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Background: Frailty, characterized by vulnerability, reduced reserves and increased susceptibility to severe events, is a significant concern in chronic haemodialysis (HD) patients. Sarcopenia, corresponding to the progressive loss of muscle mass and strength, may contribute to frailty by reducing functional capacity, mobility and autonomy. However, consensus lacks on the optimal bedside frailty index for chronic HD patients. This study investigated the influence of frailty on chronic HD patient survival and explored the associated factors. Methods: A total of 135 patients were enrolled from January to April 2019 and then followed up prospectively until April 2022. At inclusion, frailty was assessed by the Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests including gait speed, standing balance and lower limb muscle strength. Results: From a total of 114 prevalent chronic HD patients (66% men, age 67.6 ± 15.1 years), 30 died during the follow-up period of 23.7 months (range 16.8-34.3). Deceased patients were older, had more comorbidities and a higher sarcopenia prevalence (P < .05). The TUG and SPPB test scores were significantly reduced in patients who had died [SPPB total score: 7.2 ± 3.3 versus 9.4 ± 2.5; TUG time 8.7 ± 5.8 versus 13.8 ± 10.5 (P < .05)]. Multivariate analysis showed that a higher SPPB score (total value >9) was associated with a lower mortality risk [hazard ratio 0.83 (95% confidence interval 0.74-0.92); P < .03). Each component of the SPPB test was also associated with mortality in univariate analysis, but only the SPPB balance test remained protective against mortality in multivariate analysis. Older age, lower handgrip strength and lower protein catabolic rate were associated with SPPB total scores <9, SPPB balance score and TUG time >10 s. Conclusions: Screening for frailty is crucial in chronic HD patients, and incorporating SPPB, especially the balance test, provides valuable insights. Diminished muscle strength and inadequate protein intake negatively influence the SPPB score and balance in chronic HD patients. Effective identification and management of frailty can therefore improve outcomes. CLINICAL TRIAL REGISTRATION ClinicalTrialsgov: NCT03845452.
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AIM: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and development of emphysema. Among the comorbidities associated with COPD, skeletal muscle dysfunction is known to affect exercise capacity and the survival rate of patients. Pulmonary rehabilitation (PR), via exercise training, is essential for COPD patients. However, the response to PR is most often moderate. An animal model that recapitulates critical features of chronic human disease and provides access to muscle function should therefore be useful to improve PR benefits. METHODS: We used a rat model of induced emphysema based on pulmonary instillations of elastase (ELA) and lipopolysaccharides (LPS). We assessed the long-term effects of ELA/LPS and the potential effectiveness of endurance training on the skeletal muscle function. In vivo strength of the animals, and ex vivo contractility, endurance, type 1 fiber proportion, fiber cross-sectional area, and capillarization of both soleus and extensor digitorum longus (EDL) were assessed. RESULTS: An impaired overall muscle strength with decreased force, reduced capillarization, and atrophy of type 1 fiber of EDL was observed in ELA/LPS rats. Soleus was not affected. Endurance training was able to reduce fatigability, and increase type 1 fiber proportion and capillarization of soleus, and improve force, endurance, and capillarization of EDL in control and ELA/LPS rats. CONCLUSION: Our rat model of induced emphysema, which shares some features with the phenotype present in patients with COPD, could represent a suitable model to study skeletal muscle dysfunction and the effects of exercise training on muscle function in patients.
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Modelos Animales de Enfermedad , Músculo Esquelético , Condicionamiento Físico Animal , Enfisema Pulmonar , Animales , Enfisema Pulmonar/fisiopatología , Músculo Esquelético/fisiopatología , Condicionamiento Físico Animal/fisiología , Ratas , Masculino , Fuerza Muscular/fisiología , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease involving airway closure and parenchyma destruction (emphysema). Cardiovascular diseases are the main causes of morbi-mortality in COPD and, in particular, hypertension and heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link has currently been established between the onset of COPD, elevated blood pressure (BP) and systemic vascular impairment (endothelial dysfunction). Thus, we aimed to characterize BP and vascular function and remodeling in a rat model of exacerbated emphysema focusing on the role of sympathetic hyperactivity. Emphysema was induced in male Wistar rats by four weekly pulmonary instillations of elastase (4UI) and exacerbation by a single dose of lipopolysaccharides (LPS). Five weeks following the last instillation, in vivo and ex vivo cardiac and vascular functions were investigated. Exacerbated emphysema induced cardiac dysfunction (HFpEF) and a BP increase in this COPD model. We observed vasomotor changes and hypotrophic remodeling of the aorta without endothelial dysfunction. Indeed, changes in contractile and vasorelaxant properties, though endothelium-dependent, were pro-relaxant and NO-independent. A ß1-receptor antagonist (bisoprolol) prevented HFpEF and vascular adaptations, while the effect on BP increase was partial. Endothelial dysfunction would not trigger hypertension and HFpEF in COPD. Vascular changes appeared as an adaptation to the increased BP. The preventing effect of bisoprolol revealed a pivotal role of sympathetic hyperactivation in BP elevation. The mechanistic link between HFpEF, cardiac sympathetic activation and BP deserves further studies in this exacerbated-emphysema model, as well as in COPD patients.
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Enfisema , Insuficiencia Cardíaca , Hipertensión , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Masculino , Ratas , Animales , Bisoprolol , Presión Sanguínea , Ratas Wistar , Volumen SistólicoRESUMEN
BACKGROUND: Endothelial dysfunction is a key-feature in acute COVID-19. However, follow-up data regarding endothelial dysfunction and injury after COVID-19 infection are lacking. We aimed to investigate the changes in endothelium-dependent vasorelaxation at baseline and four months after hospital discharge in COVID-19 patients. METHODS: Twenty COVID-19 patients were compared to 24 healthy controls. Clinical and morphological data were collected after hospital admission for SARS-CoV-2 infection and reactive hyperaemia index (RHI) measurement was performed with a delay between 24 and 48 h after hospital admission and four months after hospital discharge in the outpatient clinics. Blood tests including inflammatory markers and measurement of post-occlusive vasorelaxation by digital peripheral arterial tonometry were performed at both visits. RESULTS: At baseline, COVID-19 patients exhibited reduced RHI compared to controls (p < 0.001), in line with an endothelial dysfunction. At four months follow-up, there was a 51% increase in the RHI (1.69 ± 0.32 to 2.51 ± 0.91; p < 0.01) in favor of endothelium-dependent vascular relaxation recovery. RHI changes were positively correlated with baseline C-reactive protein (r = 0.68; p = 0.02). Compared to COVID-19 patients with a decrease in RHI, COVID-19 patients with an increase in RHI beyond the day-to-day variability (i.e. >11%) had less severe systemic inflammation at baseline. CONCLUSION: Convalescent COVID-19 patients showed a recovery of systemic artery endothelial dysfunction, in particular patients with lower inflammation at baseline. Further studies are needed to decipher the interplay between inflammation and endothelial dysfunction in COVID-19 patients.
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COVID-19 , Enfermedades Vasculares , Humanos , Proyectos Piloto , Endotelio Vascular , COVID-19/complicaciones , COVID-19/terapia , SARS-CoV-2 , InflamaciónRESUMEN
Chronic obstructive pulmonary disease (COPD) is a clinical entity of increasing significance. COPD involves abnormalities of the airways and, in emphysema, parenchymal pulmonary destruction. Cardiovascular disease has emerged as a significant comorbidity to COPD. Heart failure with preserved ejection fraction (HFpEF) appears to be particularly associated with COPD-emphysema. Traditional treatments have shown limited efficacy in improving COPD-associated HFpEF. This lack of therapeutic efficacy highlights the need to identify potential mechanisms that link COPD-emphysema to HFpEF. Therefore, we aimed to study the delayed cardiac physiological impacts in a rat model with acute exacerbated emphysema. Emphysema was induced by four weekly 4 units elastase (ELA) intratracheal pulmonary instillations and exacerbation by one final additional lipolysaccharide (LPS) instillation in male Wistar rats. At 5 weeks after the ELA and LPS exposure, in vivo and ex vivo pulmonary and cardiac measurements were performed. Experimental exacerbated emphysema resulted in decreased pulmonary function and exercise intolerance. Histological analysis revealed parenchymal pulmonary destruction without signs of inflammation or cardiac fibrosis. In vivo cardiac functional analysis revealed diastolic dysfunction and tachycardia. Ex vivo analysis revealed a cellular cardiomyopathy with decreased myofilament Ca2+ sensitivity, cross-bridge cycling kinetics, and increased adrenergic PKA (protein kinase A)-dependent phosphorylation of troponin-I. Experimental exacerbated emphysema was associated with exercise intolerance that appeared to be secondary to increased ß-adrenergic tone and subsequent cardiac myofilament dysfunction. A ß1-receptor antagonist treatment (bisoprolol) started 24 hours after ELA-LPS instillation prevented in vivo and ex vivo diastolic dysfunction. These results suggest that novel treatment strategies targeted to the cardiac myofilament may be beneficial to combat exacerbated emphysema-associated HFpEF.
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Cardiomiopatías , Enfisema , Insuficiencia Cardíaca , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Masculino , Ratas , Animales , Insuficiencia Cardíaca/complicaciones , Lipopolisacáridos , Volumen Sistólico/fisiología , Ratas Wistar , Enfisema Pulmonar/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Cardiomiopatías/complicacionesRESUMEN
Chronic obstructive pulmonary disease (COPD) is a worldwide prevalent respiratory disease mainly caused by tobacco smoke exposure. COPD is now considered as a systemic disease with several comorbidities. Among them, skeletal muscle dysfunction affects around 20% of COPD patients and is associated with higher morbidity and mortality. Although the histological alterations are well characterized, including myofiber atrophy, a decreased proportion of slow-twitch myofibers, and a decreased capillarization and oxidative phosphorylation capacity, the molecular basis for muscle atrophy is complex and remains partly unknown. Major difficulties lie in patient heterogeneity, accessing patients' samples, and complex multifactorial process including extrinsic mechanisms, such as tobacco smoke or disuse, and intrinsic mechanisms, such as oxidative stress, hypoxia, or systemic inflammation. Muscle wasting is also a highly dynamic process whose investigation is hampered by the differential protein regulation according to the stage of atrophy. In this review, we report and discuss recent data regarding the molecular alterations in COPD leading to impaired muscle mass, including inflammation, hypoxia and hypercapnia, mitochondrial dysfunction, diverse metabolic changes such as oxidative and nitrosative stress and genetic and epigenetic modifications, all leading to an impaired anabolic/catabolic balance in the myocyte. We recapitulate data concerning skeletal muscle dysfunction obtained in the different rodent models of COPD. Finally, we propose several pathways that should be investigated in COPD skeletal muscle dysfunction in the future.
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Enfermedad Pulmonar Obstructiva Crónica , Contaminación por Humo de Tabaco , Humanos , Atrofia Muscular/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Músculo Esquelético/metabolismo , Inflamación/metabolismo , Hipoxia/metabolismoRESUMEN
This work investigates the behavior of commercial and custom Quartz tuning forkss (QTF) under humidity variations. The QTFs were placed inside a humidity chamber and the parameters were studied with a setup to record the resonance frequency and quality factor by resonance tracking. The variations of these parameters that led to a 1% theoretical error on the Quartz Enhanced Photoacoustic Spectroscopy (QEPAS) signal were defined. At a controlled level of humidity, the commercial and custom QTFs present similar results. Therefore, commercial QTFs appear to be a very good candidates for QEPAS as they are also affordable and small. When the humidity increases from 30 to 90 %RH, the variations in the custom QTFs' parameters remain suitable, while commercial QTFs show unpredictable behavior.
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Skeletal muscle wasting, whether related to physiological ageing, muscle disuse or to an underlying chronic disease, is a key determinant to quality of life and mortality. However, cellular basis responsible for increased catabolism in myocytes often remains unclear. Although myocytes represent the vast majority of skeletal muscle cellular population, they are surrounded by numerous cells with various functions. Animal models, mostly rodents, can help to decipher the mechanisms behind this highly dynamic process, by allowing access to every muscle as well as time-course studies. Satellite cells (SCs) play a crucial role in muscle regeneration, within a niche also composed of fibroblasts and vascular and immune cells. Their proliferation and differentiation is altered in several models of muscle wasting such as cancer, chronic kidney disease or chronic obstructive pulmonary disease (COPD). Fibro-adipogenic progenitor cells are also responsible for functional muscle growth and repair and are associated in disease to muscle fibrosis such as in chronic kidney disease. Other cells have recently proven to have direct myogenic potential, such as pericytes. Outside their role in angiogenesis, endothelial cells and pericytes also participate to healthy muscle homoeostasis by promoting SC pool maintenance (so-called myogenesis-angiogenesis coupling). Their role in chronic diseases muscle wasting has been less studied. Immune cells are pivotal for muscle repair after injury: Macrophages undergo a transition from the M1 to the M2 state along with the transition between the inflammatory and resolutive phase of muscle repair. T regulatory lymphocytes promote and regulate this transition and are also able to activate SC proliferation and differentiation. Neural cells such as terminal Schwann cells, motor neurons and kranocytes are notably implicated in age-related sarcopenia. Last, newly identified cells in skeletal muscle, such as telocytes or interstitial tenocytes could play a role in tissular homoeostasis. We also put a special focus on cellular alterations occurring in COPD, a chronic and highly prevalent respiratory disease mainly linked to tobacco smoke exposure, where muscle wasting is strongly associated with increased mortality, and discuss the pros and cons of animal models versus human studies in this context. Finally, we discuss resident cells metabolism and present future promising leads for research, including the use of muscle organoids.
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Enfermedad Pulmonar Obstructiva Crónica , Regeneración , Animales , Humanos , Regeneración/fisiología , Células Endoteliales , Calidad de Vida , Músculo Esquelético/patología , Atrofia Muscular/patología , Caquexia/patología , Modelos Animales , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
Background: Obstructive sleep apnea syndrome (OSA) is common in patients with acute myocardial infarction (AMI). Whether OSA impacts on the ventricular remodeling post-AMI remains unclear. We compared cardiac ventricular remodeling in patients assessed by cardiac magnetic resonance (CMR) imaging at baseline and six months after AMI based on the presence and severity of OSA. Methods: This prospective study included 47 patients with moderate to severe AMI. They all underwent CMR at inclusion and at six months after an AMI, and a polysomnography was performed three weeks after AMI. Left and right ventricular remodeling parameters were compared between patients based on the AHI, AHI in REM and NREM sleep, oxygen desaturation index, and daytime sleepiness. Results: Of the 47 patients, 49% had moderate or severe OSA with an AHI ≥ 15/h. No differences were observed between these patients and those with an AHI < 15/h for left ventricular end-diastolic and end-systolic volumes at six months. No association was found for left and right ventricular remodeling parameters at six months or for the difference between baseline and six months with polysomnographic parameters of OSA severity, nor with daytime sleepiness. Conclusions: Although with a limited sample size, our proof-of-concept study does not report an association between OSA and ventricular remodeling in patients with AMI. These results highlight the complexity of the relationships between OSA and post-AMI morbi-mortality.
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The screening of skeletal muscle diseases constitutes an unresolved challenge. Currently, exercise tests or plasmatic tests alone have shown limited performance in the screening of subjects with an increased risk of muscle oxidative metabolism impairment. Intensity-adjusted energy substrate levels of lactate (La), pyruvate (Pyr), ß-hydroxybutyrate (BOH) and acetoacetate (AA) during a cardiopulmonary exercise test (CPET) could constitute alternative valid biomarkers to select "at-risk" patients, requiring the gold-standard diagnosis procedure through muscle biopsy. Thus, we aimed to test: (1) the validity of the V'O2-adjusted La, Pyr, BOH and AA during a CPET for the assessment of the muscle oxidative metabolism (exercise and mitochondrial respiration parameters); and (2) the discriminative value of the V'O2-adjusted energy and redox markers, as well as five other V'O2-adjusted TCA cycle-related metabolites, between healthy subjects, subjects with muscle complaints and muscle disease patients. Two hundred and thirty subjects with muscle complaints without diagnosis, nine patients with a diagnosed muscle disease and ten healthy subjects performed a CPET with blood assessments at rest, at the estimated 1st ventilatory threshold and at the maximal intensity. Twelve subjects with muscle complaints presenting a severe alteration of their profile underwent a muscle biopsy. The V'O2-adjusted plasma levels of La, Pyr, BOH and AA, and their respective ratios showed significant correlations with functional and muscle fiber mitochondrial respiration parameters. Differences in exercise V'O2-adjusted La/Pyr, BOH, AA and BOH/AA were observed between healthy subjects, subjects with muscle complaints without diagnosis and muscle disease patients. The energy substrate and redox blood profile of complaining subjects with severe exercise intolerance matched the blood profile of muscle disease patients. Adding five tricarboxylic acid cycle intermediates did not improve the discriminative value of the intensity-adjusted energy and redox markers. The V'O2-adjusted La, Pyr, BOH, AA and their respective ratios constitute valid muscle biomarkers that reveal similar blunted adaptations in muscle disease patients and in subjects with muscle complaints and severe exercise intolerance. A targeted metabolomic approach to improve the screening of "at-risk" patients is discussed.
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Prueba de Esfuerzo , Enfermedades Musculares , Biomarcadores , Ejercicio Físico/fisiología , Prueba de Esfuerzo/métodos , Tolerancia al Ejercicio/fisiología , Humanos , Músculos , Oxidación-Reducción , Consumo de Oxígeno/fisiologíaRESUMEN
Lectures constitute a basic component of physiology instruction in scientific and healthcare curricula. Technological progress has allowed a switch from face to face to video lectures, yet there is no evidence of video efficacy in physiology. Because videos increase the cognitive load during a learning task, identifying tools that decrease students' cognitive load during video lectures is critical. Segmenting videos with pauses and inducing joint attention with eye movement modeling examples (EMME) could reduce the cognitive load and improve second-year medical students' learning in physiology video lectures. Second-year medical students were randomized into four groups [EMME + pauses (EMME + P), EMME without pause`s (EMME-NoP), pauses only (NoEMME + P), and no EMME and no pause (NoEMME-NoP)], took pretest quizzes, watched a renal physiology video lecture, and answered a cognitive load questionnaire and posttest quizzes on the Moodle learning management system. Student prior knowledge was assessed by a pretest, and learning gains were assessed by the difference between posttest and pretest scores. One hundred ninety-five students completed the experiment. Pauses improved learning gains (P < 0.01) but not EMME (P = 0.11). Student prior knowledge has several interactions with other variables: low-prior knowledge students obtained better learning gains (P < 0.001) and high-prior knowledge students had lower learning gains with EMME (P < 0.05). Our study shows the potential role of tools designed to reduce students' cognitive load during a renal physiology video lecture and the critical need for empirical validation of pedagogical solutions that are adapted to the specificities of physiology lectures.
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Movimientos Oculares , Estudiantes de Medicina , Cognición , Curriculum , Evaluación Educacional , Humanos , Aprendizaje , Estudiantes de Medicina/psicologíaRESUMEN
Chronic obstructive pulmonary disease (COPD) patients have an increased risk of cardiovascular disease. Muscle biopsies have revealed that the muscle vasculature in COPD patients was characterized by a capillary rarefaction with reduced pericyte coverage. Thus, an imbalance of the plasma Angiopoietin-1 / Angiopoietin-2 (Ang2/Ang1) ratio could constitute a non-invasive marker of the muscle vascular impairment. In 14 COPD patients (65.5±5.1-year-old) and 7 HC (63.3±5.8-year-old), plasma samples were obtained at 3 time-points: before, after 5 weeks (W5), and after 10 weeks (W10) of exercise training. COPD patients showed a muscle capillary rarefaction at baseline with a reduced capillary coverage at W5 and W10. The plasma Ang2/Ang1 ratio was significantly higher in COPD patients vs. HC during the training (Group: p=0.01). The plasma Ang2/Ang1 ratio was inversely correlated with the pericyte coverage index regardless of the time period W0 (r=-0.51; p=0.02), W5 (r=-0.48; p=0.04), and W10 (r=-0.61; p<0.01). Last, in ECFC/MSC co-cultures exposed to the W10 serum from COPD patients and HC, the plasma Ang2/Ang1 at W10 were inversely correlated with calponin staining (r=-0.64. p=0.01 and r= 0.71. p<0.01, Fig. 1B), in line with a role of this plasma Ang2/Ang1 in the MSC differentiation into pericytes. Altogether, plasma Ang2/Ang1 ratio could constitute a potential marker of the vascular impairment in COPD patients.
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Angiopoyetina 1 , Angiopoyetina 2 , Rarefacción Microvascular , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Angiopoyetina 1/sangre , Angiopoyetina 2/sangre , Biomarcadores/sangre , Humanos , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
BACKGROUND: Obesity is a major public health issue. Combining exercise training, nutrition, and therapeutic education in metabolic rehabilitation (MR) is recommended for obesity management. However, evidence from randomized controlled studies is lacking. In addition, MR is associated with poor patient adherence. Mobile health devices improve access to MR components. OBJECTIVE: The aim of this study is to compare the changes in body composition, anthropometric parameters, exercise capacity, and quality of life (QOL) within 12 weeks of patients in the telerehabilitation (TR) program to those of usual care patients with obesity. METHODS: This was a parallel-design randomized controlled study. In total, 50 patients with obesity (BMI>30 kg/m²) were included in a TR group (TRG) or a usual care group (UCG) for 12 weeks. Patients underwent biometric impedance analyses, metabolic exercise tests, actimetry, and QOL and satisfaction questionnaires. The primary outcome was the change in fat mass at 12 weeks from baseline. Secondary outcomes were changes in body weight, metabolic parameters, exercise capacity, QOL, patients' adhesion, and satisfaction. RESULTS: A total of 49 patients completed the study. No significant group × time interaction was found for fat mass (TRG: mean 1.7 kg, SD 2.6 kg; UCG: mean 1.2 kg, SD 2.4 kg; P=.48). Compared with the UCG, TRG patients tended to significantly improve their waist to hip ratios (TRG: -0.01 kg, SD 0.04; UCG: +0.01 kg, SD 0.06; P=.07) and improved QOL physical impact (TRG: +21.8, SD 43.6; UCG: -1.2, SD 15.4; P=.005). Significant time effects were observed for body composition, 6-minute walk test distance, exercise metabolism, sedentary time, and QOL. Adherence (95%) and satisfaction in the TRG were good. CONCLUSIONS: In adults with obesity, the TR program was not superior to usual care for improving body composition. However, TR was able to deliver full multidisciplinary rehabilitation to patients with obesity and improve some health outcomes. Given the patients' adherence and satisfaction, pragmatic programs should consider mobile health devices to improve access to MR. Further studies are warranted to further establish the benefits that TR has over usual care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03396666; http://clinicaltrials.gov/ct2/show/NCT03396666.
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Calidad de Vida , Telerrehabilitación , Adulto , Ejercicio Físico , Humanos , Obesidad , Evaluación de Resultado en la Atención de SaludRESUMEN
Among the comorbidities associated with chronic obstructive pulmonary disease (COPD), skeletal muscle weakness and atrophy are known to affect patient survival rate. In addition to muscle deconditioning, various systemic and intrinsic factors have been implicated in COPD muscle dysfunction but an impaired COPD muscle adaptation to contraction has never been extensively studied. We submitted cultured myotubes from nine healthy subjects and nine patients with COPD to an endurance-type protocol of electrical pulse stimulation (EPS). EPS induced a decrease in the diameter, covered surface and expression of MHC1 in COPD myotubes. Although the expression of protein degradation markers was not affected, expression of the protein synthesis marker mTOR was not induced in COPD compared to healthy myotubes after EPS. The expression of the differentiation markers p16INK4a and p21 was impaired, while expression of Myf5 and MyoD tended to be affected in COPD muscle cells in response to EPS. The expression of mitochondrial biogenesis markers PGC1α and MFN2 was affected and expression of TFAM and COX1 tended to be reduced in COPD compared to healthy myotubes upon EPS. Lipid peroxidation was increased and the expression of the antioxidant enzymes SOD2 and GPx4 was affected in COPD compared to healthy myotubes in response to EPS. Thus, we provide evidence of an impaired response of COPD muscle cells to contraction, which might be involved in the muscle weakness observed in patients with COPD.
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Terapia por Estimulación Eléctrica , Células Musculares/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudios de Casos y Controles , Diferenciación Celular , Femenino , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Fibras Musculares Esqueléticas/patología , Biogénesis de Organelos , Estrés Oxidativo , ProteolisisRESUMEN
Introduction. Exhaled breath acetone (ExA) has been investigated as a biomarker for heart failure (HF). Yet, barriers to its use in the clinical field have not been identified. The aim of this systematic review and meta-analysis was to assess the ExA heterogeneity and factors of variability in healthy controls (HC), to identify its relations with HF diagnosis and prognostic factors and to assess its diagnosis and prognosis accuracy in HF patients.Methods. A systematic search was conducted in PUBMED and Web of Science database. All studies with HC and HF patients with a measured ExA were included and studies providing ExA's diagnosis and prognosis accuracy were identified.Results. Out of 971 identified studies, 18 studies involving 833 HC and 1009 HF patients were included in the meta-analysis. In HC, ExA showed an important heterogeneity (I2= 99%). Variability factors were fasting state, sampling type and analytical method. The mean ExA was 1.89 times higher in HF patients vs. HC (782 [531-1032] vs. 413 [347-478] ppbv;p< 0.001). One study showed excellent diagnosis accuracy, and one showed a good prognosis value. ExA correlated with New York Heart Association (NYHA) dyspnea (p< 0.001) and plasma brain natriuretic peptide (p< 0.001). Studies showed a poor definition and reporting of included subjects.Discussion. Despite the between-study heterogeneity in HC, the evidence of an excellent diagnosis and prognosis value of ExA in HF from single studies can be extended to clinical populations worldwide. Factors of variability (ExA procedure and breath sampling) could further improve the diagnosis and prognosis values of this biomarker in HF patients.
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Acetona , Insuficiencia Cardíaca , Biomarcadores , Pruebas Respiratorias/métodos , Insuficiencia Cardíaca/diagnóstico , Humanos , PronósticoRESUMEN
BACKGROUND AND OBJECTIVES: Age and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis. For statistical analysis, mean comparison and multiple regression tests were used. RESULTS: In patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy. CONCLUSIONS: In this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02794142 and NCT02040363.
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Fibras Musculares Esqueléticas/patología , Músculo Cuádriceps/patología , Músculo Cuádriceps/fisiopatología , Diálisis Renal , Proteínas Adaptadoras Transductoras de Señales/genética , Autofagosomas/patología , Biopsia , Estudios de Casos y Controles , Femenino , Humanos , Trasplante de Riñón , Masculino , Proteínas de la Membrana/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , Mitocondrias/patología , Mitofagia , Fibras Musculares Esqueléticas/metabolismo , Fuerza Muscular , Fenotipo , Resistencia Física , Proteínas Proto-Oncogénicas/genética , Transducción de Señal , Factores de Tiempo , Proteínas Supresoras de Tumor/genética , Listas de Espera , Prueba de PasoRESUMEN
BACKGROUND: Pulmonary rehabilitation (PR) improves exercise capacity, health-related quality of life (HRQoL) and dyspnea in chronic obstructive pulmonary disease (COPD) patients. Maintenance programs can sustain the benefits for 12 to 24 months. Yet, the long-term effects (> 12 months) of pragmatic maintenance programs in real-life settings remain unknown. This prospective cohort study assessed the yearly evolution in the outcomes [6-min walking distance (6MWD), HRQoL, dyspnea] of a supervised self-help PR maintenance program for COPD patients followed for 5 years. The aim was to assess the change in the outcomes and survival probability for 1 to 5 years after PR program discharge in COPD patients following a PR maintenance program supported by supervised self-help associations. METHODS: Data were prospectively collected from 144 COPD patients who followed a pragmatic multidisciplinary PR maintenance program for 1 to 5 years. They were assessed yearly for 6MWD, HRQol (VQ11) and dyspnea (MRC). The 5-year survival probability was compared to that of a control PR group without a maintenance program. A trajectory-based cluster analysis identified the determinants of long-term response. RESULTS: Maintenance program patients showed significant PR benefits at 4 years for 6MWD and VQ11 and 5 years for MRC. The 5-year survival probability was higher than for PR patients without PR maintenance. Two clusters of response to long-term PR were identified, with responders being the less severe COPD patients. CONCLUSIONS: This study provides evidence of the efficacy of a pragmatic PR maintenance program in a real-life setting for more than 3 years. In contrast to short-term PR, long-term PR maintenance appeared more beneficial in less severe COPD patients.
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Bases de Datos Factuales/tendencias , Terapia por Ejercicio/métodos , Terapia por Ejercicio/tendencias , Tolerancia al Ejercicio/fisiología , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Anciano , Estudios de Cohortes , Terapia por Ejercicio/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND: Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients. METHODS: Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median). RESULTS: From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7-82.0) years], 44 died during the follow-up period of 23.7 (12.4-34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18-7.61; P = 0.02]. CONCLUSIONS: Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage.
Asunto(s)
Fallo Renal Crónico , Debilidad Muscular , Sarcopenia , Anciano , Creatinina , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Debilidad Muscular/diagnóstico , Debilidad Muscular/etiología , Atrofia Muscular/diagnóstico , Atrofia Muscular/etiología , Estudios Prospectivos , Diálisis Renal/efectos adversos , Sarcopenia/diagnóstico , Sarcopenia/etiologíaRESUMEN
Improvements in skeletal muscle endurance and oxygen uptake are blunted in patients with chronic obstructive pulmonary disease (COPD), possibly because of a limitation in the muscle capillary oxygen supply. Pericytes are critical for capillary blood flow adaptation during angiogenesis but may be impaired by COPD systemic effects, which are mediated by circulating factors. This study compared the pericyte coverage of muscle capillaries in response to 10 wk of exercise training in patients with COPD and sedentary healthy subjects (SHS). Fourteen patients with COPD were compared with seven matched SHS. SHS trained at moderate intensity corresponding to an individualized moderate-intensity patient with COPD trained at the same relative (%VÌo2: COPD-RI) or absolute (mL·min-1·kg-1: COPD-AI) intensity as SHS. Capillary-to-fiber ratio (C/F) and NG2+ pericyte coverage were assessed from vastus lateralis muscle biopsies, before and after 5 and 10 wk of training. We also tested in vitro the effect of COPD and SHS serum on pericyte morphology and mesenchymal stem cell (MSC) differentiation into pericytes. SHS showed greater improvement in aerobic capacity (VÌo2VT) than both patients with COPD-RI and patients with COPD-AI (Group × Time: P = 0.004). Despite a preserved increase in the C/F ratio, NG2+ pericyte coverage did not increase in patients with COPD in response to training, contrary to SHS (Group × Time: P = 0.011). Conversely to SHS serum, COPD serum altered pericyte morphology (P < 0.001) and drastically reduced MSC differentiation into pericytes (P < 0.001). Both functional capacities and pericyte coverage responses to exercise training are blunted in patients with COPD. We also provide direct evidence of the deleterious effect of COPD circulating factors on pericyte morphology and differentiation.NEW & NOTEWORTHY This work confirms the previously reported impairment in the functional response to exercise training of patients with COPD compared with SHS. Moreover, it shows for the first time that pericyte coverage of the skeletal capillaries is drastically reduced in patients with COPD compared with SHS during training-induced angiogenesis. Finally, it provides experimental evidence that circulating factors are involved in the impaired pericyte coverage of patients with COPD.
Asunto(s)
Terapia por Ejercicio/métodos , Músculo Esquelético/irrigación sanguínea , Neovascularización Fisiológica , Pericitos/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Anciano , Capilares/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiología , Pericitos/metabolismo , Pericitos/fisiología , Enfermedad Pulmonar Obstructiva Crónica/terapiaRESUMEN
Myogenic differentiation mechanisms are generally assessed using a murine cell line placed in low concentrations of an animal-derived serum. To more closely approximate in vivo pathophysiological conditions, recent studies have combined the use of human muscle cells with human serum. Nevertheless, the in vitro studies of the effects of a human microenvironment on the differentiation process of human myoblasts require the identification of the culture conditions that would provide an optimal and reproducible differentiation process of human muscle cells. We assessed the differentiation variability resulting from the use of human myoblasts and serums from healthy subjects by measuring the myotube diameter, fusion index and surface covered by myotubes. We showed the preserved cell-dependent variability of the differentiation response of myoblasts cultured in human serums compared to FBS. We found that using a pool of serums reduced the serum-dependent variability of the myogenic response compared to individual serums. We validated our methodology by showing the atrophying effect of pooled serums from COPD patients on healthy human myotubes. By replacing animal-derived tissues with human myoblasts and serums, and by validating the sensitivity of cultured human muscle cells to a pathological microenvironment, this human cell culture model offers a valuable tool for studying the role of the microenvironment in chronic disease.