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This study tested the accuracy of a novel, limited-availability web application (H2Q™) for predicting sweat rates in a variety of sports using estimates of energy expenditure and air temperature only. The application of predictions for group water planning was investigated for soccer match play. Fourteen open literature studies were identified where group sweat rates were reported (n = 20 group means comprising 230 individual observations from 179 athletes) with fidelity. Sports represented included: walking, cycling, swimming, and soccer match play. The accuracy of H2Q™ sweat rates was tested by comparing to measured group sweat rates using the concordance correlation coefficient (CCC) with 95% confidence interval [CI]. The relative absolute error (RAE) with 95% [CI] was also assessed, whereby the mean absolute error was expressed relative to an acceptance limit of 0.250 L/h. The CCC was 0.98 [0.95, 0.99] and the RAE was 0.449 [0.279, 0.620], indicating that the prediction error was on average 0.112 L/h. The RAE was < 1.0 for 19/20 observations (95%). Drink volumes modeled as a proxy for sweat losses during soccer match play prevented dehydration (< 1% loss of body mass). The H2Q™ web application demonstrated high group sweat prediction accuracy for the variety of sports activities tested. Water planning for soccer match play suggests the feasibility of easily and accurately predicting sweat rates to plan group water needs and promote optimal hydration in training and/or competition.
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PURPOSE: There is growing interest in the measurement of plasma levels of arginine vasopressin (AVP) for the assessment of mild dehydration. However, the principles of biological variation have not been applied to the study of AVP and understanding biological variation of AVP may provide insights regarding measurement thresholds. The purpose of this investigation was to determine the biological variation of AVP in healthy euhydrated individuals to understand the potential for establishing both static and/or change thresholds of importance. METHODS: We studied 29 healthy volunteers (24 men and 5 women) while controlling for hydration and pre-analytical factors. All subjects completed between 2-8 trials where biological variation was determined using widely published methods. We determined the intraindividual, interindividual, and analytical coefficients of variation (CVI, CVG, and CVA, respectively) and subsequently the index of individuality and heterogeneity (II and IH, respectively). RESULTS: AVP did not reach the IH threshold required to be considered useful in the dynamic assessment of physiological deviations from normal. AVP levels approached the II threshold required to be considered useful in the static assessment of physiological deviations from normal. CONCLUSIONS: This analysis demonstrates that AVP assessment is unlikely to yield useful information about hydration status.
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Arginina Vasopressina/sangue , Adolescente , Adulto , Algoritmos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Estado de Hidratação do Organismo , Adulto JovemRESUMO
BACKGROUND: Small sample volumes may artificially elevate plasma osmolality (Posm) measured by freezing point depression. The purpose of this study was to compare two widely different sample volumes of measured Posm (mmol/kg) to each other, and to calculated osmolarity (mmol/L), across a physiological Posm range (~50 mmol/kg). METHODS: Posm was measured using freezing point depression and osmolarity calculated from measures of sodium, glucose, and blood urea nitrogen. The influence of sample volume was investigated by comparing 20 and 250 µL Posm samples (n = 126 pairs). Thirty-two volunteers were tested multiple times while EUH (n = 115) or DEH (n = 11) by -4.0% body mass. Protinol™ (240, 280, and 320 mmol/kg) and Clinitrol™ (290 mmol/kg) reference solutions were compared similarly (n = 282 pairs). RESULTS: The 20 µL samples of plasma showed a 7 mmol/kg positive bias compared to 250 µL samples and displayed a nearly constant proportional error across the range tested (slope = 0.929). Calculated osmolarity was lower than 20 µL Posm by the same negative bias (-6.9 mmol/kg) but not different from 250 µL Posm (0.1 mmol/kg). The differences between 20 and 250 µL samples of Protinol™ were significantly higher than Clinitrol™. CONCLUSIONS: These results demonstrate that Posm measured by freezing point depression will be ~7 mmol/kg higher when using 20 µL vs 250 µL sample volumes. Approximately half of this effect may be due to plasma proteins. Posm sample volume should be carefully considered when calculating the osmole gap or assessing hydration status.
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Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Concentração Osmolar , Adolescente , Adulto , Glicemia/análise , Nitrogênio da Ureia Sanguínea , Feminino , Humanos , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Sódio/análise , Adulto JovemRESUMO
Although doxorubicin (DOX) is a highly effective anti-tumour agent used to treat a variety of cancers, DOX administration is associated with significant side effects, including myopathy of both cardiac and skeletal muscles. The mechanisms responsible for DOX-mediated myopathy remain a topic of debate. We tested the hypothesis that both increased mitochondrial reactive oxygen species (ROS) emission and activation of the cysteine protease calpain are required for DOX-induced myopathy in rat cardiac and skeletal muscle. Cause and effect was determined by administering a novel mitochondrial-targeted anti-oxidant to prevent DOX-induced increases in mitochondrial ROS emission, whereas a highly-selective pharmacological inhibitor was exploited to inhibit calpain activity. Our findings reveal that mitochondria are a major site of DOX-mediated ROS production in both cardiac and skeletal muscle fibres and the prevention of DOX-induced increases in mitochondrial ROS emission protects against fibre atrophy and contractile dysfunction in both cardiac and skeletal muscles. Furthermore, our results indicate that DOX-induced increases in mitochondrial ROS emission are required to activate calpain in heart and skeletal muscles and, importantly, calpain activation is a major contributor to DOX-induced myopathy. Taken together, these findings show that increased mitochondrial ROS production and calpain activation are significant contributors to the development of DOX-induced myopathy in both cardiac and skeletal muscle fibres.
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Calpaína/metabolismo , Doxorrubicina/farmacologia , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Doenças Musculares/metabolismo , Miocárdio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Feminino , Coração/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/patologia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: Mechanical ventilation is a lifesaving measure for patients with respiratory failure. However, prolonged mechanical ventilation results in diaphragm weakness, which contributes to problems in weaning from the ventilator. Therefore, identifying the signaling pathways responsible for mechanical ventilation-induced diaphragm weakness is essential to developing effective countermeasures to combat this important problem. In this regard, the forkhead boxO family of transcription factors is activated in the diaphragm during mechanical ventilation, and forkhead boxO-specific transcription can lead to enhanced proteolysis and muscle protein breakdown. Currently, the role that forkhead boxO activation plays in the development of mechanical ventilation-induced diaphragm weakness remains unknown. DESIGN: This study tested the hypothesis that mechanical ventilation-induced increases in forkhead boxO signaling contribute to ventilator-induced diaphragm weakness. SETTING: University research laboratory. SUBJECTS: Young adult female Sprague-Dawley rats. INTERVENTIONS: Cause and effect was determined by inhibiting the activation of forkhead boxO in the rat diaphragm through the use of a dominant-negative forkhead boxO adeno-associated virus vector delivered directly to the diaphragm. MEASUREMENTS AND MAIN RESULTS: Our results demonstrate that prolonged (12 hr) mechanical ventilation results in a significant decrease in both diaphragm muscle fiber size and diaphragm-specific force production. However, mechanically ventilated animals treated with dominant-negative forkhead boxO showed a significant attenuation of both diaphragm atrophy and contractile dysfunction. In addition, inhibiting forkhead boxO transcription attenuated the mechanical ventilation-induced activation of the ubiquitin-proteasome system, the autophagy/lysosomal system, and caspase-3. CONCLUSIONS: Forkhead boxO is necessary for the activation of key proteolytic systems essential for mechanical ventilation-induced diaphragm atrophy and contractile dysfunction. Collectively, these results suggest that targeting forkhead boxO transcription could be a key therapeutic target to combat ventilator-induced diaphragm dysfunction.
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Diafragma/fisiopatologia , Fatores de Transcrição Forkhead/antagonistas & inibidores , Respiração Artificial/efeitos adversos , Animais , Diafragma/patologia , Feminino , Hemodinâmica , Contração Muscular , Atrofia Muscular , Proteínas do Tecido Nervoso , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced diaphragm atrophy and contractile dysfunction coincided with marked increases in STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727). STAT3 activation was accompanied by its translocation into mitochondria within diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling during CMV prevented phosphorylation of both target sites on STAT3, eliminated the accumulation of phosphorylated STAT3 within the mitochondria, and reversed the pathologic alterations in mitochondrial function, reduced oxidative stress in the diaphragm, and maintained normal diaphragm contractility. In addition, JAK inhibition during CMV blunted the activation of key proteolytic pathways in the diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3 signaling in the development of diaphragm muscle atrophy and dysfunction during CMV and suggest that the delayed extubation times associated with CMV can be prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L., Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S., Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D., Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C., Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder, A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S., Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.
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Diafragma/metabolismo , Janus Quinases/metabolismo , Respiração Artificial/efeitos adversos , Transdução de Sinais/fisiologia , Animais , Interleucina-6/metabolismo , Masculino , Mitocôndrias/metabolismo , Debilidade Muscular/metabolismo , Atrofia Muscular/metabolismo , Estresse Oxidativo/fisiologia , Fosforilação/fisiologia , Proteólise , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Serina/metabolismo , Tirosina/metabolismoRESUMO
BACKGROUND: Mechanical ventilation (MV) is a method of maintaining appropriate gas exchange in patients who are unable to sustain adequate alveolar ventilation. While lifesaving in the short-term, prolonged MV leads to altered cardiovascular responses and enhanced lung injury, but the exact mechanism is unknown. Therefore, we investigated the involvement of the sympathoadrenergic and renin-angiotensin system in MV-induced altered cardiovascular responses. METHODS: Sprague-Dawley rats were divided into six groups: (1) spontaneous breathing (SB); (2) SB + enalapril (100 µg/kg intravenous infusion); (3) SB + losartan (100 µg/kg infusion); (4) 12 h of MV; (5) MV + enalapril; and (6) MV + losartan. After the animals were sacrificed, blood and tissue samples were collected. Tyrosine hydroxylase, dopamine beta hydroxylase, and neuropeptide Y were measured in adrenal medulla and hypothalamus, whereas AT1 was measured in lung tissues by Western blot. Norepinephrine enzyme-linked immunosorbent assay and total antioxidant capacity were assayed in plasma. RESULTS: Our findings indicated that MV increases the sympathetic activation markers in adrenal medulla and hypothalamus. Moreover, oxidative stress was increased in lung and brain tissues. Treatment with enalapril or losartan reduced the lipid peroxidation in lung and brain tissues, while preserving the tissue glutathione content and plasma antioxidant capacity. CONCLUSIONS: These data demonstrate that the inhibition of the renin-angiotensin system by enalapril or losartan may reduce the MV-induced increase in sympathetic activity markers and oxidative stress, and thus, may have a beneficial effect as adjuvant therapy.
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Medula Suprarrenal/metabolismo , Enalapril/farmacologia , Hipotálamo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Respiração Artificial/efeitos adversos , Medula Suprarrenal/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Enalapril/uso terapêutico , Feminino , Hipotálamo/efeitos dos fármacos , Losartan/farmacologia , Losartan/uso terapêutico , Pneumopatias/prevenção & controle , Ratos , Ratos Sprague-Dawley , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
Mechanical ventilation (MV) is used clinically to maintain gas exchange in patients that require assistance in maintaining adequate alveolar ventilation. Common indications for MV include respiratory failure, heart failure, drug overdose, and surgery. Although MV can be a life-saving intervention for patients suffering from respiratory failure, prolonged MV can promote diaphragmatic atrophy and contractile dysfunction, which is referred to as ventilator-induced diaphragm dysfunction (VIDD). This is significant because VIDD is thought to contribute to problems in weaning patients from the ventilator. Extended time on the ventilator increases health care costs and greatly increases patient morbidity and mortality. Research reveals that only 18-24 h of MV is sufficient to develop VIDD in both laboratory animals and humans. Studies using animal models reveal that MV-induced diaphragmatic atrophy occurs due to increased diaphragmatic protein breakdown and decreased protein synthesis. Recent investigations have identified calpain, caspase-3, autophagy, and the ubiquitin-proteasome system as key proteases that participate in MV-induced diaphragmatic proteolysis. The challenge for the future is to define the MV-induced signaling pathways that promote the loss of diaphragm protein and depress diaphragm contractility. Indeed, forthcoming studies that delineate the signaling mechanisms responsible for VIDD will provide the knowledge necessary for the development of a pharmacological approach that can prevent VIDD and reduce the incidence of weaning problems.
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Diafragma/fisiopatologia , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Atrofia Muscular/etiologia , Atrofia Muscular/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/reabilitação , Animais , Humanos , Modelos Biológicos , Respiração Artificial , Insuficiência Respiratória/complicaçõesRESUMO
BACKGROUND: Mechanical ventilation is a life-saving intervention for patients with respiratory failure. Unfortunately, a major complication associated with prolonged mechanical ventilation is ventilator-induced diaphragmatic atrophy and contractile dysfunction, termed ventilator-induced diaphragmatic dysfunction (VIDD). Emerging evidence suggests that positive pressure ventilation (PPV) promotes lung damage (ventilator-induced lung injury [VILI]), resulting in the release of signaling molecules that foster atrophic signaling in the diaphragm and the resultant VIDD. Although a recent report suggests that negative pressure ventilation (NPV) results in less VILI than PPV, it is unknown whether NPV can protect against VIDD. Therefore, the authors tested the hypothesis that compared with PPV, NPV will result in a lower level of VIDD. METHODS: Adult rats were randomly assigned to one of three experimental groups (n = 8 each): (1) acutely anesthetized control (CON), (2) 12 h of PPV, and (3) 12 h of NPV. Dependent measures included indices of VILI, diaphragmatic muscle fiber cross-sectional area, diaphragm contractile properties, and the activity of key proteases in the diaphragm. RESULTS: Our results reveal that no differences existed in the degree of VILI between PPV and NPV animals as evidenced by VILI histological scores (CON = 0.082 ± 0.001; PPV = 0.22 ± 0.04; NPV = 0.25 ± 0.02; mean ± SEM). Both PPV and NPV resulted in VIDD. Importantly, no differences existed between PPV and NPV animals in diaphragmatic fiber cross-sectional area, contractile properties, and the activation of proteases. CONCLUSION: These results demonstrate that NPV and PPV result in similar levels of VILI and that NPV and PPV promote comparable levels of VIDD in rats.
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Diafragma/fisiopatologia , Respiração com Pressão Positiva/efeitos adversos , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Respiradores de Pressão Negativa/efeitos adversos , Animais , Atrofia , Citocinas/análise , Diafragma/patologia , Feminino , Pulmão/patologia , Estresse Oxidativo , Ratos , Ratos Sprague-DawleyRESUMO
Equivocal findings have been reported in the few studies that examined the impact of ambient temperature (T a) and hypohydration on cognition and dynamic balance. The purpose of this study was to determine the impact of acute exposure to a range of ambient temperatures (T(a) 10-40 °C) in euhydration (EUH) and hypohydration (HYP) states on cognition, mood and dynamic balance. Thirty-two men (age 22 ± 4 years, height 1.80 ± 0.05 m, body mass 85.4 ± 10.8 kg) were grouped into four matched cohorts (n = 8), and tested in one of the four T(a) (10, 20, 30, 40 °C) when EUH and HYP (-4 % body mass via exercise-heat exposure). Cognition was assessed using psychomotor vigilance, 4-choice reaction time, matching to sample, and grammatical reasoning. Mood was evaluated by profile of mood states and dynamic postural balance was tested using a Biodex Balance System. Thermal sensation (TS), core (T core) and skin temperature (T(sk)) were obtained throughout testing. Volunteers lost -4.1 ± 0.4 % body mass during HYP. T sk and TS increased with increasing T(a), with no effect of hydration. Cognitive performance was not altered by HYP or thermal stress. Total mood disturbance (TMD), fatigue, confusion, anger, and depression increased during HYP at all T(a). Dynamic balance was unaffected by HYP, but 10 °C exposure impaired balance compared to all other T(a). Despite an increase in TMD during HYP, cognitive function was maintained in all testing environments, demonstrating cognitive resiliency in response to body fluid deficits. Dynamic postural stability at 10 °C appeared to be hampered by low-grade shivering, but was otherwise maintained during HYP and thermal stress.
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Afeto , Cognição , Desidratação/fisiopatologia , Desidratação/psicologia , Transtornos de Estresse por Calor/fisiopatologia , Transtornos de Estresse por Calor/psicologia , Hipertermia Induzida , Hipotermia Induzida , Equilíbrio Postural , Adulto , Análise de Variância , Regulação da Temperatura Corporal , Resposta ao Choque Frio , Transtornos de Estresse por Calor/etiologia , Resposta ao Choque Térmico , Humanos , Masculino , Massachusetts , Medicina Militar , Testes Neuropsicológicos , Exame Físico , Desempenho Psicomotor , Tempo de Reação , Sensação Térmica , Fatores de Tempo , Equilíbrio Hidroeletrolítico , Adulto JovemRESUMO
Introduction: Recent success in predicting individual sweat losses from air temperature and energy expenditure measurements suggests a potential for forecasting individual sweat losses for future combinations of environment and exercise. The purpose of this study is to determine the plausibility of accurately forecasting exercise sweat losses from meteorological air temperature forecasts and individual running energy expenditure forecasts. The potential impact on plasma sodium is also estimated when setting drinking rates equal to forecast sweat losses. Materials and methods: Individual exercise sweat losses (equated to water needs) and energy expended while running were measured in 33 participants along with air temperature and compared with forecasts of the same. Forecast inputs were used in a web app to forecast exercise sweat losses for comparison with observed values. The bias between forecast and observed exercise sweat losses was used to calculate the potential drinking impact on plasma sodium. Results: The concordance correlation coefficient between forecast and observed values was 0.95, 0.96, and 0.91 for air temperature, energy expenditure, and exercise sweat losses, respectively, indicating excellent agreement and no significant differences observed via t-test. Perfect matching of water intake to sweat losses would lower plasma sodium concentrations from 140 to 138â mmol/L; calculations using the 95% limits of agreement for bias showed that drinking according to forecast exercise sweat losses would alter plasma sodium concentrations from 140 to between 136 and 141â mmol/L. Conclusions: The outcomes support the strong potential for accurately forecasting exercise sweat losses from commonly available meteorological air temperature forecasts and energy expenditure from forecast running distance.
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A methodological discrepancy exists in the hydration assessment literature regarding the establishment of euhydration, as some investigations utilize a pre-hydration technique, while others do not (overnight fluid/food fast). However, the degree that plasma osmolality (P (osm)) dilutes when using the pre-hydration method and how body mass/composition might influence the results is not known. Thirty subjects (22 M, 8 F; 20 ± 2 years (mean ± SD); 1.8 ± 0.1 m; 75.8 ± 13.5 kg) had P (osm) measured after an 8-h food and fluid fast (overnight fast) and 90 min after a 500-mL (4-9 mL/kg) water bolus (pre-hydration). From pre- to post-bolus, participants' P (osm) declined from 297 ± 3.5 to 295 ± 3.8 mmol/kg (p < 0.05; ∆ -1.7 ± 3.5 mmol/kg). One-third of the sample diluted to more than -3 mmol/kg. The effect of body mass on P (osm) dilution was investigated by comparing dilution in the ten lightest (62.8 ± 3.4 kg) and heaviest (92.0 ± 9.8 kg) participants; however, the change between the light (∆ -1.9 ± 3.8 mmol/kg) versus heavy groups (∆ -1.1 ± 3.0 mmol/kg) was not different (p > 0.05). The correlation between body mass or total body water and change in P (osm) was weak (p > 0.05), as was the correlation between relative fluid intake based on mass and change in P (osm) (p > 0.05). The two methodologies appear to produce similar P (osm) values when measured in most individuals. However, the potential for significant dilution (>3 mmol/kg) should be considered when choosing the pre-hydration methodology.
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Sangue/metabolismo , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Água/farmacologia , Adolescente , Adulto , Análise Química do Sangue , Peso Corporal/fisiologia , Desidratação/sangue , Desidratação/prevenção & controle , Feminino , Humanos , Masculino , Concentração Osmolar , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/fisiologia , Adulto JovemRESUMO
Mechanical ventilation (MV) is a life-saving intervention for many critically ill patients. Unfortunately, prolonged MV results in the rapid development of inspiratory muscle weakness due to diaphragmatic atrophy and contractile dysfunction (termed ventilator-induced diaphragm dysfunction (VIDD)). Although VIDD is a major risk factor for problems in weaning patients from MV, a standard therapy to prevent VIDD does not exist. However, emerging evidence suggests that pharmacological blockade of angiotensin II type 1 receptors (AT1Rs) protects against VIDD. Nonetheless, the essential characteristics of AT1R blockers (ARBs) required to protect against VIDD remain unclear. To determine the traits of ARBs that are vital for protection against VIDD, we compared the efficacy of two clinically relevant ARBs, irbesartan and olmesartan; these ARBs differ in molecular structure and effects on AT1Rs. Specifically, olmesartan blocks both angiotensin II (AngII) binding and mechanical activation of AT1Rs, whereas irbesartan prevents only AngII binding to AT1Rs. Using a well-established preclinical model of prolonged MV, we tested the hypothesis that compared with irbesartan, olmesartan provides greater protection against VIDD. Our results reveal that irbesartan does not protect against VIDD whereas olmesartan defends against both MV-induced diaphragmatic atrophy and contractile dysfunction. These findings support the hypothesis that olmesartan is superior to irbesartan in protecting against VIDD and are consistent with the concept that blockade of mechanical activation of AT1Rs is a required property of ARBs to shield against VIDD. These important findings provide a foundation for future clinical trials to evaluate ARBs as a therapy to protect against VIDD.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Diafragma/patologia , Respiração Artificial/efeitos adversos , Animais , Atrofia/etiologia , Atrofia/prevenção & controle , Diafragma/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Imidazóis/administração & dosagem , Irbesartana/administração & dosagem , Ratos , Respiração Artificial/instrumentação , Tetrazóis/administração & dosagem , Ventiladores Mecânicos/efeitos adversosRESUMO
This proof-of-concept study used a web application to predict runner sweat losses using only energy expenditure and air temperature. A field study (FS) of n = 37 runners was completed with n = 40 sweat loss observations measured over 1 h (sweat rate, SR). Predictions were also compared with 10 open literature (OL) studies in which individual runner SR was reported (n = 82; 109 observations). Three prediction accuracy metrics were used: for FS, the mean absolute error (MAE) and concordance correlation coefficient (CCC) were calculated to include a 95% confidence interval [CI]; for OL, the percentage concordance (PC) was examined against calculation of accumulated under- and over-drinking potential. The MAE for FS runners was 0.141 kg [0.105, 0.177], which was less than estimated scale weighing error on 85% of occasions. The CCC was 0.88 [0.82, 0.93]. The PC for OL was 96% for avoidance of both under- and over-drinking and 93% overall. All accuracy metrics and their CIs were below acceptable error tolerance. Input errors of ±10% and ±1 °C for energy expenditure and air temperature dropped the PC to between 84% and 90%. This study demonstrates the feasibility of accurately predicting SR from energy expenditure and air temperature alone. Novelty Results demonstrate that accurate runner SR prediction is possible with knowledge of only energy expenditure and air temperature. SR prediction error was smaller than scale weighing error in 85% of observations. Accurate runner SR prediction could help mitigate the common risks of over- and under-drinking.
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Metabolismo Energético , Corrida/fisiologia , Sudorese , Temperatura , Adolescente , Adulto , Algoritmos , Ingestão de Líquidos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudo de Prova de Conceito , Software , Adulto JovemRESUMO
Water planning is an important risk management concern for road race event organizers. PURPOSE: To compare water and cup prediction outputs from a mobile application (app) planning tool against: 1) measured group sweat losses, 2) documented event water and cup usage, and 3) traditional mathematical planning solutions. METHODS: Group mean sweating rates (L·h) from 12 published outdoor running studies were each compared to 12 composite averages using the Road Race Water Planner© (RRWP) app. Estimated water (gallons) and cup (number) needs were also compared with documented usage at a large marathon event and to traditional mathematical solutions. RESULTS: Thirteen group mean sweating rates from 286 runners were compared to composite RRWP estimates. Predicted sweating rate accuracy was 92% for RRWP and ranged from 0% to 69% for traditional mathematical solutions. The 2017 Boston marathon included 27,222 runners on a day averaging 21.5°C. Water and cup usage was 31,740 gallons and 1,036,003 cups, respectively. The RRWP estimates were 33,505 gallons and 1,072,160 cups, respectively. The difference in gallons expressed as liters was 0.236 L per person. For an approximately 4-h marathon, the difference per person as a rate was <60 mL·h. The difference in cups was a 3.5% error. All traditional solutions gave inferior estimates to RRWP due to large errors related to fluctuations in weather, as well as complications related to water station numbers. CONCLUSIONS: The results of the RRWP analysis indicate that it can provide event organizers with a valid, quantitative way to narrow the uncertainties of water planning related to changes in participant numbers, race distance, and weather. "Rule of thumb" alternatives are also discussed.
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Água Potável , Aplicativos Móveis , Corrida , Adulto , Aniversários e Eventos Especiais , Feminino , Humanos , Masculino , Técnicas de Planejamento , Sudorese , Adulto JovemRESUMO
Oral rehydration solutions (ORS) are specifically formulated with an osmolality to optimize fluid absorption. However, it is unclear how many ORS products comply with current World Health Organization (WHO) osmolality guidelines and the osmotic shelf-life stability is not known. Therefore, the purpose of this investigation was to examine the within and between ORS product osmolality variation in both pre-mixed and reconstituted powders. Additionally, the osmotic stability was examined over time. The osmolality of five different pre-mixed solutions and six powdered ORS products were measured. Pre-mixed solutions were stored at room temperatures and elevated temperatures (31 °C) for two months to examine osmotic shelf stability. Results demonstrated that only one pre-mixed ORS product was in compliance with the current guidelines both before and after the prolonged storage. Five of the six powdered ORS products were in compliance with minimal inter-packet variation observed within the given formulations. This investigation demonstrates that many commercially available pre-mixed ORS products do not currently adhere to the WHO recommended osmolality guidelines. Additionally, due to the presence of particular sugars and possibly other ingredients, the shelf-life stability of osmolality for certain ORS products may be questioned. These findings should be carefully considered in the design of future ORS products.
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Comércio , Armazenamento de Medicamentos , Soluções para Reidratação/química , Temperatura , Administração Oral , Comércio/normas , Estabilidade de Medicamentos , Armazenamento de Medicamentos/normas , Fidelidade a Diretrizes , Guias como Assunto , Concentração Osmolar , Controle de Qualidade , Soluções para Reidratação/administração & dosagem , Soluções para Reidratação/normas , Fatores de TempoRESUMO
BACKGROUND: Mechanical ventilation (MV) is a life-saving measure for patients in respiratory failure. However, prolonged MV results in significant diaphragm atrophy and contractile dysfunction, a condition referred to as ventilator-induced diaphragm dysfunction (VIDD). While there are currently no clinically approved countermeasures to prevent VIDD, increased expression of heat shock protein 72 (HSP72) has been demonstrated to attenuate inactivity-induced muscle wasting. HSP72 elicits cytoprotection via inhibition of NF-κB and FoxO transcriptional activity, which contribute to VIDD. In addition, exercise-induced prevention of VIDD is characterized by an increase in the concentration of HSP72 in the diaphragm. Therefore, we tested the hypothesis that increased HSP72 expression is required for the exercise-induced prevention of VIDD. We also determined whether increasing the abundance of HSP72 in the diaphragm, independent of exercise, is sufficient to prevent VIDD. METHODS: Cause and effect was determined by inhibiting the endurance exercise-induced increase in HSP72 in the diaphragm of exercise trained animals exposed to prolonged MV via administration of an antisense oligonucleotide targeting HSP72. Additional experiments were performed to determine if increasing HSP72 in the diaphragm via genetic (rAAV-HSP72) or pharmacological (BGP-15) overexpression is sufficient to prevent VIDD. RESULTS: Our results demonstrate that the exercise-induced increase in HSP72 protein abundance is required for the protective effects of exercise against VIDD. Moreover, both rAAV-HSP72 and BGP-15-induced overexpression of HSP72 were sufficient to prevent VIDD. In addition, modification of HSP72 in the diaphragm is inversely related to the expression of NF-κB and FoxO target genes. CONCLUSIONS: HSP72 overexpression in the diaphragm is an effective intervention to prevent MV-induced oxidative stress and the transcriptional activity of NF-κB and FoxO. Therefore, overexpression of HSP72 in the diaphragm is a potential therapeutic target to protect against VIDD.
Assuntos
Exercício Físico/fisiologia , Proteínas de Choque Térmico HSP72/metabolismo , Respiração Artificial/métodos , Animais , Diafragma/fisiopatologia , Feminino , Humanos , RatosRESUMO
Background: The beverage hydration index (BHI) assesses the hydration potential of any consumable fluid relative to water. The BHI is a relatively new metric, and the impact of body mass, sex, and reproducibility has yet to be investigated. Objectives: To assess the independent impact of body mass and sex on BHI using beverages not previously assessed, including an amino acid-based oral rehydration solution (AA-ORS), a glucose-containing ORS (G-ORS), and a sports drink (SpD), compared with water (control). The reproducibility of the results was examined using statistical modeling (bootstrap analysis). Design: Using a repeated-measures design, 40 euhydrated and fasted subjects (17 male, 23 female; urine specific gravity <1.025) were studied on 4 separate occasions. During each trial, subjects ingested 1 L of each beverage, and urine output was measured immediately postingestion and at 1-h intervals for the next 4 h. The BHI was calculated as a ratio of each individual's cumulative urine output after drinking 1 L of water over their cumulative urine output after drinking each of the test beverages. Results: The calculated mean ± SD BHIs of the beverages were as follows: water (1.0 ± 0.0), AA-ORS (1.15 ± 0.28), G-ORS (1.21 ± 0.28), and SpD (1.09 ± 0.26). The BHI for both AA-ORS and G-ORS was greater than that for water (P < 0.05). Despite overall differences in body mass, neither body mass nor sex independently affected BHI. Based upon statistical modeling, our results demonstrate excellent reproducibility of outcomes and external validity. Conclusions: Our results suggest that the BHI may be used and interpreted with confidence independently of body mass or sex. Furthermore, a novel carbohydrate-free AA-ORS and a traditional commercially available G-ORS were superior to water in optimizing hydration, whereas SpD was not. This trial was registered at clinicaltrials.gov as NCT03262597.
Assuntos
Bebidas , Peso Corporal , Equilíbrio Hidroeletrolítico , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Projetos Piloto , Fatores Sexuais , Adulto JovemRESUMO
Mechanical ventilation (MV) results in the rapid development of ventilator-induced diaphragm dysfunction (VIDD). While the mechanisms responsible for VIDD are not fully understood, recent data reveal that prolonged MV activates autophagy in the diaphragm, which may occur as a result of increased cellular reactive oxygen species (ROS) production. Therefore, we tested the hypothesis that (1) accelerated autophagy is a key contributor to VIDD; and that (2) oxidative stress is required to increase the expression of autophagy genes in the diaphragm. Our findings reveal that targeted inhibition of autophagy in the rat diaphragm prevented MV-induced muscle atrophy and contractile dysfunction. Attenuation of VIDD in these animals occurred as a result of increased diaphragm concentration of the antioxidant catalase and reduced mitochondrial ROS emission, which corresponded to reductions in the activity of calpain and caspase-3. To determine if increased ROS production is required for the upregulation of autophagy biomarkers in the diaphragm, rats that were administered the mitochondrial-targeted peptide SS-31 during MV. Results from this study demonstrated that mitochondrial ROS production in the diaphragm during MV is required for the increased expression of key autophagy genes (i.e. LC3, Atg7, Atg12, Beclin1 and p62), as well as for increased activity of cathepsin L. Together, these data reveal that autophagy is required for VIDD, and that autophagy inhibition reduces MV-induced diaphragm ROS production and prevents a positive feedback loop whereby increased autophagy is stimulated by oxidative stress, resulting in further increases in ROS and autophagy.
Assuntos
Diafragma/fisiologia , Mitocôndrias/metabolismo , Atrofia Muscular/metabolismo , Respiração Artificial/efeitos adversos , Animais , Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Contração Muscular , Atrofia Muscular/etiologia , Estresse Oxidativo/genética , Proteólise , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
Mechanical ventilation (MV) is a life-saving intervention for many critically ill patients. Unfortunately, prolonged MV results in the rapid development of diaphragmatic atrophy and weakness. Importantly, endurance exercise training results in a diaphragmatic phenotype that is protected against ventilator-induced diaphragmatic atrophy and weakness. The mechanisms responsible for this exercise-induced protection against ventilator-induced diaphragmatic atrophy remain unknown. Therefore, to investigate exercise-induced changes in diaphragm muscle proteins, we compared the diaphragmatic proteome from sedentary and exercise-trained rats. Specifically, using label-free liquid chromatography-mass spectrometry, we performed a proteomics analysis of both soluble proteins and mitochondrial proteins isolated from diaphragm muscle. The total number of diaphragm proteins profiled in the soluble protein fraction and mitochondrial protein fraction were 813 and 732, respectively. Endurance exercise training significantly (P<0.05, FDR <10%) altered the abundance of 70 proteins in the soluble diaphragm proteome and 25 proteins of the mitochondrial proteome. In particular, key cytoprotective proteins that increased in relative abundance following exercise training included mitochondrial fission process 1 (Mtfp1; MTP18), 3-mercaptopyruvate sulfurtransferase (3MPST), microsomal glutathione S-transferase 3 (Mgst3; GST-III), and heat shock protein 70 kDa protein 1A/1B (HSP70). While these proteins are known to be cytoprotective in several cell types, the cyto-protective roles of these proteins have yet to be fully elucidated in diaphragm muscle fibers. Based upon these important findings, future experiments can now determine which of these diaphragmatic proteins are sufficient and/or required to promote exercise-induced protection against inactivity-induced muscle atrophy.