-
Journal of the American College of... May 2024In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics.
OBJECTIVES
This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM.
METHODS
Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints.
RESULTS
A total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better V/Vco (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of -2.1 (95% CI: -3.6 to -0.6; P = 0.006), with no significant difference in peak VO (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: -2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; P = 0.04).
CONCLUSIONS
In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a phase 3 study.
Topics: Humans; Cardiomyopathy, Hypertrophic; Female; Male; Middle Aged; Double-Blind Method; Treatment Outcome; Aged; Oxygen Consumption
PubMed: 38599256
DOI: 10.1016/j.jacc.2024.03.387 -
Scientific Reports Oct 2023Conventionally, efficiency is indirectly estimated through a respiratory gas analyser (oxygen, carbon dioxide), which is a complex and rather costly calculation method...
Conventionally, efficiency is indirectly estimated through a respiratory gas analyser (oxygen, carbon dioxide), which is a complex and rather costly calculation method that is difficult to perform in many situations. Therefore, the present study proposed a modified definition of efficiency, called the efficiency factor (EF) (i.e., the ratio of work to the corresponding exercise intensity), and evaluated the relation between the EF and maximal oxygen uptake ([Formula: see text]), as well as compared the prediction models established based on the EF. The heart rate (maximal heart rate: 186 ± 6 beats min), rating of perceived exertion (19 ± 1), and [Formula: see text] (39.0 ± 7.1 mL kg min) of 150 healthy men (age: 20 ± 2 years; height: 175.0 ± 6.0 cm; weight: 73.6 ± 10.7 kg; body mass index [BMI]: 24.0 ± 3.0 kg m; percent body fat [PBF]: 17.0 ± 5.7%) were measured during the cardiopulmonary exercise test (CPET). Through multiple linear regression analysis, we established the BMI model using age and BMI as parameters. Additionally, we created the PBF model utilizing weight, PBF, and heart rate reserve (HRR) and developed PBF model and PBF model by incorporating EF6 from the exercise stage 6 and EF7 from the exercise stage 7 during the CPET, respectively. EF6 (r = 0.32, p = 0.001) and EF7 (r = 0.31, p = 0.002) were significantly related to [Formula: see text]. Among the models, the PBF model showed the highest accuracy, which could explain 62.6% of the variance in the [Formula: see text] at with a standard error of estimate (SEE) of 4.39 mL kg min (%SEE = 11.25%, p < 0.001). These results indicated that the EF is a significant predictor of [Formula: see text], and compared to the other models, the PBF model is the best model for estimating [Formula: see text].
Topics: Male; Humans; Adolescent; Young Adult; Adult; Feasibility Studies; Oxygen Consumption; Exercise; Exercise Test; Oxygen
PubMed: 37798330
DOI: 10.1038/s41598-023-43307-3 -
BMC Plant Biology Oct 2023Conventional methods to measure oxygen consumption, such as Clark-type electrodes, have limitations such as requiring a large amount of starting material. Moreover,...
BACKGROUND
Conventional methods to measure oxygen consumption, such as Clark-type electrodes, have limitations such as requiring a large amount of starting material. Moreover, commercially available kits for high-throughput methods are usually optimized for animal cells and mitochondria. Here, we present a novel method to measure the oxygen consumption rate using a high-throughput assay in isolated mitochondria of European beech seeds. To perform the measurements, we adapted the Agilent Seahorse XF Cell Mito Stress Test Kit protocol for measurements on plant mitochondria.
RESULTS
The optimized protocol for OCR measurement of mitochondria isolated from beech seeds allowed the observation of storage period-dependent gradual decreases in non-phosphorylating respiration, phosphorylating respiration and maximal FCCP-stimulated respiration. The longer the seeds were stored, the greater the impairment of respiratory function.
CONCLUSIONS
Thanks to this method it is possible to minimize the amount of plant material and conduct research to obtain information on the respiratory condition and activity of plant mitochondria, including the efficiency of oxidative phosphorylation and the maximum oxidative capacity of the respiratory chain. We demonstrated that the improved protocol is suitable for study of plant material.
Topics: Animals; Cell Respiration; Mitochondria; Oxygen Consumption; Electron Transport; Oxidation-Reduction; Plants; Oxygen
PubMed: 37845628
DOI: 10.1186/s12870-023-04516-0 -
Arquivos Brasileiros de Cardiologia Dec 2023Central Illustration : Prediction of Peak Oxygen Consumption in Patients with Heart Disease Based on Performance on the Timed Up and Go Test CPET: cardiopulmonary...
BACKGROUND
Central Illustration : Prediction of Peak Oxygen Consumption in Patients with Heart Disease Based on Performance on the Timed Up and Go Test CPET: cardiopulmonary exercise test; TUG: timed up and go test; VO2peak: peak oxygen consumption.
BACKGROUND
The use of the timed up and go (TUG) test to assess cardiorespiratory fitness in patients with heart disease has not been well defined in the literature.
OBJECTIVES
Test the association between TUG and peak oxygen consumption (VO2peak), construct an equation based on TUG to predict VO2peak, and determine a cutoff point to estimate VO2peak ≥ 20 mL/kg/min.
METHODS
This cross-sectional study included 201 patients with coronary artery disease or heart failure, between 36 and 92 years of age, who underwent TUG and cardiopulmonary exercise test. Correlation, ROC curve, multiple linear regression, and Bland-Altman analyses were performed. The significance level was set at p < 0.05.
RESULTS
The mean age of the total sample was 67 ± 13 years, and 70% of participants were male. The mean VO2peak was 17 ± 6 mL/kg/min, and the mean TUG time was 7 ± 2.5 seconds. The correlation between VO2peak and TUG was r = -0.54 (p < 0.001), and R2 was 0.30. The following equation was developed based on TUG: V O 2 peak = 33.553 + ( - 0.149 × age ) + ( - 0.738 × TUG ) + ( - 2.870 × sex ) ; a value of 0 was assigned to the male sex and 1 to the female sex (adjusted R: 0.41; adjusted R2: 0.40). The VO2peak estimated by the equation was 18.81 ± 3.2 mL/kg/min, and the VO2peak determined by cardiopulmonary exercise test was 18.18 ± 5.9 mL/kg/min (p > 0.05). The best cutoff point in the TUG for VO2peak ≥ 20 mL/kg/min was ≤ 5.47 seconds (area under the curve: 0.80; 95% confidence interval: 0.74 to 0.86).
CONCLUSIONS
TUG and VO2peak showed a significant association. A prediction equation for VO2peak was developed and validated internally with good performance. The cutoff point in the TUG to predict VO2peak ≥ 20 mL/kg/min was ≤ 5.47 seconds.
Topics: Humans; Male; Female; Middle Aged; Aged; Aged, 80 and over; Cross-Sectional Studies; Postural Balance; Time and Motion Studies; Exercise Test; Heart Failure; Oxygen Consumption
PubMed: 38126569
DOI: 10.36660/abc.20230338 -
Journal of Science and Medicine in Sport Jul 2023To evaluate the effects of brain endurance training (BET) on endurance and cognitive performance in road cyclists.
OBJECTIVES
To evaluate the effects of brain endurance training (BET) on endurance and cognitive performance in road cyclists.
DESIGN
Two independent randomized controlled pretest-posttest training studies.
METHODS
In both studies cyclists trained five times/week for six weeks and completed either cognitive response inhibition tasks (Post-BET group) or listened to neutral sounds (control group) after each training session. In Study-1, 26 cyclists performed a time to exhaustion (TTE) test at 80 % peak power output (PPO), followed by a 30-min Stroop task, and a TTE test at 65 % PPO. In Study-2, 24 cyclists performed a 5-min time trial, followed by a 30-min Stroop task, 60-min submaximal incremental test, and a 20-min . Heart rate, lactate, rating of perceived exertion (RPE), Stroop reaction time and accuracy were also measured.
RESULTS
During Study 1, Post-BET improved TTE at 80 % (p = 0.032) and 65 % PPO (p = 0.011) significantly more than control with lower RPE (all p < 0.043). In Study 2, 5-min TT performance did not differ between groups. During the 60-min submaximal incremental test, RPE was lower in the Post-BET group compared to the control group (p = 0.034) and 20-min TT performance improved significantly more in the Post-BET group than in the control group (all p < 0.031). No group differences were found in physiological measures. In both studies, Stroop reaction times improved significantly more in the Post-BET group than in the control group (all p < 0.033).
CONCLUSIONS
These findings suggest that Post-BET may be used to improve the performance of road cyclists.
Topics: Humans; Endurance Training; Lactic Acid; Heart Rate; Cognition; Brain; Bicycling; Physical Endurance; Oxygen Consumption
PubMed: 37301613
DOI: 10.1016/j.jsams.2023.05.008 -
Nutrients Aug 2023The effects of intake of STGs containing esterified eicosapentaenoic acid (EPA) and medium-chain triglycerides (MCTs) on cardiorespiratory endurance have not yet been... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The effects of intake of STGs containing esterified eicosapentaenoic acid (EPA) and medium-chain triglycerides (MCTs) on cardiorespiratory endurance have not yet been reported. This study aimed to examine the efficacy of interesterified structured lipids EPA and MCTs on cardiorespiratory endurance.
METHODS
This 8-week randomized double-blind placebo-controlled parallel-group study involved 19 healthy men. The participants were randomly assigned to a group that received interesterified structured lipids EPA and MCTs (STG group, 9 participants) or a group receiving a PM of EPA and MCTs (PM group, 10 participants). The outcome measures were time to exhaustion (TTE) and time to reach the anaerobic threshold in the peak oxygen uptake (VOpeak) test, VOpeak, and anaerobic threshold.
RESULTS
The increase in TTE in the VOpeak test after the intervention period compared with before the intervention period was significantly greater in the STG group (53 ± 53 s) than in the PM group (-10 ± 63 s; < 0.05). Similarly, the increase in time to reach the anaerobic threshold was significantly greater in the STG group (82 ± 55 s) than in the PM group (-26 ± 52 s; < 0.001).
CONCLUSION
This study demonstrated that the consumption of interesterified structured lipids EPA and MCTs improved endurance in humans.
Topics: Male; Humans; Eicosapentaenoic Acid; Nutritional Status; Health Status; Anaerobic Threshold; Triglycerides
PubMed: 37686724
DOI: 10.3390/nu15173692 -
BMC Pediatrics Nov 2023This study [PROSPERO CRD42023416272] systematically analysed the effects of a physical activity intervention on cardiorespiratory fitness in obese children and... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study [PROSPERO CRD42023416272] systematically analysed the effects of a physical activity intervention on cardiorespiratory fitness in obese children and adolescents and elucidated the factors that influenced those effects.
METHODS
A systematic review of the literature on physical activity interventions for improving cardiopulmonary fitness in obese children and adolescents from January 1, 2011, to March 1, 2023, was conducted. The search was performed on the Web of Science and PubMed databases, and the selected literature was first screened and then assessed for quality. Finally, a systematic review was conducted.
RESULTS
Out of the initially identified 1424 search records, 28 studies were eventually included in the systematic review. These studies encompassed a total of 2724 participants aged 5 to 18 years, with the publication dates of the literature primarily ranging from 2011 to 2023. Physical activity was found to effectively improve the following parameters in obese children and adolescents: weight [mean difference (MD), -2.03 (95% confidence interval, -2.59 to -1.47), p < 0.00001], maximal oxygen consumption [MD, -1.95 (95% CI, -1.06 to -2.84), p < 0.0001], heart rate [MD, -2.77 (95% CI, -4.88 to -0.67), p = 0.010], systolic blood pressure [MD, -8.11 (95% CI, -11.41 to -4.81), p < 0.00001], and diastolic blood pressure [MD, -4.18 (95% CI, -5.32 to -3.03), p < 0.00001]. High-intensity exercise was found to yield greater improvements than low- to moderate-intensity exercise in maximal oxygen consumption [MD, 1.43 (95% CI, 0.04 to 2.82), p = 0.04] and diastolic blood pressure [MD, -6.94 (95% CI, -10.61 to -3.26), p = 0.0002] in obese children and adolescents.
CONCLUSION
Physical activity can effectively improve the body weight, maximal oxygen consumption, heart rate, systolic blood pressure, and diastolic blood pressure of obese children and adolescents. The type of physical activity directly influences the participation interest of obese children and adolescents, with moderate- to high-intensity physical activity showing the most significant impact on intervention outcomes. High-frequency, long-term interventions yield better results than short-term interventions.
Topics: Humans; Child; Adolescent; Pediatric Obesity; Exercise; Cardiorespiratory Fitness; Oxygen Consumption; Physical Fitness
PubMed: 37932667
DOI: 10.1186/s12887-023-04381-8 -
Biology Nov 2023To ensure optimal feed intake, growth, and general fish health in aquaculture sea cages, interactions between drivers that affect oxygen conditions need to be...
To ensure optimal feed intake, growth, and general fish health in aquaculture sea cages, interactions between drivers that affect oxygen conditions need to be understood. The main drivers are oxygen consumption and water exchange, caused by flow through the cage. Swimming energetics in rainbow trout () in normoxia and hypoxia at 10, 15, and 20 °C were determined. Using the determinations, a conceptual model of oxygen conditions within sea cages was created. By applying the model to a case study, results show that with a temperature increase of 10 °C, oxygen concentration will decrease three times faster. To maintain optimal oxygen concentration within the cage, the flow velocity must be increased by a factor of 3.7. The model is highly relevant for current farms since the model predictions can explain why and when suboptimal conditions occur within the cages. Using the same method, the model can be used to estimate the suitability of potential new aquaculture sites.
PubMed: 37998007
DOI: 10.3390/biology12111408 -
BMC Medical Genomics Aug 2023Functional changes in subcutaneous adipose tissue (SAT) occur earlier in the aging process and play an important role in the occurrence and development of age-related...
BACKGROUND
Functional changes in subcutaneous adipose tissue (SAT) occur earlier in the aging process and play an important role in the occurrence and development of age-related metabolic diseases. The mechanism of this phenomenon is still unclear, and the change in adipose tissue with age is poorly understood.
METHODS
We used transcriptome sequencing (RNA seq) to screen differentially expressed genes at the mRNA level, and analyzed the functional characteristics of the differential genes through GO and KEGG analysis in human SAT of all ages. In order to clarify the specific mechanism of the functional change, we analyzed the chromatin accessibility in the promoter region in the same SAT used in the RNA seq by the assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and obtained the functional genes in SAT changed with age. To verify these changes, we enlarged our sample content of human SAT. The primary mice adipocytes were extracted and stimulated by thyroid hormone of different concentration to construct an animal model, and the expression of the genes were determined through real-time Polymerase Chain Reaction(RT-PCR). The oxygen consumption test and immunofluorescence staining were used to determine the mitochondrial function of SAT.
RESULTS
RNA-seq showed characteristic gene expression of young and old human SAT, in which 331 genes were up-regulated and 349 genes were down-regulated. ATAC-seq, RNA-seq, combined with the mouse prediction model, determined the functional changed characteristics of seven genes. All these genes expressed differently in SAT of different ages, in which, NCF1, NLRP3, DUOX1 showed positive correlation with age; The expression of IFI30, P2RX1, P2RX6, PRODH, however, decreased with age. And all these genes showed dose dependent alternations under treatment of triiodothyroxine in mice SAT. The oxygen consumption rate revealed significant changes of the mitochondrial function and ROS accumulation in human SAT of different ages.
CONCLUSION
In elderly individuals, the function, in addition to distribution, of SAT undergoes significant changes, primarily in mitochondria, which may be due to insensitivity to thyroid hormone signaling. These results identified seven novel genes regulated by thyroid hormone, exhibiting significant changes in SAT of different age, and are probably related to the dysfunction of the aged SAT due to the mitochondrial damage and ROS accumulation.
Topics: Aged; Humans; Animals; Mice; Reactive Oxygen Species; Subcutaneous Fat; Adipose Tissue; Chromatin; Disease Models, Animal; Aging
PubMed: 37626392
DOI: 10.1186/s12920-023-01641-5 -
Heliyon Aug 2023Respiratory function is thought to improve with long-term meditation. This study aimed to assess respiratory function in a cohort of healthy long-term meditators and...
PURPOSE
Respiratory function is thought to improve with long-term meditation. This study aimed to assess respiratory function in a cohort of healthy long-term meditators and non-meditators in Sri Lanka.
METHODS
Respiratory function of healthy, skilled long-term meditators (n = 20) practicing Buddhist meditation consistently >3 years, and age-sex matched non-meditators (n = 20) were assessed by assessing resting respiratory rate, spirometry, breath-holding time and six-minute-walk distance. Data were analyzed with SPSS-23 statistical software.
RESULTS
The long-term meditators; 45% male, mean (SD) total lifetime meditation experience 12.8 (6.5) years, aged 45.8 (8.74) years, BMI 23.68 (2.23) kgm, and non-meditators; 45% male, mean (SD) age 45.3 (8.05) years, BMI 23.68 (3.28) kgm, were comparable. Long-term meditators had slower resting respiratory rates [mean (SD); 13.35 (1.9) vs. 18.37 (2.31) breaths/minute; p < 0.001], higher peak expiratory flow rates [mean (SD); 9.89 (2.5) vs. 8.22 (2.3) L/s; p = 0.03], and higher inspiratory breath-holding times [mean (SD); 74 (29.84) vs. 53.61 (26.83) seconds, p = 0.038] compared to non-meditators. There was no significant difference in the six-minute-walk distance and estimated maximal oxygen consumption between the two groups.Resting respiratory rate of long-term meditators, showed a significant negative correlation with total lifetime meditation practice in years (r = -0.444, p = 0.049), and the average length of a meditation session per day (r = -0.65, p = 0.002). The long-term meditators with longer duration of retreat participation demonstrated lower resting respiratory rate (r = -0.522, p = 0.018) and higher tidal volumes (r = 0.474, p = 0.04).
CONCLUSIONS
Long-term meditators had significantly slower resting respiratory rates and longer breath-holding times, with better spirometry parameters than non-meditators. Greater practice duration and retreat experience appear to be associated with improved resting respiratory function in long-term meditators.
PubMed: 37554788
DOI: 10.1016/j.heliyon.2023.e18585