Maturation of baseline breathing and of hypercapnic  and hypoxic ventilatory responses in newborn mice

Breathing during the first postnatal hours has not been examined in mice, the preferred mammalian species for genetic studies. We used whole body plethysmography to measure ventilation (V˙e), breath duration (TTOT), and tidal volume (Vt) in mice delivered vaginally (VD) or by cesarean section (CS). In experiment 1, 101 VD and 100 CS pups aged 1, 6, 12, 24, or 48 h were exposed to 8% CO2 or 10% O2for 90 s. In experiment 2, 31 VD pups aged 1, 12, or 24 h were exposed to 10% O2 for 5 min. Baseline breathing maturation was delayed in CS pups, but V˙eresponses to hypercapnia and hypoxia were not significantly different between VD and CS pups [at postnatal age of 1 h (H1): 48 ± 44 and 18 ± 32%, respectively, in VD and CS pups combined]. TheV˙e increase induced by hypoxia was greater at H12 (46 ± 27%) because of TTOT response maturation. At all ages, hypoxic decline was ascribable mainly to a Vtdecrease, and posthypoxic decline was ascribable to a TTOTincrease with apneas, suggesting different underlying neuronal mechanisms.

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Whole body plethysmography reveals differential ventilatory responses to ozone in rat models of cardiovascular disease

Inhalation Toxicology ◽

10.3109/08958378.2014.954167 ◽

2015 ◽

Vol 27 (sup1) ◽

pp. 14-25 ◽

Cited By ~ 13

Author(s):

Janice A. Dye ◽

Allen D. Ledbetter ◽

Mette C. Schladweiler ◽

Daniel L. Costa ◽

Urmila P. Kodavanti

Keyword(s):

Cardiovascular Disease ◽

Whole Body ◽

Body Plethysmography ◽

Rat Models ◽

Ventilatory Responses ◽

Whole Body Plethysmography

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Novel whole body plethysmography system for the continuous characterization of sleep and breathing in a mouse

Journal of Applied Physiology ◽

10.1152/japplphysiol.00818.2011 ◽

2012 ◽

Vol 112 (4) ◽

pp. 671-680 ◽

Cited By ~ 24

Author(s):

A. B. Hernandez ◽

J. P. Kirkness ◽

P. L. Smith ◽

H. Schneider ◽

M. Polotsky ◽

...

Keyword(s):

Tidal Volume ◽

Gold Standard ◽

Inbred Mouse ◽

Respiratory Movement ◽

Whole Body ◽

Mouse Strains ◽

Obese Mouse ◽

Body Plethysmography ◽

Breathing Patterns ◽

Whole Body Plethysmography

Sleep is associated with marked alterations in ventilatory control that lead to perturbations in respiratory timing, breathing pattern, ventilation, pharyngeal collapsibility, and sleep-related breathing disorders (SRBD). Mouse models offer powerful insight into the pathogenesis of SRBD; however, methods for obtaining the full complement of continuous, high-fidelity respiratory, electroencephalographic (EEG), and electromyographic (EMG) signals in unrestrained mice during sleep and wake have not been developed. We adapted whole body plethysmography to record EEG, EMG, and respiratory signals continuously in unrestrained, unanesthetized mice. Whole body plethysmography tidal volume and airflow signals and a novel noninvasive surrogate for respiratory effort (respiratory movement signal) were validated against simultaneously measured gold standard signals. Compared with the gold standard, we validated 1) tidal volume (correlation, R2 = 0.87, P < 0.001; and agreement within 1%, P < 0.001); 2) inspiratory airflow (correlation, R2 = 0.92, P < 0.001; agreement within 4%, P < 0.001); 3) expiratory airflow (correlation, R2 = 0.83, P < 0.001); and 4) respiratory movement signal (correlation, R2 = 0.79–0.84, P < 0.001). The expiratory airflow signal, however, demonstrated a decrease in amplitude compared with the gold standard. Integrating respiratory and EEG/EMG signals, we fully characterized sleep and breathing patterns in conscious, unrestrained mice and demonstrated inspiratory flow limitation in a New Zealand Obese mouse. Our approach will facilitate studies of SRBD mechanisms in inbred mouse strains and offer a powerful platform to investigate the effects of environmental and pharmacological exposures on breathing disturbances during sleep and wakefulness.

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Automatic classification of activity and apneas using whole body plethysmography in newborn mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00803.2004 ◽

2005 ◽

Vol 98 (1) ◽

pp. 365-370 ◽

Cited By ~ 22

Author(s):

B. Matrot ◽

E. Durand ◽

S. Dauger ◽

G. Vardon ◽

C. Gaultier ◽

...

Keyword(s):

Spectral Analysis ◽

Intraclass Correlation ◽

Correlation Coefficients ◽

Automatic Classification ◽

Whole Body ◽

Body Plethysmography ◽

Newborn Mice ◽

Respiratory Signal ◽

Whole Body Plethysmography

An increasing number of studies in newborn mice are being performed to determine the mechanisms of sleep apnea, which is the hallmark of early breathing disorders. Whole body plethysmography is the method of choice, as it does not require immobilization, which affects behavioral states and breathing. However, activity inside the plethysmograph may disturb the respiratory signal. Visual classification of the respiratory signal into ventilatory activity, activity-related disturbances, or apneas is so time-consuming as to considerably hamper the phenotyping of large pup samples. We propose an automatic classification of activity based on respiratory disturbances and of apneas based on spectral analysis. This method was validated in newborn mice on the day of birth and on postnatal days 2, 5, and 10, under normoxic and hypoxic (5% O2) conditions. For both activity and apneas, visual and automatic scores showed high Pearson's correlation coefficients (0.92 and 0.98, respectively) and high intraclass correlation coefficients (0.96–0.99), supporting strong agreement between the two methods. The present results suggest that breathing disturbances may provide a valid indirect index of activity in freely moving newborn mice and that automatic apnea classification based on spectral analysis may be efficient in terms of precision and of time saved.

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Brain stem serotonin protects blood pressure in neonatal rats exposed to episodic anoxia

Journal of Applied Physiology ◽

10.1152/japplphysiol.00970.2013 ◽

2013 ◽

Vol 115 (12) ◽

pp. 1733-1741 ◽

Cited By ~ 11

Author(s):

Hsiao T. Yang ◽

Kevin J. Cummings

Keyword(s):

Tidal Volume ◽

Brain Stem ◽

Sudden Infant Death ◽

Whole Body ◽

Sudden Infant ◽

Breathing Frequency ◽

Body Plethysmography ◽

Rat Pups ◽

Time Required ◽

Whole Body Plethysmography

In neonatal rodents, a loss of brain stem serotonin [5-hydroxytryptamine (5-HT)] in utero or at birth compromises anoxia-induced gasping and the recovery of heart rate (HR) and breathing with reoxygenation (i.e., autoresuscitation). How mean arterial pressure (MAP) is influenced after an acute loss of brain stem 5-HT content is unknown. We hypothesized that a loss of 5-HT for ∼1 day would compromise MAP during episodic anoxia. We injected 6-fluorotryptophan (20 mg/kg ip) into rat pups (postnatal days 9–10 or 11–13, n = 22 treated, 24 control), causing a ∼70% loss of brain stem 5-HT. Pups were exposed to a maximum of 15 anoxic episodes, separated by 5 min of room air to allow autoresuscitation. In younger pups, we measured breathing frequency and tidal volume using “head-out” plethysmography and HR from the electrocardiogram. In older pups, we used whole body plethysmography to detect gasping, while monitoring MAP. Gasp latency and the time required for respiratory, HR, and MAP recovery following each episode were determined. Despite normal gasp latency, breathing frequency and a larger tidal volume ( P < 0.001), 5-HT-deficient pups survived one-half the number of episodes as controls ( P < 0.001). The anoxia-induced decrease in MAP experienced by 5-HT-deficient pups was double that of controls ( P = 0.017), despite the same drop in HR ( P = 0.48). MAP recovery was delayed ∼10 s by 5-HT deficiency ( P = 0.001). Our data suggest a loss of brain stem 5-HT leads to a pronounced, premature loss of MAP in response to episodic anoxia. These data may help explain why some sudden infant death syndrome cases die from what appears to be cardiovascular collapse during apparent severe hypoxia.

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Measurement of respiratory function by whole body plethysmography in unanesthetized and unrestrained monkeys

Journal of Pharmacological and Toxicological Methods ◽

10.1016/j.vascn.2008.05.112 ◽

2008 ◽

Vol 58 (2) ◽

pp. 173

Author(s):

Kazuaki Sasaki ◽

Y. Nakamura ◽

H. Iizuka ◽

M. Imaizumi ◽

H. Atai

Keyword(s):

Respiratory Function ◽

Whole Body ◽

Body Plethysmography ◽

Whole Body Plethysmography

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Ventilatory behavior after hypoxia in C57BL/6J and A/J mice

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.5.1962 ◽

2001 ◽

Vol 91 (5) ◽

pp. 1962-1970 ◽

Cited By ~ 42

Author(s):

Fang Han ◽

Shyam Subramanian ◽

Thomas E. Dick ◽

Ismail A. Dreshaj ◽

Kingman P. Strohl

Keyword(s):

Airway Resistance ◽

Minute Ventilation ◽

Genetic Effect ◽

Strain Differences ◽

Whole Body ◽

Environmental Forcing ◽

Ventilatory Responses ◽

Term Potentiation ◽

Genetic Mechanisms ◽

Whole Body Plethysmography

Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (V˙e), respiratory frequency (f), tidal volume (Vt), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease inV˙e on reoxygenation with either air (−11%) or 100% O2 (−20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in V˙e (−28.4 vs. −38.7%, air vs. 100% O2) and f (−13.8 vs. −22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase inV˙e (+116%) and f (+62.2%) during air reoxygenation and significant increase in V˙e (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.

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