Ventilatory changes in the golden hamster, Mesocricetus auratus, compared with the laboratory rat, Rattus norvegicus, during hypercapnia and/or hypoxia

Tidal volume, respiratory frequency, and minute volume were measured with total body plethysmography. Both hypercapnic (0-7% CO2) and hypoxic (13-21% O2) gas mixtures caused "dose" related hyperventilation in the hamsters. However, there was no synergism between combined stimuli. Rats exhibited greater hyperventilation than the hamsters during hypercapnic + hypoxic and hypercapnic exposures. Hamsters responded more than the rats to hypoxia alone. Greater blood buffering capacity of hamsters is a possible explanation for the species differences in ventilatory sensitivity.     

Calibration of respiratory inductive plethysmography during quiet and active sleep in lambs

Respiratory inductive plethysmography provides a noninvasive method of measuring breathing patterns. Calibration of respiratory inductive plethysmography requires calculation of gain factors for ribcage and abdomen transducers utilizing 2 breathing patterns with different ribcage and abdomen contributions and tidal volume measured by either spirometry or integrated pneumotachography. The purpose of this study was to determine if respiratory inductive plethysmography can be calibrated to provide accurate measurements during quiet and active sleep in lambs. We used a least squares linear regression calibration technique with breaths selected from quiet sleep and active sleep to calculate gain factors in 6 tracheostomized lambs. Validation of gain factors was performed by comparing tidal volumes obtained simultaneously by respiratory inductive plethysmography and pneumotachography during quiet sleep and active sleep. Tidal volume differences between respiratory inductive plethysmography and pneumotachography on validation runs of 15 consecutive breaths each revealed 90% of validation breaths within +/- 20% during quiet sleep and 82% of validation breaths within +/- 20% during active sleep. These data provide evidence that respiratory inductive plethysmography can be calibrated to allow breathing pattern measurement during sleep.     

The process of cardiorespiratory autoresuscitation in intact newborn rats

To examine the process of spontaneous autoresuscitation and the recovery of the hypoxic ventilatory response (HVR) after prolonged anoxia, we monitored respiratory frequency (f, by body plethysmography) and heart rate (HR, by ECG) in intact newborn rats (n = 12, day 2-4) before, during, and after 100% N2 exposure. The rat before anoxia showed signs of HVR: f changes at acute hypoxia (10% O2) and hyperoxia (100% O2). During anoxia, the spontaneous respiratory movement "gasping" appeared for 21 min (mean). At O2 restoration (with 100% O2), gasping stopped and no respiratory flow was detected for 1 min. One rat failed to autoresuscitate and had heart arrhythmia during the transient apnea, but 11 rats recovered respiration after the HR acceleration. Despite the successful autoresuscitation, the rats did not show HVR at 10 min into the recovery period and the recovery of HVR required more than 30 min. The results indicate that O2 inhalation is useful to trigger autoresuscitation even when the rat has already been in a state of profound hypoxic depression, but the rat becomes transiently insensitive to HVR after autoresuscitation. We estimate that reform of the respiratory control system in newborn rats is not yet firmly established to track HVR early in the recovery phase after prolonged anoxia.     

A servo-controlled respiration system for inhalation studies in anesthetized animals

Rosenthal, Frank S., and Changhong Li. Aservo-controlled respiration system for inhalation studies inanesthetized animals. J. Appl.Physiol. 83(5): 1768-1774, 1997.To facilitate aerosol deposition experiments and aerosol exposures in anesthetized animals, a servo-controlled respiration system was developed and tested. The system induces ventilation by varying extrathoracic pressure in a whole body respirator in which an intubated animal isplaced. The pressure inside the whole body respirator is varied with athree-way servo-controlled spool valve connected to sources of positiveand negative pressure. A computer-based system detects respiratory flowand computes the controlling signal for the valve by using aproportional-integral-derivative algorithm, to achieve desired patternsof flow and volume vs. time. The system was used with dogs and found toaccurately induce various single-breath breathing patterns involvingconstant-flow inspirations and expirations as well as breath-holdperiods. A similar system was used to induced repeated breaths withdesired parameters for continuous exposure to particles and forventilation of animals between experiments.

     

Measuring Respiratory Function in Mice Using Unrestrained Whole-body Plethysmography

Respiratory dysfunction is one of the leading causes of morbidity and mortality in the world and the rates of mortality continue to rise. Quantitative assessment of lung function in rodent models is an important tool in the development of future therapies. Commonly used techniques for assessing respiratory function including invasive plethysmography and forced oscillation. While these techniques provide valuable information, data collection can be fraught with artefacts and experimental variability due to the need for anesthesia and/or invasive instrumentation of the animal. In contrast, unrestrained whole-body plethysmography (UWBP) offers a precise, non-invasive, quantitative way by which to analyze respiratory parameters. This technique avoids the use of anesthesia and restraints, which is common to traditional plethysmography techniques. This video will demonstrate the UWBP procedure including the equipment set up, calibration and lung function recording. It will explain how to analyze the collected data, as well as identify experimental outliers and artefacts that results from animal movement. The respiratory parameters obtained using this technique include tidal volume, minute volume, inspiratory duty cycle, inspiratory flow rate and the ratio of inspiration time to expiration time. UWBP does not rely on specialized skills and is inexpensive to perform. A key feature of UWBP, and most appealing to potential users, is the ability to perform repeated measures of lung function on the same animal.     

Detecting lung overdistention in newborns treated with high-frequency oscillatory ventilation.

Positive airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV) increases lung volume and can lead to lung overdistention with potentially serious adverse effects. To date, no method is available to monitor changes in lung volume (DeltaVL) in HFOV-treated infants to avoid overdistention. In five newborn piglets (6-15 days old, 2.2-4.2 kg), we investigated the use of direct current-coupled respiratory inductive plethysmography (RIP) for this purpose by evaluating it against whole body plethysmography. Animals were instrumented, fitted with RIP bands, paralyzed, sedated, and placed in the plethysmograph. RIP and plethysmography were simultaneously calibrated, and HFOV was instituted at varying Paw settings before (6-14 cmH(2)O) and after (10-24 cmH(2)O) repeated warm saline lung lavage to induce experimental surfactant deficiency. Estimates of Delta VL from both methods were in good agreement, both transiently and in the steady state. Maximal changes in lung volume (Delta VL(max)) from all piglets were highly correlated with Delta VL measured by RIP (in ml) = 1.01 x changes measured by whole body plethysmography - 0.35; r(2) = 0.95. Accuracy of RIP was unchanged after lavage. Effective respiratory system compliance (Ceff) decreased after lavage, yet it exhibited similar sigmoidal dependence on Delta VL(max) pre- and postlavage. A decrease in Ceff (relative to the previous Paw setting) as Delta VL(max) was methodically increased from low to high Paw provided a quantitative method for detecting lung overdistention. We conclude that RIP offers a noninvasive and clinically applicable method for accurately estimating lung recruitment during HFOV. Consequently, RIP allows the detection of lung overdistention and selection of optimal HFOV from derived Ceff data.     

Influence of housing conditions from weaning to adulthood on the ventilatory, thermoregulatory, and endocrine responses to hypoxia of adult female rats

Housing conditions affect animal physiology. We previously showed that the hypoxic ventilatory and thermoregulatory responses to hypoxia of adult male rats housed in triads during the juvenile period (postnatal day 21 to adulthood) were significantly reduced compared with animals housed in pairs. Because sex hormones influence development and responsiveness to environmental stressors, this study investigated the impact of housing on the respiratory and thermoregulatory physiology of female rats. Since neonatal stress attenuates the hypoxic ventilatory response (HVR) of female rats at adulthood, experiments were performed both on "control" (undisturbed) animals and rats subjected to neonatal maternal separation (NMS; 3 h/day, postnatal days 3-12). At adulthood, ventilatory activity was measured by whole body plethysmography under normoxic and hypoxic conditions [fraction of inspired oxygen (Fi(O(2))) = 0.12; 20 min]. The ventilatory and body temperature responses to hypoxia of female rats raised in triads were reduced compared with rats housed in pairs. Housing female rats in triads did not affect basal or hypoxic plasma corticosterone levels but did increase levels of estradiol significantly. We conclude that modest changes in housing conditions (pairs vs. triads) from weaning to adulthood does influence basic homeostatic functions such as temperature and respiratory regulation. Triad housing can reverse the manifestations of respiratory instability at adulthood induced by stressful neonatal treatments. This should raise awareness of the benefits of increasing social interactions in clinical settings but also caution researchers of the potential impact of such subtle changes on experimental protocols and interpretation of results.     

Effects of induced bronchoconstriction on pulmonary blood flow

Allergic bronchoconstriction may be associated with hemodynamic alterations due to changes in respiratory mechanics (or the associated changes in arterial blood gas composition) or the cardiovascular effects of chemical mediators. In an attempt to differentiate between these two possible mechanisms, we obtained measurements of hemodynamics, respiratory mechanics, and O2 consumption (VO2) in nine asymptomatic adult ragweed asthmatics before and after inhalation challenge with either ragweed extract or methacholine. We measured specific airway conductance (sGaw) by body plethysmography, pleural pressure with an esophageal balloon catheter, pulmonary blood flow (Q) and VO2 by a rebreathing technique, and heart rate. For a similar degree of bronchoconstriction after the two types of challenge (mean +/- SD sGaw 0.06 +/- 0.03 and 0.05 +/- 0.02 cmH2O-1 . s-1, P = NS), mean Q increased by 29 and 29%, and mean VO2 by 33 and 37% 15-20 min after ragweed and methacholine, respectively. Since heart rate did not change, there was a concomitant increase in mean stroke volume by 25 and 35%, respectively (P less than 0.05). The respiratory pleural pressure swings during quiet breathing and the rebreathing maneuver and the work of breathing during rebreathing also increased to a similar degree after the two types of challenge. These observations suggest that, if chemical mediators are released into the circulation during antigen-induced bronchoconstriction, their blood concentrations are too low for appreciable cardiovascular effects. The increase in rebreathing cardiac output during allergic and nonallergic bronchoconstriction is probably due to increases in intrathoracic pressure swings and in the work of breathing.     

Influence of juvenile housing conditions on the ventilatory, thermoregulatory, and endocrine responses to hypoxia of adult male rats

"Extreme" housing conditions, such as isolation (single housing) or crowding, are stressful for rats, and their deleterious impact on behavior is well documented. To determine whether more subtle variations in housing can affect animal physiology, the present study tested the hypothesis that the hypoxic ventilatory response (HVR) of adult male rats housed in pairs during the juvenile period (postnatal day 21 to adulthood) does not differ from that of animals housed in triads. Because neonatal stress augments the neuroendocrine responsiveness to stress and HVR, experiments were performed both on "control" (undisturbed) animals and rats subjected to neonatal maternal separation (NMS; 3 h/day, postnatal days 3-12). At adulthood, ventilatory activity was measured by whole body plethysmography under normoxic and hypoxic conditions (inspired fraction of O(2) = 0.12; 20 min). The ventilatory and body temperature responses to hypoxia of rats raised in triads were less than those of rats housed in pairs. For the HVR, however, the attenuation induced by triad housing was more important in NMS rats. Triad housing decreased "basal" plasma corticosterone, but increased estradiol and testosterone levels. Much like the HVR, housing-related decrease in corticosterone level was greater in NMS than control rats. We conclude that modest changes in housing conditions (pairs vs. triads) during the juvenile period can influence basic homeostatic functions, such as temperature, endocrine, and respiratory regulation. Housing conditions can influence (even eliminate) the manifestations of respiratory plasticity subsequent to deleterious neonatal treatments. Differences in neuroendocrine function likely contribute to these effects.     

The role of neuropeptide S and neuropeptide S receptor 1 in regulation of respiratory function in mice

Genome-wide screening and positional cloning have linked neuropeptide S receptor 1 (NPSR1) with asthma and airway hyperresponsiveness. However, the mechanism by which NPSR1 regulates pulmonary responses remains elusive. Because neuropeptide S and its receptor NPSR1 are expressed in brain regions that regulate respiratory rhythm, and Npsr1-deficient mice have impaired stress and anxiety responses, we aimed to investigate whether neuropeptide S and NPSR1 regulate respiratory function through a central-mediated pathway. After neuropeptide S intracerebroventricular administration, respiratory responses of wildtype and Npsr1-deficient mice were monitored by whole-body or invasive plethysmography with or without serial methacholine inhalation. Airway inflammatory and hyperresponsiveness were assessed in allergen-challenged (ovalbumin or Aspergillus fumigatus) Npsr1-deficient mice. Analysis of breathing patterns by whole-body plethysmography revealed that intracerebroventricular neuropeptide S, as compared with the artificial cerebral spinal fluid control, increased respiratory frequency and decreased tidal volume in an NPSR1-dependent manner but did not affect enhanced pause. Following serial methacholine inhalation, intracerebroventricular neuropeptide S increased respiratory frequency in wildtype mice, but not in Npsr1-deficient mice, and had no effect on tidal volume. Intracerebroventricular neuropeptide S significantly reduced airway responsiveness to methacholine as measured by whole-body plethysmography. Npsr1 deletion had no impact on airway inflammation or hyperresponsiveness in ovalbumin- or A. fumigatus-induced experimental asthma. Our results demonstrate that neuropeptide S and NPSR1 regulate respiratory function through a central nervous system-mediated pathway.     

Anesthesia alters the pattern of aerosol retention in hamsters

General anesthesia was used to produce nonventilated areas of the lung, and aerosol inhalation was used to locate these areas, assuming that no aerosol deposits in a nonventilated region. Male Syrian golden hamsters were anesthetized with pentobarbital sodium (90 mg/kg), which reduced respiratory frequency, tidal volume, minute volume, and O2 consumption to 61, 41, 24, and 36%, respectively, of the corresponding awake levels. Awake and anesthetized hamsters were exposed to the aerosol for 30 min; then the lungs were excised, dried at total lung capacity, sliced into sections, and dissected into pieces. Autoradiographs were made of slices, and the activity and weight of pieces were determined. The evenness index (EI), a measure of the uniformity of retention, was calculated for each piece. With complete uniformity of retention, all EI's would be 1.0. In awake animals, only 0.2% (by wt) of the lungs had little or no retention (EI's less than 0.20). More particles deposited in the apex than in the base of the lungs. General anesthesia for extended periods of time with no deep breaths alters ventilation and therefore the distribution of aerosol retention. Many regions of the lungs in the anesthetized animals received few or no particles (11.6% of lungs had EI less than 0.20); however, no consistent pattern was observed in the location of these areas from animal to animal. The apex-to-base gradient for retention in these animals was also reversed. Radioactive aerosols can be used as probes to indicate the extent and distribution of nonventilated areas in the lungs.     

Apparatus for measuring rat body volume: a methodological proposition.

We propose a communicating-vessels system to measure body volume in live rats through water level detection by hydrostatic weighing. The reproducibility, accuracy, linearity, and reliability of this apparatus were evaluated in two tests using previously weighed water or six aluminum cylinders of known volume after proper system calibration. The applicability of this apparatus to measurement of live animals (Wistar rats) was tested in a transversal experiment with five rats, anesthetized and nonanesthetized. We took 18 measurements of the volume under each condition (anesthetized and nonanesthetized), totaling 90 measurements. The addition of water volumes (50-700 ml) produced a regression equation with a slope of 1.0006 +/- 0.0017, intercept of 0.75 +/- 0.81 (R(2) = 0.99999, standard error of estimate = 0.58 ml), and bias of approximately 1 ml. The differences between cylinders of known volumes and volumes calculated by the system were <0.4 ml. Mean volume errors were 0.01-0.07%. Among the live models, the difference between the volumes obtained for anesthetized and nonanesthetized rats was 0.31 +/- 2.34 (SD) ml (n = 90). These data showed that animal movement does not interfere with the volume measured by the proposed apparatus, and neither anesthesia nor fur shaving is needed for this procedure. Nevertheless, some effort should be taken to eliminate air bubbles trapped in the apparatus or the fur. The proposed apparatus for measuring rat body volume is inexpensive and may be useful for a range of scientific purposes.     

Comparison of the phagocytosis of two types of cyclosporin (SDZ OXL 400 and SDZ IMM 125) by alveolar macrophages from hamsters

The aim of this study was to compare two types of cyclosporin (Cs) particles, SDZ OXL 400 and SDZ IMM 125, the latter being more hydrophilic, to understand their uptake by airway macrophages. Alveolar macrophages (AM), harvested by bronchoalveolar lavage (BAL) of hamster lungs, were cultured with two different doses (0.1 mg and 0.5 mg) for 1 h, 6 h, and 24 h. Control incubations without Cs particles or with latex particles were carried out simultaneously. Cell viability, cell activation (i.e., respiratory burst, interleukin-6 (IL-6) synthesis) and mean volume of particles phagocytosed per macrophage were measured. Both types of Cs particles did not modify the AM viability, and failed to induce IL-6 synthesis during phagocytosis but slightly decreased the cell oxidative respiratory burst. The comparison between SDZ OXL 400 and SDZ IMM 125 showed that for the lower dose the mean volume of both Cs types phagocytosed was similar at 1 h and 6 h. At 24 h an increase of the mean volume phagocytosed was seen for SDZ IMM 125 but not for SDZ OXL 400. For the higher dose the mean volume of SDZ IMM 125 phagocytosed was higher than SDZ OXL 400 at 1 h and 6 h and comparable for both types at 24 h. SDZ IMM 125 particles were phagocytosed more rapidly than SDZ OXL 400. The mean volume of phagocytosed latex particles increased with time and dose and was higher than for both Cs particle types. In conclusion, AM were seen to phagocytose particles of different physical properties (i.e., form, size, and shape), chemical properties (i.e., inert or peptidic) and degrees of hydrophilicity in a different manner.     

一种测量镇静大鼠气道反应性的非侵入式新方法

将腹腔注射地西泮而镇静的ＳＤ大鼠,置于体积描记器,测定其自主呼吸变化。吸入氯化乙酰甲胆碱和氯化乙酰胆碱气雾对呼吸幅度无明显影响,可深度依赖性地增加呼吸频率,且两药的作用强度相似,但ＭＣｈ作用维持１１ｍｉｎ,Ａｃｈ仅维持３ｍｉｎ。乌拉坦麻醉可抑制呼吸和对ＭＣｈ的反应;硫酸阿托品,硫酸沙丁胺醇和氨茶碱抑制ＭＣｈ引起的频率增快;吸入抗原气雾后６ｈ能增强致敏大鼠对ＭＣｈ的敏感性。     

Effect of body size on breathing pattern and fine-particle deposition in children.

Interchild variability in breathing patterns may contribute to variability in fine particle lung deposition and morbidity in children associated with those particles. Fractional deposition (DF) of fine particles (2-microm monodisperse, carnauba wax particles) was measured in healthy children, age 6-13 yr (n = 36), while they followed a resting breathing pattern previously determined by respiratory inductance plethysmography. Interchild variation in DF, measured by photometry at the mouth, was most strongly predicted by their tidal volume (Vt) (r =0.79, P < 0.001). Multiple regression analysis further showed that, for any given height and age, Vt increased with increasing body mass index (BMI) (P < 0.001). The overweight children (> or =95th percentile BMI) (n = 8) had twice the DF of those in the lowest BMI quartile (<25th percentile) (n = 9; 0.28 +/- 0.13 vs. 0.15 +/- 0.06, respectively; P < 0.02). In the same groups, resting minute ventilation was also significantly higher in the overweight children (8.5 +/- 2.2 vs. 5.9 +/- 1.1 l/min; P < 0.01). Consequently, the rate of deposition (i.e., particles depositing/time) in the overweight children was 2.8 times that of the leanest children (P < 0.02). Among all children, the rate of deposition was significantly correlated with BMI (r = 0.46, P = 0.004). These results suggest that increased weight in children may be associated with increased risk from inhalation of pollutant particles in ambient air.     

Phagocytic properties of hepatic endothelial cells and splenic macrophages compensating for a decreased phagocytic function of Kupffer cells in the chronically ethanol-fed rats

The balance of phagocytic function among Kupffer cells, hepatic endothelial cells and splenic macrophages in the chronically ethanol-fed rats has been investigated. Clearance of latex particles in the blood was measured to estimate the function of the reticuloendothelial system. Phagocytosis of latex particles by Kupffer cells, hepatic endothelial cells or splenic macrophages in vivo was measured by counting the number of ingested particles in a cell after isolation of hepatic nonparenchymal cells or spleen cells following injection of different amounts of latex particles. Latex particle clearance was suppressed in the ethanol-fed rats, demonstrating a decreased phagocytic capacity of the reticuloendothelial system. Markedly decreased phagocytic function was found in 40% of Kupffer cells of the chronically ethanol-fed rats. In contrast, the number of latex particles in hepatic endothelial cells and in splenic macrophages was increased after injection of a triggering dose of latex particles. From these results it may be concluded that an increased phagocytosis of hepatic endothelial cells and splenic macrophages could compensate for the decreased phagocytic function of Kupffer cells.     

Respiratory measurements of unsedated small laboratory mammals using nonrebreathing valves

The respiratory frequency, tidal volume, minute volume, oxygen uptake and carbon dioxide output of unsedated hamsters, rats, guinea pigs and rabbits were measured to obtain comparative data and to evaluate the performance of those species as unsedated subjects. The animals were trained to remain stationary and breathe through nonrebreathing valves while expired gas was collected and respiratory frequency was monitored. Measurements of dogs also were conducted to obtained comparative data by similar methods. Hamsters were readily trained and performed reliably during repeated trials. Rats and guinea pigs were more difficult to train and performed erratically. The rabbits' performance was intermediate between that of hamsters and the other species. The back pressures caused by the small animal nonrebreathing valves at estimated peak flow rates were either similar to or less than those encountered by dogs. Measured respiratory values were compared to values predicted by published equations based on body weight. Data from this study generally reflected species differences related to body weight and metabolic rate similar to those predicted by the equations, but values from the four smaller species also may have reflected differences related to behavior.     

体描箱在评估婴幼儿急性下呼吸道感染肺功能改变中的价值

摘要 目的：探讨体描箱评估婴幼儿急性下呼吸道感染（ALRTI）肺功能改变的价值。方法：收集2020年10月至2021年6月于我院收治的76例ALRTI婴幼儿,根据感染部位分为肺炎组与支气管炎组,根据有无喘息症状分为喘息性组和非喘息性组,采用体描箱测量潮气呼吸参数、体描箱特有指标,分别进行两组间肺功能比较,分析各参数之间相关性,采用受试者工作特征（ROC）曲线评估体描特有指标在婴幼儿ALRTI中的诊断价值。结果：肺炎组与支气管炎组比较,各潮气呼吸参数及功能残气量（FRCp）无明显差异（P>0.05）,而有效气道阻力（Reff）和特殊有效气道阻力（sReff）有明显差异（P<0.05）;对于喘息性组与非喘息性组,sReff有显著差异（P<0.05）;76例ALRTI患儿潮气量（VT）与每公斤体质量潮气量（VT/kg）呈正相关（P<0.05）,VT、VT/kg均与呼吸频率（RR）、达峰时间比（TPTEF/TE）呈负相关（P<0.05）, TPTEF/TE与达峰容积比（VPTEF/VE）呈正相关（P<0.05）,sReff与FRCp、Reff均呈正相关（P<0.05）;ROC曲线显示,sReff在诊断肺炎与支气管炎、喘息性和非喘息性的价值最高,ROC曲线下面积分别为0.704、0.688。结论：对于ALRTI患儿,体描箱参数Reff和sReff可帮助判断感染部位,且sReff可直接反映小气道阻塞情况,诊断价值较高,值得临床推广应用。     

Micron-sized intrapulmonary particle deposition in the developing rat lung

Little is known about the effects of postnatal developmental changes in lung architecture and breathing patterns on intrapulmonary particle deposition. We measured deposition in the developing Wistar-Kyoto rat, whose lung development largely parallels that of humans. Deposition of 2-μm sebacate particles was determined in anesthetized, intubated, spontaneously breathing rats on postnatal days (P) 7 to 90 by aerosol photometry (Karrasch S, Eder G, Bolle I, Tsuda A, Schulz H. J Appl Physiol 107: 1293-1299, 2009). Respiratory parameters were determined by body plethysmography. Tidal volume increased substantially from P7 (0.19 ml) to P90 (2.1 ml) while respiratory rate declined from 182 to 107/min. Breath-specific deposition was lowest (9%) at P7 and P90 and markedly higher at P35 (almost 16%). Structural changes of the alveolar region include a ninefold increase in surface area (Bolle I, Eder G, Takenaka S, Ganguly K, Karrasch S, Zeller C, Neuner M, Kreyling WG, Tsuda A, Schulz H. J Appl Physiol 104: 1167-1176, 2008). Particle deposition per unit of time and surface area peaked at P35 and showed a minimum at P90. At an inhaled particle number concentration of 10(5)/cm(3), there was an estimated 450, 690, and 330 particles/(min × cm(2)) at P7, P35, and P90, respectively. Multiple regression models showed that deposition depends on the mean linear intercept as structural component and the breathing parameters, tidal volume, and respiratory rate (r(2) > 0.9). In conclusion, micron-sized particle deposition was dependent on the stage of postnatal lung development. A maximum was observed during late alveolarization (P35), which corresponds to human lungs of about eight years of age. Children at this age may therefore be more susceptible to micron-sized airborne environmental health hazards.     

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

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, R(2) = 0.87, P < 0.001; and agreement within 1%, P < 0.001); 2) inspiratory airflow (correlation, R(2) = 0.92, P < 0.001; agreement within 4%, P < 0.001); 3) expiratory airflow (correlation, R(2) = 0.83, P < 0.001); and 4) respiratory movement signal (correlation, R(2) = 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.