Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic ...metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function.
We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell-derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and postconditioning therapeutic agents.
Analysis of human complex trait genetics indicates that variants in the
genetic locus are significantly associated with cardiac and cerebrovascular ischemic injuries. Using human induced pluripotent stem cell-derived cardiomyocytes in vitro and murine ex vivo heart models, we demonstrate that genetic ablation of ASIC1a improves cardiomyocyte viability after acute IRI. Therapeutic blockade of ASIC1a using specific and potent pharmacologic inhibitors recapitulates this cardioprotective effect. We used an in vivo model of myocardial infarction and 2 models of ex vivo donor heart procurement and storage as clinical models to show that ASIC1a inhibition improves post-IRI cardiac viability. Use of ASIC1a inhibitors as preconditioning or postconditioning agents provided equivalent cardioprotection to benchmark drugs, including the sodium-hydrogen exchange inhibitor zoniporide. At the cellular and whole organ level, we show that acute exposure to ASIC1a inhibitors has no effect on cardiac ion channels regulating baseline electromechanical coupling and physiologic performance.
Our data provide compelling evidence for a novel pharmacologic strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.
Chemical components of organic aerosol (OA) selectively absorb light at short wavelengths. In this study, the prevalence, sources, and optical importance of this so-called brown carbon (BrC) aerosol ...component are investigated throughout the North American continental tropospheric column during a summer of extensive biomass burning. Spectrophotometric absorption measurements on extracts of bulk aerosol samples collected from an aircraft over the central USA were analyzed to directly quantify BrC abundance. BrC was found to be prevalent throughout the 1 to 12 km altitude measurement range, with dramatic enhancements in biomass-burning plumes. BrC to black carbon (BC) ratios, under background tropospheric conditions, increased with altitude, consistent with a corresponding increase in the absorption Aangstrom exponent (AAE) determined from a three-wavelength particle soot absorption photometer (PSAP). The sum of inferred BC absorption and measured BrC absorption at 365 nm was within 3 % of the measured PSAP absorption for background conditions and 22 % for biomass burning. A radiative transfer model showed that BrC absorption reduced top-of-atmosphere (TOA) aerosol forcing by ~ 20 % in the background troposphere. Extensive radiative model simulations applying this study background tropospheric conditions provided a look-up chart for determining radiative forcing efficiencies of BrC as a function of a surface-measured BrC : BC ratio and single scattering albedo (SSA). The chart is a first attempt to provide a tool for better assessment of brown carbon's forcing effect when one is limited to only surface data. These results indicate that BrC is an important contributor to direct aerosol radiative forcing.
Lightning is one of the most important sources of upper tropospheric NOx; however, there is a large spread in estimates of the global emission rates (2–8 Tg N yr−1). We combine upper tropospheric in ...situ observations from the Deep Convective Clouds and Chemistry (DC3) experiment and global satellite‐retrieved NO2 tropospheric column densities to constrain mean lightning NOx (LNOx) emissions per flash. Insights from DC3 indicate that the NOx lifetime is ~3 h in the region of outflow of thunderstorms, mainly due to production of methyl peroxy nitrate and alkyl and multifunctional nitrates. The lifetime then increases farther downwind from the region of outflow. Reinterpreting previous analyses using the 3 h lifetime reduces the spread among various methods that have been used to calculate mean LNOx emissions per flash and indicates a global LNOx emission rate of ~9 Tg N yr−1, a flux larger than the high end of recent estimates.
Key Points
The upper tropospheric NOx lifetime is shorter than typically assumed
A shorter NOx lifetime improves agreement among various methods used to calculate mean lightning NOx emission rates per flash
Global lightning NOx emission rates are estimated to be ~9 Tg N yr−1
Plain Language Summary
Lightning is an important source of upper troposphere nitrogen oxides; however, there is high uncertainty in the amount of nitrogen oxides produced from lightning. Using recent updates in upper tropospheric nitrogen oxides chemistry, this study decreases this uncertainty from a factor of 4 to less than a factor of 2 and shows that the amount of nitrogen oxides produced from lightning should be higher.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The air quality of South Korea was the focus of the NASA/NIER KORean -United States Air Quality (KORUS-AQ) mission of 2016. KORUS-AQ was planned for the period after the spring peak in outbreaks of ...Asian dust. Regardless of this strategic planning, quantifiable dust was still observed via instrumentation on the NASA DC-8 in early May. A novel analysis of supermicron dust and associated supermicron ionic relationships was completed using two size dependent instruments. This supermicron dust provided surface area for heterogeneous chemistry between CaCO3, the gases HNO3, NO2, and SO2, and particulate (NH4)2SO4. Uptake of the pollutant gases is greatly enhanced by formation of an aqueous layer on the surface of the dust particles. More water is attracted to particles where uptake of HNO3 has replaced surface CaCO3 with Ca(NO3)2 generating a dynamic aqueous layer on the dust particle. We propose that particulate (NH4)2SO4 coagulated with dust to form (NH4)2Ca(SO4)2 on the particle surface, which rapidly formed CaSO4 and NH4+ in a Ca(NO3)2 facilitated aqueous layer. A conceptual model is proposed to explain these dust uptake chemical processes. We define the nanoequivalent concentration of supermicron SO42− plus NO3− over the nanoequivalent concentration of supermicron NH4+ plus Ca2+ as the Dust Pollution Index (DPI), used to quantify the extent to which carbonate dust has been modified. DPI values range from 0 (pure dust) to 1 (completely reacted); thus, it represents the conversion of CaCO3 into secondary salts. This mechanism should be used to better predict chemical dynamics in atmospheric models while also helping to further explain the importance of dust and secondary coating on cloud formation processes and dust optical properties. Air masses containing dust that traversed industrial China while mixing with polluted southern air had significantly higher DPI values (average = 0.82, 1σ = 0.10) compared to air masses that limited interaction with such pollution (average = 0.51, 1σ = 0.13).
•Supermicron dust collected during KORUS-AQ was chemically modified during transport, taking up HNO3 and (NH4)2SO4.•(NH4)2SO4 particles coagulated with dust while gas phase HNO3 reacted and modified the dust to be hygroscopic.•A conceptual model and the Dust Pollution Index are proposed to explain these uptake mechanisms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Heart transplantation from donation after circulatory death (DCD) donors is a rapidly expanding practice. In this review, we describe the history and challenges of DCD heart transplantation and ...overview the procurement protocols and methods of limiting ischemic injury, current outcomes, and future directions. There are now at least three protocols that permit resuscitation and viability assessment of the DCD heart either in situ or ex situ. While the retrieval protocol for hearts from DCD donors will depend on local regulations, the outcomes of DCD heart transplant recipients reported to date are excellent regardless of the retrieval protocol and are comparable to the outcomes of heart transplant recipients from donation after brain death (DBD) donors. In the two centers with the largest published experience, DCD heart transplantation now accounts for one third of their heart transplant activity. With international trends indicating that there is an increasing utilisation of the DCD pathway, it is expected that DCD donors will become a major source of heart donation worldwide.
In situ measurements of ozone, photochemically active bromine compounds, and other trace gases over the Arctic Ocean in April 2008 are used to examine the chemistry and geographical extent of ozone ...depletion in the arctic marine boundary layer (MBL). Data were obtained from the NOAA WP-3D aircraft during the Aerosol, Radiation, and Cloud Processes affecting Arctic Climate (ARCPAC) study and the NASA DC-8 aircraft during the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) study. Fast (1 s) and sensitive (detection limits at the low pptv level) measurements of BrCl and BrO were obtained from three different chemical ionization mass spectrometer (CIMS) instruments, and soluble bromide was measured with a mist chamber. The CIMS instruments also detected Br2. Subsequent laboratory studies showed that HOBr rapidly converts to Br2 on the Teflon instrument inlets. This detected Br2 is identified as active bromine and represents a lower limit of the sum HOBr + Br2. The measured active bromine is shown to likely be HOBr during daytime flights in the arctic. In the MBL over the Arctic Ocean, soluble bromide and active bromine were consistently elevated and ozone was depleted. Ozone depletion and active bromine enhancement were confined to the MBL that was capped by a temperature inversion at 200–500 m altitude. In ozone-depleted air, BrO rarely exceeded 10 pptv and was always substantially lower than soluble bromide that was as high as 40 pptv. BrCl was rarely enhanced above the 2 pptv detection limit, either in the MBL, over Alaska, or in the arctic free troposphere.
In-situ airborne measurements of trace gases, aerosol size distributions, chemistry and optical properties were conducted over Mexico and the Eastern North Pacific during MILAGRO and INTEX-B. ...Heterogeneous reactions between secondary aerosol precursor gases and mineral dust lead to sequestration of sulfur, nitrogen and chlorine in the supermicrometer particulate size range. Simultaneous measurements of aerosol size distributions and weak-acid soluble calcium result in an estimate of 11 wt% of CaCO3 for Asian dust. During transport across the North Pacific, ~5–30% of the CaCO3 is converted to CaSO4 or Ca(NO3)2 with an additional ~4% consumed through reactions with HCl. The 1996 to 2008 record from the Mauna Loa Observatory confirm these findings, indicating that, on average, 19% of the CaCO3 has reacted to form CaSO4 and 7% has reacted to form Ca(NO3)2 and ~2% has reacted with HCl. In the nitrogen-oxide rich boundary layer near Mexico City up to 30% of the CaCO3 has reacted to form Ca(NO3)2 while an additional 8% has reacted with HCl. These heterogeneous reactions can result in a ~3% increase in dust solubility which has an insignificant effect on their optical properties compared to their variability in-situ. However, competition between supermicrometer dust and submicrometer primary aerosol for condensing secondary aerosol species led to a 25% smaller number median diameter for the accumulation mode aerosol. A 10–25% reduction of accumulation mode number median diameter results in a 30–70% reduction in submicrometer light scattering at relative humidities in the 80–95% range. At 80% RH submicrometer light scattering is only reduced ~3% due to a higher mass fraction of hydrophobic refractory components in the dust-affected accumulation mode aerosol. Thus reducing the geometric mean diameter of the submicrometer aerosol has a much larger effect on aerosol optical properties than changes to the hygroscopic:hydrophobic mass fractions of the accumulation mode aerosol. In the presence of dust, nitric acid concentrations are reduced to <50% of total nitrate (nitric acid plus particulate nitrate). NOy as a fraction of total nitrogen (NOy plus particulate nitrate), is reduced from >85% to 60–80% in the presence of dust. These observations support previous model studies which predict irreversible sequestration of reactive nitrogen species through heterogeneous reactions with mineral dust during long-range transport.
Most intensive field studies investigating aerosols have been conducted in summer, and thus, wintertime aerosol sources and chemistry are comparatively poorly understood. An aerosol mass spectrometer ...was flown on the National Science Foundation/National Center for Atmospheric Research C‐130 during the Wintertime INvestigation of Transport, Emissions, and Reactivity (WINTER) 2015 campaign in the northeast United States. The fraction of boundary layer submicron aerosol that was organic aerosol (OA) was about a factor of 2 smaller than during a 2011 summertime study in a similar region. However, the OA measured in WINTER was almost as oxidized as OA measured in several other studies in warmer months of the year. Fifty‐eight percent of the OA was oxygenated (secondary), and 42% was primary (POA). Biomass burning OA (likely from residential heating) was ubiquitous and accounted for 33% of the OA mass. Using nonvolatile POA, one of two default secondary OA (SOA) formulations in GEOS‐Chem (v10‐01) shows very large underpredictions of SOA and O/C (5×) and overprediction of POA (2×). We strongly recommend against using that formulation in future studies. Semivolatile POA, an alternative default in GEOS‐Chem, or a simplified parameterization (SIMPLE) were closer to the observations, although still with substantial differences. A case study of urban outflow from metropolitan New York City showed a consistent amount and normalized rate of added OA mass (due to SOA formation) compared to summer studies, although proceeding more slowly due to lower OH concentrations. A box model and SIMPLE perform similarly for WINTER as for Los Angeles, with an underprediction at ages <6 hr, suggesting that fast chemistry might be missing from the models.
Key Points
Wintertime organic aerosol (OA) was almost as oxidized as in summer studies, with wood burning OA being an important contributor to primary OA
SOA formation rate and amount is similar to summer (accounting for lower OH). A box model reproduces SOA, but fast chemistry may be missing
The default GEOS‐Chem formulation with nonvolatile POA shows large errors. The SIMPLE and semivolatile parameterizations perform better
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Bulk aerosol composition and aerosol size distributions measured aboard the DC‐8 aircraft during the Deep Convective Clouds and Chemistry Experiment mission in May/June 2012 were used to investigate ...the transport of mineral dust through nine storms encountered over Colorado and Oklahoma. Measurements made at low altitudes (<5 km mean sea level (MSL)) in the storm inflow region were compared to those made in cirrus anvils (altitude > 9 km MSL). Storm mean outflow Ca2+ mass concentrations and total coarse (1 µm < diameter < 5 µm) aerosol volume (Vc) were comparable to mean inflow values as demonstrated by average outflow/inflow ratios greater than 0.5. A positive relationship between Ca2+, Vc, ice water content, and large (diameter > 50 µm) ice particle number concentrations was not evident; thus, the influence of ice shatter on these measurements was assumed small. Mean inflow aerosol number concentrations calculated over a diameter range (0.5 µm < diameter < 5.0 µm) relevant for proxy ice nuclei (NPIN) were ~15–300 times higher than ice particle concentrations for all storms. Ratios of predicted interstitial NPIN (calculated as the difference between inflow NPIN and ice particle concentrations) and inflow NPIN were consistent with those calculated for Ca2+ and Vc and indicated that on average less than 10% of the ingested NPIN were activated as ice nuclei during anvil formation. Deep convection may therefore represent an efficient transport mechanism for dust to the upper troposphere where these particles can function as ice nuclei cirrus forming in situ.
Key Points
Dust transport through convection examined using aircraft observations
Less than half of the inflow coarse dust removed by cloud processes
Influence of ice particle shatter on observations appears minimal
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Our current understanding of atmospheric mercury lacks fundamental details. Gas phase elemental mercury (Hg°) was measured aboard the NASA DC‐8 research aircraft during the Intercontinental Chemical ...Transport Experiment‐Phase B (INTEX‐B) conducted in spring 2006 over the North Pacific. Our data confirm efficient chemical cycling of Hg° in the tropopause region and show that it is strongly anti‐correlated with O3 there, yielding a tropospheric‐stratospheric mixing curve of ∼−0.20 ppqv Hg°/ppbv O3. In addition, we found frequent total depletion of Hg° in upper tropospheric (8–12 km) air masses impacted by stratospheric influence. When O3 mixing ratios were >300 ppbv, Hg° was rarely detected. It appears that in the tropopause and stratosphere Hg° is oxidized on the order of days followed by heterogeneous transformation to particulate mercury. These processes constitute an effective chemical sink for Hg° at the top of the troposphere, which may recycle mercury back to the gas phase as stratospheric aerosols are eventually dispersed into the troposphere.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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