Respiration physiology最新文献

We used pressure plethysmography to study breathing patterns of neonatal and adult rats acutely exposed to elevated levels of CO₂. Ventilation ($\text{V}\text{̇}$e) increased progressively with increasing inspired CO₂. The rise in $\text{V}\text{̇}$e was associated with an increase in tidal volume, but not respiratory rate. In all animals studied, the CO₂ sensitivity (determined from the slope of the $\text{V}\text{̇}$e vs. inspired % CO₂ curve) was variable on a day to day basis. Chemosensitivity was high in neonates 1 day after birth (P1) and fell throughout the first week to a minimum at about P8. Chemosensitivity rose again to somewhat higher values in P10 through adult rats. The developmental pattern of these in vivo ventilatory responses was different than individual locus coeruleus (LC) neuron responses to increased CO₂. The membrane potential (V_m) of LC neurons was measured using perforated patch (amphotericin B) techniques in brain slices. At all ages studied, LC neurons increased their firing rate by ∼44% in response to hypercapnic acidosis (10% CO₂, pH 7.0). Thus the in vivo ventilatory response to hypercapnia was not correlated with the V_m response of individual LC neurons to hypercapnic acidosis in neonatal rats. These data suggest that CO₂ sensitivity of ventilation in rats may exist in two forms, a high-sensitivity neonatal (or fetal) form and a lower-sensitivity adult form, with a critical window of very low sensitivity during the period of transition between the two (∼P8).

To determine the effect of exercise on serum levels of Clara cell protein (CC16) and surfactant-associated protein A (SP-A), serum was collected from 14 healthy subjects 1 h after maximal and sub-maximal exercise. Healthy volunteers participated on separate occasions in a control (no exercise) session, simulated firefighting tasks for 30 min (n=14), and intermittent treadmill exercise at near maximal heart rates for 60 min (n=10). Serum samples and induced sputum samples were collected 1 h post exercise. Induced sputum fluid was analyzed for tumor necrosis factor alpha (TNF-α), an inflammatory mediator produced by pulmonary macrophages. Serum CC16 levels increased significantly with both firefighting tasks (15±13 μg/L vs. 9±4 μg/L, P=0.047) and treadmill exercise (15±8 μg/L vs. 9±4 μg/L, P<0.01). Serum SP-A concentrations did not change compared to control with either firefighting tasks (247±106 μg/L vs. 247±96 μg/L, P=0.84) or treadmill exercise (251±89 μg/L vs. 285±87 μg/L, P=0.44). TNF-α concentrations in sputum supernatant showed no significant difference from controls. These results show an increase in serum CC16 after exercise. This must be considered when utilizing serum CC16 to determine the presence of lung injury in settings that combine exercise and toxic exposures.

This study was carried out to investigate the relationship between the conduction velocity of the vagal afferents arising from the rat lungs and their sensitivities to capsaicin, other chemical irritants, and lung inflation. We recorded single-unit activities of vagal pulmonary afferents (n=205) in anesthetized, open-chest rats, and distinguished C fibers (conduction velocity<2 m/sec) from myelinated afferents; the latter group was further classified into rapidly adapting pulmonary receptors (RARs) and slowly adapting pulmonary stretch receptors (SARs) on the basis of their adaptation indexes to lung inflation. Right-atrial injection of capsaicin (1 μg/kg) evoked an abrupt and intense stimulatory effect in 88.9% (64/72) of the pulmonary C fibers tested, but only a mild stimulation in 6.3% (3/48) of the RARs and none of the SARs. Other inhaled and injected chemical stimulants (e.g., cigarette smoke, lactic acid) activated 68.9% (42/61) of the pulmonary C fibers. The same chemical irritants exerted a mild stimulatory effect in only 14.5% (8/55) of the RARs; this subgroup of RARs exhibited a low or no baseline activity, and half of them were located near the hilum. Chemical stimulants had little or no effect on SARs. The response of pulmonary C fibers to lung inflation (tracheal pressure=30 cm H₂O) was not only extremely weak, but also showed a longer onset latency and an irregular pattern. In a sharp contrast, lung inflation evoked rapid and vigorous discharges in both RARs and SARs. In conclusion, C fibers are the primary type of chemosensitive vagal pulmonary afferents in rat lungs.

A lumped parameter model of a human pulmonary acinus is derived using results from gas mixing simulations in an anatomically-based asymmetric multi-branching model of the acinus coupled to a symmetric conducting airway model. The model respiratory airways change length in proportion to the cube root of their volume change, and the diameters are updated accordingly assuming constant duct cross-sectional area. The lumped parameter model applies a flux boundary condition at the end of a transitional bronchiole during inspiration to enable realistic concentration changes at this position; during expiration inspiratory parameters are used to predict concentrations at the end of the associated transitional bronchiole. The predicted concentrations are used as time-varying fixed boundary conditions at the end of the transitional bronchiole in conducting airway models during expiration. The current lumped parameter model is most accurate for tidal volumes between 500 and 1500 ml, and equal inspiration and expiration durations of 2 sec. The model's accuracy decreases for changes in breath duration.

It is important to understand the mechanisms by which a deep inspiration (DI) affects bronchoconstriction in rodents so that their relevance as animal models of asthma can be assessed. We investigated the effect of DI on respiratory input impedance after methacholine inhalation in four groups of rats: a control group, a group receiving DI prior to challenge, and two groups receiving different degrees of DI after challenge. We measured respiratory input impedance for 15 min following a challenge. This provided time-courses approximating the resistance of the conducting airways and the impedance of the respiratory tissues. We found no significant difference in the peak changes in airway resistance comparing the control group and any of the DI groups following challenge. However, the peak increase in tissue impedance was reduced in the group receiving the largest DI after challenge. Our results thus suggest that the DIs that we administered were neither bronchodilatory nor bronchoprotective, but that they were able to reduce the amount of airway closure occurring following bronchoconstriction.

Opioid modulation of breathing during postnatal development through to the adult was investigated in the rat. Respiratory frequency, tidal volume and minute volume were recorded in unanesthetized, unrestrained rat pups and adults using barometric plethysmography. Subjects were administered the highly selective μ opioid agonists dermorphin and fentanyl. Fentanyl, which readily crosses the blood-brain barrier, was included to ensure that developmental changes in blood-brain barrier restrictions did not mask some of the dermorphin effects in older neonates. Drugs were administered subcutaneously in neonates and adults, although dermorphin was given by intracerebroventricular route only in adults. In neonates, μ agonist administration caused a gasping-like pattern of breathing, characterized by a marked fall in frequency and a smaller increase in tidal volume. The gasping response was prevented by pre-treatment with the long-acting μ₁ antagonist naloxonazine (NALZ). In the presence of NALZ, μ agonists elicited only a small, but significant, reduction in tidal volume. Both dermorphin and fentanyl showed more potent activity in younger pups than in older pups, possibly in the case of dermorphin because of developmental maturation of blood-brain barrier function. In adults, fentanyl and dermorphin both caused a reduction in frequency and minute volume. The response of adults to fentanyl, but not dermorphin, was prevented by NALZ. These results suggest that both μ₁ and μ₂ receptors contribute to opioid-induced respiratory depression during neonatal and adult life.

The contributions of respiratory and conducting airway asymmetry, gas exchange, and non-uniform ventilation to the sloping alveolar plateau in phase III of the gas washout curve are investigated using mathematical models of the human lung. The models range from fully symmetric, to a detailed asymmetric conducting airway model coupled with 29 445 lumped parameter respiratory airway models. A gas transport equation is solved in the models using a Lagrange-Galerkin method. The alveolar slope is normalised by the mean expired gas concentration to give S_n. The model results confirm that first breath S_n is influenced mainly by respiratory airway asymmetry, and that at near-normal levels of ventilation the conducting airway asymmetry contributes a significant amount to further increases in S_n. Gas exchange moderates the plot of S_n against breath number, such that it approaches a plateau in later breaths. Non-uniform flow also alters S_n, indicating that an accurate description of the pleural pressure gradient will be necessary for more accurate simulations.

Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319±24 to 459±27 and from 58±16 to 270±35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.