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Mice are a valuable model for elegant studies of complex, system-dependent diseases, including pulmonary diseases. Current tools to assess lung function in mice are either terminal or lack accuracy. We set out to develop a low-cost, accurate, headout variable-pressure plethysmography system to allow for repeated, nonterminal measurements of lung function in mice. Current head-out plethysmography systems are limited by air leaks that prevent accurate measures of volume and flow. We designed an inflatable cuff that encompasses the mouse’s neck preventing air leak. We wrote corresponding software to collect and analyze the data, remove movement artifacts, and automatically calibrate each dataset. This software calculates volume, inspiratory/expiratory time, breaths per minute, mid-expiratory flow, and end-inspiratory pause. To validate the use, we established that our plethysmography system accurately measured tidal breathing, the bronchoconstrictive response to methacholine, sex- and age-associated changes in breathing, and breathing changes associated with house dust mite sensitization. Our estimates of volume, flow, and timing of breaths are in line with published estimates, we observed dose-dependent decreases in volume and flow in response to methacholine (P < 0.05), increased lung volume, and decreased breathing rate with aging (P < 0.05), and that house dust mite sensitization decreased volume and flow (P < 0.05) while exacerbating the methacholine-induced increase in inspiratory time (P < 0.05). We describe an accurate, sensitive, low-cost, head-out plethysmography system that allows for longitudinal studies of pulmonary disease in mice. [ABSTRACT FROM AUTHOR]

Water transport and local (airway) hydration are critical for the normal functioning of lungs and airways. Currently, there is uncertainty regarding the effects of systemic dehydration on pulmonary function. Our aims were 1) to clarify the impact of exercise- or fluid restriction-induced dehydration on pulmonary function in healthy adults; and 2) to establish whether systemic or local rehydration can reverse dehydration-induced alterations in pulmonary function. Ten healthy participants performed four experimental trials in a randomized order (2 h exercise in the heat twice and 28 h fluid restriction twice). Pulmonary function was assessed using spirometry and whole body plethysmography in the euhydrated, dehydrated, and rehydrated states. Oral fluid consumption was used for systemic rehydration and nebulized isotonic saline inhalation for local rehydration. Both exercise and fluid restriction induced mild dehydration (2.7 ± 0.7% and 2.5 ± 0.4% body mass loss, respectively; P < 0.001) and elevated plasma osmolality (P < 0.001). Dehydration across all four trials was accompanied by a reduction in forced vital capacity (152 ± 143 mL, P < 0.01) and concomitant increases in residual volume (216 ± 177 mL, P < 0.01) and functional residual capacity (130 ± 144 mL, P < 0.01), with no statistical differences between modes of dehydration. These changes were normalized by fluid consumption but not nebulization. Our results suggest that, in healthy adults: 1) mild systemic dehydration induced by exercise or fluid restriction leads to pulmonary function impairment, primarily localized to small airways; and 2) systemic, but not local, rehydration reverses these potentially deleterious alterations. [ABSTRACT FROM AUTHOR]

Acid-sensing ion channels (ASICs) are voltage-insensitive cation channels that contribute to cellular excitability. We previously reported that ASIC1 in pulmonary artery smooth muscle cells (PASMC) contribute to pulmonary vasoreactivity and vascular remodeling during the development of chronic hypoxia (CH)-induced pulmonary hypertension. However, the roles of ASIC2 and ASIC3 in regulation of pulmonary vasoreactivity and the development of CH-induced pulmonary hypertension are unknown. We tested the hypothesis that ASIC2 and ASIC3 contribute to increased pulmonary vasoreactivity and development of CH-induced pulmonary hypertension using ASIC2- and ASIC3- knockout (-/-) mice. In contrast to this hypothesis, we found that ASIC2-/- mice exhibit enhanced CH-induced pulmonary hypertension compared with WT and ASIC3-/- mice. This response was not associated with a change in ventilatory sensitivity or systemic cardiovascular function but was instead associated with direct changes in pulmonary vascular reactivity and pulmonary arterial morphology in ASIC2-/- mice. This increase in reactivity correlated with enhanced pulmonary arterial basal tone, elevated basal PASMC [Ca2+] and store-operated calcium entry (SOCE) in PASMC from ASIC2-/- mice. This increase in PASMC [Ca2+] and vasoreactivity was dependent on ASIC1-mediated Ca2+ influx but was not contingent upon an increase in ASIC1 mRNA or protein expression in PASMC from ASIC2-/- mice. Together, the results from this study demonstrate an important role for ASIC2 to regulate pulmonary vascular reactivity and for ASIC2 to modulate the development of CH-induced pulmonary hypertension. These data further suggest that loss of ASIC2 enhances the contribution of ASIC1 to overall pulmonary vascular reactivity. [ABSTRACT FROM AUTHOR]

Multiple breath nitrogen washout (MBNW) indices provide insight into ventilation heterogeneity globally [lung clearance index (LCI)] and within acinar (Sacin) and conducting (Scond) airways. Normal aging leads to an accelerated deterioration of Sacin in older adults, but little is known about the contribution of peripheral airway function to changes in pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] with aging. We aimed to examine associations between MBNW and FEV1/FVC as well as RV/TLC in healthy adults, and to determine if these relationships differ in older (≥50 yr) versus younger subjects (<50 yr). Seventy-nine healthy adult volunteers aged 23-89 yr with no cardiac or respiratory disease and a smoking history of <5 pack-years underwent spirometry, plethysmography, and MBNW. After adjustment for sex, height, and body mass index, the following relationships were present across the entire cohort: Sacin was inversely related to FEV1/FVC (R² = 0.22, P < 0.001); Sacin and Scond were positively related to RV/TLC (R² = 0.53, P < 0.001); on separate analyses, the relationship between Sacin and FEV1/FVC was strongest in the older group (R² = 0.20, P = 0.003) but markedly weaker in the younger group (R² = 0.09, P = 0.04); and Sacin and Scond were related to RV/TLC in older (R² = 0.20, P = 0.003) but not younger subgroups. No relationships were observed between LCI and FEV1/FVC or RV/TLC. Changes in FEV1/FVC and RV/TLC are at least in part due to changes in peripheral airway function with aging. Further studies of the relationships between MBNW and standard pulmonary function indices may prove useful for their combined application and interpretation in obstructive airways disease. NEW & NOTEWORTHY This study explores associations between multiple breath nitrogen washout (MBNW) and standard pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] in healthy adults across a wide range of ages. We have demonstrated statistically significant relationships between MBNW and FEV1/FVC as well as RV/TLC. These findings provide novel evidence of the contribution of peripheral airway function to changes in standard pulmonary function indices with aging. [ABSTRACT FROM AUTHOR]

Determining the presence of thoracoabdominal asynchrony in chronic obstructive pulmonary disease (COPD) patients is clinically relevant, but there is no consensus on the optimal parameters for performing this analysis. We assessed 22 COPD patients (FEV1 40 ± 10% predicted) and 13 healthy controls during rest and exercise with optoelectronic plethysmography (70% maximum workload) on a cycle ergometer. Thoracoabdominal asynchrony was calculated by using phase angle and phase shift parameters following a three-compartment model involving the upper and lower rib cages and abdomen. Patients were classified as having thoracoabdominal asynchrony (TAA+) or not (TAA-) based on control values (mean ± 2 SDs). The chest wall volume and compartmental contribution were also measured. Thoracoabdominal asynchrony was observed in the lower rib cage. The phase angle detected more TAA+ patients at rest (15 vs. 7 patients) and during exercise (14 vs. 8 patients) compared with the phase shift. TAA+ patients also presented a lower chest wall volume, lower rib cage contribution, and higher abdominal contribution to chest wall volume compared with the control and TAA- patients. Thoracoabdominal asynchrony was more detectable during rest and exercise using the phase angle parameter, and it was observed in the lower rib cage compartment, reducing the chest wall volume during exercise in patients with COPD. NEW & NOTEWORTHY This study contributes to advance the knowledge over the previous lack of consensus on the assessment of thoracoabdominal asynchrony. We rigorously evaluated the related features that interfere in the measurement of the asynchrony (measurement tool, chest wall model and calculation parameter). Our results suggest that phase angle detects more suitably thoracoabdominal asynchrony that occurs on the lower ribcage and leads to a reduction in the chest wall volume during exercise in COPD patients. [ABSTRACT FROM AUTHOR]

The pathophysiologic processes distinguishing classic asthma (CA), cough-variant asthma (CVA), and methacholine (MCh)-induced cough but normal airway sensitivity (COUGH) are inadequately understood and may be a result of differences in the ability to bronchodilate following a deep inspiration (DI). The purpose of this study was to compare the bronchodilating effect of DIs in individuals with CA, CVA, and COUGH using high-dose MCh. Individuals aged 18-65 yr with CA or suspected CVA completed high-dose MCh testing to a maximum change in forced expiratory volume in 1 s (FEV1) of 50% from baseline (MAX). Impulse oscillometry (IOS) measurements and partial and maximal-flow volume curves (used to calculate a DI index) were recorded at baseline and at each dose of MCh. Body plethysmography was performed at baseline and MAX. Twenty-eight subjects [25 women, 39.8 ± 11.9 yr (means ± SD)] were studied (n = 11 CA, n = 10 CVA, and n = 7 COUGH). At MAX, the percent change in FEV1 was greater in subjects with CA compared with those with CVA (P < 0.001) and COUGH (P < 0.001), and the percent change in forced vital capacity was greater in those with CA than with COUGH (P = 0.017). Subjects with CA and CVA developed dynamic hyperinflation and gas trapping. In subjects with CA and CVA, all IOS parameters were significantly increased from baseline to MAX, except for central respiratory resistance (R20). In individuals with COUGH, total respiratory resistance, R20, and resonant frequency were significantly increased from baseline. At MAX, the DI index was positive in all groups, suggesting preserved bronchodilation (CA, 0.67 ± 0.97; CVA, 0.51 ± 0.73; COUGH, 0.01 ± 0.36; P = 0.211). We conclude that the bronchodilating effect of DIs is preserved in individuals with CA, CVA, and borderline with COUGH; however, hyperinflation and gas trapping are avoided in subjects with COUGH alone. [ABSTRACT FROM AUTHOR]

Current guidelines recommend severity of chronic obstructive pulmonary disease be graded using forced expiratory volume in 1 s (FEV1). But this measurements is biased by thoracic gas compression depending on lung volume and airflow resistance. The aim of this study was to test the hypothesis that the effect of thoracic gas compression on FEV1 is greater in emphysema than chronic bronchitis due to larger lung volumes and this influences severity classification and prognosis. FEV1 was simultaneously measured by spirometry and body plethysmography (FEV1-pl) in 47 subjects with dominant emphysema and 51 with dominant chronic bronchitis. Subjects with dominant emphysema had larger lung volumes, lower diffusion capacity and lower FEV1 than those with dominant chronic bronchitis. However, FEV1-pl, patient-centered variables (dyspnea, quality of life, exercise tolerance, exacerbation frequency), arterial blood gases, and respiratory impedance were not significantly different between groups. Using FEV1-pl instead of FEV1 shifted severity distribution towards less severe classes in dominant emphysema more than chronic bronchitis. The Body mass, Obstruction, Dyspnea, and Exercise (BODE) index was significantly higher in dominant emphysema than chronic bronchitis but this difference significantly decreased when FEV1-pl was substituted for FEV1. In conclusion, the FEV1 is biased by thoracic gas compression more in subjects with dominant emphysema than in those with chronic bronchitis. This variably and significantly affects the severity grading systems currently recommended. [ABSTRACT FROM AUTHOR]

When exposed to a hypoxic environment, the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR and is termed ventilatory acclimatization to hypoxia (VAH). This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. The mechanisms of HVR plasticity are currently poorly understood. We hypothesized that changes in neuronal nitric oxide synthase (nNOS) activity or expression in the nucleus tractus solitarius contribute to this plasticity and underlie VAH in rats. To test this, we treated rats held in normoxia or 10% O2 (CSH, PI... = 70 Torr) for 7-9 days and measured ventilation in conscious, unrestrained animals before and after microinjecting the general NOS antagonist L-NG-Nitroarginine methyl ester into the nucleus tractus solitarius (NTS) or systemically injecting the nNOS-specific antagonist S-methyl-l-thiocitrulline. Localization of injection sites in the NTS was confirmed by histology following the experiment. We found that 1) neither NTS-specific nor systemic nNOS antagonism had any effect on hypoxia-mediated changes in breathing or metabolism (P > 0.05), but 2) nNOS protein expression was increased in the middle and caudal NTS by CSH. A persistent HVR after nNOS blockade in the NTS contrasts with results in awake mice, and our findings do not support the hypotheses that nNOS in the NTS contribute to the HVR or VAH in awake rats. [ABSTRACT FROM AUTHOR]

Prostaglandin E2 (PGE2) serves as a critical mediator of hypoxia, infection, and apnea in term and preterm babies. We hypothesized that the prostaglandin E2 receptor type 3 (EP3R) is the receptor responsible for PGE2-induced apneas. Plethysmographic recordings revealed that IL-1β (ip) attenuated the hypercapnic response in C57BL/6J wild-type (WT) but not in neonatal (P9) EP3R_/_ mice (P < 0.05). The hypercapnic responses in brain stem spinal cord en bloc preparations also differed depending on EP3R expression whereby the response was attenuated in EP3R_/_ preparations (P < 0.05). After severe hypoxic exposure in vivo, IL-1β prolonged time to autoresuscitation in WT but not in EP3R mice. Moreover, during severe hypoxic stress EP3R_/_ mice had an increased gasping duration (P < 0.01) as well as number of gasps (P < 0.01), irrespective of intraperitoneal treatment, compared with WT mice. Furthermore, EP3R_/_ mice exhibited longer hyperpneic breathing efforts when exposed to severe hypoxia (P < 0.01). This was then followed by a longer period of secondary apnea before autoresuscitation occurred in EP3R__/_ mice (P < 0.05). In vitro, EP3R_/_ brain stem spinal cord preparations had a prolonged respiratory burst activity during severe hypoxia accompanied by a prolonged neuronal arrest during recovery in oxygenated medium (P < 0.05). In conclusion, PGE2 exerts its effects on respiration via EP3R activation that attenuates the respiratory response to hypercapnia as well as severe hypoxia. Modulation of the EP3R may serve as a potential therapeutic target for treatment of inflammatory and hypoxic-induced detrimental apneas and respiratory disorders in neonates. [ABSTRACT FROM AUTHOR]

When exposed to a hypoxic environment, the body's first response is a reflex increase in ventilation, termed the hypoxic ventilatory response (HVR). With chronic sustained hypoxia (CSH), such as during acclimatization to high altitude, an additional time-dependent increase in ventilation occurs, which increases the HVR and is termed ventilatory acclimatization to hypoxia (VAH). This secondary increase persists after exposure to CSH and involves plasticity within the circuits in the central nervous system that control breathing. The mechanisms of HVR plasticity are currently poorly understood. We hypothesized that changes in neuronal nitric oxide synthase (nNOS) activity or expression in the nucleus tractus solitarius contribute to this plasticity and underlie VAH in rats. To test this, we treated rats held in normoxia or 10% O2 (CSH, PIO2 = 70 Torr) for 7-9 days and measured ventilation in conscious, unrestrained animals before and after microinjecting the general NOS antagonist L-NG-Nitroarginine methyl ester into the nucleus tractus solitarius (NTS) or systemically injecting the nNOS-specific antagonist S-methyl-l-thiocitrulline. Localization of injection sites in the NTS was confirmed by histology following the experiment. We found that 1) neither NTS-specific nor systemic nNOS antagonism had any effect on hypoxia-mediated changes in breathing or metabolism (P > 0.05), but 2) nNOS protein expression was increased in the middle and caudal NTS by CSH. A persistent HVR after nNOS blockade in the NTS contrasts with results in awake mice, and our findings do not support the hypotheses that nNOS in the NTS contribute to the HVR or VAH in awake rats. [ABSTRACT FROM AUTHOR]

Central blood volume loss to venous pooling in the lower extremities and vasoconstrictor response are commonly viewed as key factors to distinguish between individuals with high and low tolerance to orthostatic stress. In this study, we analyzed calf vasoconstriction as a function of venous pooling during simulated orthostatic stress. We hypothesized that high orthostatic tolerance (OT) would be associated with greater vasoconstrictor responses to venous pooling compared with low OT. Nineteen participants underwent continuous stepped lower body negative pressure at - 10, -20, -30, -40, -50, and -50 mmHg each for 5 min or until exhibiting signs of presyncope. Ten participants completed the lower body negative pressure procedure without presyncope and were categorized with high OT; the remaining nine were categorized as having low OT. Near-infrared spectroscopy measurements of vasoconstriction (Hachiya T, Blaber A, Saito M. Acta Physiologica 193: 117-127, 2008) in calf muscles, along with heart rate (HR) responses for each participant, were evaluated in relation to calf blood volume, estimated by plethysmography. The slopes of this relationship between vasoconstriction and blood volume were not different between the high- and low-tolerance groups. However, the onset of vasoconstriction in the high-tolerance group was delayed. Greater HR increments in the low-tolerance group were also observed as a function of lower limb blood pooling. The delayed vasoconstriction and slower HR increments in the high-tolerance group to similar venous pooling in the low group may suggest a greater vascular reserve and possible delayed reduction in venous return. [ABSTRACT FROM AUTHOR]

In a recent study (Huang YH et al. Respir Physiol Neurobiol 143: 1-8, 2004), we showed that prenatal nicotine exposure (PNE) increased the frequency of spontaneous apneic events on the first 2 days of life in unanesthetized neonatal rats. Here we test the hypothesis that PNE blunts chemoreceptor reflexes. Ventilatory responses to three levels each of hypoxia (inspired O2 fraction: 16, 12, and 10%) and hypercapnia (3, 6, and 9% inspired CO2 fraction, all in 50% O2, balance N2), and one level each of combined hypoxia-hypercapnia (H/H: 12% inspired O2 fraction/5% inspired CO2 fraction) and hyperoxia (50% O2 50% N2) were recorded with head-out plethysmography in neonatal rats exposed to either nicotine (N = 12) or physiological saline (N = 12) in the prenatal period. Recordings were made on postnatal day 1 (P1), P3, P6, P9, P12, and P18, in each animal. The change in ventilation in response to hypoxia was blunted in PNE animals on P1 and P3, but there were no other treatment effects. Hyperoxia significantly depressed ventilation in both groups from P3-P18, but there were no significant treatment effects. The ventilatory response to 3,6, and 9% inspired CO2 was significantly blunted in PNE animals at all ages studied, due exclusively to a blunted tidal volume response. PNE also blunted the ventilatory response to H/H at all ages, due primarily to blunting of the tidal volume response. PNE had no significant effect on body mass or metabolic rate, except that PNE animals had a slightly higher mass on P18 and a lower metabolic rate on P1. As shown by others. PNE has small and inconsistent effects on hypoxic ventilatory responses, but here we show that responses to hypercapnia and H/H are consistently blunted by PNE due to a diminished tidal volume response. The combination of reduced hypoxic and hypercapnic sensitivity over the first 3 days of life may define an especially vulnerable developmental period. [ABSTRACT FROM AUTHOR]

Effects of hypoxia on cerebral circulation are important for occupational, high-altitude, and aviation medicine. Increased risk of fainting might be attributable to altered cerebral circulation by hypoxia. Dynamic cerebral autoreg ulation is reportedly impaired immediately by mild hypoxia. How ever, continuous exposure to hypoxia causes hyperventilation, result ing in hypocapnia. This hypocapnia is hypothesized to restore im paired dynamic cerebral autoregulation with reduced steady-state cerebral blood flow (CBF). However, no studies have examined hourly changes in alterations of dynamic cerebral autoregulation and steady-state CBF during sustained hypoxia. We therefore examined cerebral circulation during 5-h exposure to 15% O2 hypoxia and 21% O2 in 13 healthy volunteers in a sitting position. Waveforms of blood pressure and CBF velocity in the middle cerebral artery were mea sured using finger plethysmography and transcranial Doppler ultra sonography. Dynamic cerebral autoregulation was assessed by spec tral and transfer function analysis. As expected, steady-state CBF velocity decreased significantly from 2 to 5 h of hypoxia, accompa nying 2 to 3-Ton decreases in end-tidal CO2 (ETCO2). Furthermore, transfer function gain and coherence in the very-low-frequency range increased significantly at the beginning of hypoxia, indicating im paired dynamic cerebral autoregulation. However, contrary to the proposed hypothesis, indexes of dynamic cerebral autoregulation showed no significant restoration despite ETCO2 reductions, resulting in persistent higher values of very-low-frequency power of CBF velocity variability during hypoxia (214 ± 40% at 5 h of hypoxia vs. control) without significant increases in blood pressure variability. These results suggest that sustained mild hypoxia reduces steady-state CBF and continuously impairs dynamic cerebral autoregulation, im plying an increased risk of shortage of oxygen supply to the brain. [ABSTRACT FROM AUTHOR]

The abdominal and rib cage contributions to tidal breathing differ between rapid-eye-movement (REM) and non-NREM sleep. We hypothesized that abdominal relative contribution during NREM and REM sleep would be altered in different directions when comparing sleep on Earth with sleep in sustained microgravity (μG), due to conformational changes and differences in coupling between the rib cage and the abdominal compartment induced by weightlessness. We studied respiration during sleep in five astronauts before, during, and after two Space Shuttle missions. A total of 77 full-night (8 h) polysomnographic studies were performed; abdominal and rib cage respiratory movements were recorded using respiratory inductive plethysmography. Breath-by- breath analysis of respiration was performed for each class: awake, light sleep, deep sleep, and REM sleep. Abdominal contribution to tidal breathing increased in μG, with the first measure in space being significantly higher than preflight values, followed by a return toward preflight values. This was observed for all classes. Preflight, rib cage, and abdominal movements were found to be in phase for all but REM sleep, for which an abdominal lead was observed. The abdominal leading role during REM sleep increased while deep sleep showed the opposite behavior, the rib cage taking a leading role in-flight. In μG, the percentage of inspiratory time in the overall breath, the duty cycle (TI/TTot), decreased for all classes considered when compared with preflight, while normalized inspiratory flow, taking the awake values as reference, increased in-flight for light sleep, deep sleep, and REM. Changes in abdominal-rib cage displacements probably result from a less efficient operating point for the diaphragm and a less efficient coupling between the abdomen and the apposed portion of the rib cage in μG. However, the preservation of total ventilation suggests that short-term adaptive mechanisms of ventilatory control compensate for these mechanical changes. [ABSTRACT FROM AUTHOR]

A number of deposition models for humans, as well as experimental animals, have been described. However, no breath-by-breath deposition measurement in rats has been reported to date. The objective of this study is to determine lung deposition of micrometer-sized particles as a function of breathing parameters in the adult rat lung. A new aerosol photometry system was designed to measure deposition of nonhygroscopic, 2-μm sebacate particles in anesthetized, intubated, and spontaneously breathing 90-day-old Wistar-Kyoto rats placed in a size-adjusted body plethysmograph box. Instrumental dead space of the system was minimized down to 310 μl (i.e., ∼20% of respiratory dead space). The system allows continuous monitoring of particle concentration in the respired volume. Breathing parameters, such as respiratory rate (f), tidal volume (VT), as well as inspiration/expiration times, were also monitored at different levels of anesthesia. The results showed that VT typically varied between 1.5 and 4.0 ml for regular breathing and between 4.0 and 10.0 ml for single-sigh breaths; f ranged from 40 to 200 breaths/mi Corresponding deposition values varied between 5 and 50%, depending on breath-by-breath breathing patterns. The best fit of deposition (D) was achieved by a bilinear function of VT and f and found to be D = 11.0 0.09·f + 3.75·VT. We conclude that our approach provides more realistic conditions for the measurement of deposition than conventional models using ventilated animals and allows us to analyze the correlation between breath-specific deposition and spontaneous breathing patterns. [ABSTRACT FROM AUTHOR]

We investigated whether obesity is associated with airway hyperresponsiveness in otherwise healthy humans and, if so, whether this correlates with a restrictive lung function pattern or a decreased number of sighs at rest and/or during walking. Lung function was studied before and after inhaling methacholine (MCh) in 41 healthy subjects with body mass index ranging from 20 to 56. Breathing pattern was assessed during a 60-mm rest period and a 30-mm walk. The dose of MCh that produced a 50% decrease in the maximum expiratory flow measured in a body plethysmograph (PD50MCh) was inversely correlated with body mass index (r2 = 0.32, P < 0.001) and waist circumference (r2 = 0.25, P < 0.001). Significant correlations with body mass index were also found with the maximum changes in respiratory resistance (r2 = 0.19, P < 0.001) and reactance (r2 0.40, P < 0.001) measured at 5 Hz. PD50MCh was also positively correlated with functional residual capacity (r2 = 0.56, P < 0.001) and total lung capacity (r2 = 0.59, P < 0.00 1) in men, but not in women. Neither PD50MCh nor body mass index correlated with number of sighs, average tidal volume, ventilation, or breathing frequency. In this study, airway hyperresponsiveness was significantly associated with obesity in otherwise healthy subjects. In obese men, but not in women, airway hyperresponsiveness was associated with the decreases in lung volumes. [ABSTRACT FROM AUTHOR]

At birth, the initiation of pulmonary gas exchange is dependent on air entry into the lungs, and recent evidence indicates that pressures generated by inspiration may be involved. We have used simultaneous plethysmography and phase-contrast X-ray imaging to investigate the contribution of inspiration and expiratory braking maneuvers (EBMs) to lung aeration and the formation of a functional residual capacity (FRC) after birth. Near-term rabbit pups (n = 26) were delivered by cesarean section, placed in a water plethysmograph, and imaged during the initiation of spontaneous breathing. Breath-by-breath changes in lung gas volumes were measured using plethysmography and visualized using phase- contrast X-ray imaging. Pups rapidly (1-5 breaths) generate a FRC (16.2 ± 1.2 ml/kg) by inhaling a greater volume than they expire (by 2.9 ± 0.4 ml∙kg-1∙breath-1 over the first 5 breaths). As a result, 94.8 ± 1.4% of lung aeration occurred during inspiration over multiple breaths. The incidence of EBMs was rare early during lung aeration, with most (>80%) occurring after >80% of max FRC was achieved. Although EBMs were associated with an overall increase in FRC, 34.8 ± 5.3% of EBMs were associated with a decrease in FRC. We conclude that lung aeration is predominantly achieved by inspiratory efforts and that EBMs help to maintain FRC following its formation. [ABSTRACT FROM AUTHOR]

Autoresuscitation is a critical survival-promoting mechanism in mammals that allows recovery from primary apnea via hypoxia-induced gasping. Here we show, using head-out plethysmography, that gasping behavior is altered during autoresuscitation, and the autoresuscitation response is delayed, in neonatal 5-hydroxytryptamine (5-HT) neuron-deficient Pet-i homozygous (Pet-1-/-) mice. When exposed to 97% N2-3% CO2 on postnatal day 4.5, unanesthetized Pet-1-/- mice required over four times longer than age-matched wild-type controls to initiate gasping following primary apnea. When oxygen was made available before the first gasp, allowing autoresuscitation to occur, gasping frequency was decreased and the duration of the gasping period was extended in the Pet-1 mutants compared with wild type, resulting in a nearly threefold increase in the time needed for successful autoresuscitation. However, when the exposure to anoxia was unrelenting, gasping frequency, the form of the gasps, the total number of gasps produced, the duration of the gasping period, and time to last gasp were comparable to controls. Plethysmographic testing of the same mutants on postnatal day 9.5 revealed that their autoresuscitation responses, although improved compared with day 4.5, remained significantly longer than in wild-type controls. Our data indicate that despite a severe deficiency of central 5-HT neurons, Pet-1-/- neonatal mice are capable of gasping, but their gasping pattern is altered during autoresuscitation, leading to a prolongation of the time required to recover from hypoxia-induced apnea. [ABSTRACT FROM AUTHOR]

The factors regulating lung aeration and the initiation of pulmonary gas exchange at birth are largely unknown, particularly in infants born very preterm. As hydrostatic pressure gradients may play a role, we have examined the effect of a positive end-expiratory pressure (PEEP) on the spatial and temporal pattern of lung aeration in preterm rabbit pups mechanically ventilated from birth using simultaneous phase-contrast X-ray imaging and plethysmography. Preterm rabbit pups were delivered by caesarean section at 28 days of gestational age, anesthetized, intubated, and placed within a water-filled plethysmograph (head out). Pups were imaged as they were mechanically ventilated from birth with a PEEP of either 0 cmH2O or 5 cmH2O. The peak inflation pressure was held constant at 35 cmH2O. Without PEEP, gas only entered into the distal airways during inflation. The distal airways collapsed during expiration, and, as a result, the functional residual capacity (FRC) did not increase above the lung's anatomic dead space volume (2.5 ± 0.8 ml/kg). In contrast, ventilation with 5-cmH2O PEEP gradually increased aeration of the distal airways, which did not collapse at end expiration. The FRC achieved in pups ventilated with PEEP (19.9 ± 3.2 ml/kg) was significantly greater than in pups ventilated without PEEP (-2.3 ± 3.5 ml/kg). PEEP greatly facilitates aeration of the distal airways and the accumulation of FRC and prevents distal airway collapse at end expiration in very preterm rabbit pups mechanically ventilated from birth. [ABSTRACT FROM AUTHOR]

Double-chamber plethysmography is a well established noninvasive method of assessing airflow obstruction in small lab animals, it allows measurement of the specific airway resistance (sRaw), which unlike enhanced pause (Penh), is a meaningful airway mechanics parameter. Since sRaw is measured in spontaneously breathing mice, a limitation of the method is the inability to exclude nasal resistance changes. We recently showed that mice are not truly obligate nasal breathers and that after nasal occlusion, nasally breathing mice can transition to an oral mode of breathing. We now show that it is experimentally possible to algebraically separate the average nasal and pulmonary (including laryngeal) components of total airway resistance change by a series of measurements made across groups of mice breathing nasally or orally, assuming that oral resistance remains constant. Using this approach, we show that nasal resistance change comprises one-half or more of the total resistance change during methacholine challenge. Inhibition of mucin secretion from airway goblet cells attenuates pulmonary but not nasal airway hyperresponsiveness (AHR), and nasal AHR in a murine model of rhinitis may be related to edema. [ABSTRACT FROM AUTHOR]

An acoustic whole body plethysmograph was developed to estimate specific airway resistance (sRaw) in unrestrained mice. The plethysmograph uses acoustic principles to measure the thoracic breathing pattern and simultaneously measures the airflow entering and/or leaving the plethysmograph. Similarly to traditional methods utilizing a double-chamber plethysmograph, these measurements were combined to estimate sRaw. To evaluate the new system, we placed six conscious A/J mice individually in a whole body plethysmograph (Buxco System) for a 2-min exposure to aerosolized methacholine chloride dissolved in saline (0, 5, 10, and 20 mg/mI), which is known to increase sRaw in mice. Three minutes after exposure, the mice were transferred to the acoustic plethysmograph for 2 mm for data collection. The mean baseline value of sRaw was 0.93 ± 0.10 cmH2O·s. A dose-dependent increase in sRaw was shown, with an approximate tripling of sRaw at the highest dose. These results demonstrate the ability of the system to estimate sRaw based on plethysmograph airflow and acoustic amplitude. [ABSTRACT FROM AUTHOR]

The double sigmoidal nature of the mouse pressure-volume (PV) curve is well recognized but largely ignored. This study systematically examined the effect of inflating the mouse lung to 40 cm H2O transrespiratory pressure (Prs) in vivo. Adult BALB/c mice were anesthetized, tracheostomized, and mechanically ventilated. Thoracic gas volume was calculated using plethysmography and electrical stimulation of the intercostal muscles. Lung mechanics were tracked during inflation-deflation maneuvers using a modification of the forced oscillation technique. Inflation beyond 20 cm H2O caused a shift in subsequent PV curves with an increase in slope of the inflation limb and an increase in lung volume at 20 cm H2O. There was an overall decrease in tissue elastance and a fundamental change in its volume dependence. This apparent "softening" of the lung could be recovered by partial degassing of the lung or applying a negative transrespiratory pressure such that lung volume decreased below functional residual capacity. Allowing the lung to spontaneously recover revealed that the lung required ∼1 h of mechanical ventilation to return to the original state. We propose a number of possible mechanisms for these observations and suggest that they are most likely explained by the unfolding of alveolar septa and the subsequent redistribution of the fluid lining the alveoli at high transrespiratory pressure. [ABSTRACT FROM AUTHOR]

Recent studies described the in vivo ventilatory phenotype of mutant newborn mice with targeted deletions of genes involved in the organization and devel- opment of the respiratory-neuron network. Whole body flow barometric pleth- ysmography is the noninvasive method of choice for studying unrestrained newborn mice. Breathing-pattern abnormalities with apneas occur in mutant newborn mice that lack genes involved in the development and modulation of rhythmogenesis. Studies of deficits in ventilatory responses to hypercapnia and/or hypoxia helped to identify genes involved in chemosensitivity to oxygen and carbon dioxide. Combined studies in mutant newborn mice and in humans have shed light on the pathogenesis of genetically determined respiratory- control abnormalities such as congenital central hypoventilation syndrome, Rett syndrome, and Prader-Willi syndrome. The development of mouse models has opened up the field of research into new treatments for respiratory-control disorders in humans. [ABSTRACT FROM AUTHOR]

Measurement of breathing volumes in neonatal mice is of growing importance in order to characterize the influence of development and genetic modifications on respiratory control to evaluate hypotheses concerned with human infant deficits that may affect sudden infant death syndrome, for example. Current techniques require undesirable physical constraints or incur possible artifacts specific to very small animals. We have examined the utility of a recently proposed approach using an acoustic resonance procedure that does not require undue physical constraint beyond placement in the acoustic plethysmograph. We show here that this approach can be applied to baby mice 5 days after birth and that it can be accurately calibrated. In addition, this approach should be useful to study unrestrained neonatal mice under conditions where body temperature approaches environmental temperature and barometric plethysmography cannot be used. [ABSTRACT FROM AUTHOR]

The assessment of lung mechanical function in small animals, particularly mice, is essential for investigations into the pathophysiology of pulmonary disease. The most accurate and specific methods for making this assessment are highly invasive and so provide data of questionable relevance to normality. By contrast, present noninvasive methods based on unrestrained plethysmography have no direct link to the mechanical properties of the lung. There is thus a need for a completely noninvasive method for determining lung mechanical function in small animals. In the present study, we demonstrate an extension of unrestrained plethysmography in which changes in lung volume are estimated via orthogonal video imaging of the thorax. These estimates are combined with the pressure swings recorded as mice breathe inside a heated and humidified chamber to yield an estimate of specific airway resistance (sRaw). We used this new technique, which we term "unrestrained video-assisted plethysmography" (UVAP), to measure sRaw in 11 BALB/c mice exposed to aerosols of saline, methacholine, and albuterol and obtained mean values of 0.71, 1.23 and 1.10 cmH2O·s, respectively. Mean breathing frequency was 4.3, 3.4, and 3.6 breaths/s, respectively, while the corresponding mean tidal volumes were 0.36, 0.44 and 0.37 ml, respectively. We conclude that UVAP, a noninvasive method, is able to provide usefully accurate estimates of sRaw and breathing pattern parameters in mice. [ABSTRACT FROM AUTHOR]

Substance P is known to be involved in respiratory rhythm and central pattern-generating mechanisms, especially during early development. We therefore studied respiratory responses in transgenic newborn mice (Tacl-/-) lacking substance P and neurokinin A (NKA). In vivo, the effects of intermittent isocapnic hypoxia (IH) and hypercapnia were studied using whole body flow plethysmography at P2-3 and P8-10. In vitro, anoxic responses and the effects of hypocapnic and hypercapnic conditions were studied in brain stem-spinal cord preparations (C4 activity) at P2. Hypoxic challenge considerably modified the respiratory activity in transgenic mice displayed in vivo as an attenuated increase in tidal volume during IH. Transgenic mice also showed a more prominent posthypoxic frequency decline in vivo, and posthypoxic neuronal arrests appeared more often in vitro. We recognized two types of sigh activity: with or without a following pause. During IH, the amount of sighs with a pause decreased and those without increased, a redistribution that became stronger with age only in controls. Intermittent anoxia induced long-term facilitation effects in controls, but not in Tacl-/- animals, manifested as an increase in burst frequency in vitro and by an augmentation of ventilation during posthypoxic periods in vivo. Thus our data demonstrate that a functional substance PJNKA system is of great importance for the generation of an adequate respiratory response to hypoxic provocation in newborn mice and during early maturation. It also indicates that substance P (and/or NKA) is involved in the development of the plasticity of the respiratory system. [ABSTRACT FROM AUTHOR]

The mouse is the most extensively studied animal species in respiratory research, yet the technologies available to assess airway function in conscious mice are not universally accepted. We hypothesized that whole body plethysmography employing noninvasive restraint (RWBP) could be used to quantify specific airway resistance (sRaw-RWBP) and airway responsiveness in conscious mice. Methacholine responses were compared using sRaw-RWBP vs. airway resistance by the forced oscillation technique (Raw-FOT) in groups of C57, A/J, and BALB/c mice. sRaw-RWBP was also compared with sRaw derived from double chamber plethysmography (sRaw-DCP) in BALB/c. Finally, airway responsiveness following allergen challenge in BALB/c was measured using RWBP. sRaw-RWBP in C57, A/J, and BALB/c mice was 0.51 ± 0.03, 0.68 ± 0.03, and 0.63 ± 0.05 cmls, respectively. sRaw derived from Raw-FOT and functional residual capacity (Raw∗functional residual capacity) was 0.095 cm/s, approximately one-fifth of sRaw-RWBP in C57 mice. The intra- and interanimal coefficients of variations were similar between sRaw-RWBP (6.8 and 20.1%) and Raw-FOT (3.4 and 20.1%, respectively). The order of airway responsiveness employing sRaw-RWBP was AJ > BALBc > C57 and for Raw-FOT was AJ > BALB/c = C57. There was no difference between the airway responsiveness assessed by RWBP vs. DCP; however, baseline sRaw-RWBP was significantly lower than sRaw-DCP. Allergen challenge caused a progressive decrease in the provocative concentration of methacholine that increased sRaw to 175% postsaline values based on sRaw-RWBP. In conclusion, the technique of RWBP was rapid, reproducible, and easy to perform. Airway responsiveness measured using RWBP, DCP, and FOT was equivalent. Allergen responses could be followed longitudinally, which may provide greater insight into the pathogenesis of chronic airway disease. [ABSTRACT FROM AUTHOR]

Venous compliance is lower in older adults compared with younger adults. It is possible that alterations in venous smooth muscle tone and responsiveness may contribute to the age-related differences in venous compliance. To determine the effects of sympathetic activation [cold pressor test (cold pressor test); rhythmic ischemic handgrip (rhythmic ischemic handgrip)I and endothelium-independent decreases in smooth muscle tone [sublingual nitroglycerin (nitroglycerin)I on venous compliance in young and older adults, forearm and calf venous compliance was measured in 12 young (22 ± 1 yr) and 12 old (65 ± 1 yr) supine subjects using venous occlusion plethysmography. Venous compliance was assessed at baseline, during the cold pressor test and rhythmic ischemic handgrip tests, and after nitroglycerin administration. All pressure-volume relationships were modeled with a quadratic regression equation, and β1 and β2 were used as indexes of venous compliance. A repeated-measures ANOVA was used to determine the effect of the age and trial on venous compliance. Calf regression parameters β1 (0.0639 ± 0.0126 vs. 0.0503 ± 0.0059, young vs. older; P < 0.05) and β2 (-0.00054 ± 0.00011 vs. -0.00041 ± 0.00005, young vs. older; P < 0.05) were significantly less in older adults at baseline. Similarly, forearm regression parameters, β1 and β2 were lower in older adults at baseline. Venous compliance was not effected by the cold pressor test test, rhythmic ischemic handgrip, or sublingual nitroglycerin in either group. Data suggest that forearm and calf venous compliance is lower in older adults compared with young. However, this difference probably cannot be explained by alterations in smooth muscle tone or responsiveness. [ABSTRACT FROM AUTHOR]

Electrical stimulation of intercostal muscles was employed to measure thoracic gas volume (TGV) during airway occlusion in the absence of respiratory effort at different levels of lung inflation. In 15 tracheostomized and mechanically ventilated CBA/Ca mice, the value of TGV obtained from the spontaneous breathing effort available in the early phase of the experiments (TGVsp) was compared with those resulting from muscle stimulation (TGVst) at transrespiratory pressures of 0, 10, and 20 cmH2O. A very strong correlation (r² = 0.97) was found, although with a systematically (∼16%) higher estimation of TGVst relative to TGVsp, attributable to the different durations of the stimulated (∼50 ms) and spontaneous (∼200 ms) contractions. Measurements of TGVst before and after injections of 0.2, 0.4, and 0.6 ml of nitrogen into the lungs in six mice resulted in good agreement between the change in TGVst and the injected volume (r² = 0.98). In four mice, TGVsp and TGVst were compared at end expiration with air or a helium-oxygen mixture to confirm the validity of isothermal compression in the alveolar gas. The TGVst values measured at zero transrespiratory pressure in all CBA/Ca mice [0.29 ± 0.05 (SD) ml] and in C57BL/6 (N = 6; 0.34 ± 0.08 ml) and BALB/c (N = 6; 0.28 ± 0.06 ml) mice were in agreement with functional residual capacity values from previous studies in which different techniques were used. This method is particularly useful when TGV is to be determined in the absence of breathing activity, when it must be known at any level of lung inflation or under non-steady-state conditions, such as during pharmaceutical interventions. [ABSTRACT FROM AUTHOR]

Application of compression stockings to the lower extremities is a widely used therapeutic intervention to improve venous return, but there is little information about the effects of compression on local arterial perfusion. Therefore, we tested the hypothesis that a positive external pressure increases forearm perfusion. The relation of increasing external pressure induced by standardized compression to the arterial inflow and arterial flow reserve of the forearm was critically evaluated in a group of healthy young men (n = 9). Flow was measured with venous occlusion plethysmography after a 10-mm application of six different stockings with compression pressure increasing from 13 to 23 mmHg. During compression, the arterial inflow increased significantly from 3.7 ± 0.85 to 8.8 ± 2.01 ml·min-1 100 ml tissue-1 (P < 0.001) and the arterial flow reserve increased from 17.7 ± 4.7 to 28.3 ± 7.0 ml·min-1·100 ml tissue-1. The flow increase was persistent after 3 h of constant application of external pressure and also during simultaneous low-intensity hand grip. Similar results obtained with occlusion plethysmography were seen with MRI. During the interventions, forearm temperature was unchanged, and the volunteers reported no discomfort. In conclusion, 1) arterial perfusion of the human forearm increases more than twofold during application of external compression over a pressure range of 13-23 mmHg, and 2) the result is interpreted as an autoregulatory response following the decrease of the vascular transmural pressure gradient. [ABSTRACT FROM AUTHOR]

Prolonged microgravity alters the regulation of the peripheral vasculature. The influence of reduced food intake, as often observed in astronauts, on vascular function is unclear. In a randomized, four-phase, crossover study, the effect of simulated microgravity (13 days of bed rest), energetic restriction (-25%, fat reduced), and their combination on endothelium-dependent and -independent vasodilation was compared with ambulatory control conditions. Using venous occlusion plethysmography, cumulative intra-arterial dose-response curves to endothelium- dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators were constructed in 10 healthy male volunteers before and on day 13 of each of the four intervention periods. Bed rest combined with normoenergetic nutrition impaired the dose-response to acetylcholine (ANOVA, P = 0.004) but not to sodium nitroprusside, whereas hypoenergetic diet under ambulatory conditions improved responses to acetylcholine (P = 0.044) and sodium nitroprusside (P < 0.001), When bed rest was combined with hypoenergetic diet, acetylcholine responses did not change. Similarly, under control conditions, no change was observed. Individual changes in the total cholesterol-to-HDL ratio were correlated with changes in endothehial and vascular smooth muscle relaxation. In conclusion, short-term bed rest impairs endothelium-dependent arterial relaxation in humans. A hypoenergetic, low-fat diet modulates serum lipids, improves endothelium-dependent and -independent relaxation, and may antagonize the unfavorable effects of simulated microgravity on endothelial function. [ABSTRACT FROM AUTHOR]

The influence of age on limb vasodilator capacity in women is unclear. The objectives of this study were to characterize and compare age-associated changes in forearm and calf peak vascular conductance (VCpeak; a functional index of arterial structure) in women and to identify physiological characteristics predictive of variation in limb-specific VCpeak. Peak conductance (plethysmographic flow/mean arterial pressure), VCpeak of the forearm (forearm VCpeak), and calf (calf VCpeak) after 10 mm of arterial occlusion were measured in 58 healthy, normally active women aged 21-79 yr. Aerobic capacity (cycle peak oxygen uptake), arterial health (pulse-wave velocity, ankle-brachial index), total cholesterol, limb-specific tissue composition (dual-energy X-ray absorptiometry), and isometric strength (handgrip, plantar flexion) were also assessed. The relative decline in calf VCpeak with age (-6.8% per decade, P < 0.001) was greater than the forearm (-4.4% per decade, P = 0.004), in contrast to results previously reported for men (forearm decline > calf decline). Limb VCpeak per kilogram muscle declined with age in the calf (-6.0% per decade; P = 0.002), but not the forearm (P = 0.12). Age, cholesterol, and regional tissue composition were significant predictors of peak conductance in both limbs; however, age was a stronger predictor of peak conductance in the calf. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in women, but the magnitude of this effect is region specific. Further research will be required to determine whether the decline in lower extremity vasodilator capacity with age explains diminished exercising leg vasodilation in older women. [ABSTRACT FROM AUTHOR]

We developed a method for measuring airway resistance (Raw) in mice that does not require a measurement of airway flow. An analysis of Raw induced by alveolar gas compression showed the following relationship for an animal breathing spontaneously in a closed box: Raw = AbtVb/[Vt (Ve + 0.5Vt)]. Here Abt is the area under the box pressure-time curve during inspiration or expiration, Vb is box volume, Vt is tidal volume, and Ve is functional residual capacity (FRC). In anesthetized and conscious unrestrained mice, from experiments with both room temperature box air and body temperature humidified box air, the contributions of gas compression to the box pressure amplitude were 15 and 31% of those due to the temperature-humidity difference between box and alveolar gas. We corrected the measured Abt and Vt for temperature-humidity and gas compression effects, respectively, using a sinusoidal analysis. In anesthetized mice, Raw averaged 4.3 cmH2O·ml-1·s, fourfold greater than pulmonary resistance measured by conventional methods. In conscious mice with an assumed FRC equal to that measured in the anesthetized mice, the corrected Raw at room temperature averaged 1.9 cmH2O·ml-1·s. In both conscious mice and anesthetized mice, exposure to aerosolized methacholine with room temperature box air significantly increased Raw by around eightfold. Here we assumed that in the conscious mice both Vt and FRC remained constant. In both conscious and anesthetized mice, body temperature humidified box air reduced the methacholine-induced increase in Raw observed at room temperature. The method using the increase in Abt with bronchoconstriction provides a conservative estimate for the increase in Raw in conscious mice. [ABSTRACT FROM AUTHOR]

Uncertainty exists as to whether a period of passive arterial occlusion (PAO) or ischemic exercise (IE) results in peak lower leg vascular conductance (LVC). This uncertainty is due to the different body positions, active muscle mass, and occlusion times used for PAO or IE. The purpose of this study was to examine whether 10 min of PAO elicits a similar LVC compared with ischemic dorsiflexion (IDF), ischemic plantar flexion (IPF), and ischemic plantar-dorsiflexion (IPDF). Ten subjects (5 women, 27 ± 9 yr, 68 ± 3 kg) were studied on 3 days over 1 wk in a semireclined position with the right foot attached to an isokinetic dynamometer. Mean arterial pressure (Finapres) and lower leg blood flow (LBF, venous occlusion plethysmography) were measured at rest and after PAO and IE. PAO was administered randomly on 1 of the 3 days and before IE. IE protocols consisted of maximal isokinetic dorsiflexion and/or plantar flexion at 120 and 60%, respectively. In a second experiment, an additional eight subjects (4 women, 29 ± 12 yr, 77 ± 12 kg) were studied to examine the effect of isokinetic speed during IDF on peak LBF and LVC. Peak LVC (ml·min-1·100 ml-1·mmHg-1) was similar among IPF (0.590 ± 0.16), IPDF (0.532 ± 0.17), and PAO (0.511 ± 0.18), and significantly lower after IDF (0.334 ± 0.15). No differences in peak LBF and LVC were observed after IDF using different isokinetic speeds. We conclude that 10 min of PAO, IPF, and IPDF performed in a similar posture are adequate stimuli to elicit peak LVC. [ABSTRACT FROM AUTHOR]

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% 02) 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. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the effects of the different states of alertness on 1) nonnutritive swallowing (NNS) frequency, 2) the relationship between NNS and the respiratory cycle, and 3) the association of NNS with spontaneous apneas. Recordings of sleep states, diaphragm and laryngeal constrictor electrical activity, nasal flow, electrocardiogram, respiratory inductance plethysmography, and pulse oximetry were obtained from six preterm lambs without sedation. Analysis of 2,468 NNS showed that 1) NNS frequency was higher during quiet wakefulness and active sleep (AS) than in quiet sleep; 2) in all states of alertness, a greater number of NNS (38%) were preceded and followed by an inspiration; 3) although NNS and central apneas were rarely coincidental, AS appeared to favor their association; and 4) most obstructive apneas occurred in AS and were coincidental with bursts of NNS. Compared with results in full-term lambs, premature birth does not modify the NNS-respiratory coordination. However, AS in preterm lambs is characterized by a higher association of NNS bursts with obstructive apneas. [ABSTRACT FROM AUTHOR]

Differences in breathing pattern between awake C57BL/6J (B6) and A/J mice are such that A/J mice breathe slower, deeper, and with greater variability than B6. We theorized that urethane anesthesia, by affecting cortical and subcortical function, would test the hypothesis that strain differences require a fully functional neuroaxis. We anesthetized B6 and A/J mice with urethane, placed them in a whole-body plethysmograph, and measured the durations of inspiration and expiration, respiratory frequency (FR), and peak amplitude during exposure to room air (21% O2), hyperoxia (5 min, 100% O2), hypoxia (5 min, 8% O2), and posthypoxic reoxygenation (5 min, 100% O2). Breathing variability was assessed by calculating the coefficient of variation (CV) and by applying spatial statistics to Poincaré plots constructed from the timing and amplitude data. Even though FR in anesthetized B6 and A/J mice was greater than that for unanesthetized animals, anesthetized A/J mice still breathed slower, deeper, and with greater variability than B6 mice at rest and during hyperoxia. During the fourth minute of hypoxia, FR and its CV were not significantly different between strains. Even though FR was similar between strains immediately after hypoxia, its CV was significantly greater for B6 than A/J mice. Posthypoxic FR was significantly less than baseline FR in B6 but not A/J mice, and the CV for posthypoxic FR was greater for B6 but less for AJ mice compared with baseline CV. This difference in patterning was confirmed by spatial statistical analysis. We conclude that strain-specific differences in respiratory pattern and its variability are robust genetic traits. The neural substrate for these differences, at least partially, exists within subcortical structures generating the breathing pattern. [ABSTRACT FROM AUTHOR]

There has been significant utilization of the technique described by Hamelmann et al. (Am J Respir Crit Care Med 156: 766-775, 1997) in which a parameter, enhanced pause (Penh), related to airways responsiveness is noninvasively measured by unrestrained plethysmography (UP). Investigating this technique, we sought to answer these questions: 1) How do changes in Penh compare with changes in traditional plethysmographic and lung mechanical parameters? 2) How do tIP parameters perform in two different mouse strains? Awake immunized and control BALB/c (n = 16) and C57BL/6 (n = 14) mice were placed in the UP chamber and exposed to doses of aerosolized methacholine while the following parameters were measured at each concentration: inspiratory time (TI), expiratory time (TE), total time (Ttot), TI/Ttot, peak inspiratory pressure, peak expiratory pressure, Pause, Penh, tidal volume (VT), VT/TI, VT/TE, and VT/Ttot. The next day, lung resistance (RL) and compliance (CL) were invasively measured in the same animals. For the BALB/c, the parameters with the highest magnitude of correlation coefficient vs. RL are (in order) 1) CL, 2) Pause and Penh, 3) parameters of breathing frequency (TE, Ttot, TI), and 4) parameters related to VT (inspiratory pressure, expiratory pressure). Flow parameters (VT/Ttot, VT/TE, VT/TI) and duty cycle parameters (TI/Ttot) had insignificant correlations. This ordering is significantly different in C57BL/6 mice, in which the parameters with the largest correlations are 1) CL, 2) parameters of breathing frequency, and 3) flow parameters. Pause, Penh, VT, and duty cycle parameters had insignificant correlations. These data show that Penh is problematic in the sense that it is strain specific; it behaves very differently in BALB/c and C57BL/6 mice. We suggest that UP parameters largely originate as part of reflex control of breathing processes, rather than in the lung mechanics and conclude that it is inappropriate to use LIP parameters in general, and Penh specifically, as substitute variables for invasive mechanical indexes such as RL. [ABSTRACT FROM AUTHOR]

Evaluates two venous occlusion plethysmography systems used for assessing forearm blood flow. Use of mercury-in-Silastic strain gauges in the Hokanson system; Ability of F2001 to measure capillary permeability; Advantages and disadvantages of the Hokanson system and F2001.

Presents a study on the measurement of rate of exchange of oxygen and carbon dioxide between alveolar gas and pulmonary capillary blood on a breath-by-breath (BbB) basis. Measurement of gas transit time from mouthpiece to oxygen meter; Changes in the amount of oxygen and carbon dioxide stored in alveolar gas; Ability of optoelectronic plethysmography to track BbB changes in end-expiratory lung volume.

Assesses the effect of 18 days of bed rest on leg and arm venous properties. Hypothesis that the magnitude of the venous changes would be related to orthostatic intolerance; Increase in leg venous flow resistance after bed rest; Expression of maximal lower body negative pressure tolerance as cumulative stress.

Investigates whether keratinocyte growth factor alters pulmonary function variables. Examination on pulmonary function by body plethysmography; Correlation between cell hyperplasia and a reduction in tidal volume and increase in breathing frequency; Reduction of vital capacity of pulmonary functions.

Investigates whether administration of nitrogen oxide substrate of L-arginine protects against ischemia-perfusion-induced endothelial dysfunction in humans. Measurement of forearm blood flow; Use of venous occlusion plethysmography; Recovery of endothelium-dependent vasodilation.

Determines how the variation of lung volume affects specific measures of swallowing physiology. Use of simultaneous video fluoroscopy and respiratory inductance plethysmography; Total lung capacity; Pharyngeal activity duration of deglutition.

Examines the various methods available for the assessment of lung function in mice. Comparison of methods in terms of the phenotyping uncertainty principle; Unrestrained plethysmography in conscious mice; Measurement of input impedance in anesthetized, paralyzed and tracheotomized mice.

Assesses the feasibility of double-chamber plethysmography in mice, in particular by defining conditions under which the psychological constraints linked to stress can be kept to a minimum. Differences linked to somatic growth, strain and sex on the double-chamber plethysmographic pulmonary function values; Reference values in growing male and female conscious and healthy BALB/c and C57BL/6 mice.

Develops a method to assess factors determining diaphragm fiber length using optoelectronic plethysmography. Measurement of volume displacements of the rib cage and anterolateral abdominal wall; Ultrasound measurements of changes in diaphragm fiber length in the area of apposition.