Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

Effects of Electrical Stimulation on Delayed Onset Muscle Soreness (DOMS): Evidences from Laboratory and In-Field Studies.

Intense, long exercise can increase oxidative stress, leading to higher levels of inflammatory mediators and muscle damage. At the same time, fatigue has been suggested as one of the factors giving rise to delayed-onset muscle soreness (DOMS). The aim of this study was to investigate the efficacy of a specific electrical stimulation (ES) treatment (without elicited muscular contraction) on two different scenarios: in the laboratory on eleven healthy volunteers (56.45 ± 4.87 years) after upper limbs eccentric exercise (Study 1) and in the field on fourteen ultra-endurance athletes (age 47.4 ± 10.2 year) after an ultra-running race (134 km, altitude difference of 10,970 m+) by lower exercising limbs (Study 2). Subjects were randomly assigned to two experimental tasks in cross-over: Active or Sham ES treatments. The ES efficacy was assessed by monitoring the oxy-inflammation status: Reactive Oxygen Species production, total antioxidant capacity, IL-6 cytokine levels, and lactate with micro-invasive measurements (capillary blood, urine) and scales for fatigue and recovery assessments. No significant differences (p > 0.05) were found in the time course of recovery and/or pre-post-race between Sham and Active groups in both study conditions. A subjective positive role of sham stimulation (VAS scores for muscle pain assessment) was reported. In conclusion, the effectiveness of ES in treating DOMS and its effects on muscle recovery remain still unclear.

EPR spectroscopic evidence of iron-catalysed free radical formation in chronic mountain sickness: Dietary causes and vascular consequences.

Chronic mountain sickness (CMS) is a high-altitude (HA) maladaptation syndrome characterised by elevated systemic oxidative-nitrosative stress (OXNOS) due to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability. To better define underlying mechanisms and vascular consequences, this study compared healthy male lowlanders (80 m, n = 10) against age/sex-matched highlanders born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 10) and without (CMS-, n = 10) CMS. Cephalic venous blood was assayed using electron paramagnetic resonance spectroscopy and reductive ozone-based chemiluminescence. Nutritional intake was assessed via dietary recall. Systemic vascular function and structure were assessed via flow-mediated dilatation, aortic pulse wave velocity and carotid intima-media thickness using duplex ultrasound and applanation tonometry. Basal systemic OXNOS was permanently elevated in highlanders (P = <0.001 vs. lowlanders) and further exaggerated in CMS+, reflected by increased hydroxyl radical spin adduct formation (P = <0.001 vs. CMS-) subsequent to liberation of free 'catalytic' iron consistent with a Fenton and/or nucleophilic addition mechanism(s). This was accompanied by elevated global protein carbonylation (P = 0.046 vs. CMS-) and corresponding reduction in plasma nitrite (P = <0.001 vs. lowlanders). Dietary intake of vitamins C and E, carotene, magnesium and retinol were lower in highlanders and especially deficient in CMS + due to reduced consumption of fruit and vegetables (P = <0.001 to 0.028 vs. lowlanders/CMS-). Systemic vascular function and structure were also impaired in highlanders (P = <0.001 to 0.040 vs. lowlanders) with more marked dysfunction observed in CMS+ (P = 0.035 to 0.043 vs. CMS-) in direct proportion to systemic OXNOS (r = -0.692 to 0.595, P = <0.001 to 0.045). Collectively, these findings suggest that lifelong exposure to iron-catalysed systemic OXNOS, compounded by a dietary deficiency of antioxidant micronutrients, likely contributes to the systemic vascular complications and increased morbidity/mortality in CMS+. TRIAL REGISTRY: ClinicalTrials.gov; No: NCT01182792; URL: www.clinicaltrials.gov.

High-altitude mountain telemedicine.

INTRODUCTION: An innovative teleconsultation platform has been designed, developed and validated between summer 2017 and winter 2018, in five mountain huts and in three remote outpatient clinical centres of the Italian region Valle d'Aosta of the Mont Blanc massif area. METHODS: An ad-hoc videoconference system was developed within the framework of the e-Rés@MONT (Interreg ALCOTRA) European project, to tackle general health problems and high-altitude diseases (such as acute mountain sickness, high-altitude pulmonary and cerebral oedema). The system allows for contacting physicians at the main hospital in Aosta to perform a specific diagnosis and to give specific advice and therapy to the patients in an extreme environment out-hospital setting. At an altitude between 1500-3500 m, five trained nurses performed clinical evaluations (anamnesis, blood pressure, heart rate, oxygen saturation), electrocardiographic and echography monitoring on both tourists and residents as necessary; all of the collected data were sent to the physicians in Aosta. RESULTS: A total of 702 teleconsultation cases were performed: 333 dismissed (47%), 356 observed (51%) and 13 immediate interventions (2%). In 30 cases the physicians decided there was no need for helicopter and ambulance rescue intervention and hospital admissions. The main physiological measures, the classified pathologies, the severe cases and the cost savings are described in this article. DISCUSSION: The e-Rés@MONT teleconsultation platform has been discussed in terms of treated cases, feasibility, proactivity in reducing complexities, direct and indirect advantages, and diagnostics help; moreover, general and specific pros and cons have been debated, and future steps have been exposed.

Sport in Town: The Smart Healthy ENV Project, a Pilot Study of Physical Activity with Multiparametric Monitoring.

BACKGROUND: Increasing evidence links meteorological characteristics and air pollution to physiological responses during sports activities in urban areas with different traffic levels. OBJECTIVE: The main objective of the Smart Healthy ENV (SHE, "Smart Monitoring Integrated System For A Healthy Urban Environment In Smart Cities") project was to identify the specific responses of a group of volunteers during physical activity, by monitoring their heart rates and collecting breath samples, combined with data on meteorological determinants and pollution substances obtained through fixed sensor nodes placed along city routes and remotely connected to a dedicated data acquisition server. METHODS: Monitoring stations were placed along two urban routes in Pisa, each two km long, with one located within the park beside the Arno river (green route) and the other in a crowded traffic zone (red route). Our sample participants were engaged in sports activities (N = 15, with different levels of ability) and were monitored through wearable sensors. They were first asked to walk back and forth (4 km) and then to run the same route. The experimental sessions were conducted over one day per route. A breath sample was also collected before each test. A questionnaire concerning temperature and fatigue perception was administered for all of the steps of the study over the two days. RESULTS: The heart rates of the participants were monitored in the baseline condition, during walking, and while running, and were correlated with meteorological and pollutant data and with breath composition. Changes in the heart rates and breath composition were detected during the experimental sessions. These variations were related to the physical activity and to the meteorological conditions and air pollution levels. CONCLUSIONS: The SHE project can be considered a proof-of-concept study aimed at monitoring physiological and environmental variables during physical activity in urban areas, and can be used in future studies to provide useful information to those involved in sports and the broader community.

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Misperceptions and hallucinatory experiences in ultra-trailer, high-altitude runners.

BACKGROUND: The Mountain Activities Neuro-behavioural Research Programme is a research project born in the 2 nd Unit of Psychiatry, Department of Clinical and Experimental Medicine at the University of Pisa to investigate the effects of altitude on the mental and neuro-behavioural aspects of people performing activities in mountainous areas. METHODS: In this study, after elaborating a standardised data collection form, based on traditional psychopathology notions, to classify the misperceptions reported by the athletes taking part, we investigated the various types of these misperceptions in 21 athletes (including only one female), with a mean age of 44.90 ± 8.51 (min 33 and max 58). RESULTS: The athletes reported different kinds of misperceptions. It was possible to highlight three different clusters of athletes, based on the similarities between the kinds of misperceptions reported in each cluster: (a) anomalies in the intrinsic characteristics of perceptions (i.e. depersonalisation and derealisation), (b) illusions and (c) hallucinations. CONCLUSIONS: This study supports the concept that anomalous perceptual experiences may occur independently of the context of psychiatric or neurological disorders. The chance of observing hallucinatory phenomena outside the context of psychiatric disorders and in extreme environmental conditions among ultra-trail runners may offer a unique opportunity to those intending to study psychopathological conditions in a 'para-physiological' context.

Heat warning and public and workers' health at the time of COVID-19 pandemic.

The humanity is currently facing the COVID-19 pandemic challenge, the largest global health emergency after the Second World War. During summer months, many countries in the northern hemisphere will also have to counteract an imminent seasonal phenomenon, the management of extreme heat events. The novelty this year concerns that the world population will have to deal with a new situation that foresees the application of specific measures, including adjunctive personal protective equipment (i.e. facemasks and gloves), in order to reduce the potential transmission of the SARS-CoV-2 virus. These measures should help to decrease the risk of the infection transmission but will also represent an aggravating factor to counteract the heat effects on the population health both at occupational and environmental level. The use of a specific heat health warning system with personalized information based on individual, behavioural and environmental characteristics represents a necessary strategy to help a fast adaptation of the population at a time where the priority is to live avoiding SARS-CoV-2 infection.

Acute Effects of Triathlon Race on Oxidative Stress Biomarkers.

The response to strenuous exercise was investigated by reactive oxygen species (ROS) production, oxidative damage, thiol redox status, and inflammation assessments in 32 enrolled triathlon athletes (41.9 ± 7.9 yrs) during Ironman® (IR), or half Ironman® (HIR) competition. In biological samples, inflammatory cytokines, aminothiols (glutathione (GSH), homocysteine (Hcy), cysteine (Cys), and cysteinylglycine (CysGly)), creatinine and neopterin, oxidative stress (OxS) biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS)), and ROS were assessed. Thirteen HIR and fourteen IR athletes finished the race. Postrace, ROS (HIR +20%; IR +28%; p < 0.0001), TBARS (HIR +57%; IR +101%), PC (HIR +101%; IR +130%) and urinary neopterin (HIR +19%, IR +27%) significantly (range p < 0.05-0.0001) increased. Moreover, HIR showed an increase in total Cys +28%, while IR showed total aminothiols, Cys, Hcy, CysGly, and GSH increase by +48, +30, +58, and +158%, respectively (range p < 0.05-0.0001). ROS production was significantly correlated with TBARS and PC (R 2 = 0.38 and R 2 = 0.40; p < 0.0001) and aminothiols levels (range R 2 = 0.17-0.47; range p < 0.01-0.0001). In particular, ROS was directly correlated with the athletes' age (R 2 = 0.19; p < 0.05), with ultraendurance years of training (R 2 = 0.18; p < 0.05) and the days/week training activity (R 2 = 0.16; p < 0.05). Finally, the days/week training activity (hours/in the last 2 weeks) was found inversely correlated with the IL-6 postrace (R 2 = -0.21; p < 0.01). A strenuous performance, the Ironman® distance triathlon competition, alters the oxidant/antioxidant balance through a great OxS response that is directly correlated to the inflammatory parameters; furthermore, the obtained data suggest that an appropriate training time has to be selected in order to achieve the lowest ROS production and IL-6 concentration at the same time.

Atrial Fibrillation in Patients with Septic Shock: A One-Year Observational Pilot Study.

OBJECTIVE: The negative effect of sepsis on the myocardium affects its electric functionality. This study aims to evaluate the incidence of atrial fibrillation (AF) in patients with septic shock, and the mortality rate of patients with AF versus patients that maintained sinus rhythm (SR). METHODS: This is a one-year observational prospective pilot study. It was conducted at the Department of Anaesthesia and Intensive Care of Pisa University. Patients with septic shock were enrolled in this study. They were divided in two groups based on the occurrence of AF while in the ICU. Data were collected at admission and after 72 hours, and the data consisted of anamnesis, vital parameters, blood results and severity score. RESULTS: Out of 27 patients, 9 developed AF during the first 72 hours. At admission and at 72 hours, SOFA was statistically higher in the patients with AF (p=0.012 and p=0.002, respectively). In the AF group, the overall mortality was 66.7%, whereas, it was 11.1% (p=0.006) in the patients with SR. Age, rhythm and noradrenaline dosage were univariate predictors of total mortality. CONCLUSION: In patients with septic shock, AF has a high incidence, and it correlated with a worse outcome. Patients with higher SOFA score are at a greater risk of developing arrhythmia.

Gait training using a robotic hip exoskeleton improves metabolic gait efficiency in the elderly.

Robotic exoskeletons are regarded as promising technologies for neurological gait rehabilitation but have been investigated comparatively little as training aides to facilitate active aging in the elderly. This study investigated the feasibility of an exoskeletal Active Pelvis Orthosis (APO) for cardiopulmonary gait training in the elderly. Ten healthy elderly volunteers exhibited a decreased (-26.6 ± 16.1%) Metabolic Cost of Transport (MCoT) during treadmill walking following a 4-week APO-assisted training program, while no significant changes were observed for a randomly assigned control group (n = 10) performing traditional self-paced overground walking. Moreover, robot-assisted locomotion was found to require 4.24 ± 2.57% less oxygen consumption than free treadmill walking at the same speed. These findings support the adoption of exoskeletal devices for the training of frail individuals, thus opening new possibilities for sustainable strategies for healthy aging.

Acute Cardiovascular Adaptation to Strenuous Exercise: An Integrative Ultrasound Study.

OBJECTIVES: The aim of this study was to evaluate the acute effects of participation in an Ironman distance triathlon competition on arterial function by ultrasound, in relation to cardiac function and body water content. METHODS: Twenty-eight male triathletes participating in an Ironman distance competition underwent carotid, femoral, and cardiac ultrasound examinations. Moreover, the presence of extravascular lung water was identified by lung echo B-lines (echogenic coherent wedge-shaped signal with a narrow origin from the hyperechoic pleural line) at rest and within 20 minutes of arrival. RESULTS: At the end of the competition, athletes showed an increased heart rate (mean ± SD, from 60.2 ± 13.1 to 82.8 ± 15.6 beats/min; P < .0001) and unchanged mean blood pressure (from 93 ± 14 to 91 ± 10 mm Hg; P > .05) in the presence of negligible dehydration (total body water from 48.0 ± 4.0 to 46.5 ± 3.9 kg; P > .05). Cardiac output increased (from 5.5 ± 1.2 to 6.7 ± 2.4 L/min; P < .05) in the presence of an unchanged stroke volume (from 64 ± 14 to 59 ± 16 mL; P > .05) and unchanged left ventricular elastance (from 1.52 ± 0.48 to 1.39 ± 0.48 mm Hg/mL/m2 ; P > .05). The mean carotid diameter increased (from 7.19 ± 0.65 to 7.61 ± 0.76 mm; P < .05), whereas the mean femoral diameter was unchanged at the end of the competition (from 10.41 ± 0.83 to 10.49 ± 0.82 mm; P > .05). Carotid intima-media thickness was significantly reduced (from 537 ± 70 to 495 ± 70 µm; P < .05), whereas B-lines increased significantly after the competition (from 1 [0-4] to 12 [5-23]; P < .0001). CONCLUSIONS: These data suggest different acute functional adaptation in central arteries with respect to peripheral leg vessels.

Indoor air pollution exposure effects on lung and cardiovascular health in the High Himalayas, Nepal: An observational study.

BACKGROUND: Exposure to indoor biomass fuel smoke is associated with increased morbidity and mortality. The aim of this study is to evaluate the association between exposure to indoor biomass burning and early pulmonary and cardiovascular damage. METHODS: The indoor levels of particulate matter (PM) [PM10, PM2.5] and black carbon (BC) were monitored in 32 houses in a Himalayan village. Seventy-eight subjects were submitted to spirometry and cardiovascular evaluation [carotid to femoral pulse wave velocity (PWV) and echocardiography]. RESULTS: Peak indoor BC concentration up to 100 µg m-3 and PM10 - PM2.5 up to 1945-592 µg m-3 were measured. We found a non-reversible bronchial obstruction in 18% of subjects ≥40 yr; mean forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25-75) <80% in 54% of subjects, suggestive of early respiratory impairment, significantly and inversely related to age. Average BC was correlated with right ventricular-right atrium gradient (R = 0.449,p = .002), total peripheral resistances (TPR) (R = 0.313,p = .029) and PWV (R = 0.589,p < .0001) especially in subjects >30 yr. In multiple variable analysis, BC remained an independent predictor of PWV (ß = 0.556,p = .001), and TPR (ß = 0.366;p = .018). CONCLUSIONS: Indoor pollution exposure is associated to early pulmonary and cardiovascular damages, more evident for longer duration and higher intensity exposure.

Exaggerated systemic oxidative-inflammatory-nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression.

KEY POINTS: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. We examined if exaggerated oxidative-inflammatory-nitrosative stress (OXINOS) and corresponding decrease in vascular nitric oxide bioavailability in patients with CMS (CMS+) is associated with impaired cerebrovascular function and adverse neurological outcome. Systemic OXINOS was markedly elevated in CMS+ compared to healthy HA (CMS-) and low-altitude controls. OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. These findings are the first to suggest that a physiological continuum exists for hypoxaemia-induced systemic OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of more specialist neurological assessment and targeted support. ABSTRACT: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. The present cross-sectional study examined to what extent exaggerated systemic oxidative-inflammatory-nitrosative stress (OXINOS), defined by an increase in free radical formation and corresponding decrease in vascular nitric oxide (NO) bioavailability, is associated with impaired cerebrovascular function, accelerated cognitive decline and depression in CMS. Venous blood was obtained from healthy male lowlanders (80 m, n = 17), and age- and gender-matched HA dwellers born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 23) and without (CMS-, n = 14) CMS. We sampled blood for oxidative (electron paramagnetic resonance spectroscopy, HPLC), nitrosative (ozone-based chemiluminescence) and inflammatory (fluorescence) biomarkers. We employed transcranial Doppler ultrasound to measure cerebral blood flow (CBF) and reactivity. We utilised psychometric tests and validated questionnaires to assess cognition and depression. Highlanders exhibited elevated systemic OXINOS (P < 0.05 vs. lowlanders) that was especially exaggerated in the more hypoxaemic CMS+ patients (P < 0.05 vs. CMS-). OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. Collectively, these findings are the first to suggest that a physiological continuum exists for hypoxaemia-induced OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of specialist neurological assessment and support.

Right Heart-Pulmonary Circulation at High Altitude and the Development of Subclinical Pulmonary Interstitial Edema.

Most healthy subjects can develop a subclinical interstitial pulmonary edema that is a complex and multifactor phenomenon, still with unanswered questions, and might be one line of defense against the development of severe symptomatic lung edema. Whether the acute, reversible increase in lung fluid content is really an innocent and benign part of the adaptation to extreme physiologic condition or rather the clinically relevant marker of an individual vulnerability to life-threatening high altitude pulmonary edema remains to be established in future studies. Thus the question if encouraging more conservative habits to climb is right or not remains open.

The Right Heart International Network (RIGHT-NET): Rationale, Objectives, Methodology, and Clinical Implications.

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

Vascular Function Is Improved After an Environmental Enrichment Program: The Train the Brain-Mind the Vessel Study.

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65-89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid-femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P=0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10-3; P=0.009); only the latter remained significant after adjustment for confounders (P=0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P=0.006; P=0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34+ cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa-1; P=0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34+ cells, and preserved carotid distensibility. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01725178.

Relationship Between Occupational Physical Activity and Subclinical Vascular Damage in Moderate-Altitude Dwellers.

Ujka, Kristian, Rosa Maria Bruno, Luca Bastiani, Eva Bernardi, Paolo Sdringola, Nenad Dikic, Bikash Basyal, Sanjeeb Sundarshan Bhandari, Buddha Basnyat, Annalisa Cogo, and Lorenza Pratali. Relationship between occupational physical activity and subclinical vascular damage in moderate-altitude dwellers. High Alt Med Biol. 18:249-257, 2017. BACKGROUND: Occupational physical activity (OPA) has been associated with increased cardiovascular (CV) events. The aim of this study was to investigate the association between OPA and markers of subclinical vascular damage among a moderate-altitude population living in the rural village of Chaurikharka (Nepal; 2600 m sea level). METHODS: Seventy-two individuals (age 42 ± 15 years, ranges 15-85 years, 23 men) were enrolled. Physical activity (PA) was evaluated using the International Physical Activity Questionnaire (IPAQ). Carotid-femoral pulse wave velocity (PWV), carotid ultrasound assessment, and flow-mediated dilation (FMD) were performed. RESULTS: OPA was 9860 ± 5385 Metabolic Equivalent of Task (MET)-minutes/week, representing 77% of total energy expenditure, with 97% of the population performing high-intensity PA. In the univariate analysis, OPA was significantly associated with PWV (ß = 0.474, p = 0.001) and carotid stiffness (CS) (ß = 0.29, p = 0.019). In the multivariate analysis, including age, sex, oxygen saturation, mean blood pressure, low-density lipoprotein (LDL), and OPA, OPA remained an independent predictor of PWV (ß = 0.403, p = 0.001) but not of CS (ß = 0.028, p = 0.8). OPA remained an independent predictor of PWV independently from the Framingham risk score (FRS). CONCLUSION: High-intensity OPA shows a positive, independent association with aortic stiffness in Himalayan moderate-altitude dwellers. This study suggests how vigorous OPA performed in moderate altitude may be a CV risk factor.

Air blood barrier phenotype correlates with alveolo-capillary O2 equilibration in hypobaric hypoxia.

The O2 diffusion limitation across the air blood barrier (DO2 and subcomponents Dm and Vc) was evaluated in 17 healthy participants exposed to hypobaric hypoxia (HA, 3840m, PIO2 ∼90mmHg). A 10% decrease in alveolar volume (VA) in all participants suggested the development of sub-clinical interstitial lung edema. In >80% of participants DO2/VA increased, reflecting an individual strategy to cope with the hypoxia stimulus by remodulating Vc or Dm. Opposite changes in Dm/Vc ratio were observed and participants decreasing Vc showed reduced alveolar blood capillary transit time. The interplay between diffusion and perfusion (cardiac output) was estimated in order to investigate the individual adaptive response to hypoxia. It appears remarkable that despite individual differences in the adaptive response to HA, diffusion limitation did not exceed ∼11% of the alveolar-venous PO2 gradient, revealing an admirable functional design of the air-blood barrier to defend the O2 diffusion/perfusion function when facing hypobaric hypoxia corresponding to 50mmHg decreased PAO2.