Acute Pulmonary Embolism Decreases Adenosine Plasma Levels in Anesthetized Pigs

Adenosine plays a role in pulmonary arterial (PA) resistance due to its vasodilator properties. However, the behavior of adenosine plasma levels (APLs) during pulmonary embolism remains unknown. We investigated the effects of gradual pulmonary embolism on right ventricular (RV) contractility and PA coupling and on APLs in an piglet experimental model of RV failure. PA distal resistance by pressure-flow relationships and pulmonary vascular impedance were measured. RV contractility was determined by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. APLs were measured before and during gradual pulmonary embolization. PA embolism increased PA resistance and elastance, increased Ea from 1.08 ± 0.15 to 5.62 ± 0.32 mmHg/mL, decreased Ees from 1.82 ± 0.10 to 1.20 ± 0.23 mmHg/mL, and decreased Ees/Ea from 1.69 ± 0.15 to 0.21 ± 0.07. APLs decreased from 2.7 ± 0.26 to 1.3 ± 0.12 μM in the systemic bed and from 4.03 ± 0.63 to 2.51 ± 0.58 μM in the pulmonary bed during embolism procedure. Pulmonary embolism worsens PA hemodynamics and RV-PA coupling. APLs were reduced, both in the systemic and in the pulmonary bed, leading then to pulmonary vasoconstriction

Cardiopulmonary Response to Exercise in COPD and Overweight Patients: Relationship between Unloaded Cycling and Maximal Oxygen Uptake Profiles

Cardiopulmonary response to unloaded cycling may be related to higher workloads. This was assessed in male subjects: 18 healthy sedentary subjects (controls), 14 hypoxemic patients with chronic obstructive pulmonary disease (COPD), and 31 overweight individuals (twelve were hypoxemic). They underwent an incremental exercise up to the maximal oxygen uptake (VO 2 max), preceded by a 2 min unloaded cycling period. Oxygen uptake (VO 2 ), heart rate (HR), minute ventilation (VE), and respiratory frequency (fR) were averaged every 10 s. At the end of unloaded cycling period, HR increase was significantly accentuated in COPD and hypoxemic overweight subjects (resp., +14 ± 2 and +13 ± 1.5 min −1 , compared to +7.5 ± 1.5 min −1 in normoxemic overweight subjects and +8 ± 1.8 min −1 in controls). The fR increase was accentuated in all overweight subjects (hypoxemic: +4.5 ± 0.8; normoxemic: +3.9 ± 0.7 min −1 ) compared to controls (+2.5 ± 0.8 min −1 ) and COPDs (+2.0 ± 0.7 min −1 ). The plateau VE increase during unloaded cycling was positively correlated with VE values measured at the ventilatory threshold and VO 2 max. Measurement of ventilation during unloaded cycling may serve to predict the ventilatory performance of COPD patients and overweight subjects during an exercise rehabilitation program

Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation

International audienceBackground: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold‑storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold‑preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. Methods: The preservation solution Celsior saturated with pure argon (Argon‑Celsior) or xenon (Xenon‑Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air‑Celsior). The left kidney was removed, and Air‑Celsior (n = 8 pigs), Argon‑Celsior (n = 8) or Xenon‑Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air‑Celsior was used. Hetero‑ topic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. Results: The use of Argon‑Celsior vs. Air‑Celsior: (1) improved function recovery as monitored via creatinine clear‑ ance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2–3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day‑21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the " reduced ascorbic acid/thiobarbituric acid reactive substances " ratio and Hsp27 expression; (6) limited the inflamma‑ tory response as shown by expression of TNF‑alpha, IL1‑beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon‑Celsior was detrimental, no animal surviving by day‑8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. Conclusions: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation

Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder. Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013–June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia. We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined “BNP-cTnI” levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers. We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Global response of Plasmodium falciparum to hyperoxia: a combined transcriptomic and proteomic approach

<p>Abstract</p> <p>Background</p> <p>Over its life cycle, the <it>Plasmodium falciparum </it>parasite is exposed to different environmental conditions, particularly to variations in O₂pressure. For example, the parasite circulates in human venous blood at 5% O₂pressure and in arterial blood, particularly in the lungs, at 13% O₂pressure. Moreover, the parasite is exposed to 21% O₂levels in the salivary glands of mosquitoes.</p> <p>Methods</p> <p>To study the metabolic adaptation of <it>P. falciparum </it>to different oxygen pressures during the intraerythrocytic cycle, a combined approach using transcriptomic and proteomic techniques was undertaken.</p> <p>Results</p> <p>Even though hyperoxia lengthens the parasitic cycle, significant transcriptional changes were detected in hyperoxic conditions in the late-ring stage. Using PS 6.0™ software (Ariadne Genomics) for microarray analysis, this study demonstrate up-expression of genes involved in antioxidant systems and down-expression of genes involved in the digestive vacuole metabolism and the glycolysis in favour of mitochondrial respiration. Proteomic analysis revealed increased levels of heat shock proteins, and decreased levels of glycolytic enzymes. Some of this regulation reflected post-transcriptional modifications during the hyperoxia response.</p> <p>Conclusions</p> <p>These results seem to indicate that hyperoxia activates antioxidant defence systems in parasites to preserve the integrity of its cellular structures. Moreover, environmental constraints seem to induce an energetic metabolism adaptation of <it>P. falciparum</it>. This study provides a better understanding of the adaptive capabilities of <it>P. falciparum </it>to environmental changes and may lead to the development of novel therapeutic targets.</p