Absence of nonadrenergic noncholinergic relaxation in the cat cervical trachea

Published in vivo experiments have not supported in vitro reports of the presence of nonadrenergic noncholinergic (NANC) inhibitory pathways in the cat trachea. We therefore examined these pathways, measuring tension in an innervated tracheal segment, flow resistance in more distal airways, and dynamic compliance, in 10 anesthetized mechanically ventilated cats. Initially, cervical vagal stimulation evoked contraction followed by relaxation of smooth muscle of trachea and lower airways; sympathetic stimulation evoked relaxation only. After muscarinic blockade and restoration of smooth muscle tone with 5-hydroxytryptamine (5-HT) applied topically to the tracheal mucosa, vagal stimulation did not affect tracheal segment tension, whereas sympathetic-evoked relaxation was preserved. Similar results were found when tone was restored with intravenous 5-HT, with vagal stimulation also decreasing resistance and increasing compliance. We conclude that NANC pathways are present in lower airways but not in the cervical trachea of the cat. We hypothesize that parasympathetic constriction of cat airway smooth muscle can occur without simultaneous NANC activation, whereas NANC activity occurs only in tandem with parasympathetic stimulation.     

Functional anatomy of the vagal innervation of the cervical trachea of the dog.

The canine cervical trachea has been used for numerous studies regarding the neural control of tracheal smooth muscle. The purpose of the present study was to determine whether there is lateral dominance by either the left or right vagal innervation of the canine cervical trachea. In anesthetized dogs, pressure in the cuff of the endotracheal tube was used as an index of smooth muscle tone in the trachea. After establishment of tracheal tone, as indicated by increased cuff pressure, either the right or left vagus nerve was sectioned followed by section of the contralateral vagus. Sectioning the right vagus first resulted in total loss of tone in the cervical trachea, whereas sectioning the left vagus first produced either a partial or no decrease in tracheal tone. After bilateral section of the vagi, cuff pressure was recorded during electrical stimulation of the rostral end of the right or left vagus. At the maximum current strength used, stimulation of the left vagus produced tracheal constriction that averaged 28.5% of the response to stimulation of the right vagus (9.0 +/- 1.8 and 31.6 +/- 2.5 mmHg, respectively). In conclusion, the musculature of cervical trachea in the dog appears to be predominantly controlled by vagal efferents in the right vagus nerve.     

An accurate recording system and its use in breath sounds spectral analysis

An accurate recording system was set up and used for analyzing normal and asthmatic breath-sound features. Breath sounds are recorded at the trachea simultaneously with the airflow signal at 0.5- and 1-1/s levels. The study was carried out in the frequency domain using a fast-fourier transform (FFT). FFTs are taken on 1,024-sample blocks (one block = 200 ms) over a duration of about 20 s. Different characteristics of the spectra are calculated in the range 60-1,260 Hz for 11 normal and 10 asthmatic subjects. This allows the computation of an index that discriminates (P less than 0.0005) asthma cases from normal cases. Spectral features strongly depend on the flow rate both for normal and asthmatic subjects. Increasing the flow rate raises the high-frequency components of the spectra.     

哮喘儿童父母知识知晓率、用药依从性及影响因素分析

目的:了解哮喘儿童父母的对疾病知识的掌握情况以及儿童的服药依从情况和影响因素,为提高哮喘儿童的控制率提供参考依据。方法:选择2015年1月-2015年12月于上海市第十人民医院儿科门诊诊治的支气管哮喘儿童93例,调查其哮喘控制情况、哮喘服药依从性和父母基本情况与相关知识。依从性与知识知晓率的比较采用双向有序的检验,影响因素采用有序结果的累积优势Logistic回归分析。结果:本次调查93例哮喘儿童中,哮喘完全控制率为23.7%,儿童服药依从性好的比率为25.8%,哮喘儿童父母相关知识知晓率高的比率为25.8%,儿童哮喘控制率与服药依从性之间存在相关性(P=0.029),哮喘儿童服药依从性与哮喘儿童父母相关知识知晓率之间存在相关性(P=0.035)。哮喘儿童的服药依从性受到儿童性别(OR=1.153,95%CI:1.04-1.96)、家族史(OR=1.402,95%CI:1.20-2.33)、知识知晓率(OR=1.828,95%CI:1.05-3.17)和病程(OR=0.758,95%CI:0.35-0.97)等因素的影响(P0.05)。结论:哮喘儿童的服药依从性受到儿童性别、家族史、知识知晓率和病程等因素的影响,要充分发挥儿童父母的作用,从医院内干预逐渐进入家庭干预,通过对父母或者监护人的认知或用药知识的提高,切实提高哮喘儿童的用药依从性和哮喘的控制率。     

Influence of ventrolateral surface of medulla on reflex tracheal constriction

To assess the role of structures located superficially near the ventrolateral surface of the medulla on the reflex constriction of tracheal smooth muscle that occurs when airway and pulmonary receptors are stimulated mechanically or chemically, experiments were conducted in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Pressure changes within a bypassed segment of the trachea were used as an index of alterations smooth muscle tone. The effects of focal cooling of the intermediate areas or topically applied lidocaine on the ventral surface of the medulla on the response of the trachea to mechanical and chemical stimulation of airway receptors were examined. Atropine abolished tracheal constriction induced by mechanical stimulation of the carina or aerosolized histamine, showing that the responses were mediated over vagal pathways. Moderate cooling of the intermediate area (20 degrees C) or local application of lidocaine significantly decreased the tracheal constrictive response to mechanical activation of airway receptors. Furthermore, when the trachea was constricted by histamine, cooling of the intermediate area significantly diminished the increased tracheal tone, whereas rewarming restored tracheal tone to the previous level. These findings suggest that under the conditions of the experiments the ventral surface of the medulla plays an important role in constriction of the trachea by inputs from intrapulmonary receptors and in the modulation of parasympathetic outflow to airway smooth muscle.     

Influence of the ventral surface of the medulla on tracheal responses to CO2

These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone.     

Prostaglandin D2 causes accumulation of eosinophils in the lumen of the dog trachea

Prostaglandin D2 (PGD2), the major product of arachidonic acid metabolism via the cyclooxygenase pathway in most mast cells, is present in the airways of atopic asthmatic patients after antigen challenge. Because eosinophilia is characteristic of asthma, we asked whether PGD2 causes eosinophils to accumulate in the airways in vivo. Using an endotracheal tube with two inflatable balloons we isolated a segment of trachea in four anesthetized mechanically ventilated dogs, and we superfused this segment with either a control solution (Hanks' balanced salt solution and antibiotics) or solution containing PGD2 (10(-6) M). Total and differential cell counts were determined at base line and every hour for 4 h during the study. PGD2 caused eosinophil accumulation in the trachea [7.0 +/- 3.4, 28.7 +/- 17.8, 33.7 +/- 13.6, and 35.4 +/- 10.7 (SD) cells/cm2 trachea after 1, 2, 3, and 4 h, respectively, P less than 0.05 vs. controls] but had no significant effect on neutrophil accumulation. The effect of PGD2 on eosinophil accumulation was significantly inhibited by the prostaglandin receptor antagonist SKF 88046 (5 mg/kg iv). We conclude that PGD2 is a selective stimulus that causes accumulation of eosinophils in the tracheal lumen of dogs in vivo.     

Tracheal hysteresis in sleep apnea

The collapsibility of pharyngeal walls, characteristic of patients with obstructive sleep apnea, likely results from reduced tone of the pharyngeal muscles. This reduction in the upper airway muscle tone may not end at the pharynx but may extend further distally, e.g., into the trachea. Because tracheal tone cannot be measured directly in conscious humans, we inferred the tone from the relative hysteresis of the tracheal area compared with the lung. Relative hysteresis was measured by plotting the cross-sectional area of a tracheal segment obtained by the acoustic reflection technique vs. lung volume. All measurements were performed during wakefulness. We found that in 42 patients with obstructive sleep apnea (apnea/hypopnea index greater than 10), relative hysteresis of the proximal trachea was predominantly clockwise, i.e., smaller than that of the lung parenchyma; in the 33 nonapneic patients (apnea/hypopnea index less than or equal to 10), it was predominantly counter-clockwise, i.e., larger than that of the lung parenchyma. For the distal trachea all patients, apneic and nonapneic, had similar, clockwise, relative hysteresis. We conclude that reduction in the upper airway muscle tone in patients with obstructive sleep apnea extends into the trachea.     

Tracheal venous blood and lymph collection: a model to study airway injury in sheep

Airway injury is a frequent result of the inhalation or aspiration of toxic material. Although upper airway damage can be identified endoscopically, pathophysiological changes are difficult to evaluate. This paper describes an animal model in which changes in tracheal blood and lymph flow rates, wet-to-dry weight ratios, and lymph-to-plasma protein ratios can be evaluated after injury. In this model, 12 cm of the cervical trachea were isolated using a double-cuffed endotracheal tube and injured with cotton smoke at near room temperature. Injury to the trachea was evaluated in twenty-five anesthetized sheep 4 (n = 3), 8 (n = 3), 24 (n = 3), 48 (n = 3), 96 (n = 3), and 192 (n = 2) h after smoke exposure and compared with sham control animals (n = 8). A significant increase in tracheal venous blood flow from 1.3 +/- 0.4 (SD) ml.min-1.cm-1 for the noninjured trachea to 2.8 +/- 1.2 was noted 24 h after injury (P less than 0.01). Lymph flow significantly increased from 1.3 +/- 0.4 microliters.min-1.cm-1 for the noninjured trachea to 9.8 +/- 3.3 24 h after injury while wet-to-dry weight ratios were elevated from 3.0 +/- 0.2 for noninjured trachea to 4.6 +/- 0.9 from 4 to 24 h after injury (P less than 0.01) and decreased to 3.7 +/- 0.5 by 96 h. Cast material consisting of airway exudate, cellular debris, and intact ciliated epithelial cells was both expectorated and found in the trachea when the animals were killed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tracheal length changes during zebra finch song and their possible role in upper vocal tract filtering

Sounds produced in the avian vocal organ may be modified by filter properties of the upper vocal tract. Possible mechanisms to actively control filter characteristics include movements of the beak, tongue, and larynx and adjustments of tracheal length. We investigated whether length changes of the trachea are a likely mechanism for adjusting upper vocal tract filter properties during song in the zebra finch (Taeniopygia guttata). Tracheal length was monitored at the basal end using sonomicrometry and was recorded together with subsyringeal air sac pressure and acoustic output. Tracheal shortening occurred at the onset of song bouts, and during each motif the tracheal length decreased during expiratory pressure pulses and increased during the short inspirations. A bilateral tracheal syringeal nerve cut confirmed that the initial shortening at the onset of the song bout is an active shortening of the trachea (i.e., mediated by syringeal muscle activity). The modulation of length during the motif was not affected by the denervation and is most likely driven by the pressurization of the interclavicular air sac. The absolute length change during the motif was small (<0.2 mm) and not clearly related to acoustic features of the song. For example, some high-frequency syllables, which are generated during inspiration, were accompanied by tracheal elongation. Because this elongation shifts tube resonances to lower frequencies, it is inconsistent with an active adjustment of length to enhance high frequency sounds. The small magnitude and inconsistent nature of dynamic tracheal length changes during song make it unlikely that they significantly affect vocal tract filter properties if the trachea is modeled as a rigid tube.     

Distal projection of insufflated gas during tracheal gas insufflation.

Tracheal gas insufflation (TGI) flushes expired gas from the ventilator circuitry and central airways, augmenting CO2 clearance. Whereas a significant portion of this washout effect may occur distal to the injection orifice, the penetration and mixing behavior of TGI gas has not been studied experimentally. We examined the behavior of 100% oxygen TGI injected at set flow rates of 1-20 l/min into a simulated trachea consisting of a smooth-walled, 14-mm-diameter tube. Models incorporating a separate coaxial TGI injector, a rough-walled trachea, and a bifurcated trachea were also studied. One-hundred percent nitrogen, representing expiratory flow, passed in the direction opposite to TGI at set flow rates of 1-25 l/min. Oxygen concentration within the "trachea" was mapped as a function of axial and radial position. Three consistent findings were observed: 1) mixing of expiratory and TGI gases occurred close to the TGI orifice; 2) the oxygenated domain extended several centimeters beyond the endotracheal tube, even at high-expiratory flows, but had a defined distal limit; and 3) more distally from the site of gas injection, the TGI gas tended to propagate along the tracheal wall, rather than as a central projection. We conclude that forward-directed TGI penetrates a substantial distance into the central airways, extending the compartment susceptible to CO2 washout.     

Effect of tracheal smooth muscle tone on collapsibility of immature airways

To test the influence of smooth muscle tone on extremely immature airways, tracheal segments (n = 19) were excised from premature lambs at 114-121 days gestation and mounted in a chamber filled with Krebs solution. Inflation (Si) and collapsing (Sc) compliance were determined by altering transmural pressure from 30 to 0 Torr and -30 to 0 Torr, respectively, both during control (C) and after acetylcholine (ACh) administration (experimental, E). Flow (V = 2-15 l/min) was then introduced through the tracheal lumen while chamber pressure (Pc) was increased from 0 to 30 Torr and driving pressure (Pd) was recorded for both C and E conditions. Tracheae were found to be extremely compliant; both Si and Sc were significantly (P less than 0.005) lower after ACh administration. Resistance to airflow (R = Pd/V) was also significantly (P less than 0.05) lower after ACh administration at each compressive pressure and each flow value. These results suggest that the highly compliant preterm trachea exhibits pressure-flow characteristics similar to a Starling resistor, and the effects of compressive pressures may be attenuated by ACh-induced smooth muscle contraction. Comparison of these results with data from adult and newborn animals suggests a developmental difference in tracheal mechanics and pressure-flow relationships, as well as in the way airway function is altered by smooth muscle stimulation.     

A finite-element model of tracheal collapse

The trachea has been approximated by an appropriate finite-element model. The three-dimensional equilibrium problems set by the tracheal deformation under various stresses have been solved using a convenient augmented Lagrangian functional. The dimensions were obtained from human tracheae. Mechanical constants for the anatomic components were calculated from the stress-strain relationships. The compressive narrowing is essentially due to the invagination of the posterior membrane in the tracheal lumen for transmural pressures down to -7 kPa. A surface of contact between the membranous wall and the lateral walls appears when the transmural pressure equals -6 kPa. The transmural pressure-area relationship is sigmoidal with a compliance equal to 0.08 kPa-1 for a transmural pressure of -2 kPa. The tracheal collapse is greater when the material constants of the membranous wall decrease or when the tracheal segment is subjected to a longitudinal tension. A slight flexion of the trachea induces an asymmetric deformation.     

Tracheal narrowing during histamine-induced bronchoconstriction

To determine whether tracheal narrowing accompanies histamine-induced bronchoconstriction and whether a cholinergic reflex is involved in the tracheal and bronchial responses, we determined specific pulmonary resistance between the carina and the pleura (sRL) and tracheal volume (Vtr) with an indicator-dilution technique in conscious sheep. Immediately postdelivery of histamine aerosol (7.5 mg histamine base) mean sRL increased by 223% (P less than 0.05), and mean Vtr decreased by 25% (P less than 0.05). The duration of the changes was similar, with a return to base-line values within 60 min. With increasing doses of histamine up to 30 mg, there was a corresponding increase in mean sRL, whereas the maximum effect on Vtr was already reached after 7.5 mg of histamine. Atropine (0.2 mg/kg iv) increased mean Vtr by 77% (P less than 0.05) and blunted the histamine effects on sRL, whereas the histamine effects on Vtr were abolished. Intravenous histamine or carbachol aerosol had similar effects on sRL and Vtr. We conclude that in conscious sheep 1) histamine produces both tracheal and bronchial constriction with a similar time course, 2) there is a base-line vagal tone in the trachea and not the bronchi, 3) the cholinergic reflex component of histamine-induced constriction is greater in the trachea than the bronchi, and 4) this difference between the trachea and bronchi is not due to differential aerosol deposition or cholinergic responsiveness.     

Analysis of tracheal mechanics and applications.

We have developed a mathematical model for a tracheal ring that consists of a "horseshoe" of cartilage with its tips joined by a membrane. The ring is subjected to a uniform transmural pressure (Ptm) difference. The model was used to calculate the cross-sectional area (A) of the trachea. Whereas the mechanics of the deformation of the cartilage were analyzed using elastica theory, the posterior membrane was treated as a simple membrane that is inextensible under changes in Ptm. The membrane can be specified to be of any length less than baseline and thus can represent a posterior membrane under tension. The cartilage can have specifiable nonuniform unstressed curvature as well as nonuniform bending stiffness. We have investigated the effect on the tracheal A-Ptm curve of posterior membrane length and tensile force in the membrane, cartilage shape and elasticity, and localized weakening of the cartilage. The model predictions are in good agreement with magnetic resonance imaging data from rabbit tracheas and show that the shape of the horseshoe as well as the posterior membrane force are important determinants of tracheal compliance.     

Tracheal stenosis: a flow dynamics study.

Patients referred for treatment of tracheal stenosis typically are asymptomatic until critical narrowing of the airway occurs, which then requires immediate intervention. To understand how tracheal stenosis affects local pressure drops and explore how a dramatic increase in pressure drop could possibly be detected at an early stage, a computational fluid dynamics (CFD) study was undertaken. We assessed flow patterns and pressure drops over tracheal stenoses artificially inserted into a realistic three-dimensional upper airway model derived from multislice computed tomography images obtained in healthy men. Solving the Navier-Stokes equations (with a Yang-shih k-epsilon turbulence model) for different degrees of tracheal constriction located approximately one tracheal diameter below the glottis, the simulated pressure drop over the stenosis (DeltaP) was seen to dramatically increase only when well over 70% of the tracheal lumen was obliterated. At 30 l/min, DeltaP increased from 7 Pa for a 50% stenosis to, respectively, 46 and 235 Pa for 80% and 90% stenosis. The pressure-flow relationship in the entire upper airway model (between mouth and end of trachea) in the flow range 0-60 l/min showed a power law relationship with best-fit flow exponent of 1.77 in the absence of stenosis. The exponent became 1.92 and 2.00 in the case of 60% and 85% constriction, respectively. The present simulations confirm that the overall pressure drop at rest is only affected in case of severe constriction, and the simulated flow dependence of pressure drop suggests a means of detecting stenosis at a precritical stage.     

Osmotic stimuli induce epithelial-dependent relaxation in the guinea pig trachea

Epithelium in airways, like endothelium in blood vessels, may regulate responses of adjacent smooth muscle. To study the intact trachea from guinea pigs we developed an in vitro preparation that permits independent stimulation from either the inner epithelial surface or the outer serosal surface. The whole guinea pig trachea was excised, cannulated, and perfused at a constant flow with Krebs-Henseleit (KH) solution that was in direct contact with the inner epithelial-lined surface. The outer serosal surface of the trachea was immersed in a separate system (bath) containing KH solution. Tracheal responses were assessed by measuring the pressure drop between the tracheal inlet and the outlet under conditions of constant flow. When the trachea was precontracted with carbachol or KCl, hyperosmolar stimuli (KCl, mannitol, urea, or NaCl) produced concentration-dependent relaxation when applied to the inner epithelial surface. Relaxation was not produced when the hyperosmolar stimulus was applied to the serosal surface and was markedly reduced or abolished when the epithelial surface had been physically damaged or removed. These results indicate that hyperosmotic stimuli induce epithelial-dependent relaxation of trachea. A defect in this mechanism may be partially responsible for the bronchoconstriction seen in asthmatic subjects after exercise.     

Effects of antigen on tracheal circulation and smooth muscle in sheep of different ages

The effects of Ascaris suum antigen on tracheal circulation and tracheal smooth muscle tone were compared in two groups of sheep: the first group was 1 yr old (14 sheep) and the second 5 yr old (8 sheep). Cranial tracheal arteries of anesthetized and paralyzed sheep were perfused at constant flow with monitoring of perfusion pressure. Tracheal smooth muscle tone was assessed by measuring changes in the external diameter of the cranial trachea. Close-arterial injection of antigen (1-20 micrograms) in young sheep produced dose-dependent vasodilation (6.1-15.5% fall in perfusion pressure) and smooth muscle contraction (0.06-0.28 mm reduction in tracheal diam). In old sheep, antigen (1-20 micrograms) produced vasoconstriction (4.1-16.8%) but no smooth muscle response. The smooth muscle contraction in young sheep was blocked by mepyramine (2 mg/kg iv) suggesting mediation by release of histamine. The vasodilation in young sheep and the vasoconstriction in old sheep were reduced by indomethacin (5 mg/kg iv), and the residual response was further reduced by FPL 55712 (2 mg/kg iv), suggesting mediation by both cyclooxygenase products and leukotrienes. Thus antigen given in the tracheal vasculature releases a mixture of inflammatory mediators. This mixture of mediators or their actions on the tracheal vasculature and smooth muscle may depend on the age of the sheep.     

Changes in tracheal cross-sectional area during Mueller and Valsalva maneuvers in humans

Pressure-area behavior of the excised trachea is well documented, but little is known of tracheal compliance in vivo. Extratracheal tissue pressures are not directly measurable, but transmural pressure for the intrathoracic trachea is inferred from intra-airway and pleural pressure differences. Extramural pressure of the cervical trachea is assumed to be atmospheric. The difference in transmural pressure between the intra- and extrathoracic tracheal segments should be exaggerated during Mueller and Valsalva maneuvers. We used the acoustic reflection technique to measure tracheal areas above and below the thoracic inlet during these isovolume-pressure maneuvers. We found that 10 cmH2O positive pressure increased tracheal area in the extrathoracic segment by 34 +/- 16% (mean +/- SD) and in the intrathoracic segment by 35 +/- 15%. There was a reduction in area of 27 +/- 16 and 24 +/- 14%, respectively, for the extra- and intrathoracic segments with 10 cmH2O negative pressure. We conclude that the effective transmural pressure gradients do not vary significantly between intra- and extrathoracic tracheal segments.     

PPARγ agonist rosiglitazone prevents perinatal nicotine exposure-induced asthma in rat offspring

Perinatal exposure to maternal smoke is associated with adverse pulmonary effects, including reduced lung function and increased incidence of asthma. However, the mechanisms underlying these effects are unknown, and there is no effective preventive and/or therapeutic intervention. Recently, we suggested that downregulation of homeostatic mesenchymal peroxisome proliferator-activated receptor-γ (PPARγ) signaling following in utero nicotine exposure might contribute to chronic lung diseases such as asthma. We used an in vivo rat model to determine the effect of perinatal nicotine exposure on 1) offspring pulmonary function, 2) mesenchymal markers of airway contractility in trachea and lung tissue, and 3) whether administration of a PPARγ agonist, rosiglitazone (RGZ), blocks the molecular and functional effects of perinatal nicotine exposure on offspring lung. Pregnant Sprague-Dawley rat dams received placebo, nicotine, or nicotine + RGZ daily from embryonic day 6 until postnatal day 21, when respiratory system resistance, compliance, tracheal contractility, and the expression of markers of pulmonary contractility were determined. A significant increase in resistance and a decrease in compliance under basal conditions, with more pronounced changes following methacholine challenge, were observed with perinatal nicotine exposure compared with control. Tracheal constriction response and expression of mesenchymal markers of airway contractility were also significantly increased following perinatal nicotine exposure. Concomitant treatment with RGZ completely blocked the nicotine-induced alterations in pulmonary function, as well as the markers of airway contractility, at proximal and distal airway levels. These data suggest that perinatal smoke exposure-induced asthma can be effectively blocked by PPARγ agonists.