Subclinical vascular, hemodynamic and arterial stiffness changes in adults with cystic fibrosis: cross-sectional observational study.

Cardiovascular diseases can be an emerging complication in cystic fibrosis (CF), as the median life expectancy has improved considerably. The objective of this study was to compare vascular, hemodynamic parameters and arterial stiffness in adult CF patients with healthy participants pared by sex and age, and to assess the factors associated with arterial stiffness in the CF group. This is a cross-sectional observational study. The evaluation of cardiovascular parameters was performed non-invasively using Mobil-O-Graph. 36 individuals with CF and 35 controls were evaluated. The mean arterial pressure (96.71 ± 10.98 versus 88.61 ± 7.40 mmHg, p = 0.0005), cardiac output (4.86 ± 0.57 versus 4.48 ± 0.44 L/min, p = 0.002) and systolic volume (64.30 ± 11.91 versus 49.02 ± 9.31 ml, p < 0.0001) were significantly lower in the CF group. The heart rate was higher in the CF when compared to the control (77.18 ± 10.47 versus 93.56 ± 14.57 bpm, p < 0.0001). The augmentation index (AIx@75) was higher in the CF than control (29.94 ± 9.37 versus 16.52 ± 7.179%, p < 0.0001). In the multivariate model controlled by body mass index and Forced Expiratory Volume in the first second, central systolic blood pressure and reflection coefficient directly related to AIx@75. Negatively related to AIx@75 were age and systolic volume. The adjusted determination coefficient was 87.40%. Individuals with CF presented lower arterial blood pressures and changes in cardiac function with lower stroke volume and cardiac output. The AIx@75, an indirect index of arterial stiffness and direct index of left ventricular overload, is increased in this population. The subclinical findings suggest the need for earlier cardiovascular assessment in this population due to increased risks of cardiovascular disease.

Aortic pulse wave comparison between controls and triathletes in baseline conditions and in response to acute maximum exercise.

To determine the effects of intense training on aortic pulse wave variables and hemodynamic parameters at baseline and at recovery from maximal exercise testing (MaxET) in triathletes compared with sedentary individuals. In this prospective and experimental study, 21 triathletes and 21 sedentary individuals were recruited and evaluated prior and two minutes after the MaxET using the Mobil-O-Graph®, which estimates the aortic pulse wave from the brachial artery pressure. The augmentation index (AIx@75) was lower in triathletes after the MaxET compared to control group (16.34 ± 5.95 vs. 23.5 ± 8.53%, p = 0.001), while the pulse wave velocity (PWV) was similar between groups. The heart rate was significantly lower at baseline and after MaxET in triathletes group (55.70 ± 8.95 bpm 91.49 ± 11.39 bpm) compared with control group (62.11 ± 6.70 bpm; 102.08 ± 10.85 bpm). The stroke volume was significantly higher at baseline (96.08 ± 13.96 ml; 86.17 ± 11.24 ml) and after MaxET in triathletes group (69.15 ± 6.51 ml, 58.38 ± 6.99 ml) compared with control group. Triathetes show lower value of AIx@75 after MaxET in comparison with the control group. AIx@75, in addition to being an indirect measure of arterial stiffness, is also a measure of left ventricular afterload. Thus, the lower AIx@75 in triathletes may be due to their lower left ventricular afterload, lower myocardial oxygen demand, and greater coronary perfusion than sedentary individuals. The hemodynamic changes observed in triathletes at rest and during an acute exercise bout are distinctive characteristics of aerobic physical training.

Factors associated with arterial stiffness assessed by pulse pressure amplification in healthy children and adolescents: a cross-sectional study.

BACKGROUND: Increasing evidence suggests that reducing pulse pressure amplification (PPA) plays an important role in pathogenesis and progression of cardiovascular disease. This is a cross-sectional, observational, and analytical study in which we evaluated the associated factors with a greater chance of reducing PPA in 136 healthy children and adolescents aged 8 to 19 years old stratified by gender and age group. METHODS: Arterial stiffness and vascular and hemodynamic parameters were non-invasively measured using Mobil-O-Graph® (IEM, Stolberg, Germany), a cuff-based oscillometric device. PPA was expressed as the peripheral-to-central pulse pressure ratio (PPp / PPc). Participants with PPA < 1.49 were considered as part of the arterial stiffness group. RESULTS: In a univariate model, the increase in total vascular resistance, the reflection coefficient and the augmentation pressure were more likely to have arterial stiffness in all groups. The factors most likely to have arterial stiffness (as assessed by the reduction of the PPA) in the multivariate model were increasing age, the reflection coefficient and cardiac index in the total sample, male group and child and adolescent groups. In addition to age in the female group, cardiac output, stroke volume, and AIx@75 were the factors most likely to present arterial stiffness. CONCLUSIONS: The results show for the first time in children and adolescents that the factors most likely to reduce PPA are related to the reflection wave, which determines aortic pressures and, therefore, left ventricular afterload.

Pediatric obstructive sleep-disordered breathing is associated with arterial stiffness.

The association between obstructive sleep-disordered breathing (oSDB) and arterial stiffness, an independent predictor of cardiovascular outcomes, is not well established in children. This study compared cardiovascular parameters between healthy and oSDB children and aimed to identify predictors of arterial stiffness indices in children with oSDB. Cross-sectional study realized in a tertiary hospital from June 2018 to January 2020. Forty-eight children (3 to 10 years old) with clinical diagnosis of oSDB and indication for adenotonsillectomy and 24 controls were evaluated. Cardiovascular parameters were measured non-invasively by brachial artery oscillometry with a portable device. The main arterial stiffness indices assessed were augmentation index and pulse wave velocity, both derived from the aortic pulse wave. In the oSDB group, the questionnaires Obstructive Sleep Apnea-18 (OSA-18) and Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) were applied. The oSDB group had higher values of reflection coefficient (p = 0.044) and augmentation index (p = 0.003) than the control group. Stepwise multiple regression analysis revealed that age, female sex, reflection coefficient, and systolic volume were independent predictors of augmentation index. Higher pulse wave velocity values were associated with worse quality of life assessed by PedsQL 4.0 questionnaire. There was no association with OSA-18. The vascular and hemodynamic parameters were similar in both groups.Conclusion: Children with oSDB have increased augmentation index, an independent predictor of cardiovascular outcomes. The early identification of subclinical cardiovascular changes reinforces the importance of treating the disease, as well as changing lifestyle habits, to prevent complications in adulthood. What is Known: • The association between oSDB and cardiovascular risk in adults is well described in the literature. • Children with oSDB, regardless of their weight or sex, have higher PWV values when compared to non-snoring children. What is New: • Children with oSDB have augmented arterial stiffness, evidenced by the increase in AIx@75, measured non-invasively by brachial artery oscillometry with a portable device. • Low quality of life and therefore a high disease burden in children with oSDB may be a risk factor for arterial stiffness.

Angiotensin-(1-7)/Mas receptor modulates anti-inflammatory effects of exercise training in a model of chronic allergic lung inflammation.

AIMS: Exercise training increases circulating and tissue levels of angiotensin-(1-7) [Ang-(1-7)], which was shown to attenuate inflammation and fibrosis in different diseases. Here, we evaluated whether Ang-(1-7)/Mas receptor is involved in the beneficial effects of aerobic training in a chronic model of asthma. MATERIAL AND METHODS: BALB/c mice were subjected to a protocol of asthma induced by ovalbumin sensitization (OVA; 4 i.p. injections) and OVA challenge (3 times/week for 4 weeks). Simultaneously to the challenge period, part of the animals was continuously treated with Mas receptor antagonist (A779, 1 µg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1 h/day, 5 days/week during 4 weeks). PGC1-α mRNA expression (qRT-PCR), plasma IgE and lung cytokines (ELISA), inflammatory cells infiltration (enzymatic activity assay) and airway remodeling (by histology) were evaluated. KEY FINDINGS: Blocking the Mas receptor with A779 increased IgE and IL-13 levels and prevented the reduction in extracellular matrix deposition in airways in OVA-TRE mice. Mas receptor blockade prevented the reduction of myeloperoxidase activity, as well as, prevented exercise-induced IL-10 increase. These data show that activation of Ang-(1-7)/Mas receptor pathway is involved in the anti-inflammatory and anti-fibrotic effects of aerobic training in an experimental model of chronic asthma. SIGNIFICANCE: Our results support exercise training as a non-pharmacological tool to defeat lung remodeling induced by chronic pulmonary inflammation. Further, our result also supports development of new therapy based on Ang-(1-7) or Mas agonists as important tool for asthma treatment in those patients that cannot perform aerobic training.

Oral Formulation of Angiotensin-(1-7) Promotes Therapeutic Actions in a Model of Eosinophilic and Neutrophilic Asthma.

The presence of eosinophils and neutrophils in the lungs of asthmatic patients is associated with the severity of the disease and resistance to corticosteroids. Thus, defective resolution of eosinophilic and neutrophilic inflammation is importantly related to exacerbation of asthma. In this study, we investigated a therapeutic action of angiotensin-(1-7) (Ang-(1-7)) in a model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS). Balb-c mice were sensitized and challenged with OVA. Twenty-three hours after the last OVA challenge, experimental groups received LPS, and 1 h and 7 h later, mice were treated with oral formulation of Ang-(1-7). On the next day, 45 h after the last challenge with OVA, mice were subjected to a test of motor and exploratory behavior; 3 h later, lung function was evaluated, and bronchoalveolar lavage fluid (BALF) and lungs were collected. Motor and exploratory activities were lower in OVA + LPS-challenged mice. Treatment with Ang-(1-7) improved these behaviors, normalized lung function, and reduced eosinophil, neutrophil, myeloperoxidase (MPO), eosinophilic peroxidase (EPO), and ERK1/2 phosphorylation (p-ERK1/2) in the lungs. In addition, Ang-(1-7) decreased the deposition of mucus and extracellular matrix in the airways. These results extended those of previous studies by demonstrating that oral administration of Ang-(1-7) at the peak of pulmonary inflammation can be valuable for the treatment of neutrophil- and eosinophil-mediated asthma. Therefore, these findings potentially provide a new drug to reverse the natural history of the disease, unlike the current standards of care that manage the disease symptoms at best.

Treatment with inhaled formulation of angiotensin-(1-7) reverses inflammation and pulmonary remodeling in a model of chronic asthma.

Asthma is characterized by inflammation, pulmonary remodeling and bronchial hyperresponsiveness. We have previously shown that treatment with angiotensin-(1-7) [Ang-(1-7)] promotes resolution of eosinophilic inflammation and prevents chronic allergic lung inflammation. Here, we evaluated the effect of treatment with the inclusion compound of Ang-(1-7) in hydroxypropyl ß-cyclodextrin (HPßCD) given by inhalation on pulmonary remodeling in an ovalbumin (OVA)-induced chronic allergic lung inflammation. Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged 3 times per week, for 4 weeks (days 21-46). After the 2nd week of challenge, mice were treated with Ang-(1-7) by inhalation (4.5 µg of Ang-(1-7) included in 6.9 µg of HPßCD for 14 days, i.e. days 35-48). Mice were killed 72 h after the last challenge and blood, bronchoalveolar lavage fluid (BALF) and lungs were collected. Histology and morphometric analysis were performed in the lung. Metalloproteinase (MMP)-9 and MMP-12 expression and activity, IL-5, CCL11 in the lung and plasma IgE were measured. After 2 weeks of OVA challenge there was an increase in plasma IgE and in inflammatory cells infiltration in the lung of asthmatic mice. Treatment with inhaled administration of Ang-(1-7)/HPßCD for 14 days reduced eosinophils, IL5, CCL11 in the lung and plasma IgE. Treatment of asthmatic mice with Ang-(1-7)/HPßCD by inhalation reversed pulmonary remodeling by reducing collagen deposition and MMP-9 and MMP-12 expression and activity. These results show for the first time that treatment by inhalation with Ang-(1-7) can reverse an installed asthma, inhibiting pulmonary inflammation and remodeling.

Augmentation index, a predictor of cardiovascular events, is increased in children and adolescents with primary nephrotic syndrome.

BACKGROUND: Arterial stiffness is associated with an increased risk of cardiovascular diseases. Augmentation index (AIx@75), a measure of arterial stiffness and wave reflection, has not been evaluated in patients with primary nephrotic syndrome (PNS). We investigated whether central and peripheral vascular profiles, hemodynamic parameters, and biochemical tests are associated with AIx@75 in PNS patients. METHODS: This observational study involved 38 children and adolescents with PNS (12.14 ± 3.65 years) and 37 healthy controls (13.28 ± 2.80 years). Arterial stiffness and vascular and hemodynamic parameters were measured noninvasively using the Mobil-O-Graph® (IEM, Stolberg, Germany). In the PNS group, biochemical tests and corticosteroid dosage/treatment time were analyzed. RESULTS: Peripheral and central systolic blood pressure (SBPp, SBPc) Z-scores were significantly higher in the PNS patients. AIx@75 was significantly higher in the PNS patients (25.14 ± 9.93%) than in controls (20.84 ± 7.18%). In the control group, AIx@75 negatively correlated with weight (r = - 0.369; p = 0.025), height (r = - 0.370; p = 0.024), and systolic volume/body surface (r = - 0.448; p = 0.006). In the PNS group, a univariate linear correlation showed that AIx@75 negatively correlated with weight (r = - 0.360; p = 0.027), height (r = 0.381; p = 0.18), and systolic volume/body surface (r = - 0.447; p < 0.002) and positively with the Z-score of SBPp (r = 0.407; p = 0.011), peripheral diastolic blood pressure (DBPp, r = 0.452; p = 0.004), SBPc (r = 0.416; p = 0.009), DBPc (r = 0.407; p = 0.011), triglycerides (r = 0.525; p = 0.001), and cholesterol [total (r = 0.539; p < 0.001), LDLc (r = 0.420; p = 0.010), and non-HDLc (r = 0.511; p = 0.001)]. CONCLUSIONS: Early abnormalities of AIx@75 and vascular parameters suggest that patients with PNS, even in stable condition, present subclinical indicators for the development of cardiovascular disease.

Oral formulation angiotensin-(1-7) therapy attenuates pulmonary and systemic damage in mice with emphysema induced by elastase.

Angiotensin-(1-7) [Ang-(1-7)], a peptide of the renin-angiotensin system, has anti-inflammatory, anti-fibrotic and antiproliferative effects in acute or chronic inflammatory disease of respiratory system. In this study, we evaluated the effect of treatment with Ang-(1-7) on pulmonary tissue damage and behavior of mice submitted to experimental model of elastase-induced pulmonary emphysema (PE). Initially, male C57BL/6 mice were randomly assigned into two main groups: control (CTRL) and PE. In the PE group, the animals received three intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals (0.2 IU in 50 µL of saline). The CTRL group received the same volume of saline solution (50 µL). Twenty-four hours after the last instillation, animals of the PE group were randomly divided into two groups: PE and PE + Ang-(1-7). The PE + Ang-(1-7) group was treated with 60 µg/kg of Ang-(1-7) and 92 µg kg of HPßCD in gavage distilled water, 100 µl. The CTRL and PE groups were treated with vehicle (HPßCD- 92 µg/kg in distilled water per gavage, 100 µl), orally daily for 3 weeks. On the 19th day of treatment, all groups were tested in relation to locomotor activity and exploratory behavior. After 48 h, the animals were euthanized and lungs were collected. The animals of PE group presented rupture of alveolar walls and consequently reduction of alveolar tissue area. Treatment with Ang-(1-7) partially restored the alveolar tissue area. The PE reduced the locomotor activity and the exploratory behavior of the mice in relation to the control group. Treatment with Ang-(1-7) attenuated this change. In addition, it was observed that Ang-(1-7) reduced lung levels of IL-1ß and increased levels of IL-10. These results show an anti-inflammatory effect of Ang-(1-7), inducing the return of pulmonary homeostasis and attenuation of the behavioral changes in experimental model of PE by elastase.

Positive end-expiratory pressure attenuates hemodynamic effects induced by an overload of inspiratory muscles in patients with COPD.

BACKGROUND: Inspiratory muscle training (IMT) using a Threshold® device is commonly used to improve the strength and endurance of inspiratory muscles. However, the effect of IMT, alone or with positive end-expiratory pressure (PEEP), on hemodynamic parameters in patients with chronic obstructive pulmonary disease (COPD) remains unknown. OBJECTIVE: To assess the effects of an overload of inspiratory muscles using IMT fixed at 30% of the maximal inspiratory pressure (MIP), and IMT associated with 5 cmH2O of PEEP (IMT + PEEP), on the echocardiographic parameters in healthy subjects and patients with COPD. METHODS: Twenty patients with COPD (forced expiratory volume in 1 second 53.19±24.71 pred%) and 15 age-matched healthy volunteers were evaluated using spirometry, MIP, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) dyspnea scale. The E- (fast-filling phase) and A- (atrial contraction phase) waves were evaluated at the tricuspid and mitral valves during inspiration and expiration in the following sequence: at basal conditions, using IMT, and using IMT + PEEP. RESULTS: Patients with COPD had reduced MIPs versus the control group. Ten patients had CAT scores <10 and 12 patients had mMRC scores <2. E-wave values at the mitral valve were significantly decreased with IMT during the inspiratory phase in both groups. These effects were normalized with IMT + PEEP. During the expiratory phase, use of IMT + PEEP normalized the reduction in E-wave values in the COPD group. During inspiration at the tricuspid valve, reduction in E-wave values during IMT was normalized by IMT + PEEP in COPD group. During the expiratory phase, the value of the E-waves was significantly reduced with overload of the inspiratory muscles in both groups, and these effects were normalized with IMT + PEEP. A-waves did not change under any conditions. CONCLUSION: Acute hemodynamic effects induced by overloading of the inspiratory muscles were attenuated and/or reversed by the addition of PEEP in COPD patients.

Vascular function in asthmatic children and adolescents.

BACKGROUND: Epidemiological studies have demonstrated an increased incidence of cardiovascular events in patients with bronchial asthma, but little is known about the relationship between asthma and vascular function. The purpose of this study was to evaluate endothelial function and arterial stiffness in children and adolescents with asthma. METHODS: A cross-sectional controlled study was designed. Measurements of endothelial function and arterial stiffness in asthmatic (13.6 ± 0.6 years) and control groups (14.9 ± 0.7 years) were taken by the non-invasive peripheral arterial tonometry (EndoPAT2000) determined by using the natural logarithm of the reactive hyperemia index (LnRHI) and the augmentation index (AIx@75%), respectively. Patients with asthma were also administered two questionnaires to evaluate asthma control and quality of life. Exercise functional capacity was evaluated using the Shuttle Walking Test (SWT). Only male participants were included in the present study. RESULTS: LnRHI and the walked distance during the SWT were similar between groups (p = 0.23 and p = 0.50, respectively). AIx@75% was significantly higher in the asthmatic group (-7.75 ± 1.7) compared to the control group (-15.25 ± 1.8), p < 0.04. In the control group, the LnRHI correlated positively with baseline systolic blood pressure (r = 0.53, p = 0.02) and mean arterial pressure (r = 0.50, p = 0.03), age (r = 0.61, p = 0.007), weight (r = 0.63, p = 0.004) and height (r = 0.56, p = 0.015). Besides that LnRHI correlated with FVC (r = 0.69, p = 0.002), FEV1, (r = 0.53, p = 0.03) and negatively with Tiffeneau index (FEV1/FVC%, r = -0.49 p = 0.04). The LnRHI of the asthmatic group did not correlate with the different variables evaluated. CONCLUSION: The increased AIx@75% without changes in LnRHI in asthmatic patients could mean that an early detection of vascular impairment may precede endothelial dysfunction, and that different mechanisms may contribute to the pathogenesis and progression of cardiovascular events in this population. A large prospective and randomized controlled study should be done to evaluate the physiopathological mechanisms underlying the association between arterial stiffness and asthma.

Chronic allergic pulmonary inflammation is aggravated in angiotensin-(1-7) Mas receptor knockout mice.

The angiotensin-(1-7) [ANG-(1-7)]/Mas receptor pathway is currently recognized as a counterbalancing mechanism of the renin-angiotensin system in different pathophysiological conditions. We have previously described that treatment with ANG-(1-7) attenuates lung inflammation and remodeling in an experimental model of asthma. In the present study, we investigated whether lack of the Mas receptor could alter the inflammatory response in a model of chronic allergic lung inflammation induced by ovalbumin (OVA). Mas receptor wild-type (MasWT) and knockout (MasKO) mice were subjected to four doses of OVA (20 µg/mice ip) with a 14-day interval. At the 21st day, nebulization with OVA (1%) was started, three times per week until the 46th day. Control groups received saline (0.9% ip) and were nebulized with saline (0.9%). MasWT-OVA developed a modest inflammatory response and minor pulmonary remodeling to OVA challenge. Strikingly, MasKO-OVA presented a significant increase in inflammatory cell infiltrate, increase in extracellular matrix deposition, increase in thickening of the alveolar parenchyma, increase in thickening of the smooth muscle layer of the pulmonary arterioles, increase in proinflammatory cytokine and chemokine levels in the lungs, characteristic of chronic asthma. Additionally, MasKO-OVA presented an increase in ERK1/2 phosphorylation compared with MasWT-OVA. Furthermore, MasKO-OVA showed a worse performance in a test of maximum physical exercise compared with MasWT-OVA. Our study shows that effects triggered by the Mas receptor are important to attenuate the inflammatory and remodeling processes in a model of allergic lung inflammation in mice. Our data indicate that impairment of the ANG-(1-7)/Mas receptor pathway may lead to worsening of the pathophysiological changes of asthma.

Depression diagnosed by the mini international neuropsychiatric interview plus (MINI) in patients with chronic obstructive pulmonary disease: relationship with functional capacity and quality of life.

BACKGROUND: The prevalence of depression in patients with chronic obstructive pulmonary disease (COPD) is associated with a worsening of prognosis. Most studies classify COPD patients as depressive or non-depressive based on symptoms, rather than on a diagnosis using specific tools. Thus, the aim of this study was to determine the impact of depression, as diagnosed by the Mini International Neuropsychiatric Interview Plus (MINI), on functional capacity estimated by the 6-minute walk test (6MWT) and unsupported upper-limb exercise test, and quality of life estimated by Saint George's Respiratory Questionnaire (SGRQ), among patients with COPD. RESULTS: Using the MINI as a diagnostic tool, 22.2 % of all patients (6.6 % of all men and 41.6 % of all women) were diagnosed with depression. No significant differences were found between depressive and non-depressive patients with regard to anthropometric measurements, lung function, functional capacity, or quality of life variables. The best models for the dependent variables representing functional capacity and quality of life revealed that the covariates SGRQTOTAL and gender (R(2) = 16.7 %) were significant in explaining the response variable for functional capacity of the upper limbs. Results also showed that age, monthly income, insomnia, and the results of a 6MWT were significant in explaining overall quality of life (R(2) = 46 %), and that the percentage of the predicted forced expiratory volume in the first second post-bronchodilator and gender were significant in explaining walking distance (R(2) = 22 %). Depression, as diagnosed by the MINI, was not significant in explaining any of the dependent variables. CONCLUSIONS: Despite a high prevalence of depression in COPD patients, especially in women, depression, as diagnosed by the MINI, was not correlated with functional capacity tests or quality of life in patients with moderate to very severe COPD in the present study. This suggests that depression identified by this diagnostic test may be more accurate than depression diagnosed by tests that evaluate symptoms, as they may be influenced by the perceptions of the patient in relation to their health.

Effect of lung fibrosis on glycogen content in different extrapulmonary tissues.

PURPOSE: Patients with pulmonary fibrosis often exhibit reduced lung function and diminished health-related quality of life. Studies have shown that paraquat-induced, extrapulmonary, acute lung injury affects the metabolic profile of glycogen content in different tissues. The purpose of the present study was to investigate whether the process of pulmonary fibrosis induced by continuous exposure to the toxic herbicide paraquat or by a local insult from bleomycin affects the glycogen content in tissues. METHODS: In the paraquat experiment, Wistar rats (n = 5 per group) received either saline (controls) or an intraperitoneal injection of a paraquat solution (7.0 mg/kg; experimental group) once a week for 4 weeks. In the bleomycin experiment, Balb/c mice (n = 5 per group) received either saline (controls) or 6.25 U/kg of bleomycin through intratracheal instillation in single dose (experimental group). Glycogen content in different tissues (mg/g tissue) was measured using the anthrone reagent. The lungs submitted to histopathological and quantitative analyses of fibrosis. RESULTS: Paraquat-induced fibrosis led to lower glycogen content in the gastrocnemius muscle (2.7 ± 0.1 vs. 3.4 ± 0.1; 79 %) compared with the controls, whereas no changes in glycogen content were found in the diaphragm or heart. Bleomycin-induced fibrosis led to lower glycogen content in the diaphragm (0.43 ± 0.02 vs. 0.79 ± 0.09, 54 %), gastrocnemius muscle (0.62 ± 0.11 vs. 1.18 ± 0.06, 52 %), and heart (0.68 ± 0.11 vs. 1.39 ± 0.1, 49 %) compared with the controls (p < 0.05). Moreover, the area of fibrous connective tissue (µm(2)) in the lungs was significantly increased in paraquat-induced fibrosis (3,463 ± 377 vs. 565 ± 89) and bleomycin-induced fibrosis (3,707 ± 433.9 vs. 179 ± 51.28) compared with the controls. CONCLUSIONS: The findings suggest that the effects of fibrogenesis in the lungs are not limited to local alterations but also lead to a reduction in glycogen content in the heart and other muscles. This reduction could partially explain the impaired muscle performance found in patients with pulmonary fibrosis.