Hg Resistance Research Articles

Mercury emission from industrially contaminated soils in relation to chemical, microbial, and meteorological factors

The Minamata Convention entered into force in 2017 with the aim to phase-out the use of mercury (Hg) in manufacturing processes such as the chlor-alkali or vinyl chloride monomer production. However, past industrial use of Hg had already resulted in extensive soil pollution, which poses a potential environmental threat. We investigated the emission of gaseous elemental mercury (Hg0) from Hg polluted soils in settlement areas in the canton of Valais, Switzerland, and its impact on local air Hg concentrations. Most soil Hg was found as soil matrix-bound divalent Hg (HgII). Elemental mercury (Hg0) was undetectable in soils, yet we observed substantial Hg0 emission (20–1392 ng m−2 h−1) from 27 soil plots contaminated with Hg (0.2–390 mg Hg kg−1). The emissions of Hg0 were calculated for 1274 parcels covering an area of 8.6 km2 of which 12% exceeded the Swiss soil remediation threshold of 2 mg Hg kg−1. The annual Hg0 emission from this area was approximately 6 kg a−1, which is almost 1% of the total atmospheric Hg emissions in Switzerland based on emission inventory estimates. Our results show a higher abundance of Hg resistance genes (merA) in soil microbial communities with increasing soil Hg concentrations, indicating that biotic reduction of HgII is likely an important pathway to form volatile Hg0 in these soils. The total soil Hg pool in the top 20 cm of the investigated area was 4288 kg; hence, if not remediated, these contaminated soils remain a long-term source of atmospheric Hg, which is prone to long-range atmospheric transport.

Low-Molecular-Weight Thiols and Thioredoxins Are Important Players in Hg(II) Resistance in Thermus thermophilus HB27.

Mercury (Hg), one of the most toxic and widely distributed heavy metals, has a high affinity for thiol groups. Thiol groups reduce and sequester Hg. Therefore, low-molecular-weight (LMW) and protein thiols may be important cell components used in Hg resistance. To date, the role of low-molecular-weight thiols in Hg detoxification remains understudied. The mercury resistance (mer) operon of Thermus thermophilus suggests an evolutionary link between Hg(II) resistance and low-molecular-weight thiol metabolism. The mer operon encodes an enzyme involved in methionine biosynthesis, Oah. Challenge with Hg(II) resulted in increased expression of genes involved in the biosynthesis of multiple low-molecular-weight thiols (cysteine, homocysteine, and bacillithiol), as well as the thioredoxin system. Phenotypic analysis of gene replacement mutants indicated that Oah contributes to Hg resistance under sulfur-limiting conditions, and strains lacking bacillithiol and/or thioredoxins are more sensitive to Hg(II) than the wild type. Growth in the presence of either a thiol-oxidizing agent or a thiol-alkylating agent increased sensitivity to Hg(II). Furthermore, exposure to 3 μM Hg(II) consumed all intracellular reduced bacillithiol and cysteine. Database searches indicate that oah2 is present in all Thermus sp. mer operons. The presence of a thiol-related gene was also detected in some alphaproteobacterial mer operons, in which a glutathione reductase gene was present, supporting the role of thiols in Hg(II) detoxification. These results have led to a working model in which LMW thiols act as Hg(II)-buffering agents while Hg is reduced by MerA.IMPORTANCE The survival of microorganisms in the presence of toxic metals is central to life's sustainability. The affinity of thiol groups for toxic heavy metals drives microbe-metal interactions and modulates metal toxicity. Mercury detoxification (mer) genes likely originated early in microbial evolution in geothermal environments. Little is known about how mer systems interact with cellular thiol systems. Thermus spp. possess a simple mer operon in which a low-molecular-weight thiol biosynthesis gene is present, along with merR and merA In this study, we present experimental evidence for the role of thiol systems in mercury resistance. Our data suggest that, in T. thermophilus, thiolated compounds may function side by side with mer genes to detoxify mercury. Thus, thiol systems function in consort with mer-mediated resistance to mercury, suggesting exciting new questions for future research.

Sex-based differences in veterans with pulmonary hypertension: Results from the veterans affairs-clinical assessment reporting and tracking database.

Women have an increased risk of pulmonary hypertension (PH) but better survival compared to men. Few studies have explored sex-based differences in population-based cohorts with PH. We sought to determine whether sex was associated with hemodynamics and survival in US veterans with PH (mean pulmonary artery pressure [mPAP] ≥ 25 mm Hg) from the Veterans Affairs Clinical Assessment, Reporting, and Tracking database. The relationship between sex and hemodynamics was assessed with multivariable linear mixed modeling. Cox proportional hazards models were used to compare survival by sex for those with PH and precapillary PH (mPAP ≥ 25 mm Hg, pulmonary artery wedge pressure [PAWP] ≤ 15 mm Hg and pulmonary vascular resistance [PVR] > 3 Wood units) respectively. The study population included 15,464 veterans with PH, 516 (3%) of whom were women; 1,942 patients (13%) had precapillary PH, of whom 120 (6%) were women. Among those with PH, women had higher PVR and pulmonary artery pulse pressure, and lower right atrial pressure and PAWP (all p <0.001) compared with men. There were no significant differences in hemodynamics according to sex in veterans with precapillary PH. Women with PH had 18% greater survival compared to men with PH (adjusted HR 0.82, 95% CI 0.69–0.97, p = 0.020). Similarly, women with precapillary PH were 29% more likely to survive as compared to men with PH (adjusted HR 0.71, 95% CI 0.52–0.98, p = 0.040). In conclusion, female veterans with PH have better survival than males despite higher pulmonary afterload.

Evaluación diagnóstica en hipertensión arterial pulmonar

Pulmonary arterial hypertension is a rare pathological condition of the pulmonary circulation, and is defined as the increase in pulmonary arterial pressure (PAPm) ≥ 25mm Hg with a trough of ≤ 15mm Hg and pulmonary vascular resistance (PVR) of > 3 Wood Units, determined at rest and using right-heart catheterisation. Pulmonary arterial hypertension belongs to Group 1 of the pulmonary hypertension classification, a group consisting of conditions considered as “rare”, and its diagnosis requires ruling out the presence of other causes of pulmonary hypertension. The complexity of the disease and the use of highly specialised procedures for its diagnosis makes it necessary and desirable to refer to experienced or reference centres in the management of the disease. However, there are diagnostic approaches that could be brought forward in Primary Health Care centres and thus, speed up the diagnostic process.

Predictors of Waitlist Mortality in Portopulmonary Hypertension.

The current Organ Procurement Transplantation Network policy grants Model for End-Stage Liver Disease (MELD) exception points to patients with portopulmonary hypertension (POPH), but potentially important factors, such as severity of liver disease and pulmonary hypertension, are not included in the exception score, and may affect survival. The purpose of this study was to identify significant predictors of waitlist mortality in patients with POPH. We performed a retrospective cohort study of patients in the Organ Procurement and Transplantation Network database with hemodynamics consistent with POPH (defined as mean pulmonary arterial pressure >25 mm Hg and pulmonary vascular resistance [PVR] ≥240 dynes·s·cm) who were approved for a POPH MELD exception between 2006 and 2014. Using a Cox proportional hazards model, we identified predictors of waitlist mortality (or removal for clinical deterioration). One hundred ninety adults were included. Age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.08; P = 0.0499), initial native MELD score (HR, 1.11; 95% CI, 1.05-1.17; P < 0.001), and initial PVR (HR, 1.12 per 100 dynes·s·cm; 95% CI, 1.02-1.23; P = 0.02) were the only significant univariate predictors of waitlist mortality and remained significant predictors in a multivariate model, which had a c-statistic of 0.71. PVR and mean pulmonary arterial pressure were not significant predictors of posttransplant mortality. Both the severity of liver disease and POPH (as assessed by MELD and PVR, respectively) were significantly associated with waitlist, but not posttransplant, mortality in patients with approved MELD exceptions for POPH. Both factors should potentially be included in the POPH MELD exception score to more accurately reflect waitlist mortality risk.

Occurrence, abundance, and distribution of sulfonamide and tetracycline resistance genes in agricultural soils across China

The prevalence and proliferation of antibiotic resistance genes (ARGs) have been identified as an emerging contaminant of concern and a crucial threat to public health worldwide. In this study, we carried out a nation-wide sampling campaign across China to investigate the distribution and abundances of 8 major ARGs in agricultural soils. The levels of sulfonamide (sul) and tetracycline (tet) resistance genes in China's agricultural soils ranged from 10−6–10−2 to 10−8–10−2 gene copies/16S rRNA gene copies, respectively. Northeast China is the hot-spot of ARGs, likely due to long-term wastewater irrigation in the area. Redundancy analysis was further performed to assess the influences of environmental variables on ARG abundances. Sulfonamide resistance genes displayed strong correlations with meteorological parameters (mean annual precipitation and temperature), and decreased from north to south. In comparison, tetracycline resistance genes were more closely related to soil organic matter and pH. Co-selection between heavy metals and ARGs was significant among Cu, Hg and sulfonamide resistance genes. This study highlighted the current status of ARG contamination and their influencing factors in China's agricultural soils. Findings are valuable to identify effective management options for reducing the release of antibiotics and control ARG spread in the agriculture sector across the world.

Alkaline Phosphatase Inhibitors Attenuate Renovascular Responses to Norepinephrine.

Tissue nonspecific alkaline phosphatase (TNAP) contributes to the production of adenosine by the kidney, and A1-receptor activation enhances renovascular responses to norepinephrine. Therefore, we hypothesized that TNAP regulates renovascular responsiveness to norepinephrine. In isolated, perfused rat kidneys, the TNAP inhibitor l-p-bromotetramisole (0.1 mmol/L) decreased renal venous levels of 5'-AMP (adenosine precursor) and adenosine by 61% (P<0.0384) and 62% (P=0.0013), respectively, at 1 hour into treatment and caused a 10-fold rightward shift of the concentration-response relationship to exogenous norepinephrine (P<0.0001). Similarly, 2 other TNAP inhibitors, levamisole (1 mmol/L) and 2,5-dimethoxy-N-(quinolin-3-yl)benzenesulfonamide (0.02 mmol/L), also right shifted the concentration-response relationship to norepinephrine. The ability of TNAP inhibition to blunt renovascular responses to norepinephrine was mostly prevented or reversed by restoring A1-adenosinergic tone with the A1-receptor agonist 2-chloro-N6-cyclopentyladenosine (100 nmol/L). All 3 TNAP inhibitors also attenuated renovascular responses to renal sympathetic nerve stimulation, suggesting that TNAP inhibition attenuates renovascular responses to endogenous norepinephrine. In control propranolol-pretreated rats, acute infusions of norepinephrine (10 μg/kg/min) increased mean arterial blood pressure from 95±5 mm Hg to a peak of 169±4 mm Hg and renovascular resistance from 12±2 mm Hg/mL/min to a peak of 55±12 mm Hg/mL/min; however, in rats also treated with intravenous l-p-bromotetramisole (30 mg/kg), the pressor and renovascular effects of norepinephrine were significantly attenuated (blood pressure: basal and peak, 93±7 and 146±6 mm Hg, respectively; renovascular resistance: basal and peak, 13±2 and 29±5 mm Hg/mL/min, respectively). TNAP inhibitors attenuate renovascular and blood pressure responses to norepinephrine, suggesting that TNAP participates in the regulation of renal function and blood pressure.

Paleomicrobiology to investigate copper resistance in bacteria: isolation and description of Cupriavidus necator B9 in the soil of a medieval foundry

Remains of a medieval foundry were excavated by archaeologists in 2013 in Verdun (France). Ancient workshops specialized in brass and copper alloys were found with an activity between 13th to 16th c. Levels of Cu, Zn and Pb reached 20000, 7000 and 6000 mg kg-1 (dw), respectively, in several soil horizons. The objective of the present work was to examine the microbial community in this contaminated site. A total of 8-22 106 reads were obtained by shotgun metagenomics in four soil horizons. Bioinformatic analyses suggest the presence of complex bacterial communities dominated by Proteobacteria. The structure of the community was not affected by metals, contrary to the set of metal-resistance genes. Using selective media, a novel strain of Cupriavidus necator (eutrophus), strain B9, was isolated. Its genome was sequenced and a novel metal resistance gene cluster with Hg resistance genes (merRTPCA) followed by 24 copper-resistance genes (actP, cusCBAF, silP, copK1, copH4QLOFGJH3IDCBARS, copH2H1, copK2) was found. This cluster is partly homologous to the cop genes of Cupriavidus gilardii CR3 and C. metallidurans CH34. Proteomics indicated that the four copH genes were differentially expressed: CopH1 and CopH2 were mostly induced by Cd while CopH4 was highly expressed by Cu.

Usefulness of Echocardiography/Doppler to Reliably Predict Elevated Left Ventricular End-Diastolic Pressure in Patients With Pulmonary Hypertension

The ability of echocardiography (echo)/Doppler to predict elevated left ventricular (LV) end-diastolic pressure (EDP) specifically among patients with pulmonary hypertension is not well defined. This was a retrospective analysis of 161 patients referred to a specialized pulmonary hypertension clinic. A model based on an American Society of Echocardiography (ASE)/European Association of Echocardiography (EAE) joint statement was evaluated, and a new model was developed using univariate linear regression and multivariable logistic regression for potentially better prediction of elevated LVEDP. The study cohort had a median pulmonary arterial pressure was 34.0mm Hg and pulmonary vascular resistance was 3.7 Wood units; 81 patients (51%) had LVEDP >15mm Hg on invasive testing. Doppler E/A, E/e' (septal, lateral, and average), e'/a' (lateral and average), and left atrial volume and diameter all had significant correlation with LVEDP (p <0.05). The ASE/EAE model performed poorly (sensitivity 54% and specificity 66%) for detecting elevated LVEDP. Only echo/Doppler grade 3 diastolic dysfunction had an LVEDP significantly different from other grades (grade 0 to 2, median 15mm Hg, interquartile range 13 to 22mm Hg; grade 3, median 22mm Hg, interquartile range 19 to 32mm Hg; p <0.01). An experimental model was statistically significant in its prediction of elevated LVEDP (area under the receiver operating characteristic curve 0.7, p <0.001) but demonstrated poor performance (sensitivity 67% and specificity 61%). In conclusion, numerous echo/Doppler measurements correlate with elevated LV filling pressure. However, both the ASE/EAE model and our experimental model had poor test performance that did not permit confident identification of elevated LVEDP.

Co-selection of Mercury and Multiple Antibiotic Resistances in Bacteria Exposed to Mercury in the Fundulus heteroclitus Gut Microbiome.

The emergence and spread of antibiotic-resistant pathogenic bacteria is currently one of the most serious challenges to human health. To combat this problem, it is critical to understand the processes and pathways that result in the creation of antibiotic resistance gene pools in the environment. In this study, we examined the effects of mercury (Hg) exposure on the co-selection of Hg and antibiotic-resistant bacteria that colonize the gastrointestinal tract of the mummichog (Fundulus heteroclitus), a small, estuarine fish. We examined this connection in two experimental systems: (i) a short-term laboratory exposure study where fish were fed Hg-laced food for 15days and (ii) an examination of environmental populations from two sites with very different levels of Hg contamination. In the lab exposure study, fish muscle tissue accumulation of Hg was proportional to food Hg concentration (R 2=0.99; P<0.0001). In the environmental study, fish from the contaminated site contained threefold more Hg compared to fish from the reference site (P<0.05). Further, abundance of the Hg resistance gene mercuric reductase was more than eightfold higher (P<0.0001) in DNA extracts of ingesta of fish from the contaminated site, suggesting adaptation to Hg. Finally, resistance to three or more antibiotics was more common in Hg-resistant as compared to Hg-sensitive bacterial colonies that were isolated from fish ingesta (P<0.001) demonstrating co-selection of Hg and antibiotic resistances. Together, our results highlight the possibility for the creation of antibiotic resistance gene pools as a result of exposure to Hg in contaminated environments.

Mercury resistance and volatilization by Pseudoxanthomonas sp. SE1 isolated from soil

Abstract A mercury resistant bacterial strain SE1 isolated from contaminated soil was identified as Pseudoxanthomonas based on 16s rRNA sequencing. The Hg resistance was examined in both nutrient-rich media as well as low nutrient media and expressed as EC50 and MIC values. Estimated EC50 and MIC values in nutrient-rich media and low nutrient media had the following respective recordings — 22.6 mg L−1; 23.1 mg L−1 and 1.4 mg L−1 and 1.7 mg L−1. The isolate was able to volatilize inorganic mercury demonstrated by a modified photographic film experiment and subsequently revealed its ability to remove mercury from the solution. The ICP-QQQ-MS analysis of SE1 inoculated solution showed almost 60% of 1.5 mg L−1 mercury was volatilized in 6 h and almost 40% were accumulated in cell pellets. The mercuric reductase gene merA was identified in the genome of isolate SE1 and sequenced. The deduced amino acid sequence of merA gene indicated a sequence homology with different organisms from the alpha proteobacteria group and eukaryotic fungi. merA encoded enzyme mercuric reductase activity was evident in the crude protein of the isolate. The isolate’s ability to resist Hg, it’s Hg volatilization potential and the presence of merA gene and mercuric reductase enzyme demonstrates the potential application of this strain in mercury bioremediation.

Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort.

Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s(-1)·cm(-5) at reassessment correlated with worse long-term survival. Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.

Shape of the Pulmonary Artery Doppler-Flow Profile Predicts the Hemodynamics of Pulmonary Hypertension Caused by Left-Sided Heart Disease.

Previous studies demonstrated a relationship between pulmonary hemodynamics and shape of pulmonary artery (PA) Doppler-flow profiles in a mixed pulmonary hypertension (PH) cohort. Shape of PA Doppler-flow profiles could illustrate the hemodynamic characteristics of pulmonary venous hypertension (PVH), especially identifying it with or without pulmonary vascular disease (PVD). We retrospectively analyzed hemodynamic, echocardiographic, and clinical data from 47 patients referred for PH caused by left-sided heart disease (PH-LHD). All patients underwent right-sided heart catheterization within 1 week of echocardiography. We concluded a simple echocardiographic prediction rule to give hemodynamic differentiation of PVH with PVD, defined as capillary wedge pressure >15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units (WU). The PA Doppler-flow profiles were categorized into 2 groups, no notch (NN) and MSN/LSN. The PVR was higher in the MSN/LSN group at 4.04 WU (interquartile range, 3.1-5.3) vs the NN group at 1.91 WU (interquartile range, 1.8-3.0; P < 0.001). Pulmonary artery Doppler-flow notching (MSN and LSN) was highly associated with PVR >3 WU, whereas the NN pattern predicted a PVR ≤3 WU (odds ratio: 19.8, 95% confidence interval: 4.3-91.3) and normal transpulmonary pressure gradient ≤12 mm Hg (odds ratio: 4.7, 95% confidence interval: 1.3-16.2). The NN pattern had 74% specificity and 88% sensitivity for PVR ≤3 WU. Absence of PA Doppler-flow notching was highly associated with PVH, and a notching pattern indicated PVH with PVD in the PH-LHD cohort.

Abstract 15284: Blessing in Disguise: Absent Pulmonary Valve in an Adult Without Ventricular Septal Defect

Introduction: Congenital absence of the pulmonary valve (APV) is a rare cardiac malformation. Adults with this condition generally need corrective surgery before the age of 20. We report a unique case of an isolated APV in a Jamaican female who remained asymptomatic until presentation at the age of 39. Case: Patient presented to a local cardiologist with recent onset of NYHA II symptoms and atrial fibrillation. Her cardiovascular exam revealed a right ventricular (RV) heave , III/VI holosystolic murmur along right lower sternal border, III/VI early diastolic murmur in pulmonic area, no clinical signs of right heart failure (RHF). Diagnostics: An echocardiogram showed dilated RV outflow tract, APV, dilated main pulmonary artery (MPA) and severe pulmonary regurgitation (PR) (Figure 1A). RV size and function were quantified with cardiac MRI demonstrating RV end diastolic volume: 340 ml/m2 (Z score 11.9) and RVEF: 46% ( Z score -2.8) (Figure 1B). Flow data of the MPA showed a flow of 4.9L/min, severe PR with a regurgitant fraction of 48% and Qp/Qs of 1.1:1 (Figure 1C). Right heart catheterization demonstrated equalization of diastolic pressure in both RV and PA (52/10 mm Hg) diagnostic of free PR. (Figure 1D). Mean PA pressure was 24 mm Hg and pulmonary vascular resistance was 3 wu. On cardiopulmonary stress testing, the patient completed 10.6 METS, achieving a peak VO2 of 18.5 ml/kg/min at RER 1.1. Discussion: APV is commonly categorized as with or without ventricular septal defect (VSD). APV with VSD is commonly associated with tetralogy of Fallot (TOF). The distinguishing features from TOF are: unobstructed RV infundibulum and aneurysmally dilated PA. APV in its severe form presents in infancy with severe respiratory distress from bronchial obstruction caused by massively dilated PAs. Isolated APV (non VSD type) is a rare variant. Our report is the first in literature to illustrate isolated APV in an asymptomatic adult approaching the fourth decade of her life.

Mercury Reduction and Methyl Mercury Degradation by the Soil Bacterium Xanthobacter autotrophicus Py2.

Two previously uncharacterized potential broad-spectrum mercury (Hg) resistance operons (mer) are present on the chromosome of the soil Alphaproteobacteria Xanthobacter autotrophicus Py2. These operons, mer1 and mer2, contain two features which are commonly found in mer operons in the genomes of soil and marine Alphaproteobacteria, but are not present in previously characterized mer operons: a gene for the mercuric reductase (MerA) that encodes an alkylmercury lyase domain typical of those found on the MerB protein, and the presence of an additional gene, which we are calling merK, with homology to glutathione reductase. Here, we demonstrate that Py2 is resistant to 0.2 μM inorganic mercury [Hg(II)] and 0.05 μM methylmercury (MeHg). Py2 is capable of converting MeHg and Hg(II) to elemental mercury [Hg(0)], and reduction of Hg(II) is induced by incubation in sub toxic concentrations of Hg(II). Transcription of the merA genes increased with Hg(II) treatment, and in both operons merK resides on the same polycistronic mRNA as merA. We propose the use of Py2 as a model system for studying the contribution of mer to Hg mobility in soil and marine ecosystems.

Abstract P148: Neck Circumference as an Independent Contributor to Cardio Metabolic Risk Factors - ELSA BRASIL

Background: Neck circumference is a proxy for upper body fat and it is a simple anthropometric measure. Therefore it could be a useful tool to identify individuals with cardiometabolic risk factors in the context of primary care. Hypothesis: Neck circumference is independently associated to cardiometabolic risk factors in an apparently healthy population. Methods: This is a cross-sectional analysis of baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a cohort of 15105 civil servants aged 35-74 years. We excluded from this analysis those who fulfilled American Diabetes Association criteria for diabetes diagnosis, were taking antihypertensive and/or lipid-lowering drugs. A sex-specific analysis was conducted. Partial correlation (age-adjusted) was used. Risk factors were set as low HDL&lt;50mg/dL for women and &lt;40mg/dL for men, hypertriglyceridemia ≥ 150 mg/dl , hypertension as systolic blood pressure ≥130 mg/dl or diastolic blood pressure ≥85 mm Hg and insulin resistance(HOMA-IR ≥ 75th percentile). Logistic regression models were built to analyze the association between individual and clustered risk factors as dependent variables and 1-SD increase in neck circumference as independent variable. Multiple adjustments were subsequently performed for age, smoking, alcohol, body-mass index, waist and physical activity. Receiver Operating Curves were employed to find the best NC cut-off points for clustered risk factors. Results: We analyzed 3810 men (mean age= 49.0 ±8.3 yrs) and 4916 women (49.2 ±8.0 yrs). Mean NC was 38.9 (±2.6)cm for men and 33.4(±2.6)cm for women. NC positively correlated with systolic and diastolic blood pressure (r=0.21 and r=0.27), HOMA - IR (r=0.44), triglycerides (r=0.31) and negatively correlated with HDL (r= -0.21) in men (p&lt;0.001 for all) with similar results in women. Fully adjusted Odds Ratio (OR) (95% CI) of risk factor per SD increase in neck circumference in men and women were 1.29(1.14;1.46) and 1.42(1.28;1.57) for insulin resistance; 1.24(1.11;1.39) and 1.25(1.11;1.40) for hypertension; 1.33(1.19;1.49) and 1.42(1.29;1.63) for hypertriglyceridemia; 1.07(0.92;1.23) and 1.32 (1.19;1.43) for low HDL. Fully adjusted OR (95% CI) of 2 clustered risk factor per SD increase in neck circumference in men and women were 1.29(1.14;1.48) and 1.37(1.21;1.54 ). Fully adjusted OR (95% CI) of 3 or more clustered risk factors per SD increase in neck circumference in men and women were 1.33 (1.02;1.74) and 1.62 (1.33;1.92). Values of neck circumference of &gt;40 cm for men and &gt;34.1 cm for women were the best cut-off points for 3 or more clustered risk factors. Conclusion: Neck circumference is significantly and independently associated to cardiometabolic risk factors in a well-defined non-treated population. It should be considered as a marker of cardio metabolic risk factors in primary care settings.

Advanced Imaging Tools Rather Than Hemodynamics Should Be the Primary Approach for Diagnosing, Following, and Managing Pulmonary Arterial Hypertension

Pulmonary hypertension (PH) is currently defined based on invasive measurements: a resting pulmonary artery pressure ≥ 25 mm Hg. For pulmonary arterial hypertension, a pulmonary arterial wedge pressure ≤ 15 mm Hg and pulmonary vascular resistance > 3 Wood units are also required. Thus, right heart catheterization is inevitable at present. However, the diagnosis, follow-up, and management of PH by noninvasive techniques is progressing. Significant advances have been achieved in the imaging of pulmonary vascular disease and the right ventricle. We review the current sensitivities and specificities of noninvasive imaging of PH and discuss its role and future potential to replace hemodynamics as the primary approach to screening, diagnosing, and following/managing PH.

SUCCESSFUL MEDICATION THERAPY OF ACUTE RIGHT VENTRICLE INSUFFICIENCY IN RECIPIENT WITH SIGNIFICANT PULMONARY HYPERTENSION AFTER HEART TRANSPLANTATION

Acute right ventricular failure in the early period after orthotopic heart transplantation is a severe complication and can often lead to a fatal outcome. This is especially important in patients with high pulmonary arteries resistance. Drug therapy has shown effectiveness only for the treatment of primary pulmonary hypertension. Patient K., 23 years old with signifi cant pulmonary hypertension (mean pulmonary artery pressure of 60 mm Hg, PVR – 6 Wood units) underwent orthotopic heart transplantation. Acute right ventricular failure occurred at early postoperative period which required multicomponent inotropic support. In order to reduce resistance of the pulmonary circulation the patient received sildenafi l (daily dose 50 mg) in combination with inhaled Ventavis (5 mcg a dose every 3 hours) and receipt of Tracleer (bosentan) (at a dose of 125 mg per day). Complex drug therapy resulted in reduction of right ventricular failure, normalization of biochemical parameters. Invasive pulmonary artery pressure decreased to 30 mm Hg and pulmonary vascular resistance was 1.1 Wood units at the moment of discharge. We also revealed right ventricle end-diastolic volume reduction from 70 ml to 62 ml and ejection fraction of the right ventricle (RV EF) increased from 47,7% to 62% in 2 months. Our clinical observation demonstrates the high effi ciency of acute right heart failure complex therapy including inotropic agents in combination with drugs that reduce the pulmonary vascular resistance.

INVESTIGATION OF CENTRAL HEMODYNAMICS VIA RIGHT HEART AND PULMONARY ARTERY CATHETERIZATION IN PATIENTS WITH SYSTEMIC CONNECTIVE TISSUE DISEASES

Pulmonary arterial hypertension (PAH) associated with systemic connective tissue diseases (SCTD) is a poor prognostic manifestation of the latter that result in death if untreated. The invasive determination of hemodynamic parameters is prominent in diagnosing the disease and determining its treatment policy and prognosis. Objective : to analyze the results of catheterization in PAH-SCTD patients admitted to the V.A. Nasonova Research Institute of Rheumatology. Subjects and methods . The investigation included 59 patients admitted to the V.A. Nasonova Research Institute of Rheumatology from September 2009 to September 2014. PAH was diagnosed in accordance with the conventional guidelines. All the patients underwent right heart and pulmonary artery (PA) catheterization at the diagnosis and over time during treatment. Results and discussion. All the patients included in the trial met the pre-capillary pulmonary hypertension (PH) criteria: mean pulmonary artery pressure (MPAP) ≥25 mm Hg; and PA wedge pressure (PAWP) 15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units could diagnose PAH in all our patients. There was a statistically highly significant association between pathological hemodynamic changes and functional class (FC). FC was found to be most closely correlated with right atrial pressure (RAP), cardiac output (CO), PVR, and cardiac index (CI). Among the most common manifestations of heart failure, only the presence of peripheral edemas was associated with worse hemodynamic parameters in PAH. It should be noted that out of two biomarkers (N-terminal pro-brain natriuretic peptide and uric acid), the former is largely related to the magnitude of changes in hemodynamic factors. The critical values of hemodynamic parameters were due to extreme edema – anasarca (RAP >17 mm Hg, PVR >20 Wood units, CI <14 ml/m2). Analysis of clinical and instrumental parameters in relation to FC revealed a linear relationship of RAP, CO, and PVR between the level of these parameters and FC; moreover, the highest correlation coefficients were observed for the hemodynamic parameters characterizing right ventricular systolic function. It is remarkable that no MPAP changes were found; only patients with FC IV showed its slight increase (from 51±8 to 55±8 mm Hg; р = 0.087). PAWP remained unchanged regardless of FC. Conclusion. Thus, the hemodynamic parameters determined in patients with PAH-SCTD during right heart and LA catheterization are closely related to the manifestations of respiratory and heart failure, the biomarkers, and FC of PAH.

The Prognostic Significance of Inspiratory Capacity in Pulmonary Arterial Hypertension

Background: Patients with pulmonary arterial hypertension (PAH) present with an altered inspiratory capacity (IC) reflecting dynamic hyperinflation (DH) that leads to mechanical constraints and excessive ventilatory demand, particularly during exercise, resulting in exertional dyspnea. Objectives: Assessment of the long-term consequences of altered IC and DH in PAH. Methods: 50 patients with newly diagnosed PAH were prospectively recruited. All patients were assessed by means of right heart catheterization, 6-min walking distance (6MWD) test, lung function and cardiopulmonary exercise testing, including the assessment of IC. Results: 37 patients with idiopathic PAH and 13 patients with conditions associated with PAH (29 female; mean age 51.6 ± 15.1 years; World Health Organization, WHO class, 2.7 ± 0.6) presented with a mean pulmonary arterial pressure of 42.8 ± 15.9 mm Hg and pulmonary vascular resistance (PVR) of 737.2 ± 592.8 dyn*s/cm⁵. The mean IC at rest was 87.2 ± 17.3% pred. Kaplan-Meier analysis revealed that patients with an IC at rest >89% pred. had a significantly better 5-year survival than those with lower values (94.1 vs. 75.1%; log-rank p = 0.036). Univariate analysis identified IC at rest (% pred.) as a predictor of survival with a hazard ratio (HR) of 5.05 (95% confidence interval, CI, 0.97-26.24, p = 0.054). In multivariate analysis including PVR, WHO class, 6MWD and peak oxygen uptake as covariates, IC at rest remained an independent predictor of survival (HR: 8.06, 95% CI 0.92-70.34; p = 0.059). DH expressed as ΔIC or static hyperinflation expressed as IC/total lung capacity at rest revealed no prognostic significance. Conclusion: In patients with PAH, IC at rest is of prognostic significance at the time of diagnosis.