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Experimental Physiology Dec 2020What is the topic of this review? The work presented here focuses mostly on testing the theory of blood flow redistribution from the locomotor to the respiratory muscles... (Review)
Review
NEW FINDINGS
What is the topic of this review? The work presented here focuses mostly on testing the theory of blood flow redistribution from the locomotor to the respiratory muscles during heavy exercise in healthy participants and in patients with COPD. What advances does it highlight? Studies presented and the direct experimental approach to measure muscle blood flow by indocyanine green dye detected by near infrared spectroscopy, show that exercise interferes with respiratory muscle blood flow especially in COPD, but even in healthy.
ABSTRACT
We have developed an indicator-dilution method to measure muscle blood flow at rest and during exercise using the light absorbing tracer indocyanine green dye (ICG) injected as an intravenous bolus, with surface optodes placed over muscles of interest to record the ICG signal by near-infrared spectroscopy. Here we review findings for both quadriceps and intercostal muscle blood flow (measured simultaneously) in trained cyclists and in patients with chronic obstructive pulmonary disease (COPD). During resting hyperpnoea in both athletes and patients, intercostal muscle blood flow increased with ventilation, correlating closely and linearly with the work of breathing, with no change in quadriceps flow. During graded exercise in athletes, intercostal flow at first increased, but then began to fall approaching peak effort. Unexpectedly, in COPD, intercostal muscle blood flow during exercise fell progressively from resting values, contrasting sharply with the response to resting hyperpnoea. During exercise at peak intensity, we found no quadriceps blood flow reduction in favour of the respiratory muscles in either athletes or patients. In COPD at peak exercise, when patients breathed 21% oxygen in helium or 100% oxygen, there was no redistribution of blood flow observed between legs and respiratory muscles in either direction. Evidence of decrease in leg blood flow and increase in respiratory muscle flow was found only when imposing expiratory flow limitation (EFL) during exercise in healthy individuals. However, because EFL caused substantial physiological derangement, lowering arterial oxygen saturation and raising end-tidal and heart rate, these results cannot be projected onto normal exercise.
Topics: Animals; Exercise; Humans; Intercostal Muscles; Locomotion; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Regional Blood Flow
PubMed: 32103536
DOI: 10.1113/EP088104 -
The Journal of Physiology Feb 2023Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate...
Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild-type male mice. Peak oxygen uptake ( ), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower (24.7 ± 4 vs. 42.5 ± 11.4 mL kg min , respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min , P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of , P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg , P = 0.020) than controls. No between-group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near-maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease. KEY POINTS: Physically active McArdle patients show an exceptional fat oxidation capacity. Maximal fat oxidation rate occurs near-maximal exercise capacity in these patients. McArdle patients' exercise tolerance might rely on maximal fat oxidation rate capacity. Hyperpnoea might cloud substrate oxidation measurements in some patients. An animal model revealed overall no higher molecular markers of lipid transport/metabolism.
Topics: Male; Female; Animals; Mice; Glycogen Storage Disease Type V; Glycogen; Oxidation-Reduction; Muscle, Skeletal; Exercise Test; Lipids; Oxygen Consumption; Adipose Tissue
PubMed: 36370371
DOI: 10.1113/JP283743 -
Nature Communications May 2023While respiratory adaptation to exercise is compulsory to cope with the increased metabolic demand, the neural signals at stake remain poorly identified. Using neural...
While respiratory adaptation to exercise is compulsory to cope with the increased metabolic demand, the neural signals at stake remain poorly identified. Using neural circuit tracing and activity interference strategies in mice, we uncover here two systems by which the central locomotor network can enable respiratory augmentation in relation to running activity. One originates in the mesencephalic locomotor region (MLR), a conserved locomotor controller. Through direct projections onto the neurons of the preBötzinger complex that generate the inspiratory rhythm, the MLR can trigger a moderate increase of respiratory frequency, prior to, or even in the absence of, locomotion. The other is the lumbar enlargement of the spinal cord containing the hindlimb motor circuits. When activated, and through projections onto the retrotrapezoid nucleus (RTN), it also potently upregulates breathing rate. On top of identifying critical underpinnings for respiratory hyperpnea, these data also expand the functional implication of cell types and pathways that are typically regarded as "locomotor" or "respiratory" related.
Topics: Mice; Animals; Up-Regulation; Neurons; Running; Spinal Cord; Mesencephalon; Locomotion
PubMed: 37217517
DOI: 10.1038/s41467-023-38583-6 -
Evidence Report/technology Assessment Jan 2010The objectives are: (1) To assess diagnostic test characteristics of six alternative index tests compared with the selected reference standard-a standardized exercise... (Review)
Review
OBJECTIVES
The objectives are: (1) To assess diagnostic test characteristics of six alternative index tests compared with the selected reference standard-a standardized exercise challenge test (ECT) in patients with suspected exercise-induced bronchoconstriction or asthma (EIB/EIA); (2) to determine the efficacy of a single prophylactic dose of four pharmacologic and one nonpharmacologic interventions vs. placebo to attenuate EIB/EIA in patients with diagnosed EIB/EIA; and (3) to determine if regular daily treatment with short-acting or long-acting beta-agonists (SABA or LABA) causes patients with EIA to develop tachyphylaxis when additional prophylactic doses are used pre-exercise.
DATA SOURCES
A systematic and comprehensive literature search was conducted in 14 electronic databases (Diagnosis) and the Cochrane Airways Register (Therapy).
REVIEW METHODS
Study selection, quality assessment, and data extraction were conducted independently by two reviewers. The primary outcome was the maximum percent fall in the post-exercise forced expiratory volume in 1 second (percent fall FEV1). The diagnostic threshold for a positive ECT was a percent fall FEV1 of 10% or more. Sensitivity (SN) and specificity (SP) were calculated. For therapy, mean differences (MD) in the percent fall FEV1 and 95% confidence intervals (CI) (random effects model) were calculated. A positive MD indicates the intervention works better than the control.
RESULTS
For the diagnostic reviews, 5,318 citations yielded 28 relevant studies; for the therapy reviews, 1,634 citations yielded 109 relevant RCTs. Diagnostic test results versus ECT: self-reported history (2 studies) SN=36-8 percent; SP=85-86 percent; sport specific challenges (5 studies) SN=0-100 percent, SP=0-100 percent; eucapnic voluntary hyperpnea (7 studies) SN=25-90 percent, SP=0-71 percent; free running asthma screening test (3 studies) SN=60-67 percent, SP=47-67 percent; mannitol (3 studies) SN=58-96 percent, SP=65-78 percent. All SN and SP calculations indicated substantial heterogeneity that could not be explained by sensitivity or subgroup analyses. Therapy results: SABA offered greater protection than mast cell stabilizers (MCS) (12 studies); MD=6.8 (95 percent CI: 4.5, 9.2) but combining them offered no additional benefit; SABA versus MCS plus SABA (5 studies) MD=1.3 (95 percent CI: -6.3, 8.9). Leukotriene receptor antagonists (LTRA), MCS, ipratropium bromide, and interval warmup routines provided statistically significant attenuation of EIA when compared with placebo; inhaled corticosteroids (ICS) and other warmup routines did not. Single-dose intervention versus placebo results are: LTRA (9 studies) MD=8.9 (95 percent CI: 6.9, 11.0); MCS (nedocromil sodium) (17 studies) MD=15.6 (95 percent CI: 13.2, 18.2); interval warmup versus no warmup (4 studies) MD=10.6 (95 percent CI: 6.5, 14.7); ICS (4 studies) MD=5.0 (95 percent CI: 0.0, 9.9); continuous low intensity warmup versus no warmup (3 studies) MD=12.6 (95 percent CI: -1.5, 26.7); continuous high intensity warmup versus no warmup (2 studies) MD=9.8 (95 percent CI: -6.4, 26.0). After daily LABA (salmeterol) use for 3 to 4 weeks (4 studies), the percent fall FEV1 following an ECT at 2 and 4 weeks was greater than at day 1 in the LABA arm indicating that tachyphylaxis to prophylactic LABA use occurred. Daily SABA use for 1 week (1 study) also indicated development of tachyphylaxis. However, both LABA and SABA continued to have an attenuating effect on EIA.
CONCLUSIONS
Given the small number of studies comparing EIB/EIA diagnostic tests, the heterogeneity of the study populations, and the varied study methodologies, there is no clear evidence that any of the index tests are a suitable replacement for a standardized ECT to diagnose EIB/EIA in the general population. All bronchodilator agents and most anti-inflammatory agents when used as pretreatment are somewhat effective in attenuating the percent fall FEV1 associated with EIA.
Topics: Adrenergic beta-Agonists; Asthma, Exercise-Induced; Azides; Humans; Male; Randomized Controlled Trials as Topic; Serotonin
PubMed: 20726625
DOI: No ID Found -
Swiss Medical Weekly Dec 2003Cheyne-Stokes Respiration (CSR) is a breathing pattern characterised by rhythmic oscillation of tidal volume with regularly recurring periods of hyperpnoea, hypopnoea... (Review)
Review
Cheyne-Stokes Respiration (CSR) is a breathing pattern characterised by rhythmic oscillation of tidal volume with regularly recurring periods of hyperpnoea, hypopnoea and apnoea. CSR is no longer solely regarded as a symptom of severe congestive heart failure (CHF), but has been recognised as an independent risk factor for worsening heart failure and reduced survival in patients with CHF. CSR is associated with frequent awakening that fragment sleep and with concomitant sympathetic activation both of which may worsen CHF. Cheyne-Stokes Respiration is very common in patients with severe CHF and its prevalence may have been underestimated in the past due to technical limitations that precluded respiratory monitoring outside sleep laboratories. Since treatment of CSR appears to be beneficial and safe, patients at risk should be promptly diagnosed and treated. Treatment of CSR has been demonstrated to improve left ventricular ejection fraction and potentially prolongs survival in patients with severe CHF. This article briefly summarises the current knowledge of the patho-physiology, prevalence and therapy of Cheyne-Stokes respiration.
Topics: Age Distribution; Cheyne-Stokes Respiration; Comorbidity; Female; Heart Failure; Humans; Male; Oximetry; Prevalence; Prognosis; Pulmonary Gas Exchange; Respiration, Artificial; Risk Assessment; Severity of Illness Index; Sex Distribution; Survival Analysis
PubMed: 14745666
DOI: 10.4414/smw.2003.10268 -
Frontiers in Physiology 2018Respiratory/inspiratory muscle training (RMT/IMT) has been proposed to improve the endurance performance of athletes in normoxia. In recent years, due to the increased... (Review)
Review
Respiratory/inspiratory muscle training (RMT/IMT) has been proposed to improve the endurance performance of athletes in normoxia. In recent years, due to the increased use of hypoxic training method among athletes, the RMT applicability has also been tested as a method to minimize adverse effects since hyperventilation may cause respiratory muscle fatigue during prolonged exercise in hypoxia. We performed a review in order to determine factors potentially affecting the change in endurance performance in hypoxia after RMT in healthy subjects. A comprehensive search was done in the electronic databases MEDLINE and Google Scholar including keywords: "RMT/IMT," and/or "endurance performance," and/or "altitude" and/or "hypoxia." Seven appropriate studies were found until April 2018. Analysis of the studies showed that two RMT methods were used in the protocols: respiratory muscle endurance (RME) (isocapnic hyperpnea: commonly 10-30', 3-5 d/week) in three of the seven studies, and respiratory muscle strength (RMS) (Powerbreathe device: commonly 2 × 30 reps at 50% MIP (maximal inspiratory pressure), 5-7 d/week) in the remaining four studies. The duration of the protocols ranged from 4 to 8 weeks, and it was found in synthesis that during exercise in hypoxia, RMT promoted (1) reduced respiratory muscle fatigue, (2) delayed respiratory muscle metaboreflex activation, (3) better maintenance of SaO and blood flow to locomotor muscles. In general, no increases of maximal oxygen uptake (VO) were described. Ventilatory function improvements (maximal inspiratory pressure) achieved by using RMT fostered the capacity to adapt to hypoxia and minimized the impact of respiratory stress during the acclimatization stage in comparison with placebo/sham. In conclusion, RMT was found to elicit general positive effects mainly on respiratory efficiency and breathing patterns, lower dyspneic perceptions and improved physical performance in conditions of hypoxia. Thus, this method is recommended to be used as a pre-exposure tool for strengthening respiratory muscles and minimizing the adverse effects caused by hypoxia related hyperventilation. Future studies will assess these effects in elite athletes.
PubMed: 30697170
DOI: 10.3389/fphys.2018.01970 -
Turkish Journal of Anaesthesiology and... Sep 2018Acute respiratory distress syndrome (ARDS) is not a failure of the neurological command of the ventilatory muscles or of the ventilatory muscles; it is an oxygenation... (Review)
Review
Acute respiratory distress syndrome (ARDS) is not a failure of the neurological command of the ventilatory muscles or of the ventilatory muscles; it is an oxygenation defect. As positive pressure ventilation impedes the cardiac function, paralysis under general anaesthesia and controlled mandatory ventilation should be restricted to the interval needed to control the acute cardio-ventilatory distress observed upon admission into the critical care unit (CCU; "salvage therapy" during "shock state"). Current management of early severe diffuse ARDS rests on a prolonged interval of controlled mechanical ventilation with low driving pressure, paralysis (48 h, too often overextended), early proning and positive end-expiratory pressure (PEEP). Therefore, the time interval between arrival to the CCU and switching to spontaneous ventilation (SV) is not focused on normalizing the different factors involved in the pathophysiology of ARDS: fever, low cardiac output, systemic acidosis, peripheral shutdown (local acidosis), supine position, hypocapnia (generated by hyperpnea and tachypnea), sympathetic activation, inflammation and agitation. Then, the extended period of controlled mechanical ventilation with paralysis under general anaesthesia leads to CCU-acquired pathology, including low cardiac output, myoneuropathy, emergence delirium and nosocomial infection. The stabilization of the acute cardio-ventilatory distress should primarily itemize the pathophysiological conditions: fever control, improved micro-circulation and normalized local acidosis, 'upright' position, minimized hypercapnia, sympathetic de-activation (normalized sympathetic activity toward baseline levels resulting in improved micro-circulation with alpha-2 agonists administered immediately following optimized circulation and endotracheal intubation), lowered inflammation and 'cooperative' sedation without respiratory depression evoked by alpha-2 agonists. Normalised metabolic, circulatory and ventilatory demands will allow one to single out the oxygenation defect managed with high PEEP (diffuse recruitable ARDS) under early spontaneous ventilation (airway pressure release ventilation+SV or low-pressure support). Assuming an improved overall status, PaO/FiO≥150-200 allows for extubation and continuous non-invasive ventilation. Such fast-tracking may avoid most of the CCU-acquired pathologies. Evidence-based demonstration is required.
PubMed: 30263856
DOI: 10.5152/TJAR.2018.01947 -
Frontiers in Medicine 2021Arousals from sleep during the hyperpneic phases of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure are thought to cause...
Arousals from sleep during the hyperpneic phases of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure are thought to cause ventilatory overshoot and a consequent longer apnea, thereby sustaining and exacerbating ventilatory instability. However, data supporting this model are lacking. We investigated the relationship between arousals, hyperpnea and post-hyperpnea apnea length during CSR-CSA. Breath-by-breath changes in ventilation associated with the occurrence of arousal were evaluated in 18 heart failure patients with CSR-CSA, apnea-hypopnea index ≥15/h and central apnea index ≥5/h. The change in apnea length associated with the presence of arousal during the previous hyperpnea was also evaluated. Potential confounding variables (chemical drive, sleep stage) were controlled for. Arousals were associated with a large increase in ventilation at the beginning of the hyperpnea (+76 ± 35%, < 0.0001), that rapidly declined during its crescendo phase. Around peak hyperpnea, the change in ventilation was -8 ± 26% ( = 0.14). The presence of arousal during the hyperpnea was associated with a median increase in the length of the subsequent apnea of +4.6% (Q1, Q2: -0.7%, 20.5%; range: -8.5%, 36.2%) ( = 0.021). The incidence of arousals occurring at the beginning of hyperpnea and mean ventilation in the region around its peak were independent predictors of the change in apnea length ( = 0.004 and = 0.015, respectively; R = 0.78). Arousals from sleep during CSR-CSA in heart failure patients are associated with a rapidly decreasing ventilatory overshoot at the beginning of the hyperpnea, followed by a tendency toward a slight ventilatory undershoot around its peak. On average, arousals are also associated with a modest increase in post-hyperpnea apnea length; however, large increases in apnea length (>20%) occur in about a quarter of the patients.
PubMed: 34977056
DOI: 10.3389/fmed.2021.742458 -
Cureus May 2022Joubert syndrome (JS) is a rare autosomal recessive neurodevelopmental disorder with characteristic clinical presentation of hyperpnea-apnea spells, hypotonia,...
Joubert syndrome (JS) is a rare autosomal recessive neurodevelopmental disorder with characteristic clinical presentation of hyperpnea-apnea spells, hypotonia, dysmorphic facies, and nystagmus and imaging features of molar tooth sign and cerebellar vermian hypoplasia-dysplasia. Early diagnosis is needed for timely management and favorable outcome. We present a case of neonatal JS with renal involvement presenting with respiratory distress and highlight the characteristic clinical and imaging findings. On examination, the baby had low set ears, a large protruding tongue, hypertelorism, and a depressed nasal bridge. Ultrasonography (USG) abdomen showed echogenic kidneys with cortical and medullary cysts. Magnetic Resonance Imaging (MRI) brain showed classical molar tooth sign, vermian hypoplasia-dysplasia, and thinning of the corpus callosum.
PubMed: 35698700
DOI: 10.7759/cureus.24907 -
Respiratory Physiology & Neurobiology Nov 2013Control of ventilation dictates various breathing patterns. The respiratory control system consists of a central pattern generator and several feedback mechanisms that... (Review)
Review
Control of ventilation dictates various breathing patterns. The respiratory control system consists of a central pattern generator and several feedback mechanisms that act to maintain ventilation at optimal levels. The concept of loop gain has been employed to describe its stability and variability. Synthesizing all interactions under a general model that could account for every behavior has been challenging. Recent insight into the importance of these feedback systems may unveil therapeutic strategies for common ventilatory disturbances. In this review we will address the major mechanisms that have been proposed as mediators of some of the breathing patterns in health and disease that have raised controversies and discussion on ventilatory control over the years.
Topics: Carbon Dioxide; Chemoreceptor Cells; Cheyne-Stokes Respiration; Humans; Hypercapnia; Oxygen; Respiratory Mechanics; Sleep Apnea Syndromes
PubMed: 23681082
DOI: 10.1016/j.resp.2013.04.020