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D B Yeates

Publications and source records attributed to D B Yeates.

At least 19 recordsLinked to original sources
PubMed1992

Tracheal ciliary beat frequency in baboons: effects of peripheral histamine and capsaicin.

To determine if tracheal ciliary beat frequency (CBFt) in the nonhuman primate could be stimulated indirectly, either by an inhaled irritant or by a mediator potentially released from an inhalation challenge, saline (0.9%), capsaicin (3 x 10(-9) M), or histamine (8 mg/ml) were delivered for three minutes as 100 ml aerosol (0.25 micron MMAD) boluses at the beginning of each breath, followed by 10 sec breath hold. Each of five adult baboons (17-27 kg, Papio cynocephalus) underwent three studies using a randomized block design. The baboons were anesthetized and ventilated eucapnically through an endotracheal tube whose cuff was inflated in the distal trachea. CBFt was measured in the mid-trachea proximal to the cuff at one minute intervals using heterodyne laser light scattering. There was no change in CBFt from a baseline of 7.2 +/- 0.6 Hz (mean +/- SE) following inhalation of saline deposited peripherally. Capsaicin stimulated CBFt for over 80 min reaching a maximum of 14.7 +/- 6.3 Hz 46 min after aerosol delivery. Histamine stimulated CBFt for 90 minutes reaching a maximum of 19.3 +/- 9.9 Hz 67 min after aerosol delivery. The prolonged stimulatory responses of CBFt to peripherally deposited capsaicin and histamine most likely involve both cellular and neural pathways through which the tracheobronchial airways, in response to an alveolar challenge, are cleansed of secretions thus enabling the maintenance of effective gas transport.

Animals↗
PubMed1992

A pore transport model for pulmonary alveolar epithelium.

Hydrodynamic heteropore flow models for transport of solutes across alveolar epithelial tissue have been developed. A two-size cylindrical pore model and a similar parallel-plate model were formulated, tested and used to predict effective pore sizes from literature data on transport in bullfrog, canine and rat lungs. The best fit equivalent pore-size estimates were obtained using a modified, nonlinear least squares procedure, with alveolar surface area to volume ratio (S/V) and small-pore area fraction of total pore area as parameters. Small-pore and large-pore width estimates of 4 nm (84% of total flow area) and 10 nm, respectively, with an average deviation of 20% from experimentally derived permeabilities were obtained from the bullfrog alveolar epithelium parallel-plate pore model (13 solutes, diameters 0.3 to 2.8 nm). The equivalent cylindrical pore model diameter estimates were 5 nm and 10 nm, with small-pore area fraction and percentage deviations similar to the parallel-plate model estimates. Eighty-eight percent of the bulk water driven by a sucrose osmotic gradient was predicted to be transported through the small pores. The rat alveolus parallel-plate pore model (6 solutes) yielded small-pore and large-pore widths of 0.4 nm and 50 nm, respectively. Clearance rate-constant data for dextran macromolecules (3,000 to 250,000 Daltons), using a single parallel-plate pore model, resulted in a pore width estimate of 98 nm for canine alveoli with an average deviation of the predicted rate constants of 18% from literature experimental values. In all cases tested, the parallel-plate pore model predicted lower small-pore size estimates than did the cylindrical pore model, and both models had appreciably smaller percentage deviations from experimental data than previous models.

Animals↗
PubMed1992

Alveolar epithelial permeability in baboons: histamine and capsaicin.

1. We investigated if changes in alveolar epithelial permeability could be initiated by various doses of the irritant capsaicin through stimulation of pulmonary afferent nerves either directly, or indirectly through the release of an intermediate cell mediator, and whether mediation of permeability involved histamine H1 and/or H2 receptors. 2. Alveolar epithelial permeability was indicated by the clearance of peripherally deposited 99mTc-DTPA (technetium-99m-diethylenetriamine pentaacetate) aerosol in baboons. Aerosol challenge experiments were performed twice with histamine (32 mg/ml), once each with capsaicin (10(-6), 10(-5), 10(-4) and 10(-3) M), and once each with histamine (32 mg/ml) preceded by H1 (terfenadine) and H2 (ranitidine) antagonists alone and combined. 3. Mean half-time for 99mTc-DTPA clearance was 66 +/- 4 min. After histamine, it decreased to 41 +/- 5 min (P < 0.05), and after capsaicin it was 70 +/- 5 min (combined doses). Pretreatment with the H1 and H2 antagonists, either separately or in combination, did not consistently inhibit increases in 99mTc-DTPA permeability. 4. Capsaicin caused tachypnoea only at 10(-3) M (P < 0.05). Inhibition of histamine-induced tachypnoea required both antagonists (P < 0.05) suggesting the existence of a population of peripheral sensory neurons possessing H1 and H2 receptors. Changes in permeability were unrelated to the changes in respiratory frequency. Thus, neither the mechanisms that stimulate respiratory frequency, nor the respiratory frequency per se, were responsible for increased alveolar epithelial permeability. 5. Capsaicin did not change epithelial permeability at doses that cause capsaicin-sensitive C fibre stimulation as delineated by increases in respiratory frequency. Nor does C fibre stimulation, induced by mediators released from pulmonary cells activated by low doses of capsaicin, increase epithelial permeability. These data suggest that in the primate, histamine increases epithelial permeability to small solutes by a mechanism independent of the activation of capsaicin-sensitive C fibres and capsaicin-initiated release of cell mediators. 6. These findings do not support a role for C fibre activation in regulating epithelial permeability of small solutes.

Animals↗
PubMed1992

Work of adhesion of respiratory tract mucus.

A method was devised to measure the work of adhesion (WA) to a substrate of mucus, a viscoelastic gel, from the measured contact angle of glycerol on a mucus substrate and the known physical properties of a Teflon surface. Fifteen sputum samples from cystic fibrosis (CF) patients were compared with 25 mucus samples from canine tracheal pouches (CP), studied in the hydrated and partially dehydrated states. Apparent viscosity (eta A) and recoverable shear strain (SR) were measured by fluxgate magnetometry, and water content was inferred from vapor pressure osmometry. Na+, K+, and Ca2+ concentrations were measured with specific ion electrodes and Cl- with a chloridimeter. The Cl- concentration of the CP mucus was inversely proportional to its osmolality, and the Cl- concentration of the CP mucus was 102.5 +/- 1.6 meq/l compared with 55.6 +/- 2.5 meq/l for CF sputum. When CP mucus osmolality was increased from 316.0 +/- 5.5 to 430.0 +/- 7.5 mosmol/kg, WA increased from 25.1 +/- 1.8 to 31.1 +/- 1.2 ergs/cm2 and eta A increased from 391 +/- 55 to 622 +/- 121 P, respectively. CF sputum WA was 30.2 +/- 0.6 ergs/cm2, eta A was 1,110 +/- 316 P, and osmolality was 466.0 +/- 14.0 mosmol/kg. The increased WA and eta A of mucus in CF patients may thus be dependent on the hydration of mucus, which is related to the documented Cl- transport defect.

Adolescent↗
PubMed1992

Short-term interaction of airway and tissue oxygen tensions on ciliary beat frequency in dogs.

The responses of canine tracheal ciliary beat frequency (CBFt) to total lung, tracheal lumen, and peripheral lung hyperoxia, to tracheal lumen anoxia with or without peripheral lung hypoxia, and to isolated tracheal lumen hyperoxia combined with a beta-antagonist were delineated in anesthetized beagle dogs. CBFt was measured using a heterodyne laser light-scattering technique. When oxygen mixtures were delivered to the whole lung, a dose-dependent increase in maximal CBFt was observed from 6.3 +/- 1.0 Hz on air to 13.8 +/- 1.2 Hz on 100% oxygen. When oxygen mixtures were delivered to the isolated tracheal lumen, a dose-dependent increase in maximal CBFt from 6.9 +/- 1.3 Hz on air to 25.7 +/- 6.3 Hz on 100% oxygen was observed. CBFt was unchanged under conditions of peripheral lung hyperoxia. There were no significant changes from room air baseline CBFt of 7.6 +/- 1.5 Hz due to either isolated tracheal anoxia alone or in combination with alveolar hypoxia. CBFt stimulated with 100% oxygen insuffiated to the isolated tracheal lumen decreased from 14.1 +/- 3.2 to 9.5 +/- 1.9 Hz and from 16.5 +/- 1.2 to 9.7 +/- 1.2 Hz in response to 6 and 18 micrograms/kg of intravenous esmolol, respectively. This study demonstrates that short-term, local hyperoxia stimulates CBFt and that a pulmonary or systemically derived factor can be activated to inhibit this stimulation. It indicates that acute airway anoxia and alveolar and blood hypoxia do not suppress ciliary beat frequency. It also suggests that the adrenergic system is involved in the oxygen-induced stimulation of ciliary beat.

Adrenergic beta-Antagonists↗
PubMed1992

Luminal purinergic regulatory mechanisms of tracheal ciliary beat frequency.

To investigate the modulation of tracheal ciliary beat frequency (CBFt) by purine nucleotides and nucleosides acting on luminal receptors, aerosolized ATP, GTP, AMP-PNP, GMP-PNP, adenosine, and guanosine were each administered separately to the tracheal lumen in eucapnically ventilated, barbiturate-anesthetized beagles. Four studies were conducted in each of seven dogs from a cohort of eight dogs. The CBFt responses were measured on the right lateral surface of the mid-trachea using heterodyne mode correlation analysis laser light scattering. Aerosolized 10(-6) M and 10(-5) M ATP stimulated CBFt from the baseline of 5.9 +/- 1.4 Hz to maxima of 12.1 +/- 1.4 Hz and 13.3 +/- 1.6 Hz, respectively, while the same corresponding ATP-analogue (AMP-PNP) concentrations stimulated baseline CBFt to maxima of 12.7 +/- 4.1 Hz and 18.1 +/- 2.1 Hz, respectively. Similarly, 10(-6) M and 10(-5) M GTP stimulated baseline CBFt to maxima of 14.8 +/- 1.1 Hz and 12.8 +/- 4.6 Hz, respectively. The corresponding GTP-analogue (GMP-PNP) concentrations stimulated CBFt to maxima of 14.5 +/- 2.1 Hz and 18.8 +/- 4.4 Hz, respectively. Prior delivery of 10(-5) M adenosine reduced all these nucleotide-induced stimulatory responses. Prior delivery of 10(-5) guanosine partially reduced the GTP- and the GMP-PNP-induced stimulatory responses. These data demonstrate that nucleotides and nucleosides modulate CBFt through specific P2 and P1 purinergic receptors on the luminal surface, thus providing a direct mechanism within the airways to enhance the transport of mucus.

Adenosine↗
PubMed1991

Pathways of substance P stimulation of canine tracheal ciliary beat frequency.

Substance P (SP), an inflammatory neuropeptide, may be released by intraepithelial nerves in response to an irritant or inflammatory stimulus. To investigate the neural and humoral pathways mediating the response of tracheal ciliary beat frequency (CBF) to topically applied SP, CBF was measured on the ventral midtracheal surface of anesthetized beagles by using heterodyne-mode correlation analysis laser light scattering. In the first study, aerosolized SP, delivered to the lungs of eight beagle dogs, stimulated CBF in a dose-dependent manner from a baseline of 4.9 +/- 0.4 Hz to a maximum of 14.9 +/- 1.5 Hz at dose of 10(-7) M. In the second study, the tracheal lumen was isolated from the bronchial airways by inflating the cuff of an endotracheal tube near the carina. Intravenous hexamethonium bromide (2 mg/kg), ipratropium bromide (0.5 micrograms/kg), and indomethacin (2 mg/kg) were used as blocking agents to inhibit the nicotinic, muscarinic, and cyclooxygenase pathways, respectively. Aerosolized 10(-9), 10(-8), or 10(-7) M SP was delivered sequentially to the tracheal lumen for 3 min at 30-min intervals. SP caused two distinct CBF stimulatory episodes at 4 min (mean time of the maximal response) and at 18 min (mean time of the maximal response) after onset of delivery and returned to baseline after 25 min. SP stimulated CBF from the baseline of 5.1 +/- 0.4 Hz to a maximum of 14.2 +/- 2.5 Hz during the first episode (P less than 0.01) and to 10.4 +/- 0.6 Hz during the second episode (P less than 0.01) at dose of 10(-8) M. These responses were inhibited by all the blocking agents. These data suggest that SP stimulates CBF via a cyclooxygenase-dependent parasympathetic reflex.

Aerosols↗
PubMed1990

Regulatory pathways for the stimulation of canine tracheal ciliary beat frequency by bradykinin.

1. The effects of bradykinin, a potent inflammatory nanopeptide, on tracheal ciliary beat frequency in vivo were investigated using barbiturate-anaesthetized beagles. Tracheal ciliary beat frequency was measured using heterodyne mode correlation analysis laser light scattering, a technique that does not require surgical intervention. 2. Aerosolized 10(-5) M-bradykinin in 0.9% saline administered for 3 min to eight barbiturate-anaesthetized beagles stimulated tracheal ciliary beat frequency from the baseline of 5.3 +/- 0.1 Hz to a maximum of 16.6 +/- 2.0 Hz, 8 min after aerosol delivery, and ciliary beat frequency remained above baseline for the following 35 min. 3. Intravenously injected hexamethonium bromide, ipratropium bromide or indomethacin did not change baseline tracheal ciliary beat frequency. That down-regulation of ciliary beat frequency below baseline values was not observed with either the neural or the cyclooxygenase blocking agents suggests that neither of these pathways is involved in the maintenance of the observed basal ciliary beat frequency. 4. Bradykinin-induced stimulation of tracheal ciliary beat frequency is blocked by hexamethonium bromide, ipratropium bromide or indomethacin. These data suggest that the stimulation of ciliary beat frequency by bradykinin acts through both cellular cyclooxygenase and parasympathetic pathways in series.

Anesthesia, General↗
PubMed1990

Stimulation of tracheal ciliary beat frequency by localized tissue incision.

Since measurements of basal ciliary beat frequency (CBF) were significantly lower in our intact canine experiments than reports of ciliary activity in rabbits involving surgical intervention, we hypothesized that local tissue trauma stimulates CBF. The effects of minor neck surgery on tracheal CBF in eight barbiturate-anesthetized eucapnically ventilated beagles were investigated. Each dog underwent two studies. Measurements of CBF were made at 1-min intervals on the right lateral midtracheal surface by means of heterodyne mode correlation analysis laser light scattering. In the control study, CBF was measured in each dog for at least 160 min. In the incision study, base-line CBF was measured for at least 40 min. The overlying sternohyoidus muscles were then separated, and a longitudinal 2- to 3-cm incision was made in the trachea caudally from the fourth to the fifth cartilage ring. CBF was measured at least 5 cm distally from the site of tracheal injury for an additional 120 min. Electrocardiogram, rectal temperature, tracheal pressure, exhaled CO2, and arterial blood pressure, PO2, PCO2, and pH remained stable throughout both studies. The mean base-line CBF was 4.7 +/- 0.4 Hz. It increased to 19.5 +/- 2.9 Hz (P less than 0.0001) 100 min after the incision and remained elevated until the end of the study period (P less than 0.0001). The mechanism(s) causing this stimulation may also be responsible for the high "basal" CBF observed in other studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Stimulation of tracheal ciliary beat frequency by capsaicin.

To determine the possible involvement of neural and cyclooxygenase pathways whereby irritants might affect cilia activity in vivo, the temporal response of canine tracheal ciliary beat frequency (CBF) to the inhaled surrogate irritant capsaicin was studied. CBF was measured on the ventral midtracheal surface of barbiturate-anesthetized eucapnically ventilated beagle dogs by heterodyne-mode laser light scattering. After base-line CBF was established, hexamethonium bromide (2 mg/kg iv), ipratropium bromide (0.5 microgram/kg iv), indomethacin (2 mg/kg iv), or intravenous 0.9% saline was administered. Aerosolized 3 Z 10(-9) M capsaicin in 0.9% saline was delivered for 2 min, and CBF was measured for the following 60 min. Control experiments used 0.9% saline sham aerosol with a 0.9% saline sham block. Aerosolized capsaicin stimulated CBF from a base line of 6.2 +/- 1.4 (SD) Hz (n = 230) to a mean maximum of 17.7 +/- 7.3 Hz (n = 16) 23 min after aerosol delivery, and CBF returned to base line within 60 min. Neither hexamethonium bromide, ipratropium bromide, nor indomethacin changed CBF from base-line values. The episodic CBF stimulatory response to capsaicin after commencement of aerosol was completely inhibited by hexamethonium bromide. Ipratropium bromide partially inhibited the first 15 min and totally inhibited the following 45 min of stimulatory response. Indomethacin inhibited the initial 15 min but had less effect on the following 45 min of stimulatory response. These data indicate that multiple stimulatory mechanisms function over a prolonged period of time to affect the removal of irritants from the airways and that these mechanisms differ from those involved in the maintenance of basal CBF.

Aerosols↗
PubMed1988

Stimulation of ciliary beat frequency by autonomic agonists: in vivo.

beta 2-Adrenergic bronchodilator and muscarinic cholinergic bronchoconstrictor agonists both stimulate ciliary activity in vitro. To test the hypothesis that increases in autonomic activity would result in increases in ciliary beat frequency (CBF) in vivo, a correlation analysis heterodyne laser light-scattering system was developed and validated to measure the stimulating effects of sympathomimetic and parasympathomimetic agonists on tracheal CBF in intact, anesthetized beagles. The mean baseline CBF from 42 studies of 274 measurements in 9 (5 male and 4 female) adult beagles was 6.6 +/- 1.1 Hz. The stimulating effects of a beta 2-adrenergic agonist, fenoterol, and a muscarinic cholinergic agonist, methacholine, on CBF were studied on four and eight beagles, respectively. The studies were randomized and blinded. Aerosolized 10(-5) M fenoterol stimulated the CBF from the base line of 6.8 +/- 2.5 to 32.0 +/- 17.9 Hz in four dogs. Aerosolized methacholine stimulated the CBF from the base line of 5.8 +/- 0.7 to 9.4 +/- 3.0 Hz for 10(-8) M, and to 12.6 +/- 3.1 Hz for 10(-6) M in eight dogs. These are the first data obtained in intact animals that demonstrate CBF in the lower respiratory tract is regulated by autonomic agonists.

Animals↗
PubMed1988

Regulation of ciliary beat frequency by autonomic mechanisms: in vitro.

The ciliated epithelium of the mammalian trachea separates the neurohumoral milieu of the tissue from that of the environment of the airway lumen. To determine whether specific autonomic receptors regulating ciliary beat frequency (CBF) were located on mucosal or serosal sides, we measured CBF by heterodyne mode correlation analysis laser light scattering in bovine tracheal tissues mounted in a two-sided chamber. A beta 2-adrenergic agonist, fenoterol, at 10(-7) M, stimulated serosal CBF from 7.9 +/- 1.3 to 20.2 +/- 5.8 Hz (P less than 0.01) and mucosal CBF from 6.6 +/- 0.9 to 14.7 +/- 4.6 Hz (P less than 0.01). A muscarinic cholinergic agonist, methacholine, at 10(-7) M, increased mucosal CBF from 8.4 +/- 1.0 to 19.5 +/- 5.5 Hz (P less than 0.01) and serosal CBF from 8.0 +/- 0.9 to 15.4 +/- 5.0 Hz (P less than 0.01). The differences in stimulation of CBF on the mucosal and serosal sides between fenoterol and methacholine were significant (P less than 0.01). Studies in which these autonomic agonist stimulating effects were inhibited by their respective antagonists, propranolol and atropine sulfate, demonstrated that CBF can be regulated independently by mediators both in the submucosa and within the mucus lining.

Animals↗
PubMed1987

In-line measurement of pulmonary metabolic function in the anesthetized rabbit.

Quantitative assessment of lung metabolic function is thought to provide biochemical information reflecting integrity of the pulmonary microcirculation. Although multiple indicator-dilution techniques are useful in such pharmacokinetic studies, the need for fractionation and subsequent processing of blood samples greatly prolongs data generation. Accordingly, we designed and tested an in-line system which rapidly can quantify single-pass disposition of photon-emitting substances in the pulmonary circulation of intact animals. The nuclear detection system consisted of a phoswich scintillation probe optically coupled to a photomultiplier tube. Pulses were discriminated for height and shape and counts recorded in a counter-timer, the output of which was interfaced with a personal computer. A mixture of an intravascular reference substance (99mTc-sulfur colloid) and an inhibitor of angiotensin-converting enzyme, N-[1(S)-carboxy-(4-OH-3-[125I]-phenyl) ethyl]-L-alanyl-L-proline (125I-CPAP), was injected as a bolus in the right heart of anesthetized ventilated rabbits and arterial blood was diverted through a flow-cell cuvette directly apposed to the phoswich detector. Single-pass extraction of 125I-CPAP was 39 +/- 3% (mean +/- SE; n = 20) and was depressed in a dose-dependent fashion by the addition of unlabeled CPAP (1-10 micrograms/kg) to the injection. These data indicate that we can now quantify, in the intact animal, saturable binding of an inhibitor to angiotensin-converting enzyme expressed on the surface of the pulmonary microvascular endothelium. Furthermore, such data can be obtained rapidly.

Animals↗
PubMed1986

Automated measurement of ciliary beat frequency.

Measurements of ciliary beat frequency using video images are dependent on observer interpretation. To obtain objective estimates of ciliary beat frequency from video-image sequences, a computer-based method was developed. Regions of interest of video-image sequences were selected and digitized. Variations in numerical values representing light intensity resulting from cilia beating were extracted and analyzed using autocorrelation techniques. The ciliary beat frequencies obtained for 14 in vitro experiments on ciliated cells or epithelium from the frog palate (Rana catesbeiana) over the range of frequencies 2-25 Hz correlated well with independent observer measurements (r = 0.979). The addition of such computer-based methods to video observer-based systems allows more objective and efficient determinations of ciliary beat frequency.

Animals↗
PubMed1986

Effect of orally administered orciprenaline on tracheobronchial mucociliary clearance.

The relative effects of beta-2-adrenergic stimulation of mucociliary transport in the trachea and the bronchial airways was determined in 12 healthy non-smoking males using radioaerosol techniques with and without the oral administration of 20 mg of orciprenaline. Orciprenaline increased tracheal mucociliary transport rates (TMTR) from a control mean of 4.4 +/- 2.4 mm/min to 6.6 +/- 4.0 mm/min (p less than 0.01), but the percentage of particles cleared from the lung in 2 h was not significantly different in the drug study (44 +/- 14%) compared to the control study (48 +/- 19%). Furthermore, a strong positive correlation existed between TMTR and bronchial clearance that was lost after administration of orciprenaline. This study demonstrates that low doses of orally administered orciprenaline increased tracheal mucociliary transport but not bronchial clearance in healthy adults.

Adult↗
PubMed1986

Hand-rearing baboons for laboratory investigations.

To conduct laboratory studies in unsedated animals that were similar anatomically and physiologically to man, five full term baboons (four Papio cynocephalus anubis, one Papio cynocephalus cynocephalus) were hand-reared. These infants were used as unsedated animal models in short-term lung clearance studies conducted from birth to 2 years of age. The hand-rearing techniques described here encouraged the formation of an infant-human rearer bond that permitted us to control the level of expressed aggressive behavior as the infant matured. These techniques resulted in baboons which displayed subordinate behavior, showed positive reception to human contact (without evidence of negative stereotypic behavioral anomalies) and remained cooperative subjects for our investigations of short-term pulmonary clearance. The baboons generally were above average in weight in comparison to conspecifically-reared baboons of similar age, sex and species. Representative lung retention curves presented on one baboon demonstrate the feasibility of lung clearance studies in these hand-reared animals. Due to its suitability for unsedated studies, this baboon model may be considered for other types of laboratory investigations.

Aging↗