Changes in 24 h ambulatory blood pressure and effects of angiotensin II receptor blockade during acute and prolonged high-altitude exposure: a randomized clinical trial.

AIM: Many hypertensive subjects travel to high altitudes, but little is known on ambulatory blood pressure (ABP) changes and antihypertensive drugs' efficacy under acute and prolonged exposure to hypobaric hypoxia. In particular, the efficacy of angiotensin receptor blockers in this condition is unknown. This may be clinically relevant considering that renin-angiotensin system activity changes at altitude. The HIGHCARE-HIMALAYA study assessed changes in 24 h ABP under acute and prolonged exposure to increasing altitude and blood pressure-lowering efficacy and safety of an angiotensin receptor blockade in this setting. METHODS AND RESULTS: Forty-seven healthy, normotensive lowlanders were randomized to telmisartan 80 mg or placebo in a double-blind, parallel group trial. Conventional and Ambulatory BPs were measured at baseline and on treatment: after 8 weeks at sea level, and under acute exposure to 3400 and 5400 m altitude, the latter upon arrival and after 12 days (Mt. Everest base camp). Blood samples were collected for plasma catecholamines, renin, angiotensin, and aldosterone. In both groups, exposure to increasing altitude was associated with: (i) significant progressive increases in conventional and 24 h blood pressure, persisting throughout the exposure to 5400 m; (ii) increased plasma noradrenaline and suppressed renin-angiotensin-aldosterone system. Telmisartan lowered 24 h ABP at the sea level and at 3400 m (between-group difference 4.0 mmHg, 95% CI: 2.2-9.5 mmHg), but not at 5400 m. CONCLUSION: Ambulatory blood pressure increases progressively with increasing altitude, remaining elevated after 3 weeks. An angiotensin receptor blockade maintains blood pressure-lowering efficacy at 3400 m but not at 5400 m.

Circulating factors are involved in hypoxia-induced hepcidin suppression.

Hepcidin transcription is strongly down-regulated under hypoxic conditions, however whether hypoxia inhibits hepcidin directly or indirectly is still unknown. We investigated the time course of hypoxia-mediated hepcidin down-regulation in vivo in healthy volunteers exposed to hypobaric hypoxia at high altitude and, based on the hypothesis that circulating factors are implicated in hepcidin inhibition, we analyzed the effect of sera of these volunteers exposed to normoxia and hypoxia on hepcidin expression in Huh-7 cell lines. Hypoxia led to a significant hepcidin down-regulation in vivo that was almost complete within 72h of exposure and followed erythropoietin induction. This delay in hepcidin down-regulation suggests the existence of soluble factor/s regulating hepcidin production. We then stimulated HuH-7 cells with normoxic and hypoxic sera to analyze the effects of sera on hepcidin regulation. Hypoxic sera had a significant inhibitory effect on hepcidin promoter activity assessed by a luciferase assay, although the amount of such decrease was not as relevant as that observed in vivo. Cellular mRNA analysis showed that a number of volunteers' sera inhibited hepcidin expression, concurrently with ID1 inhibition, suggesting that inhibitory factor(s) may act through the SMAD-pathway.

Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure.

AIMS: We assessed the haemodynamic changes induced by exposure to high altitude hypoxia and the effects on them of acetazolamide, a drug prescribed to prevent and treat mountain sickness. METHODS AND RESULTS: In 42 subjects (21 males, age 36.8 ± 8.9 years) randomized to double blind acetazolamide 250 mg b.i.d. or placebo, pulse wave velocity and pulse wave parameters were assessed (PulsePen) at baseline; after 2-day treatment at sea level; within 6 h and on 3rd day of exposure to high altitude. Exposure to high altitude significantly increased diastolic (P < 0.005) and mean blood pressure (BP) (P < 0.05, after prolonged exposure) in placebo but not in the acetazolamide group. Therefore, subjects on acetazolamide showed significantly lower values of diastolic (P < 0.005) and mean BP (P < 0.05) at altitude. Furthermore, they also showed significantly lower values of systolic BP (P < 0.05). Pulse wave velocity did not change at high altitude, while the augmentation index, normalized for a theoretical heart rate of 75 b.p.m., significantly increased (P < 0.05) under placebo, but not under acetazolamide. In a multivariate model, unadjusted augmentation index at high altitude was not affected by BP changes, while significant determinants were heart rate and gender. CONCLUSION: Acute exposure to high altitude induced a rise in brachial BP and changes in pulse waveform-derived parameters, independent from changes in mean BP and partly counteracted by treatment with acetazolamide. The impact of acetazolamide on the haemodynamic alterations induced by hypobaric hypoxia may be considered among the beneficial effects of this drug in subjects prone to mountain sickness. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2010-019986-27.

Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project.

Iron is tightly connected to oxygen homeostasis and erythropoiesis. Our aim was to better understand how hypoxia regulates iron acquisition for erythropoiesis in humans, a topic relevant to common hypoxia-related disorders. Forty-seven healthy volunteers participated in the HIGHCARE project. Blood samples were collected at sea level and after acute and chronic exposure to high altitude (3400-5400 m above sea level). We investigated the modifications in hematocrit, serum iron indices, erythropoietin, markers of erythropoietic activity, interleukin-6, and serum hepcidin. Hepcidin decreased within 40 hours after acute hypoxia exposure (P < .05) at 3400 m, reaching the lowest level at 5400 m (80% reduction). Erythropoietin significantly increased (P < .001) within 16 hours after hypoxia exposure followed by a marked erythropoietic response supported by the increased iron supply. Growth differentiation factor-15 progressively increased during the study period. Serum ferritin showed a very rapid decrease, suggesting the existence of hypoxia-dependent mechanism(s) regulating storage iron mobilization. The strong correlation between serum ferritin and hepcidin at each point during the study indicates that iron itself or the kinetics of iron use in response to hypoxia may signal hepcidin down-regulation. The combined and significant changes in other variables probably contribute to the suppression of hepcidin in this setting.

Pretreated residual biomasses in fluidized beds for chemical looping Gasification: Experimental devolatilizations and characterization of ashes behavior.

The European research project CLARA (G.A. 817841) has studied pretreated residual biomasses for chemical looping gasification. This work investigated devolatilizations of wheat straw pellets (raw, torrefied, and torrefied-washed) at 700 °C, 800 °C, and 900 °C, performed in fluidized beds made of sand or three oxygen carriers (OCs): integral-average values (gas yield, H2/CO molar ratio, and carbon conversion) were calculated; instantaneous peaks of released syngas were evaluated by regression straight lines. For all biomasses and bed materials, the temperature increase (from 700 to 900 °C) was the dominant parameter, positively affecting all integral-average values. The OCs appeared more active at 900 °C. Biomass pretreatments improved the H2/CO molar ratio and decreased carbon conversion. SEM analyses showed that the purpose of washing (removal of low-melting elements) may be jeopardized by OCs' composition.

Continuous positive airway pressure increases haemoglobin O2 saturation after acute but not prolonged altitude exposure.

AIMS: It is unknown whether subclinical high-altitude pulmonary oedema reduces spontaneously after prolonged altitude exposure. Continuous positive airway pressure (CPAP) removes extravascular lung fluids and improves haemoglobin oxygen saturation in acute cardiogenic oedema. We evaluated the presence of pulmonary extravascular fluid increase by assessing CPAP effects on haemoglobin oxygen saturation under acute and prolonged altitude exposure. METHODS AND RESULTS: We applied 7 cm H(2)O CPAP for 30 min to healthy individuals after acute (Capanna Margherita, CM, 4559 m, 2 days permanence, and <36 h hike) and prolonged altitude exposure (Mount Everest South Base Camp, MEBC, 5350 m, 10 days permanence, and 9 days hike). At CM, CPAP reduced heart rate and systolic pulmonary artery pressure while haemoglobin oxygen saturation increased from 80% (median), 78-81 (first to third quartiles), to 91%, 84-97 (P < 0.001). After 10 days at MEBC, haemoglobin oxygen saturation spontaneously increased from 77% (74-82) to 86% (82-89) (P < 0.001) while heart rate (from 79, 64-92, to 70, 54-81; P < 0.001) and respiratory rate (from 15, 13-17, to 13, 13-15; P < 0.001) decreased. Under such conditions, these parameters were not influenced by CPAP. CONCLUSION: After ascent excessive lung fluids accumulate affecting haemoglobin oxygen saturation and, in these circumstances, CPAP is effective. Acclimatization implies spontaneous haemoglobin oxygen saturation increase and, after prolonged altitude exposure, CPAP is not associated with HbO(2)-sat increase suggesting a reduction in alveolar fluids.

Kinetic Characterization of Tar Reforming on Commercial Ni-Catalyst Pellets Used for In Situ Syngas Cleaning in Biomass Gasification: Experiments and Simulations under Process Conditions.

Filtering-catalytic candles, filled with an annular packed-bed of commercial Ni-catalyst pellets (∼600 g), were successfully tested for in situ syngas cleaning in a fluidized-bed biomass steam gasifier [Fuel Process. Technol.2019, 191, 44-53, DOI: 10.1016/j.fuproc.2019.03.018]. Those tests enabled the macroscopic evaluation of gasification and gas cleaning as a whole, requiring a more specific assessment of the catalyst performance inside the filter candle. To this end, steam reforming tests of tar key compounds (naphthalene and toluene; thiophene in traces to observe sulfur deactivation) were performed with a laboratory-scale packed-bed reactor containing the same catalyst pellets (<7 g). A lumped kinetics was derived, referred to a pseudocomponent representing tars. This was then validated by simulation of the annular catalytic packed bed inside the filter candle, obtaining numerical results in fair agreement with gasifier outputs. As a result, the lab-scale investigation with a small amount of catalyst provides reliable predictions of tar catalytic reforming in industrial-scale filtering-catalytic candles.

Steam gasification of lignite and solid recovered fuel (SRF) in a bench scale fluidized bed gasifier.

The reduction of CO2 emissions and solid waste disposal are critical issues with high importance for the environmental protection. Gasification is a promising process for sustainable energy production, because it can produce a versatile gaseous fuel starting from a wide range of organic feedstocks, and with reduced greenhouse gas emissions compared to combustion. Lignite is an abundant carbonaceous resource in Europe and in this work, gasification tests were carried out with lignite and a lignite and Solid Recovered Fuel (SRF) mixture, to evaluate the quality of gas produced from co-gasification of waste materials, in view of the final uses of the gas. Experimental gasification tests were carried out in a bench scale fluidized bed gasifier at different operating temperatures; the results were evaluated in terms of gas composition, tar content and conversion rates. In addition, characterization analyses were carried out on materials before and after the tests, and pressure fluctuation signals were analysed in order to evaluate the fluidization quality of the bed inventory.

Effects of acute exposure to moderate altitude on blood pressure and sleep breathing patterns.

BACKGROUND: Acute exposure to high altitude (>2500 m) is known to induce a rise in blood pressure (BP) and the appearance of sleep related breathing alterations, in particular central sleep apneas and periodic breathing. Little information is available on whether this is the case in humans also for acute exposure to moderate altitude (between 1500 and 2500 m). Aim of this study was to evaluate the effects of acute exposure of healthy volunteers to moderate altitude on conventional and ambulatory BP as well as on the frequency and severity of breathing alterations during sleep. METHODS: Forty-four healthy lowlanders underwent 24-hour ambulatory BP monitoring and nocturnal cardio-respiratory sleep study at sea level and during acute (1-2 days after arrival) exposure to moderate altitude (2035 m, Sestriere, Italy). The key variables investigated included average systolic and diastolic BP and heart rate over daytime, night-time and 24 h, the frequency of obstructive and central apneas/hypopnoeas and the behaviour of oxygen saturation during sleep. RESULTS: Compared to sea level, during moderate altitude exposure mean systolic/diastolic BP increased significantly during daytime (respectively from 125.6 ±â€¯10.9 to 130.6 ±â€¯12.3, p = 0.0032 and from 78.8 ±â€¯6.7 to 81.8 ±â€¯7.7 mmHg, p = 0.0048) and during night-time (respectively from 102.4 ±â€¯12.4 to 107.4 ±â€¯12.7, p = 0.0028, and from 62.0 ±â€¯8.2 to 65.8 ±â€¯8.2 mmHg, p = 0.0014), with no change in nocturnal BP dipping. BP increase was more evident in participants aged over 40 years. Apnea-hypopnea index (AHI) increased from 1.60 (0.40-2.90) to 5.4 (2.90-10.60), p < 0.0001), mainly because of increasing frequency of hypopneas and central apneas, in particular in males aged over 40 years. No association was found between size of BP changes and AHI. CONCLUSION: Our results indicate that in healthy subjects even exposure to moderate altitude may induce significant, although mild, changes in ambulatory BP and in respiratory patterns during sleep with gender and age-related differences. Further studies are needed to explore the clinical relevance of these findings.

Home blood pressure telemonitoring improves hypertension control in general practice. The TeleBPCare study.

BACKGROUND: Self blood pressure monitoring at home may improve blood pressure control and patients' compliance with treatment, but its implementation in daily practice faces difficulties. Teletransmission facilities may offer a more efficient approach to long-term home blood pressure monitoring. METHODS: Twelve general practitioners screened 391 consecutive uncontrolled mild-moderate hypertensive patients (80% treated), 329 of whom (58 +/- 11 years, 54% men) were randomized to either usual care on the basis of office blood pressure (group A, n = 113) or to integrated care on the basis of teletransmitted home blood pressure (group B, n = 216). Twenty-four-hour ambulatory blood pressure monitoring was performed at baseline and after 6 months, during which treatment was optimized according to either office (group A) or home (group B) blood pressure values. We compared differences between groups in the rate of daytime ambulatory blood pressure normalization (<130/80 mmHg), need of treatment changes during follow-up, quality of life scores, and healthcare costs. RESULTS: Baseline office blood pressures were 149 +/- 12/89 +/- 9 and 148 +/- 13/89 +/- 7 mmHg in groups A (n = 111) and B (n = 187) respectively, the corresponding daytime values being 140 +/- 11/84 +/- 8 and 139 +/- 11/84 +/- 8 mmHg. The percentage of daytime blood pressure normalization was higher in group B (62%) than in group A (50%) (P < 0.05). There were less frequent treatment changes in group B than in group A (9 vs. 14%, P < 0.05). Quality of life tended to be higher and costs lower in group B. CONCLUSION: Patients' management based on home blood pressure teletransmission led to a better control of ambulatory blood pressure than with usual care, with a more regular treatment regimen.

Renin-Angiotensin-Aldosterone System Is Not Involved in the Arterial Stiffening Induced by Acute and Prolonged Exposure to High Altitude.

This randomized, double-blind, placebo-controlled study was designed to explore the effects of exposure to very high altitude hypoxia on vascular wall properties and to clarify the role of renin-angiotensin-aldosterone system inhibition on these vascular changes. Forty-seven healthy subjects were included in this study: 22 randomized to telmisartan (age, 40.3±10.8 years; 7 women) and 25 to placebo (age, 39.3±9.8 years; 7 women). Tests were performed at sea level, pre- and post-treatment, during acute exposure to 3400 and 5400-m altitude (Mt. Everest Base Camp), and after 2 weeks, at 5400 m. The effects of hypobaric hypoxia on mechanical properties of large arteries were assessed by applanation tonometry, measuring carotid-femoral pulse wave velocity, analyzing arterial pulse waveforms, and evaluating subendocardial oxygen supply/demand index. No differences in hemodynamic changes during acute and prolonged exposure to 5400-m altitude were found between telmisartan and placebo groups. Aortic pulse wave velocity significantly increased with altitude (P<0.001) from 7.41±1.25 m/s at sea level to 7.70±1.13 m/s at 3400 m and to 8.52±1.59 m/s at arrival at 5400 m (P<0.0001), remaining elevated during prolonged exposure to this altitude (8.41±1.12 m/s; P<0.0001). Subendocardial oxygen supply/demand index significantly decreased with acute exposure to 3400 m: from 1.72±0.30 m/s at sea level to 1.41±0.27 m/s at 3400 m (P<0.001), remaining significantly although slightly less reduced after reaching 5400 m (1.52±0.33) and after prolonged exposure to this altitude (1.53±0.25; P<0.001). In conclusion, the acute exposure to hypobaric hypoxia induces aortic stiffening and reduction in subendocardial oxygen supply/demand index. Renin-angiotensin-aldosterone system does not seem to play any significant role in these hemodynamic changes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu/. Unique identifier: 2008-000540-14.

Effects of hypobaric hypoxia exposure at high altitude on left ventricular twist in healthy subjects: data from HIGHCARE study on Mount Everest.

AIMS: Previous studies investigating the effect of hypoxia on left ventricle focused on its global function, an approach that may not detect a selective dysfunction of subendocardial layers that are most sensitive to an inadequate oxygen supply. In the HIGHCARE study, aimed at exploring the effects of high altitude hypoxia on multiple biological variables and their modulation by an angiotensin receptor blocker, we addressed the effects of hypobaric hypoxia on both systolic and diastolic left ventricular geometry and function, focusing on echocardiographic assessment of left ventricle twist to indirectly examine subendocardial left ventricular systolic function. METHODS AND RESULTS: In 39 healthy subjects, physiological and echocardiographic variables, including left ventricular twist and a simplified torsion-to-shortening ratio (sTSR), were recorded at sea level, at 3400 m, and at 5400 m altitude (Mount Everest base camp). Both left ventricular twist and sTSR were greater at 5400 m than at sea level (12.6° vs. 9.6° and 0.285 vs. 0.202, P < 0.05 for both), were linearly related to the reduction in arterial oxygen partial pressure (P < 0.01 for both), and were associated with significant changes in LV dimensions and contractility. No effects of angiotensin receptor blockade were observed on these variables throughout the study. CONCLUSION: Our study, for the first time, demonstrates an increase in left ventricular twist at high altitude in healthy subjects exposed to high altitude hypoxia, suggesting the occurrence of subendocardial systolic dysfunction in such condition.

Ambulatory blood pressure in untreated and treated hypertensive patients at high altitude: the High Altitude Cardiovascular Research-Andes study.

UNLABELLED: Blood pressure increases during acute exposure to high altitude in healthy humans. However, little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this condition. Objectives of High Altitude Cardiovascular Research (HIGHCARE)-Andes Lowlanders Study were to investigate the effects of acute high-altitude exposure on 24-hour ambulatory blood pressure in hypertensive subjects and to assess antihypertensive treatment efficacy in this setting. One hundred untreated subjects with mild hypertension (screening blood pressure, 144.1±9.8 mm Hg systolic, 92.0±7.5 mm Hg diastolic) were randomized to double-blind placebo or to telmisartan 80 mg+modified release nifedipine 30 mg combination. Twenty-four-hour ambulatory blood pressure monitoring was performed off-treatment, after 6 weeks of treatment at sea level, on treatment during acute exposure to high altitude (3260 m) and immediately after return to sea level. Eighty-nine patients completed the study (age, 56.4±17.6 years; 52 men/37 women; body mass index, 28.2±3.5 kg/m(2)). Twenty-four-hour systolic blood pressure increased at high altitude in both groups (placebo, 11.0±9 mm Hg; P<0.001 and active treatment, 8.1±10.4 mm Hg; P<0.001). Active treatment reduced 24-hour systolic blood pressure both at sea level and at high altitude (147.9±11.1 versus 132.6±12.4 mm Hg for placebo versus treated; P<0.001; 95% confidence interval of the difference 10.9-19.9 mm Hg) and was well tolerated. Similar results were obtained for diastolic, for daytime blood pressure, and for nighttime blood pressure. Treatment was well tolerated in all conditions. Our study demonstrates that (1) 24-hour blood pressure increases significantly during acute high-altitude exposure in hypertensive subjects and (2) treatment with angiotensin receptor blocker-calcium channel blocker combination is effective and safe in this condition. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830530.

Changes in subendocardial viability ratio with acute high-altitude exposure and protective role of acetazolamide.

High-altitude tourism is increasingly frequent, involving also subjects with manifest or subclinical coronary artery disease. Little is known, however, on the effects of altitude exposure on factors affecting coronary perfusion. The aim of our study was to assess myocardial oxygen supply/demand ratio in healthy subjects during acute exposure at high altitude and to evaluate the effect of acetazolamide on this parameter. Forty-four subjects (21 men, age range: 24-59 years) were randomized to double-blind acetazolamide 250 mg bid or placebo. Subendocardial viability ratio and oxygen supply/demand ratio were estimated on carotid artery by means of a validated PulsePen tonometer, at sea level, before and after treatment, and after acute and more prolonged exposure to high altitude (4559 m). On arrival at high altitude, subendocardial viability ratio was reduced in both placebo (from 1.63±0.15 to 1.18±0.17; P<0.001) and acetazolamide (from 1.68±0.25 to 1.35±0.18; P<0.001) groups. Subendocardial viability ratio returned to sea level values (1.65±0.24) after 3 days at high altitude under acetazolamide but remained lower than at sea level under placebo (1.42±0.22; P<0.005 versus baseline). At high altitude, oxygen supply/demand ratio fell both under placebo (from 29.6±4.0 to 17.3±3.0; P<0.001) and acetazolamide (from 32.1±7.0 to 22.3±4.6; P<0.001), its values remaining always higher (P<0.001) on acetazolamide. Administration of acetazolamide may, thus, antagonize the reduction in subendocardial oxygen supply triggered by exposure to hypobaric hypoxia. Further studies involving also subjects with known or subclinical coronary artery disease are needed to confirm a protective action of acetazolamide on myocardial viability under high-altitude exposure.

Acute high-altitude exposure reduces lung diffusion: data from the HIGHCARE Alps project.

The causes and development of lung fluid, as well as the integrity of the alveolar-capillary membrane at high altitude, are undefined. This study was conceived to see whether fluid accumulates within the lung with acute high altitude exposure, and whether this is associated with alveolar capillary membrane damage. We studied lung carbon monoxide diffusion (DLCO), its components - membrane diffusion (DM) and capillary volume (VC) and alveolar volume (VA) measured in 43 healthy subjects in Milan (122 m) and after 1 and 3 days at Capanna Regina Margherita (4559 m). DLCO measurement was adjusted for hemoglobin and inspired oxygen. We also measured plasma surfactant derived protein B (SPB) and Receptor of Advanced Glycation End-products (RAGE) as markers of alveolar-capillary membrane damage, and ultrasound lung comets as a marker of extravascular lung water. 21 subjects received acetazolamide and 22 placebo. DLCO was lower at Capanna Regina Margherita (day 1: 24.3 ± 4.7 and day 3: 23.6 ± 5.4 mL/mmHg/min), than in Milan (25.8 ± 5.5; p<0.001 vs. day 1 and 3) due to DM reduction (Milan: 50.5 ± 14.6 mL/mmHg/min, Capanna Regina Margherita day 1: 45.1 ± 11.5 mL/mmHg/min, day 3: 43.2 ± 13.9 mL/mmHg/min; p<0.05 Milan vs. day 3) with a partially compensatory VC increase (Milan: 96 ± 37 mL, Capanna Regina Margherita day 1: 152 ± 66 mL, day 3: 153 ± 59 mL; p<0.001 Milan vs. day 1 and day 3). Acetazolamide did not prevent the fall in DLCO albeit, between day 1 and 3, such a trend was observed. Regardless of treatment lung comets increased from 0 to 7.2 ± 3.6 (p<0.0001). SPB and RAGE were unchanged. Lung fluid increased at high altitude without evidence from plasma measurements, supporting alveolar-capillary damage.

Modulation of urinary peptidome in humans exposed to high altitude hypoxia.

The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia and to evaluate pharmacological approaches potentially useful as a therapy for chronic diseases related to hypoxia. We explored the urinary peptidome to detect alterations induced by the exposure of subjects to different altitudes (sea level, high altitude = 3500 m, very high altitude = 5400 m) and to pharmacological treatment. Urine samples were collected from 47 subjects, randomly and blindly assigned to placebo (n = 24) or Telmisartan (n = 23). Samples were purified by the use of magnetic beads, then analysed by MALDI-TOF MS. Results showed that the urinary peptidome is not affected by the administration of Telmisartan, neither at the sea level nor at high and very high altitudes. In contrast, the urinary protein profiles are modified when subjects are exposed to high and very high altitudes, and we detected six peptides differentially expressed in hypobaric hypoxia at high or very high altitude compared to the sea level. Two of them were identified as fragments of the glycoprotein uromodulin and of the α1-antitrypsin. This is the first proteomic study showing that hypobaric hypoxia conditions affect the urinary peptidome.

Effects of slow deep breathing at high altitude on oxygen saturation, pulmonary and systemic hemodynamics.

Slow deep breathing improves blood oxygenation (Sp(O2)) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2-3 days (Study A; N = 39) or at 5400 m for 12-16 days (Study B; N = 28). Study variables, including Sp(O2) and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in Sp(O2) (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion.

High-altitude exposure of three weeks duration increases lung diffusing capacity in humans.

BACKGROUND: high-altitude adaptation leads to progressive increase in arterial Pa(O2). In addition to increased ventilation, better arterial oxygenation may reflect improvements in lung gas exchange. Previous investigations reveal alterations at the alveolar-capillary barrier indicative of decreased resistance to gas exchange with prolonged hypoxia adaptation, but how quickly this occurs is unknown. Carbon monoxide lung diffusing capacity and its major determinants, hemoglobin, alveolar volume, pulmonary capillary blood volume, and alveolar-capillary membrane diffusion, have never been examined with early high-altitude adaptation. METHODS AND RESULTS: lung diffusion was measured in 33 healthy lowlanders at sea level (Milan, Italy) and at Mount Everest South Base Camp (5,400 m) after a 9-day trek and 2-wk residence at 5,400 m. Measurements were adjusted for hemoglobin and inspired oxygen. Subjects with mountain sickness were excluded. After 2 wk at 5,400 m, hemoglobin oxygen saturation increased from 77.2 ± 6.0 to 85.3 ± 3.6%. Compared with sea level, there were increases in hemoglobin, lung diffusing capacity, membrane diffusion, and alveolar volume from 14.2 ± 1.2 to 17.2 ± 1.8 g/dl (P < 0.01), from 23.6 ± 4.4 to 25.1 ± 5.3 ml·min(-1)·mmHg(-1) (P < 0.0303), 63 ± 34 to 102 ± 65 ml·min(-1)·mmHg(-1) (P < 0.01), and 5.6 ± 1.0 to 6.3 ± 1.1 liters (P < 0.01), respectively. Pulmonary capillary blood volume was unchanged. Membrane diffusion normalized for alveolar volume was 10.9 ± 5.2 at sea level rising to 16.0 ± 9.2 ml·min(-1)·mmHg(-1)·l(-1) (P < 0.01) at 5,400 m. CONCLUSIONS: at high altitude, lung diffusing capacity improves with acclimatization due to increases of hemoglobin, alveolar volume, and membrane diffusion. Reduction in alveolar-capillary barrier resistance is possibly mediated by an increase of sympathetic tone and can develop in 3 wk.

Statins, antihypertensive treatment, and blood pressure control in clinic and over 24 hours: evidence from PHYLLIS randomised double blind trial.

OBJECTIVE: To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring. DESIGN: Randomised placebo controlled double blind trial. SETTING: 13 hospitals in Italy PARTICIPANTS: 508 patients with mild hypertension and hypercholesterolaemia, aged 45 to 70 years. INTERVENTION: Participants were randomised to antihypertensive treatment (hydrochlorothiazide 25 mg once daily or fosinopril 20 mg once daily) with or without the addition of a statin (pravastatin 40 mg once daily). Main outcome measures Clinic and ambulatory blood pressure measured every year throughout an average 2.6 year treatment period. RESULTS: Both the group receiving antihypertensive treatment without pravastatin (n=254) (with little change in total cholesterol) and the group receiving antihypertensive treatment with pravastatin (n=253) (with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour, and day and night, systolic and diastolic blood pressure. Pravastatin performed slightly worse than placebo, and between group differences did not exceed 1.9 (95% confidence interval -0.6 to 4.3, P=0.13) mm Hg throughout the treatment period. This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately. CONCLUSIONS: Administration of a statin in hypertensive patients in whom blood pressure is effectively reduced by concomitant antihypertensive treatment does not have an additional blood pressure lowering effect. Trial registration BRISQUI_*IV_2004_001 (registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali-National Monitoring Centre on Clinical Research with Medicines).