Strenuous resistive breathing induces proinflammatory cytokines and stimulates the HPA axis in humans

1999 ◽  
Vol 277 (4) ◽  
pp. R1013-R1019 ◽  
Author(s):  
Theodoros Vassilakopoulos ◽  
Spyros Zakynthinos ◽  
Charis Roussos ◽  
Keyword(s):  
Hpa Axis ◽  
Proinflammatory Cytokines ◽  
Respiratory Muscles ◽  
Whole Body ◽  
Resistive Load ◽  
Maximal Inspiratory Pressure ◽  
Rest Point ◽  
Healthy Humans ◽  
Resistive Breathing ◽  
Plasma Cytokines

Interleukin-1β (IL-1β) and interleukin-6 (IL-6), powerful stimulants of the hypothalamic-pituitary-adrenal (HPA) axis, increase in response to whole body exercise. Strenuous inspiratory resistive breathing (IRB), a form of clinically relevant “exercise” for the respiratory muscles, produces β-endorphin through a largely unknown mechanism. We investigated (in 11 healthy humans) whether strenuous IRB produces proinflammatory cytokines and β-endorphin in parallel with stimulation of the HPA axis, assessed by concurrent measurement of ACTH. Subjects underwent either severe [at 75% of maximal inspiratory pressure (Pm max)] or moderate (at 35% of Pm max) IRB. Plasma cytokines, β-endorphin, and ACTH were measured at rest ( point R), at the point at which the resistive load could not be sustained ( point F), and at exhaustion [15 min later ( point E)]. During severe IRB, IL-1β increased from 0.83 ± 0.12 pg/ml at point R to 1.88 ± 0.53 and 4.06 ± 1.27 pg/ml at points F and E, respectively ( P < 0.01). IL-6 increased from 5.30 ± 1.02 to 10.33 ± 2.14 and 11.66 ± 2.29 pg/ml at points F and E, respectively ( P = 0.02). ACTH and β-endorphin fluctuated from 20.87 ± 5.49 and 25.03 ± 3.97 pg/ml at point R to 22.97 ± 4.41 and 26.32 ± 3.93 pg/ml, respectively, at point F and increased to 46.96 ± 8.55 and 40.32 ± 5.94 pg/ml, respectively, at point E ( P< 0.01, point E vs. point F). There was a positive correlation between the IL-6 at point F and the ACTH and β-endorphin at point E ( r= 0.88 and 0.94, respectively; P < 0.01) as well as between the increase in IL-6 (between points R and F) and the increases in ACTH and β-endorphin (between points F and E, r= 0.91 and 0.92, respectively; P < 0.01). Moderate IRB did not produce any change. We conclude that severe IRB produces proinflammatory cytokines and stimulates the HPA axis in humans secondary to the production of cytokines (especially IL-6).

scholarly journals Inspiratory flow-resistive breathing, respiratory muscle-induced systemic oxidative stress, and diaphragm fatigue in healthy humans

2020 ◽  
Vol 129 (1) ◽  
pp. 185-193
Author(s):  
David R. Briskey ◽  
Kurt Vogel ◽  
Michael A. Johnson ◽  
Graham R. Sharpe ◽  
Jeff S. Coombes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Respiratory Muscle ◽  
Respiratory Muscles ◽  
Inspiratory Flow ◽  
Resistive Load ◽  
Healthy Humans ◽  
Systemic Oxidative Stress ◽  
Resistive Breathing ◽  
Diaphragm Fatigue

We examined whether the respiratory muscles of humans contribute to systemic oxidative stress following inspiratory flow-resistive breathing, whether the amount of oxidative stress is influenced by the level of resistive load, and whether the amount of oxidative stress is related to the degree of diaphragm fatigue incurred. It is only when sufficiently strenuous that inspiratory flow-resistive breathing elevates plasma F2-isoprostanes, and our novel data show that this is not related to a reduction in transdiaphragmatic twitch pressure.

N-acetylcysteine administration alters the response to inspiratory loading in oxygen-supplemented rats

1997 ◽  
Vol 82 (4) ◽  
pp. 1119-1125 ◽  
Author(s):  
G. S. Supinski ◽  
D. Stofan ◽  
R. Ciufo ◽  
A. Dimarco
Keyword(s):  
Free Radical ◽  
Respiratory Failure ◽  
Respiratory Muscles ◽  
Treated Group ◽  
Respiratory Arrest ◽  
Saline Group ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Resistive Load ◽  
Loaded Breathing

Supinski, G. S., D. Stofan, R. Ciufo, and A. DiMarco. N-acetylcysteine administration alters the response to inspiratory loading in oxygen-supplemented rats. J. Appl. Physiol. 82(4): 1119–1125, 1997.—Based on recent studies, it has been suggested that free radicals are elaborated in the respiratory muscles during strenuous contractions and contribute to the development of muscle fatigue. If this theory is correct, then it should be possible to attenuate the development of diaphragm fatigue and/or delay the onset of respiratory failure during loaded breathing by administering a free radical scavenger. The purpose of the present experiment was, therefore, to examine the effect of N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, on the evolution of respiratory failure in decerebrate unanesthetized rats breathing against a large inspiratory resistive load. We compared the inspiratory volume and pressure generation over time in animals pretreated with either saline or NAC (150 mg/kg) and then loaded until respiratory arrest. After arrest, the diaphragm was excised, and samples were assayed for reduced (GSH) and oxidized glutathione. As a control, we also assessed respiratory function and glutathione concentrations in groups of nonloaded saline- and NAC-treated animals. We found that NAC-treated animals were able to tolerate loading better than the saline-treated group, maintaining higher inspiratory pressures and sustaining higher inspired volumes. Administration of NAC also increased the time that animals could tolerate loading before the development of respiratory arrest. In addition, although saline-treated loaded animals had significant reductions in diaphragmatic GSH levels compared with unloaded controls, the magnitude of this reduction was blunted by NAC administration (i.e., GSH averaged 965 ± 113, 568 ± 83, 907 ± 39, and 784 ± 61 nmol/g for unloaded-saline, loaded-saline, unloaded-NAC, and loaded-NAC groups, P< 0.05, with the value for the loaded-saline group lower than the values for the two unloaded groups; GSH for the loaded-NAC group was not different, however, from unloaded controls). These data demonstrate that administration of NAC, a free radical scavenger, slows the rate of development of respiratory failure during inspiratory resistive loading.

scholarly journals Casein and Soy Protein Meals Differentially Affect Whole-Body and Splanchnic Protein Metabolism in Healthy Humans

2005 ◽  
Vol 135 (5) ◽  
pp. 1080-1087 ◽  
Author(s):  
Yvette C. Luiking ◽  
Nicolaas E. P. Deutz ◽  
Martin Jäkel ◽  
Peter B. Soeters
Keyword(s):  
Soy Protein ◽  
Protein Metabolism ◽  
Whole Body ◽  
Healthy Humans

scholarly journals Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

2010 ◽  
Vol 298 (5) ◽  
pp. E920-E929 ◽  
Author(s):  
Esben S. Buhl ◽  
Thomas Korgaard Jensen ◽  
Niels Jessen ◽  
Betina Elfving ◽  
Christian S. Buhl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Whole Body ◽  
Oral Glucose ◽  
Red Muscle ◽  
Hpa Axis Activity

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4–5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phospho enolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser473phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW ( P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion ( P < 0.05 vs. Cx), whole body insulin resistance ( P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression ( P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser473phosphorylation. The ESC treatment normalized corticosterone secretion ( P < 0.05 vs. LBW), whole body insulin sensitivity ( P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression ( P < 0.05), and red muscle PKB Ser473phosphorylation ( P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

Vasodilator reserve in respiratory muscles during maximal exertion in ponies

1986 ◽  
Vol 60 (5) ◽  
pp. 1571-1577 ◽  
Author(s):  
M. Manohar
Keyword(s):  
Blood Flow ◽  
Maximal Exercise ◽  
Respiratory Muscles ◽  
Aortic Pressure ◽  
Whole Body ◽  
Adenosine Infusion ◽  
Base Line ◽  
Triceps Brachii ◽  
Vasodilator Reserve ◽  
Mean Aortic Pressure

Eight healthy adult grade ponies were studied at rest as well as during maximal exertion carried out with and without adenosine infusion (3 microM X kg-1 X min-1 into the pulmonary artery) on a treadmill to compare levels of blood flow in respiratory muscles with those in other vigorously working muscles and to ascertain whether there remained any unutilized vasodilator reserve in respiratory muscles of maximally exercising ponies. Radionuclide-labeled 15-micron-diam microspheres, injected into the left ventricle, were used to study tissue blood flows. During maximal exertion, there were increases above base-line values in heart rate (336%), mean aortic pressure (41%), cardiac output (722%), and arterial O2 content (56%). The whole-body O2 consumption was 123 +/- 11 ml X min-1 X kg-1, and the stride/respiratory frequency of the galloping ponies was 138 +/- 4/min. With adenosine infusion during maximal exertion, mean aortic pressure decreased (P less than 0.05), but none of the above variables was different from maximal exercise alone. During maximal exertion, blood flow in the adrenal glands, myocardium, respiratory, and limb muscles increased, whereas that in the kidneys decreased and the cerebral perfusion remained unaltered. With adenosine infusion during maximal exercise, renal vasoconstriction intensified, whereas adrenal and coronary beds exhibited further vasodilatation. During maximal exertion, blood flow in the equine diaphragm (265 +/- 36 ml X min-1 X 100 g-1) was not different from that in the gluteus medius (253 +/- 36) and biceps femoris (233 +/- 29); both are principal muscles of propulsion in the equine subjects) or the triceps brachii (227 +/- 26) muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhibition of brain proinflammatory cytokine synthesis reduces hypothalamic excitation in rats with ischemia-induced heart failure

2008 ◽  
Vol 295 (1) ◽  
pp. H227-H236 ◽  
Author(s):  
Yu-Ming Kang ◽  
Zhi-Hua Zhang ◽  
Baojian Xue ◽  
Robert M. Weiss ◽  
Robert B. Felder
Keyword(s):  
Heart Failure ◽  
Hpa Axis ◽  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Left Ventricular ◽  
Prostaglandin E ◽  
Renin Angiotensin ◽  
Intracerebroventricular Infusion ◽  
Cytokine Synthesis ◽  
The Brain

The expression of proinflammatory cytokines increases in the hypothalamus of rats with heart failure (HF). The pathophysiological significance of this observation is unknown. We hypothesized that hypothalamic proinflammatory cytokines upregulate the activity of central neural systems that contribute to increased sympathetic nerve activity in HF, specifically, the brain renin-angiotensin system (RAS) and the hypothalamic-pituitary-adrenal (HPA) axis. Rats with HF induced by coronary ligation and sham-operated controls (SHAM) were treated for 4 wk with a continuous intracerebroventricular infusion of the cytokine synthesis inhibitor pentoxifylline (PTX, 10 μg/h) or artificial cerebrospinal fluid (VEH). In VEH-treated HF rats, compared with VEH-treated SHAM rats, the hypothalamic expression of proinflammatory cytokines was increased, along with key components of the brain RAS (renin, angiotensin-converting enzyme, angiotensin type 1 receptor) and corticotropin-releasing hormone, the central indicator of HPA axis activation, in the paraventricular nucleus (PVN) of the hypothalamus. The expression of other inflammatory/excitatory mediators (superoxide, prostaglandin E2) was also increased, along with evidence of chronic neuronal excitation in PVN. VEH-treated HF rats had higher plasma levels of norepinephrine, ANG II, interleukin (IL)-1β, and adrenocorticotropic hormone, increased left ventricular end-diastolic pressure, and increased wet lung-to-body weight ratio. With the exception of plasma IL-1β, an indicator of peripheral proinflammatory cytokine activity, all measures of neurohumoral excitation were significantly lower in HF rats treated with intracerebroventricular PTX. These findings suggest that the increase in brain proinflammatory cytokines observed in rats with ischemia-induced HF is functionally significant, contributing to neurohumoral excitation by activating brain RAS and the HPA axis.

scholarly journals A Case of Progressive Ossifying Fibrodysplasia of Tracheobronchial Respiratory Muscles

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Nouraly Habib ◽  
Anhum Konan ◽  
Tra Bi Zamble Olivier Didier
Keyword(s):  
Smooth Muscles ◽  
Respiratory Muscles ◽  
Whole Body ◽  
X Rays ◽  
Heterotopic Ossifications ◽  
Whole Body Ct ◽  
Body Ct

The authors report a case of progressive ossifying myositis (POM) in a 13-year-old boy, revealed by dry cough and dyspnea. Conventional chest x-rays and whole-body CT showed extraskeletal ossification that seems to affect the left bronchial strain and trachea. This lesional topography, if established, not yet described to our knowledge, contrasts with the observations of all the authors, including Munchmeyer, for whom smooth muscles and muscles attached to the skeleton by a single end are spared by the heterotopic ossifications characteristic of the disease. Therefore, this observation raises the question of the ubiquity of muscle ossifications during POM.

Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial

2013 ◽  
Vol 305 (7) ◽  
pp. E879-E889 ◽  
Author(s):  
Britt Christensen ◽  
Birgitte Nellemann ◽  
Mads S. Larsen ◽  
Line Thams ◽  
Peter Sieljacks ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Exercise Capacity ◽  
Uncoupling Protein ◽  
Metabolic Effects ◽  
Whole Body ◽  
Mrna Levels ◽  
Healthy Humans ◽  
Ucp2 Mrna

Erythropoietin (Epo) administration improves aerobic exercise capacity and insulin sensitivity in renal patients and also increases resting energy expenditure (REE). Similar effects are observed in response to endurance training. The aim was to compare the effects of endurance training with erythropoiesis-stimulating agent (ESA) treatment in healthy humans. Thirty-six healthy untrained men were randomized to 10 wk of either: 1) placebo ( n = 9), 2) ESA ( n = 9), 3) endurance training ( n = 10), or 4) ESA and endurance training ( n = 8). In a single-blinded design, ESA/placebo was injected one time weekly. Training consisted of biking for 1 h at 65% of wattmax three times per week. Measurements performed before and after the intervention were as follows: body composition, maximal oxygen uptake, insulin sensitivity, REE, and palmitate turnover. Uncoupling protein 2 (UCP2) mRNA levels were assessed in skeletal muscle. Fat mass decreased after training ( P = 0.003), whereas ESA induced a small but significant increase in intrahepatic fat ( P = 0.025). Serum free fatty acid (FFA) levels and palmitate turnover decreased significantly in response to training, whereas the opposite pattern was found after ESA. REE corrected for lean body mass increased in response to ESA and training, and muscle UCP2 mRNA levels increased after ESA ( P = 0.035). Insulin sensitivity increased only after training ( P = 0.011). In conclusion: 1) insulin sensitivity is not improved after ESA treatment despite improved exercise capacity, 2) the calorigenic effects of ESA may be related to increased UCP2 gene expression in skeletal muscle, and 3) training and ESA exert opposite effects on lipolysis under basal conditions, increased FFA levels and liver fat fraction was observed after ESA treatment.

Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism

1998 ◽  
Vol 274 (5) ◽  
pp. E801-E807 ◽  
Author(s):  
Dominique Darmaun ◽  
Susan Welch ◽  
Annie Rini ◽  
Brenda K. Sager ◽  
Astride Altomare ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Oral Treatment ◽  
Healthy Adults ◽  
Whole Body ◽  
Dependent Manner ◽  
Glutamine Concentration ◽  
Body Protein ◽  
Healthy Humans ◽  
Appearance Rate

The present study was designed to determine whether sodium phenylbutyrate (ΦB) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g ⋅ kg−1 ⋅ day−1) of ΦB were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an ≈25% decline for a dose of 0.36 g ΦB ⋅ kg−1 ⋅ day−1. A second group of six healthy adults received 5-h infusions ofl-[1-14C]leucine andl-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with ΦB (0.36 g ⋅ kg−1 ⋅ day−1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an ≈26% decline in plasma glutamine concentration from 514 ± 24 to 380 ± 15 μM (means ± SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 ± 7 vs. 117 ± 5 μmol ⋅ kg−1 ⋅ h−1; not significant); 3) an ≈22% rise in leucine oxidation (Ox) from 23 ± 2 to 28 ± 2 μmol ⋅ kg−1 ⋅ h−1( P < 0.01), resulting in an ≈11% decline in nonoxidative leucine disposal (NOLD = Ra − Ox), an index of protein synthesis, from 100 ± 6 to 89 ± 5 μmol ⋅ kg−1 ⋅ h−1( P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a “glutamine trap” to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decreases estimates of whole body protein synthesis.

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