Biomedical subjects

D B Yeates

Publications and source records attributed to D B Yeates.

At least 19 recordsLinked to original sources

PubMed2001

Ion transport and regulation of respiratory tract fluid output in dogs.

To investigate the regulation of respiratory tract fluid output (RTFO), we collected the RTFO in an anesthetized canine model after a series of pharmacological interventions (inhibition of Na(+)-K(+)-ATPase or Na(+)-K(+)-2Cl(-) cotransporter, 250 microl) and physiological challenges (ionic and/or osmotic perturbation in airway lumen, 250 microl). Whereas 250 microl of aerosolized 0.9% saline caused a transient increase in RTFO, a 250-microl bumetanide-induced increase in RTFO was evident for 18 min and a 250-microl acetylstrophanthidin-induced increase in RTFO persisted for at least 30 min. Dry air ventilation decreased the responses of RTFO to the saline (sham) and acetylstrophanthidin intervention but not the bumetanide intervention. Delivery of 250 mosmol/kgH(2)O ion-free mannitol (250 microl) caused marked increases in RTFO that were little affected by the administration of acetylstrophanthidin or bumetanide 30 min before these challenges. A 250-microl 550 mosmol/kgH(2)O ion-free mannitol challenge caused a more marked and prolonged increase in RTFO. Thus aerosol delivery of a low dose of a cardiac glycoside or a near-isosmotic, ion-free, impermeant osmolyte solution may be therapeutically useful by increasing the clearance of secretions from the tracheobronchial airways.

Animals↗

PubMed2001

Regulation of vocal fold transepithelial water fluxes.

Vocal fold hydration is critical to phonation. We hypothesized that the vocal fold generates bidirectional water fluxes, which are regulated by activity of the Na(+)-K(+)- ATPase. Western blots and immunohistochemistry demonstrated the presence of the alpha-subunit Na(+)-K(+)-ATPase in the canine vocal fold (n = 11). Luminal cells, basal and adjacent one to two layers of suprabasal cells within stratified squamous epithelium, were immunopositive, as well as basolateral membranes of submucosal seromucous glands underlying transitional epithelia. Canine (n = 6) and ovine (n = 14) vocal fold mucosae exhibited transepithelial potential differences of 8.1 +/- 2.8 and 9.3 +/- 1.3 mV (lumen negative), respectively. The potential difference and short-circuit current (ovine = 31 +/- 4 microA/cm(2); canine = 41 +/- 10 microA/cm(2)) were substantially reduced by luminal administration of 75 microM acetylstrophanthidin (P < 0.05). Ovine (n = 7) transepithelial water fluxes decreased from 5.1 +/- 0.3 to 4.3 +/- 0.3 microl x min(-1) x cm(-2) from the basal to luminal chamber and from 5.2 +/- 0.2 to 3.9 +/- 0.3 microl x min(-1) x cm(-2) from the luminal to basal chamber by luminal acetylstrophanthidin (P < 0.05). The presence of the Na(+)-K(+)-ATPase in the vocal fold epithelium and the electrolyte transport derived from its activity provide the intrinsic mechanisms to regulate cell volume as well as vocal fold hydration.

Animals↗

PubMed2001

Inhaled environmental/occupational irritants and allergens: mechanisms of cardiovascular and systemic responses. Introduction.

The articles in this monograph focus on the mechanisms whereby ambient particulate matter (PM) and co-pollutants deposited in the respiratory tract cause cardiovascular and systemic effects, especially in persons with preexisting conditions such as allergic hyperresponsiveness and pulmonary, cardiac, and vascular diseases. During the past few years, it has become clear that inhaled pollutants cause adverse effects outside the respiratory tract and that these effects may in some cases be more important than respiratory effects. Investigators pursuing traditional approaches to understanding mechanisms of air pollution effects need to be brought together with those outside that community who have expertise in pathogenetic mechanisms by which deposited air pollutants might affect nonrespiratory organs. To this end, a workshop was held and papers were developed from a broad range of scientists having specialized expertise in allergic and cardiovascular physiology. The overall goal of this monograph is to benchmark current thinking and enhance progress toward identifying and understanding the mechanisms by which nonrespiratory health effects occur and, by extension, to facilitate the appropriate management of relationships between air quality and health. This monograph contains a compilation of multidisciplinary research that forms a framework for generating and testing plausible new research hypotheses. Not only will this information stimulate the thinking of researchers, but it will also provide an improved foundation for funding agencies and advisory groups to frame research strategies, programs, and priorities.

Air Pollutants↗

PubMed2001

Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses.

We examine the respiratory, bronchomotor, cardiac, and vascular responses to histamine and ragweed allergen delivered to the bronchi or alveoli compartments and the potential role of sensory nerves and reflexes mediating the histamine-induced responses. The masses of aerosols deposited in the bronchi and alveoli were quantitated using radioaerosol techniques. Activation of sensory nerves and/or histamine-induced mediator release were characterized by depositing nedocromil sodium aerosol prior to histamine challenge. The histamine-induced responses due to vagosympathetic transmission were determined by performing bilateral vagotomy. Both histamine and ragweed increased respiratory rate, ventilation, and bronchomotor tone whether deposited in the bronchial or alveolar regions. However, these responses were not elicited when histamine was administered intravenously. Precipitous allergen-induced decreases in heart rate and systolic and diastolic pressure were maximal 72 sec following ragweed deposition in alveolar regions of the lungs. Increases in respiratory rate were mediated via the vagus whether delivered to the bronchi, alveoli, or vasculature. Histamine-induced increases in respiratory rate and bronchomotor tone were attenuated by nedocromil. When histamine was delivered to the alveolar regions, increases in lung resistance appeared to be mediated primarily via the vagus and when delivered to the bronchial airways primarily by its action on smooth muscle or local reflexes. Histamine-induced hypotension and bradycardia appear to be mediated by the direct action of histamine on the cardiovascular system rather than through a vagally mediated reflex.

Allergens↗

PubMed2000

Bidirectional transepithelial water transport: chloride-dependent mechanisms.

We hypothesized that inhibition and activation of basolateral to luminal chloride transport mechanisms were associated with respective decreases and increases in basolateral to luminal water fluxes. The luminal to basolateral (J(W)(L-->B)) and basolateral to luminal (J(W)(B-->L)) water fluxes across ovine tracheal epithelia were measured simultaneously. The mean J(W)(L-->B) (6.5 microl/min/cm(2)) was larger than J(W)(B-->L) (6.1 microl/min/cm(2)). Furosemide reduced J(W)(B-->L) from 6.0 to 5.6 microl/min/cm(2). Diphenylamine-2-carboxylate (DPC) reduced J(W)(B-->L) from 7.9 to 7. 3 microl/min/cm(2) and reduced the membrane potential difference by 38%. Furosemide together with DPC decreased J(W)(L-->B) by 30% and J(W)(B-->L) by 15%. Norepinephrine increased J(W)(B-->L) from 4.9 to 6.0 microl/min/cm(2). Neuropeptide Y in the presence of norepinephrine decreased J(W)(L-->B) (6.4 to 5.2 microl/min/cm(2)) and returned J(W)(B-->L) to its baseline value. Vasopressin increased J(W)(B-->L) from 4.1 to 5.1 microl/min/cm(2). Endothelin-1 induced a simultaneous increase in J(W)(B-->L) (7.0 to 7.7 microl/min/cm(2)) and decrease in J(W)(L-->B) (7.4 to 6.4 microl/min/cm(2)); and decreased the membrane resistance. These data indicate that in tracheal epithelia under homeostatic conditions J(W)(B-->L) has a approximately 15% actively coupled component. Consistent with our hypothesis, inhibition and receptor-induced stimulation of chloride effluxes were associated with decreases and increases in J(W)(B-->L), respectively. However, as inhibition of transcellular chloride transport always decreased J(W)(L-->B) more than J(W)(B-->L), reducing transepithelial chloride transport did not result in less water being transported into the airway lumen.

Adrenergic alpha-Agonists↗

PubMed2000

Aldosterone regulates Na,K-ATPase and increases lung edema clearance in rats.

Aldosterone increases the Na,K-ATPase function in renal cells involved in active Na(+) transport. Because the alveolar type 2 (AT2) cells participate in active Na(+) transport, we studied whether aldosterone regulates the Na,K-ATPase in rat AT2 cells and whether aldosterone delivered by aerosols to spontaneously breathing rats affects edema clearance in a model of isolated-perfused lungs. The AT2 cells treated with aldosterone had increased Na,K-ATPase beta1-subunit mRNA and protein, which was associated with a 4-fold increase in the Na,K-ATPase hydrolytic activity and the ouabain-sensitive (86)Rb(+) uptake. In physiologic experiments, 24 h after aldosterone was delivered by aerosols to the rat air spaces, the active Na(+) transport and lung edema clearance increased by approximately 53% as compared with control rats and rats in which saline aerosols were delivered. The data suggest that increased active Na(+) transport and lung edema clearance induced by aldosterone is probably due to Na,K-ATPase regulation in alveolar epithelial cells. Conceivably, aldosterone may be used as a strategy to increase lung edema clearance.

Aldosterone↗

PubMed2000

Differentiation of ion-associated and osmotically driven water transport in canine airways.

We hypothesized that water transport associated with fluxes of Na(+) and Cl(-) across airway epithelium coexists and is distinct from osmotically driven water transport. To investigate this, we anesthetized and mechanically ventilated dogs (n = 8) with warm humid air. The trachea of each dog was sequentially challenged with 250-mOsm and 950-mOsm mannitol aerosols given 30 min apart. Respiratory tract fluid output (RTFO) was collected at the posterior commissure at 6-min intervals. The percentages of mannitol in the RTFO were determined with fluorescent tracers and were subtracted from the RTFO to give airway secretory output (ASO). Unbound [Na(+)] and [Cl(-)] in the RTFO were measured. Following the 250-mOsm mannitol challenge, the ASO as well as its Na(+) and Cl(-) contents increased. Following the 950-mOsm challenge, there was a further increase in ASO without any further increases in Na(+) and Cl(-) contents. Increased mucociliary transport accounted for only part of the increase in ASO. These data are consistent with the hypothesis that net water transport into the airway lumen is the vectorial sum of the water fluxes associated with actively driven intracellular Na(+) and Cl(-) transport and the water flux due to osmosis.

Aerosols↗

PubMed1999

Bidirectional transepithelial water transport: measurement and governing mechanisms.

In the search for the mechanisms whereby water is transported across biological membranes, we hypothesized that in the airways, the hydration of the periciliary fluid layer is regulated by luminal-to-basolateral water transport coupled to active transepithelial sodium transport. The luminal-to-basolateral (JWL-->B) and the basolateral-to-luminal (JWB-->L) transepithelial water fluxes across ovine tracheal epithelia were measured simultaneously. The JWL-->B (6.1 microliter/min/cm2) was larger than JWB-->L (4.5 microliter/min/cm2, p < 0.05, n = 30). The corresponding water diffusional permeabilities were PdL-->B = 1.0 x 10(-4) cm/s and PdB-->L = 7.5 x 10(-5) cm/s. The activation energy (Ea) of JWL-->B (11.6 kcal/mol) was larger than the Ea of JWB-->L (6.5 kcal/mol, p < 0.05, n = 5). Acetylstrophanthidin (100 microM basolateral) reduced JWL-->B from 6.1 to 4.4 microliter/min/cm2 (p < 0. 05, n = 5) and abolished the PD. Amiloride (10 microM luminal) reduced JWL-->B from 5.7 to 3.7 microliter/min/cm2 (p < 0.05, n = 5) and reduced PD by 44%. Neither of these agents significantly changed JWB-->L. These data indicate that in tracheal epithelia under homeostatic conditions, JWB-->L was dominated by diffusion (Ea = 4.6 kcal/mol), whereas approximately 30% of JWL-->B was coupled to the active Na+,K+-ATPase pump (Ea = 27 kcal/mol).

Animals↗

PubMed1998

Neuropeptide Y inhibits ciliary beat frequency in human ciliated cells via nPKC, independently of PKA.

The intracellular mechanisms whereby the inhibitory neurotransmitter neuropeptide Y (NPY) decreases ciliary beat frequency (CBF) were investigated in cultured human tracheal and bronchial ciliated cells. CBF was measured by nonstationary analysis laser light scattering. NPY at 1 and 10 microM decreased CBF from a baseline of 6.7 +/- 0.5 (n = 12) to 6.1 +/- 0.5 (P < 0.05) and 5.8 +/- 0.4 (P < 0.01) Hz, respectively. Prior application of PYX-1, an NPY antagonist, prevented the decreases of CBF induced by both doses of NPY. Two broad protein kinase C (PKC) kinase inhibitors, staurosporine and calphostin C, also abolished the NPY-induced decrease in CBF. The NPY-induced decrease in CBF was abolished by GF 109203X, a novel PKC (nPKC) isoform inhibitor, whereas this decrease in CBF was not attenuated by Gö-6976, a specific inhibitor of conventional PKC isoforms. Because pretreatment with NPY did not block the stimulation of CBF by forskolin and pretreatment with forskolin did not abolish the NPY-induced inhibition of CBF, this NPY receptor-mediated signal transduction mechanism appears to be independent of the adenylate cyclase-protein kinase A (PKA) pathway. Inhibition of Ca2+-ATPase by thapsigargin also prevented the suppression of CBF induced by subsequent application of NPY. These novel data indicate that, in cultured human epithelia, NPY decreases CBF below its basal level via the activation of an nPKC isoform and Ca2+-ATPase, independent of the activity of PKA. This is consistent with the proposition that NPY is an autonomic efferent inhibitory neurotransmitter regulating mucociliary transport.

Adenylyl Cyclases↗

PubMed1998

Controlled dissolution from wax-coated aerosol particles in canine lungs.

Treatment of pulmonary and systemic diseases may be improved and toxicity reduced by pulmonary deposition of drug-containing aerosols exhibiting delayed dissolution. Aqueous disodium fluorescein and pentamidine aerosols were dried, concentrated, and condensation coated with paraffin wax. The apparent mass median aerodynamic diameters of the coated fluorescein particles were 2.8-4.0 microns. Wax-to-fluorescein ratios were 0.38-1.05. The dissolution half times determined using a single-pass flow system were 1.5 min for uncoated fluorescein and 0.8 min for uncoated pentamidine. These increased over threefold when the aerosols were coated with paraffin wax to maxima of 5.3 and 2.6 min, respectively. Wax-coated aerosols generated from fluorescein mixed with 99mTc-labeled iron oxide colloid delivered to the canine lungs demonstrated a 3.4-fold increase in the absorption half time of disodium fluorescein compared with uncoated fluorescein (11.2 vs. 38.4 min). The absence of changes in pulmonary function on inhalation of these wax-coated aerosols, together with a high drug load and delayed release, establishes a foundation for future therapeutic applications.

Adsorption↗

PubMed1998

Epidermal growth factor increases lung liquid clearance in rat lungs.

Epidermal growth factor (EGF) has been reported to stimulate the proliferation of epithelial cells and increase Na+ flux and Na+-K+-ATPase function in alveolar epithelial cell monolayers. Increases in Na+-K+-ATPase in alveolar type II cells (AT2) have been associated with increased active Na+ transport and lung edema clearance across the rat alveolar epithelium in a model of proliferative lung injury. Thus we tested whether administration of aerosolized EGF to rat lungs would increase active Na+ transport and lung liquid clearance. Sixteen adult Sprague-Dawley male rats were randomized to three groups. To a group of six rats, an aerosol generated from 20 microgram of EGF in saline was delivered to the lungs, to a second group of five rats only aerosolized saline was delivered, and a third group of five rats without treatment served as the control. Forty-eight hours postaerosolization of rat lungs with EGF there was an approximately 40% increase in active Na+ transport and lung liquid clearance compared with control rats, in the absence of changes in 22Na+, [3H]mannitol, and albumin permeabilities. The Na+-K+-ATPase activity in AT2 cells harvested from these lungs was increased in rats that received aerosolized EGF compared with AT2 cells from both control rats and rats receiving aerosolized saline. These results support the hypothesis that in vivo delivery of EGF aerosols upregulates alveolar epithelial Na+-K+-ATPase and increases lung liquid clearance in rats.

Animals↗

PubMed1997

Interaction between ion transporters and the mucociliary transport system in dog and baboon.

To gain insight into the role of epithelial ion channels, pumps, and cotransporters in regulating airway water and mucociliary transport, we administered inhibitors of the Na+ channel (amiloride), 3Na-2K-adenosinetriphosphatase (acetylstrophanthidin), and Na-K-2Cl cotransporter (furosemide) to anesthetized dogs and/or baboons. Tracheal ciliary beat frequency was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) or lung mucociliary clearance were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output was collected by using a secretion-collecting endotracheal tube. In six dogs, amiloride aerosol -lung deposition, 96 +/- 11 microg (means +/- SE)- had minimal effect, whereas acetylstrophanthidin aerosol (lung deposition, 71 +/- 9 microg) increased BMC, and furosemide (40 mg iv) markedly increased TMV. In five baboons, TMV increased after iv furosemide administration (2 mg/kg) as well as by aerosol (lung deposition, 20 +/- 3 mg), coincident with increases in ciliary-mucus coupling from 11.5 +/- 0. 1 to 29.5 +/- 0.4 and 46.5 +/- 0.7 microm/beat, respectively. Furosemide also increased lung mucociliary clearance in baboons. In dogs, respiratory tract fluid output increased after intravenous furosemide from 2.2 +/- 0.5 to 6.8 +/- 1.7 mg/min. When combined with dry-air inhalation, furosemide failed to stimulate TMV and reversed the inhibition of BMC by dry air. Thus pharmacological manipulation of the Na-K-2Cl cotransporter and the 3Na-2K-adenosinetriphosphatase pump may provide increases of clinical relevance in airway hydration and mucociliary transport.

Administration, Inhalation↗

PubMed1997

Roles of hydration, sodium, and chloride in regulation of canine mucociliary transport system.

To gain insight into the homeostatic mechanisms regulating airway ion/water fluxes and mucociliary transport, the canine tracheobronchial airway fluid was perturbed by deposition of hypo- and hyperosmotic aerosols for >1 h. Tracheal ciliary beat frequency (CBF) was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output (RTFO) was collected by using a secretion-collecting endotracheal tube. In six dogs, CBF increased during water deposition in the airways to 180 +/- 30 mg/min and RTFO increased from 2.2 +/- 0.5 to 18.3 +/- 1.6 mg/min, accounting for <10% of the fluid deposition. TMV and BMC were unchanged. CBF, TMV, and BMC were markedly increased by inhalation of aerosolized 3.4 M NaCl. Aerosolized 0.85 M NaCl, in contrast, decreased BMC. In this case, RTFO represented 24% of aerosol deposition. Aerosolized 0.85 M choline chloride and 0.85 M sodium gluconate enhanced BMC and TMV concurrent with a decrease in CBF. RTFO of sodium gluconate studies exceeded 50% of aerosol deposition. Thus the airways appear to have transepithelial compensatory mechanisms that reduce the impact of a moderate increases in NaCl and hydration load, but when these responses cannot adequately respond because of the delivery of impermeable ions or very high tonicity, removal of the challenges are affected by a stimulation of mucociliary transport.

Aerosols↗

PubMed1997

Bronchial and alveolar allergen-induced anaphylaxis and the stimulation of bronchial mucociliary clearance in ragweed-sensitized dogs.

In allergic airways disease, we hypothesized that an acute allergen inhalation activates cells in the bronchial and alveolar regions of the lungs to initiate cardiopulmonary anaphylactic responses that include the stimulation of bronchial mucociliary clearance. Seven beagles were neonatally sensitized to ragweed allergen, and four were sham-sensitized. Adult dogs were anesthetized with propofol and etomidate. Bronchial retention of radiotagged particles deposited in the lungs was monitored with a gamma camera. Then 0.4-1.8 micrograms of ragweed allergen was deposited either proximally or peripherally in the lungs while achieving a similar total mass deposited. Both proximal and peripheral allergen deposition elicited cardiopulmonary responses characteristic of anaphylaxis. Following proximal allergen deposition, the mean bronchial mucuciliary clearance at 60 min increased from 27.5% +/- 4.9% to 59.9% +/- 3.3% (p < .01), and following peripheral deposition it increased from 5.9% +/- 3.1% to 52.9% +/- 7.2% (p < .01). No allergen-induced suppression of bronchial mucociliary clearance was detected within the 140-min postexposure period. No changes in cardiopulmonary responses or bronchial mucociliary clearance in the unsensitized dogs could be ascribed to the inhalation of allergen. Both the bronchi and alveoli are target sites for the initiation of allergen-induced respiratory and cardiovascular anaphylactic responses and the stimulation of bronchial mucociliary clearance.

Allergens↗

PubMed1994

Stationary and nonstationary correlation-frequency analysis of heterodyne mode laser light scattering: magnitude and periodicity of canine tracheal ciliary beat frequency in vivo.

Stationary and nonstationary correlation-frequency analysis of heterodyne laser light scattering were utilized to make automated, on-line, objective measurements of tracheal ciliary beat frequency (CBF) in intact, anesthetized canines. The stationary correlation-frequency analysis laser light-scattering technique was used to assess the magnitude of the CBF stimulatory responses induced by aerosolized 10(-5) M fenoterol (sympathomimetic), and 10(-8) M and 10(-6) M methacholine (parasympathomimetic) delivered to the whole lungs of eight barbiturate-anesthetized beagles. The nonstationary correlation-frequency analysis laser light-scattering technique was used to measure the effect on tracheal CBF of increasing the cytosolic calcium ion concentration with a calcium ionophore, A23187. Aerosolized A23187 was delivered to the isolated tracheal lumens of eight beagle dogs in cumulative doses ranging from 10(-9)M to 10(-6) M. Administration of the ionophore synchronized the CBF with a period of 5.3 min. Dose dependencies were observed in both the time to the peak CBF stimulation and the magnitude of the stimulatory response. The magnitude of CBF stimulation was inhibited by prior administration of aerosolized nifedipine (2 mg/ml), a voltage-operated calcium channel blocker. The A23187-induced modulation period of tracheal CBF, was unchanged by nifedipine. These are the first data to demonstrate that the magnitude and periodicity of CBF are two independent coupled processes. The cooperativity of these two processes could be determined in the effectiveness of mucociliary transport.

Algorithms↗

PubMed1994

Capsaicin-activated bronchial- and alveolar-initiated pathways regulating tracheal ciliary beat frequency.

We questioned whether the prolonged stimulation of ciliary beat frequency (CBF) to a short exposure of low-dose capsaicin (Wong et al. J. Appl. Physiol. 68: 257-2580, 1990) could be due to the activation of indirect pathways involving neural reflexes initiated independently in the bronchi and alveoli. Tracheal CBF (CBFtr) was measured temporally in anesthetized groups of 10 dogs by means of heterodyne-mode correlation analysis laser light scattering. To elucidate the site of the afferent neural stimulation and the efferent mediators affecting the ciliated epithelium, capsaicin (3 nM) aerosol was delivered for 4 min, either predominantly to the bronchi or to the alveolar regions, with use of pulsed aerosol techniques. This resulted in 13 pg of bronchial (85%) and 10 pg of alveolar (96%) capsaicin deposited, which caused marked stimulation of CBFtr with maxima at 7 and 35 min, respectively. Prior administration of aerosolized indomethacin to the bronchi or aerosolized cromolyn to the alveoli inhibited the bronchial and alveolar responses, respectively. Prior administration of aerosolized hexamethonium to the tracheal lumen blocked the stimulatory CBFtr responses from both capsaicin challenges. Ipratropium or propranolol aerosols delivered to the tracheal lumen also inhibited these responses. It is proposed that these pathways comprise one set of sensitive mechanisms to ensure a prolonged stimulation of CBF to effect the removal of secretions and the irritant from the lungs.

Aerosols↗

PubMed1994

Tracheal reconstruction using an epithelial equivalent.

The application of a rapidly vascularized epithelial equivalent that inhibits wound contraction would have great potential in the prevention and repair of tracheal stenosis. An animal model was developed to simulate the effects of circumferential tracheal injury and an autologous epithelial equivalent was created from a fibroblast-collagen matrix and subsequently implanted in the traumatized site in an attempt to prevent stenosis. Postinjury physiologic and histologic evaluation revealed near-normal mucosal flow analysis in the treated sites and an area of less than 20% stenosis versus 95+% in controls. This study's findings indicate that tracheal stenosis can be limited by the use of an epithelial equivalent.

Animals↗

PubMed1993

Nature of the mammalian ciliary metachronal wave.

The temporal and spatial coordination of ciliary beat (metachronicity) is fundamental to effective mucociliary transport. Metachronal wave period (MWP) and ciliary beat frequency (CBF) of fresh excised sheep and canine tracheal epithelial tissues were measured with the use of a newly developed alternating focal spot laser light scattering system. MWP was determined from cross correlation of the heterodyne signals from the alternating focal spots. CBF was determined by autocorrelation of the heterodyne signals from each of the spots. MWP and CBF were measured in four sheep tracheal epithelial tissues with the use of longitudinal interfocal spot distances of 6 and 18 microns. In three canine tracheal epithelial tissues MWP and CBF were measured both longitudinally and circumferentially with interfocal spot distances of 5, 15, 65, 87, and 96 microns. For the sheep tracheal epithelial tissues the mean CBF was 5.9 +/- 0.4 Hz (mean of means; range 3.6 +/- 0.5 to 9.9 +/- 1.5 Hz), whereas the mean MWPs for 6- and 18-microns interfocal spot distances were 0.50 +/- 0.1 and 0.47 +/- 0.1 s, respectively. For the canine tracheal epithelial tissues the mean CBF was 4.0 +/- 0.2 Hz (2.0 +/- 0.8 to 7.2 +/- 3.2 Hz), whereas the mean longitudinal MWP was 1.5 s and the mean circumferential MWP was 2.1 s. Geometric combination of the MWP components leads to a derived MWP of 2.6 s with a propagation direction of 54 degrees with respect to the longitudinal axis of the trachea. MWP was found to be episode modulated with 12- to 20-min intervals in the longitudinal direction, but modulation was not as apparent in the circumferential direction. These data suggest that MWP and CBF are regulated by separate intracellular, intercellular, and intraciliary mechanisms.

Absorptiometry, Photon↗