Decrease In VO2 Research Articles

Exercise gas exchange phenotyping according to body mass index: a population-based study in an apparently healthy population

Abstract Background Obesity is a widespread medical condition consisting in a BMI > 30 kg/m2. The link between BMI, exercise performance and cardiovascular risk is not well defined on large set of apparently healthy subjects. Aim In this population-based trial of apparently healthy individuals we aimed at defining the exercise gas exchange phenotype by cardiopulmonary exercise testing (CPET) according to BMI strata. Methods 932 subjects (54.7% females) presenting with none to five major cardiovascular risk factors (MCVRFs; hypertension, diabetes, tabagism, dyslipidaemia, BMI> 25), underwent CPET and were divided in 3 categories (normal weight; NW, overweight; OW and obese; Ob). Cohort analysis was carried out by dividing and analysing patients into groups based on BMI, sex, and number of MCVRFs. Peak VO2 was considered normal for a predicted value > 80%. Composite endpoint was defined as the combination of the following events: cardiovasular mortality, cardiovascular hospitalization, coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), percutaneous coronary intervention (PCI), TAVI (Transcatheter aortic valve implantation), cardiac surgery, acute pulmonary oedema or stroke/transient ischemic attack (TIA). Results the number of MCVRFs significantly increased (CI 95%, p-value 0,009) through BMI strata being in NW, OW and Ob 1.6, 2.7, 2.9 respectively. Peak VO2 significantly (CI 95%, p-value <0,001) decreased with rise in BMI (21.8ml/min/kg, 18.7 ml/min/kg, 15.5 ml/min/kg for NW, OW and Ob, respectively; p-value <0,001). A significant correlation between the increase in number of MCRVFs and the decrease in peak VO2 was documented for BMI<30 (-0.44 for NW and -0.30 for OW; p-value <0,001), whereas Ob exhibited the lowest mean peak VO2 which was unaffected by the increasing number of MCVRFs. (figure 1). HRR (Heart rate reserve) was significantly lower in Ob subjects compared to OW and NW (respectively 0.59, 0.68, 0.72 p-value <0,001). Regression models showed that neither risk factors nor CPET variables were predictive for composite endpoint in NW. Interestingly, peak VO2 (OR 0,93 [CI 0,86-0,99] p-value 0,039) and VE/VCO2 slope (OR 1,06 [CI 1,00-1,11] p-value 0,047) were predictive of composite endpoint just in OW with Ob subjects showing similar trend not reaching statistical power; Diabetes was predictive of composite endpoint in Ob cohort. KM curves reported higher event rates in OW subjects with higher VE/VCO2 slope and lower peak VO2. (figure 2) Conclusions As far as obesity is concerned, regardless of the number of MCVRFs, BMI is the single strong determinant of exercise performance and gas exchange phenotype. In OW and NW cohorts, the cumulative number of MCVRFs impacts on worse exercise performance and gas exchange inefficiency. Lower peak VO2 and higher VE/VCO2 slope are predictive of CV composite endpoint in OW and a similar trend was observed in Ob.BMI and peak VO2KM BMI 25-30

Effect of Deep Hypothermia (18°C) on Dioxygen Metabolism During Pulmonary Thromboendarterectomy Surgery

Objectives: The aim of this physiological pilot study was to investigate the effect of deep hypothermia on oxygen extraction (OE) and consumption (VO2) in normothermic conditions (36-37°C) then at different stages of cooling: 30°C, 25°C and 18°C. Design: For three months, we conduct a prospective study on patients that underwent pulmonary thromboendarterectomy. Settings: This is a single center study done in a university teaching hospital. ParticipantsPatients that underwent pulmonary thromboendarterectomy during the inclusion period. InterventionsHemodynamic and biological data were recorded from arterial and venous blood gas samples withdrawn first at normothermia, then at 30°C, 25°C and 18°C.. Measurements and Main Results24 patients were included in the final analysis. Indexed VO2 decreased from 65.9 ml to 25.1 ml of O2/min/m2 between 36°C and 18°C (p<0.001). The OE decreased from 18% to 9% between 36°C and 18°C (p<0.001). At normal temperature and at 18°C, the median venoarterial difference of O2 bound to hemoglobin was 2.22 [1.68-2.58] and 0.03 [0.01-0.07] ml of O2/100 ml of blood, respectively (p<0.001). Whereas the median venoarterial difference of dissolved O2 was 0.78 [0.66-0.92] and 1.09 [1.03-1.32] ml of O2/100 ml of blood, respectively (p=0.0013). Conclusion: There is a VO2 and OE decrease of more than half of their baseline value at 18°C. Seeing that the metabolic needs are essentially supplied from dissolved O2 during cooling from 30°C to 18°C, we suggest that PaO2 should be increased during the period of cooling and/or of deep hypothermia to prevent hypoxia.

High-intensity aerobic exercise training improves exercise capacity, dyspnea, and fatigue in patients with severe asthma using triple inhaler.

Asthma is a chronic respiratory disease that affects millions of people worldwide and causes severe symptoms such as wheezing, coughing, and breathing difficulty. Despite modern treatments, 3%-10% of patients develop severe asthma, which requires high-dose medications, and they may still experience frequent and severe symptoms, exacerbations, and psychological impacts. This study aimed to investigate the effects of high-intensity aerobic exercise training (HIAET) in patients with severe asthma. Patients with severe asthma were recruited, and cardiopulmonary exercise tests, dyspnea, and leg fatigue scores were performed before HIAET. Participants underwent a 12-week hospital-based HIAET, which involved exercising twice weekly to reach 80% of their peak oxygen uptake (VO2). Eighteen patients with severe asthma underwent HIAET, which resulted in significant improvement in peak VO2 (1214.0 ± 297.9-1349.4 ± 311.2 mL/min, P = 0.004) and work rate (80.6 ± 21.2-96.2 ± 24.8 watt, P < 0.001) and decrease in dyspnea (5.1 ± 1.8-4.1 ± 1.2, P = 0.017) and fatigue scores (5.2 ± 2.3-4.0 ± 1.2, P = 0.020) at peak exercise. No significant changes were observed in spirometry results, respiratory muscle strength, or circulatory parameters. HIAET can lead to improved exercise capacity and reduced dyspnea and fatigue scores at peak exercise without changes in spirometry, respiratory muscle strength, and circulatory parameters.

A facile pathway to fabricate VO2(M) nanoparticles via sol-gel method for flexible thermochromic films with efficient infrared stealth

Large-scale production of uniformly sized Monoclinic vanadium dioxide (VO2(M)) nanoparticles for the flexible films with efficient thermochromic properties remains a challenge. Herein, we reported a facile, scalable sol-gel method combined with post-annealing to synthesize spherical VO2(M) nanoparticles by controlling the concentration of H2O2 solution, the oxygen intake, annealing time and annealing temperature. Optimized VO2(M) nanoparticles had a particle size of about 64.1 ± 25.4 nm and a phase transition temperature of 72.0 ± 1.2 °C with an accompanying latent heat of 25.52 ± 1.89 J/g. The flexible films containing optimal VO2(M) nanoparticles exhibited excellent thermochromic performances with solar modulation efficiency of 8.9 ± 0.6 % and luminescence transmittance of 56.4 ± 2.3 %, and also showed distinct infrared stealth characteristics. This work demonstrated a promising route to prepare uniform nano-oxides via sol-gel method, and proved that the size decrease of VO2(M) nanoparticles facilitates to the improvement of the flexible films thermochromic properties.

Changes in physical performance after Fontan operation: a follow-up study

Abstract Background Maximal oxygen consumption (peak VO2) is markedly compromised in patients with Fontan circulation compared to healthy subjects. In addition to the natural aging process, adaptive mechanisms inherent to univentricular physiology may further contribute to a decline in peak VO2 over time. These patients may have limitations in their ability to engage in physical activity, which may exacerbate the decline in peak VO2. This study aims to quantify the impairment of functional capacity over time in patients in the late postoperative period of Fontan operation and the relationship with a sedentary lifestyle. Method We studied 46 patients, 57% female, with a median age of 28 (24 - 35) years and 17 (15 - 21) years after Fontan surgery. Maximum and submaximal variables were analyzed from two standardized cardiopulmonary exercise tests (CPET) on a treadmill and performed with a range of five (4 - 9) years between them. All patients' physical activity levels were ranked using the short version of the International Physical Activity Questionnaire (IPAQ), comparing the functional capacity between active and sedentary patients. Clinical and surgical data were extracted from medical records. We performed a descriptive analysis of the demographic, clinical, and surgical data and a comparative analysis between the variables of the first and second CPET. The annual change was calculated by dividing the differences between the last and first tests by the time interval between them. Maximal variables were analyzed only for patients who achieved a maximum test (respiratory exchange ratio was equal to or greater than ≥ 1.1, heart rate &amp;gt; 85% of the predicted, and signs of intense effort. Results Among the 46 patients in the study, 40 performed maximum CPET. The characteristics of patients are shown in Table 1. There was an annual decrease in peak VO2 of 0.42 (1.17- -0.71) mL/kg/min and 0.72 (-2.14 - 0.71) % of predicted VO2. Impaired submaximal parameters occurred in all patients. There was an increased number of sedentary subjects on the second test compared with the first (p=0.009) (Table 2). Comparing the functional capacity of inactive patients with active, we found lower values in peak VO2: 23.1 (20.8-25.1) vs. 35.1 (32.0-35.4) mL/kg/min (p&amp;lt;0.001) and in a percentage of predicted 62 (59-67) vs. 84 (76-97) % (p=0.012). When analyzing the ejection fraction of the systemic ventricle by most recent echocardiogram and brain natriuretic peptide (BNP) plasmatic level, these variables were not significantly changed. Conclusion Functional capacity decreased over time in the studied population, represented mainly by a significant annual loss in peak VO2 and the predicted age values. Reduced functional capacity was observed in the inactive patients compared with active. No change in ventricular function was identified, as well as in BNP plasmatic level over time.Table_1Table_2

Cardiopulmonary Test As A Component in the Diagnostic Algorithm for Heart Failure with Preserved Left Ventricular Ejection Fraction in Patients with Atrial Fibrillation

Background: Patients with heart failure with preserved ejection fraction account for more than half of all hospitalizations because of heart failure. On the other hand, atrial fibrillation and heart failure are quite often diagnosed together and one disease influences the development of the other. Timely and accurate diagnosis of heart failure with preserved ejection fraction is the basis for effective treatment of this category of patients. In 2019, the HFA-PEFF algorithm of diagnosis heart failure with preserved ejection fraction (including patients with atrial fibrillation) was proposed. However, the algorithm implies cardiac catheterization in patients at intermediate risk, which involves certain difficulties and cannot be used in routine practice. As an alternative to cardiac catheterization in the diagnosis of heart failure with preserved ejection fraction, we proposed a noninvasive diagnostic method cardiopulmonary test. However, the value of cardiopulmonary test technique has not been conclusively studied, especially in patients with a combination of chronic heart failure and atrial fibrillation. Aim: The aim of the study was to evaluate the role of the cardiopulmonary test in the diagnosis of heart failure with preserved ejection fraction in patients with atrial fibrillation. Methods: 138 patients with atrial fibrillation were included in our study. Using HFA-PEFF algorithm (algorithm for diagnosis of heart failure with preserved left ventricular ejection fraction) all patients were initially divided into 3 groups: low probability of heart failure 23 patients, intermediate probability 96 and high probability 19 patients. The stress-test allowed to precisely assess of patients at intermediate risk and finally form the groups: Group 1 without heart failure, 85 patients (61.6%); Group 2 patients with heart failure and preserved ejection fraction, 53 patients (38.4%). The next diagnostic stage was cardiopulmonary test. Results: During cardiopulmonary test, the anaerobic exercise threshold was 6.8 and 4.85 METs for the first and second groups, respectively (p 0.001), reflecting lower exercise tolerance in the second group of patients. Analysis of variance (ANOVA) demonstrated a statistically significant increase in pro-BNP levels with a decrease in peak VO2 (p 0.001). Also, analysis of variance demonstrated a significant statistical difference with respect to systolic pulmonary artery pressure in the subgroups with severely, moderately reduced oxygen consumption and in the group with normal peak VO2 (p=0.01). ROC analysis determined a peak VO2 of 20 ml/kg/min, above which the HFA-PEFF algorithm was unlikely to detect heart failure (AUC 0.73; confidence interval 0.650.82; p=0.043; sensitivity 85%; specificity 51%). Conclusion: The cardiopulmonary test is a reliable instrumental non-invasive method in the diagnosis of heart failure with preserved ejection fraction.

Metabolic Manipulation and Therapeutic Hypothermia.

Hypothermia has multiple physiological effects, including decreasing metabolic rate and oxygen consumption (VO2). There are few human data about the magnitude of change in VO2 with decreases in core temperature. We aimed to quantify to magnitude of reduction in resting VO2 as we reduced core temperature in lightly sedated healthy individuals. After informed consent and physical screening, we cooled participants by rapidly infusing 20 mL/kg of cold (4°C) saline intravenously and placing surface cooling pads on the torso. We attempted to suppress shivering using a 1 mcg/kg intravenous bolus of dexmedetomidine followed by titrated infusion at 1.0 to 1.5 μg/(kg·h). We measured resting metabolic rate VO2 through indirect calorimetry at baseline (37°C) and at 36°C, 35°C, 34°C, and 33°C. Nine participants had mean age 30 (standard deviation 10) years and 7 (78%) were male. Baseline VO2 was 3.36 mL/(kg·min) (interquartile range 2.98-3.76) mL/(kg·min). VO2 was associated with core temperature and declined with each degree decrease in core temperature, unless shivering occurred. Over the entire range from 37°C to 33°C, median VO2 declined 0.7 mL/(kg·min) (20.8%) in the absence of shivering. The largest average decrease in VO2 per degree Celsius was by 0.46 mL/(kg·min) (13.7%) and occurred between 37°C and 36°C in the absence of shivering. After a participant developed shivering, core body temperature did not decrease further, and VO2 increased. In lightly sedated humans, metabolic rate decreases around 5.2% for each 1°C decrease in core temperature from 37°C to 33°C. Because the largest decrease in metabolic rate occurs between 37°C and 36°C, subclinical shivering or other homeostatic reflexes may be present at lower temperatures.

P286 IMPACT OF PERSONAL PROTECTIVE MASKS ON CARDIORESPIRATORY VARIABLES IN HEALTHY SUBJECTS AND PATIENTS WITH HEART FAILURE: AN INTERIM ANALYSIS

Abstract Background protective masks are a powerful mean to contain COVID–19. However, a general feeling that masks alter the normal dynamics of breathing may reduce its application. Patients with heart failure (HF) experience dyspnea even during daily life activities (ADLs). Aim of the study is to evaluate cardiorespiratory parameters during ADLs, cardiopulmonary exercise test (CPET) to highlight differences related to protective masks. Methods 9 healthy subjects (age 59±11, 2F) and 10 HF patients (age 64±11, 2F, EF &amp;lt;45%) underwent a set of tests twice, wearing a protective surgical mask and without it. We performed the following tests: standard spirometry; CPET; a set of tests recorded by a wearable ergospirometer (Cosmed K5), including ADLs), six–minute walking test (6MWT) and two 4–minute treadmill exercises (TREAD2 and TREAD3 at a speed of 2 km/h and 3 km/h, respectively). Results Spirometry showed a reduction of forced expiratory volume in 1s (3.29±0.75 L vs 2.65±0.57 L as for healthy subjects, p= 0.002; 2.45±0.6 L vs 1.97±0.54 L as for HF patients, p= 0.002) and forced vital capacity (4.14±0.92 L vs 3.39±0.83 L as for healthy subjects, p= 0.004; 2.93±0.76 L vs 2.59±0.73 L as for HF patients, p= 0.01) in both the groups from no mask to mask. Both healthy and HF patients showed: a trend of reduction of peak oxygen pulse (p&amp;lt;0.005 in healthy) and peak oxygen consumption (VO2); a decrease of tidal volume (Vt) at peak exercise (peak Vt: 2.283±0.449 L vs 1.864±0.359 L in healthy, p= 0.022; 1.6±0.41 L vs 1.448±0.431 L in HF, p= 0.02), with no significative variations of resting and peak ventilation (VE). HF patients experienced a statistically significative decrease of VO2 at the anaerobic threshold (AT) (794±227 vs 682±151 mL · min–1, p=0.01). Task–related VO2 was significantly reduced from no mask to mask in ALDs and 6MWT in the healthy, whereas HF patients experienced a significative reduction more physically demanding tasks. Both healthy and HF subjects showed an increase in the basal and task–related ratio of VE vs carbon dioxide production (VE/VCO2) in the two protocol conditions. Conclusions Surgical masks influences cardiorespiratory variables in healthy and HF patients at rest and during both mild and maximal physical activity. The physiological impact of the mask is far from being clinically relevant The use of masks seems to be safe both in the general population and in HF patients. These data should be confirmed in a larger group of patients.

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

The effects of overfeeding highly palatable diets via the cafeteria feeding diet method (Café) has been shown to be a reliable experimental model to induce diet induced thermogenesis (DIT) in young adult normally lean rats of several strains. Groups of young adult lean LA/Ntul//-cp rats were offered a Purina chow diet (CHOW) or the same diet plus a daily café supplement both ad libitum from 10 until 24 weeks of age. The drug α-methylparatyrosine (α-MPT) was administered to groups (250 mg α-MPT/kg BW, i.p.) to ablate sympathetic (SNS) activity or a sham injection of physiologic saline given, and measures of fasting resting thermogenesis obtained at thermal neutrality (30°C) before and after the α-MPT or sham administration. The Café diet resulted in a 67% increase in body weight (BW) and a ~25% increase in resting oxygen consumption (VO2) following café overfeeding in both groups, while only a 40% increase in BW and no additional increase in VO2 occurred in normally CHOW fed rats while the sham injection was without any variations from normal physiologic responses as predicted. Sympathetic blockade with α-MPT was associated with modest decreases in body temperature and an average ~12-15% decrease in VO2 in the café treated group, but when the VO2 data were arithmetically corrected to isothermal conditions only a net 3% decrease occurred in CHOW fed rats and was without effect on the SHAM group. Serum T3 concentrations increased by 92% and urinary catecholamine excretion of VMA &gt;250% following the café diet, but the urinary vanilmandelic acid (VMA) excretion was virtually nil following the sympathetic blockade. These observations indicate that the SNS-mediated contribution component to DIT following prolonged café overfeeding under conditions of thermal neutrality contribute approximately 50% of the thermic response. while under normal long term CHOW feeding the SNS component may be as little as 3 % of the thermic response, and thus, the total thermic response of DIT likely represents a combination of short acting SNS and longer acting non-SNS mechanisms, including a likely significant thyroidal component in normally lean animals.

166 IMPACT OF PERSONAL PROTECTIVE MASKS ON CARDIORESPIRATORY VARIABLES IN HEALTHY SUBJECTS AND PATIENTS WITH HEART FAILURE: AN INTERIM ANALYSIS

Abstract Background protective masks have emerged as a powerful mean to contain the COVID-19 pandemic. However, a general feeling that masks alter the normal dynamics of breathing may reduce the application of this protective device. Patients with heart failure (HF) experience dyspnea even during daily life activities (ADLs). Aim of the study is to evaluate cardiorespiratory parameters during ADLs, cardiopulmonary exercise test (CPET) and sleep to highlight any difference related to protective masks. Methods 9 healthy subjects (age 59±11, 2 female) and 10 HF patients (age 64±11, 2 female, ejection fraction &amp;lt;45%, stable conditions) underwent a set of cardiopulmonary tests twice, wearing a protective surgical mask and without it. We performed the following tests: standard spirometry; CPET; a set of tests recorded by a wearable ergospirometer (Cosmed K5), including ADLs (ADL1: getting dressed, ADL2: folding eight towels, ADL3: putting away 6 bottles, ADL4: making a bed, ADL5: sweeping the floor for 4 minutes, ADL6: climbing 1 flight of stairs carrying a load), six-minute walking test (6MWT) and two 4-minute treadmill exercises (TREAD2 and TREAD3 at a speed of 2 km/h and 3 km/h, respectively); home polysomnography (HPS). Results Both healthy subjects and HF patients completed the protocol with no adverse events. Spirometry showed a reduction of forced expiratory volume in 1s (3.29±0.75 L vs 2.65±0.57 L as for healthy subjects, p= 0.002; 2.45±0.6 L vs 1.97±0.54 L as for HF patients, p= 0.002) and forced vital capacity (4.14±0.92 L vs 3.39±0.83 L as for healthy subjects, p= 0.004; 2.93±0.76 L vs 2.59±0.73 L as for HF patients, p= 0.01) in both the groups from no mask to mask. As for the CPET, both healthy and HF patients showed: a trend of reduction of peak oxygen pulse (p&amp;lt;0.005 in healthy) and peak oxygen consumption (VO2); a decrease of tidal volume (Vt) at peak exercise (peak Vt: 2.283±0.449 L vs 1.864±0.359 L in healthy, p= 0.022; 1.6±0.41 L vs 1.448±0.431 L in HF, p= 0.02), with no significative variations of resting and peak ventilation (VE). HF patients experienced a statistically significative decrease of VO2 at the anaerobic threshold (AT) (794±227 vs 682±151 mL · min-1, p=0.01). No significant differences in the other CPET parameters were observed. As for tests recorded by a wearable cart, task-related VO2 was significantly reduced from no mask to mask in ALDs and 6MWT in the healthy, whereas HF patients experienced a significative reduction in ADL1, ADL4, 6MWT and TREADs (probably more physically demanding tasks). Both healthy and HF subjects showed an increase in the basal and task-related ratio of VE vs carbon dioxide production (VE/VCO2) between the two protocol conditions. No difference in the main HPS parameters were observed from no mask to mask. Conclusions Surgical masks slightly influences cardiorespiratory variables in healthy and HF patients at rest and during both mild and maximal physical activity. The physiological impact of the mask is far from being clinically relevant and no main differences between the groups were noted, except for an early AT in patients with HF. Since no main limitations were observed, the use of masks seems to be safe both in the general population and in HF patients. Moreover, it does not have a significant impact on sleep neither in healthy subjects nor in patients with HF, these ones particularly at risk of sleep apneas. These data should be confirmed in a larger group of patients.

Effect of phenotype on thyroidal parameters and metabolic sequelae in Wistar fatty rats

To determine the effects of phenotype on parameters of peripheral thyroid hormone and actions, groups of adult male lean (LN) and obese (OB) Wistar Fatty Rats were fed a nutritionally adequate semisynthetic diet containing 54% carbohydrate, 16% mixed fats, 20% protein plus essential vitamins, minerals, and cellulose fiber for 8 weeks. Measures of weight gain (WG), feed efficiency ratio (FER), Resting (RMR) and norepinephrine (NE) stimulated VO2, serum triiodothyronine (T3), and in vitro T4-5’ deiodinase (5’DI) activity in liver (LVR), kidney (KID), gastrocnemius muscle (GNM) and interscapular brown adipose tissue (IBAT) were determined at baseline and after dithiothreitol (DTT) stimulation to optimize in vitro deiodination activity. The WG and FER of OB &gt;&gt; LN phenotype and FER increased over time in both phenotypes, with the greatest increase in the OB phenotype. The RMR of LN &gt; OB, and NE-stimulation (200 µg/kg BW, sc) increased VO2 by 180% in LN but only ~30% in OB phenotype. Serum T3 of LN &gt;&gt; OB. Baseline 5’DI of OB &gt; LN in LIV and KID and were of similar magnitude in both phenotypes in GNM and IBAT. After DTT stimulation, LIV increased ~200% in LN, ~30% in OB; In LN rats, KID +DTT increased ~200%, but only modest increases in OB phenotype, while in LN GNM, DTT resulted in 264% increase vs. +70% in OB rats. In IBAT, DTT resulted in ~ 30-fold increase in 5’DI in LN, and a 16-fold increase in 5’DI in the OB phenotype. These results indicate that parameters of thyroidal actions including circulating plasma levels of T3 and maximum capacity to generate T3 in peripheral tissues via 5’DI, although increased in the OB phenotype, were associated with decreases in RMR and NE-stimulated VO2. These observations occurred in association with an improved efficiency of FER and weight gain and dysregulation of intracellular T3 actions including parameters of T3 receptor affinity kinetics are likely to be among key contributors to the epigenetic expression of the OB+NIDDM phenotype in this strain and are consistent with a reduced affinity of T3- mediated cellular components of intermediary metabolism.

P-type conversion of distorted SnOx thin film by mild thermal annealing treatment in pure N2 environment

Tin oxide semiconductors can achieve both n- and p-type conduction, depending on the oxidation state of Sn. An n-type conduction can easily be fabricated; however, considerable optimization is required for fabrication of a p-type behavior. In this study, n-type SnOx thin films, prepared by reactive magnetron sputtering, were converted to p-type behavior using only post-deposition annealing at 600 °C in a pure nitrogen atmosphere. The annealing-temperature-dependent electrical properties of the SnOx thin films led to a remarkable increase in the yield of p-type behavior at 600 °C. X-ray diffraction analysis revealed that the SnOx film had a SnO2-dominant crystal phase and also suggested that N2 molecules dissociated at 600 °C and filled the oxygen vacancy (VO) site as atomic nitrogen. A detailed analysis of the binding state by x-ray photoelectron spectroscopy confirmed an increase in SnO-derived components, the appearance of peaks derived from N–Sn bonding, a decrease in VO caused by nitrogen doping, and charge transfer. Thus, we found that addition of nitrogen atoms promotes a chemical shift from Sn4+ to Sn2+ and that simultaneously passivates VO and contributes to hole generation.

Exercise Limitation after Critical Versus Mild COVID-19 Infection: A Metabolic Perspective.

Exercise limitation in COVID-19 survivors is poorly explained. In this retrospective study, cardiopulmonary exercise testing (CPET) was coupled with an oxidative stress assessment in COVID-19 critically ill survivors (ICU group). Thirty-one patients were included in this group. At rest, their oxygen uptake (VO2) was elevated (8 [5.6–9.7] mL/min/kg). The maximum effort was reached at low values of workload and VO2 (66 [40.9–79.2]% and 74.5 [62.6–102.8]% of the respective predicted values). The ventilatory equivalent for carbon dioxide remained within normal ranges. Their metabolic efficiency was low: 15.2 [12.9–17.8]%. The 50% decrease in VO2 after maximum effort was delayed, at 130 [120–170] s, with a still-high respiratory exchange ratio (1.13 [1–1.2]). The blood myeloperoxidase was elevated (92 [75.5–106.5] ng/mL), and the OSS was altered. The CPET profile of the ICU group was compared with long COVID patients after mid-disease (MLC group) and obese patients (OB group). The MLC patients (n = 23) reached peak workload and predicted VO2 values, but their resting VO2, metabolic efficiency, and recovery profiles were similar to the ICU group to a lesser extent. In the OB group (n = 15), no hypermetabolism at rest was observed. In conclusion, the exercise limitation after a critical COVID-19 bout resulted from an altered metabolic profile in the context of persistent inflammation and oxidative stress. Altered exercise and metabolic profiles were also observed in the MLC group. The contribution of obesity on the physiopathology of exercise limitation after a critical bout of COVID-19 did not seem relevant.

Cardiopulmonary exercise testing versus pulmonary function test in the assessment of respiratory impairment in chronic obstructive pulmonary disease patients.

Cardiopulmonary exercise testing (CPET) is a non-invasive method for the determination of disability and comprehensive evaluation of exercise responses involving the cardiovascular, pulmonary and musculoskeletal systems. To assess exercise performance measured by CPET in different chronic obstructive pulmonary disease (COPD) stages and to compare between pulmonary function test (PFT) and CPET in assessing the degree of respiratory impairment. Sixty patients diagnosed with COPD were enrolled in the study. Modified Medical Research Council scale (mMRC) and COPD assessment test (CAT) to evaluate dyspnea symptom. PFT and CPET were performed. There was a significant decrease in peak VO2 and anaerobic threshold in patients with stages III, IV (P < 0.001), while COPD stage I, II had significantly higher minute ventilation, tidal volume and oxygen pulse (P < 0.001). 76.67% of patients were similarly classified by CPET and PFT, while 23.33% were found to be less impaired according to CPET when compared to PFT. A significant correlation between both VE/VO2 (r = 0.31, 95% CI 0.19-0.92, P < 0.001) and VE/VCO2 (r = 0.69, 95% CI 0.86-1.08, P < 0.001) with FEV1. Whereas, an inverse correlation were found between both VE/VCO 2 (r = -0.34, 95% CI -0.77 -1.11, P < 0.001) and VE/VO2 (r = -0.55, 95% CI -0.88 to -0.15, P < 0.001), with the degree of air trapping as estimated by RV/TLC ratio. No significant correlation between neither CAT nor MRC and exercise testing parameters. CPET is an extremely valuable method for the determination of functional capacity and exercise intolerance in COPD rather than PFT. CPET is considered a gold-standard tool for better evaluation of respiratory impairment in COPD.

Progressive right ventricular dysfunction and exercise impairment in patients with heart failure and diabetes mellitus: insights from the T.O.S.CA. Registry

BackgroundFindings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF.MethodsPatients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D.ResultsCompared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p < 0.01) and worse right ventricular(RV)-arterial uncoupling (RVAUC) (TAPSE/PASP ratio 0.52 ± 0.2, 0.6 ± 0.3, and 0.6 ± 0.3 in T2D, EU and IR, respectively, p < 0.05). Likewise, impairment in peak oxygen consumption (peak VO2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p < 0.003). Longitudinal data demonstrated higher deterioration of RVAUC, RV dimension, and peak VO2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2).ConclusionThe higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis.Trial registration ClinicalTrials.gov identifier: NCT023358017

Sympathetic blockade on diet induced thermogenesis in the congenic LA/Ntul//-cp rat

The effects of overfeeding highly palatable diets via the cafeteria feeding diet method (Café) has been shown to be a reliable experimental model to induce diet induced thermogenesis (DIT) in young adult normally lean rats of several strains. Groups of young adult lean LA/ Ntul//-cp rats were offered a Purina chow diet (CHOW) or the same diet plus a daily café supplement both ad libitum from 10 until 24 weeks of age. The drug α-methylparatyrosine (α-MPT) was administered to groups (250 mg α-MPT/kg BW, i.p.) to ablate sympathetic (SNS) activity or a sham injection of physiologic saline given, and measures of fasting resting thermogenesis obtained at thermal neutrality (30°C) before and after the α-MPT or sham administration. The Café diet resulted in a 67% increase in body weight (BW) and a ~25% increase in resting oxygen consumption (VO2) following café overfeeding in both groups, while only a 40% increase in BW and no additional increase in VO2 occurred in normally CHOW fed rats while the sham injection was without any variations from normal physiologic responses as predicted. Sympathetic blockade with α-MPT was associated with modest decreases in body temperature and an average ~12-15% decrease in VO2 in the café treated group, but when the VO2 data were arithmetically corrected to isothermal conditions only a net 3% decrease occurred in CHOW fed rats and was without effect on the SHAM group. Serum T3 concentrations increased by 92% and urinary catecholamine excretion of VMA &gt;250% following the café diet, but the urinary vanilmandelic acid (VMA) excretion was virtually nil following the sympathetic blockade. These observations indicate that the SNS-mediated contribution component to DIT following prolonged café overfeeding under conditions of thermal neutrality contribute approximately 50% of the thermic response. While under normal long term CHOW feeding the SNS component may be as little as 3% of the thermic response, and thus, the total thermic response of DIT likely represents a combination of short acting SNS and longer acting non-SNS mechanisms, including a likely significant thyroidal component in normally lean animals.

Effects of an individualized and progressive multicomponent exercise program on blood pressure, cardiorespiratory fitness, and body composition in long-term care residents: Randomized controlled trial

This study analyzed the effects of an individualized and progressive multicomponent exercise program on blood pressure, cardiorespiratory fitness, and body composition in long-term care residents. This was a single-blind, multicenter, randomized controlled trial performed in 10 long-term care settings and involved 112 participants. Participants were randomly assigned to a control group or an intervention group. The control group participated in routine activities; the intervention group participated in a six-month individualized and progressive multicomponent exercise program focused on strength, balance, and walking recommendations. The intervention group maintained peak VO2, oxygen saturation, and resting heart rate, while the control group showed a significant decrease in peak VO2 and oxygen saturation and an increase in resting heart rate throughout the six-month period. Individualized and progressive multicomponent exercise programs comprising strength, balance, and walking recommendations appear to be effective in preventing cardiorespiratory fitness decline in older adults living in long-term care settings.

Changes in carbon dioxide production and oxygen uptake evaluated using indirect calorimetry in mechanically ventilated patients with sepsis

BackgroundSeveral clinical guidelines recommend monitoring blood lactate levels and central venous oxygen saturation for hemodynamic management of patients with sepsis. We hypothesized that carbon dioxide production (VCO2) and oxygen extraction (VO2) evaluated using indirect calorimetry (IC) might provide additional information to understand the dynamic metabolic changes in sepsis.MethodsAdult patients with sepsis who required mechanical ventilation in the intensive care unit (ICU) of our hospital between September 2019 and March 2020 were prospectively enrolled. Sepsis was diagnosed according to Sepsis-3. Continuous measurement of VCO2 and VO2 using IC for 2 h was conducted within 24 h after tracheal intubation, and the changes in VCO2 and VO2 over 2 h were calculated as the slopes by linear regression analysis. Furthermore, temporal lactate changes were evaluated. The primary outcome was 28-day survival.ResultsThirty-four patients with sepsis were enrolled, 26 of whom survived 76%. Significant differences in the slope of VCO2 (− 1.412 vs. − 0.446) (p = 0.012) and VO2 (− 2.098 vs. − 0.851) (p = 0.023) changes were observed between non-survivors and survivors. Of note, all eight non-survivors and 17 of the 26 survivors showed negative slopes of VCO2 and VO2 changes. For these patients, 17 survivors had a median lactate of − 2.4% changes per hour (%/h), whereas non-survivors had a median lactate of 2.6%/hr (p = 0.023).ConclusionsThe non-survivors in this study showed temporal decreases in both VCO2 and VO2 along with lactate elevation. Monitoring the temporal changes in VCO2 and VO2 along with blood lactate levels may be useful in predicting the prognosis of sepsis.

The Effect of Voxelotor on Exercise Capacity of Youths with Sickle Cell Anemia

Background/Hypothesis: Children and adults with sickle cell anemia (SCA) exhibit decreased cardiopulmonary fitness. Anemia is directly related to oxygen carrying capacity and is one factor that affects cardiopulmonary fitness. The new sickle cell drug voxelotor raises hemoglobin in patients with SCA treated or untreated with hydroxyurea. We hypothesized that voxelotor improves exercise capacity in youths with SCA.Methods: A single-center, open-label, single-arm longitudinal interventional pilot study was conducted for patients with SCA age > 12. Participants performed baseline Cardiopulmonary Exercise Testing (CPET#1), took 1500mg voxelotor for 2 months, then CPET was repeated (CPET#2). A modified Bruce Protocol using 2-minute stages was performed on a motorized treadmill, for a goal of 8-12 minutes of exercise. Breath by breath gas exchange data were collected and analyzed using a VMax Encore 29C metabolic cart. The metabolic test included standard monitoring of heart rate, EKG ST changes, arrhythmias, and O2 saturation. A respiratory quotient >1.1 was used as evidence of participant effort. Peak oxygen consumption (peak VO2), anaerobic threshold (AT), O2 pulse, VE/VCO2 slope, and time exercised in CPET#1 and CPET#2 were compared for each participant. The primary endpoint was peak VO2.Hemoglobin (Hgb), reticulocyte count, and bilirubin were measured before CPET#1 and CPET#2. Pill count was used to monitor medication adherence and left shift of the P50 oxygen dissociation curve was used to document biochemical effect of voxelotor. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected at the end of the study.Statistical analysis was performed using Student's paired T-test.Results: Nine SCA patients ages 12-20, including 4 males and 5 females, completed the study. All had Hgb SS and were stably maintained on hydroxyurea, which was continued without dose change during the study. After 2 months of voxelotor, all participants demonstrated expected hematologic changes, including mean rise in Hgb +1.3 g/dL (95% C.I.= 0.8, 1.7), mean decrease in reticulocyte count -2.4% (95% C.I.= -4.1, -0.8), and mean decrease in bilirubin -0.4 mg/dL (95% C.I.= -0.8, -0.1). All participants demonstrated voxelotor adherence and leftward shift of p50 (Table 1).Oxygen consumption, measured as percent predicted peak VO2 (ml/kg/min), ranged from 52% to 80% in CPET#1 and from 55% to 71% in CPET#2. The changes in peak VO2 for individual participants ranged from -10% to +10% of predicted peak VO2, with a mean difference of -2.2% (95% CI = -7.1, 2.7), which is insignificant (p=0.3). Using +/- 6% as variability in peak VO2 measurement, 5 participants exhibited no change, 3 participants had decrease in peak VO2 of -7%, -9%, and -10%, while peak VO2 increased by +10% for a single participant, who started to exercise on his own after starting voxelotor. Changes in individuals' anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were not significant and did not correlate with changes in peak VO2. All participants achieved respiratory quotient >1.1, assuring participant effort during CPET (Table 2).On the 7-point PGIC questionnaire evaluating activity limitations, symptoms, emotions, and overall quality of life, 7 out of 9 participants reported positive change, including “a great deal better,” “definite,” and “moderate” improvements. Two participants reported minimal to no change, and no participants reported worsening. In comparison, clinicians reported “minimal” to “much” improvement on CGIC for all participants. Overall, patient impression of improvement was higher than clinician impression of improvement.Conclusion: This pilot study demonstrated the feasibility of using CPET to evaluate exercise capacity longitudinally in youths with SCA. After addition of voxelotor to hydroxyurea for 2 months, all patients perceived global improvement. Peak VO2 did not change in 8 out of 9 participants and improved for 1 participant who exercised between the 2 CPETs. To increase peak VO2, higher Hgb increase, concurrent regular exercise, and longer exposure to voxelotor may be necessary.This study was funded by Global Blood Therapeutics [Display omitted] DisclosuresLarkin: Forma Therapeutics, Inc.: Research Funding. Dulman: Pfizer: Other: own stock. Kuypers: Forma Therapeutics, Inc.: Research Funding.

Mechanisms of Exercise Capacity Improvement after Cardiac Rehabilitation Following Myocardial Infarction Assessed with Combined Stress Echocardiography and Cardiopulmonary Exercise Testing.

Cardiac rehabilitation (CR) is indicated in all patients after acute myocardial infarction (AMI) to improve prognosis and exercise capacity (EC). Previous studies reported that up to a third of patients did not improve their EC after CR (non-responders). Our aim was to assess the cardiac and peripheral mechanisms of EC improvement after CR using combined exercise echocardiography and cardiopulmonary exercise testing (CPET-SE). The responders included patients with an improved EC assessed as a rise in peak oxygen uptake (VO2) ≥ 1 mL/kg/min. Peripheral oxygen extraction was calculated as arteriovenous oxygen difference (A-VO2Diff). Out of 41 patients (67% male, mean age 57.5 ± 10 years) after AMI with left ventricular ejection fraction (LVEF) ≥ 40%, 73% improved their EC. In responders, peak VO2 improved by 27% from 17.9 ± 5.2 mL/kg/min to 22.7 ± 5.1 mL/kg/min, p < 0.001, while non-responders had a non-significant 5% decrease in peak VO2. In the responder group, the peak exercise heart rate, early diastolic myocardial velocity at peak exercise, LVEF at rest and at peak exercise, and A-VO2Diff at peak exercise increased, the minute ventilation to carbon dioxide production slope decreased, but the stroke volume and cardiac index were unchanged after CR. Non-responders had no changes in assessed parameters. EC improvement after CR of patients with preserved LVEF after AMI is associated with an increased heart rate response and better peripheral oxygen extraction during exercise.