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[Effects of As2O3, MNNG and B(a)P on epithelia of human fetal tracheae and rat tracheae in organ culture].

The effects of As2O3, MNNG and B(a)P on epithelia of human fetal tracheae and rat tracheae in organ culture were studied. In human fetal trachea, a small dose of arsenic (1 mumol As) induced hyperplasia of the epithelium; 3-9 mumol As induced hyperplasia and cellular atypia in the epithelium, and hyperplasia and squamous metaplasia in the adenoepithelium. Similar effects were not observed in rat tracheae. MNNG and B(a)P induced hyperplasia, squamous metaplasia and dysplasia in human fetal tracheal and rat tracheal epithelia respectively, and MNNG also induced hyperplasia and squamous metaplasia in human fetal tracheal adenoepithelium. The data suggest that 1) arsenic may be carcinogenic to the human respiratory tract but not to the rat; and 2) human tissues in organ culture are very useful for detecting carcinogens and for studying carcinogenesis.

Animals

Surgical treatment of adenoid cystic carcinoma of the left main bronchus and trachea by left pneumonectomy, resection of 7.5 cm of trachea, and direct reanastomosis of right lung.

A 23-year-old woman, who had suffered recurrent acute bronchitis, dyspnoea, and stridor, was found to have a tracheal stenosis and complete left main bronchus obstruction. Biopsy of the tumour showed an adenoid cystic carcinoma. After pneumonectomy the trachea was closed through tumour tissue. Two weeks later a right thoracotomy showed that a tumour had invaded the trachea from the carina up to 6 cm and the right stem bronchus for 1 cm. Under extracorporeal circulation 7.5 cm of the trachea and right bronchus were resected. A direct tracheal anastomosis was easy to perform. Spontaneous respiration with efficient coughing returned after five days. Unfortunately, one month later, high fever caused by a lung abscess developed, which provoked a massive haemoptysis with fatal outcome.

Adult

[Reconstruction of trachea, carina and bronchus for tumors of the trachea, carina and lung].

This paper reports on 70 patients with tumors of the trachea, bronchus and lung treated by reconstruction of the trachea, carina and the main bronchus (21 cases) and sleeve lobectomy (49 cases). Postoperatively, 2 patients died of tracheo-innominate artery fistula and 2 developed empyema which was healed. There was no mortality in the sleeve lobectomy patients. The 3- and 5-year survival rates of the cancer patients treated by reconstruction of trachea, carina and main bronchus were 54.5%(6/11) and 33.3%(3/9), respectively. The 3- and 5-year survival rates of lung cancer patients treated by sleeve lobectomy were 46.6% (14/30) and 33.3% (7/21), respectively.

Adenocarcinoma

"Saber-Sheath" Trachea: A Clinical and Functional Study of Marked Coronal Narrowing of the Intrathoracic Trachea.

Data are presented from thirteen patients with marked coronal narrowing of the intrathoracic trachea associated with widening of the corresponding sagittal diameter. The term "saber-sheath" trachea describes this deformity which can simulate a mediastinal mass. The absence of mediastinal masses and the presence of obstructive pulmonary abnormalities in each patient, either as a clinical diagnosis (11 of 13), functional abnormality (10 of 11) or both (8 of 11), suggest that the "saber-sheath" trachea may be a useful sign of chronic obstructive pulmonary disease.

Aged

Vitamin A deficiency and keratin biosynthesis in cultured hamster trachea.

Tracheas from vitamin A-deficient hamsters in organ culture in vitamin A-free medium developed squamous metaplasia. Addition of retinyl acetate to the medium prevented squamous metaplasia and a mucociliary epithelium was maintained. Indirect immunofluorescent staining with antikeratin antibodies AE1 and AE3 indicated positive reactions with epithelium of tracheas either cultured in vitamin A-free or retinyl acetate (RAc)-containing medium. The "stratum corneum"-like squames in metaplastic tracheas were strongly stained by AE3. Immunoprecipitation of cytoskeletal extracts from [35S]methionine labeled tracheas with a multivalent keratin antiserum indicated that the concentration of keratins synthesized in tracheas cultured in vitamin A-free medium was greater than that observed in tracheas cultured in the presence of RAc. In addition, new species of keratin were expressed in tracheas cultured in RAc-free medium. Alterations in the program of keratin synthesis were clearly detectable after 1 d in vitamin A-free medium, even though squamous metaplasia was not yet obvious. Squamous tracheas were shown by immunoblot analysis to contain keratins of 50, 48, 46.5, and 45 kilodalton (kd) detected with AE1; and 58, 56, and 52 kd detected with AE3. Immunoblot analysis with monospecific antimouse keratin sera also demonstrated the presence of 60, 55, and 50 kd keratins in the metaplastic tracheas. All these various species of keratins were either absent or present in much reduced quantity in mucociliary tracheas in RAc-containing medium. Interestingly, the induction of squamous metaplasia in tracheal epithelium did not result in the expression of the 59 and 67 kd keratins which are characteristically expressed in the differentiated layers of the epidermis. Therefore, this study shows that squamous metaplasia of tracheas due to vitamin A-free cultivation is accompanied by an increase in keratin synthesis as well as by the appearance of keratin species not normally present in mucociliary tracheal epithelium.

Animals

Residual strains in porcine and canine trachea.

Residual strains exist in canine and porcine tracheas. They are revealed by cutting the trachea first perpendicular to its axis into rings, then radially into sectors. Each sector is characterized by an opening angle which is defined as the angle subtended between two radii joining the middle point of the inner wall to the tips of the inner wall. The trachea being non-axisymmetric, the opening angle depends on the position of the radial cut. The trachea being also nonuniform in the axial direction, the opening angle varies along the length of the trachea. In the dog, the opening angle of the trachea cut at the anterior position (cartilaginous) is about 100 degrees at the larynx; it increases fairly linearly to 180 degrees midway down the trachea; then increases slowly to about 200 degrees at the lower end where the trachea bifurcates into the main bronchi. Dog trachea cut in the posterior (muscular) position have an opening angle of about 50 degrees at the larynx, which increases to about 70 degrees three-quarters of the way down the trachea, then drops to 60 degrees at the lower end. In the pig, the opening angle of the trachea is much smaller, the values at anterior and posterior cuts are similar (without significant difference), and their mean value decreases from about 15 degrees at the laryngeal end to about 5 degrees at the lower end. These species and regional differences are discussed in relation to tracheal geometry and structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Non-adrenergic, non-cholinergic contractions in the electrically field stimulated guinea-pig trachea.

1. The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea-pig trachea. 2. In the presence of indomethacin (3 microM) and propranolol (1 microM) two contractile phases were evident in both the proximal and distal trachea. The first rapid phase was abolished by atropine (0.1 microM), whereas the prolonged, second phase was abolished by capsaicin (10 microM) pretreatment. Tetrodotoxin (3 microM) abolished the initial response and greatly inhibited the second phase. In proximal trachea this second phase was evident only in 9 of 22 preparations. The addition of the peptidase inhibitor thiorphan (10 microM) however, caused a second phase to be seen in all the proximal tissues examined. 3. The two phases of the contractions to EFS were differentially sensitive to the pulse duration applied. The initial, cholinergic contractions were evident at lower pulse durations than were the prolonged capsaicin-sensitive contractions, with the first phase being approximately 10 fold more sensitive than the second phase. 4. The magnitude of the capsaicin-sensitive contraction to EFS was significantly greater in the distal trachea than in the proximal trachea. This difference prevailed in the presence of thiorphan, an inhibitor of neutral endopeptidase. In contrast, concentration-response curves to capsaicin were similar in segments of proximal and distal trachea. 5. The non-adrenergic non-cholinergic (NANC) relaxant responses were studied in tissues in which excitatory neurogenic responses were pharmacologically abolished by capsaicin and atropine treatment. The NANC relaxant responses in the proximal trachea were evident at lower pulse frequencies and were of greater magnitude compared with NANC relaxant responses in the distal trachea. 6. These results indicate that, by pharmacologically manipulating the trachea and by selecting optimum stimulation parameters, a NANC contractile response to EFS can be seen throughout the length of the guinea-pig trachea. This NANC response is most likely to be due to the release of tachykinins from capsaicin-sensitive sensory fibres. It is suggested that NANC relaxant responses mask NANC contractile responses especially in the proximal trachea where NANC relaxant responses predominate.

Animals

Mechanism of endothelin-induced contraction in guinea-pig trachea: comparison with rat aorta.

1. Endothelin (1 nM-0.3 microM) produced a concentration-dependent contraction of guinea-pig epithelium-containing (intact) trachea (EC50 = 30.9 nM). Endothelin was a less potent agonist than leukotriene D4 (LTD4; EC50 = 0.77 nM), but was more potent than carbachol (EC50 = 0.15 microM) or substance P (EC50 = 1.4 microM). Endothelin was a more potent contractile agent in rat endothelium-denuded aorta (EC50 = 2.1 nM) than in guinea-pig trachea. 2. Endothelin-induced contraction in guinea-pig trachea was unaffected by mepyramine (10 microM), atropine (1 microM), SK&F 104353 (10 microM), a leukotriene receptor antagonist, or SQ 29,548 (1 microM), a thromboxane receptor antagonist. The contraction produced by 0.3 microM endothelin was potentiated by cyclo-oxygenase inhibition with 5 microM indomethacin. 3. Nicardipine (0.01 or 0.1 microM) or incubation in calcium-free medium +0.1 mM EGTA for 30 min had a relatively minor or no effect on endothelin concentration-response curves in guinea-pig intact trachea, but markedly inhibited responses produced by endothelin in endothelium-denuded aorta of the rat. Increasing the EGTA concentration in calcium-free medium to 1 mM abolished endothelin-induced contraction in guinea-pig trachea. 4. In guinea-pig trachea, ryanodine (10 microM) produced a 2.1 fold shift to the right of endothelin concentration-response curves and reduced the maximum response elicited by 0.3 microM endothelin. 5. Staurosporine (0.01 microM and 0.1 microM), a protein kinase C inhibitor, was without effect on endothelin- or carbachol-induced contraction in guinea-pig trachea, but markedly inhibited the response produced by endothelin in rat aorta. 6. Endothelin (3 nM-0.3 microM) produced a concentration-dependent stimulation of phosphatidylinositol (PI) turnover in guinea-pig intact trachea, with an EC50 value of 45.9 nM. 7. Removal of the epithlium markedly potentiated endothelin-induced contraction in guinea-pig trachea, producing a 4.7 fold leftward shift in endothelin concentration-response curves and an increase in the contractile response elicited by 0.3 microM endothelin. 8. These data indicate that endothelin is a potent agonist in guinea-pig trachea whose response is markedly enhanced by removal of the airway epithelium. Endothelin-induced contraction is not mediated to a marked extent by calcium influx via dihydropyridine-sensitive calcium channels and does not involve the release of histamine, acetylcholine, leukotrienes or thromboxane. Rather, endothelin appears to produce contraction of guinea-pig trachea via a direct action which involves stimulation of PI turnover and utilization of calcium from intracellular stores and, also, calcium influx via a pathway that is not sensitive to dihydropyridine calcium channel inhibitors. Endothelin-induced contraction of rat aorta was more sensitive to the effects of incubation in Ca2 +-free medium, nicardipine or staurosporine, suggesting that differences exist in the relative mechanisms whereby endothelin produces contraction in different tissues.

Animals

Cooling-induced contraction of trachea isolated from normal and sensitized guinea-pigs.

Fast (-7 degrees C/min) cooling of guinea-pig isolated trachea produced a rapidly developing, transient contraction followed by relaxation. Cooling-induced contraction was dependent on temperature (30, 20 or 10 degrees C) and responses in trachea obtained from actively sensitized guinea pigs were significantly greater (20 and 10 degrees C) than those observed in normal trachea. Cooling to 20 degrees C was selected for subsequent experiments. Pretreatment with sufficient concentrations of atropine, clemastine, cromoglycate, indomethacin, or nordihydroguaiaretic acid did not depress contraction to cooling in either normal or sensitized trachea. This indicates a direct effect of cooling. The contraction produced by cooling was resistant to verapamil (1 mumol/l) or dantrolene (0.3 mmol/l). Calmodulin antagonists (trifluoperazine, W-7 and calmidazolium; all of them at 10-100 mumol/l) inhibited contraction in sensitized and normal trachea. Activators of protein kinase C (phorbol 12,13-diacetate, 1 mumol/l) enhanced while inhibitors (H-7, 20 mumol/l; staurosporine, 10 mumol/l) depressed cooling-induced contraction in both normal and sensitized tissues. Incubation (20 min) in a Ca(2+)-free solution inhibited cooling-induced contraction in normal but not in sensitized trachea. Exposure to a low Na+ (25 mmol/l) or a K(+)-free medium abolished contraction to cooling in normal and sensitized trachea. Ouabain (0.1-10 mumol/l) and vanadate (0.01-5 mmol/l) inhibited cooling-induced contraction to a greater extent in normal than in sensitized trachea. Polymyxin B (0.5 mmol/l) selectively depressed responses to cooling in sensitized trachea. In a separate series of experiments, it was shown that sensitized trachea was hyperresponsive to ouabain and vanadate. Previous cooling to 20 degrees C abolished responses to ouabain but only attenuated those to vanadate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea.

1 A new in vitro preparation, the isolated lung strip of the cat, is described for investigating the direct effect of drugs on the smooth muscle of the peripheral airways of the lung. The preparation comprises a thin strip of lung parenchyma which can be mounted in a conventional organ bath for isometric tension recording. Its pharmacological responses have been characterized and compared with the isolated tracheal preparation of the cat. 2 The lung strip exhibited an intrinsic tone which was relaxed by catecholamines, aminophylline and flufenamate. It was contracted strongly by histamine, prostaglandin F2alpha, acetylcholine, compound 48/80, potassium depolarizing solution and alternating current field stimulation. In contrast, the cat trachea was unresponsive to histamine and prostaglandin F2alpha and did not exhibit an intrinsic tone. 3 (-)-Isoprenaline and (-)-adrenaline were much more potent in relaxing the lung strip than the trachea. The potency order of relaxation responses to isoprenaline, adrenaline and (+/-)-noradrenaline in the lung strip was isoprenaline greater than adrenaline greater than noradrenaline but in the trachea was isoprenaline greater than noradrenaline greater than or equal to adrenaline. 4 beta2-Adrenoceptor selective agonists salbutamol and terbutaline were more potent in the lung strip than the trachea, suggesting beta2-adrenoceptors predominated in the lung strip. Propranolol was equipotent in inhibiting isoprenaline relexations of the lung strip and trachea, whereas practolol was much less effective in inhibiting lung strip than trachea, further supporting a predominance of beta2-adrenoceptors in lung strip and beta1-adrenoceptors in trachea. 5 Strong Schultz-Dale type contractions were elicited in both lung strips and trachea by Ascaris lumbricoides antigen in actively sensitized cats. The initial phase of the contractile response of the lung strip following challenge was shown to be due to histamine release and was absent in the trachea. The delayed phase of the contraction which took several minutes to develop in both the mepyramine-treated lung strip and trachea was not due to prostaglandins E1, F2alpha or bradykinin, the probable mediator being slow reacting substance of anaphylaxis (SRS-A). 6 It is concluded that the isolated lung strip of the cat is useful as an in vitro model for investigating the effect of drugs on the smooth muscle of the peripheral airways of the lungs.

Adrenergic beta-Agonists

Effects of vasoactive intestinal polypeptide antagonists on cholinergic neurotransmission in dog and cat trachea.

1. The effects of vasoactive intestinal polypeptide (VIP) antagonists [AC-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP on excitatory neuroeffector transmission in the dog and cat trachea were investigated by use of microelectrode, double sucrose-gap and tension recording methods. 2. In the dog trachea, repetitive stimuli at high frequency (20 Hz) markedly enhanced the amplitude of contraction, the amplitude of contractions evoked by 50 stimuli at 20 Hz relative to that evoked by 5 stimuli being 14.2 +/- 3.8 times (n = 7, +/- s.d.). In the cat, the summation was much less marked, the amplitude of contractions evoked by 50 stimuli relative to that evoked by 5 stimuli being only 2.1 +/- 0.6 times (n = 5, +/- s.d.). Neither VIP antagonist had any effect on the relationship between the number of stimuli at 20 Hz and the relative amplitude of contraction in the dog trachea, but did enhance the amplitude of contractions to 1.1-1.5 times control in the cat trachea. 3. VIP antagonists dose-dependently enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by a single stimulus in the cat trachea, without changing the resting membrane potential or input membrane resistance of the smooth muscle cells. However, neither antagonist had any effect on the amplitude of the e.j.p. in the dog trachea. 4. Neither VIP antagonist had any effect on the post-junctional response of smooth muscle cells to exogenously applied acetylcholine (ACh; 10(-9)-10(-5) M) in the dog or cat trachea.5. In the cat trachea, VIP (10-11 M) suppressed the ej.p. amplitude to 0.74 +/- 0.09 times the control value (n = 6). However, after pretreatment of the tissue with the VIP antagonists [Ac-Tyr', D-Phe2]-GRF(1-29)- H2 (10-8M) and [4-Cl-D-Phe6, Leu17]-VIP (10-8M), VIP (10-11 M) did not suppress the ej.p. amplitude, indicating that VIP antagonists block the presynaptic inhibitory action of exogenous VIP.6. In parallel with the enhancement of contraction, ej.ps showed marked summation when repetitive field stimulations were applied at high frequency (20 Hz) in the dog trachea. The relationship between the relative amplitude of the ej.p. and number of stimuli at 20 Hz was linear and the slope was 2.2 +/- 0.3 mV/stimulation. VIP antagonists did not affect this relationship. However, in the cat trachea, summation of ej.ps was not at all marked and a linear relationship was not observed with the double sucrose-gap method. Incubation of the cat tracheal tissue with either of the VIP antagonists (10-8 or 10-7M) markedly enhanced the summation of ej.ps evoked by repetitive field stimulation at 20 Hz, and after the treatment a linear relationship between the number of stimuli and the amplitude of ej.ps was observed, the slopes being 0.6 +/- 0.1 (n = 8) and 0.55 +/- 0.1 mV/stimulation (n = 5), respectively.7. These results indicate that both VIP antagonists, [Ac-Tyr', D-Phe2]-GRF(1-29)-NH2 and [4-Cl-DPhe6, Leu17]-VIP, have a prejunctional action accelerating the excitatory neuroeffector transmission, presumably by enhancing transmitter release from the vagus nerves in the cat, but not in the dog trachea.

Acetylcholine

Comparison of the effects of cromakalim in trachea isolated from normal and albumin-sensitive guinea-pigs.

The effects of the K(+)-channel activator, cromakalim, on spontaneous tone and constrictor responses to vagal stimulation or acetylcholine were compared in trachea isolated from groups of guinea-pigs that were: untreated; sensitized and chronically exposed to inhaled albumin; or sham sensitized. Responses were assessed as changes in intraluminal pressure in the isolated, Krebs-filled trachea, increases and decreases in intraluminal pressure directly reflecting constriction and dilatation, respectively. Cromakalim reduced resting intraluminal pressure in normal trachea but in sensitized trachea mixed effects occurred, many preparations exhibiting increases in intraluminal pressure, particularly at lower concentrations of cromakalim. Cromakalim attenuated the frequency-dependent increases in intraluminal pressure evoked by stimulation of the vagus nerve in a concentration-dependent manner and to a similar degree in trachea from each of the three groups tested. The degree of attenuation was similar in the absence and presence of the cyclo-oxygenase inhibitor flurbiprofen. In untreated trachea, responses to a range of concentrations of applied acetylcholine were attenuated by cromakalim. In sensitized trachea the response to the lowest concentration of applied acetylcholine was attenuated by cromakalim but responses to higher concentrations of were unaffected. The results indicate that the direct relaxant effect of cromakalim is altered in sensitized trachea, which may indicate abnormal K(+)-channel behaviour in the smooth muscle cell membrane. Attenuation by cromakalim of vagal responses occurs in both normal and sensitized trachea, due chiefly to a pre-junctional effect on cholinergic neurotransmission which is independent of the generation of cyclo-oxygenase products.

Acetylcholine

Modulation of cholinergic neurotransmission by the peptide VIP, VIP antiserum and VIP antagonists in dog and cat trachea.

1. Comparative studies on the effects of vasoactive intestinal polypeptide (VIP), commercially available VIP antiserum or VIP antagonists [Ac-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP on excitatory neuroeffector transmission in the dog and cat trachea were performed with microelectrode, double sucrose-gap, and tension recording methods. 2. VIP (10(-11)-10(-9) M) had no effect on the resting membrane potential or on the input resistance of the smooth muscle cells of dog and cat trachea. However, with increased concentrations (greater than 10(-8) M) VIP hyperpolarized the membrane and decreased the input resistance of the membrane in both tissues. 3. VIP (10(-10)-10(-7) M) dose-dependently reduced the amplitude of the contractions evoked through the nervous structure excited by field stimulation in the combined presence of indomethacin (10(-5) M) and guanethidine (10(-6) M) in the dog, and in the presence of guanethidine (10(-6) M) in cat trachea. In parallel with actions on twitch contractions, VIP (10(-11)-10(-7) M) reduced the amplitude of the excitatory junction potentials (EJPs) evoked through the nervous structure excited by single pulse field stimulation in both tissues. 4. VIP (10(-9) M) had no effect on the post-junctional response of smooth muscle cells to exogenous acetylcholine (ACh) (10(-9)-10(-5) M). 5. During repetitive field stimulation at the stimulus frequency of 0.033-0.1 Hz, the amplitude of the EJPs was gradually reduced, and VIP (10(-9) M) enhanced this depression phenomenon in the dog and cat trachea. 6. EJPs also showed summation when repetitive field stimulation was applied at high frequency (20 Hz) in the dog trachea. The slope of the relationship between the relative amplitude of the EJP and number of stimuli at 20 Hz was 2.2 +/- 0.4 mV/stimulation (n = 4) in the dog trachea. However, in the cat trachea, summation of EJPs was not prominent, giving a mean slope of 0.6 +/- 0.2 mV/stimulation (n = 6) measured by the microelectrode method. VIP (10(-9) M) shifted downward the relationship between the relative amplitude of the EJP and the number of stimuli at 20 Hz in both tissues. 7. Overnight incubation with VIP antiserum (10(-6) g/ml) had little effect on the depression of the EJP in the dog and cat trachea, or the summation of the EJP observed in the dog trachea.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine

Epithelium-derived inhibition of [3H]acetylcholine release from the isolated guinea-pig trachea.

To investigate presynaptic, regulatory mechanisms on parasympathetic nerve fibres innervating the airways, the release of newly-synthesized [3H]acetylcholine from the isolated trachea was studied. Reverse phase HPLC followed by liquid scintillation spectrometry was used to separate and quantify the radioactive compounds choline, phosphorylcholine and acetylcholine in the incubation medium and the tissue. During the incubation of the tracheae with [3H]choline a significant synthesis of [3H]acetylcholine (35,000 dpm/preparation) and [3H]phosphorylcholine (500,000 dpm/preparation) occurred. In epithelium-deficient tracheae the formation of [3H]phosphorylcholine was enhanced, whereas the content of [3H]acetylcholine remained unchanged. The spontaneous outflow of tritium consisted mainly of [3H]phosphorylcholine (900 dpm/3 min) and [3H]choline (800 dpm/3 min); [3H]acetylcholine was only a minor fraction (50 dpm/3 min). Electrical stimulation of tracheae with intact epithelium caused only a small release of [3H]acetylcholine (460 dpm in the sample obtained during stimulation), but a considerable outflow of [3H]phosphorylcholine (1,900 dpm) without affecting the outflow of [3H]choline. Electrical stimulation of epithelium-deficient tracheae, however, induced a substantial release of [3H]acetylcholine (2,400 dpm), but only a small outflow of [3H]phosphorylcholine. Chemical stimulation (30 mumol/l veratridine) also caused a large release of [3H]acetylcholine (1,700 dpm) without affecting the outflow of [3H]phosphorylcholine or [3H]choline. Indomethacin (3 mumol/l) enhanced the electrically-evoked release of [3H]acetylcholine from tracheae with intact epithelium by 89%. The present experiments demonstrate a strong inhibition by the epithelium of the electrically-evoked release of [3H]acetylcholine from the isolated guinea-pig trachea. Cyclooxygenase products of arachidonic acid do not appear as the main mediators of the epithelium-derived inhibition of acetylcholine release.

Acetylcholine

Experimental studies on an artificial trachea of collagen-coated poly(L-lactic acid) mesh or unwoven cloth combined with a periosteal graft.

Artificial tracheas were fabricated from poly(L-lactic acid) mesh or unwoven cloth coated with collagen in order to reconstruct the respiratory airway by self regeneration without retaining the prosthesis at the replacement site, thus preventing infection, air leakage, granulation tissue formation, and displacement of the prosthesis. Nine weeks after placing a periosteal autologous graft from the tibia around the cervical trachea of a rabbit, bone rings formed without infection. Two weeks after replacement of an 8 X 8 mm window-shaped section of the cervical trachea with autologous periosteum, the internal surface of the trachea was well epithelialized without local complications, but ossification was not seen. One week after cervical substitution with our 2 cm long artificial trachea combined with the periosteal graft, cartilage was produced around the mesh material but neither ossification nor epithelization was observed thereafter, probably due to local infection. On the other hand, cartilage, bone, and epithelium did not form around the unwoven cloth artificial trachea after the substitution, probably because of severe infection due to collapse of the tracheal lumen. However, the formation of bone rings around the trachea suggests preservation of the neotracheal lumen, which may have potential for the treatment of tracheomalacia and/or bronchomalacia.

Animals