levels of endothelin converting enzyme-1 (ECE-1) subisoforms, ET-1, and ET receptor profiles were determined. The gene expression of ET-1 precursor, ECE-1a, and ET(A) was upregulated 4-, 3-, and 2-fold, respectively, with CHF. Pulmonary tissue ET-1 was increased to 13 +/- 2 fmol/mg protein from control values of 5 +/- 1 fmol/mg protein (P <.05), and ECE-1 activity was augmented from 3,264 +/- 665 fmol/mg protein in control animals to 14,073 +/- 654 fmol/mg protein per hour in CHF animals (P <.05). The ET(B) receptor density decreased, whereas ET(A) receptors were increased in CHF, indicating a shift in the ET(A) to ET(B) ratio. CONCLUSIONS: Both the increased synthesis and the decreased clearance of ET-1 via ET(B) receptors may contribute to the increased systemic and pulmonary ET-1 levels in CHF.


Asunto(s)
Ácido Aspártico Endopeptidasas/metabolismo , Endotelina-1/biosíntesis , Insuficiencia Cardíaca/metabolismo , Pulmón/metabolismo , Receptores de Endotelina/metabolismo , Animales , Enzimas Convertidoras de Endotelina , Metaloendopeptidasas , Modelos Animales , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , Receptores de Endotelina/genética , Porcinos
19.
Immunobiology ; 204(5): 649-58, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11846230

RESUMEN

Gammaherpesviruses (gammaHV) establish a life-long latency in the host and are associated with a number of malignant human diseases. It is generally believed that T cells play a major role in controlling the initial acute infection and subsequently maintaining the virus in a quiescent state. However, the nature of the T cell response to gamma-herpesvirus infections is poorly understood. In the current report we took advantage of a mouse model of gammaHV infection (murine herpesvirus-68, MHV-68) to investigate the T cell response to different phases of the infection. Intranasal infection with MHV-68 induces an acute infection in lung epithelial cells and long-term latency in B cells. The kinetics of the CD8+ T cell response to different lytic cycle and latency-associated antigens was highly complex and distinct patterns of response could be identified. These responses were regulated by multiple factors including differences in temporal expression of the relevant antigens, differences in the presentation of antigen in different organs, and differential expression of antigen in different types of antigen presenting cells. For example, some antigens were expressed at distinct phases of the infection and in specific organs or subsets of antigen presenting cells. In addition, recent data suggest that in addition to B cells, both macrophages and dendritic cells harbor latent MHV-68 infection, adding further complexity to their role in controlling the T cell response to this infection.


Asunto(s)
Antígenos Virales/genética , Expresión Génica , Infecciones por Herpesviridae/virología , Rhadinovirus/inmunología , Infecciones Tumorales por Virus/virología , Animales , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/virología , Linfocitos B/inmunología , Linfocitos B/virología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Células Dendríticas/inmunología , Células Dendríticas/virología , Infecciones por Herpesviridae/inmunología , Humanos , Ratones , Rhadinovirus/genética , Infecciones Tumorales por Virus/inmunología
20.
J Card Fail ; 7(4): 348-54, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11782859

RESUMEN

BACKGROUND: We examined whether and to what degree long-term angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 (AT(1))-receptor blockade, or combined inhibition in developing congestive heart failure (CHF) alter myocardial interstitial bradykinin (BF) levels. METHODS AND RESULTS: Pigs (27-30 kg) underwent rapid pacing-induced CHF (240 bpm, 3 weeks; n = 10); pacing CHF with concomitant ACE inhibition (benezaprilat, 3.75 mg/day; n = 10); pacing CHF and concomitant AT(1)-receptor blockade (valsartan, 60 mg/day; n = 10); pacing CHF and combined inhibition (benezaprilat/valsartan, 1.87/60 mg/day, respectively; n = 10); or served as controls (no pacing, no treatment; n = 10). Steady-state myocardial interstitial BK levels were quantitated by microdialysis. Cardiac output decreased to 1.95 +/- 0.18 L/min in pacing CHF compared with control (3.78 +/- 0.38; P < .05). Cardiac output increased from untreated CHF values with concomitant ACE inhibition (3.91 +/- 0.27 L/min), AT(1)-receptor blockade (3.30 +/- 0.41 L/min), or combined ACE/AT(1)-receptor inhibition (4.13 +/- 0.32 L/min; all P < .05 v CHF). With pacing CHF, myocardial interstitial BK levels were reduced by approximately 50% from control values and were normalized in the ACE inhibition and combined inhibition groups. CONCLUSIONS: Long-term ACE inhibition increases myocardial interstitial BK levels with CHF; addition of AT(1)-receptor blockade does not seem to abrogate these effects.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Estimulación Cardíaca Artificial/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Receptores de Angiotensina/uso terapéutico , Animales , Bradiquinina/metabolismo , Modelos Animales de Enfermedad , Hemodinámica/efectos de los fármacos , Masculino , Modelos Cardiovasculares , Miocardio/metabolismo , Receptor de Angiotensina Tipo 1 , Porcinos , Tiempo , Función Ventricular Izquierda/efectos de los fármacos , Función Ventricular Izquierda/fisiología
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