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Experimental Lung Research Feb 2022Signal disruptions in small animals during the realization of the Forced Oscillation Technique are a well-known cause of data loss as it leads to non-reliable...
Signal disruptions in small animals during the realization of the Forced Oscillation Technique are a well-known cause of data loss as it leads to non-reliable estimations of the respiratory impedance. In this work, we assessed the effects of removing the disrupted epoch when a 3-seconds input signal composed of one and a half 2-seconds full cycle is used. We tested our hypothesis in 25 SAMR1 mice under different levels of bronchoconstriction due to methacholine administration by iv bolus injections in different doses (15 animals) and by iv continuous infusion in different infusion rates (10 animals). Signal disruptions were computationally simulated as sharp drops in the pressure signal within a short timescale, and signal processing was performed using own developed algorithms. We found that the model goodness of fit worsens when averaging techniques to estimate the input respiratory impedance are not used. However, no statistically significant differences were observed in the comparison between Constant Phase Model parameters of the full 3-s signal and the 2-s non disrupted epoch in all doses or infusion rates for both methacholine delivery strategies. The proposed technique presents reliable outcomes that can reduce animal use in Forced Oscillation Technique realization.
Topics: Airway Resistance; Animals; Bronchoconstriction; Methacholine Chloride; Mice; Respiratory Function Tests; Respiratory Mechanics
PubMed: 34935573
DOI: 10.1080/01902148.2021.2019355 -
Pulmonary Pharmacology & Therapeutics Feb 2015Mice with Plp1 gene duplication model the most common form of Pelizaeus-Merzbacher disease (PMD), a CNS disease in which patients may suffer respiratory complications....
Mice with Plp1 gene duplication model the most common form of Pelizaeus-Merzbacher disease (PMD), a CNS disease in which patients may suffer respiratory complications. We hypothesized that affected mice would lack airway responsiveness compared to wild-type and carrier mice during methacholine challenge. Wild-type (n = 10), carrier female (n = 6) and affected male (n = 8) mice were anesthetized-paralyzed, tracheostomized and ventilated. Respiratory mechanics were recorded at baseline and during escalating doses of nebulized methacholine followed by albuterol. Lung resistance (RL) was the primary endpoint. Lung tissues were assayed for inflammatory and histological differences. At baseline, phase angles were higher in carrier and affected mice than wild-type. Dose-response RL curves in affected and carrier mice indicated a lack of methacholine response. Albuterol reduced RL in wild-type and carrier, but not affected mice. Affected mice exhibited lower interleukin (IL)-6 tissue levels and alveolar inflammatory infiltrates. Affected and carrier mice, compared to wild-type, lacked airway reactivity during methacholine challenge, but only affected mice exhibited decreased lung tissue levels of IL-6 and inflammation.
Topics: Albuterol; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gene Duplication; Interleukin-6; Male; Methacholine Chloride; Mice; Myelin Proteolipid Protein; Pelizaeus-Merzbacher Disease; Pneumonia; Respiratory Mechanics
PubMed: 25445931
DOI: 10.1016/j.pupt.2014.10.004 -
American Journal of Respiratory and... Jan 2001
Topics: Bronchoconstrictor Agents; Exercise Test; Humans; Methacholine Chloride; Practice Guidelines as Topic
PubMed: 11208661
DOI: 10.1164/ajrccm.163.1.16310b -
Toxicology and Applied Pharmacology Sep 2022Workers involved in oil exploration and production in the upstream petroleum industry are exposed to crude oil vapor (COV). COV levels in the proximity of workers during...
Workers involved in oil exploration and production in the upstream petroleum industry are exposed to crude oil vapor (COV). COV levels in the proximity of workers during production tank gauging and opening of thief hatches can exceed regulatory standards, and several deaths have occurred after opening thief hatches. There is a paucity of information regarding the effects of COV inhalation in the lung. To address these knowledge gaps, the present hazard identification study was undertaken to investigate the effects of an acute, single inhalation exposure (6 h) or a 28 d sub-chronic exposure (6 h/d × 4 d/wk × 4 wks) to COV (300 ppm; Macondo well surrogate oil) on ventilatory and non-ventilatory functions of the lung in a rat model 1 and 28 d after acute exposure, and 1, 28 and 90 d following sub-chronic exposure. Basal airway resistance was increased 90 d post-sub-chronic exposure, but reactivity to methacholine (MCh) was unaffected. In the isolated, perfused trachea preparation the inhibitory effect of the airway epithelium on reactivity to MCh was increased at 90 d post-exposure. Efferent cholinergic nerve activity regulating airway smooth muscle was unaffected by COV exposure. Acute exposure did not affect basal airway epithelial ion transport, but 28 d after sub-chronic exposure alterations in active (Na and Cl¯) and passive ion transport occurred. COV treatment did not affect lung vascular permeability. The findings indicate that acute and sub-chronic COV inhalation does not appreciably affect ventilatory properties of the rat, but transient changes in airway epithelium occur.
Topics: Airway Resistance; Animals; Inhalation Exposure; Lung; Methacholine Chloride; Petroleum; Rats
PubMed: 35798068
DOI: 10.1016/j.taap.2022.116154 -
Journal of Applied Physiology... Jul 2022Mice are a valuable model for elegant studies of complex, system-dependent diseases, including pulmonary diseases. Current tools to assess lung function in mice are...
Mice are a valuable model for elegant studies of complex, system-dependent diseases, including pulmonary diseases. Current tools to assess lung function in mice are either terminal or lack accuracy. We set out to develop a low-cost, accurate, head-out variable-pressure plethysmography system to allow for repeated, nonterminal measurements of lung function in mice. Current head-out plethysmography systems are limited by air leaks that prevent accurate measures of volume and flow. We designed an inflatable cuff that encompasses the mouse's neck preventing air leak. We wrote corresponding software to collect and analyze the data, remove movement artifacts, and automatically calibrate each dataset. This software calculates volume, inspiratory/expiratory time, breaths per minute, mid-expiratory flow, and end-inspiratory pause. To validate the use, we established that our plethysmography system accurately measured tidal breathing, the bronchoconstrictive response to methacholine, sex- and age-associated changes in breathing, and breathing changes associated with house dust mite sensitization. Our estimates of volume, flow, and timing of breaths are in line with published estimates, we observed dose-dependent decreases in volume and flow in response to methacholine ( < 0.05), increased lung volume, and decreased breathing rate with aging ( < 0.05), and that house dust mite sensitization decreased volume and flow ( < 0.05) while exacerbating the methacholine-induced increase in inspiratory time ( < 0.05). We describe an accurate, sensitive, low-cost, head-out plethysmography system that allows for longitudinal studies of pulmonary disease in mice. We describe a low-cost, variable-pressure head-out plethysmography system that can be used to assess lung function in mice. A balloon cuff is inflated around the mouse's neck to prevent air leak, allowing for accurate measurements of lung volume and air flow. Custom software facilitates system calibration, removes movement artifacts, and eases data analysis. The system was validated by measuring tidal breathing, responses to methacholine, and changes associated with house dust mite sensitization, sex, and aging.
Topics: Animals; Bronchoconstriction; Lung; Lung Volume Measurements; Methacholine Chloride; Mice; Plethysmography; Tidal Volume
PubMed: 35608203
DOI: 10.1152/japplphysiol.00835.2021 -
Journal of Investigational Allergology... 2015Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic... (Review)
Review
Nasal hyperreactivity is the abnormal reaction of nasal tissue to a stimulus that is innocuous to most people. This response is caused by dysregulation of the autonomic nervous system at various levels of the nasal autonomic reflex arc. Various stimuli (methacholine, histamine, adenosine 5'-monophosphate, cold air, mannitol, rapsaicin, phentolamine, and distilled water) have been used in an attempt to find the test that most reliably differentiates between healthy individuals and patients and also between different types of rhinitis. Despite the small number of publications available, in the present review, we provide an update on current nonspecific nasal provocation techniques. The studies published to date are not comparable: the stimuli applied act through different mechanisms and are used to assess different pathways, and the methodologies differ in terms of selection of participants, concentrations used, and assessment of response (criteria for positivity). Given the limited use of nonspecific nasal provocation tests in routine clinical practice, we believe that more studies are warranted to address the research issues we present at the end of the present review, for example, the need to standardize the methodology for each test or even the clinical benefits of knowing whether or not a patient has nasal hyperreactivity.
Topics: Histamine; Humans; Methacholine Chloride; Nasal Provocation Tests; Rhinitis, Allergic
PubMed: 26817136
DOI: No ID Found -
Experimental Biology and Medicine... Apr 2020Respiratory mechanics studies are associated with fundamental research and translational studies; the present work thus investigates this particular matter. Our current...
Respiratory mechanics studies are associated with fundamental research and translational studies; the present work thus investigates this particular matter. Our current research describes differences and similarities between two different ways of administrating a very prevalent bronchoconstrictor (methacholine) in an aging process scenario. The core issue of our work is related with troubles we find with the bolus protocol and the application of the mathematical model used to assess the respiratory mechanics. Our findings reveal the continuous infusion as an alternative to these problems and we hope to provide the proper foundations to a more reliable assessment in the respiratory field.
Topics: Animals; Bronchoconstrictor Agents; Infusions, Intravenous; Methacholine Chloride; Mice; Models, Theoretical; Respiratory Mechanics; Respiratory System
PubMed: 32183551
DOI: 10.1177/1535370220912393 -
Lung 2001Forty-eight patients suffering from intermittent bronchial asthma underwent methacholine challenge test. Response was stronger in 29 patients and less pronounced in 19.... (Comparative Study)
Comparative Study
Forty-eight patients suffering from intermittent bronchial asthma underwent methacholine challenge test. Response was stronger in 29 patients and less pronounced in 19. The two groups had the same characteristics except for the cumulative methacholine dose which was lower in severe hyperresponsiveness. The patients were studied both in the phase of induced bronchospasm and in the subsequent phase of spontaneous recovery. Dose-response curves to methacholine were analyzed as FEV1% decline/methacholine dose for the induction phase of bronchoconstriction and as FEV1% increase*methacholine dose/time after PD20FEV1 for the recovery phase. The phase of induced bronchospasm as well as spontaneous recovery had a linear pattern in severe hyperresponsiveness; in patients with moderate response, induced bronchoconstriction had a curvilinear pattern whereas spontaneous recovery had a linear pattern. This latter group had to break down an amount of methacholine that was fivefold greater than the former, therefore the mechanism of local homeostasis recovery may be more efficient in moderate hyperresponsiveness. However, in both groups recovery after the bronchospasm was not complete after 60 min (p < 0.01 versus baseline). Furthermore, recovery was faster in the first 15 min than in the remaining time. In conclusion the behavior of methacholine-induced bronchospasm and its spontaneous recovery in both severe and moderate hyperresponsiveness seem to be different although several and not well-established mechanisms may be responsible for this phenomenon.
Topics: Administration, Inhalation; Adult; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Dose-Response Relationship, Drug; Forced Expiratory Volume; Humans; Methacholine Chloride; Recovery of Function; Severity of Illness Index; Time Factors
PubMed: 11891604
DOI: 10.1007/s004080000056 -
Anesthesiology Sep 1997Sevoflurane is a new volatile anesthetic agent that may be a useful alternative to halothane for anesthesia in children. However, there is insufficient information about... (Comparative Study)
Comparative Study
BACKGROUND
Sevoflurane is a new volatile anesthetic agent that may be a useful alternative to halothane for anesthesia in children. However, there is insufficient information about its effects on respiratory mechanics, particularly in the presence of constrictor stimuli.
METHODS
Eighteen piglets had anesthesia induced and maintained with either pentobarbital (control: n = 8), 1 minimum alveolar concentration (MAC) sevoflurane (sevo: n = 5), or 1 MAC halothane (halo: n = 5). Pressure, flow, and volume were measured at the airway opening and used to calculate lung compliance (C(L)) and resistance (R(L)). Resistance was partitioned into airway (Raw) and parenchymal (Vti) components using alveolar pressure. Methacholine was infused intravenously in a dose sufficient (15 microg x kg(-1) x h(-1)) to approximately double R(L).
RESULTS
The increase in R(L) seen in the control group was almost entirely due to an increase in Vti. Sevoflurane and halothane prevented the increase in R(L) and Vti (both P < 0.02) and the decrease in C(L) (both P < 0.02).
CONCLUSIONS
Sevoflurane and halothane can prevent methacholine-induced changes in lung function.
Topics: Airway Resistance; Anesthetics, Inhalation; Animals; Ethers; Halothane; Lung Compliance; Methacholine Chloride; Methyl Ethers; Respiration; Sevoflurane; Swine
PubMed: 9316964
DOI: 10.1097/00000542-199709000-00019 -
Anesthesiology Feb 2001The protective properties of common volatile agents against generalized lung constriction have previously been addressed only via estimations of parameters that combine...
BACKGROUND
The protective properties of common volatile agents against generalized lung constriction have previously been addressed only via estimations of parameters that combine airway and tissue mechanics. Their effectiveness in preventing airway constriction have not been compared systematically. Therefore, the authors investigated the abilities of halothane, isoflurane, sevoflurane, and desflurane to provide protection against airway constriction induced by methacholine.
METHODS
Low-frequency pulmonary impedance data were collected in open-chest rats under baseline conditions and during three consecutive intravenous infusions of methacholine (32 microg x kg(-1) x min(-1)) while the animals were anesthetized with intravenous pentobarbital (control group). Methacholine challenges were performed in four other groups of rats, first during intravenous anesthesia and then repeated during the inhalation of halothane, isoflurane, sevoflurane, or desflurane at concentrations of 1 and 2 minimum alveolar concentration (MAC). Airway resistance and inertance, parenchymal damping, and elastance were estimated from the impedance data by model fitting.
RESULTS
The methacholine-induced increases in airway resistance during intravenous pentobarbital anesthesia (204 +/- 53%) were markedly and significantly (P < 0.005) reduced by 1-MAC doses of halothane (80 +/- 48%), isoflurane (112 +/- 59%), sevoflurane (68 +/- 34%), and desflurane (96 +/- 34%), with no significant difference between the gases applied. Increasing the concentration to 2 MAC did not lead to any significant further protection against the increase in airway resistance.
CONCLUSIONS
These data demonstrate that isoflurane, sevoflurane, and desflurane are as effective as the widely accepted halothane in protecting against methacholine-induced airway constriction.
Topics: Anesthetics, Inhalation; Animals; Bronchoconstriction; Desflurane; Dose-Response Relationship, Drug; Isoflurane; Male; Methacholine Chloride; Methyl Ethers; Rats; Rats, Sprague-Dawley; Sevoflurane
PubMed: 11176101
DOI: 10.1097/00000542-200102000-00026