Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge

2017 ◽  
Vol 122 (3) ◽  
pp. 503-510 ◽  
Author(s):  
S. Dubsky ◽  
G. R. Zosky ◽  
K. Perks ◽  
C. R. Samarage ◽  
Y. Henon ◽  
...  
Keyword(s):  
Dynamic Imaging ◽  
Lung Mechanics ◽  
Imaging Method ◽  
Response Distribution ◽  
Interconnected System ◽  
Airway Response ◽  
Airway Responses ◽  
And Control

Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house dust-mite-sensitized and control mice during intravenous methacholine (MCh) infusion. Airway diameters were measured pre- and post-MCh challenge, and the results compared demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo. NEW & NOTEWORTHY Information on the distribution of airway diameters during bronchoconstriction in situ is critical for understanding the regional response of the lungs. We have developed an imaging method to quantify and compare the size of hundreds of airways in vivo during bronchoconstriction in mice. The results demonstrate large heterogeneity with both constriction and paradoxical dilation of airways, confirming the importance of considering the lung as an interconnected system rather than a collection of independent units.

Bronchoprotective and bronchodilatory effects of deep inspiration in rabbits subjected to bronchial challenge

2001 ◽  
Vol 91 (6) ◽  
pp. 2511-2516 ◽  
Author(s):  
S. J. Gunst ◽  
X. Shen ◽  
R. Ramchandani ◽  
R. S. Tepper
Keyword(s):  
Human Subjects ◽  
Inhibitory Effect ◽  
Airway Responsiveness ◽  
Deep Inspiration ◽  
Contractile Apparatus ◽  
Airway Reactivity ◽  
Airway Response ◽  
Normal Human ◽  
Airway Responses

The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.

Paradoxical conducting airway responses and heterogeneous regional ventilation after histamine inhalation in rabbit studied by synchrotron radiation CT

2009 ◽  
Vol 106 (6) ◽  
pp. 1949-1958 ◽  
Author(s):  
Sam Bayat ◽  
Liisa Porra ◽  
Heikki Suhonen ◽  
Pekka Suortti ◽  
Anssi R. A. Sovijärvi
Keyword(s):  
Synchrotron Radiation ◽  
Bronchial Tree ◽  
Regional Ventilation ◽  
Conducting Airway ◽  
Ventilation Heterogeneity ◽  
Airway Response ◽  
Poor Ventilation ◽  
Airway Responses ◽  
Conducting Airways

We studied both central conducting airway response and changes in the distribution of regional ventilation induced by inhaled histamine in healthy anesthetized and mechanically ventilated rabbit using a novel xenon-enhanced synchrotron radiation computed tomography (CT) imaging technique, K-edge subtraction imaging (KES). Images of specific ventilation were obtained using serial KES during xenon washin, in three axial lung slices, at baseline and twice after inhalation of histamine aerosol (50 or 125 mg/ml) in two groups of animals ( n = 6 each). Histamine inhalation caused large clustered areas of poor ventilation, characterized by a drop in average specific ventilation (sV̇m), but an increase in sV̇m in the remaining lung zones indicating ventilation redistribution. Ventilation heterogeneity, estimated as coefficient of variation (CV) of sV̇m significantly increased following histamine inhalation. The area of ventilation defects and CV were significantly larger with the higher histamine dose. In conducting airways, histamine inhalation caused a heterogeneous airway response combining narrowing and dilatation in individual airways of different generations, with the probability for constriction increasing peripherally. This finding provides further in vivo evidence that airway reactivity in response to inhaled histamine is complex and that airway response may vary substantially with location within the bronchial tree.

The Development of an In Situ Assay for bFGF Release

1993 ◽  
Vol 331 ◽  
Author(s):  
S. K. Hobbs ◽  
L. M. Periolat ◽  
L. G. Cima ◽  
M. Nugent ◽  
M. Leunig ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Dorsal Skinfold Chamber ◽  
Control Growth ◽  
Vessel Growth ◽  
And Control ◽  
Tissue Reactivity ◽  
In Situ Assay

AbstractThere is a need for an in situ assay to quantify tissue reactivity to sustained release of bFGF to better understand and control growth factor-induced angiogenesis. To this end we have adapted the alginate/heparin-sepharose release system for use in the mouse dorsal skinfold chamber. A mathematical model was used to predict the time dependence of bFGF release as a function of bFGF loading, heparin concentration, and device geometry. The model predictions agreed well with previously reported in vitro data. In vivo studies to correlate blood vessel growth as a function of release rate are in progress.

scholarly journals Seeing the Light: The Use of Zebrafish for Optogenetic Studies of the Heart

2021 ◽  
Vol 12 ◽  
Author(s):  
Jonathan S. Baillie ◽  
Matthew R. Stoyek ◽  
T. Alexander Quinn
Keyword(s):  
Experimental Model ◽  
Optical Measurement ◽  
Cardiac Activity ◽  
Experimental Models ◽  
Spatially Resolved ◽  
And Control ◽  
Spatiotemporal Control ◽  
Insight Into

Optogenetics, involving the optical measurement and manipulation of cellular activity with genetically encoded light-sensitive proteins (“reporters” and “actuators”), is a powerful experimental technique for probing (patho-)physiological function. Originally developed as a tool for neuroscience, it has now been utilized in cardiac research for over a decade, providing novel insight into the electrophysiology of the healthy and diseased heart. Among the pioneering cardiac applications of optogenetic actuators were studies in zebrafish, which first demonstrated their use for precise spatiotemporal control of cardiac activity. Zebrafish were also adopted early as an experimental model for the use of optogenetic reporters, including genetically encoded voltage- and calcium-sensitive indicators. Beyond optogenetic studies, zebrafish are becoming an increasingly important tool for cardiac research, as they combine many of the advantages of integrative and reduced experimental models. The zebrafish has striking genetic and functional cardiac similarities to that of mammals, its genome is fully sequenced and can be modified using standard techniques, it has been used to recapitulate a variety of cardiac diseases, and it allows for high-throughput investigations. For optogenetic studies, zebrafish provide additional advantages, as the whole zebrafish heart can be visualized and interrogated in vivo in the transparent, externally developing embryo, and the relatively small adult heart allows for in situ cell-specific observation and control not possible in mammals. With the advent of increasingly sophisticated fluorescence imaging approaches and methods for spatially-resolved light stimulation in the heart, the zebrafish represents an experimental model with unrealized potential for cardiac optogenetic studies. In this review we summarize the use of zebrafish for optogenetic investigations in the heart, highlighting their specific advantages and limitations, and their potential for future cardiac research.

scholarly journals Dynamic spatiotemporal coordination of neural stem cell fate decisions through local feedback in the adult vertebrate brain

2020 ◽  
Author(s):  
Nicolas Dray ◽  
Laure Mancini ◽  
Udi Binshtok ◽  
Felix Cheysson ◽  
Willy Supatto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Life Time ◽  
Population Level ◽  
Dynamic Imaging ◽  
Cell Fate Decisions ◽  
Vertebrate Brain ◽  
And Control

SUMMARYNeural stem cell (NSC) populations persist in the adult vertebrate brain over a life time, and their homeostasis is controlled at the population level. The nature and properties of these coordination mechanisms remain unknown. Here we combine dynamic imaging of entire NSC populations in their in vivo niche over weeks, pharmacological manipulations, mathematical modeling and spatial statistics, and demonstrate that NSCs use spatiotemporally resolved local feedbacks to coordinate their decision to divide. These involve a Notch-mediated inhibition from transient neural progenitors, and a dispersion effect from dividing NSCs themselves, exerted with a delay of 9-12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that they are linked by lineage progression and control the spatiotemporal distribution of output neurons. These results highlight how local and temporally delayed interactions occurring between brain germinal cells generate self-propagating dynamics that maintain NSC population homeostasis with specific spatiotemporal correlations.

Augmented bidirectional HCO3 transport by rat distal tubules in chronic alkalosis

1991 ◽  
Vol 261 (2) ◽  
pp. F308-F317 ◽  
Author(s):  
D. E. Wesson ◽  
G. M. Dolson
Keyword(s):  
Metabolic Alkalosis ◽  
Distal Tubule ◽  
Free Flow ◽  
Proton Secretion ◽  
Nephron Segment ◽  
Distal Tubules ◽  
And Control

Free-flow micropuncture studies show both augmented net HCO3 reabsorption in the distal tubule of rats with chronic metabolic alkalosis and higher HCO3 delivery to this nephron segment. The present studies in rats used in vivo microperfusion of surface distal tubules to investigate whether the augmented net reabsorption 1) was due to decreased HCO3 secretion and/or to increased proton secretion or 2) depended on the higher HCO3 delivery to the distal tubule. Artificial perfusates were designed to simulate in situ deliveries of HCO3 to the distal tubules of both alkalotic and control animals and to represent extremes of in situ Cl deliveries. Rather than being decreased, both measured and calculated HCO3 secretion were higher in the alkalotic animals for each perfusate used. Similarly, calculated proton secretion (difference between net HCO3 reabsorption and calculated HCO3 secretion) was higher for the alkalotic animals using each HCO3-containing perfusate. Augmented net HCO3 reabsorption by alkalotic animals was more clearly demonstrated using higher HCO3 deliveries and Cl-free perfusates. These studies demonstrate that both the reabsorptive and secretory components of net HCO3 transport are increased in the distal tubule of animals with chronic metabolic alkalosis.

scholarly journals An advanced in situ imaging method using heavy metal-doped hollow tubes to evaluate the biokinetics of carbon nanotubes in vivo

2015 ◽  
Vol 7 (7) ◽  
pp. e203-e203 ◽  
Author(s):  
Shinsuke Kobayashi ◽  
Shuji Tsuruoka ◽  
Yuki Usui ◽  
Hisao Haniu ◽  
Kaoru Aoki ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Heavy Metal ◽  
Imaging Method ◽  
Metal Doped ◽  
In Situ Imaging

scholarly journals 221.Effects of exogenous gonadotrophin stimulation on ovarian tissue grafts in the mouse

2004 ◽  
Vol 16 (9) ◽  
pp. 221
Author(s):  
H. Yang ◽  
S. Cox ◽  
J. Shaw ◽  
G. Jenkin
Keyword(s):  
Subcutaneous Tissue ◽  
Ovarian Tissue ◽  
Control Group ◽  
Control Groups ◽  
Hybrid Strain ◽  
Tissue Grafts ◽  
And Control

Ovarian tissue grafts commonly contain only limited numbers of follicles. The functional life span and ability to retrieve as many mature oocytes as possible from ovarian grafts is important when grafting is used to restore fertility. This study aimed to determine whether ovarian grafts responded to exogenous hormones in a similar manner to that of in situ ovaries. Ovaries of C57BlxCBA F1 mice were cut in half and grafted to one of three different graft sites in females of the same F1 line; bursal capsule (BC, n = 12), kidney capsule (KC, n = 6), subcutaneous tissue (SC, n = 24). Three weeks after grafting, half of the graft recipients in each group were treated with 5IU PMSG followed by 5IU hCG 48 hours later. Oocytes were collected directly from the grafted ovaries 10 hours after the hCG injection and fertilized in vitro. Oocytes from the ovaries of superovulated normal mice (n = 4) of the same hybrid strain were used as controls. Two-cell embryos were transferred to pseudopregnant recipients and collected at day 15 of gestation or the animals were allowed to go to term. Mature fertilisable MII oocytes were retrieved from stimulated grafts from all graft sites, however, the number (BC 9, KC 5, SC 2 oocytes per ovary) and proportion of two-cell embryos in each grafted group (BC 52%, KC 32%, SC 32%) was significantly (P < 0.05) lower than in the in vivo matured control (16 oocytes, 85% two-cell). The fetal and placental weights of fetuses produced from graft-derived oocytes were not significantly different to the control group. Phenotypically normal pups were born in each of the graft and control groups. In conclusion, ovarian grafts treated with exogenous gonadotrophins produce significantly fewer mature oocytes and two cell embryos compared to in situ ovaries. Work supported by ARC and NIH RFA.

Apparatus to Determine the Macroscopic and Microscopic Biaxial Swelling Response of the Annulus Fibrosus

2002 ◽  
Author(s):  
Paul Hulme ◽  
Sabina Bruehlmann ◽  
Neil A. Duncan
Keyword(s):  
Annulus Fibrosus ◽  
Biaxial Loading ◽  
Mechanical Response ◽  
Swelling Behaviour ◽  
Vertebral Bodies ◽  
And Control ◽  
Bearing Structure ◽  
Outer Annulus Fibrosus

The intervertebral disc (IVD) is a “hydrostatic load-bearing structure” [1], found between the vertebral bodies of the spine. The IVD is composed of the inner and outer annulus fibrosus and a gelatinous center, the nucleus pulposus. Fluid is the largest component of the IVD. Swelling affects the macroscopic mechanical response of the tissue, as well as the microscopic nutrient and solute transport to the cells of the IVD. Previous studies describing the macroscopic swelling behaviour of the annulus fibrosus have been uniaxial in nature [2,3]. However, the behaviour of the annulus is markedly affected by its geometry [3]. By examining a biaxial section of annulus fibrosus with a portion of the bone attachment present, the structure of the annular test section will be maintained and by inference so should its function [4]. Therefore, the objective of this study was to develop an apparatus to investigate simultaneously both the macroscopic and microscopic swelling behaviour of the annulus fibrosus subjected to realistic biaxial loading. The biaxial loading device should maintain the annulus fibrosus in vivo geometry and environment, monitor stress and control tissue strain, while positioning the tissue in a manner that allows for in situ visualization of the cells.

scholarly journals Ecto-5′-nucleotidase is not required for ischemic preconditioning in rabbit myocardium in situ

1998 ◽  
Vol 275 (4) ◽  
pp. H1329-H1337 ◽  
Author(s):  
Takayuki Miki ◽  
Tetsuji Miura ◽  
Rolf Bünger ◽  
Katsuo Suzuki ◽  
Jun Sakamoto ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Cardiovascular Responses ◽  
Adenosine Diphosphate ◽  
Rabbit Heart ◽  
Area At Risk ◽  
Inotropic Effects ◽  
And Control

This study tested the hypothesis that cardiac ecto-5′-nucleotidase (ecto-5′-NT) activity during ischemic preconditioning (PC) contributes to augmented tolerance against ischemia, thereby reducing infarct size in the rabbit heart in situ. The effects of α,β-methylene-adenosine diphosphate (AOPCP), a selective inhibitor of ecto-5′-NT, on cardiovascular responses to AMP were measured to establish in vivo activities of the enzyme and its inhibitor. Left atrial infusion of AOPCP (0.75 mg ⋅ kg−1⋅ min−1) raised AOPCP plasma levels to 138 μM; under these conditions negative chronotropic and inotropic effects of AMP were blocked, demonstrating essentially full inhibition of ecto-5′-NT in the heart in situ. This AOPCP-blocked heart in situ model was used to examine the proposed contribution of ecto-5′-NT in ischemic PC. Myocardial infarction caused by 30-min ischemia was followed by 3-h reperfusion. Infarct size (IS) was measured and expressed as a percentage of the size of the area at risk (%IS/AR). In untreated controls, %IS/AR was 38.1 ± 3.8%; PC (5-min ischemia, 5-min reperfusion) markedly reduced %IS/AR to 10.0 ± 2.0%. Essentially identical IS reductions by PC were observed in AOPCP-blocked animals (%IS/AR = 13.8 ± 2.2 and 13.3 ± 1.8% in rabbits receiving AOPCP at 0.75 and 1.50 mg ⋅ kg−1⋅ min−1, respectively); here plasma AOPCP levels were established before and during PC but not during the subsequent prolonged ischemia. As expected, AOPCP also did not affect %IS/AR in non-PC controls (%IS/AR = 35.5 ± 3.7%). In contrast but as predicted, adenosine-receptor blockade by 8-phenyltheophylline (10 mg/kg iv) substantially attenuated IS reduction by PC in both AOPCP-blocked and control hearts (%IS/AR = 25.2 ± 4.3 and 21.8 ± 2.2%, respectively; P < 0.05 vs. PC alone). The results demonstrate that cardiac ecto-5′-NT is not required for ischemic PC against infarction in the rabbit.

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