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Prenatal development of the human trachea.

The tracheas of 46 human foetuses were examined: 26 male, 20 female with C-R length of 99-255 mm. The analysis of the total length of the trachea was carried out and its transverse dimension was presented on three levels: on the first tracheal cartilage, in the mid-length of the trachea, and at the bifurcation into the main bronchi; also the proportions between these dimensions and the C-R length were analysed. The length of the trachea was measured in a straight line--from the end of larynx to the bifurcation of the trachea. Comparing tracheas to a tunnel with two openings, it was observed that the transverse dimension, the "laryngeal", is greater than the "bronchial"--in the case of smaller foetuses by 2 mm, but in foetuses with C-R length of over 250 mm by 1 mm. Moreover, no significant differences between male and female sex were noticed. All the measurements were taken with the use of a slide caliper. The results should be useful in the detection of abnormalities in the structure of the trachea, in problems with respiratory physiology and in endotracheal intubation, endoscopy or tracheostomy.

Anthropometry↗

[The investigation of tracheas transplantation by wrapping in a muscle flap].

OBJECTIVE: To investigate the possibility of tracheas transplantation by wrapping it in a muscle flap. METHODS: With a dog model, a number of tracheas were separately wrapped in the unilateral sternocephalic muscle flap and the bilateral sternohyoid-sternothyroid muscle flap, and placed in the original site. The tracheas autografting was used as a control. The viability was evaluated by the examination of fiberoptic bronchoscopy, histopathology and microangiography, the measurement of tracheal mucosal blood flow and the calculation of survival rate and percentage of patency. RESULTS: The submucosal blood flow of the transplanted tracheas was detected in the unilateral sternocephalic muscle flap group and the bilateral sternohyoid-sternothyroid muscle flap group 1 week after the surgery and gradually reached the level close to the normal in 4 weeks, while the vascular ingrowth was also shown from the wrapped muscle flap into the transplanted tracheas by using a microangiography technique. The histopathological examination demonstrated that the structure of the transplanted tracheas was quite same as the original one and its inner surface was also covered with pseudostratified columnar ciliary epithelia. However, in the control group, the mucous membranes turned black one week after the transplantation and all dogs died from the graft necrosis. CONCLUSION: The tracheas wrapped in a muscular flap could survive well for a long time.

Animals↗

[The cialit-conserved trachea homograft (author's transl)].

After all techniques for reconstruction of tracheal segments with trachea-homografts, known from the literature, have failed to show satisfactory functional results, we have carried out further experiments concerning this subject. Our main interest was focused on the following topics: 1. the regeneration pattern of the respiratory epithelium in the trachea, 2. possibilities of the conservation of trachea-transplants, 3. the behaviour of the receptor area against trachea homografts. We found, that in correspondence with clinical observations, even large circumferencial defected epithelial areas in the mucous layer of the trachea have been regenerated in a form of new mucous membrane which showed no morphological difference from normal structure. Segments of trachea can be preserved in Cialit solution. Prefixation in formaldehydsaline fixative improves the preservation of the tissue structure. Homografts obtained in the above described technique could almost always be made to heal, either directly in the trachea or in the subcutaneous tissue of the recipient-animals. The behaviour of the cartilage and the epithelium is demonstrated by histological methods as well as by scanning electronmicroscopy.

Animals↗

Morphological studies on the venous drainage of the trachea in the neck of sheep.

Systemic venous drainage of the cervical portion of the trachea from the cricoid cartilage to the sternal notch was observed in 50 adult sheep. In all animals, the first five to six tracheal rings starting at the cricoid cartilage were drained by the thyroid veins (v. thyroideae) bilaterally to the external jugular veins (v. jugularis externa). A venous complex draining the remaining cervical portion of the trachea was observed only on the left side of the trachea. This complex drained to the cranial vena cava (vena cava cranialis). India ink or Evans blue dye were infused into small vessels draining this area for verification. Variations in this venous complex were classified into three types based upon length of trachea drained. Type I was found in 26%, type II found in 58%, and type III found in 16% of the sheep studied and drained 23 +/- 5%, 58 +/- 11% and 78 +/- 10% of the cervical portion of the trachea, respectively. Blood flow from this area of the trachea was 85 +/- 28 mL/min/100 g wet issue. This study identified and classified the venous drainage of the cervical portion of the trachea in sheep.

Animals↗

[Primary tumors of the trachea: their diagnosis and surgical treatment].

The authors present the analysis of the results of examination and treatment of 156 patients (84 females and 72 males aged from 7 to 69 years) with primary tumors of the trachea. Morphological types of primary benign and malignant tumors of the trachea and peculiarities of their clinical features are described. Diagnosis was based on clinical symptoms, results of roentgenologic examination and tracheobronchoscopy with biopsy. Surgical methods of treatment were endoscopic and open operations on the trachea. Endoscopic methods are of great importance in removal of benign tumors of the trachea as well as a preliminary stage before elective operation in subcompensated and decompensated neoplastic stenosis for elimination of stridor respiratory insufficiency and for decrease of secondary inflammatory disturbances in respiratory airways. In cases of extended resections of the trachea a series of special modes was provided for elimination of tension during anastomosis formation. Follow-up results of resections of the trachea for benign tumors are quite favourable. In cases of malignancies they are significantly worse. Survival of patients depends on histological type of the tumor and on the variant of resection of the trachea.

Adolescent↗

[Anesthesia and operative approach of resection of the trachea].

OBJECTIVE: Review and discuss anesthesia and operative approach of resection of the trachea for different tracheal diseases, especially for the resection of long-segment of trachea. At the same time to introduce the method of reconstruction of long-segment of trachea with Zhao's (two-stage procedure with memory-alloy mesh) artificial trachea. METHODS: Retrospective study of 18 cases of tracheal resection, analysis of the relation between the choice of anesthetic and operative approach. RESULTS: General anesthesia through cut open the trachea with local anesthesia in 2 cases, general anesthesia through previous tracheotomy in 2 cases, extracorporeal circulation in 2 cases, general anesthesia through endotracheal tube in 12 cases. There were no anesthetic or operative death. Local resection in 3 cases, segmental resection in 15 cases. The longest segmental resection was 8.0 cm. Primary anastomosis after segmental resection in 8 cases, Reconstruction with Zhao's artificial trachea in 7 cases. Postoperative follow-up was 5 months to 8 years. Four cases died from systemic metastasis or other reasons at 4, 11 and 12 months, respectively. CONCLUSIONS: Different methods of anesthetic and operative procedures should be used for different patients. Extracorporeal circulation used for patient with highest dangerous condition, or, for which could be inserted endotracheal tube by tracheotomy with local anesthesia. Conservative local resection performed only for patients with very bad general condition. Segmental resection less than 5 cm long could be reconstructed with primary reanastomosis. Resection longer than 5.5 cm could be reconstructed with Zhao's artificial trachea.

Adolescent↗

THE RESPONSES OF THE GUINEA-PIG ISOLATED INTACT TRACHEA TO TRANSMURAL STIMULATION AND THE RELEASE OF AN ACETYLCHOLINE-LIKE SUBSTANCE UNDER CONDITIONS OF REST AND STIMULATION.

A preparation of the guinea-pig isolated intact trachea is described which allows transmural stimulation of the intrinsic nerves of the tracheal muscle with simultaneous measurement of the volume changes of the trachea caused by contraction or relaxation of the tracheal muscle. The apparatus allows fluid to be removed from the lumen and outside of the trachea for assay of acetylcholine. The response to transmural stimulation over a range of 1 to 50 shocks/sec is first a contraction followed by a relaxation. The contraction is best seen at high frequencies of stimulation and is abolished by atropine. The contraction is enhanced by treatment of the trachea with the anticholinesterase NN-diisopropylphosphodiamidic fluoride (mipafox), and is thus probably due to stimulation of intrinsic cholinergic nerves. The relaxation is maximal at low frequencies of stimulation. After treatment with mipafox a substance resembling acetylcholine is released in the absence of stimulation. The acetylcholine output rises following transmural stimulation, probably due to release of acetylcholine from cholinergic motor nerves. No relationship between frequency of transmural stimulation and release of acetylcholine has been seen in nine of ten experiments. The resting and stimulated release of acetylcholine is not greatly reduced by attempted separation of the tracheal muscle from the bulk of the trachea. This result suggests that acetylcholine outputs from the intact trachea are a measure of release from the smaller tracheal muscle.

Acetylcholine↗

Diagnostic aspects and syndromal associations of short trachea with bronchial intubation.

Conditions with disproportionately short trachea, with a reduced number of tracheal cartilage rings and a high level of tracheal bifurcation, have been reported. We have seen accidental bronchial intubation in nine patients with short trachea. This risk can be reduced by recognition of conditions associated with short trachea, by awareness that methods for calculating endotracheal tube length from body length can overpredict tube length for patients with short trachea, and when feasible, by use of preintubation chest roentgenograms showing air bronchograms to establish the thoracic level of tracheal bifurcation. Twelve patients with short trachea, four with bronchial intubation, and six conditions not previously associated with short trachea, are reported. Three of the patients also had laryngeal hypoplasia.

Child↗

Morphological and quantitative study of the intrinsic nerve plexuses of the canine trachea as revealed by immunohistochemical staining of protein gene product 9.5.

BACKGROUND: The ganglionated nervous plexuses in the trachea play an important role in the regulation of respiration. Although the tracheal tissue of the dog has frequently been used in physiological and pharmacological studies, little is known about the morphology of the intrinsic nervous plexuses in the dog trachea and quantitative data about the ganglia and nerve cell bodies are lacking. The structure of the nervous plexuses and detailed morphometric data about the intrinsic neurons of the dog have not previously been reported. METHODS: The structure of the intrinsic nerves in the dog trachea was examined by a combination method of digestion with KOH and immunohistochemical attaining of protein gene product 9.5. In addition, areas of nerve cell profiles, numbers of nerve cell bodies per ganglion and densities of nerve cell bodies per ganglion were estimated in preparations from five dogs. RESULTS: In the dog trachea, the peritracheal plexus, outer submucosal plexus, inner submucosal plexus, and mucosal plexus were identified from adventitia to epithelium in that order. The peritracheal plexus, situated in the lamina adventitia of the trachea, consisted of thick nerve bundles that were densely distributed in the membranous wall. The peritracheal plexus contained ganglia with round or oval nerve cell bodies. In the trachealis muscle, the intramuscular plexus, which was a well-developed, three-dimensional nervous network, was observed. It did not include ganglia and consisted of inter- and intrafascicular networks. The outer submucosal plexus was observed as small clusters in the inside of the trachealis muscle. A few round nerve cells were observed in the outer submucosal plexus as small clusters. The ganglionated inner submucosal plexus was identified in the superficial layer of the submucosal layer. A finer meshwork, namely, the mucosal plexus, was observed in the lamina propria. Among the entire length of the trachea, we counted 2,134-2,873 ganglia (average, 2,389) and 13,902-24,232 nerve cell bodies (average,18,461) were counted in the peritracheal plexuses of five dogs. The densities of ganglia and nerve cell bodies were high near the carina and low near the thoracic inlet. The number of nerve cell bodies per ganglion was estimated as 6.5-8.8 (average, 7.7). The average maximum area of nerve cell profiles was 522 +/- 223 microm2. CONCLUSIONS: The structure of the tracheal plexuses in the dog is more complex than those in other smaller animals. The constitution of the plexuses seems to be that of the intestine. The numerous nerve cells in the peritracheal plexus in the adventitia can be expected to play important roles in airway regulation and in the pathogenesis of tracheal collapse.

Animals↗

Stimulatory effect of cigarette smoke on the metabolism and covalent binding of benzo(a)pyrene in the trachea of the rat.

The activity of aryl hydrocarbon hydroxylase (substrate: benzo(a)pyrene) was increased in the tracheas of rats exposed to cigarette smoke for 1 h daily for either 1 or 10 days. However the degree of increase in activity was lower in the trachea than in the lung. After a single exposure, activity in the trachea was at its highest level 12 h following exposure (3.2-fold compared to the control), but had returned to the control level within 24 h. Also, the amounts of covalently bound metabolites of benzo(a)pyrene were increased (2-fold) in nucleic acid and protein fractions of the trachea, when the rats were killed 12 h after a single cirgarette smoke exposure. No significant changes in activity of epoxide hydratase (substrate: styrene oxide) could be detected in the trachea. After repeated exposures the activity of UDP-glucuronosyltransferase (substrate: methylumbelliferone) was increased (1.7-fold) in the trachea.

Animals↗

Ultrasound-guided injection and occlusion of the trachea in fetal sheep.

OBJECTIVES: To access the fetal sheep trachea by ultrasound-guided transthoracic injection in order to deliver gene therapy vectors or occlude the trachea with a detachable balloon. METHODS: Fetal sheep were operated on at a mean gestational age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance, either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an occlusive balloon) needle was inserted via the fetal thorax into the fetal trachea. RESULTS: Using the 20-G spinal needle the trachea was accessed successfully in 33/36 fetuses, with 97% survival. Failure to inject was related to fetal position and gestational age. Blood vessel damage causing significant morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by puncturing the trachea with the 16-G needle and advancing an endoluminal balloon in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100% survival. In one case, the balloon became sited within the accessory lobe bronchus and was not inflated. At postmortem examination 21 days later, all balloons remained inflated and occluded the trachea, and the lung-to-body weight ratio and airways morphometric indices were consistent with relative pulmonary hyperplasia in the obstructed lungs. CONCLUSIONS: Ultrasound-guided transthoracic tracheal puncture is a reliable technique in fetal sheep, with low morbidity and mortality. Using this technique, a detachable endotracheal balloon can be placed to provoke pulmonary growth. Advances in needle design and balloon size may improve the success rate.

Animals↗

[Malignant tracheal tumors--surgical experiences in 6 patients with primary malignancies of the trachea. Current diagnosis and therapy].

In a retrospective study six patients with malignant tumours of the trachea located distal to the cricoid and proximal to the carina tracheae were operated on during the period of December 1983 to July 1995 in the Department of Thoracic Surgery in Hannover (Heidehaus). Histopathological examination revealed two adenoid cystic carcinomas, two squamous cell carcinomas, one mucoepidermoid carcinoma, and one low-grade sarcoma. Laser bronchoscopic resection was performed in one patient and tracheotomy one other avoid imminent asphyxia. Physical examination mainly showed a range of symptoms such as stridor and dyspnoea; spirography showed increased airway resistance, and X-ray of the trachea was important in the diagnostic process. The tracheal tumours were diagnosed by histopathological examination of excised material obtained by bronchoscopy. Three patients underwent resection and primary reconstruction of the trachea, with a length of resection between 2.0 and 3.5 cm and end-to-end anastomosis. Endotracheal afterloading was necessary in the case of one female patient with tumour infiltration of the proximal end of the upper trachea. Neoadjuvant irradiation was followed by resection of the whole trachea and implantation of a tracheal prosthesis (Neville) in the case of a patient with extensive endo- and extraluminal tumour infiltration. An extensive recurrence led to the death of this patient 5 months after the surgical intervention. Because of the distal location, resection of the tracheal bifurcation was necessary in two patients, in one combined with a pneumonectomy on the right side. Stenosis of the main bronchus and development of granuloma made stent implantation unavoidable. Dislocation of the stents and recurrent pneumonia caused the patients deaths 74 days and 18 months postoperatively. On follow up 17, 93, and 120 months postoperatively none of the other patients had recurrences. Current diagnostic and therapeutic options for malignant tracheal tumours are discussed.

Adult↗

Neurogenic inflammation in the rat trachea. I. Changes in venules, leucocytes and epithelial cells.

This study was done to characterize the morphological changes in the respiratory mucosa that occur in neurogenic inflammation, which is a type of inflammation mediated by substances released from sensory nerves. Neurogenic inflammation was produced in the trachea and bronchi of atropine-treated Long-Evans rats by electrically stimulating the left or right superior laryngeal and vagus nerves. This procedure is known to increase vascular permeability in the airways, presumably as a consequence of antidromic activation of sensory vagal axons (Lundberg & Saria, 1982). By using a particulate tracer (Monastral blue, 30 mg kg-1 i.v.) that does not cross the walls of normal tracheal blood vessels but does cross the endothelium of abnormally permeable vessels, it was possible to identify which blood vessels were affected in neurogenic inflammation. Light and electron microscopic examination of tracheas prepared after 2 or 5 min of vagal stimulation revealed that postcapillary venules and collecting venules 7-80 micron in diameter were labelled by extravasated Monastral blue but capillaries, arterioles, and larger venules were not. Venules from which the extravasation occurred had gaps as wide as 1.5 micron between endothelial cells. Most of the abnormally permeable venules were located just beneath the airway epithelium in regions between the cartilaginous rings. Extravasation also occurred from venules in the mucosa overlying the posterior membrane of the extrathoracic trachea, but little occurred in the posterior membrane of the intrathoracic trachea. After unilateral vagal stimulation, vascular permeability was increased on both sides of the trachea; it was also increased in first through fourth order bronchi but only on the side of stimulation. Leucocytes (principally monocytes and neutrophils) were adherent to the endothelium of some of the abnormally permeable venules. Erythrocytes and platelets also were adherent to the walls of some venules. These changes in venules were accompanied by a degranulation of epithelial secretory cells, widening of the spaces between tracheal epithelial cells, and probably an increase in epithelial permeability. Neurogenic inflammation in the trachea and bronchi of rats is thus characterized by increased permeability of postcapillary venules and collecting venules in specific regions of the respiratory mucosa as well as adherence of leucocytes, erythrocytes and platelets to the endothelium of these venules and prominent changes in the respiratory epithelium.

Animals↗

Mycoplasma pneumoniae infection of intact guinea pig tracheas cultured in a unique matrix-embed/perfusion system.

A new method for the in vitro culture of entire, intact tracheas from adult guinea pigs is described. Matrix-embed/perfusion (MEP) culture is based on an immobilization of the tissue in nutrient agar The tubular piece of agar-embedded organ was contained in a special perfusion block with two wells for liquid medium at either end. When incubated on a rocker platform, liquid medium flows through the trachea and supplies oxygen an nutrients. In this configuration, tracheas maintain near-normal metabolism (ATP content and dehydrogenase activity), structure (as determined by light and electron microscopy), and function (ciliary motion). Tissues could be maintained in vitro in a normal for at least 4 wk, with reduced ciliary motion and cell metabolism detectable for at least 6 wk. Agar-embedded tissues from the MEP cultures were nearly identical to those cultivated with standard tracheal ring explant techniques. Tracheas in the MEP cultures were infected with Mycoplasma pneumoniae. Attachment was neuraminidase-sensitive. Mycoplasma attachment was lowest on the epithelium along the dorsal ridge, but was uniform along the length of the trachea. Ciliostasis and cytonecrosis induced by M. pneumoniae was dose dependent. The matrix-embed/perfuse technique appears to have considerable potential for several types of in vitro studies on trachea or other tubular organs.

Adhesiveness↗

Regulation of the synthesis of mucin glycoproteins in swine trachea explants.

Swine tracheal epithelium has been cultured as explants in a chemically defined medium for periods of up to 2 wk. The viability of the explants was shown by the preservation of the ultrastructural features of cells in the epithelial layer and by the active incorporation of radioactive glucosamine and sulfate into secreted mucin glycoproteins. The rate of secretion of mucin glycoprotein was about 0.035 mg per cm2 per d. After initial 24 h lag period was shown to be due to the equilibration of intracellular mucin glycoprotein pools with radioactive precursors. The rate of secretion of glycoprotein showed a linear dependence on the area of the explant, and maximal incorporation was observed at 200 microM glucosamine. A higher concentration of 35SO4, 1000 microM, was required for maximal incorporation of the precursor. Insulin at 0.1 to 1 microgram/ml increased the rate of secretion twofold, whereas 0.1 to 100 micrograms/ml of hydrocortisone and 0.1 to 100 micrograms/ml of epinephrine significantly decreased the rate of secretion. Vitamin A had little or no effect of normal trachea explants at low concentrations, and, at higher concentrations, 10(-5) M, it decreased the secretion of mucin glycoproteins. Vitamin A, at a concentration of 10(-9) M, increased the rate of synthesis of glycoprotein at least fourfold in trachea explants from vitamin A-deficient rats. Mucus secretions collected from the surface of swine trachea and from the culture medium of trachea explants were purified. The mucus was solubilized by reduction and carboxymethylation, and the high molecular weight mucin glycoproteins were purified by chromatography on Sepharose CL-6B columns under dissociating conditions in 2 M guanidine HCl. The mucin glycoproteins purified from swine trachea and from the culture medium of trachea explants were virtually indistinguishable. They showed the same properties when examined by gel electrophoresis and immunoprecipitation. The purified glycoproteins contained about 25% protein, and serine, threonine, and proline were the principal amino acids present. More than 80% of the carbohydride chains in both samples were released by treatment with alkaline borohydride. Nearly the same molar ratio of N-acetylgalactosamine, N-acetylglucosamine, galactose, fucose, sulfate, and sialic acid was found in both preparations.

Animals↗

Synthesis of mucin glycoproteins by epithelial cells isolated from swine trachea by specific proteolysis.

Mucus-producing cells were isolated from swine trachea mucosa by a method that included enzymatic digestion of the epithelial surface with Dispase, a neutral protease from Bacillus polymyxa, and differential attachment of the washed cells to culture flasks coated with collagen. Epithelial cells were the major cell type isolated by these procedures. Ciliated cells that did not attach to the flasks were removed by decantation , and fibroblasts were destroyed by the bacterial protease. The isolated cells synthesized respiratory mucins and the rate of secretion was increased about threefold when tracheas were exposed to sulfur dioxide. The cultured cells incorporated both [35S]O4 and [I-14C]N-acetylglucosamine into secreted mucin glycoproteins. The secretion of glycoprotein increased for about 3 d until the cells became confluent, and then a constant rate was observed for a period of at least 7 d. This increase in the output of mucin glycoprotein during the initial 3 d of culture was accompanied by a corresponding increase in the number of mucus-producing cells in the flasks. The results obtained in these and subsequent studies suggest that the rate of formation of mucus-producing cells may be a rate limiting step in the regulation of mucin glycoprotein synthesis in tracheal epithelium. The chemical, physical, and immunological properties of the glycoprotein secreted by isolated tracheal epithelial cells were very similar to the mucin glycoprotein purified from washes of swine trachea epithelium. The purified mucin glycoproteins showed complete cross-reaction with antibodies to trachea mucin glycoprotein. They were eluted near the void volume during gel filtration of Sepharose CL-6B columns. The glycoprotein isolated from culture media under the standard assay conditions had nearly the same carbohydrate composition as samples purified from washes of trachea epithelium. Reduced oligosaccharides released by beta-elimination with dilute alkaline borohydride showed similar elution profiles during chromatography on Bio Gel P-6 columns. Taken collectively, these results suggest that the isolated epithelial cells secreted mucin glycoproteins that were very similar to those synthesized by the intact trachea epithelium under standard incubation conditions.

Animals↗

K+ channel openers produce epithelium-dependent relaxation of the guinea-pig trachea.

The relaxant effects of the K+ channel openers, NIP-121, (+)-7,8-dihydro-6,6-dimethyl-7-hydroxy-8-(2-oxo-piperidin-1-yl)-6H - pyrano[2,3-f]benz-2,1,3-oxadiazole, and cromakalim, were investigated in epithelium-intact and -denuded tracheal spirals isolated from guinea-pigs. In the presence of 5 microM indomethacin, NIP-121 (0.01-1 microM) and cromakalim (0.1-10 microM) relaxed, in a concentration-dependent manner, epithelium-intact and -denuded trachea precontracted with a thromboxane A2 mimetic, U46619, 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy-prostaglandin F2 alpha (30 nM). The relaxations of epithelium-denuded trachea were significantly decreased as compared with those of epithelium-intact trachea. The relaxations induced by salbutamol or aminophylline were not affected by epithelium removal. In epithelium-intact trachea, the NIP-121- and cromakalim-induced relaxations were not modulated by the neutral endopeptidase inhibitor, phosphoramidon (10 microM), or the nitric oxide synthesis inhibitor, N omega-nitro-L-arginine (100 microM). However, the guanylate cyclase inhibitor, methylene blue (100 microM), significantly reduced NIP-121- and cromakalim-induced relaxation of epithelium-intact trachea. Methylene blue also reduced sodium nitroprusside-induced relaxation but did not affect isoprenaline-induced relaxation. These findings suggest that the K+ channel openers, NIP-121 and cromakalim, may induce, at least in part, epithelium-dependent and methylene blue-sensitive relaxation of the guinea-pig isolated trachea.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Studies of desensitization and cross-desensitization to immunologic and nonimmunologic stimuli that evoke contraction and histamine release in superfused guinea pig trachea.

This study examined the possibility that there is cross-desensitization between immunologic and nonimmunologic stimuli that evoke contraction and histamine release (HR) in the isolated guinea pig trachea. Compound 48/80 and D-tubocurarine were found to cause homologous and heterologous desensitization for both contraction and HR from superfused trachea. Specific antigen challenge of trachea obtained from animals sensitized with either IgG1 (ovalbumin [OA]) or IgE (oxazalone-human serum albumin [OX-HSA]) also resulted in homologous desensitization for both contraction and HR. However, in experiments with animals sensitized with both IgG1 and IgE antibodies, prechallenge with OA resulted in cross-desensitization to OX-HSA, whereas the reverse sequence was ineffective in eliciting this phenomenon. This may be related to the type of desensitization produced by each antigen (specific versus nonspecific) or to heterogeneity of mast cells in the tissue. Prechallenge of the trachea with compound 48/80 or D-tubocurarine failed to alter subsequent effects of antigen after active sensitization with OA or passive sensitization with either IgG1 or IgE antibodies. Small but statistically significant decreases in tracheal responses to D-tubocurarine were observed after antigen prechallenge to active both IgG1 and IgE antibodies. This is the first study to demonstrate a cross-desensitization between compound 48/80 and D-tubocurarine and the first to examine cross-desensitization with IgG1 and IgE antibodies in the guinea pig trachea. The overall conclusion is that there is no major overlap in the desensitization mechanisms between immunologic and nonimmunologic stimuli in the guinea pig trachea.

Animals↗