Expired Gas Analysis Research Articles

Discordance Between Measured vs Calculated Oxygen Consumption in Adults With Congenital Heart Disease: Limitations and Clinical Implications.

Oxygen consumption (VO2) is frequently estimated using derived formulas for ease of use. We performed a prospective study to assess the correlation and limits of agreement between measured and assumed VO2 (mL/min) in adults with congenital heart disease (CHD). Consecutive adults with CHD who have undergone cardiac catheterization at Mayo Clinic Rochester from January 2018 to December 2019 were retrospectively enrolled in the study. Expired gas analysis was performed to measure VO2. We estimated VO2 using LaFarge (VO2L), Dehmer (VO2D), and Bergstra (VO2B) formulas. Bland-Altman and linear-regression analyses were used to assess the correlation between measured and calculated VO2. We enrolled 84 patients with a mean age of 43 ± 12 years; 66% were men. Linear correlation analysis showed a moderate correlation of VO2L and VO2B with VO2M (r = 0.58; P<.001 and r = 0.44; P<.01, respectively) and good correlation of VO2D with VO2M (r = 0.79; P<.001). The large spread of limits of agreement assessed using Bland-Altman analysis demonstrates poor agreement of VO2L and VO2B with VO2M (bias, -58; 95% confidence interval [CI], -258 to 48) and bias, 38; 95% CI, -91 to 167, respectively). The limits of agreement for VO2D have a large spread, demonstrating a low degree of agreement with VO2M (bias, 13; 95% CI, -64 to 89). VO2L predominantly misclassified patients as low cardiac index and VO2D and VO2B misclassified patients as normal/ high cardiac index. In adults with CHD, assumed VO2 will lead to a significant error while assessing invasive intracardiac hemodynamics.

Novel noninvasive estimation of mixed venous oxygen saturation by echocardiography and expired gas analysis.

Mixed venous oxygen (O2) saturation ([Formula: see text]) is an important measure for evaluating the sufficiency of cardiac output (CO) relative to whole body O2 consumption (V̇o2), while clinical use is limited to the required invasive catheterization. According to Fick's equation, V̇o2 (mL/min) = CO (L/min) × Hb (g/dL) × 1.36 (mL/g) × ([Formula: see text] - [Formula: see text])/10 (Hb = hemoglobin concentration, [Formula: see text] = arterial blood O2 saturation). Because V̇o2, CO, Hb, and [Formula: see text] can be measured noninvasively with expired gas analysis, echocardiography, a simple blood test, and percutaneous O2 saturation, respectively, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. In 47 patients (29 men; mean age, 70 ± 12 yr) who underwent right heart catheterization, [Formula: see text] was directly measured by sampling pulmonary artery blood. Noninvasively calculated [Formula: see text] was also obtained by the method described above. The calculated [Formula: see text] was significantly correlated with the measured [Formula: see text] (r = 0.79, P < 0.001) and was significantly smaller than the measured [Formula: see text] (70 ± 5.1 vs. 72.1 ± 4.9%, P < 0.001). Bias at [Formula: see text] was -2.2% (95% confidence interval, -3.2 to -1.1%) with limits of agreement from -9.5 to 5.2%, demonstrating acceptable agreement. The optimal cutoff value of calculated [Formula: see text] was 69% for reduced measured [Formula: see text] < 70% with an area under the curve of 0.94. Reduced calculated [Formula: see text] < 69% indicated a sensitivity of 92.9% and a specificity of 90.9% for reduced measured [Formula: see text] < 70%. Noninvasive [Formula: see text] calculated from echocardiography, expired gas analysis, percutaneous arterial blood O2 saturation, and hemoglobin level significantly correlated and agreed well with direct [Formula: see text] measured by catheterization. This novel method allows for practical evaluation of [Formula: see text] to assess the sufficiency of CO according to whole body metabolism.NEW & NOTEWORTHY Clinical use of mixed venous oxygen saturation ([Formula: see text]) is limited to the required invasive procedure. With Fick's equation, expired gas analysis, echocardiography, simple blood tests, and percutaneous oxygen saturation, [Formula: see text] can be calculated noninvasively. We hypothesized that noninvasively calculated [Formula: see text] shows a significant correlation and agrees well with invasively measured [Formula: see text]. The present study examined the relationship between measured [Formula: see text] and calculated [Formula: see text] in patients who underwent right heart catheterization and demonstrated acceptable agreement. This novel method can expand the indication of evaluating [Formula: see text].

Paretic knee extensor strength, gait velocity, and fat mass are major determinants of peak aerobic capacity in subacute stroke: observational cohort study

The purpose of this study is to investigate major determinants of peak aerobic capacity in subacute stroke patients among body composition, balance function, walking capacity, and lower limb muscular strength. This was a retrospective observational cohort study. Eighty-three subacute stroke patients were enrolled and their medical records were retrospectively reviewed in the study (47 males; mean age: 62.95 ± 13.9 years). Gait capacity was assessed by gait velocity (10 m walk velocity:10MWV) and gait endurance (6 min walk distance:6MWD). Balance function was evaluated with Berg Balance Scale (BBS). The isometric muscular strengths of bilateral knee extensors were measured with an isokinetic dynamometer. Cardiovascular fitness was evaluated with an expired gas analyzer. In backward linear regression analyses, paretic isometric extensor strength (p < 0.001), fat mass (p = 0.005) and 10MWV (p < 0.001) are significantly correlated with peak aerobic capacity (adjusted R2 = 0.499) in all patients. Our results confirmed that paretic knee extensor strength, gait velocity, and fat mass were major determinants of peak aerobic capacity in subacute stroke. Therefore, therapeutic approaches should focus on improving gait velocity and paretic knee extensor strength in the early stages of recovery from stroke.

The effect of an airflow restriction mask (ARM) on metabolic, ventilatory, and electromyographic responses to continuous cycling exercise.

This study analyzed the physiological adjustments caused by the use of the Elevation training mask® (2.0), an airflow restriction mask (ARM) during continuous exercise. Eighteen physically active participants (12 men and 6 women) were randomized to two protocols: continuous exercise with mask (CE-ARM) and continuous exercise without mask (CE). Exercise consisted of cycling for 20 minutes at 60% of maximum power. Metabolic variables, lactate, and gas concentration were obtained from arterialized blood samples at pre and post exercise. Continuous expired gases and myoelectric activity of the quadriceps were performed at rest and during the test. We observed no reduction in oxygen saturation in CE-ARM, leading to lower pH, higher carbon dioxide, and greater hematocrit (all p <0.05). The expired gas analysis shows that the CE-ARM condition presented higher oxygen uptake and expired carbon dioxide concentrations (p <0.05). The CE-ARM condition also presented lower ventilatory volume, ventilatory frequency, and expired oxygen pressure (p <0.05). No changes in electromyography activity and lactate concentrations were identified. We conclude that using ARM does not induce hypoxia and represents an additional challenge for the control of acid-base balance, and we suggest the use of ARM as being suitable for respiratory muscle training.

Iloprost and exercise haemodynamics in heart failure with preserved ejection fraction—the ILO‐HOPE randomised controlled trial

AimsA dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). This study was designed to determine whether iloprost inhalation could improve exercise haemodynamics and cardiac reserve in patients with HFpEF.MethodsThirty‐four HFpEF patients were enrolled in this double‐blind, randomized, placebo‐controlled, parallel‐group trial. Patients received both cardiac catheterization and underwent expired gas analysis at rest, during exercise, and before and 10 minutes after treatment with either inhaled iloprost or placebo. The primary endpoint was decrease in exercise PCWP.ResultsAt baseline, enrolled patients showed an increase in PCWP during exercise (from 16 [range, 14–23] mmHg to 27 [21–36] mmHg; P &lt; .0001). After iloprost inhalation, exercise PCWP was significantly reduced compared to placebo (adjusted mean: 20 [16–29] mmHg vs 23 [17–32] mmHg; P = .002). There was no difference for cardiac output reserve with exercise in the 2 groups (0.2 [−1.3–1.2] L/min vs –0.7 [−1.9–0.1] L/min; P = .099). Iloprost improved the pulmonary artery pressure flow relationships in HFpEF with exercise compared to placebo.ConclusionIloprost inhalation improved haemodynamic deficits during exercise in patients with HFpEF. Prospective trials testing long‐term iloprost therapy in this population are warranted.

Recuperação cardiopulmonar em atletas de Rugby em Cadeira de Rodas: efeito de nível competitivo e classificação funcional

Introdução: o Rugby em Cadeira de Rodas (RCR) é uma modalidade com grande demanda energética. Objetivo: comparar a recuperação cardiopulmonar de atletas de RCR de elite internacional (EI, n=16) e nacional (EN, n=06), além de investigar a correlação entre a recuperação e a classificação funcional (CF) dos atletas.Métodos: o teste de esforço cardiopulmonar foi realizado em cicloergômetro para membros superiores, com análise dos gases expirados. Consumo de oxigênio (VO2) e ventilação pulmonar (VE) foram avaliados no pico do esforço e na recuperação (primeiro, segundo e terceiro minutos). Resultados: EI apresentou uma maior recuperação do VO2 e da VE. Correlações fortes e muito fortes foram encontradas entre CF e recuperação percentual de VO2 para EN, enquanto que, no EI, as correlações foram fracas e regulares.Conclusão: Atletas com maior volume de prática do RCR (EI) têm maior capacidade de recuperação cardiopulmonar. Sugere-se que o tempo de treinamento pode minimizar a influência da CF na capacidade de recuperação do atleta.

Beneficial effects of riociguat on hemodynamic responses to exercise in CTEPH patients after balloon pulmonary angioplasty - A randomized controlled study.

BackgroundAlthough balloon pulmonary angioplasty (BPA) improves symptoms and pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH), the effects of riociguat on hemodynamics and exercise capacity in patients after BPA remain to be elucidated.Methods and ResultsThis study was a single-center, prospective, randomized, open-label trial. From November 2015 to November 2018, we prospectively examined 21 patients with CTEPH (65 ± 9 years old, M/F 2/19) who showed hemodynamic improvement with mean pulmonary arterial pressure (mPAP) < 30 mmHg after BPA without any vasodilators. We performed hemodynamic evaluation and expired gas analysis both at rest and during exercise in supine position using cycle ergometer. After right heart catheterization during exercise, they were randomly assigned to 2 groups with minimized method, using age, sex, and resting mPAP; riociguat (N = 10) and control (N = 11) groups. After 6 months, exercise capacity evaluated by 6-min walk distance and cardiopulmonary exercise testing, and resting hemodynamic parameters were comparable in both groups. However, cardiac output (CO) (6.0 ± 1.7–7.4 ± 1.6, P < 0.01) and pulmonary vascular resistance (4.8 ± 1.8–3.2 ± 0.7 Wood units, P = 0.02) at peak workload were significantly improved in the riociguat group as compared with the control group. The slope of linearized mPAP-CO relationship was significantly decreased in the riociguat group [14.5 (7.8, 14.7) to 6.41 (5.1, 11.4), P < 0.01] but not in the control group.ConclusionsThese results indicate that riociguat exerts beneficial effects on hemodynamic response to exercise in CTEPH patients even after hemodynamic improvement by BPA.

Hemodynamic and Functional Impact of Epicardial Adipose Tissue in Heart Failure With Preserved Ejection Fraction

ObjectivesThis study determined the impact of excess epicardial adipose tissue (EAT) in patients with the obese phenotype of heart failure with preserved ejection fraction (HFpEF). BackgroundPatients with HFpEF and an elevated body mass index differ from nonobese patients, but beyond generalized obesity, fat distribution may be more important. Increases in EAT are associated with excess visceral adiposity, inflammation, and cardiac fibrosis, and EAT has been speculated to play an important role in the pathophysiology of HFpEF, but no study has directly evaluated this question. MethodsPatients with HFpEF and obesity (n = 169) underwent invasive hemodynamic exercise testing with expired gas analysis and echocardiography. Increased EAT was defined by echocardiography (EAT thickness ≥9 mm). ResultsCompared with obese patients without increased EAT (HFpEFEAT−, n = 92), obese patients with HFpEF with increased EAT (HFpEFEAT+; n = 77) displayed a higher left ventricular eccentricity index, indicating increased pericardial restraint, but similar resting biventricular structure and function. In contrast, hemodynamics were more abnormal in patients with HFpEFEAT+, with higher right atrial, pulmonary artery, and pulmonary capillary wedge pressures at rest and during exercise compared with those of patients with HFpEFEAT−. Peak oxygen consumption (VO2) was reduced in both groups but was 20% lower in patients with HFpEFEAT+ (p < 0.01). ConclusionsAmong patients with the obese phenotype of HFpEF, the presence of increased EAT is associated with more profound hemodynamic derangements at rest and exercise, including greater elevation in cardiac filling pressures, more severe pulmonary hypertension, and greater pericardial restraint, culminating in poorer exercise capacity. Further study is needed to understand the biology and treatment of excessive EAT in patients with HFpEF.

Utilizing Causal Pathway Analysis To Predict Change In Cardiorespiratory Fitness In The STRRIDE Randomized Trials

Exploring high-throughput data in a causal pathway framework facilitates accurate and parsimonious multivariable predictive models for clinical outcomes. Developing these models elucidates mechanisms by which regular exercise elicits health benefits. PURPOSE: As a proof-of-concept, we tested the utility of causal pathway discovery for predicting changes in V̇O2peak across the STRRIDE trials. METHODS: A total of 532 adults from three STRRIDE studies were randomized to one of 7 exercise interventions, ranging from doses of 8-22 kcal/kg/week; intensities of 50-75% V̇O2peak; and durations of 6-9 months. Six groups included aerobic exercise, two included resistance training, and one included dietary intervention. Graded maximal exercise treadmill testing with expired gas analysis determined Absolute V̇O2peak. The Fast Causal Inference algorithm was applied to discover the mechanistic relationship among 231 clinical and transcriptomic variables with 200 bootstrap resamples to assess the stability of the discovered causal graph. To estimate effect sizes, V̇O2peak was regressed on variables in its local causal neighborhood. RESULTS: Forty-four variables were identified in the causal vicinity (within three edges away) of V̇O2peak following exercise intervention in more than 50% of bootstrap resampling runs. Exercise intensity, age, and pre-training V̇O2peak were identified as the direct causes of post-training V̇O2peak. Among the studied variables, none mediated the effect of exercise dose. The following exercise combinations were the most effective in changing V̇O2peak: high amount/vigorous intensity aerobic training (β=0.39 L/min); low amount/vigorous intensity aerobic plus resistance training (β=0.33 L/min); low amount/vigorous intensity aerobic training (β=0.27 L/min); high amount/moderate intensity aerobic training (β=0.26 L/min); low amount/moderate intensity aerobic training (β=0.19 L/min); and resistance training (β=0.18 L/min). CONCLUSIONS: Multivariable causal graph-based inference confirmed an exercise dose-response for V̇O2peak. As we develop and incorporate additional molecular data, our future research will use this approach to maximize predictive ability for other clinical phenotypes to help make personalized lifestyle medicine a functional reality.

Effects Of Polyester Wicking Versus Cotton Fabric T-shirt On Sweat Rate In Obese Males

The effects of different t-shirt fabrics on thermoregulation during exercise remain to be elucidated. PURPOSE: This crossover study investigated the effects of cotton (C) versus polyester (P) t-shirts on sweat rate and skin temperature at the torso (chest, back) and peripheral (forearm, forehead) regions of physically active, obese males. METHODS: Seven participants (21.7 ± 1.7 yr; 35.7 ± 6.7 kg·m-2) completed 4 visits (separated by 48 hrs); visit 1 was to complete the informed consent, ACSM health questionnaire, PAR-Q, and body composition assessment using air displacement plethysmography. Visit 2 was a VO2max test (30-sec averaging for expired gas analysis), followed by two treadmill walking sessions (30 min at 30 - 39% VO2reserve) in either C or P t-shirt (randomized, counterbalanced sequence) on the third and fourth visits. Exercise was performed in a hot and dry (27 C°, 10 ± 2% relative humidity) environment. Sweat rate was determined as ∆ nude body weight (pre- minus post-exercise body weight) using a digital scale. Skin temperature was measured during exercise using a skin thermometer. Torso skin temperature (Tsktorso) was the sum of 0.5TChest + 0.5TBack. Peripheral site skin temperatures were analyzed separately. A dependent t-test was used to compare sweat rates. Separate two-way ANOVAs were performed to investigate fabric type, time, and their interactions on skin temperature by body region. RESULTS: On average, participants’ VO2max and body fat were 36.8 ± 8.7 mL·kg-1·min-1 and 34.7 ± 4.3%, respectively. There was no difference between C and P conditions in sweat rates (∆ body weight = -.35 ± .11 kg; -.37 ± .20 kg, respectively, p = .754). A significant interaction effect was detected between Tsktorso and fabric (p = .022) with C > P. Interaction effects of skin temperature in the peripheral regions (forearm, p = .195; forehead, p = .057) were nonsignificant. CONCLUSION: Though the sweat rate was similar across cotton and polyester trials, polyester appears to be effective for temperature regulation, especially in the torso region during low intensity aerobic exercises in young, obese males. Future research should explore the impact of C vs. P fabric on sweat rate and skin temperature during different intensities and modalities of exercise.

Modification of Cooper’s 12-min Run Test to Predict Maximum Oxygen Uptake in Indian Cricketers

Cooper’s 12-minute run test (CRT) for prediction of maximum oxygen uptake (VO2max) has not yet been explored in Indian sportspersons. Present investigation was conducted to evaluate the applicability of CRT in Indian cricketers. 75 male and 45 female cricket players were randomly recruited from reputed cricket academies of Kolkata, India and were randomly assigned into the study group (male = 45, female = 25) and confirmatory group (male = 30, female = 20). Incremental cycle ergometer exercise was used for direct estimation of VO2max by expired gas analysis and the indirect prediction of VO2max (PVO2max) was performed by CRT method. The current protocol of CRT was found to be inapplicable in both the genders of Cricketers due to a significant difference between PVO2max and VO2max and a large limit of agreement between PVO2max and VO2max in the study groups. A significant correlation (r = 0.76 in males and r = 0.79 in females, p&lt;0.001) was depicted between VO2max and distance covered in CRT. Regression equations were computed based on the significant correlation. The application of these equations in the confirmatory groups revealed an insignificant difference between PVO2max and VO2max and narrow limits of agreement. Standard errors of the estimate of the regression norms were also minimal. Therefore, modified equations are recommended for CRT application for valid and precise evaluation of cardiorespiratory fitness in terms of VO2max in male and female Indian cricketers.

Cardiorespiratory fitness and accelerometer-determined physical activity following one year of free-living high-intensity interval training and moderate-intensity continuous training: a randomized trial

BackgroundFree-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT).MethodsNinety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models.ResultsCRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018).ConclusionDespite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

Functional mitral regurgitation and left atrial myopathy in heart failure with preserved ejection fraction

Mild to moderate functional mitral regurgitation (MR) is common in patients with heart failure and preserved ejection fraction (HFpEF) where it is usually considered as an innocent bystander. We hypothesized that MR in HFpEF reflects greater left atrial (LA) myopathy, leading to more adverse haemodynamics and poorer exercise reserve. Patients with HFpEF (n= 280) with and without MR underwent echocardiography, invasive haemodynamic exercise testing, and expired gas analysis. As compared to non-MR-HFpEF (n= 163), patients with MR-HFpEF (n= 117; 78 mild and 39 moderate, central jet in 90%) were older, more likely female, with lower body mass and higher prevalence of atrial fibrillation (AF). HFpEF patients with MR displayed greater LA volume, reduced LA strain and compliance, and greater mitral annular dilatation, which was strongly correlated with LA dilatation (r=0.63, P< 0.0001) but was only weakly related to left ventricular remodelling (r=0.37). Patients with MR-HFpEF displayed worse biventricular function, more adverse pulmonary haemodynamics, impaired pulmonary vasodilatation, blunted right ventricular reserve, and reduced cardiac output with exercise as compared to non-MR-HFpEF. Importantly, these findings were maintained after excluding patients with HFpEF and AF, suggesting a role for LA myopathy in contributing to MR in HFpEF, independent of rhythm. Functional MR in patients with HFpEF reflects LA myopathy, even in the absence of AF, and is associated with greater haemodynamic severity of disease and poorer functional capacity. Further study is required to better define causal mechanisms and potential treatments for MR and LA dysfunction in patients with HFpEF.

Long-term therapeutic effect of Fontan conversion with an extracardiac conduit.

The aim of this study was to identify the long-term therapeutic effect of total cavopulmonary connection (TCPC) conversion with an extracardiac conduit. Between 1991 and 2014, 36 patients underwent TCPC conversion with an extracardiac conduit. Half of these patients were diagnosed with tricuspid atresia or its variant. The left ventricle was dominant in 26 patients (72.2%). Median age at conversion and interval from initial Fontan operation to conversion were 24.1 years (interquartile range 18.9-29.2) and 17.8 years (15.4-20.9), respectively. Surgical cryoablation was concomitantly performed in 32 patients (88.9%). Cardiac catheter examination was performed preoperatively (36 patients, 100%) and at 1 year (31 patients, 86%), 5 years (25 patients, 69%) and 10 years (13 patients, 36%) after TCPC conversion. Symptom-limited treadmill exercise with expired gas analysis was performed preoperatively (32 patients, 88.9%) and at 1 year (27 patients, 75.0%), 5 years (20 patients, 55.6%) and 10 years (12 patients, 33.3%) after conversion. All patients received follow-up; the mean follow-up period was 8.2 ± 4.8 years. Actuarial survival rate, protein-losing enteropathy-free survival rate and rate of survival with sinus rhythm maintenance at 10 years were 79.2%, 67.8% and 48.5%, respectively. The survival curve declined steeply when the duration of Fontan circulation exceeded 25 years. New cases of protein-losing enteropathy developed postoperatively in 2 patients. Permanent pacemakers were implanted in 12 patients (33%), but atrial tachyarrhythmia was not sustained in any of the remaining patients. Pulmonary arterial pressure (11.0 ± 3.1 to 9.5 ± 3.6 mmHg, P = 0.003), pulmonary vascular resistance (2.1 ± 0.7 to 1.3 ± 0.5 WU/m2, P < 0.0001) and cardiac index (2.0 ± 0.3 to 2.9 ± 0.6 l/min/m2, P < 0.0001) significantly improved from preoperative evaluation to 1 year after the conversion, and these improvements were maintained during the entire follow-up period. Peak oxygen uptake remained unchanged from the preoperative evaluation (49.7 ± 11.5% predicted) to 1 year (52.5 ± 12.0%), 5 years (56.2 ± 9.6%) and 10 years (51.2 ± 9.4%) after conversion (P = 0.19). Owing to its anti-arrhythmic effect and Fontan pathway recruitment effect, TCPC conversion with an extracardiac conduit prevented the natural decline of exercise tolerance that is seen in classic Fontan patients.

Garlic oil suppresses high-fat diet induced obesity in rats through the upregulation of UCP-1 and the enhancement of energy expenditure.

Garlic (Allium sativum L.) has long been used as a medicinal food. Indeed, garlic and its constituents have been shown to possess potent regulatory activities in bodily functions, including blood coagulation, lipid metabolism, immunity and xenobiotic metabolism. In this study, we aimed to examine the anti-obesity effects of garlic oil and to elucidate the possible underlying mechanisms. For this purpose, garlic oil (GO; 80 mg/kg body weight, p.o.) or corn oil alone as a vehicle-control were administered to male Sprague-Dawley rats every other day for 10 weeks. The results revealed that GO administration significantly reduced body weight gain and white adipose tissue (WAT) mass, which had been increased by feeding on the AIN-76-based high-fat diet (60% kcal fat). Expired gas analysis was performed at 9 weeks following the GO administration to calculate fuel oxidation. GO administration enhanced O2 consumption during the dark period (at night) and increased energy expenditure through fat oxidation during the light period (daytime); however, carbohydrate oxidation remained unaltered. Western blot analysis revealed that GO administration increased UCP1 protein expression in brown adipose tissue (BAT). On the whole, the findings of this study indicated that GO suppressed body weight gain and WAT mass in the rat model of high-fat diet-induced obesity by increasing UCP1 expression and by enhancing fat oxidation and energy expenditure.

Stress Echocardiography-Derived E/e’ Predicts Abnormal Exercise Hemodynamics in Heart Failure With Preserved Ejection Fraction

BackgroundThe correlation between echocardiographic parameters and hemodynamics data in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. It is important to find a non-invasive echocardiographic parameter for predicting exercise pulmonary capillary wedge pressure (PCWP).AimThis study sought to determine the correlation between echocardiographic parameters and hemodynamics data at rest and during exercise in HFpEF patients.Methods and ResultsThis study was a cross-sectional cohort exploratory analysis of baseline data from the ILO-HOPE trial. A total of 34 HFpEF patients were enrolled. The average age was 70 ± 12 years, and most (74%) were women. The patients underwent invasive cardiac catheterization and expired gas analysis at rest and during exercise. Echocardiography including tissue Doppler imaging was performed, and global longitudinal strain and other novel diastolic function indexes were analyzed at rest and during exercise. At rest, no significant correlation was noted between resting PCWP and echocardiographic parameters. However, a significant correlation was observed between post-exercise PCWP and stress E/e′ (septal, lateral, and mean) ratio (p = 0.003, 0.031, 0.012). Moreover, post-exercise ΔPCWP showed a good correlation with stress E/e′ (septal, lateral, and mean; all p ≤ 0.001) and global longitudinal strain (GLS) during exercise (p = 0.03). After multivariate regression analysis with adjustment for possible confounding factors including age and sex, there was still a significant correlation between post-exercise ΔPCWP and E/e′ (r = 0.62, p < 0.001 for E/e′mean).ConclusionOnly stress echocardiography derived tissue Doppler E/e′ ratio is closely correlated with abnormal exercise hemodynamics (PCWP and post-exercise ΔPCWP) in HFpEF. This echocardiographic marker is substantially more sensitive than other novel echocardiographic parameters during exercise, and may have significant diagnostic utility for ambulatory HFpEF patients with dyspnea.Clinical Trial Registrationhttps://www.clinicaltrials.gov, identifier NCT03620526.

Topical cutaneous application of carbon dioxide via a hydrogel for improved fracture repair: results of phase I clinical safety trial

BackgroundClinicians have very limited options to improve fracture repair. Therefore, it is critical to develop a new clinically available therapeutic option to assist fracture repair biologically. We previously reported that the topical cutaneous application of carbon dioxide (CO2) via a CO2 absorption-enhancing hydrogel accelerates fracture repair in rats by increasing blood flow and angiogenesis and promoting endochondral ossification. The aim of this study was to assess the safety and efficacy of CO2 therapy in patients with fractures.MethodsPatients with fractures of the femur and tibia were prospectively enrolled into this study with ethical approval and informed consent. The CO2 absorption-enhancing hydrogel was applied to the fractured lower limbs of patients, and then 100% CO2 was administered daily into a sealed space for 20 min over 4 weeks postoperatively. Safety was assessed based on vital signs, blood parameters, adverse events, and arterial and expired gas analyses. As the efficacy outcome, blood flow at the level of the fracture site and at a site 5 cm from the fracture in the affected limb was measured using a laser Doppler blood flow meter.ResultsNineteen patients were subjected to complete analysis. No adverse events were observed. Arterial and expired gas analyses revealed no adverse systemic effects including hypercapnia. The mean ratio of blood flow 20 min after CO2 therapy compared with the pre-treatment level increased by approximately 2-fold in a time-dependent manner.ConclusionsThe findings of the present study revealed that CO2 therapy is safe to apply to human patients and that it can enhance blood flow in the fractured limbs.Trial registrationThis study has been registered in the UMIN Clinical Trials Registry (Registration number: UMIN000013641, Date of registration: July 1, 2014).

Healthy Aging and Cardiovascular Function: Invasive Hemodynamics During Rest and Exercise in 104 Healthy Volunteers

ObjectivesThe aim of this study was to evaluate the association between age and invasive cardiovascular hemodynamics during upright exercise among healthy adults. BackgroundThe marked age-related decline in maximal exercise oxygen uptake (peak VO2) may contribute to the high burden of heart failure among older individuals and their greater severity of exertional symptoms. However, the mechanisms underlying this decline are not well understood. MethodsA total of 104 healthy community-dwelling volunteers age 20 to 76 years well screened for cardiovascular disease underwent exhaustive upright exercise with brachial and pulmonary artery catheters; radionuclide ventriculography; and expired gas analysis for the measurement of peak VO2, cardiac output, left ventricular stroke volume, end-diastolic volume, end-systolic volume, ejection fraction, pulmonary capillary wedge pressure, and arteriovenous oxygen difference. ResultsOver a 5.5-decade age range, there was a 40% decline in peak VO2 due primarily to reduced peak exercise cardiac output; peak arteriovenous oxygen difference was unaffected by age. The lower age-related exercise cardiac output was related to lower peak exercise heart rate and stroke volume. Aging was also associated with lower peak exercise ejection fraction, indicating reduced inotropic reserve. Peak exercise end-diastolic volume was lower with aging despite similar left ventricular filling pressure, suggesting age-related reduced diastolic compliance limiting the use of the Frank-Starling mechanism to compensate for reduced chronotropic and inotropic reserves. These age relationships were unaffected by sex. ConclusionsThe age-related decline in exercise capacity among healthy persons is due predominantly to cardiac mechanisms, including reduced chronotropic and inotropic reserve and possibly reduced Frank-Starling reserve. Peak exercise left ventricular filling pressure and arteriovenous oxygen difference are unchanged with healthy aging.

The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction

Increases in extravascular lung water (EVLW) during exercise contribute to symptoms, morbidity, and mortality in patients with heart failure and preserved ejection fraction (HFpEF), but the mechanisms leading to pulmonary congestion during exercise are not well-understood. Compensated, ambulatory patients with HFpEF (n = 61) underwent invasive haemodynamic exercise testing using high-fidelity micromanometers with simultaneous lung ultrasound, echocardiography, and expired gas analysis at rest and during submaximal exercise. The presence or absence of EVLW was determined by lung ultrasound to evaluate for sonographic B-line artefacts. An increase in EVLW during exercise was observed in 33 patients (HFpEFLW+, 54%), while 28 (46%) did not develop EVLW (HFpEFLW-). Resting left ventricular function was similar in the groups, but right ventricular (RV) dysfunction was two-fold more common in HFpEFLW+ (64 vs. 31%), with lower RV systolic velocity and RV fractional area change. As compared to HFpEFLW-, the HFpEFLW+ group displayed higher pulmonary capillary wedge pressure (PCWP), higher pulmonary artery (PA) pressures, worse RV-PA coupling, and higher right atrial (RA) pressures during exercise, with increased haemoconcentration indicating greater loss of water from the vascular space. The development of lung congestion during exercise was significantly associated with elevations in PCWP and RA pressure as well as impairments in RV-PA coupling (area under the curve values 0.76-0.84). Over half of stable outpatients with HFpEF develop increases in interstitial lung water, even during submaximal exercise. The acute development of lung congestion is correlated with increases in pulmonary capillary hydrostatic pressure that favours fluid filtration, and systemic venous hypertension due to altered RV-PA coupling, which may interfere with fluid clearance. NCT02885636.

P4430Physical activity in leisure time: complying with the recommendations of clinical practice guidelines increases maximum oxygen consumption

Abstract Introduction/Objectives The promotion of physical activity is a universal recommendation for prevention of cardiovascular diseases. Clinical practice guidelines recommend at least 150 min/week of moderate or severe physical activity or ≥75 min of severe intensity.Our objective was to analyze whether reaching the physical activity levels recommended in the clinical practice guidelines evaluated by validated questionnaires and accelerometry, is associated with higher level of VO2 max. Methods We conducted a prospective cross-sectional study of 243 participants in the PREDIMED PLUS study (site: Vitoria-Gasteiz), (82 women), 65±4,9 years old, with metabolic syndrome and overweight/obesity. They performed a maximum exercise testing with expired gas analyses. Physical activity in leisure time was evaluated using subjective methods: self-reported questionnaires REGICOR and RAPA 1 and objective methods: chair test and accelerometry (91 subjects). Sedentarism was analyzed with the Nurses Health Study questionnaire and accelerometry Results Subjects who claimed to comply with the recommendations of the PA guidelines in the REGICOR questionnaire achieved higher maximum oxygen consumption (21.3±4.6 vs 18±4.4 ml/kg/min; P&lt;0.001) and those who reported more physical activity in the RAPA 1 test showed a maximum oxygen consumption 18% higher than the less active group (P &lt; . 001). However, those who performed ≥150 min/week of moderate/intense physical activity by accelerometry did not differ significantly from those who did not (21.1±4.7 vs 19.9±4.7 ml/kg/min; P: 0.644). Conclusions Subjects with metabolic syndrome and overweight/obesity who claim to meet PA recommendations in the REGICOR and RAPA tests achieve higher máximum oxygen consumption