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PURPOSE: Blood-flow restriction (BFR) endurance training may increase endurance performance and muscle strength similar to traditional endurance training while requiring a lower training intensity. We aimed to compare acute cardiorespiratory responses to low-intensity interval exercise under BFR with moderate-intensity traditional interval exercise (TRA). METHODS: We conducted a randomized crossover study. The protocol involved three cycling intervals interspersed with 1 min resting periods. With a 48-h washout period, individuals performed the protocol twice in random order: once as BFR-50 (i.e., 50% incremental peak power output [IPPO] and 50% limb occlusion pressure [LOP]) and once as TRA-65 (65% IPPO without occlusion). TRA-65 intervals lasted 2 min, and time-matched BFR-50 lasted 2 min and 18 s. Respiratory parameters were collected by breath-by-breath analysis. The ratings of perceived breathing and leg exertion (RPE, 0 to 10) were assessed. Linear mixed models were used for analysis. RESULTS: Out of the 28 participants initially enrolled in the study, 24 healthy individuals (18 males and 6 females) completed both measurements. Compared with TRA-65, BFR-50 elicited lower minute ventilation (VE, primary outcome) (-3.1 l/min [-4.4 to -1.7]), oxygen consumption (-0.22 l/min [-0.28 to -0.16]), carbon dioxide production (-0.25 l/min [-0.29 to -0.20]) and RPE breathing (-0.9 [-1.2 to -0.6]). RPE leg was significantly greater in the BFR-50 group (1.3 [1.0 to 1.7]). CONCLUSION: BFR endurance exercise at 50% IPPO and 50% LOP resulted in lower cardiorespiratory work and perceived breathing effort compared to TRA at 65% IPPO. BFR-50 could be an attractive alternative for TRA-65, eliciting less respiratory work and perceived breathing effort while augmenting perceived leg muscle effort. TRIAL REGISTRATION: NCT05163600; December 20, 2021.
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Objective: To investigate the ventilatory and circulatory differences between eccentric (ECC) and concentric (CON) cycling exercise at submaximal, low-dose intensity from onset to end-exercise in healthy middle-aged participants. Design: Randomized controlled crossover trial. Setting: The participants underwent 1 ECC and 1 CON test according to stepwise incremental exercise protocols at identical, submaximal intensities. Breath-by-breath analyses of ventilatory gas exchange and echocardiography were used to assess cardiopulmonary function during exercise. Participants: 24 healthy middle-aged, untrained participants (14 women, 10 men, 50±14 years) were included. Interventions: 1 ECC and 1 CON test at submaximal intensities. Main Outcome Measure: The main outcome was oxygen uptake (V'O2). Results: The V'O2 increase was reduced by -422 mL/min (-52%, 95% confidence interval: -513 to -292, P<.001) during ECC, as well as the ventilatory drive. Echocardiographic parameters, heart rate (-14%), cardiac output (-21%), stroke volume (-15%), and pulmonary artery pressure by tricuspid regurgitation pressure gradient (TRPG) (-26%) were also significantly reduced during ECC compared with CON at identical intensities. Participants reported significantly less dyspnea and unchanged perceived leg fatigue in ECC. Conclusion: ECC was well tolerated, and significant reductions were observed in V'O2, ventilation, and right ventricular load compared with CON, even at low intensity levels. This study, conducted on healthy middle-aged participants, did not raise concerns that would hinder further investigation of the effects of ECC in patients with severely limited cardiopulmonary disease, and it calls for further research on this topic.
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Over 80 Mio people worldwide live >2500 m, including at least as many patients with pulmonary vascular disease (PVD), defined as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), as elsewhere (estimated 0.1). Whether PVD patients living at high altitude have altered disease characteristics due to hypobaric hypoxia is unknown. In a cross-sectional study conducted at the Hospital Carlos Andrade Marin in Quito, Ecuador, located at 2840 m, we included 36 outpatients with PAH or CTEPH visiting the clinic from January 2022 to July 2023. We collected data on diagnostic right heart catheterization, treatment, and risk factors, including NYHA functional class (FC), 6-min walk distance (6MWD), and NT-brain natriuretic peptide (BNP) at baseline and at last follow-up. Thirty-six PVD patients (83% women, 32 PAH, 4 CTEPH, mean ± SD age 44 ± 13 years, living altitude 2831 ± 58 m) were included and had the following baseline values: PaO2 8.2 ± 1.6 kPa, PaCO2 3.9 ± 0.5 kPa, SaO2 91 ± 3%, mean pulmonary artery pressure 53 ± 16 mmHg, pulmonary vascular resistance 16 ± 4 WU, 50% FC II, 50% FC III, 6MWD 472 ± 118 m, BNP 490 ± 823 ng/L. Patients were treated for 1628 ± 1186 days with sildenafil (100%), bosentan (33%), calcium channel blockers (33%), diuretics (69%), and oxygen (nocturnal 53%, daytime 11%). Values at last visit were: FC (II 75%, III 25%), 6MWD of 496 ± 108 m, BNP of 576 ± 5774 ng/L. Compared to European PVD registries, ambulatory PVD patients living >2500 m revealed similar blood gases and relatively low and stable risk factor profiles despite severe hemodynamic compromise, suggesting that favorable outcomes are achievable for altitude residents with PVD. Future studies should focus on long-term outcomes in PVD patients dwelling >2500 m.
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Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are the main precapillary forms of pulmonary hypertension (PH) summarized as pulmonary vascular diseases (PVD). PVDs are characterized by exertional dyspnoea and oxygen desaturation, and reduced quality of life and survival. Medical therapies improve life expectancy and physical performance of PVD patients, of whom many wish to participate in professional work and recreational activities including traveling to high altitude. The exposure to the hypobaric hypoxic environment of mountain regions incurs the risk of high altitude adverse events (AEHA) due to severe hypoxaemia exacerbating symptoms and further increase in pulmonary artery pressure, which may lead to right heart decompensation. Recent prospective and randomized trials show that altitude-induced hypoxaemia, pulmonary haemodynamic changes and impairment of exercise performance in PVD patients are in the range found in healthy people. The vast majority of optimally treated stable PVD patients who do not require long-term oxygen therapy at low altitude can tolerate short-term exposure to moderate altitudes up to 2500 m. PVD patients that reveal persistent severe resting hypoxaemia ( S p O 2 ${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ <80% for >30 min) at 2500 m respond well to supplemental oxygen therapy. Although there are no accurate predictors for AEHA, PVD patients with unfavourable risk profiles at low altitude, such as higher WHO functional class, lower exercise capacity with more pronounced exercise-induced desaturation and more severely impaired haemodynamics, are at increased risk of AEHA. Therefore, doctors with experience in PVD and high-altitude medicine should counsel PVD patients before any high-altitude sojourn. This review aims to summarize recent literature and clinical recommendations about PVD patients travelling to high altitude.
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BACKGROUND: Our objective was to investigate the effect of a day-long exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: In a randomised controlled crossover trial, stable patients with PAH or distal CTEPH without resting hypoxaemia at low altitude performed two incremental exercise tests to exhaustion: one after 3-5â h at high altitude (2500â m) and one at low altitude (470â m). RESULTS: In 27 patients with PAH/CTEPH (44% females, mean±sd age 62±14â years), maximal work rate was 110±64â W at 2500â m and 123±64â W at 470â m (-11%, 95% CI -16- -11%; p<0.001). Oxygen saturation measured by pulse oximetry and arterial oxygen tension at end-exercise were 83±6% versus 91±6% and 6.1±1.9 versus 8.6±1.9â kPa (-8% and -29%; both p<0.001) at 2500 versus 470â m, respectively. Maximal oxygen uptake was 17.8±7.5â L·min-1·kg-1 at high altitude versus 20±7.4â L·min-1·kg-1 at low altitude (-11%; p<0.001). At end-exercise, the ventilatory equivalent for carbon dioxide was 43±9 at 2500â m versus 39±9 at 470â m (9%, 95% CI 2-6%; p=0.002). No adverse events occurred during or after exercise. CONCLUSIONS: Among predominantly low-risk patients with stable PAH/CTEPH, cycling exercise during the first day at 2500â m was well tolerated, but peak exercise capacity, blood oxygenation and ventilatory efficiency were lower compared with 470â m.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Altitud , Estudios Cruzados , Hipertensión Pulmonar Primaria Familiar , Prueba de Esfuerzo , Oxígeno/uso terapéuticoRESUMEN
Ever since the second world symposium on pulmonary hypertension (PH) held in Evian, France, in 1998, PH has been classified into five major clinical groups. Group 5 PH includes a variety of distinct conditions with unclear and/or multifactorial underlying pathologies. Management of these patients is challenging as the number of patients within these groups is often small, not all individuals with certain underlying conditions are affected by PH and patients exhibit distinct symptoms due to different underlying diseases. Studies and clinical trials in these groups are largely lacking and mostly restricted to case series and registry reports. Nonetheless, the worldwide burden of group 5 PH is estimated to be significant in terms of the prevalence of some associated diseases. Group 5 PH encompasses six subgroups, including haematological disorders (inherited and acquired chronic haemolytic anaemia and chronic myeloproliferative disorders), systemic disorders (sarcoidosis, pulmonary Langerhans's cell histiocytosis and neurofibromatosis type 1), metabolic disorders (glycogen storage diseases and Gaucher disease), chronic renal failure with or without haemodialysis, pulmonary tumour thrombotic microangiopathy and fibrosing mediastinitis.
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Hipertensión Pulmonar , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/etiología , PrevalenciaRESUMEN
BACKGROUND: Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH) with accessible lesions. Breathing pure oxygen (hyperoxia) during right heart catheterization (RHC) allows for the calculation of the right-to-left shunt fraction (Qs/Qt). In the absence of intracardiac shunt, Qs/Qt can be used as a marker of ventilation-perfusion mismatch in patients with CTEPH. This study involved investigating Qs/Qt after PEA and its relation to other disease-specific outcomes. STUDY DESIGN AND METHODS: This study is a retrospective study that focuses on patients with operable CTEPH who had Qs/Qt assessment during RHC before and 1 year after PEA. Additionally, 6 min walking distance (6MWD), WHO functional class (WHO-FC), and NT-proBNP were assessed to calculate a four-strata risk score. RESULTS: Overall, 16 patients (6 females) with a median age of 66 years (quartiles 55; 74) were included. After PEA, an improvement in mean pulmonary artery pressure (38 [32; 41] to 24 [18; 28] mmHg), pulmonary vascular resistance (5.7 [4.0; 6.8] to 2.5 [1.4; 3.8] WU), oxygen saturation (92 [88; 93]% to 94 [93; 95]%), WHO-FC, and risk score was observed (all p < 0.05). No improvement in median Qs/Qt could be detected (13.7 [10.0; 17.5]% to 13.0 [11.2; 15.6]%, p = 0.679). A total of 7 patients with improved Qs/Qt had a significant reduction in risk score compared to those without improved Qs/Qt. CONCLUSION: PEA did not alter Qs/Qt assessed after 1 year in operable CTEPH despite an improvement in hemodynamics and risk score, potentially indicating a persistent microvasculopathy. In patients whose shunt fraction improved with PEA, the reduced shunt was associated with an improvement in risk score.
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Care of patients with pulmonary arterial hypertension (PAH) needs a multi-facetet concept and measures, including management of adverse reactions, right heart insufficiency as well as information on pregnancy, travels by air, psychosocial support, physical exercise training and prophylaxis by vaccination.Positive study results led to an higher recommendation of specialized exercise training in pulmonary hypertension. Also, the recommendation on iron substitution was amended according to the current evidence.In the current guidelines, special focus was given to the elaboration of recommendations regarding pregnancy, including patient information, contraception and patient management in case of pregnancy.This article aims to provide an overview on the recommendations of general measuremes, special circumstances and patient management according to the ESC/ERS guidelines. Amendments to the guideline recommendations are given as comments from the authors of this article.
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Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Embarazo , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Ejercicio FísicoRESUMEN
INTRODUCTION: Dyspnea is one of the most common symptoms in patients with lung diseases. The term "dyspnea" refers to the subjective sensation of uncomfortable breathing, which is experienced and described very differently between individuals. Because of this, diagnosis can be very challenging and similar to pain, no true objective measurement parameters of dyspnea exist. A detailed symptom history and clinical examination are critical in establishing the diagnosis, but the severity of pulmonary functional impairment does not always correlate with the clinical picture. The diagnosis of lung diseases is led by pulmonary function tests and imaging techniques, which measure the response to therapy and assess the prognostic course of the disease. The purpose of this article is to review the causes of pulmonary dyspnea, present a guide to diagnostic work-up, and introduce common differential diagnoses.
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Disnea , Enfermedades Pulmonares , Humanos , Disnea/diagnóstico , Disnea/etiología , Disnea/terapia , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/diagnósticoRESUMEN
Background: The course of pulmonary arterial wedge pressure (PAWP) during exercise in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), further abbreviated as pulmonary vascular disease (PVD), is still unknown. The aim of the study was to describe PAWP during exercise in patients with PVD. Methods: In this cross-sectional study, right heart catheter (RHC) data including PAWP, recorded during semi-supine, stepwise cycle exercise in patients with PVD, were analysed retrospectively. We investigated PAWP changes during exercise until end-exercise. Results: In 121 patients (59 female, 66 CTEPH, 55 PAH, 62±17â years) resting PAWP was 10.2±4.1 mmHg. Corresponding peak changes in PAWP during exercise were +2.9â mmHg (95% CI 2.1-3.7â mmHg, p<0.001). Patients ≥50â years had a significantly higher increase in PAWP during exercise compared with those <50â years (p<0.001). The PAWP/cardiac output (CO) slopes were 3.9â WU for all patients, and 1.6â WU for patients <50â years and 4.5â WU for those ≥50â years. Conclusion: In patients with PVD, PAWP increased slightly but significantly with the onset of exercise compared to resting values. The increase in PAWP during exercise was age-dependent, with patients ≥50â years showing a rapid PAWP increase even with minimal exercise. PAWP/CO slopes >2â WU are common in patients with PVD aged ≥50â years without exceeding the PAWP of 25â mmHg during exercise.
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Aims: Pulmonary hypertension (PH) is a complex clinical condition, and left heart disease is the leading cause. Little is known about the epidemiology and prognosis of combined post- and pre-capillary PH (CpcPH). Methods and results: This retrospective analysis of the Swiss PH Registry included incident patients with CpcPH registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient baseline characteristics [age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors, including World Health Organization (WHO)-functional class (FC), 6â min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP), treatment, days of follow-up, and events (death or loss to follow-up) at last visit] were analysed by Kaplan-Meier and Cox regression analyses. Two hundred and thirty-one patients (59.3% women, age 65 ± 12 years, mPAP 48 ± 11â mmHg, PAWP 21 ± 5â mmHg, PVR 7.2 ± 4.8 WU) were included. Survival analyses showed a significantly longer survival for women [hazard ratio (HR) 0.58 (0.38-0.89); P = 0.01] and a higher mortality risk for mPAP > 46â mmHg [HR 1.58 (1.03-2.43); P = 0.04] but no association with age or PVR. Patients stratified to high risk according to four-strata risk assessment had an increased mortality risk compared with patients stratified to low-intermediate risk [HR 2.44 (1.23-4.84); P = 0.01]. A total of 46.8% of CpcPH patients received PH-targeted pharmacotherapy; however, PH-targeted medication was not associated with longer survival. Conclusion: Among patients with CpcPH, women and patients with an mPAP ≤46â mmHg survived longer. Furthermore, risk stratification by using non-invasively assessed risk factors, such as WHO-FC, 6MWD, and NT-proBNP, as proposed for pulmonary arterial hypertension, stratified survival in CpcPH, and might be helpful in the management of these patients.
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Introduction: Obesity is associated with low-grade chronic inflammation, altered levels of adipocytokines, and impaired regulation of gastrointestinal hormones. Secreted, these factors exert immunostimulatory functions directly influencing peripheral immune cells. Methods: In the realm of this study, we aimed to investigate the composition and activation status of peripheral blood immune cells in female patients with morbid obesity compared to lean controls using high-dimensional mass cytometry. Besides, we also assessed the influence of bariatric surgery with respect to its ability to reverse obesity-associated alterations within the first-year post-surgery. Results: Patients with morbid obesity showed typical signs of chronic inflammation characterized by increased levels of CRP and fibrinogen. Apart from that, metabolic alterations were characterized by increased levels of leptin and resistin as well as decreased levels of adiponectin and ghrelin compared to the healthy control population. All these however, except for ghrelin levels, rapidly normalized after surgery with regard to control levels. Furthermore, we found an increased population of monocytic CD14+, HLA-DR-, CD11b+, CXCR3+ cells in patients with morbid obesity and an overall reduction of the HLA-DR monocytic expression compared to the control population. Although CD14+, HLA-DR-, CD11b+, CXCR3+ decreased after surgery, HLA-DR expression did not recover within 9 - 11 months post-surgery. Moreover, compared to the control population, patients with morbid obesity showed a perturbed CD4+ T cell compartment, characterized by a strongly elevated CD127+ memory T cell subset and decreased naïve T cells, which was not recovered within 9 - 11 months post-surgery. Although NK cells showed an activated phenotype, they were numerically lower in patients with morbid obesity when compared to healthy controls. The NK cell population further decreased after surgery and did not recover quantitatively within the study period. Conclusions: Our results clearly demonstrate that the rapid adaptions in inflammatory parameters and adipocytokine levels that occur within the first year post-surgery do not translate to the peripheral immune cells. Apart from that, we described highly affected, distinct immune cell subsets, defined as CD127+ memory T cells and monocytic CD14+, HLA-DR, CD11b+, CXCR3+ cells, that might play a significant role in understanding and further decoding the etiopathogenesis of morbid obesity.
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Cirugía Bariátrica , Obesidad Mórbida , Femenino , Humanos , Obesidad Mórbida/cirugía , Ghrelina , Adipoquinas , Antígenos HLA-DR , Subgrupos de Linfocitos T/metabolismo , Inflamación/complicacionesRESUMEN
Background: COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100â m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP). Methods: In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2-3 who were living <800â m and had peripheral oxygen saturation (S pO2 ) >92% and arterial carbon dioxide tension <6â kPa were randomised to receive either acetazolamide (125-250â mg·day-1) or placebo capsules, starting 24â h before ascent from 760â m and during a 2-day stay at 3100â m. Echocardiography, pulse oximetry and clinical assessments were performed at 760â m and after the first night at 3100â m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG). Results: 112 patients (68% men, mean±sd age 59±8â years, forced expiratory volume in 1â s (FEV1) 61±12% pred, S pO2 95±2%) were included. Mean±sd TRPG increased from 22±7 to 30±10â mmHg in 54 patients allocated to placebo and from 20±5 to 24±7â mmHg in 58 patients allocated to acetazolamide (both p<0.05) resulting in a mean (95% CI) treatment effect of -5 (-9 to -1) mmHg (p=0.015). In patients assigned to placebo at 760/3100â m, mean±sd S pO2 was 95±2%/88±3%; in the acetazolamide group, the respective values were 94±2%/90±3% (both p<0.05), resulting in a treatment effect of +2 (1 to 3)% (p=0.001). Conclusions: In lowlanders with COPD travelling to 3100â m, preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation.
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Pulmonary vascular diseases (PVDs), defined as arterial or chronic thromboembolic pulmonary hypertension, are associated with autonomic cardiovascular dysregulation. Resting heart rate variability (HRV) is commonly used to assess autonomic function. Hypoxia is associated with sympathetic overactivation and patients with PVD might be particularly vulnerable to hypoxia-induced autonomic dysregulation. In a randomised crossover trial, 17 stable patients with PVD (resting PaO2 ≥ 7.3 kPa) were exposed to ambient air (FiO2 = 21%) and normobaric hypoxia (FiO2 = 15%) in random order. Indices of resting HRV were derived from two nonoverlapping 5-10-min three-lead electrocardiography segments. We found a significant increase in all time- and frequency-domain HRV measures in response to normobaric hypoxia. There was a significant increase in root mean squared sum difference of RR intervals (RMSSD; 33.49 (27.14) vs. 20.76 (25.19) ms; p < 0.01) and RR50 count divided by the total number of all RR intervals (pRR50; 2.75 (7.81) vs. 2.24 (3.39) ms; p = 0.03) values in normobaric hypoxia compared to ambient air. Both high-frequency (HF; 431.40 (661.56) vs. 183.70 (251.25) ms2; p < 0.01) and low-frequency (LF; 558.60 (746.10) vs. 203.90 (425.63) ms2; p = 0.02) values were significantly higher in normobaric hypoxia compared to normoxia. These results suggest a parasympathetic dominance during acute exposure to normobaric hypoxia in PVD.
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Patients with chronic obstructive pulmonary disease (COPD) may be susceptible to impairments in postural control (PC) when exposed to hypoxia at high altitude. This randomized, placebo-controlled, double-blind, parallel-design trial evaluated the effect of preventive acetazolamide treatment on PC in lowlanders with COPD traveling to 3100 m. 127 lowlanders (85 men, 42 women) with moderate to severe COPD, aged 57 ± 8 y, living below 800 m, were randomized to treatment with acetazolamide 375 mg/d starting 24 h before ascent from 760 m to 3100 m and during a 2-day sojourn in a clinic at 3100 m. PC was evaluated at both altitudes with a balance platform on which patients were standing during five tests of 30 s each. The primary outcome was the center of pressure path length (COPL). In the placebo group, COPL significantly increased from (mean ± SD) 28.8 ± 9.7 cm at 760 m to 30.0 ± 10.0 cm at 3100 m (p = 0.002). In the acetazolamide group, COPL at 760 m and 3100 m were similar with 27.6 ± 9.6 cm and 28.4 ± 9.7 cm (p = 0.069). The mean between-groups difference (acetazolamide-placebo) in altitude-induced change of COPL was -0.54 cm (95%CI -1.66 to 0.58, p = 0.289). Multivariable regression analysis confirmed an increase in COPL of 0.98 cm (0.39 to 1.58, p = 0.001) with ascent from 760 to 3100 m, but no significant effect of acetazolamide (0.66 cm, 95%CI -0.25 to 1.57, p = 0.156) when adjusting for several confounders. In lowlanders with moderate to severe COPD, an ascent to high altitude was associated with impaired postural control and this was not prevented by acetazolamide.
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OBJECTIVE: Altitude travel is increasingly popular also for middle-aged and older tourists and professionals. Due to the sensitivity of the central nervous system to hypoxia, altitude exposure may impair visuomotor performance although this has not been extensively studied. Therefore, we investigated whether a sojourn at moderately high altitude is associated with visuomotor performance impairments in healthy adults, 40y of age or older, and whether this adverse altitude-effect can be prevented by acetazolamide, a drug used to prevent acute mountain sickness. METHODS: In this randomized placebo-controlled parallel-design trial, 59 healthy lowlanders, aged 40-75y, were assigned to acetazolamide (375 mg/day, n = 34) or placebo (n = 25), administered one day before ascent and while staying at high altitude (3100m). Visuomotor performance was assessed at 760m and 3100m after arrival and in the next morning (post-sleep) by a computer-assisted test (Motor-Task-Manager). It quantified deviation of a participant-controlled cursor affected by rotation during target tracking. Primary outcome was the directional error during post-sleep recall of adaptation to rotation estimated by multilevel linear regression modeling. Additionally, adaptation, immediate recall, and correct test execution were evaluated. RESULTS: Compared to 760m, assessments at 3100m with placebo revealed a mean (95%CI) increase in directional error during adaptation and immediate recall by 1.9° (0.2 to 3.5, p = 0.024) and 1.1° (0.4 to 1.8, p = 0.002), respectively. Post-sleep recall remained unchanged (p = NS), however post-sleep correct test execution was 14% less likely (9 to 19, p<0.001). Acetazolamide improved directional error during post-sleep recall by 5.6° (2.6 to 8.6, p<0.001) and post-sleep probability of correct test execution by 36% (30 to 42, p<0.001) compared to placebo. CONCLUSION: In healthy individuals, 40y of age or older, altitude exposure impaired adaptation to and immediate recall and correct execution of a visuomotor task. Preventive acetazolamide treatment improved visuomotor performance after one night at altitude and increased the probability of correct test execution compared to placebo. CLINICALTRIALS.GOV IDENTIFIER: ClinicalTrials.gov NCT03536520.
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Acetazolamida , Mal de Altura , Adulto , Persona de Mediana Edad , Humanos , Anciano , Altitud , Hipoxia/tratamiento farmacológico , Sueño , Método Doble CiegoRESUMEN
OBJECTIVES: The aim of this study was to investigate the influence of dental prophylaxis cleaning procedures and artificial aging on veneers in human teeth. The external marginal and internal tooth veneer as well as the restoration surfaces were examined. MATERIAL AND METHODS: Thirty-two extracted premolars were restored with resin-based composite (RBC) and polymer-infiltrated ceramic network (PICN) veneers. Artificial aging by alternating thermocycling and subsequent prophylaxis procedure (glycine-based powder air polishing or ultrasonic scaling) was conducted for five consecutive cycles. The external marginal interface was examined by height profile measurements and the internal interface was investigated using micro X-ray computed tomography. In addition, the surface texture of the veneer surface was analyzed using confocal laser scanning microscopy. RESULTS: The application of both prophylaxis procedures resulted in a deepening of the marginal interface (10 µm ± 8 µm) for materials. Furthermore, the internal interface of PICN restorations showed marginal gaps after both treatments and artificial aging (16 µm ± 3 µm). In contrast to the RBC specimens, a significant increase in surface roughness was identified for PICN veneers after ultrasonic scaling. CONCLUSIONS: The marginal and internal interface regions in veneers fabricated from PICN and RBC were affected by prophylaxis procedures. Furthermore, it may result in increased veneer surface roughness, especially in PICN and after ultrasonic scaling, which might affect bioadhesion and longevity. CLINICAL RELEVANCE: After dental prophylaxis procedures, examination of the marginal and the internal interface as well as the veneer surface provides a precise insight into damage mechanisms and offers an assessment of longevity.
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Resinas Compuestas , Polímeros , Humanos , Cerámica , Materiales Dentales , Profilaxis Dental , Coronas con Frente Estético , Porcelana Dental , Ensayo de MaterialesRESUMEN
STUDY OBJECTIVES: To assess altitude-induced sleep and nocturnal breathing disturbances in healthy lowlanders 40 y of age or older and the effects of preventive acetazolamide treatment. METHODS: Clinical examinations and polysomnography were performed at 760 m and in the first night after ascent to 3100 m in a subsample of participants of a larger trial evaluating altitude illness. Participants were randomized 1:1 to treatment with acetazolamide (375 mg/day) or placebo, starting 24 h before and while staying at 3100 m. The main outcomes were indices of sleep structure, oxygenation, and apnea/hypopnea index (AHI). RESULTS: Per protocol analysis included 86 participants (mean ± SE 53 ± 7 y old, 66% female). In 43 individuals randomized to placebo, mean nocturnal pulse oximetry (SpO2) was 94.0 ± 0.4% at 760 m and 86.7 ± 0.4% at 3100 m, with mean change (95%CI) -7.3% (-8.0 to -6.5); oxygen desaturation index (ODI) was 5.0 ± 2.3 at 760 m and 29.2 ± 2.3 at 3100 m, change 24.2/h (18.8 to 24.5); AHI was 11.3 ± 2.4/h at 760 m and 23.5 ± 2.4/h at 3100 m, change 12.2/h (7.3 to 17.0). In 43 individuals randomized to acetazolamide, altitude-induced changes were mitigated. Mean differences (Δ, 95%CI) in altitude-induced changes were: ΔSpO2 2.3% (1.3 to 3.4), ΔODI -15.0/h (-22.6 to -7.4), ΔAHI -11.4/h (-18.3 to -4.6). Total sleep time, sleep efficiency, and N3-sleep fraction decreased with an ascent to 3100 m under placebo by 40 min (17 to 60), 5% (2 to 8), and 6% (2 to 11), respectively. Acetazolamide did not significantly change these outcomes. CONCLUSIONS: During a night at 3100 m, healthy lowlanders aged 40 y or older revealed hypoxemia, sleep apnea, and disturbed sleep. Preventive acetazolamide treatment improved oxygenation and nocturnal breathing but had no effect on sleep duration and structure. TRIAL REGISTRATION: The trial is registered at Clinical Trials, https://clinicaltrials.gov, NCT03561675.
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Acetazolamida , Altitud , Humanos , Femenino , Masculino , Acetazolamida/uso terapéutico , Sueño , RespiraciónRESUMEN
Background: Hypoxia and old age impair postural control and may therefore enhance the risk of accidents. We investigated whether acetazolamide, the recommended drug for prevention of acute mountain sickness, may prevent altitude-induced deterioration of postural control in older persons. Methods: In this parallel-design trial, 95 healthy volunteers, 40 years of age or older, living <1,000 m, were randomized to preventive therapy with acetazolamide (375 mg/d) or placebo starting 24 h before and during a 2-day sojourn at 3,100 m. Instability of postural control was quantified by a balance platform with the center of pressure path length (COPL) as primary outcome while pulse oximetry (SpO2) was monitored. Effects of altitude and treatment on COPL were evaluated by ordered logistic regression. www.ClinicalTrials.gov NCT03536429. Results: In participants taking placebo, ascent from 760 m to 3,100 m increased median COPL from 25.8 cm to 27.6 cm (odds ratio 3.80, 95%CI 2.53-5.70) and decreased SpO2 from 96% to 91% (odds ratio 0.0003, 95%CI 0.0002-0.0007); in participants taking acetazolamide, altitude ascent increased COPL from 24.6 cm to 27.3 cm (odds ratio 2.22, 95%CI 1.57-3.13), while SpO2 decreased from 96% to 93% (odds ratio 0.007, 95%CI 0.004-0.012). Altitude-induced increases in COPL were smaller with acetazolamide vs. placebo (odds ratio 0.58, 95%CI 0.34-0.99) while drops in SpO2 were mitigated (odds ratio 19.2, 95%CI 9.9-37.6). Conclusion: In healthy individuals, 40 years of age or older, postural control was impaired after spending a night at 3,100 m. The altitude-induced deterioration of postural control was mitigated by acetazolamide, most likely due to the associated improvement in oxygenation.