Haemodynamic Adaptive Mechanisms at High Altitude: Comparison between European Lowlanders and Nepalese Highlanders

Background: Exposure to high altitudes determines several adaptive mechanisms affecting in a complex way the whole cardiovascular, respiratory, endocrine systems because of the hypobaric hypoxic condition. The aim of our study was to evaluate the circulatory adaptive mechanisms at high altitudes, during a scientific expedition in the Himalayas. Methods: Arterial distensibility was assessed measuring carotid-radial and carotid-femoral pulse wave velocity. Tests were carried out at several altitudes, from 1350 to 5050 m above sea level, on 8 lowlander European researchers and 11 highlander Nepalese porters. Results: In Europeans, systolic blood pressure and pulse pressure increased slightly but significantly with altitude (p < 0.05 and p < 0.001, respectively). Norepinephrine showed a significant increase after the lowlanders had spent some time at high altitude (p < 0.001). With increasing altitude, a progressive increase in carotid-radial and carotid-femoral pulse wave velocity values was observed in lowlanders, showing a particularly significant increase (p < 0.001) after staying at high altitude (carotid-radial pulse wave velocity, median value (interquartile range) from 9.2 (7.9-10.0) to 11.2 (10.9-11.8) m/s and carotid-femoral pulse wave velocity from 8.5 (7.9-9.0) to 11.3 (10.9-11.8) m/s). At high altitudes (3400 and 5050 m above sea level), no significant differences were observed between highlanders and lowlanders in hemodynamic parameters (blood pressure, carotid-radial and carotid-femoral pulse wave velocity). Conclusions: The progressive arterial stiffening with altitude observed in European lowlanders could explain the increase in systolic and pulse pressure values observed at high altitudes in this ethnic group. Further studies are needed to evaluate the role of aortic stiffening in the pathogenesis of acute mountain sickness

Different Antioxidant Efficacy of Two MnII-Containing Superoxide Anion Scavengers on Hypoxia/Reoxygenation-Exposed Cardiac Muscle Cells

Oxidative stress due to excess superoxide anion ([Formula: see text]) produced by dysfunctional mitochondria is a key pathogenic event of aging and ischemia-reperfusion diseases. Here, a new [Formula: see text]-scavenging MnII complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing 2 quinoline units (MnQ2), designed to improve complex stability and cell permeability, was compared to parental MnII complex with methyls replacing quinolines (MnM2). MnQ2 was more stable than MnM2 (log K = 19.56(8) vs. 14.73(2) for the equilibrium Mn2+ + L2-, where L = Q2 and M2) due to the involvement of quinoline in metal binding and to the hydrophobic features of the ligand which improve metal desolvation upon complexation. As oxidative stress model, H9c2 rat cardiomyoblasts were subjected to hypoxia-reoxygenation. MnQ2 and MnM2 (10 μmol L-1) were added at reoxygenation for 1 or 2 h. The more lipophilic MnQ2 showed more rapid cell and mitochondrial penetration than MnM2. Both MnQ2 and MnM2 abated endogenous ROS and mitochondrial [Formula: see text], decreased cell lipid peroxidation, reduced mitochondrial dysfunction, in terms of efficiency of the respiratory chain and preservation of membrane potential (Δψ) and permeability, decreased the activation of pro-apoptotic caspases 9 and 3, and increased cell viability. Of note, MnQ2 was more effective than MnM2 to exert cytoprotective anti-oxidant effects in the short term. Compounds with redox-inert ZnII replacing the functional MnII were ineffective. This study provides clues which further our understanding of the structure-activity relationships of MnII-chelates and suggests that MnII-polyamino-polycarboxylate macrocycles could be developed as new anti-oxidant drugs

Chemical and isotopic snow variability in East Antarctica along the 2001/02 ITASE traverse

AbstractAs part of the International Trans-Antarctic Scientific Expedition (ITASE) project, a traverse was carried out from November 2001 to January 2002 through Terre Adélie, George V Land, Oates Land and northern Victoria Land, for a total length of about 1875 km. The research goal is to determine the latitudinal and longitudinal variability of physical, chemical and isotopic parameters along three transects: one west–east transect (WE), following the 2150m contour line (about 400 km inland of the Adélie, George V and Oates coasts), and two north–south transects (inland Terre Adélie and Oates Coast–Talos Dome–Victoria Land). The intersection between the WE and Oates Coast–Victoria Land transects is in the Talos Dome area. Along the traverse, eight 2 m deep snow pits were dug and sampled with a 2.5 cm depth resolution. For spatial variability, 1 m deep integrated samples were collected every 5 km (363 sampling sites). In the snow-pit stratigraphy, pronounced annual cycles, with summer maxima, were observed for nssSO42–, MSA, NO3– and H2O2. The seasonality of these chemical trace species was used in combination with stable-isotope stratigraphy to derive reliable and temporally representative snow-accumulation rates. The study of chemical, isotopic and accumulation-rate variability allowed the identification of a distribution pattern which is controlled not only by altitude and distance from the sea, but also by the complex circulation of air masses in the study area. In particular, although the Talos Dome area is almost equidistant from the Southern Ocean and the Ross Sea, local atmospheric circulation is such that the area is strongly affected only by the Ross Sea. Moreover, we observed a decrease in concentration of aerosol components in the central portion of the WE transect and in the southern portion of the Talos Dome transect; this decrease was linked to the higher stability of atmospheric pressure due to the channelling of katabatic winds

A dynamic clamping approach using in silico IK1 current for discrimination of chamber-specific hiPSC-derived cardiomyocytes

: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) constitute a mixed population of ventricular-, atrial-, nodal-like cells, limiting the reliability for studying chamber-specific disease mechanisms. Previous studies characterised CM phenotype based on action potential (AP) morphology, but the classification criteria were still undefined. Our aim was to use in silico models to develop an automated approach for discriminating the electrophysiological differences between hiPSC-CM. We propose the dynamic clamp (DC) technique with the injection of a specific IK1 current as a tool for deriving nine electrical biomarkers and blindly classifying differentiated CM. An unsupervised learning algorithm was applied to discriminate CM phenotypes and principal component analysis was used to visualise cell clustering. Pharmacological validation was performed by specific ion channel blocker and receptor agonist. The proposed approach&nbsp;improves the translational relevance of the hiPSC-CM model for studying mechanisms underlying inherited or acquired atrial arrhythmias in human CM, and for screening anti-arrhythmic agents

Study of chemical and optical properties of biomass burning aerosols during long-range transport events toward the arctic in Summer 2017

Producción CientíficaBiomass burning related aerosol episodes are becoming a serious threat to the radiative balance of the Arctic region. Since early July 2017 intense wildfires were recorded between August and September in Canada and Greenland, covering an area up to 4674 km2 in size. This paper describes the impact of these biomass burning (BB) events measured over Svalbard, using an ensemble of ground-based, columnar, and vertically-resolved techniques. BB influenced the aerosol chemistry via nitrates and oxalates, which exhibited an increase in their concentrations in all of size fractions, indicating the BB origin of particles. The absorption coefficient data (530 nm) at ground reached values up to 0.6 Mm–1, highlighting the impact of these BB events when compared to average Arctic background values, which do not exceed 0.05 Mm–1. The absorption behavior is fundamental as implies a subsequent atmospheric heating. At the same time, the AERONET Aerosol Optical Depth (AOD) data showed high values at stations located close to or in Canada (AOD over 2.0). Similarly, increased values of AODs were then observed in Svalbard, e.g., in Hornsund (daily average AODs exceeded 0.14 and reached hourly values up to 0.5). Elevated values of AODs were then registered in Sodankylä and Andenes (daily average AODs exceeding 0.150) a few days after the Svalbard observation of the event highlighting the BB columnar magnitude, which is crucial for the radiative impact. All the reported data suggest to rank the summer 2017 plume of aerosols as one of the biggest atmosphere related environmental problems over Svalbard region in last 10 years