Thoracic Gas Volume Measurements in Paralyzed Mice

Lundblad, Lennart K. A.; Thompson-Figueroa, John; Leclair, Timothy; Irvin, Charles G.; Bates, Jason H. T.

doi:10.1114/b:abme.0000042229.41098.6a

Cited by 12 publications

(10 citation statements)

References 15 publications

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“…Once anesthesia was induced, a tracheotomy was performed with a 16 gauge catheter. Mice were ventilated using a Harvard rodent ventilator with humidified room air at a tidal volume of 10 ml/kg, PEEP 3 cm H 2 O, rate 150 breaths per minute for 6 hours under continued anesthesia to a level resulting in no spontaneous respirations [14]. These settings were chosen based on published literature of physiologic murine tidal volume, respiratory rates and optimal PEEP, and confirmed as adequate to maintain adequate blood gases by blood gas determination [15].…”

Section: Methodsmentioning

confidence: 99%

Murine mechanical ventilation stimulates alveolar epithelial cell proliferation

Chess

Benson

Maniscalco

et al. 2010

Experimental Lung Research

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High tidal volume mechanical ventilation can cause inflammation and lung damage. Mechanical strain is also necessary for normal lung growth. The current work was performed to determine if mechanical ventilation with clinically utilized tidal volumes stimulates a proliferative response in the lung. Six to eight week old C57/Bl6 mice, anesthetized with ketamine/ xylozine, were ventilated for 6 hours with 10 ml/kg tidal volume, PEEP 3cm H2O. Pulmonary function testing demonstrated decreased compliance within 3 hours of ventilation. Assessment of bronchoalveolar lavage (BAL) demonstrated no significant increase in lactate dehydrogenase, total lavagable cell number or total protein after ventilation. There was evidence of inflammation in the lungs of ventilated mice, with an increased percentage of lymphocytes and neutrophils in BAL, and an increase in MIP-2 and IL-1β message in lung tissue. Immunohistochemistry of inflation-fixed lungs demonstrated increased alveolar cell proliferation as measured by both proliferating cell nuclear antigen and Ki67 staining. Dual staining confirmed that proliferating cells labeled with proSP-B demonstrating that ventilation induces proliferation of alveolar type II cells. Ventilation did not increase apoptosis in alveolar type II cells, as measured by tunel staining. Ventilation at low tidal volumes leads to a mild inflammatory response and alveolar epithelial cell proliferation.

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Section: Methodsmentioning

confidence: 99%

Murine mechanical ventilation stimulates alveolar epithelial cell proliferation

Chess

Benson

Maniscalco

et al. 2010

Experimental Lung Research

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“…After a 5-min initial stabilization period, volume history was standardized with two 0.75-ml DIs, delivered over 4 s. The DIs were delivered in a quasisinusoidal, nonsustained, and nonpressure-limited fashion in order to mimic the same tidal inflations delivered during high Vt ventilation. A volume of 0.75 ml was chosen because it is the approximate volume needed to inflate the lung to total lung capacity in a normal 25-g mouse when delivered over resting residual lung volume (35). Following volume history standardization, mice were assigned to receive one of five different ventilation protocols (matched in total minute ventilation) over 2 h: 1) low Vt (0.25 ml), 180 breaths/min, 2 cmH 2O PEEP, with two DIs (0.75 ml) every minute (LVDI; n ϭ 8); 2) low Vt (0.25 ml), 180 breaths/min, 2 cmH 2O PEEP, with two DIs (0.75 ml) every hour (LV; n ϭ 8); 3) high Vt (0.75 ml), 60 breaths/min, 2 cmH 2O PEEP (HV; n ϭ 7), equivalent to DI every second; 4) high Vt (0.75 ml), 60 breaths/min, 0 cmH 2O PEEP (HVZP; n ϭ 7) as a positive injury control; when accounting for gas compression, actual delivered Vt averaged 0.20 ml in the LV and LVDI groups (8 ml/kg) and 0.61 ml in the HV and HVZP groups (25 ml/kg); 5) a sham surgical control group (Sham; n ϭ 6) of nonmechanically ventilated mice was anesthetized with Avertin [tribromo-ethyl alcohol (Aldrich, Milwaukee, WI) in tert-amyl alcohol, 20 mg/ml] at a dose of 400 mg/kg, underwent surgical exposure of the trachea with wound closure, was allowed to recover from anesthesia, and was euthanized 2 h later for bronchoalveolar lavage (BAL) and tissue harvest.…”

Section: Methodsmentioning

confidence: 99%

Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury

Allen¹,

Suratt²,

Rinaldi³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Low tidal volume (Vt) ventilation is protective against ventilator-induced lung injury but can promote development of atelectasis. Periodic deep inflation (DI) can open the lung, but if delivered too frequently may cause damage via repeated overdistention. We therefore examined the effects of varying DI frequency on lung mechanics, gas exchange, and biomarkers of injury in mice. C57BL/6 males were mechanically ventilated with positive end-expiratory pressure (PEEP) of 2 cmH2O for 2 h. One high Vt group received a DI with each breath (HV). Low Vt groups received 2 DIs after each hour of ventilation (LV) or 2 DIs every minute (LVDI). Control groups included a nonventilated surgical sham and a group receiving high Vt with zero PEEP (HVZP). Respiratory impedance was measured every 4 min, from which tissue elastance (H) and damping (G) were derived. G and H rose progressively during LV and HVZP, but returned to baseline after hourly DI during LV. During LVDI and HV, G and H remained low and gas exchange was superior to that of LV. Bronchoalveolar lavage fluid protein was elevated in HV and HVZP but was not different between LV and LVDI. Lung tissue IL-6 and IL-1beta levels were elevated in HVZP and lower in LVDI compared with LV. We conclude that frequent DI can safely improve gas exchange and lung mechanics and may confer protection from biotrauma. Differences between LVDI and HV suggest that an optimal frequency range of DI exists, within which the benefits of maintaining an open lung outweigh injury incurred from overdistention.

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“…Anesthetized mice were installed in a custom-designed whole-body plethysmograph and connected to a small animal ventilator (flexiVent; SCIREQ, Inc., Montreal, PQ, Canada), as previously described (16).…”

Section: Animal Preparationmentioning

confidence: 99%

“…V TG was measured plethysmographically (V TG,Pleth ) by external chest compression as described previously (16,22).…”

Section: Measurement Of V Tgmentioning

confidence: 99%

Tumor Necrosis Factor–α Overexpression in Lung Disease

Lundblad

Thompson-Figueroa

Leclair

et al. 2005

Am J Respir Crit Care Med

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229

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We conclude that TNF-alpha overexpression causes pathologic changes consistent with both emphysema and pulmonary fibrosis combined with a general lung inflammation, and consequently does not model any single human disease. Our study thus confirms the pleiotropic effects of TNF-alpha, which has been implicated in multiple inflammatory disorders, and underscores the necessity of using a wide range of investigative techniques to link gene expression and phenotype in animal models of disease.

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Thoracic Gas Volume Measurements in Paralyzed Mice

Cited by 12 publications

References 15 publications

Murine mechanical ventilation stimulates alveolar epithelial cell proliferation

Murine mechanical ventilation stimulates alveolar epithelial cell proliferation

Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury

Tumor Necrosis Factor–α Overexpression in Lung Disease

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