LAMA improve tissue oxygenation more than LABA in patients with COPD.

Background The effect of bronchodilators is mainly assessed with forced expiratory volume in 1s (FEV1) in COPD. Their impact on oxygenation and lung periphery is less known. Objectives To compare the action of long-acting ß2-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD, considering their impact on proximal and peripheral ventilation as well as lung perfusion. Methods FEV1, Helium slope (SHe) from a single-breath washout test (SHe decrease reflecting a peripheral ventilation improvement), frequency dependence of resistance (R5-R19), area under reactance (AX), lung capillary blood volume (Vc) from double diffusion (DLNO/DLCO) and transcutaneous oxygenation (TcO2) were measured before and 2 hours post-LABA (day 1) and LAMA (day 3) in 30 COPD patients (FEV1 54±18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. Results TcO2 increased more (p=0.03) after LAMA (11±12%from baseline, p<0001) compared to LABA (4±11%, p=0.06) despite a lower FEV1 increase (p=0.03) and similar SHe (p=0.98), AX (p=0.63) and R5-R19 decreases (p=0.37). TcO2 and SHe changes were negatively correlated (r=-0.47, p=0.01) after LABA, not after LAMA (r=0.10, p=0.65). DLNO/DLCO decreased and Vc increased after LAMA (p=0.04; p=0.01, respectively) but not after LABA (p=0.53; p=0.24). Conclusion LAMA significantly improved tissue oxygenation in COPD patients, while only a trend was observed with LABA. The mechanisms involved may differ between both drugs: LABA increased peripheral ventilation while LAMA increased lung capillary blood volume. Should oxygenation differences persist over time, LAMA could arguably become the first therapeutic choice in COPD.

Smartphone-Derived Seismocardiography: Robust Approach for Accurate Cardiac Energy Assessment in Patients with Various Cardiovascular Conditions.

Seismocardiography (SCG), a method for measuring heart-induced chest vibrations, is gaining attention as a non-invasive, accessible, and cost-effective approach for cardiac pathologies, diagnosis, and monitoring. This study explores the integration of SCG acquired through smartphone technology by assessing the accuracy of metrics derived from smartphone recordings and their consistency when performed by patients. Therefore, we assessed smartphone-derived SCG's reliability in computing median kinetic energy parameters per record in 220 patients with various cardiovascular conditions. The study involved three key procedures: (1) simultaneous measurements of a validated hardware device and a commercial smartphone; (2) consecutive smartphone recordings performed by both clinicians and patients; (3) patients' self-conducted home recordings over three months. Our findings indicate a moderate-to-high reliability of smartphone-acquired SCG metrics compared to those obtained from a validated device, with intraclass correlation (ICC) > 0.77. The reliability of patient-acquired SCG metrics was high (ICC > 0.83). Within the cohort, 138 patients had smartphones that met the compatibility criteria for the study, with an observed at-home compliance rate of 41.4%. This research validates the potential of smartphone-derived SCG acquisition in providing repeatable SCG metrics in telemedicine, thus laying a foundation for future studies to enhance the precision of at-home cardiac data acquisition.

Body composition, cardiorespiratory fitness, and neuromuscular adaptations induced by a home-based whole-body high intensity interval training.

Background/objective: Bodyweight exercises performed at home could be a complementary approach to improve health-related fitness in people having little spare time and during stay-at-home periods. This study then investigated body composition, cardiorespiratory fitness, and neuromuscular adaptations to a home-based, video-directed, whole-body high-intensity interval training (WB-HIIT). Methods: Fourteen subjects participated to an 8-week WB-HIIT (6 females, 23 ± 1 years) and fourteen were included in a non-exercise control group (CTL; 6 females, 24 ± 4 years). All took part to pre- and post-intervention assessments of body composition, peak oxygen uptake (VO2peak) and first ventilatory threshold (VT1; index of aerobic capacity), dynamic (leg press 3-repetition maximum) and isometric strength (knee extensors maximal isometric contractions with assessment of voluntary activation), and muscle endurance during an isometric submaximal contraction maintained till exhaustion. WB-HIIT consisted in 30-s all-out whole-body exercises interspaced with 30 s of active recovery. Training sessions were performed at home by means of videos with demonstration of exercises. Heart rate was monitored during sessions. Results: WB-HIIT increased VO2peak (5%), VT1 (20%), leg lean mass (3%), dynamic (13%) and isometric strength (6%), and muscle endurance (28%; p < 0.05), while they did not improve in CTL. VO2peak increase was correlated (r = 0.56; p < 0.05) with the time spent above 80% of maximal heart rate during training sessions. Isometric strength increase was correlated with change in voluntary activation (r = 0.74; p < 0.01). Conclusion: The home-based WB-HIIT induced concomitant cardiorespiratory fitness and neuromuscular improvements. The predominant effect was observed for aerobic capacity and muscle endurance which could improve exercise tolerance and reduce fatigability.

Exercise as a non-pharmacological intervention to protect pancreatic beta cells in individuals with type 1 and type 2 diabetes.

AIMS/HYPOTHESIS: Diabetes is characterised by progressive loss of functional pancreatic beta cells. None of the therapeutic agents used to treat diabetes arrest this process; preventing beta cell loss remains a major unmet need. We have previously shown that serum from eight young healthy male participants who exercised for 8 weeks protected human islets and insulin-producing EndoC-ßH1 cells from apoptosis induced by proinflammatory cytokines or the endoplasmic reticulum (ER) stressor thapsigargin. Whether this protective effect is influenced by sex, age, training modality, ancestry or diabetes is unknown. METHODS: We enrolled 82 individuals, male or female, non-diabetic or diabetic, from different origins, in different supervised training protocols for 8-12 weeks (including training at home during the COVID-19 pandemic). EndoC-ßH1 cells were treated with 'exercised' serum or with the exerkine clusterin to ascertain cytoprotection from ER stress. RESULTS: The exercise interventions were effective and improved [Formula: see text] values in both younger and older, non-obese and obese, non-diabetic and diabetic participants. Serum obtained after training conferred significant beta cell protection (28% to 35% protection after 4 and 8 weeks of training, respectively) from severe ER stress-induced apoptosis. Cytoprotection was not affected by the type of exercise training or participant age, sex, BMI or ancestry, and persisted for up to 2 months after the end of the training programme. Serum from exercised participants with type 1 or type 2 diabetes was similarly protective. Clusterin reproduced the beneficial effects of exercised sera. CONCLUSIONS/INTERPRETATION: These data uncover the unexpected potential to preserve beta cell health by exercise training, opening a new avenue to prevent or slow diabetes progression through humoral muscle-beta cell crosstalk.

Beta-Adrenergic Receptor Blockade Effects on Cardio-Pulmonary Exercise Testing in Healthy Young Adults: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Beta-blockers are increasingly prescribed while the effects of beta-adrenergic receptor blockade on cardio-pulmonary exercise test (CPET)-derived parameters remain under-studied. METHODS: Twenty-one young healthy adults repeated three CPET at the same time with an interval of 7 days between each test. The tests were performed 3 h after a random, double-blind, cross-over single-dose intake of placebo, 2.5 mg or 5.0 mg bisoprolol, a cardio-selective beta1-adrenoreceptor antagonist. Gas exchange, heart rate (HR) and blood pressure (BP) were measured at rest and during cyclo-ergometric incremental CPET. RESULTS: Maximal workload and VO2max were unaffected by the treatment, with maximal respiratory exchange ratio > 1.15 in all tests. A beta-blocker dose-dependent effect reduced resting and maximal BP and HR and the chronotropic response to exercise, evaluated by the HR/VO2 slope (placebo: 2.9 ± 0.4 beat/ml/kg; 2.5 mg bisoprolol: 2.4 ± 0.5 beat/ml/kg; 5.0 mg bisoprolol: 2.3 ± 0.4 beat/ml/kg, p < 0.001). Ventilation efficiency measured by the VE/VCO2 slope and the ventilatory equivalent for CO2 at the ventilatory threshold were not affected by beta1-receptor blockade. Post-exercise chronotropic recovery measured after 1 min was enhanced under beta1-blocker (placebo: 26 ± 7 bpm; 2.5 mg bisoprolol: 32 ± 6 bpm; 5.0 mg bisoprolol: 33 ± 6 bpm, p < 0.01). CONCLUSION: The present results suggest that a single dose of bisoprolol does not affect metabolism, respiratory response and exercise capacity. However, beta-adrenergic blockade dose dependently reduces exercise hemodynamic response by lowering BP and the chronotropic response.

Validation Criteria for PETCO2 Kinetics during the Hyperventilation Provocation Test in the Diagnosis of Idiopathic Hyperventilation Syndrome.

Background: The hyperventilation provocation test (HPTest) is a diagnostic tool for idiopathic hyperventilation syndrome (HVS), encountered in some long-COVID patients. However, interpretation of the HPTest remains unclear regarding the relevant PETCO2 values to focus on and whether subjective symptoms should be considered. This study aimed to re-evaluate objective HPTest results for diagnosing HVS by determining accurate PETCO2 kinetics in two groups of patients previously screened via the Nijmegen questionnaire (NQ). Methods: The kinetics of PETCO2 during the HPTest were mathematically modeled and compared between 37 HVS patients (NQ ≥23/64) and 37 healthy controls (NQ <23/64) matched for gender, age, and body dimensions. AUC values with sensitivity and specificity were calculated, and analysis was monitored in a validation cohort of 152 routine HPTests. Results: A threshold value of a less than 12.8 mmHg increment of PETCO2 at the 5th minute of the recovery phase of the HPTest diagnosed HVS patients with excellent sensitivity (0.92) and specificity (0.84). These results were confirmed in the validation cohort, highlighting the presence of 24% false positives/negatives when diagnosing on the basis of complaints in the NQ. Conclusions: For HVS diagnosis, we suggest considering the HPTest, which can more reliably reflect the mechanisms of CO2 homeostasis and the response of the respiratory center to a stimulus, regardless of the subjective onset of symptoms.

Right ventricular-pulmonary arterial coupling impairment and exercise capacity in obese adults.

Background: Obesity-related exercise intolerance may be associated with pulmonary vascular and right ventricular dysfunction. This study tested the hypothesis that decreased pulmonary vascular reserve and right ventricular (RV)-pulmonary arterial (PA) uncoupling contributes to exercise limitation in subjects with obesity. Methods: Seventeen subjects with obesity were matched to normo-weighted healthy controls. All subjects underwent; exercise echocardiography, lung diffusing capacity (DL) for nitric oxide (NO) and carbon monoxide (CO) and an incremental cardiopulmonary exercise test. Cardiac output (Q), PA pressure (PAP) and tricuspid annular plane systolic excursion (TAPSE) were recorded at increasing exercise intensities. Pulmonary vascular reserve was assessed by multipoint mean PAP (mPAP)/Q relationships with more reserve defined by lesser increase in mPAP at increased Q, and RV-PA coupling was assessed by the TAPSE/systolic PAP (sPAP) ratio. Results: At rest, subjects with obesity displayed lower TAPSE/sPAP ratios (1.00 ± 0.26 vs. 1.19 ± 0.22 ml/mmHg, P < 0.05), DLCO and pulmonary capillary blood volume (52 ± 11 vs. 64 ± 13 ml, P < 0.01) compared to controls. Exercise was associated with steeper mPAP-Q slopes, decreased TAPSE/sPAP and lower peak O2 uptake (VO2peak). The changes in TAPSE/sPAP at exercise were correlated to the body fat mass (R = 0.39, P = 0.01) and VO2peak (R = 0.44, P < 0.01). Conclusion: Obesity is associated with a decreased pulmonary vascular and RV-PA coupling reserve which may impair exercise capacity.

Effectiveness of Whole-Body High-Intensity Interval Training on Health-Related Fitness: A Systematic Review and Meta-Analysis.

Due to its versatility, whole-body high-intensity interval training (WB-HIIT) can be proposed to the general population and patients to improve health-related fitness. However, its effectiveness compared to traditional aerobic continuous or interval trainings has yet to be determined. A search of four electronic databases was conducted. Studies reporting the effects of WB-HIIT on cardiorespiratory fitness (CRF), fat mass, fat-free mass, musculoskeletal fitness and metabolic risk factors were included. Standardized mean differences (SMD) between WB-HIIT and no exercise or traditional aerobic trainings were calculated. A meta-regression assessed the effect of total training time on the different outcomes. Twenty-two studies were included in the systematic review and nineteen in the meta-analysis. Compared to no exercise, WB-HIIT improves CRF (SMD: 0.75; 95%CI: 0.28, 1.23; p < 0.001), fat-free mass (SMD: 0.38; 95%CI: 0.11, 0.65; p < 0.001), fat mass (SMD: 0.40; 95%CI: 0.09, 0.72; p < 0.001) and musculoskeletal fitness (SMD: 0.84; 95%CI: 0.61, 1.08; p < 0.001). Compared to other aerobic trainings, WB-HIIT has a lower effect on CRF (SMD: −0.40; 95%CI: −0.70, −0.11; p = 0.007), a similar effect on fat-free mass (SMD: −0.04; 95%CI: −0.44, 0.35; p = 0.8) and fat mass (SMD: −0.07; 95%CI: −0.39, 0.25; p = 0.7), and a larger effect on musculoskeletal fitness (SMD: 0.42; 95%CI: 0.14, 0.71; p = 0.003). WB-HIIT overall effect and specific effect on CRF and fat mass were associated with total training time. The systematic review did not provide evidence of metabolic risk improvement. Despite a slightly lower effect on CRF, WB-HIIT is equally effective as traditional aerobic trainings to improve body composition and more effective to enhance musculoskeletal fitness, which is essential for execution of daily tasks.

Lean Mass Loss and Altered Muscular Aerobic Capacity after Bariatric Surgery.

INTRODUCTION: Patients undergoing weight loss surgery do not improve their aerobic capacity or peak oxygen uptake (VO2peak) after bariatric surgery and some still complain about asthenia and/or breathlessness. We investigated the hypothesis that a post-surgery muscular limitation could impact the ventilatory response to exercise by evaluating the post-surgery changes in muscle mass, strength, and muscular aerobic capacity, measured by the first ventilatory threshold (VT). METHODS: Thirteen patients with obesity were referred to our university exercise laboratory before and 6 months after bariatric surgery and were matched by sex, age, and height to healthy subjects with normal weight. All subjects underwent a clinical examination, blood sampling, and body composition assessment by dual-energy X-ray absorptiometry, respiratory and limb muscle strength assessments, and cardiopulmonary exercise testing on a cyclo-ergometer. RESULTS: Bariatric surgery resulted in a loss of 34% fat mass, 43% visceral adipose tissue, and 12% lean mass (LM) (p < 0.001). Absolute handgrip, quadriceps, or respiratory muscle strength remained unaffected, while quadriceps/handgrip strength relative to LM increased (p < 0.05). Absolute VO2peak or VO2peak/LM did not improve and the first VT was decreased after surgery (1.4 ± 0.3 vs. 1.1 ± 0.4 L min-1, p < 0.05) and correlated to the exercising LM (LM legs) (R = 0.84, p < 0.001). CONCLUSIONS: Although bariatric surgery has numerous beneficial effects, absolute VO2peak does not improve and the weight loss-induced LM reduction is associated to an altered muscular aerobic capacity, as reflected by an early VT triggering early exercise hyperventilation.

Exercise stress echocardiography of the pulmonary circulation and right ventricular-arterial coupling in healthy adolescents.

AIMS: To explore the effects of age and sex in adolescents vs. young or middle-aged adults on pulmonary vascular function and right ventricular-arterial (RV-PA) coupling as assessed by exercise stress echocardiography. METHODS AND RESULTS: Forty healthy adolescents aged 12-15 years were compared with 40 young adults aged 17-22 years and 40 middle-aged adults aged 30-50 years. Sex distribution was equal in the three groups. All the subjects underwent an exercise stress echocardiography. A pulmonary vascular distensibility coefficient α was determined from multipoint pulmonary vascular pressure-flow relationships. RV-PA coupling was assessed by the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio, who has been previously validated by invasive study. While cardiac index and mean PAP were not different, adolescents compared to young and middle-aged adults, respectively had higher pulmonary vascular distensibility coefficients α (1.60 ± 0.31%/mmHg vs. 1.39 ± 0.29%/mmHg vs. 1.20 ± 0.35%/mmHg, P < 0.00001). Adolescents and young adults compared to middle-aged adults, respectively had higher TAPSE/PASP ratios at rest (1.24 ± 0.18 mm/mmHg and 1.22 ± 0.17 mm/mmHg vs. 1.07 ± 0.18 mm/mmHg, P < 0.008) and during exercise (0.86 ± 0.24, 0.80 ± 0.15 and 0.72 ± 0.15 mm/mmHg, P < 0.04). The TAPSE/PASP ratio decreased with exercise. There were no sex differences in α or TAPSE/PASP. CONCLUSION: Compared to adults, adolescents present with a sex-independent more distensible pulmonary circulation. Resting and exercise RV-PA coupling is decreased in middle-aged adults.

Noninvasive Pulmonary Hemodynamic Evaluation in Athletes With Exercise-Induced Hypoxemia.

BACKGROUND: Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia (ie, a significant fall in hemoglobin oxygen saturation [Spo2]) during sea level exercise in endurance-trained athletes. It is unknown whether there are specific properties of pulmonary vascular function in athletes exhibiting oxygen desaturation. METHODS: Ten endurance-trained athletes with exercise-induced hypoxemia (EIH), nine endurance-trained athletes with no exercise-induced hypoxemia (NEIH), and 10 untrained control subjects underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for carbon monoxide (Dlco) and lung diffusion capacity for nitric oxide (Dlno) testing. Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure, pulmonary vascular resistance (PVR), cardiac output (Qc), and pulmonary vascular distensibility (alpha) mathematically determined from the curvilinearity of the multi-point mPAP/Qc relation. RESULTS: EIH athletes exhibited a lower exercise-induced PVR decrease compared with the untrained and NEIH groups (P < .001). EIH athletes showed higher maximal mPAP compared with NEIH athletes (45.4 ± 0.9 mm Hg vs 41.6 ± 0.9 mm Hg, respectively; P = .003); there was no difference between the NEIH and untrained subjects. Alpha was lower in the EIH group compared with the NEIH group (P < .05). Maximal mPAP, Pcap, and alpha were correlated with the fall of Spo2 during exercise (P < .01, P < .01, and P < .05). Dlno and Dlco increased with exercise in all groups, with no differences between groups. Dlno/Qc was correlated to the exercise-induced Spo2 changes (P < .05). CONCLUSIONS: EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility, or exercise-induced changes in PVR compared with NEIH subjects, in keeping with pulmonary capillary stress failure or intrapulmonary shunting hypotheses.

Short halt in vaping modifies cardiorespiratory parameters and urine metabolome: a randomized trial.

Propylene glycol and glycerol are e-cigarette constituents that facilitate liquid vaporization and nicotine transport. As these small hydrophilic molecules quickly cross the lung epithelium, we hypothesized that short-term cessation of vaping in regular users would completely clear aerosol deposit from the lungs and reverse vaping-induced cardiorespiratory toxicity. We aimed to assess the acute effects of vaping and their reversibility on biological/clinical cardiorespiratory parameters [serum/urine pneumoproteins, hemodynamic parameters, lung-function test and diffusing capacities, transcutaneous gas tensions (primary outcome), and skin microcirculatory blood flow]. Regular e-cigarette users were enrolled in this randomized, investigator-blinded, three-period crossover study. The periods consisted of nicotine-vaping (nicotine-session), nicotine-free vaping (nicotine-free-session), and complete cessation of vaping (stop-session), all maintained for 5 days before the session began. Multiparametric metabolomic analyses were used to verify subjects' protocol compliance. Biological/clinical cardiorespiratory parameters were assessed at the beginning of each session (baseline) and after acute vaping exposure. Compared with the nicotine- and nicotine-free-sessions, a specific metabolomic signature characterized the stop-session. Baseline serum club cell protein-16 was higher during the stop-session than the other sessions (P < 0.01), and heart rate was higher in the nicotine-session (P < 0.001). Compared with acute sham-vaping in the stop-session, acute nicotine-vaping (nicotine-session) and acute nicotine-free vaping (nicotine-free-session) slightly decreased skin oxygen tension (P < 0.05). In regular e-cigarette-users, short-term vaping cessation seemed to shift baseline urine metabolome and increased serum club cell protein-16 concentration, suggesting a decrease in lung inflammation. Additionally, acute vaping with and without nicotine decreased slightly transcutaneous oxygen tension, likely as a result of lung gas exchanges disturbances.

Assessment of energy expenditure during high intensity cycling and running using a heart rate and activity monitor in young active adults.

OBJECTIVE: Although high intensity physical activities may represent a great proportion of the total energy expenditure in active people, only sparse studies have investigated the accuracy of wearable monitors to assess activity related energy expenditure (AEE) during high intensity exercises. Therefore, the purpose of the present study was to investigate the accuracy of the Actiheart, a light portable monitor estimating AEE based on heart rate (HR) and activity counts (ACT), during two popular activities (running and cycling) performed at high intensities. The benefit of an individual calibration of the HR-AEE relationship established during a preliminary maximal test was also evaluated. METHODS: AEE was estimated in eighteen active adults (4 women and 14 men; 25 ± 4 yr) with indirect calorimetry using a respiratory gas analysis system (reference method) and the Actiheart during 5-min running and cycling at 60, 75 and 85% of maximal oxygen uptake (VO2max) previously determined during a maximal test performed on a treadmill or cycle ergometer. For the Actiheart, AEE was estimated either using the group or individual calibrated equations available in the dedicated software, and their respective HR, ACT or combined HR/ACT algorithms. RESULTS: When the HR algorithm was used for cycling and the HR or HR/ACT algorithms for running, AEE measured by the Actiheart increased proportionally to exercise intensity from 60 to 85% VO2max (P<0.001). Compared to indirect calorimetry, the Actiheart group calibrated equations slightly to moderately underestimated (3 to 20%) AEE for the three exercise intensities (P<0.001). Accuracy of AEE estimation was greatly improved by individual calibration of the HR-AEE relationship (underestimation below 5% and intraclass correlation coefficient [ICC]: 0.79-0.93) compared to group calibration (ICC: 0.64-0.79). CONCLUSION: The Actiheart enables to assess AEE during high intensity running and cycling when the appropriate algorithm is applied. Since an underestimation was present for group calibration, an individual and sport-specific calibration should be performed when a high accuracy is required.

Impact of Bariatric Surgery on Women Aerobic Exercise Capacity.

RATIONALE: Bariatric surgery has a considerable positive effect on weight loss and on metabolic and cardiovascular risks. It has therefore been extensively used this last decade to overcome obesity. However, the impact of this surgery on exercise capacity remains unclear. The aim of this study is to clarify the impact of a surgically induced weight loss on aerobic exercise capacity (VO2max) in a specific middle-aged female population. METHODS: Forty-two women with a body mass index > 40 kg/m2 (age, 42 ± 13 years; weight, 117 ± 15 kg) underwent blood analyses and a cardiopulmonary exercise test (CPET) before and 1 year after bariatric surgery. CPET was performed on a cycloergometer. The first ventilatory threshold (VT1) was measured according to the V-slope method. RESULTS: Absolute VO2max was reduced by 10% after surgery (2.0 ± 0.4 vs 1.8 ± 0.4 l/min, p < 0.01) or increased when corrected for body weight (18 ± 4 vs 23 ± 4 l/min/kg, p < 0.001) or unchanged when expressed as percentage of predicted values (111 ± 21 vs 105 ± 22, p = 0.06). Weight loss did not affect ventilatory or chronotropic response but increased maximal respiratory exchange ratio (RER) (p < 0.001), decreased maximal O2pulse (p < 0.05) and VT1 in milliliters per minute (p < 0.01). By multivariable analysis, decreased absolute VO2max after weight loss was associated with increased maximal RER and reduced maximal O2pulse (p < 0.05, p < 0.01 respectively), possibly related to a muscular mass limitation. CONCLUSIONS: Weight loss induced by bariatric surgery may reduce aerobic capacity in women in relation to muscle mass loss.

Right ventricular dyssynchrony during hypoxic breathing but not during exercise in healthy subjects: a speckle tracking echocardiography study.

NEW FINDINGS: What is the central question of this study? Right ventricular dyssynchrony in severe pulmonary hypertension is associated with a poor prognosis. However, it has recently been observed in patients with lung or connective tissue disease and pulmonary artery pressure at the upper limits of normal. The mechanisms of right ventricular dyssynchrony in pulmonary hypertension remain uncertain. What is the main finding and its importance? Acute hypoxic breathing, but not normoxic exercise, induces an increase in right ventricular dyssynchrony detected by speckle tracking echocardiography in healthy subjects. These results add new insights into the determinants of right ventricular dyssynchrony, suggesting a role for systemic factors added to afterload in the pathophysiology of right ventricular inhomogeneity of contraction. ABSTRACT: Pulmonary hypertension (PH) has been shown to be associated with regional inhomogeneity (or dyssynchrony) of right ventricular (RV) contraction. Right ventricular dyssynchrony is an independent predictor of decreased survival in advanced PH, but has also been reported in patients with only mildly elevated pulmonary artery pressure (PAP). The mechanisms of RV dyssynchrony in PH remain uncertain. Our aim was to evaluate RV regional function in healthy subjects during acute hypoxia and during exercise. Seventeen healthy subjects (24 ± 6 years) underwent a speckle tracking echocardiography of the RV at rest in normoxia and every 15 min during a 60 min exposure to hypoxic breathing ( F I O 2 12%). Ten of the subjects also underwent an incremental cycle ergometry in normoxia to 100 W, with the same echocardiographic measurements. Dyssynchrony was measured as the SD of the times to peak systolic strain of the four basal and mid RV segments corrected for the heart rate (RV-SD4). RV-SD4 increased during hypoxia from 12 ± 7 to 22 ± 11 ms in spite of mild increases in mean PAP (mPAP) from 15 ± 2 to 20 ± 2 mmHg and pulmonary vascular resistance (PVR) from 1.18 ± 0.15 to 1.4 ± 0.15 Wood units (WU). During exercise RV-SD4 did not significantly change (from 12 ± 6 ms to 14 ± 6 ms), while mPAP increased to 25 ± 2 mmHg and PVR was unchanged. These data show that in healthy subjects, RV contraction is inhomogeneous in hypoxia but not during exercise. Since PAP increases more during exercise, RV dyssynchrony in hypoxia may be explained by a combination of mechanical (RV afterload) and systemic (hypoxia) factors.

Pulmonary Vascular Function and Aerobic Exercise Capacity at Moderate Altitude.

PURPOSE: There has been suggestion that a greater "pulmonary vascular reserve" defined by a low pulmonary vascular resistance (PVR) and a high lung diffusing capacity (DL) allow for a superior aerobic exercise capacity. How pulmonary vascular reserve might affect exercise capacity at moderate altitude is not known. METHODS: Thirty-eight healthy subjects underwent an exercise stress echocardiography of the pulmonary circulation, combined with measurements of DL for nitric oxide (NO) and carbon monoxide (CO) and a cardiopulmonary exercise test at sea level and at an altitude of 2250 m. RESULTS: At rest, moderate altitude decreased arterial oxygen content (CaO2) from 19.1 ± 1.6 to 18.4 ± 1.7 mL·dL, P < 0.001, and slightly increased PVR, DLNO, and DLCO. Exercise at moderate altitude was associated with decreases in maximum O2 uptake (V˙O2max), from 51 ± 9 to 43 ± 8 mL·kg⋅min, P < 0.001, and CaO2 to 16.5 ± 1.7 mL·dL, P < 0.001, but no different cardiac output, PVR, and pulmonary vascular distensibility. DLNO was inversely correlated to the ventilatory equivalent of CO2 (V˙E/V˙CO2) at sea level and at moderate altitude. Independent determinants of V˙O2max as determined by a multivariable analysis were the slope of mean pulmonary artery pressure-cardiac output relationship, resting stroke volume, and resting DLNO at sea level as well as at moderate altitude. The magnitude of the decrease in V˙O2max at moderate altitude was independently predicted by more pronounced exercise-induced decrease in CaO2 at moderate altitude. CONCLUSION: Aerobic exercise capacity is similarly modulated by pulmonary vascular reserve at moderate altitude and at sea level. Decreased aerobic exercise capacity at moderate altitude is mainly explained by exercise-induced decrease in arterial oxygenation.

Lung diffusing capacity in sub-Saharan Africans versus European Caucasians.

Single breath measurements of lung diffusing capacity (DL) for carbon monoxide (CO) and nitric oxide (NO) were performed in age-, sex-, weight- and height-matched 32 sub-Saharan Africans (13 women) and 32 Caucasian Europeans, and repeated in 14 of each group at 80% of maximum exercise capacity. In Africans versus Caucasians respectively, DLNO was 153±31 vs 176±38ml/mmHg/min at rest (P<0.001) and 210±48 vs 241±52ml/mmHg/min at exercise (P<0.01) while hemoglobin-adjusted DLCO was 29±6 vs 34±6ml/mmHg/min at rest (P<0.001), and 46±11 vs 51±13ml/mmHg/min at exercise (P<0.01). However there were no differences in DLCO/alveolar volume(VA) (KCO) and DLNO/VA(KNO). The sitting-to-standing height ratio was lower in the Africans. Differences in lung volume with respect to body height explain lower DLNO and DLCO in sub-Saharan Africans as compared to Caucasian Europeans.