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At least 181 records · Page 10Linked to original sources
PubMed2000

The effect of the enantiomers of formoterol on inherent and induced tone in guinea-pig trachea and human bronchus.

The long-acting beta2-adrenoceptor agonist formoterol is, like all other members of this class of drugs, used as a racemate in the clinic. While the effects of the individual enantiomers have been studied on airway smooth muscle from guinea pig, comparable data on human bronchial smooth muscle are scanty or absent. Therefore, we compared the effects of the enantiomers of formoterol on inherent and induced tone in isolated human bronchi with that on guinea-pig trachea in vitro. The human bronchi either were studied under resting tension conditions or were precontracted with 10 microM carbachol or 0.1 mM histamine. The guinea-pig trachea was precontracted with 0.01, 0.1 or 1 microM carbachol. The racemate and (R,R)-formoterol caused a concentration-dependent relaxation of all preparations with an EC50 of about 1 nM. In the guinea-pig trachea, the concentration-effect curve for formoterol was moved to the right in response to an increased concentration of carbachol. In both human bronchus and guinea-pig trachea, (S,S)-formoterol was more than 1,000 times less potent than (R,R)-formoterol. Thus the relaxing effect of formoterol in human airways as well as in guinea-pig trachea was shown to lie with the (R,R)-enantiomer. Notably, (S,S)-formoterol did not exert any contractile effects within the tested concentration range in either airway preparation. Therefore, we conclude that with regard to relaxant effects the pure (R,R)-enantiomer of formoterol does not offer a benefit over the racemate.

Adrenergic beta-Agonists↗
PubMed1996

Involvement of the M2 muscarinic receptor in contractions of the guinea pig trachea, guinea pig esophagus, and rat fundus.

The involvement of the M2 muscarinic receptor in contractile responses of the guinea pig trachea, guinea pig esophagus, and rat fundus was investigated. In the standard assay, oxotremorine-M elicited contractions of the trachea with an EC50 value of approximately 73 nanoM.--2- -(Diethylamino)methyl- -1-piperidinyl-acetyl--5,11- dihydro-6H-pyrido-2,3-b--1,4- benzodiazepine-6-one (AF-DX 116) at 1 and 10 microM antagonized these contractions by 2.1- and 9.0-fold increases in the EC50 value for oxotremorine-M. These effects are consistent with antagonism of an M3-mediated contractile response. In subsequent experiments, the M3 receptors were first inactivated selectively by incubation with N-(2-chloroethyl)-4- piperidinyl diphenylacetate (4-DAMP mustard) (40 nanoM) for 1 hr in the presence of AF-DX 116 (1 microM) followed by extensive washing. In 4-DAMP mustard treated trachea, oxotremorine-M elicited contractions with an EC50 value of 0.31 microM in the presence of histamine (10 microM) and forskolin (4 microM). Under these conditions, AF-DX 116 at 1 and 10 microM antagonized contractions to oxotremorine-M by 8- and 59-fold increases in the EC50, respectively, while para- fluorohexahydrosiladiphenidol(p-F-HHSiD) (0.1 microM) had no effect. These effects are consistent with a contraction being mediated by an M2 receptor. In the guinea pig esophagus and rat fundus, AF-DX 116 and p-F-HHSiD blocked contractions measured under similar conditions with magnitudes intermediate between what would be expected from an M2 and an M3 receptor, suggesting that perhaps both subtypes contribute to the overall contractile response under these conditions. In addition, contractions of the guinea pig trachea measured in the presence of histamine and forskolin were pertussis toxin sensitive. These results that, in the trachea, M2 receptors can dominate the contractile response after a majority of the M3 receptors have been inactivated, whereas in the guinea pig esophagus and rat fundus, M2 receptors may contribute to, but do not play a dominant role in the overall response.

Adrenergic beta-Agonists↗
PubMed1993

Effects of two Ca2+ modulators in normal and albumin-sensitized guinea-pig trachea.

The voltage-dependent Ca2+ channel blocker, verapamil, and the calmodulin antagonist, trifluoperazine, each reduced resting tone and attenuated constriction induced by acetylcholine or vagal stimulation in normal guinea-pig trachea. Attenuation of vagal responses involved both pre- and post-junctional effects on cholinergic neurotransmission. In albumin-sensitized trachea both drugs caused small increases in resting tone. Vagally mediated constrictor responses were resistant to attenuation by verapamil in sensitized trachea. Trifluoperazine was less effective against acetylcholine-induced tone in sensitized, as compared to untreated, trachea. The results indicate that Ca2+ handling is altered in airway smooth muscle in this animal model of bronchial asthma. Abnormal Ca2+ handling, therefore, may underlie the hyperresponsiveness to vagal input exhibited in sensitized trachea and could contribute to the generalised airway hyperreactivity characteristic of asthma.

Acetylcholine↗
PubMed1996

Effects of in vitro 5-HT1 receptor activation in guinea pig trachea.

5-hydroxytryptamine (5-HT) has been reported to show some effects in respiratory tissues by activation of different subtype receptors. It has been demonstrated that 5-HT2 receptor activation causes in vivo and in vitro airways contraction and enhances effects of cholinergic nerve-mediated responses, whereas 5-HT1 receptor activation seems to be related to a relaxant effect. Moreover, in isolated guinea pig ascendens colon preparations 5-HT1 activation causes relaxation by involvement of nitric oxide (NO). The aim of this study was to investigate the effects of 5-HT1 receptor activation in guinea pig trachea as well as NO probable role in this activation. In tissues pretreated with both ketanserin (10 microM), an antagonist of 5-HT2 receptors, and ondansetron (10 microM), an antagonist of 5-HT3 receptors, 5-HT (from 10 nM to 10 mM) relaxed guinea pig trachea precontracted with acetylcholine (ACh, 100 microM). Carboxamidotryptamine (5-CT, from 10 nM to 10 mM), an agonist of 5-HT1 receptors, as well relaxed guinea pig trachea precontracted with ACh (100 microM). A pretreatment with NAN-190 (from 10 nM to 100 microM), a 5-HT1A selective antagonist, reduced the 5-HT and 5-CT relaxant effects but only at very high concentrations. Finally, a pretreatment with L-nitro-arginine-methyl-ester (L-NAME, 1 mM), an inhibitor of NO-synthase, and L-arginine (L-ARG, 1 mM), a precursor of NO synthesis, did not modify 5-HT and 5-CT responses in guinea pig trachea. In conclusion, this study suggests a 5-HT relaxant activity in guinea pig trachea via a 5-HT1 receptor activation without any NO pathway involvement. However, further investigations are needed to clarify which 5-HT1 receptor subtype is involved in 5-HT relaxant effect.

Acetylcholine↗
PubMed1995

Inhibitory effects of d-nicotine on the responses evoked by 1-isomer in trachea and bronchus isolated from guinea-pig and rabbit.

1. The effects of d-nicotine on the responses induced by 1-isomer were studied in tracheae and bronchi isolated from guinea-pigs and rabbits. In guinea-pigs trachea 1-nicotine produced a biphasic response consisting of initial contraction and following relaxation. In other airway preparations 1-nicotine produced only contraction. 2. d-Nicotine did not produce any responses except for the case of guinea-pig trachea. d-isomer produced only relaxation and relative potency was approximately 0.44 in guinea-pig trachea. 3. Pretreatment with d-nicotine (30-300 microM) reduced concentration response curves for 1-isomer in a non-competitive manner in all preparations used in this study. 4. 1-nicotine at the concentration of 3 microns, which did not produce any response itself, reduced the concentration response curve of 1-nicotine in guinea-pig trachea. 5. Inhibition by d-nicotine or 1-nicotine (3 microM) of the concentration-response curve of 1-nicotine may be due to desensitization of nicotine receptors.

Animals↗
PubMed1992

The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry.

The sympathetic and sensory innervation of guinea-pig trachea and lung were studied by means of retrograde neuronal tracing using fluorescent dyes, and double-labelling immunofluorescence. Sympathetic neurons supplying the lung were located in stellate ganglia and in thoracic sympathetic chain ganglia T2-T4; those supplying the trachea resided in the superior cervical and stellate ganglia. Retrogradely labelled sympathetic neurons were usually immunoreactive to tyrosine hydroxylase; the majority also contained neuropeptide Y immunoreactivity. However, a small number were non-catecholaminergic (i.e. tyrosine hydroxylase negative), but neuropeptide Y immunoreactive. Within the airways, tyrosine hydroxylase/neuropeptide Y-immunoreactive axons were found in the smooth muscle layer, around blood vessels including the pulmonary artery and vein, and to a lesser extent in the lamina propria. Periarterial axons contained in addition dynorphin immunoreactivity. Sensory neurons supplying the lung were located in jugular and nodose vagal ganglia as well as in upper thoracic dorsal root ganglia; those supplying the trachea were most frequently found bilaterally in the nodose ganglia and less frequently in the jugular ganglia. A spinal origin of tracheal sensory fibres could not be consistently demonstrated. With regard to their immunoreactivity to peptides, three types of sensory neurons projecting to the airways could be distinguished: (i) substance P/dynorphin immunoreactive; (ii) substance P immunoreactive but dynorphin negative; and (iii) negative to all peptides tested. Substance P-immunoreactive neurons innervating the airways invariably contained immunoreactivity to neurokinin A and calcitonin gene-related peptide. Retrogradely labelled neurons located in the nodose ganglia belonged almost exclusively (greater than or equal to 99%) to the peptide-negative group, whereas the three neuron types each represented about one-third of retrogradely labelled neurons in jugular and dorsal root ganglia. Within the airways, axons immunoreactive to substance P/neurokinin A and substance P/calcitonin gene-related peptide were distributed within the respiratory epithelium of trachea and large bronchi, in the lamina propria and smooth muscle from the trachea down to the smallest bronchioli (highest density at the bronchial level), in the alveolar walls, around systemic and pulmonary blood vessels, and within airway ganglia. Those axons also containing dynorphin immunoreactivity were restricted to the lamina propria and smooth muscle. The origin of nerve fibres immunoreactive for vasoactive intestinal polypeptide, of which a part were also neuropeptide Y immunoreactive, could not be determined by retrograde tracing experiments. Vasoactive intestinal polypeptide-immunoreactive fibres terminating within airway ganglia may be of preganglionic parasympathetic origin, whereas others (e.g. those found in smooth muscle) may arise from intrinsic ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Beta-adrenoceptor reactivity after epithelium removal in guinea-pig trachea in vitro.

In guinea-pig isolated tracheae precontracted with pilocarpine (2 x 10(-5)M) mechanical removal of the epithelium did not significantly modify the degree of relaxation induced by three different adrenergic agonists: epinephrine (adrenaline), isoproterenol (isoprenaline) and salbutamol. The failure of epithelium removal to modify isoproterenol relaxant activity was observed in both spontaneous tone and pilocarpine precontracted tracheae. In tracheae obtained from actively sensitized (ovalbumin) guinea-pigs, log-concentration response curves of epinephrine and salbutamol were unchanged by epithelium damage, whereas that of isoproterenol was slightly shifted to the left. In ovalbumin sensitized tracheae exposed to the antigen (ovalbumin, 50 micrograms/ml) epithelium removal enhanced the relaxant activity of the three adrenergic agonists used. Beta-adrenoceptor desensitization (isoproterenol, 10(-6)M for 20 min twice) carried out in ovalbumin actively sensitized tracheae with or without epithelium, shifted the log-concentration response curves of isoproterenol to a similar rightward position. The present data suggest that the airway epithelium plays a minor role in the regulation of guinea-pig tracheal sensitivity to beta-adrenoceptor agonists, which is evident only in a classical model of experimental asthma.

Albuterol↗
PubMed2004

Tissue-engineered trachea from sheep marrow stromal cells with transforming growth factor beta2 released from biodegradable microspheres in a nude rat recipient.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of using autologous sheep marrow stromal cells cultured onto polyglycolic acid mesh to develop helical engineered cartilage equivalents for a functional tracheal replacement. We also explored the potential benefit of local delivery of transforming growth factor beta 2 with biodegradable gelatin microspheres. METHODS: Bone marrow was obtained by iliac crest aspiration from 6-month-old sheep and cultured in monolayer for 2 weeks. At confluence, the cells were seeded onto nonwoven polyglycolic acid fiber mesh and cultured in vitro with transforming growth factor beta 2 and insulin-like growth factor 1 for 1 week. Cell-polymer constructs were wrapped around a silicone helical template. Constructs were then coated with microspheres incorporating 0.5 microg transforming growth factor beta 2. The cell-polymer-microsphere structures were then implanted into a nude rat. On removal, glycosaminoglycan content and hydroxyproline were analyzed in both native and tissue-engineered trachea. Histologic sections of both native and tissue-engineered trachea were stained with hematoxylin and eosin, safranin-O, and a monoclonal anti-type II collagen antibody. RESULTS: Cell-polymer constructs with transforming growth factor beta 2 microspheres formed stiff cartilage de novo in the shape of a helix after 6 weeks. Control constructs lacking transforming growth factor beta 2 microspheres appeared to be much stiffer than typical cartilage, with an apparently mineralized matrix. Tissue-engineered trachea was similar to normal trachea. Histologic data showed the presence of mature cartilage. Glycosaminoglycan and hydroxyproline contents were also similar to native cartilage levels. CONCLUSIONS: This study demonstrates the feasibility of engineering tracheas with sheep marrow stromal cells as a cell source. Engineering the tracheal equivalents with supplemental transforming growth factor beta 2 seemed to have a positive effect on retaining a cartilaginous phenotype in the newly forming tissue.

Absorbable Implants↗
PubMed1991

Ozone absorption into excised porcine and sheep tracheae by a bolus-response method.

The absorption of ozone (O3) into excised porcine and sheep tracheae was characterized by a bolus-response experiment in which a bolus with a peak O3 concentration of 1 ppm was rapidly injected into a steadily flowing airstream entering the trachea. Using a fast-responding chemiluminescent analyzer of our design, the O3 concentration curves at the proximal end (i.e., the bolus input) and at the distal end (i.e., the response) of the trachea were monitored. Each concentration curve was numerically integrated, and the fraction of O3 absorbed in the trachea was obtained by subtracting from unity the ratio of the response integral to the bolus input integral. Average values of ozone-absorbed fraction decreased from about 0.50 to 0.15 at increasing airflows from 50 to 200 ml/sec. A diffusion theory that includes the effects of bulk convection, axial dispersion, and first-order absorption was developed to relate the fractional absorption to an overall mass transfer coefficient (K). The results indicate that K is independent of airflow, suggesting that the diffusion resistance in mucus is much greater than that in the gas phase. The time-weighted integrals of the concentration curves were also computed, allowing the mean residence time of O3 in the trachea (delta tau) to be determined. As predicted by the diffusion theory, delta tau was inversely related to the rate of O3 absorption.

Absorption↗
PubMed1998

Action of polygodial, a sesquiterpene isolated from Drymis winteri, in the guinea-pig ileum and trachea 'in vitro'.

This study describes the action of the sesquiterpene polygodial, the major constituent isolated from the bark of Drymis winteri in the guinea pig ileum and trachea in vitro. Polygodial (5 to 128 microM), added for 20 min, did not affect the resting tone of the preparations, but caused graded inhibition, associated in some cases with rightward displacement of the acetylcholine, histamine (1 nM to 10 microM), bradykinin (0.1 nM to 1 microM) and KCl (1 to 100 mM)-contraction response curves. When assessed in the guinea-pig trachea, polygodial (5 to 342 microM) caused significant inhibition of bradykinin (10 pM to 1 microM), 9,11-dideoxy-9alpha,11alpha-methano-epoxy prostaglandin F2alpha (0.1 to 1000 nM) and KCl (1 to 100 mM)-induced contractions, although the action against bradykinin was not concentration-dependent. Polygodial (5 to 80 microM) caused a small but significant shift to the right of substance P and also the selective agonist of tachykinin NK2 receptor [beta-Ala8]neurokinin A-(4-10)-induced contractions in guinea pig trachea. This action of polygodial seems to be quite selective towards tachykinin NK2 receptors since up to 432 microM, polygodial had no effect against contraction caused by tachykinin NK1 receptor agonist, substance P methyl ester. When tested in the guinea-pig trachea from animals which had been actively sensitised to ovalbumin, polygodial (30 to 40 microM) caused time and concentration-dependent inhibition of ovalbumin-mediated contraction. In addition, polygodial (85 to 342 microM) inhibited contraction induced by compound 48/80 (1 to 1000 microg/ml), in the guinea-pig trachea from non-sensitised animals. These findings and those from our previous study are consistent with the notion that the main sesquiterpene polygodial isolated from the bark of D. winteri is responsible for most, if not all, of the relevant pharmacological action reported previously for the extract of this plant. Thus, polygodial could be of potential value in the development of a new drug for the treatment of asthma, allergy and other inflammatory processes.

Animals↗
PubMed1982

Reconstructive surgery for obstructing lesions of the intrathoracic trachea in infants and small children.

This is a report of ten infants and small children with congenital obstructive lesions of the distal trachea and main bronchi. Four were successfully resected. One with a distal segment stenosis required tracheal resection at age 6 wk, another with stenosis of the distal half of the trachea at age 18 mo, and 2 (1 with distal stenosis and 1 with tracheal hamartoma) at age 4 yr. All 4 are presently free of symptoms and their anastomoses have grown without stricture. A child with coil-spring mucosal stenosis of the left main bronchus developed an excellent airway following bronchoscopic removal of the folds, and a baby with tracheomalacia was successfully treated with a rib splint on a segment of distal tracheomalacia, but she died later of associated cyanotic congenital heart disease. Four babies died with airway obstruction in the newborn period. Two with critical distal stenoses died before tracheal reconstruction could be performed. Two died following emergency resections in which all of the congenital stenosis could not be removed. In both, stenotic trachea remained despite operation. All of these infants had complete cartilage rings the entire length of the trachea. Congenital lesions of the distal trachea may become suddenly life-threatening at birth or during the onset of a respiratory infection. An abrupt or insidious onset of airway symptoms requires an expeditious diagnostic evaluation to define the tracheobronchial anatomy, and the operating team has to be prepared for emergency tracheal reconstruction.

Abnormalities, Multiple↗
PubMed1982

Tracheoplasty for congenital stenosis of the entire trachea.

Congenital stenosis involving the entire length of the trachea has generally been regarded as a fatal disease. Tracheoplasty using costal cartilage grafts to enlarge the lumen was successfully employed in such a case, and the technique is described. A 12-mo-old female was referred with recurrent severe respiratory distress since birth. By tracheoscopy and bronchography, the entire trachea was seen to be stenotic. The left bronchus was of normal caliber by bronchogram and the left lung was over inflated, while the right lung was aplastic. Through a midsternal thoracotomy, the left bronchus was incised and cannulated for ventilation. Longitudinal incision of the entire length of the anterior wall of the trachea permitted the advance of a nasotracheal tube along the inner surface of the divided trachea to the carina. Two pieces of costal cartilage were used to fill the defect in the anterior wall of the trachea. The grafts were attached to the tracheal edges by interrupted 5-0 Dexon sutures. The endotracheal tube was successfully removed two months later. The subsequent course of the patient has been satisfactory.

Cartilage↗
PubMed1983

Effect of prosthetic airway splint on the growing trachea.

Airway splints are now used clinically to treat tracheomalacia and may also have a place in the management of tracheal stenosis. These studies in 5 to 7 Kg piglets were designed to assess the effects of prosthetic airway splints on airway growth and to establish their usefulness in the reconstruction of tracheal defects. Three experimental groups were studied: group I (n = 8). Silastic reinforced Marlex mesh or Vicryl mesh prostheses were placed around 75% of the circumference of a 3 cm segment of trachea. Pigs were sacrificed at 4 months (average weight = 78.9 +/- 9.0 Kg) and the cross-sectional area of trachea was measured. Group II (n = 5). The same prostheses were used to replace the tracheal defect created by excising three rings (50% of tracheal circumference). Tracheas were examined grossly and histologically at sacrifice. Group III (n = 5). Same as Group II except tracheal defect covered by strap muscles. Prostheses placed external to them to prevent airway collapse. Group I had 4% to 14% (mean 8%) decrease from normal cross-sectional area of trachea at site of splint. No airway obstruction and no infection was encountered. Group II, severe airway obstruction, granulation tissue, and infection at site of defect was noted. Group III showed no signs of airway obstruction, no infection, and minimal airway narrowing. Re-epithelialization of the muscle surface in contact with airway occurred in all these animals. Silastic reinforced Marlex or Vicryl splints placed around the intact rapidly growing trachea do not significantly limit its growth. In addition, these synthetic materials appear to be well-tolerated when used to reconstruct tracheal defects if placed over well-vascularized tissue such as muscle.

Animals↗
PubMed1998

Preliminary evidence that cell death may contribute to separation of the trachea from the primitive foregut in the rat embryo.

BACKGROUND/PURPOSE: The embryogenesis of many congenital tracheoesophageal abnormalities has been elucidated poorly, mainly because of an incomplete understanding of the normal mechanism of separation of the primitive foregut into the trachea and esophagus. There has been controversy about the existence and significance of the so-called tracheoesophageal septum. This study investigates the normal mechanism of tracheoesophageal separation in the rat. METHODS: Timed-pregnant Sprague-Dawley rats were killed on gestational days 11 to 16, respectively (the day on which the vaginal smear showed sperm was considered day 0 of gestation). Thirty-six embryos (six embryos from each age group) were fixed in 10% formalin. Fixed embryos from gestational day 13, 12, and 11 were sandwiched in melted agar to facilitate proper orientation before being processed. Half of the fetuses from each age group were sectioned serially in a transverse plane and the other half in a sagittal plane. The histological sections were stained with H&E. RESULTS: On gestational day 11, the foregut appears as a ventrodorsal slit in transverse section. Below the primitive pharynx, the epithelial cells on the ventral part of the foregut are actively proliferating, producing two lateral epithelial bulges (primitive bronchial buds). The epithelial cells of the dorsal aspect of the foregut show no sign of active growth. On day 12, the proximal trachea still shares a common lumen with the foregut. The distal trachea, the tracheal bifurcation, and both primary bronchi are recognized easily. At the point of tracheoesophageal separation, there is obvious debris of dead epithelial cells and condensed nuclei. These appearances were specifically located around the so-called tracheoesophageal septum and nearby grooves, resulting in enfolding cristae. There was no cell proliferation or inflammatory response in this region. On gestational day 13, the separation of the trachea and esophagus was almost complete. CONCLUSION: The present study demonstrates that a specific and consistent pattern of cell death in the region of the "tracheoesophageal septum" produced enfolding cristae that may be part of the mechanism of separation of the trachea and esophagus.

Animals↗
PubMed1995

Surgery for patients with thyroid carcinoma invading the trachea: circumferential sleeve resection followed by end-to-end anastomosis.

BACKGROUND: Curative surgery can be accomplished by tracheal resection in patients with thyroid carcinoma invading the trachea; however, there is controversy regarding the extent of the tracheal resection. In this study we investigated by means of histologic examination the mode of tracheal invasion by thyroid carcinoma. METHODS: Twenty-one patients with thyroid carcinoma invading the trachea underwent circumferential sleeve resection of the involved trachea. The extent of invasion of the tracheal wall on the adventitial and mucosal sides was compared on histologic examination. RESULTS: Three to nine tracheal rings were resected. Assessment of longitudinal spread showed that one to six rings (mean; 3.1 rings) were invaded on the adventitial side but only zero to four rings (mean; 1.9 rings) on the mucosal side, with invasion on the mucosal side never exceeding invasion on the adventitial side. In contrast, examination of circumferential spread showed invasion on the mucosal side exceeding invasion on the adventitial side in five cases. CONCLUSIONS: Our results suggest that when the extent of invasion of the adventitia is considered, carcinoma tissue may be left behind on the mucosal side of the trachea when partial wedge resection is performed and that, whenever feasible, circumferential sleeve resection should be performed in patients with thyroid carcinoma invading the trachea.

Adult↗
PubMed2001

Mechanical properties of artificial tracheas composed of a mesh cylinder and a spiral stent.

Much work has been done on the materials used for mesh-type artificial tracheas, but a precise mechanical evaluation of these structures has not yet been performed. In the present study, we determined the mechanical properties of typical mesh-type artificial tracheas and compared them with those of native trachea. Four types of artificial trachea were made and used for the mechanical tests. The basic frame of all the specimens was composed of a mesh cylinder and a spiral stent. The specimen whose mesh was sealed with collagen sponge showed almost the same behavior in the force-strain curve under compression, suggesting that collagen sealing has little effect on mechanical properties. Agreement between measured and estimated mechanical properties was good, especially in the low strain region, suggesting that artificial tracheas can be designed in terms of mechanical properties by mainly considering the basic frame structure.

Animals↗
PubMed1998

Influence of absorption enhancers (bile salts) and the preservative (benzalkonium chloride) on mucociliary function and permeation barrier function in rabbit tracheas.

Effects of bile salts and benzalkonium chloride on the ciliary beat activity (frequency) and the mucociliary transport rate of tracheas, and permeabilities of 6-carboxyfluorescein (6-CF; Mw 376) and FITC-dextrans (FD-4; Mw 4300) as hydrophilic compounds through trachea were investigated for intratracheal delivery of drugs. Ciliary beat activity was measured by an in vitro photoelectric method by using excised rabbit tracheas. Transport rate was determined by an in vivo endoscopic method in rabbit tracheas. Permeation test was carried out by using excised rabbit tracheas. The ciliary beat activities and mucociliary transport rates were not significantly affected by 1, 10 and 20 mM sodium glycocholate, while they were significantly decreased by 1 and 10 mM sodium taurodeoxycholate and immediately halted after application of 20 mM taurodeoxycholate. They were not significantly affected by 0.02% of benzalkonium chloride, whereas they were completely halted by 0.05% of benzalkonium chloride. The apparent permeability coefficients (Papp) of 6-CF and FD-4 were 2.35x10(-7) and 2.22x10(-8) cm/s, respectively. One mmol of glycocholate did not significantly increase the Papp of 6-CF and FD-4, while, 10 mM of glycocholate and 1 and 10 mM of taurodeoxycholate significantly increased the Papp. Benzalkonium chloride (0.01%) did not significantly increase the Papp of 6-CF, whereas 0.03% significantly increased the Papp of 6-CF. Benzalkonium chloride (0.01 and 0.03%) slightly increased the Papp of FD-4. Therefore, sodium glycocholate may be a safe and useful absorption enhancer for intratracheal delivery of drugs.

Animals↗
PubMed1989

Active sensitisation modifies beta-adrenoceptor reactivity in guinea-pig trachea.

The occurrence of beta-adrenoceptor desensitisation in clinical experience, after long term therapy with specific beta 2-agonists, is still an open question, even if this phenomenon is easily observed in different experimental models. Since the majority of these experiments have been performed in normal animals, we investigated the possible occurrence of beta-adrenoceptor desensitisation in the ovalbumin actively sensitised guinea-pig model of experimental asthma. The isoproterenol concentration-response curves performed in pilocarpine contracted guinea-pig trachea in vitro were shifted to the right by the beta-adrenoceptor desensitisation procedure, which was achieved by the in vitro administration of isoproterenol (10(-5) M x 2 times x 20 min each) both in normal and ovalbumin sensitised tissues. The same desensitisation procedure markedly affected epinephrine-relaxing capacity in both normal and ovalbumin actively sensitised guinea-pig tracheae. However, the ovalbumin sensitised tissue seemed to be more sensitive than normal to the specific beta 2-agonist procaterol; in parallel the beta 2-mediated relaxation was more impaired by isoproterenol-induced beta-adrenoceptor down regulation in ovalbumin sensitised trachea when compared to normal. Similar results have been obtained using salbutamol as the beta 2-adrenoceptor desensitising agent. The changes in beta-adrenoceptor reactivity between normal and ovalbumin sensitised guinea-pig tracheae seemed to depend on the active sensitisation process. No difference in the degree of beta-adrenoceptor down regulation was observed in passively ovalbumin sensitised guinea-pig trachea as compared to normal. These data suggest that, in this model of experimental asthma, beta-adrenoceptor reactivity is in some way modified and that this phenomenon might contribute to the genesis of asthma.

Animals↗