Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study

Background: Pimobendan has been shown to impart a significant survival benefit in cardiomyopathic cats who receive it as part of heart failure therapy. However, use of pimobendan remains controversial in cats with hypertrophic cardiomyopathy (HCM) due to lack of pharmacodynamic data for pimobendan in cats with HCM and due to theoretical concerns for exacerbating left ventricular outflow tract obstructions. Hypothesis/Objectives: Our objective was to investigate the cardiac effects of pimobendan in cats with HCM. We hypothesized that pimobendan would not exacerbate left ventricular outflow tract obstructions and that it would improve echocardiographic measures of diastolic function. Animals: Thirteen purpose-bred cats were studied from a research colony with naturally-occurring HCM due to a variant in myosin binding protein C. Methods: Cats underwent two examinations 24 h apart with complete standard echocardiography. On their first day of evaluation, they were randomized to receive oral placebo or 1.25 mg pimobendan 1 h prior to exam. On their second examination, they were crossed over and received the remaining treatment. Investigators were blinded to all treatments. Results: The pimobendan group had a significant increase in left atrial fractional shortening (pimobendan group 41.7% ± 5.9; placebo group 36.1% ± 6.0; p = 0.04). There was no significant difference in left ventricular outflow tract (LVOT) velocities between the groups (pimobendan group 2.8 m/s ± 0.8; placebo group 2.6 m/s ± 1.0). There were no significant differences between the number of cats with LVOT obstructions between groups (12 in pimobendan group; 11 in placebo group; p = 1.00). There were no detectable differences in any systolic measures, including left ventricular fractional shortening, mitral annular plane systolic excursion, and tricuspid annular plane systolic excursion. Doppler-based diastolic function assessment was precluded by persistent tachycardia. Conclusions: Improved left atrial function in the pimobendan group could explain some of the reported survival benefit for HCM cats in CHF. Pimobendan did not exacerbate LVOT obstructions and thus may not be contraindicated in HCM cats with LVOT obstructions. Future studies are needed to better characterize other physiologic effects, particularly regarding diastolic function assessment, and to better assess safety of pimobendan over a longer time-course.Center for Companion Animal Health at the University of California Davis, School of Veterinary Medicine [2016-15-F]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The SED of Low-Luminosity AGNs at high-spatial resolution

The inner structure of AGNs is expected to change below a certain luminosity limit. The big blue bump, footprint of the accretion disk, is absent for the majority of low-luminosity AGNs (LLAGNs). Moreover, recent simulations suggest that the torus, a keystone in the Unified Model, vanishes for nuclei with L_bol < 10^42 erg/s. However, the study of LLAGN is a complex task due to the contribution of the host galaxy, which light swamps these faint nuclei. This is specially critical in the IR range, at the maximum of the torus emission, due to the contribution of the old stellar population and/or dust in the nuclear region. Adaptive optics imaging in the NIR (VLT/NaCo) together with diffraction limited imaging in the mid-IR (VLT/VISIR) permit us to isolate the nuclear emission for some of the nearest LLAGNs in the Southern Hemisphere. These data were extended to the optical/UV range (HST), radio (VLA, VLBI) and X-rays (Chandra, XMM-Newton, Integral), in order to build a genuine spectral energy distribution (SED) for each AGN with a consistent spatial resolution (< 0.5") across the whole spectral range. From the individual SEDs, we construct an average SED for LLAGNs sampled in all the wavebands mentioned before. Compared with previous multiwavelength studies of LLAGNs, this work covers the mid-IR and NIR ranges with high-spatial resolution data. The LLAGNs in the sample present a large diversity in terms of SED shapes. Some of them are very well described by a self-absorbed synchrotron (e.g. NGC 1052), while some other present a thermal-like bump at ~1 micron (NGC 4594). All of them are significantly different when compared with bright Seyferts and quasars, suggesting that the inner structure of AGNs (i.e. the torus and the accretion disk) suffers intrinsic changes at low luminosities.Comment: 8 pages, 5 figures. To appear in the proceedings of "Astrophysics at High Angular Resolution" (AHAR 2011

Unbiased large spectroscopic surveys of galaxies selected by SPICA using dust bands

The mid-infrared (IR) range contains many spectral features associated with large molecules and dust grains such as polycyclic aromatic hydrocarbons (PAHs) and silicates. These are usually very strong compared to fine-structure gas lines, and thus valuable in studying the spectral properties of faint distant galaxies. In this paper, we evaluate the capability of low-resolution mid-IR spectroscopic surveys of galaxies that could be performed by SPICA. The surveys are designed to address the question how star formation and black hole accretion activities evolved over cosmic time through spectral diagnostics of the physical conditions of the interstellar/circumnuclear media in galaxies. On the basis of results obtained with Herschel far-IR photometric surveys of distant galaxies and Spitzer and AKARI near- to mid-IR spectroscopic observations of nearby galaxies, we estimate the numbers of the galaxies at redshift z > 0.5, which are expected to be detected in the PAH features or dust continuum by a wide (10 deg^2) or deep (1 deg^2) blind survey, both for a given observation time of 600 hours. As by-products of the wide blind survey, we also expect to detect debris disks, through the mid-IR excess above the photospheric emission of nearby main-sequence stars, and we estimate their number. We demonstrate that the SPICA mid-IR surveys will efficiently provide us with unprecedentedly large spectral samples, which can be studied further in the far-IR with SPICA.Comment: Paper accepted for publication on PASA on 18th October 2017, as part of the SPICA Special Issu

The role of SPICA-like missions and the Origins Space Telescope in the quest for heavily obscured AGN and synergies with Athena

In the BH-galaxy co-evolution framework, most of the star-formation (SF) and the black hole (BH) accretion is expected to take place in highly obscured conditions. Thus, obscured AGN are difficult to identify in optical or X-ray bands, but shine bright in the IR. Moreover, X-ray background (XRB) synthesis models predict that a large fraction of the yet-unresolved XRB is due to the most obscured (Compton thick, CT) of these AGN. In this work, we investigate the synergies between putative IR missions (using SPICA, proposed for ESA/M5 but withdrawn in October 2020, and Origins Space Telescope, OST, as `templates') and the X-ray mission Athena, which should fly in early 2030s, in detecting and characterizing AGN, with a particular focus on the most obscured ones. Using an XRB synthesis model, we estimated the number of AGN and the number of those which will be detected in the X-rays. For each AGN we associated an optical-to-FIR SED from observed AGN with both X-ray data and SED decomposition, and used these SEDs to check if the AGN will be detected by SPICA-like or OST at IR wavelengths. We expect that, with the deepest Athena and SPICA-like (or OST) surveys, we will be able to detect in the IR more than $90\,\%$ of all the AGN (down to L$_{2-10\text{keV}} \sim 10^{42}\,$erg/s and up to $z \sim 10$) predicted by XRB synthesis modeling, and we will detect at least half of them in the X-rays. Athena will be extremely powerful in detecting and discerning moderate- and high-luminosity AGN. We find that the most obscured and elusive CT-AGN will be exquisitely sampled by SPICA-like mission or OST and that Athena will allow a fine characterization of the most-luminous ones. This will provide a significant step forward in the process of placing stronger constraints on the yet-unresolved XRB and investigating the BH accretion rate evolution up to very high redshift ($z \ge 4$).Comment: Accepted for publication in PAS

Feedback and feeding in the context of galaxy evolution with SPICA: direct characterization of molecular outflows and inflows

A far-infrared observatory such as the {\it SPace Infrared telescope for Cosmology and Astrophysics} ({\it SPICA}), with its unprecedented spectroscopic sensitivity, would unveil the role of feedback in galaxy evolution during the last $\sim10$ Gyr of the Universe ($z=1.5-2$), through the use of far- and mid-infrared molecular and ionic fine structure lines that trace outflowing and infalling gas. Outflowing gas is identified in the far-infrared through P-Cygni line shapes and absorption blueshifted wings in molecular lines with high dipolar moments, and through emission line wings of fine-structure lines of ionized gas. We quantify the detectability of galaxy-scale massive molecular and ionized outflows as a function of redshift in AGN-dominated, starburst-dominated, and main-sequence galaxies, explore the detectability of metal-rich inflows in the local Universe, and describe the most significant synergies with other current and future observatories that will measure feedback in galaxies via complementary tracers at other wavelengths.Comment: This paper belongs to the SPICA Special Issue on PASA. Accepted for publication in PAS

Heart Rate and Heart Rate Variability of Rhesus Macaques (Macaca mulatta) Affected by Left Ventricular Hypertrophy

Hypertrophic cardiomyopathy (HCM) is frequently associated with sudden cardiac death, presumably due to the development of malignant arrhythmias. The risk of sudden cardiac death due to HCM has been reported to be predicted by assessing electrocardiographic (ECG) changes including frequencies and complexities of arrhythmias as well as heart rate variability (HRV) as an assessment of autonomic balance. Sudden cardiac death in association with naturally-occurring left ventricular hypertrophy (LVH) has been reported in a colony of rhesus macaques and is under investigation as a potential non-human primate model of human HCM. In the present study, 10 rhesus macaques with LVH and 10 without the signs of LVH confirmed by an echocardiographic examination were recruited for assessing ECG and HRV parameters. ECG morphology on 10-s, 6-lead ECG analysis, and the frequency and complexity of arrhythmias as well as HRV on 20-h ambulatory ECG Holter analyses were assessed. On the standard 10-s 6-lead ECG analysis, P wave and QRS complex duration as well as the QRS complex amplitude were significantly increased in the LVH-affected rhesus macaques compared to control rhesus macaques. Analysis of 20-h Holter monitoring revealed no statistically significant differences in the frequency or the complexity of arrhythmias between the LVH and the control groups. Several HRV parameters were smaller in the LVH group than the control group throughout the majority of Holter recordings showing periods of reduced variability, however, no statistically significant differences were achieved across groups and/or time points. These findings indicate that ECG analysis and Holter monitoring of rhesus macaques are feasible and that ECG morphological changes in association with LVH could be used as a possible component of an antemortem screening tool. The rhesus macaques of this study did not reveal clear indications of risk for sudden cardiac death. Further studies are necessary to determine the etiology of sudden cardiac death due in LVH affected rhesus macaques and identify if any parameters of arrhythmia assessment or HRV can be used to predict the development of sudden cardiac death

Probing the high-redshift universe with SPICA: Toward the epoch of reionisation and beyond

With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI