Selective permeability changes in the lungs and airways of sheep after toxic smoke inhalation

The effect of toxic smoke inhalation on selective microvascular sieving of macro-molecules and lymph protein flux was assessed in adult sheep to determine whether the time course of microvascular dysfunction differs between the lung and trachea. Protein flux across the lung increased sixfold 48 h after inhalation of the products of incomplete cotton combustion, whereas tracheal protein flux increased fivefold 8 h after exposure and returned to near base line 48 h after exposure. The lung and trachea selectively retained some sieving to three different protein macromolecules with molecular radii of 36, 54, and 123 A. In the lungs the sieving selectivity for these macromolecules was least 48 h after injury, and in the trachea molecular selectivity was least 8 h after injury. These data suggest that the time course of microvascular injury differs for the trachea and the lung; microvascular changes are detected earlier in the trachea than in the lung. The inhalation injury described thus permits the characterization of the time course of airway and lung microvascular changes.     

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)     

Evidence for lipoxygenase pathway involvement in allergic tracheal contraction

Challenge of actively sensitized guinea-pig trachea in vitro led to a contraction which was enhanced by the cyclo-oxygenase inhibitors, indomethacin and sodium meclofenamate. Cyclo-oxygenase inhibitors eliminated the release of PGE-like material induced by arachidonic acid (AA), histamine, and antigen challenge. AA (10 μg./ml.) and PGE₂ (100 ng./ml.) usually relaxed the trachea, whereas in the presence of cyclo-oxygenase inhibitors a contraction occurred. Phenidone and ETYA, which also blocked the lipoxygenase pathway of AA metabolism inhibited the enhancement of allergic tracheal contraction induced by cyclo-oxygenase inhibitors, decreased the time that the trachea remained contracted, and also eliminated the contraction induced by AA and PGE₂. Thus, cyclo-oxygenase inhibitors may enhance allergic tracheal contraction by diverting AA metabolism into the lipoxygenase pathway and a product of the latter pathway, possibly SRS-A, may be responsible for the enhancement and for the prolonged phase of allergic tracheal contraction. An analogous mechanism may account for aspirin-induced asthma in man.     

XB130 Deficiency Affects Tracheal Epithelial Differentiation during Airway Repair

The repair and regeneration of airway epithelium is important for maintaining homeostasis of the respiratory system. XB130 is an adaptor protein involved in the regulation of cell proliferation, survival and migration. In the human trachea, XB130 is expressed on the apical site of ciliated epithelial cells. We hypothesize that XB130 may play a role in epithelial repair and regeneration after injury. Xb130 knockout (KO) mice were generated, and a mouse isogenic tracheal transplantation model was used. Adult Xb130 KO mice did not show any significant anatomical and physiological phenotypes in comparison with their wild type (WT) littermates. The tracheal epithelium in Xb130 KO mice, however, was significantly thicker than that in WT mice. Severe ischemic epithelial injury was observed immediately after the tracheal transplantation, which was followed by epithelial cell flattening, proliferation and differentiation. No significant differences were observed in terms of initial airway injury and apoptosis. However, at Day 10 after transplantation, the epithelial layer was significantly thicker in Xb130 KO mice, and associated with greater proliferative (Ki67+) and basal (CK5+) cells, as well as thickening of the connective tissue and fibroblast layer between the epithelium and tracheal cartilages. These results suggest that XB130 is involved in the regulation of airway epithelial differentiation, especially during airway repair after injury.     

Endogenous and exogenous stem cells: a role in lung repair and use in airway tissue engineering and transplantation

Rapid repair of the denuded alveolar surface after injury is a key to survival. The respiratory tract contains several sources of endogenous adult stem cells residing within the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction, and within the alveolar epithelial surface, which contribute to the repair of the airway wall. Bone marrow-derived adult mesenchymal stem cells circulating in blood are also involved in tracheal regeneration. However, an organism is frequently incapable of repairing serious damage and defects of the respiratory tract resulting from acute trauma, lung cancers, and chronic pulmonary and airway diseases. Therefore, replacement of the tracheal tissue should be urgently considered. The shortage of donor trachea remains a major obstacle in tracheal transplantation. However, implementation of tissue engineering and stem cell therapy-based approaches helps to successfully solve this problem. To date, huge progress has been achieved in tracheal bioengineering. Several sources of stem cells have been used for transplantation and airway reconstitution in animal models with experimentally induced tracheal defects. Most tracheal tissue engineering approaches use biodegradable three-dimensional scaffolds, which are important for neotracheal formation by promoting cell attachment, cell redifferentiation, and production of the extracellular matrix. The advances in tracheal bioengineering recently resulted in successful transplantation of the world's first bioengineered trachea. Current trends in tracheal transplantation include the use of autologous cells, development of bioactive cell-free scaffolds capable of supporting activation and differentiation of host stem cells on the site of injury, with a future perspective of using human native sites as micro-niche for potentiation of the human body's site-specific response by sequential adding, boosting, permissive, and recruitment impulses.     

Evidence for lipoxygenase pathway involvement in allergic tracheal contraction

Challenge of actively sensitized guinea-pig trachea in vitro led to a contraction which was enhanced by the cyclo-oxygenase inhibitors, indomethacin and sodium meclofenamate. Cyclo-oxygenase inhibitors eliminated the release of PGE-like material induced by arachidonic acid (AA), histamine, and antigen challenge. AA (10 microgram./ml.) and PGE2 (100 ng./ml.) usually relaxed the trachea, whereas in the presence of cyclo-oxygenase inhibitors a contraction occurred. Phenidone and ETYA, which also blocked the lipoxygenase pathway of AA metabolism inhibited the enhancement of allergic tracheal contraction induced by cyclo-oxygenase inhibitors, decreased the time that the trachea remained contracted, and also eliminated the contraction induced by AA and PGE2. Thus, cyclo-oxygenase inhibitors may enhance allergic tracheal contraction by diverting AA metabolism into the lipoxygenase pathway and product of the latter pathway, possibly SRS-A, may be responsible for the enhancement and for the prolonged phase of allergic tracheal contraction. An analogous mechanism may account for aspirin-induced asthma in man.     

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.     

Nonlinear mechanical property of tracheal cartilage: a theoretical and experimental study

BACKGROUND: Despite being the stiffest airway of the bronchial tree, the trachea undergoes significant deformation due to intrathoracic pressure during breathing. The mechanical properties of the trachea affect the flow in the airway and may contribute to the biological function of the lung. METHOD: A Fung-type strain energy density function was used to investigate the nonlinear mechanical behavior of tracheal cartilage. A bending test on pig tracheal cartilage was performed and a mathematical model for analyzing the deformation of tracheal cartilage was developed. The constants included in the strain energy density function were determined by fitting the experimental data. RESULT: The experimental data show that tracheal cartilage is a nonlinear material displaying higher strength in compression than in tension. When the compression forces varied from -0.02 to -0.03N and from -0.03 to -0.04N, the deformation ratios were 11.03+/-2.18% and 7.27+/-1.59%, respectively. Both were much smaller than the deformation ratios (20.01+/-4.49%) under tension forces of 0.02 to 0.01N. The Fung-type strain energy density function can capture this nonlinear behavior very well, whilst the linear stress-strain relation cannot. It underestimates the stability of trachea by exaggerating the displacement in compression. This study may improve our understanding of the nonlinear behavior of tracheal cartilage and it may be useful for the future study on tracheal collapse behavior under physiological and pathological conditions.     

Histochemical localization of carbonic anhydrase in the trachea of the guinea pig

 Tissue specimens from guinea pigs were examined using an enzyme-histochemical reaction to explore the presence of carbonic anhydrase (CA) activity in the trachea. CA activity was detected in a group of morphologically distinct epithelial cells, in goblet cells, and in glands of the tracheal mucosa. The epithelial cells showing CA activity were distributed singly and sparsely throughout the entire trachea. These cells showed a wide morphological variability and were clearly different from those forming the pseudostratified ciliated epithelium. Their number was higher in sections closer to the tracheal bifurcation than in those near the larynx. Although the nature of these cells is unknown, based on their morphological and histochemical characteristics and their distribution, they may represent a specialized chemoreceptor. To our knowledge, this is the first report of CA localized in tracheal epithelial cells. Accepted: 6 March 1996     

Trachea enhances neurite regeneration from adult rat nodose ganglia in vitro

Trachea is intensely innervated with vagal afferent nerve fibers, and may play an important role in vagus nerve regeneration after axonal injury caused by trauma and surgical operation. We investigated the effects of tracheal tissue on neuronal cell survival and neurite regeneration in adult rat nodose ganglia (NG) in vitro. Co-culture with trachea significantly increased the average number of neurites regenerated from transected nerve terminals of NG explants, from 73.7 to 154.2 after 3 days, from 68 to 186.7 after 5 days, and from 31 to 101.5 after 7 days in culture. Dissociated NG neurons could continue to survive and extend neurites only in the co-existence with satellite cells in collagen gel. Co-cultured trachea improved the ratios of survival and neurite-bearing cells of NG neurons, from 56.7% and 11.1% to 72.3% and 37.6% after 4 days, and from 41.1% and 20.3% to 56.4% and 47.2% after 7 days in culture, respectively. These results imply that tracheal tissue secretes a factor, which could enhance neuronal cell survival and neurite regeneration in NG in the presence of satellite cells in vitro.     

香烟烟雾提取物对小鼠气管环上皮钙粘附素表达的影响

体外进行器官培养,通过免疫组织化学和原位杂交方法检测香烟烟雾提取物（CSE）作用48、72h,小鼠气管上皮细胞上皮钙粘附素（E－cd）表达的变化。结果表明,正常对照组E－cd分布于气管假复层纤毛柱状上皮细胞连接处的胞膜上,50％CSE作用后,膜上E－cd表达减少,随着作用时间延长,胞浆内E-cd表达明显增加（P＜0.05）,而细胞内E－cd mRNA含量无明显变化。提示,CSE对小鼠气管上皮细胞E-cd表达的调控在翻译后水平,胞膜上E－cd表达的下调与吸烟所致气道上皮细胞的损伤修复过程相关。     

Estimation of tracheal sound intensity during forced expiration

The tracheal sounds during forced expiration were studied using the mathematical model of forced expiration. It has been shown that separated flow in the region of dynamic constriction of the trachea during forced expiration may cause the generation of tracheal sounds.     

The tettigoniid (Orthoptera : Tettigoniidae) ear: Multiple functions and structural diversity

The ears of bushcrickets (Orthoptera : Tettigoniidae) consist of a pair of membranes situated beneath the knee of the foretibia. These membranes, or tympana, are backed by a tracheal system dedicated to sound reception. In most species, a trachea opens through a hole, the auditory spiracle, in the pleuron of the prothorax adjacent to the ventilatory spiracle. Experimental evidence clearly shows that in those species possessing such an opening, sound entering through this route is amplified by the shape of the trachea, or at least is modified through resonances created by its tracheal cavities or tubes. In some species the external surface of the tympanic membrane is surrounded by cuticular folds, which may be formed into small resonating cavities or sound guiding pinnae. In other species the tympana are naked. Sound interacts with the external surface of the tympana, either through these cuticular cavities or directly at the surface of the membrane. As with auditory tracheae, the shape of these cavities may modify sound through resonances. This review examines the role of both external and internal sound-guides in sound reception. It discusses how different species may utilize different sound receiving systems and suggests how, in some cases, both external and internal routes may respond to different frequency bands. The maximum sensitivity of the ear invariably coincides with the male's call carrier frequency. Two Australian species of tettigoniid where the ear is clearly not tuned to the male's call are described. The biology of one undescribed species belonging to the subfamily, Zaprochilinae, where not only is the ear untuned, but there is marked sexual dimorphism in ear structure, is elaborated on. The review concludes with an examination of the routes selection may have taken to arrive at the extreme morphologies present in the Tettigoniidae.     

Isolation of multipotent progenitor cells from pleura and pericardium for tracheal tissue engineering purposes

Tissue engineering (TE) of long tracheal segments is conceptually appealing for patients with inoperable tracheal pathology. In tracheal TE, stem cells isolated from bone marrow or adipose tissue have been employed, but the ideal cell source has yet to be determined. When considering the origin of stem cells, cells isolated from a source embryonically related to the trachea may be more similar. In this study, we investigated the feasibility of isolating progenitor cells from pleura and pericard as an alternative cells source for tracheal tissue engineering. Porcine progenitor cells were isolated from pleura, pericard, trachea and adipose tissue and expanded in culture. Isolated cells were characterized by PCR, RNA sequencing, differentiation assays and cell survival assays and were compared to trachea and adipose-derived progenitor cells. Progenitor-like cells were successfully isolated and expanded from pericard and pleura as indicated by gene expression and functional analyses. Gene expression analysis and RNA sequencing showed a stem cell signature indicating multipotency, albeit that subtle differences between different cell sources were visible. Functional analysis revealed that these cells were able to differentiate towards chondrogenic, osteogenic and adipogenic lineages. Isolation of progenitor cells from pericard and pleura with stem cell features is feasible. Although functional differences with adipose-derived stem cells were limited, based on their gene expression, pericard- and pleura-derived stem cells may represent a superior autologous cell source for cell seeding in tracheal tissue engineering.     

Functional anatomy of the musculature of the trachea.

The smooth musculature of the human trachea was studied and compared with earlier observations in the rabbit. The results may be summarized as follows: 1. The annular m. constrictor tracheae, previously observed in the rabbit, has also been identified in the human trachea. 2. Longitudinal muscle fibers outside the constrictor musculature were observed in man. These fibers are rudimentary and appear to be of no functional importance. 3. From a functional point of view, it appears justified to regard the outer tracheal musculature largely as a constrictor musculature. 4. The main function of the outer musculature of the trachea and the elastic cartilaginous arches is to maintain the stability of the tracheal wall. 5. The variation of the lumen of the trachea is mainly controlled by the m. trachealis in the pars membranacea.     

FGF /FGFR Signal Induces Trachea Extension in the Drosophila Visual System

The Drosophila compound eye is a large sensory organ that places a high demand on oxygen supplied by the tracheal system. Although the development and function of the Drosophila visual system has been extensively studied, the development and contribution of its tracheal system has not been systematically examined. To address this issue, we studied the tracheal patterns and developmental process in the Drosophila visual system. We found that the retinal tracheae are derived from air sacs in the head, and the ingrowth of retinal trachea begin at mid-pupal stage. The tracheal development has three stages. First, the air sacs form near the optic lobe in 42-47% of pupal development (pd). Second, in 47-52% pd, air sacs extend branches along the base of the retina following a posterior-to-anterior direction and further form the tracheal network under the fenestrated membrane (TNUFM). Third, the TNUFM extend fine branches into the retina following a proximal-to-distal direction after 60% pd. Furthermore, we found that the trachea extension in both retina and TNUFM are dependent on the FGF(Bnl)/FGFR(Btl) signaling. Our results also provided strong evidence that the photoreceptors are the source of the Bnl ligand to guide the trachea ingrowth. Our work is the first systematic study of the tracheal development in the visual system, and also the first study demonstrating the interactions of two well-studied systems: the eye and trachea.     

Progress in larynx-sparing surgery for glottic cancer through tracheal transplantation.

The current surgical treatment for unilateral, advanced glottic cancer is a total laryngectomy. Usually, the noninvolved hemilarynx needs resection because the resulting laryngeal defect cannot be reconstructed after adequate tumor resection. Experimental findings suggest that segments of autologous trachea may restore extended laryngeal defects. The authors used tracheal transplantation to save laryngeal function after the removal of advanced glottic cancer. In this case series review, 10 patients were treated during a 1.5-year period, with an average follow-up of 8 months. Evaluated factors included survival of the tracheal transplant and functional outcome with regard to the onset and quality of the airway, speech, and deglutition. The authors showed that segments of cervical trachea may restore extended laryngeal defects after initial revascularization by a radial forearm fascial flap. The fascial flap served as a vascular carrier for the transplanted trachea. Follow-up showed the stability of the reconstruction. Compared with a total laryngectomy, a striking improvement in patient comfort and function was noticed. Transplantation of the trachea is a technique that may save laryngeal function after the treatment of advanced-stage glottic cancer. These findings may improve laryngeal preservation strategies in treating laryngeal cancer.     

The fatty acyl-CoA reductase Waterproof mediates airway clearance in Drosophila

The transition from a liquid to a gas filled tubular network is the prerequisite for normal function of vertebrate lungs and invertebrate tracheal systems. However, the mechanisms underlying the process of gas filling remain obscure. Here we show that waterproof, encoding a fatty acyl-CoA reductase (FAR), is essential for the gas filling of the tracheal tubes during Drosophila embryogenesis, and does not affect branch network formation or key tracheal maturation processes. However, electron microscopic analysis reveals that in waterproof mutant embryos the formation of the outermost tracheal cuticle sublayer, the envelope, is disrupted and the hydrophobic tracheal coating is damaged. Genetic and gain-of-function experiments indicate a non-cell-autonomous waterproof function for the beginning of the tracheal gas filling process. Interestingly, Waterproof reduces very long chain fatty acids of 24 and 26 carbon atoms to fatty alcohols. Thus, we propose that Waterproof plays a key role in tracheal gas filling by providing very long chain fatty alcohols that serve as potential substrates for wax ester synthesis or related hydrophobic substances that ultimately coat the inner lining of the trachea. The hydrophobicity in turn reduces the tensile strength of the liquid inside the trachea, leading to the formation of a gas bubble, the focal point for subsequent gas filling. Waterproof represents the first enzyme described to date that is necessary for tracheal gas filling without affecting branch morphology. Considering its conservation throughout evolution, Waterproof orthologues may play a similar role in the vertebrate lung.