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Biomedical subjects

A Wanner

Publications and source records attributed to A Wanner.

At least 91 records · Page 5Linked to original sources
PubMed1989

Mobilization of mucus by airway oscillations.

The effects of high frequency asymmetric airway oscillations on mucus clearance were evaluated in excised tracheas of sheep, in an animal model of excessive mucus production, and in patients with bronchiectasis. Asymmetric high frequency ventilation (15 Hz) with expiratory biased flow profiles (expiratory peak-flow greater than inspiratory peak-flow) could move mucus droplets towards the pharynx in rigid and flexible tracheas by gas-liquid interaction. In rigid tracheas the mucus was transported towards the periphery of the model lung if the oscillations were inspiratory biased. In very collapsible tracheas, however, even inspiratory biased oscillations moved the mucus cephalad. Parameters influencing direction and speed of mucus are airflow profile, peak-flow, airway compliance and lung resistance. Gamma-camera studies showed that in anesthetized dogs radiolabeled artificial mucus followed the direction of the bias during high frequency ventilation. In five human volunteers with bronchiectasis and excessive secretions the asymmetric airway oscillations were superimposed during spontaneous breathing using a mouthpiece. Airway wall vibrations following the pressure swings of the oscillator could be observed. During forced expiration inward bulging of the posterior membranes of trachea and bronchi occurred at the negative pressure phase of the oscillations. This event was associated with increased appearance of sputum in the central airways. We conclude that high frequency ventilation with asymmetric flow profiles applied via tube or mouthpiece might be an effective future treatment of mucostasis.

Airway Resistance↗
PubMed1989

Removal of excessive bronchial secretions by asymmetric high-frequency oscillations.

The present study evaluated whether high-frequency oscillations (HFO) with biased flow profiles applied at the airway opening are capable of altering mucus clearance. In eight anesthetized sheep, artificial mucus (100 P) was infused continuously (1 ml/min) into the left main bronchus via a cannula inserted through the dorsal wall of the left main bronchus after thoracotomy. Outcoming mucus was collected every 10 min from the end of a cuffed orotracheal tube. Animals were ventilated with a Harvard respirator at a low frequency with superimposed HFO at 14 Hz with asymmetrical waveforms generated by a digitally controlled electromagnetic piston pump (expiratory bias: peak expiratory flow 3.8 l/s, peak inspiratory flow 1.3 l/s; inspiratory bias: reverse of expiratory bias). The influence of posture and of HFO airflow bias on mucus clearance was determined. In the horizontal position, mucus clearance with expiratory biased HFO was 3.5 +/- 2 (SD) ml/10 min. Head-down tilt produced a clearance of 3.1 +/- 3 ml/10 min; addition of HFO with expiratory bias increased clearance to 11.0 +/- 2.0 ml/10 min (P less than 0.05). No clearance occurred with inspiratory biased HFO during head-down tilt. These results indicate that expiratory biased HFO at the airway opening can clear excessive airway secretions and augment clearance by postural drainage.

Animals↗
PubMed1989

Developmental changes in the tracheal mucociliary system in neonatal sheep.

We studied the postnatal development of the tracheal epithelium and mucociliary system in neonatal sheep. Secretion of macromolecules (radiolabeled with 35SO4 and [3H]-threonine), unidirectional fluxes of Cl-, Na+, and water (measured with radioactive tracers), and ciliary beat frequency (CBF) were measured in tracheal tissues in vitro. Tracheal mucus transport velocity (TMV) was measured in vivo. Sheep were studied at 0, 2, 4, 8, and greater than 24 (adult) wk after birth. In newborn sheep trachea, secretion of macromolecules was significantly elevated (cf. adults), and there was basal net secretion of Cl- under short-circuit and open-circuit conditions. This induced open-circuit secretion of Na+. Secretion of macromolecules decreased rapidly by 2 wk (by 40-50%) and was not different from adult values by 4 wk. Active Na+ absorption developed rapidly, and from 2 wk onward it predominated under open-circuit conditions, inducing net Cl- absorption. These changes in secretory function were associated with an age-related increase in TMV, whereas inherent tracheal CBF was unchanged. In sheep, therefore, the newborn's trachea has elevated secretion of macromolecules and secretes Cl- and liquid under basal conditions. Normal secretory function (a reduction in secretion of macromolecules coupled with net absorption of ions and presumably of liquid also) approaches adult function by 2-4 wk of age.

Animals↗
PubMed1989

Metabolic and pharmacokinetic activity of the isolated sheep bronchial circulation.

We sought to determine bronchial vascular metabolic and pharmacokinetic activity toward benzoyl-Phe-Ala-Pro (BPAP), ADP, adenosine, and prostaglandin E2 (PGE2) by developing an isolated sheep bronchial circulation preparation. We measured mean transit time (t), uptake, and metabolism by injecting 3H-labeled substrates with [14C]sucrose into the bronchial artery of sheep lungs stripped clean of parenchymal tissue. After [3H]BPAP the t for 3H was the same as for 14C. Thirty-six percent of the injected BPAP was converted to metabolite ([3H]benzoyl-Phe) in a single pass. An inhibitor of angiotensin-converting enzyme, SQ 20,881, depressed BPAP metabolism by 50%, while perfusion of the bronchial circulation with glutaraldehyde reduced metabolism to a basal level. After [3H]ADP the t for 3H was again the same as for 14C. 3H recovery after 40 pmol [3H]ADP was less (58%) than after 400 nmol [3H]ADP (79%). Twenty-two percent of the injected radioactivity emerged in the effluent as metabolites of ADP for either dose. Adenosine and PGE2 uptake was negligible, and most of the recovered radioactivity in each case was unchanged substrate. This study suggests that the bronchial circulation is pharmacokinetically and metabolically active with respect to vasoactive mediators like angiotensin I, bradykinin, and adenine nucleotides, and that the enzymes responsible for this metabolic activity line the vascular lumen.

Adenosine↗
PubMed1989

Circulation of the airway mucosa.

The major part of tracheobronchial blood flow is distributed to the mucosa. Its microvasculature comprises 10-20% of the subepithelial tissue volume, with blood flow ranging from 30 to 95 ml.min-1.100 g wet tissue-1 in different animal species. Mucosal blood flow is influenced by vascular and airway pressures, inspired air conditions, and autonomic neurotransmitters. Several inflammatory mediators and neuropeptides are capable of enhancing the permeability for macromolecules in postcapillary venules and of augmenting tissue water volume, often with a concomitant increase in perfusion. These microvascular responses of the lower airway mucosa have an important role under various conditions of physiological stress and in airway inflammation.

Animals↗
PubMed1989

Aerosol deposition in the lung with asymmetric airways obstruction: in vivo observation.

Both the total and regional aerosol deposition were measured in six adult sheep before and after an induction of asymmetric airway obstructions, either by local instillation of carbachol solution (CS, 0.1%) distal to the right main bronchus or inhalation challenge of the right lung with carbachol aerosol (CA, 10 breaths). Total lung deposition was determined by monitoring inert monodisperse aerosols [1.0 micron mass median aerodynamic diam (MMAD)] breath-by-breath, at the mouth, by means of a laser aerosol photometer. Cumulative aerosol deposition over the first five breaths as a percent of the initial aerosol concentration (AD5) was used as a deposition index. Regional deposition pattern was determined by scintigraphic images of sulfur-colloid aerosol (1.5 microns MMAD) tagged with 99mTc. Radioactivity counts in the right (R) and left lung (L) were expressed as a percent of the whole lung count. Half-lung AD5 was then determined by multiplying AD5 by fractional radioaerosol depositions in R or L. Pulmonary airflow resistance (RL mean +/- SE), as determined by an esophageal balloon technique, increased by 111 +/- 28 and 250 +/- 96% after CA and CS, respectively (P less than 0.05). AD5 also increased in all the sheep tested by 29 +/- 3 and 52 +/- 8%, respectively, after CA and CS (P less than 0.05). Radioaerosol deposition pattern was even at base line (R/L = 51:49) but shifted toward the unchallenged L after CS (R/L = 40:60). Deposition pattern after CA was variable: a shift toward L in three, no change in one, and a shift toward the R lung in two sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1989

Lectin-detectable effects of localized pneumonia on airway mucous cell populations: role of cyclooxygenase metabolites.

We examined the airway secretory apparatus of adult sheep with experimental pneumonia to look for morphologic and lectin-binding correlates of increased mucus production. The animals were inoculated in the right caudal lobar bronchus either with starch broth containing Pasteurella haemolytica (INF, n = 6), starch broth alone (SHAM, n = 6), or with P. haemolytica and subsequently treated (INF/T, n = 5) with 2 mg/kg indomethacin, subcutaneously three times daily for 6 days. In the INF and INF/T groups, a localized pneumonic infiltrate containing P. haemolytica organisms was present. The bronchi (18-23rd generation) adjacent to the pneumonic lesion had an increased gland volume fraction (6.3 +/- 3.7% in INF, 11.3 +/- 2.4% in INF/T, and 3.1 +/- 1.9% in SHAM, p less than 0.05 among the three). The mean population densities of BSA-reactive (identifying alpha-D-gal) cells were 41.9 +/- 2.7% in the INF, 40.1 +/- 5.6% in the INF/T, versus 14.3 +/- 1.5% in the SHAM group (p less than 0.05), while the corresponding values for PNA-reactive [identifying beta-D-gal(1----3)-D-galNAc] cells were 28.8 +/- 5.1%, 0%, and 0%, respectively. Nor morphologic abnormalities were seen in the trachea, but BSA staining was shifted to morphologically different mucous cells in the INF and INF/T. We conclude that in localized P. haemolytica pneumonia in sheep (1) there are morphologic changes of the airway secretory apparatus adjacent to the lesion, (2) the glycoconjugate profile of secretory cells adjacent to and remote from the lesion is altered, and (3) cyclooxygenase products influence the chemical composition of secretory cells.

Animals↗
PubMed1989

Effects of ozone on lamb tracheal mucosa. Quantitative glycoconjugate histochemistry.

Whether or not the previously reported O3-induced abnormality in the postnatal development of tracheal secretory function in lambs is accompanied by changes in epithelial cell populations and their glycoconjugate composition was determined. Six lambs were killed at birth and 12 lambs at age 2 weeks. Of the latter 12, six were exposed to O3 (1 ppm, 4 hours daily for 5 days during the 1st week of life) and five had air-sham exposures (controls). Tracheal glycoconjugates were localized in situ with lectins to detect N-acetyl-galactosamine (galNAc), alpha-D-galactose (alpha-gal), beta-D-gal(1----3)-galNAc (beta-gal), and fucose (fuc). Mean (+/- SD) epithelial cell density (cells/mm basal lamina) was 418 +/- 57 in the newborns, 385 +/- 63 in controls (P was not significant), and 342 +/- 47 in O3-exposed lambs (P less than 0.05). Mucous cell density was 87 +/- 12 in newborns, 63 +/- 10 in controls (P less than 0.05), and 76 +/- 10 in O3 exposed lambs (P was not significant). Ciliated cells remained unchanged from birth to 2 weeks (P was not significant), but decreased (P less than 0.05) in O3-exposed lambs. All counted mucous cells contained fuc and galNAc at birth and retained these residues after sham and O3 exposure. The alpha-gal-containing mucous cells declined from 97 +/- 13 to 7 +/- 1 (P less than 0.05) and beta-gal containing cells from 39 +/- 5 to 25 +/- 4 in controls. In contrast, cells containing alpha-gal 71 +/- 10 remained at newborn levels (97 +/- 13) and beta-gal-containing cells increased from 40 +/- 5 at birth to 58 +/- 8 in O3-exposed animals (P less than 0.05). It was concluded that early postnatal exposure of lambs to O3 causes a decrease in epithelial cell density, but retards the developmental decrease in the number of tracheal mucous cells and alters the lectin detectable carbohydrate composition of mucus in these cells. These developmental defects were interpreted to be the morphologic correlates of the previously shown effects of O3 on the maturation of secretory function and mucus transport.

Acetylgalactosamine↗
PubMed1988

In vivo labeling of brain dopamine D2 receptors using the high-affinity specific D2 agonist [3H]CV 205-502.

The high-affinity selective dopamine D2 agonist [3H]CV 205-502 was utilized to in vivo label brain dopamine D2 receptors in the rat. Intravenous administration of [3H]CV 205-502 resulted in a selective accumulation of radioactivity in the striatum and in the pituitary. Smaller amounts of binding were found in the hypothalamus and cortex and non-significant binding was seen in the cerebellum. The binding of [3H]CV 205-502 was stereospecifically blocked by (+)-butaclamol but not by (-)-butaclamol. In vivo binding of [3H]CV 205-502 was also dose-dependently blocked by other neuroleptics including sulpiride, haloperidol and spiroperidol, dopamine agonists such as bromocriptin, apomorphine and C1 201-678 but not by dopamine D1 antagonists or serotonin-2 antagonists. The regional distribution of the sites labeled in vivo by [3H]CV 205-502 was investigated by autoradiography and compared with the distribution seen after in vitro labeling in the consecutive sections, following washing of the label. The autoradiograms reveal the labeling of the same areas seen when in vitro autoradiography was used. High densities of binding were localized in the nucleus accumbens, striatum and olfactory tubercle as well as in the olfactory bulb. Lower densities were seen in the substantia nigra pars compacta and in the ventral tegmental area as well as in the stratum lacunosum molecular of the hippocampus and in the superior colliculus. The intermediate lobe of the pituitary also presented high densities while in the anterior pituitary only intermediate densities of receptor binding were observed. These results demonstrate that [3H]CV 205-502 is the first high-affinity agonist useful for the autoradiographic visualization of dopamine D2 receptors after in vivo labeling. This compound could be modified for utilization in positron emission tomography imaging of dopamine D2 receptors in the living animal.

Aminoquinolines↗
PubMed1988

Tracheal narrowing during histamine-induced bronchoconstriction.

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

Aerosols↗
PubMed1988

Measurement of airway mucosal perfusion and water volume with an inert soluble gas.

The purpose of this study was to develop and validate a new in vivo technique for the measurement of tracheal mucosal blood flow (Qtr) and tissue water volume (VH2O) with an inert soluble gas. The technique was based on the notion that the uptake of dimethyl ether (VDME) from an isolated tracheal segment is governed by VH2O (transient state) and Qtr (steady state). In lightly anesthetized sheep, an endotracheal tube with two cuffs placed 14.5-16.5 cm apart was placed to create a chamber into which dimethyl ether was introduced and from which VDMME into the mucosa was determined with a sensitive pneumotachograph. Mean Qtr was 1.20 ml/min (range 0.87-1.73), and mean VH2O was 1.67 ml (range 1.27-2.26). Qtr correlated with cardiac output but not with body weight or tracheal mucosal surface area determined by He dilution. VH2O did not show a correlation with any of these parameters. The response to selected pharmacological agents suggested that the measurements of Qtr and VH2O are independent of each other and from changes in tracheal diameter. Mean Qtr was 80% of mean tracheal mucosal blood flow measured with radiolabeled microspheres. We concluded that the inert soluble gas method is capable of measuring in vivo the perfusion and a water compartment of the intact tracheal mucosa.

Animals↗
PubMed1988

Modification of bronchial blood flow during allergic airway responses.

Ascaris suum antigen effects on mean airflow resistance (RL) and bronchial arterial blood flow (Qbr) were studied in allergic anesthetized sheep with documented airway responses. Qbr was measured with electromagnetic flow probes, and supplemental O2 prevented antigen-induced hypoxemia. Aerosol challenge with this specific antigen increased RL and Qbr significantly. Cromolyn sodium aerosol pretreatment prevented antigen-induced increases in RL but not in Qbr. Intravenous cromolyn, however, prevented increases in Qbr and RL, suggesting a role for mast cell degranulation in both bronchomotor and bronchovascular responses to antigen. Antigen-induced increases in Qbr were not solely attributable to histamine release. Indomethacin pretreatment attenuated the antigen-induced increase in Qbr, thus suggesting that vasodilator cyclooxygenase products contribute to the vascular response. Antigen challenge significantly decreased Qbr after indomethacin and metiamide pretreatment, which suggests that vasoconstrictor substances released after antigen exposure also modulate Qbr; however, released vasodilators overshadow vasoconstrictor effects. Thus antigen challenge affects Qbr by locally releasing histamine and vasodilator prostaglandins as well as vasoconstrictor substances. These effects were independent of antigen-induced changes in systemic and pulmonary hemodynamics.

Airway Resistance↗
PubMed1988

Tracheal mucosal blood flow responses to autonomic agonists.

In lightly anesthetized adult sheep, we determined tracheal mucosal blood flow (Qtr) by measuring the steady-state uptake of dimethyl ether from a tracheal chamber created by an endotracheal tube provided with two cuffs. Qtr normalized for carotid arterial pressure [Qtr(n)] was determined before and after the exposure of the tracheal mucosa to aerosolized phenylephrine (0.25-2.0 mg), isoproterenol (0.05-0.8 mg), and methacholine (2.5-20 mg). The same doses of methacholine were also administered during the intravenous infusion of vasopressin. The measurements were repeated after intravenous pretreatment with the respective antagonists phentolamine, propranolol, and atropine. Mean +/- SE base-line Qtr(n) was 1.2 +/- 0.1 ml.min-1.mmHg-1.10(2). The autonomic antagonists had no effect on mean Qtr(n). Phenylephrine produced a dose-dependent decrease in mean Qtr(n) (-70% at the highest dose), which was blunted by phentolamine, and isoproterenol produced a dose-dependent increase in mean Qtr(n) (40% at the highest dose), which was blocked by propranolol. Methacholine failed to alter mean Qtr(n) even when Qtr was first decreased by vasopressin. We conclude that in lightly anesthetized adult sheep 1) base-line Qtr(n) is not under adrenergic or cholinergic control, 2) a locally administered alpha-adrenergic agonist decreases and beta-adrenergic agonist increases Qtr(n) via specific receptor activation, and 3) a locally administered cholinergic muscarinic agonist has no effect on Qtr(n).

Administration, Inhalation↗
PubMed1988

Airway responsiveness to inhaled and intravenous carbachol in sheep: effect of airway mucus.

Excessive airway mucus can alter both the mass and site of aerosol deposition, which, in turn, may affect airway responsiveness to inhaled materials. In six prone sheep, we therefore measured pulmonary airflow resistance (RL) and cumulative aerosol deposition during five standard breaths (AD5) at base line and 3 min after inhalation challenge with 2% carbachol in buffered saline (10 breaths, tidal volume = 500 ml) or after an intravenous loading dose of carbachol (3 micrograms/kg) followed by a constant infusion of 0.3 micrograms.kg-1.min-1 with and without instillation of 20 ml of a mucus simulant (MS) into the distal end of each of the main bronchi or 30 ml of MS into the right main bronchus only by means of a flexible fiber-optic bronchoscope. Before carbachol challenge, RL did not change with MS into either both lungs or one lung only. AD5 increased from 36 +/- 2% (SE) before to 42 +/- 2% after MS instillation into both lungs (P less than 0.05) but remained unchanged after MS into one lung. After carbachol inhalation, RL increased significantly by 154 +/- 20 before and 126 +/- 25% after MS into both lungs and 162 +/- 24 before and 178 +/- 31% after MS into one lung (P less than 0.05). When the percent increase in RL was normalized for total aerosol deposition (% delta RL/AD5), the normalized values were lower after MS (3.0 +/- 0.5) than before MS (4.4 +/- 0.3) into both lungs (P less than 0.05) but were not significantly different before and after MS into the right lung only.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1988

Cellular markers of inflammation in the airways of allergic sheep with and without allergen-induced late responses.

Allergic sheep respond to inhaled Ascaris suum antigen either with an acute bronchoconstriction alone (acute responders, AR) or both an acute and late bronchoconstriction (dual responders, DR). In this study, we determined if: (1) inflammatory cell composition of bronchoalveolar lavage (BAL) obtained during the late response differs between DR and AR; (2) the difference in inflammatory cells is dependent on the prechallenge BAL cell composition; and (3) drugs that block late airway responses also modify this airway inflammation. Antigen challenge caused significant immediate mean increases in specific lung resistance (SRL) both in DR (n = 28) and in AR (n = 14), but only DR had a late increase in SRL. There were no differences between the two groups in total cell returns or in the percentage of neutrophils in BAL 7.5 to 8 h after challenge, but DR had a 3.5-fold increase (p less than 0.05) in the percentage of eosinophils. Methylprednisolone succinate (15 mg/kg intravenously) given to DR (n = 7) 3 h after antigen challenge blocked the late airway response and the eosinophil response. When BAL was performed both before and after (i.e., 7.5 to 8 h) antigen challenge, similar results were observed: AR (n = 7) and DR (n = 14) exhibited characteristic airway responses. No significant differences in prechallenge BAL cell composition were observed between AR and DR; after challenge both groups showed increases in neutrophils, but only the DR showed an increase (p less than 0.05) in eosinophils. Pretreatment of DR with the antiallergic agents (cromolyn sodium or nedocromil sodium aerosol, 20 mg) blocked the immediate and late responses and the late increase in BAL eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗