Assessment of Respiratory Physiology of C57BL/6 Mice following Bleomycin Administration Using Barometric Plethysmography

Milton, Phillipa Louise; Dickinson, Hayley; Jenkin, Graham; Lim, Rebecca

doi:10.1159/000330586

Cited by 39 publications

(24 citation statements)

References 104 publications

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“…5). Similar observations were made in bleomycin-challenged mice by use of barometric plethysmography (33). A tentative explanation of these results might be that the increase in lung volume at expiration, leading initially to a loss of tidal volume, could be compensated over time by an increase of lung volume at inspiration.…”

Section: Discussionsupporting

confidence: 72%

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Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Egger

Gérard

Vidotto

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230. Am J Physiol Lung Cell Mol Physiol 306: L1064 -L1077, 2014. First published April 11, 2014 doi:10.1152/ajplung.00027.2014.-Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRIassessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis.

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Section: Discussionsupporting

confidence: 72%

“…Indeed, increased lung elastance as well as decreased compliance (the reciprocal of elastance) have been shown in humans (19,26,38) and in small rodent pulmonary fibrosis models (1,7,12,15,30,53,57,58). Moreover, changes in tidal volume and breathing cycle times have been shown in a mouse fibrosis model (33).…”

mentioning

confidence: 99%

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Egger

Gérard

Vidotto

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This significantly reduces stress and allows individual animals to be assessed multiple times, a useful feature for time course studies (J. H. Bates & Irvin, 2003; Glaab et al, 2007; Milton, Dickinson, Jenkin, & Lim, 2012). In non-invasive plethysmography, Penh is a dimensionless parameter that has been viewed as a measure of bronchoconstriction and airway resistance, though several studies claim Penh is an unreliable measure of respiratory mechanics (Adler, Cieslewicz, & Irvin, 2004; Hoymann, 2007).…”

Section: Discussionmentioning

confidence: 99%

Impaired respiratory function and heightened pulmonary inflammation in episodic binge ethanol intoxication and burn injury

Shults

Curtis

Chen

et al. 2015

Alcohol

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Clinical data indicate that cutaneous burn injuries covering greater than ten percent total body surface area are associated with significant morbidity and mortality, where pulmonary complications, including acute respiratory distress syndrome (ARDS), contribute to nearly half of all patient deaths. Approximately 50% of burn patients are intoxicated at the time of hospital admission, which increases days on ventilators by three-fold, and doubles length of hospital admittance, compared to non-intoxicated burn patients. The most common drinking pattern in the United States is binge drinking, where one rapidly consumes alcoholic beverages (4 for women, 5 for men) in 2 hours and an estimated 38 million Americans binge drink, often several times per month. Experimental data demonstrate a single binge ethanol exposure prior to scald injury, impairs innate and adaptive immune responses, thereby enhancing infection susceptibility and amplifying pulmonary inflammation, neutrophil infiltration, and edema, and is associated with increased mortality. Since these characteristics are similar to those observed in ARDS burn patients, our study objective was to determine whether ethanol intoxication and burn injury and the subsequent pulmonary congestion affects physiological parameters of lung function using non-invasive and unrestrained plethysmography in a murine model system. Furthermore, to mirror young adult binge drinking patterns, and to determine the effect of multiple ethanol exposures on pulmonary inflammation, we utilized an episodic binge ethanol exposure regimen, where mice were exposed to ethanol for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. Our analyses demonstrate mice exposed to episodic binge ethanol and burn injury have higher mortality, increased pulmonary congestion and neutrophil infiltration, elevated neutrophil chemoattractants, and respiratory dysfunction, compared to burn or ethanol intoxication alone. Overall, our study identifies plethysmography as a useful tool for characterizing respiratory function in a murine burn model and for future identification of therapeutic compounds capable of restoring pulmonary functionality.

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“…While there is controversy over the validity of Penh as a parameter for lung mechanics or resistance [40], [41], [42], [43], we use our measurements as an added indicator of physiological change during the infection process in conjunction with a number of other cellular histopathological measurements in the lung. A whole body plethysmograph (EMMS, Bordon, Hants) was used according to the manufacturer's instructions to determine Penh and breathing frequency in mice.…”

Section: Methodsmentioning

confidence: 99%

Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

et al. 2014

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Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity.

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Assessment of Respiratory Physiology of C57BL/6 Mice following Bleomycin Administration Using Barometric Plethysmography

Cited by 39 publications

References 104 publications

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Impaired respiratory function and heightened pulmonary inflammation in episodic binge ethanol intoxication and burn injury

Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

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