Changes In Oxygen Consumption Research Articles

Abstract 4129182: Transendocardial Stem Cell Therapy Improves Cardiac Parameters in Chronic Ischemic Heart Failure: A Meta-analysis of Randomized Controlled Trials

Introduction: Despite recent advances in therapy, chronic ischemic heart failure remains a significant cause of morbidity and mortality worldwide. Stem cell (SC) therapy has recently emerged as a potential therapeutic approach, yet its efficacy remains debatable. We aimed to systematically review and meta-analyze the current evidence to evaluate its effectiveness. Methods: A comprehensive literature search was conducted across the following databases: PubMed, Embase, and Cochrane, from inspection to April 2024. We identified RCTs with a blinded study design, done on patients diagnosed with chronic ischemic HFrEF, and utilized mesenchymal stem cells as an intervention in comparison to placebo/sham intervention using percutaneous endomyocardial catheter systems. Meta-analysis was conducted using RevMan v5.4 to calculate the odds ratio (OR) at 95% confidence intervals (CI) and a p-value of 0.05. I 2 was indicated for the assessment of heterogeneity. Sensitivity analysis was done in case of heterogeneity between studies. Results: A total of twenty studies were included in our meta-analysis. The overall change in left ventricular end-systolic volume (LVESV) and stress SPECT significantly favored the stem cell group (pooled effect size -7.59, 95% CI [-12.28 to -2.89], P=0.002), and (pooled effect size -5.33, 95% CI [-6.73 to -3.93], P=0.00001), respectively. Initially, the change in left ventricular end-diastolic volume (LVEDV) did not favor either group. However, sensitivity analysis which excluded one study at a time, reduced heterogeneity (P=0.01, I 2 =54%) and showed a significant effect favoring the stem cell group (pooled effect size -3.87, 95% CI [-6.77 to -0.97], P=0.009). However, the overall changes in left ventricular ejection fraction (LVEF) did not favor either of the two groups (pooled effect size 0.08, 95% CI [-0.1 to 0.26], P=0.39). Similarly, the overall change in myocardial oxygen consumption (MVO2) did not favor either group (pooled effect size 0.66, 95% CI [-0.1 to 1.32], P=0.05). Conclusion: Transendocardial SC therapy demonstrates promising results by significantly improving specific cardiac parameters. While the therapy shows potential, particularly after sensitivity adjustments, its impact on other critical measures like LVEF and MVO2 remains inconclusive. These findings highlight the need for further investigation to fully understand and enhance the therapeutic potential of stem cell interventions in heart failure management.

Exercise Training in Patients With Hypertrophic Cardiomyopathy Without Left Ventricular Outflow Tract Obstruction: A Randomized Clinical Trial.

Patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction commonly experience reduced exercise capacity. Physical training improves exercise capacity in these patients, but whether the underlying effects of exercise are a result of central hemodynamic or peripheral improvement is unclear. This study assessed whether exercise training reduces left ventricular filling pressure measured during exercise in patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction. Between March 2019 and June 2022, patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction were randomly assigned (1:1) to a 12-week (3 h/wk) supervised, moderate-intensity exercise training program or continued usual activity. The primary outcome was the change in invasively measured pulmonary capillary wedge pressure during mild exercise (25 W) from baseline to week 12. Pressure tracings were analyzed offline by a blinded investigator. Secondary outcomes included changes in peak oxygen consumption, cardiac index, quality of life, echocardiographic indices of diastolic function, and natriuretic peptides. Of 59 patients randomized (mean age, 58.1±12.2 years; 27% women), 51 (86%) completed all follow-up assessments. At week 12, the change in 25-W pulmonary capillary wedge pressure was -2.8±6.8 mm Hg in the exercise group, compared with +1.2±4.9 mm Hg in the usual-activity group (between-group difference, 4.0 mm Hg [95% CI, 0.7-7.3]; P=0.018). Peak oxygen consumption improved by +1.8±2.0 mL/kg/min in the exercise group versus -0.3±3.1 mL/kg/min in the usual-activity group (P=0.005). Exercise training improved the ventilatory efficiency (VE/VCO2) slope compared with usual activity (between-group difference, 2.0 [95% CI, 0.6-3.5]; P=0.006). Peak cardiac index improved by +0.38±1.38 L/min/m2 in exercise versus -0.85±1.20 L/min/m2 in the usual-activity group (P=0.002). Change in overall Kansas City Cardiomyopathy Questionnaire score was similar between groups. However, the change in physical limitation scores (+8.4±12.0 points in exercise versus +0.7±6.8 points in usual-activity group; P=0.034) and quality-of-life scores (+8.7±18.0 points in exercise versus 0.7±4.0 points in usual-activity group; P=0.01) differed significantly. There were no significant changes in diastolic function assessed by echocardiography or in natriuretic peptides. In patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction, a 12-week moderate-intensity exercise training program resulted in reduced left ventricular filling pressures at mild exertion and improved exercise performance. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537183.

Determinants of changes in peak oxygen consumption in patients with new onset heart failure

Abstract Background Patients with heart failure (HF) with reduced ejection fraction (HFrEF) have a high risk of mortality. Cardio-Pulmonary Exercise Test (CPET) assesses peak oxygen consumption (pVO2) which is considered a key predictor of mortality and morbidity in patients with HFrEF. Factors responsible for the changes in pVO2 could consequently be of interest, as optimizing these factors may improve prognosis and overall quality of life in patients with HFrEF. Purpose To investigate factors contributing to changes in pVO2 within a contemporary cohort of new-onset patients with HFrEF. Methods From December 2022 to September 2023, patients with new-onset HFrEF (European Society of Cardiology (ESC) criteria) were included from a HF outpatient clinic, who after referral to the clinic underwent 12 weeks of HF management according to ESC guidelines. This included physical training and optimization of pharmacological management of HFrEF. Baseline characteristics, CPET, medication and echocardiography were collected at referral and after 12 weeks. Changes in pVO2 were investigated according to baseline characteristics, changes in medication, and changes in echocardiographic parameters in both uni- and multivariable linear regression models. Significant independent variables were identified using stepwise selection (p<0.1), adjusted for age and sex. A p-value of 0.05 was considered significant. Results We included 48 patients with new-onset HFrEF with a median age of 73 (interquartile range (IQR): 60-77) years, 10 (20.8%) women, a baseline median left ventricular ejection fraction (LVEF) of 30% (IQR: 25-35), and a baseline median pVO2 of 17.3 ml/min/kg (IQR: 14.1-21.9). After 12 weeks, pVO2 improved with a mean of +2.18 ml/min/kg (95% confidence interval (CI) 1.25 to 3.10, p<0.01) and LVEF improved with a mean of +11.7% (95% CI 7.9 to 15.6, p<0.01). In univariable analyses increasing age were negatively associated with pVO2 changes (p=0.04) and increasing minute ventilation (MV) and initiation of sodium-glucose cotransporter (SGLT2) inhibitors were all positively associated with pVO2 changes (p<0.01 and p=0.03, respectively). Other clinical variables included in the analysis were not significantly associated with a change in pVO2. In the multivariable analysis, body mass index emerged as an independent variable negatively associated with pVO2 changes, and MV and initiation of SGLT2 inhibitors remained significantly positively associated with pVO2 changes. Conclusion Optimal pharmacological management and physical training in patients with new-onset HFrEF, induce a significant recovery of cardiorespiratory performance and ejection fraction. Furthermore, our results suggest that the initiation of SGLT2 inhibitors in patients with new-onset HFrEF appears to improve their pVO2 already after 12 weeks of optimal HF management.Table 1:BaselineTable 2:Associations

Feasibility of hybrid telerehabilitation and telecare in heart failure patients with implanted left ventricular assist device LVAD

Abstract Background Left ventricular assist device (LVAD) implantation is increasingly used as a treatment option for patients with advanced heart failure (HF). There is a need to provide patients with LVAD with long-term care, preferably at home. The implementation of home-based telerehabilitation (HTR) and telecare offers new opportunities in this field. Purpose The purpose of this study was to assess feasibility and safety of HTR and telecare in HF patients with implanted LVAD and evaluate patients’ acceptance of and adherene to HTR. Methods The study enrolled 30 HF patients with recent implanted LVAD (21 Heart Mate III, 9 Heart Ware) (29 males, 19–67, mean 59 years) who underwent a 12-week telecare and HTR program based on walking, respiratory and resistance training, five times weekly. HTR was telemonitored with a device adjusted to register electrocardiogram (ECG) recording and to transmit data via mobile phone network to the monitoring center. The moments of automatic ECG registration were pre-set and coordinated with exercise. The influence on physical capacity was assessed by comparing changes in peak oxygen consumption (VO2 peak; [ml/kg/min]) and workload duration (t; [sec]) in cardiopulmonary exercise test. Results HTR resulted in a significant physical capacity improvement pVO2 12.5±2.9 vs 15.1±3.0 (p<0.001), and workload duration t 628±204 vs 728±222 (p<0.001) in cardiopulmonary exercise test. There were neither deaths nor adverse events during HTR. Patients accepted HTR, including the need for interactive everyday collaboration with the medical team from monitoring center. All patients completed HTR. Conclusions HTR is a feasible, safe form of rehabilitation, well accepted by patients. The adherence to HTCR was high.

Effectiveness of hybrid comprehensive telerehabilitation in women with heart failure - subanalysis of the TELEREH-HF RCT

Abstract Background Despite the known benefits of cardiac rehabilitation, it remains underutilized among women. In particular, little is known about the effectiveness of hybrid comprehensive telerehabilitation (HCTR) in women with heart failure (HF). Purpose: The purpose of this study was to assess effectiveness and safety of HCTR in women with HF. Methods: The present analysis formed part of TELEREH-HF multicenter, randomized trial that enrolled 850 HF patients (NYHA I-III, LVEF ≤ 40%). Patients were randomized 1:1 to HCTR plus usual care (UC) or UC alone. Patients underwent either an HCTR (1 week in hospital and 8 weeks at home, five times weekly) or UC with observation. The effectiveness of HCTR was assessed by changes in peak oxygen consumption (VO2 peak), workload duration (t) in cardiopulmonary exercise test and quality of life (QoL) based on Medical Outcome Survey Short Form 36 Questionnaire (SF-36). Measurements were made before and after intervention/observation. Results: Women constituted 11.5 % of population in the TELEREH-HF study. Forty women in HCTR group and 44 women in UC group completed HCTR and observation respectively. HCTR resulted in significant improvement in VO2peak, workload duration and QoL. We did not observe these favorable results in the UC group except for an increase workload duration. In the HCTR group, there was a significantly greater improvement in physical component of QoL than in the UC group. All results are presented in Table 1. In neither group were there deaths nor major adverse events related to exercise training. Conclusion In women with HF, hybrid comprehensive telerehabilitation is safe and resulted in a significant improvement in physical capacity and QoL.

Changes in peak oxygen consumption on excercise and cardiomyopathy disease stage in Fabry disease

Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder manifesting as deficiency in the enzyme α-Galactosidase A (1) resulting in multi-organ accumulation of globotriaosylceramide (Gb3) (2) This causes predominantly cardiac, renal and cerebrovascular manifestations. Shortness of breath and exercise intolerance are common and can be related to multiple underlying mechanisms. Cardiopulmonary exercise testing (CPEX) quantifies aerobic fitness, functional capacity, chronotropic and haemodynamic response to exercise, and attributes effort intolerance to different aetiologies, including impaired cardiac and respiratory function. Purpose We hypothesise that there is progressive effort intolerance that reflects continual cardiac Gb3 accumulation, becoming common during myocardial hypertrophy and disabling in the fibrosis and inflammation stage. The aims of this study were to ascertain frequency and severity of exercise intolerance in FD by investigating the relationship between peak maximal oxygen uptake (VO2 max) and cardiac disease stage, quantified based on a four-point scale, as proposed in published literature (3). Methods This was a retrospective review of adults with FD and exercise intolerance attending a specialist clinic who had undergone either CPEX or six-minute walk testing (6MWT) in those less mobile. Biochemical, cardiac magnetic resonance (CMR) imaging and transthoracic echocardiographic (TTE) data were also collected. Results N=54 patients underwent CPEX and N=35 patient underwent 6MWT. Estimated peak VO2 max was calculated using 6MWD in those undergoing 6MWT. Median age was 54 (IQR 40-62) years and 53% were male. Patients were equally distributed across disease stage (1-4). There were significant trends in age (increasing) and gender (male predominance) from stage 1-4. Age/sex-normalised peak VO2 max values were calculated as per published literature due to the confounding effect of age and male gender. Mean normalised VO2 max was 35.5ml/kg/min for the cohort, an underperformance of 12.3 ± 8.0 ml/kg/min. The magnitude of underperformance began from stage 1 (no cardiomyopathy) and increased with each stage (Figure 1). Impairments in renal (creatinine and albumin: creatinine ratio) and cardiac biomarkers (troponin and N-terminal pro brain natriuretic peptide) was associated with reduced VO2 max (Table 1). Increased indexed left ventricular mass on CMR and impairments in atrial volume and function on TTE were also associated with a reduction in VO2 max (Table 1). Conclusion This study is the first of its kind to demonstrate impairments in peak aerobic capacity in adults with FD and no cardiomyopathy (stage 1) which impairs further with cardiac disease stage. Future work should focus on how disease-modifying therapy can target this using VO2 as an endpoint and marker of response.Normalised peak VO2 max + disease stageVO2 max and blood / imaging parameters

Comparison of exercise training modalities and change in peak oxygen consumption in heart failure with preserved ejection fraction: a secondary analysis of the OptimEx-Clin trial.

Exercise training (ET) is an effective therapy in heart failure with preserved ejection fraction (HFpEF), but the influence of different ET characteristics is unclear. We aimed to evaluate the associations between ET frequency, duration, intensity [% heart rate reserve (%HRR)] and estimated energy expenditure (EEE) with the change in peak oxygen consumption (V̇O2) over 3 months of moderate continuous training (MCT, 5×/week) or high-intensity interval training (HIIT, 3×/week) in HFpEF. ET duration and heart rate (HR) were recorded with a smartphone application. EEE was calculated using the HR data during ET and the individual HR-V̇O2 relationships during cardiopulmonary exercise testing. Differences between groups and associations between ET characteristics and peak V̇O2 change were assessed with linear regression analyses. Peak V̇O2 improved by 9.2 ± 13.2% after MCT and 8.7 ± 15.9% after HIIT (P = 0.67). The average EEE of 1 HIIT session was equivalent to ∼1.42 MCT sessions and when adjusted for EEE, the mean difference between MCT and HIIT was -0.1% (P = 0.98). For both MCT and HIIT, peak V̇O2 change was positively associated with ET frequency (MCT: R2 = 0.103; HIIT: R2 = 0.149) and duration/week (MCT: R2 = 0.120; HIIT: R2 = 0.125; all P < 0.05). Average %HRR was negatively associated with peak V̇O2 change in MCT (R2 = 0.101; P = 0.034), whereas no significant association was found in HIIT (P = 0.234). Multiple regression analyses explained ∼1/3 of the variance in peak V̇O2 change. In HFpEF, isocaloric HIIT and MCT seem to be equally effective over 3 months. Within each mode, increasing ET frequency or duration/week may be more effective to improve peak V̇O2 than increasing ET intensity.

Efficacy of mHealth-based Workplace Health Promotion Strategy in improving Cardiorespiratory Fitness in a Healthcare Setting: A Randomized Controlled Study.

To test the efficacy of a mHealth based workplace health promotion strategy in improving cardiorespiratory fitness in a healthcare setting. Seventy-seven female nurses (age: 30-45 years) meeting the inclusion criteria underwent baseline assessment and received either a 12-week mHealth or awareness intervention based on their workplace. Changes in peak oxygen consumption (VO2), fasting blood sugar and physical activity were compared within and between the groups at the end of the intervention. Thirty-seven and 33 participants in the mHealth and awareness arms respectively, completed the 12-week intervention. Peak VO2 (1.6 mL●kg-1●min-1, 7%), physical activity and step counts improved significantly in the mHealth arm. However, between-group differences were not significant. mHealth interventions offer unique opportunities to improve physical activity and cardiorespiratory fitness among health professionals in their workplace.

Effects of Microplastics on the Oxygen Consumption and Histological Changes of the Cultured Nile Tilapia Oreochromis niloticus

Effects of Microplastics on the Oxygen Consumption and Histological Changes of the Cultured Nile Tilapia Oreochromis niloticus

Variability of cardiopulmonary exercise testing in patients with atrial fibrillation and determination of exercise responders to high-intensity interval training and moderate-to-vigorous intensity continuous training.

Disabling atrial fibrillation (AF)-related symptoms and different testing settings may influence day-to-day cardiopulmonary exercise testing (CPET) measurements, which can affect exercise prescription for high-intensity interval training (HIIT) and moderate-to-vigorous intensity continuous training (M-VICT) and their outcomes. This study examined the reliability of CPET in patients with AF and assessed the proportion of participants achieving minimal detectable changes (MDC) in peak oxygen consumption (V̇O2peak) following HIIT and M-VICT. Participants were randomized into HIIT or M-VICT after completing two baseline CPETs: one with cardiac stress technologists (CPETdiag) and the other with a research team of exercise specialists (CPETresearch). Additional CPET was completed following 12 weeks of twice-weekly training. Reliability of CPETdiag and CPETresearch was assessed by intraclass correlation coefficient (ICC) and dependent t-tests. The MDC score was calculated for V̇O2peak using a reliable change index. The proportion of participants achieving MDC was compared between HIIT and M-VICT using chi-square analysis. Eighteen participants (69±7 years, 33% females) completed two baseline CPETs. ICC was significant for all measured variables. However, peak power output (POpeak: 124±40 vs. 148±40 watts, p<0.001) and HR (HRpeak: 136±22 vs. 148±30 bpm, p=0.023) were significantly greater in CPETresearch than CPETdiag. Few participants achieved MDC in V̇O2peak (5.6 mL/kg/min) with no difference between HIIT (0%) and M-VICT (10.0%, p=0.244). POpeak and HRpeak differed significantly in patients with AF when CPETs were repeated under different settings. Caution must be practiced when prescribing exercise intensity based on these measures as under-prescription may increase the number of exercise non-responders.

Efficacy and safety of macitentan in Fontan-palliated patients: 52-week randomized, placebo-controlled RUBATO Phase 3 trial and open-label extension

ObjectivesThe efficacy and safety of macitentan, an endothelin receptor antagonist, were assessed in a 52-week, prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessing the efficacy and safety of macitentan in Fontan-palliated adult and adolescent patients (RUBATO-DB) and an open-label extension trial (RUBATO-OL). MethodsPatients aged 12 years and older with New York Heart Association functional class II or III underwent total cavopulmonary connection more than 1 year before screening and showed no signs of Fontan failure/clinical deterioration. In RUBATO-DB, the primary efficacy end point was change in peak oxygen consumption from baseline to week 16; secondary end points were change from baseline over 52 weeks in peak oxygen consumption and change in mean count/minute of daily physical activity via accelerometer from baseline to week 16. Safety was assessed throughout both studies. ResultsIn RUBATO-DB, 137 patients were randomized to macitentan 10 mg (n = 68) or placebo (n = 69); 92.7% completed 52-week double-blind treatment. At week 16, mean ± SD change in peak oxygen consumption was −0.16 ± 2.86 versus −0.67 ± 2.66 mL/kg/minute with macitentan versus placebo (median unbiased treatment difference estimate, 0.62 mL/kg/minute [99% repeated CI, −0.62 to 1.85]; P = .19). No treatment effect was observed in either of the secondary end points. During RUBATO-DB, most common adverse events with macitentan were headache, nasopharyngitis, and pyrexia. Across RUBATO-DB and RUBATO-OL, most common adverse events were COVID-19, headache, and fatigue. RUBATO-OL was prematurely discontinued because RUBATO-DB did not meet its primary or secondary end point. ConclusionsThe primary end point of RUBATO-DB was not met; macitentan did not improve exercise capacity versus placebo in patients with Fontan palliation. Macitentan was generally well tolerated over long-term treatment.

High-intensity interval versus moderate-intensity continuous cycling training in Parkinson's disease: a randomized trial.

Exercise training is recommended to improve the quality of life in those living with Parkinson's disease (PD); however, the optimal prescription to improve cardiorespiratory fitness and disease-related motor symptoms remains unknown. Twenty-nine participants with PD were randomly allocated to either 10 wk of high-intensity interval training (HIIT) (n = 15; 6 female) or moderate-intensity continuous training (MICT) (n = 14; 5 female). The primary outcome was the change in maximal oxygen consumption (V̇o2peak). Secondary outcomes included changes in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score, Parkinson's Fatigue Scale (PFS)-16, resting and exercise cardiovascular measures, gait, balance, and knee extensor strength and fatigability. Exercise training increased V̇o2peak (main effect of time, P < 0.01), with a clinically meaningful difference in the change following HIIT versus MICT (Δ3.7 ± 3.7 vs. 1.7 ± 3.2 mL·kg-1·min-1, P = 0.099). The UPDRS motor score improved over time (P < 0.001) but without any differences between HIIT versus MICT (Δ-9.7 ± 1.3 vs. -8.4 ± 1.4, P = 0.51). Self-reported subjective fatigue (PFS-16) decreased over time (P < 0.01) but was similar between HIIT and MICT groups (P = 0.6). Gait, balance, blood pressure (BP), and heart rate (HR) were unchanged with training (all P > 0.09). Knee extensor strength increased over time (P = 0.03) but did not differ between HIIT versus MICT (Δ8.2 ± 5.9 vs. 11.7 ± 6.2 Nm, P = 0.69). HIIT alone increased the muscular endurance of the knee extensors during an isotonic fatigue task to failure (P = 0.04). In participants with PD, HIIT and MICT both increased V̇o2peak and led to improvements in motor symptoms and perceived fatigue; HIIT may offer the potential for larger changes in V̇o2peak and reduced knee extensor fatigability.NEW & NOTEWORTHY The optimal exercise prescription to improve cardiorespiratory fitness and disease-related motor symptoms in adults with Parkinson's disease remains unknown. In a single-center randomized trial consisting of either 10 wk of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), we found that both training modes increased V̇o2peak, with a larger clinically meaningful difference following HIIT. Both exercise modes improved motor symptoms and subjective fatigue, whereas HIIT increased the muscular endurance of the knee extensors.

Tumour-induced alterations in single-nucleus transcriptome of atrophying muscles indicate enhanced protein degradation and reduced oxidative metabolism.

Tumour-induced skeletal muscle wasting in the context of cancer cachexia is a condition with profound implications for patient survival. The loss of muscle mass is a significant clinical obstacle and is linked to reduced tolerance to chemotherapy and increased frailty. Understanding the molecular mechanisms driving muscle atrophy is crucial for the design of new therapeutics. Lewis lung carcinoma tumours were utilized to induce cachexia and muscle atrophy in mice. Single-nucleus libraries of the tibialis anterior (TA) muscle from tumour-bearing mice and their non-tumour-bearing controls were constructed using 10X Genomics applications following the manufacturer's guidelines. RNA sequencing results were analysed with Cell Ranger software and the Seurat R package. Oxygen consumption of mitochondria isolated from TA muscle was measured using an Oroboros O2k-FluoRespirometer. Mouse primary myotubes were treated with a recombinant ectodysplasin A2 (EDA-A2) protein to activate EDA-A2 receptor (EDA2R) signalling and study changes in gene expression and oxygen consumption. Tumour-bearing mice were sacrificed while exhibiting moderate cachexia. Average TA muscle weight was reduced by 11% (P=0.0207) in these mice. A total of 12335 nuclei, comprising 6422 nuclei from the control group and 5892 nuclei from atrophying muscles, were studied. The analysis of single-nucleus transcriptomes identified distinct myonuclear gene signatures and a shift towards type IIb myonuclei. Muscle atrophy-related genes, including Atrogin1, MuRF1 and Eda2r, were upregulated in these myonuclei, emphasizing their crucial roles in muscle wasting. Gene set enrichment analysis demonstrated that EDA2R activation and tumour inoculation led to similar expression patterns in muscle cells, including the stimulation of nuclear factor-kappa B, Janus kinase-signal transducer and activator of transcription and transforming growth factor-beta pathways and the suppression of myogenesis and oxidative phosphorylation. Muscle oxidative metabolism was suppressed by both tumours and EDA2R activation. This study identified tumour-induced transcriptional changes in muscle tissue at single-nucleus resolution and highlighted the negative impact of tumours on oxidative metabolism. These findings contribute to a deeper understanding of the molecular mechanisms underlying muscle wasting.

Glutamatergic signaling from melanin-concentrating hormone-producing neurons: A requirement for memory regulation, but not for metabolism control.

Melanin-concentrating hormone-producing neurons (MCH neurons), found mainly in the lateral hypothalamus and surrounding areas, play essential roles in various brain functions, including sleep and wakefulness, reward, metabolism, learning, and memory. These neurons coexpress several neurotransmitters and act as glutamatergic neurons. The contribution of glutamate from MCH neurons to memory- and metabolism-related functions has not been fully investigated. In a mouse model, we conditionally knocked out Slc17a6 gene, which encodes for vesicular glutamate transporter 2 (vGlut2), in the MCH neurons exclusively by using two different methods: the Cre recombinase/loxP system and in vivo genome editing using CRISPR/Cas9. Then, we evaluated several aspects of memory and measured metabolic rates using indirect calorimetry. We found that mice with MCH neuron-exclusive vGlut2 ablation had higher discrimination ratios between novel and familiar stimuli for novel object recognition, object location, and three-chamber tests. In contrast, there was no significant change in body weight, food intake, oxygen consumption, respiratory quotient, or locomotor activity. These findings suggest that glutamatergic signaling from MCH neurons is required to regulate memory, but its role in regulating metabolic rate is negligible.

Effects of substrate availability and mitochondrial disruption on oxidative metabolism and sperm motility in fertile dogs.

In several mammalian species, the measurement of mitochondrial oxygen consumption (MITOX) under different metabolic conditions has demonstrated a positive correlation with sperm motility and may be a sensitive indicator of mitochondrial health. In general, the maintenance of sperm motility and many key sperm functions and fertilizing events are heavily energy-dependent processes, and some species-specific substrate preferences exist. Although canine sperm have been known to undergo capacitation and maintain motility with supplementation of a wide range of energy substrates, the relationship between mitochondrial function, and the maintenance of oxidative metabolism and sperm motility remain unclear. The objective of this study was to explore the metabolic flexibility of canine sperm, and to investigate the relationship between mitochondrial function, and maintenance of motility under differing nutrient conditions. We explored substrate preferences and the bioenergetics underlying maintenance of canine sperm motility by monitoring mitochondrial oxidative function and sperm kinematics in the presence of mitochondrial effector drug treatments: FCCP, antimycin (ANTI), and oligomycin (OLIGO). We hypothesized that canine sperm possess the ability to use compensatory pathways and utilize diverse nutrient sources in the maintenance of motility. Oxygen consumption (change in pO2, oxygen partial pressure) and sperm kinematics (CASA) were measured concurrently (t0-t30) to assess the relationship between oxidative metabolism and maintenance of sperm motility in dogs. Four media were tested: containing glucose, lactate, and pyruvate (GLP), containing glucose (G), fructose (F), or lactate and pyruvate (LP). In the absence of pharmacological inhibition of the electron transport chain, energetic substrate had no effect on sperm kinematics in fertile dogs. Following mitochondrial disruption by ANTI and OLIGO, mitochondrial oxygen consumption was negatively correlated with several sperm motility parameters in GLP, G, F, and LP media. In every media, FCCP treatment quickly induced significantly higher oxygen consumption than in untreated sperm, and spare respiratory capacity, the maximal inducible oxidative metabolism, was high. With respiratory control ratios RCR >1 there was no indication of bioenergetic dysfunction in any media type, indicating that sperm mitochondria of fertile dogs have a high capacity for substrate oxidation and ATP turnover regardless of substrate. Our results suggest MITOX assessment is a valuable tool for assessing mitochondrial functionality, and that canine sperm employ flexible energy management systems which may be exploited to improve sperm handling and storage.

Metabolic recovery from submaximal exercise in hypoxia acclimated high altitude deer mice (Peromyscus maniculatus)

Animals living at high-altitude are faced with unremitting low oxygen availability. This can make it difficult to perform daily tasks that require increases in aerobic metabolism. An activity important for survival is aerobic locomotion, and the rapid recovery of muscle metabolism post exercise. Past work shows that hypoxia acclimated high-altitude mice (Peromyscus maniculatus) have a greater reliance on carbohydrates to power exercise than low altitude mice. However, it is unclear how quickly after aerobic exercise these mice can recovery and replenish muscle glycogen stores. The gastrocnemius muscle of high-altitude deer mice has a more aerobic phenotype and a greater capacity to oxidize lipids than low altitude deer mice. This suggests that high altitude mice may recover more rapidly from exercise than their lowland counterparts due to a greater capacity to support glycogen replenishment using intramuscular triglycerides (IMTG). To explore this possibility, we used low- and high-altitude native deer mice born and raised in common lab conditions and acclimated to chronic hypoxia. We determined changes in oxygen consumption following 15 min of aerobic exercise in 12% O2 and sampled skeletal muscles and liver at various time points during recovery to examine changes in key metabolites, including glycogen and IMTG. We found depletion in glycogen stores during exercise only in lowlanders, which returned to resting levels following 90 min of recovery. In contrast, IMTG did not change significantly with exercise or during recovery in either population. These data suggest that exercise recovery is influenced by altitude ancestry in deer mice.

Kv beta complex facilitates exercise-induced augmentation of myocardial perfusion and cardiac growth.

The oxygen sensitivity of voltage-gated potassium (Kv) channels regulates cardiovascular physiology. Members of the Kv1 family interact with intracellular Kvβ proteins, which exhibit aldo-keto reductase (AKR) activity and confer redox sensitivity to Kv channel gating. The Kvβ proteins contribute to vasoregulation by controlling outward K+ currents in smooth muscle upon changes in tissue oxygen consumption and demand. Considering exercise as a primary physiological stimulus of heightened oxygen demand, the current study tested the role of Kvβ proteins in exercise performance, exercise-induced adaptations in myocardial perfusion, and physiological cardiac growth. Our findings reveal that genetic ablation of Kvβ2 proteins diminishes baseline exercise capacity in mice and attenuates the enhancement in exercise performance observed after long-term training. Moreover, we demonstrate that Kvβ2 proteins are critical for exercise-mediated enhancement in myocardial perfusion during cardiac stress as well as adaptive changes in cardiac structure. Our results underscore the importance of Kvβ proteins in metabolic vasoregulation, highlighting their role in modulating both exercise capacity and cardiovascular benefits associated with training. Furthermore, our study sheds light on a novel molecular target for enhancing exercise performance and improving the health benefits associated with exercise training in patients with limited capacity for physical activity.

Efficacy of Lactococcus lactis subsp. lactis LY-66 and Lactobacillus plantarum PL-02 in Enhancing Explosive Strength and Endurance: A Randomized, Double-Blinded Clinical Trial.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review.

Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes.

Вплив етанолу та циклоспорину А на дихання ізольованих гепатоцитів щурів

It is known that ethanol affects the oxidative processes in liver mitochondria, which can be one of the mechanisms of the development of the alcoholic liver disease. A well-known immunosuppressant cyclosporine A is also an inhibitor of mitochondrial permeabi­lity transition pore. However, the pharmacological interaction of ethanol and cyclosporin A is not sufficiently studied. The aim of the study was to investigate the effect of ethanol and cyclosporine A on the respiration rate of isolated rat hepatocytes. Five male Wistar rats were used in the study. Hepatocytes were isolated by perfusion with collagenase. Cell plasma membrane integrity was assessed with trypan blue staining (0.1 %). Intact cell number was 85.7±0.92 %. The rate of oxygen consumption was measured using a polarographic device based on a Clark electrode. Protonophore FCCP was used to study the uncoupled respiration. Cell respiration was studied in the presence of glucose, pyruvate or monomethylsuccinate in solution. Statistical analysis was performed with Origin Pro 2018 software. Significance of difference between groups was evaluated with analysis of variance test. After one hour incubation with ethanol (50 mM), the rate of basal respiration of hepatocytes oxidizing glucose increased by a meager 8 %. Similar result was obtained upon the presence of pyruvate in solution. Monomethylsuccinate, however, abolished the effect of ethanol on basal respiration. he but not uncoupled respiration of hepatocytes upon glucose or pyruvate oxidation. Ethanol did not affect the uncoupled respiration of hepatocytes in presence of glucose, pyruvate of monomethylsuccinate. Incubation with cyclocporin A did not cause any changes in cell oxygen consumption in all experiments. Cyclosporin A also did not modify the effects of ethanol on basal respiration of hepatocytes. Therefore, no pharmacological no interaction between ethanol and cyclosporin A was detected, which could be evidenced by the change of mitochondrial respiration of isolated hepatocytes.