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

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.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.277.4.r1013 ◽

1999 ◽

Vol 277 (4) ◽

pp. R1013-R1019 ◽

Cited By ~ 12

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).

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Inspiratory Flow Resistive Loaded Breathing and Inspiratory Muscle Induced Systemic Oxidative Stress

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000516852.35352.1d ◽

2017 ◽

Vol 49 (5S) ◽

pp. 15

Author(s):

Dean E. Mills ◽

Kurt Vogel ◽

Michael A. Johnson ◽

Graham R. Sharpe ◽

Jeff S. Coombes ◽

...

Keyword(s):

Oxidative Stress ◽

Inspiratory Flow ◽

Inspiratory Muscle ◽

Systemic Oxidative Stress ◽

Loaded Breathing

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Chest wall kinematics and respiratory muscle action in walking healthy humans

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.3.938 ◽

1999 ◽

Vol 87 (3) ◽

pp. 938-946 ◽

Cited By ~ 34

Author(s):

A. Sanna ◽

F. Bertoli ◽

G. Misuri ◽

F. Gigliotti ◽

I. Iandelli ◽

...

Keyword(s):

Chest Wall ◽

Respiratory Muscle ◽

Respiratory Muscles ◽

Progressive Increase ◽

Muscle Action ◽

Rib Cage ◽

Healthy Humans ◽

Velocity Of Shortening ◽

Flow Generator ◽

Chest Wall Kinematics

We studied chest wall kinematics and respiratory muscle action in five untrained healthy men walking on a motor-driven treadmill at 2 and 4 miles/h with constant grade (0%). The chest wall volume (Vcw), assessed by using the ELITE system, was modeled as the sum of the volumes of the lung-apposed rib cage (Vrc,p), diaphragm-apposed rib cage (Vrc,a), and abdomen (Vab). Esophageal and gastric pressures were measured simultaneously. Velocity of shortening ( V di) and power [W˙di = diaphragm pressure (Pdi) × V di] of the diaphragm were also calculated. During walking, the progressive increase in end-inspiratory Vcw ( P < 0.05) resulted from an increase in end-inspiratory Vrc,p and Vrc,a ( P < 0.01). The progressive decrease ( P < 0.05) in end-expiratory Vcw was entirely due to the decrease in end-expiratory Vab ( P < 0.01). The increase in Vrc,a was proportionally slightly greater than the increase in Vrc,p, consistent with minimal rib cage distortion (2.5 ± 0.2% at 4 miles/h). The Vcw end-inspiratory increase and end-expiratory decrease were accounted for by inspiratory rib cage (RCM,i) and abdominal (ABM) muscle action, respectively. The pressure developed by RCM,i and ABM and Pdi progressively increased ( P < 0.05) from rest to the highest workload. The increase in V di, more than the increase in the change in Pdi, accounted for the increase inW˙di. In conclusion, we found that, in walking healthy humans, the increase in ventilatory demand was met by the recruitment of the inspiratory and expiratory reserve volume. ABM action accounted for the expiratory reserve volume recruitment. We have also shown that the diaphragm acts mainly as a flow generator. The rib cage distortion, although measurable, is minimized by the coordinated action of respiratory muscles.

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Hyperinflation with intrinsic PEEP and respiratory muscle blood flow

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.5.2440 ◽

1994 ◽

Vol 77 (5) ◽

pp. 2440-2448 ◽

Cited By ~ 24

Author(s):

Y. Kawagoe ◽

S. Permutt ◽

H. E. Fessler

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Respiratory Muscle ◽

Respiratory Muscles ◽

Fold Increase ◽

Transversus Abdominis ◽

Resistive Load ◽

Transdiaphragmatic Pressure ◽

Circulatory Effects ◽

Inspiratory Work

Increased end-expiratory lung volume and intrinsic positive end-expiratory pressure (PEEP) are common in obstructive lung disease, especially during exacerbations or exercise. This loads the respiratory muscles and may also stress the circulatory system, causing a reduction or redistribution of cardiac output. We measured the blood flow to respiratory muscles and systemic organs using colored microspheres in 10 spontaneously breathing anesthetized tracheotomized dogs. Flows during baseline breathing (BL) were compared with those during hyperinflation (HI) induced by a mechanical analogue of airway closure and with those during an inspiratory resistive load (IR) that produced an equivalent increase in inspiratory work and time-integrated transdiaphragmatic pressure. Cardiac output was unchanged during IR (3.19 +/- 0.27 l/min at BL, 3.09 +/- 0.34 l/min during IR) but was reduced during HI (2.14 +/- 0.29 l/min; P < 0.01). Among the organs studied, flow was unaltered by IR but decreased to the liver and pancreas and increased to the brain during HI. For the respiratory muscles, flow to the diaphragm increased during IR. However, despite a 1.9-fold increase in inspiratory work per minute and a 2.5-fold increase in integrated transdiaphragmatic pressure during HI, blood flow to the diaphragm was unchanged and flow to the scalenes and sternomastoid fell. The only respiratory muscle to which flow increased during HI was the transversus abdominis, an expiratory muscle. We conclude that the circulatory effects of hyperinflation in this model impair inspiratory muscle perfusion and speculate that this may contribute to respiratory muscle dysfunction in hyperinflated states.

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Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation

Journal of Applied Physiology ◽

10.1152/japplphysiol.01271.2013 ◽

2014 ◽

Vol 116 (8) ◽

pp. 970-979 ◽

Cited By ~ 4

Author(s):

Dean E. Mills ◽

Michael A. Johnson ◽

Martin J. McPhilimey ◽

Neil C. Williams ◽

Javier T. Gonzalez ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Respiratory Muscle ◽

Minute Ventilation ◽

Inspiratory Muscle ◽

Inspiratory Muscle Training ◽

Muscle Training ◽

Muscle Work ◽

Main Effect ◽

Diaphragm Fatigue

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of ( 1) passive rest and ( 2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time ( P < 0.01) for plasma interleukin-1β (IL-1β) and interleukin-6 (IL-6) concentrations and a strong trend ( P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 ± 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA ( P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1β and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1β and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation.

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P2990 Sulfhydryl angiotensin-converting enzyme inhibition induces a sustained reduction of low-density lipoprotein oxidazibility and systemic oxidative stress in patients with essential hypertension

European Heart Journal ◽

10.1016/s0195-668x(03)95768-x ◽

2003 ◽

Vol 24 (5) ◽

pp. 582

Author(s):

A LIGUORI

Keyword(s):

Oxidative Stress ◽

Essential Hypertension ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Angiotensin Converting Enzyme Inhibition ◽

Low Density ◽

Converting Enzyme ◽

Systemic Oxidative Stress ◽

Sustained Reduction ◽

Converting Enzyme Inhibition

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OXIDATIVE STRESS BIOMARKERS IN EXPIRATED AIR OF HEALTHY HUMANS AND PROMISING TECHNIQUES OF THEIR ANALYSIS DURING SPACE FLIGHT

Aerospace and Environmental Medicine ◽

10.21687/0233-528x-2020-54-3-5-21 ◽

2020 ◽

pp. 5-21

Author(s):

L.N. Mukhamedieva ◽

◽

D.S. Tsarkov ◽

D.S. Ozerov ◽

G.Yu. Grigoriev ◽

...

Keyword(s):

Oxidative Stress ◽

Space Flight ◽

Oxidative Stress Biomarkers ◽

Stress Biomarkers ◽

Healthy Humans

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Respiratory muscle function in the newborn: a narrative review

Pediatric Research ◽

10.1038/s41390-021-01529-z ◽

2021 ◽

Author(s):

Theodore Dassios ◽

Aggeliki Vervenioti ◽

Gabriel Dimitriou

Keyword(s):

Congenital Anomalies ◽

Muscle Function ◽

Respiratory Muscle ◽

Work Of Breathing ◽

Respiratory Muscles ◽

Current Evidence ◽

Muscle Fibres ◽

List Type ◽

Respiratory Muscle Function ◽

Neurally Adjusted Ventilator Assist

Abstract Our aim was to summarise the current evidence and methods used to assess respiratory muscle function in the newborn, focusing on current and future potential clinical applications. The respiratory muscles undertake the work of breathing and consist mainly of the diaphragm, which in the newborn is prone to dysfunction due to lower muscle mass, flattened shape and decreased content of fatigue-resistant muscle fibres. Premature infants are prone to diaphragmatic dysfunction due to limited reserves and limited capacity to generate force and avoid fatigue. Methods to assess the respiratory muscles in the newborn include electromyography, maximal respiratory pressures, assessment for thoraco-abdominal asynchrony and composite indices, such as the pressure–time product and the tension time index. Recently, there has been significant interest and a growing body of research in assessing respiratory muscle function using bedside ultrasonography. Neurally adjusted ventilator assist is a novel ventilation mode, where the level of the respiratory support is determined by the diaphragmatic electrical activity. Prolonged mechanical ventilation, hypercapnia and hypoxia, congenital anomalies and systemic or respiratory infection can negatively impact respiratory muscle function in the newborn, while caffeine and synchronised or volume-targeted ventilation have a positive effect on respiratory muscle function compared to conventional, non-triggered or pressure-limited ventilation, respectively. Impact Respiratory muscle function is impaired in prematurely born neonates and infants with congenital anomalies, such as congenital diaphragmatic hernia. Respiratory muscle function is negatively affected by prolonged ventilation and infection and positively affected by caffeine and synchronised compared to non-synchronised ventilation modes. Point-of-care diaphragmatic ultrasound and neurally adjusted ventilator assist are recent diagnostic and therapeutic technological developments with significant clinical applicability.

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Time Course of Redox Biomarkers in COVID-19 Pneumonia: Relation with Inflammatory, Multiorgan Impairment Biomarkers and CT Findings

Antioxidants ◽

10.3390/antiox10071126 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1126

Author(s):

Tijana Kosanovic ◽

Dragan Sagic ◽

Vladimir Djukic ◽

Marija Pljesa-Ercegovac ◽

Ana Savic-Radojevic ◽

...

Keyword(s):

Oxidative Stress ◽

Time Course ◽

Redox Homeostasis ◽

Original Data ◽

Advanced Oxidation Protein Products ◽

Oxidative Stress Parameters ◽

Systemic Oxidative Stress ◽

Dependent Relation ◽

Organ Tissue ◽

Insight Into

Although the original data on systemic oxidative stress in COVID-19 patients have recently started to emerge, we are still far from a complete profile of changes in patients’ redox homeostasis. We aimed to assess the extent of oxidative damage of proteins, lipids and DNA during the course of acute disease, as well as their association with CT pulmonary patterns. In order to obtain more insight into the origin of the systemic oxidative stress, the observed parameters were correlated with inflammatory biomarkers and biomarkers of multiorgan impairment. In this prospective study, we included 58 patients admitted between July and October 2020 with COVID-19 pneumonia. Significant changes in malondialdehyde, 8-hydroxy-2’-deoxyguanosine and advanced oxidation protein products levels exist during the course of COVID-19. Special emphasis should be placed on the fact that the pattern of changes differs between non-hospitalized and hospitalized individuals. Our results point to the time-dependent relation of oxidative stress parameters with inflammatory and multiorgan impairment biomarkers, as well as pulmonary patterns in COVID-19 pneumonia patients. Correlation between redox biomarkers and immunological or multiorgan impairment biomarkers, as well as pulmonary CT pattern, confirms the suggested involvement of neutrophils networks, IL-6 production, along with different organ/tissue involvement in systemic oxidative stress in COVID-19.

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