Superior laryngeal nerve section alters responses to upper airway distortion in sleeping dogs

Curran, Aidan K., Peter R. Eastwood, Craig A. Harms, CurtisA. Smith, and Jerome A. Dempsey. Superior laryngeal nerve sectionalters responses to upper airway distortion in sleeping dogs.J. Appl. Physiol. 83(3): 768-775, 1997.We investigated the effect of superior laryngeal nerve (SLN)section on expiratory time(TE) and genioglossuselectromyogram (EMGgg) responses to upper airway (UA) negative pressure(UANP) in sleeping dogs. The same dogs used in a similar intact study(C. A. Harms, C. A., Y.-J. Zeng, C. A. Smith, E. H. Vidruk, and J. A. Dempsey. J. Appl. Physiol. 80:1528-1539, 1996) were bilaterally SLN sectioned. After recovery,the UA was isolated while the animal breathed through a tracheostomy.Square waves of negative pressure were applied to the UA from below thelarynx or from the mask (nares) at end expiration and held until thenext inspiratory effort. Section of the SLN increased eupneicrespiratory frequency and minute ventilation. Relative to the same dogsbefore SLN section, sublaryngeal UANP caused lessTE prolongation while activation of the genioglossus required less negative pressures. Mask UANP had noeffect on TE or EMGgg activity.We conclude that the SLN 1) is notobligatory for the reflex prolongation ofTE and activation of EMGggactivity produced by UANP and 2)plays an important role in the maintenance of UA stability and thepattern of breathing in sleeping dogs.

     

MRI study of regional variations of pharyngeal wall compliance in cats

Upper airway compliance indicates the potentialof the airway to collapse and is relevant to the pathogenesis ofobstructive sleep apnea. We hypothesized that compliance would varyover the rostral-to-caudal extent of the pharyngeal airway. In aparalyzed isolated upper airway preparation in cats, we controlledstatic upper airway pressure during magnetic resonance imaging (MRI, 0.391-mm resolution). We measured cross-sectional area andanteroposterior and lateral dimensions from three-dimensionalreconstructed MRIs in axial slices orthogonal to the airway centerline.High-retropalatal (HRP), midretropalatal (MRP), and hypopharyngeal(HYP) regions were defined. Regional compliance was significantlyincreased from rostral to caudal regions as follows: HRP < MRP < HYP (P < 0.0001), and compliancedifferences among regions were directly related to collapsibility. Thusour findings in the isolated upper airway of the cat support thehypothesis that regional differences in pharyngeal compliance exist andsuggest that baseline regional variations in compliance andcollapsibility may be an important factor in the pathogenesis andtreatment of obstructive sleep apnea.

     

Respiratory transfer impedance between 8and 384Hz in guinea pigs before and after bronchial challenge

Sobh, Jamil F., Craig M. Lilly, Jeffrey M. Drazen, andAndrew C. Jackson. Respiratory transfer impedance between 8 and384 Hz in guinea pigs before and after bronchial challenge. J. Appl. Physiol. 82(1): 172-181, 1997.We report a forced oscillatory technique for noninvasivelymeasuring respiratory transfer impedance (Ztr) between 8 and 384 Hz inguinea pigs. This technique uses a device consisting of two chambers:one surrounding the animal's head that is used as a plethysmograph tomeasured flow through the airway opening and the other that surroundsthe animal's body and is used to apply pressure oscillations to thebody surface. Ztr was measured in spontaneously breathing awake guineapigs and while the animals were anesthetized in normal andmethacholine-challenged conditions. An eight-element model consistingof an airway compartment separated from a tissue compartment by a shuntgas compression compartment was fit to the data. Anesthesia increasedcentral and peripheral airway resistance and bronchial airway wallcompliance by 13, 31, and 44%, respectively, whereas it decreasedtissue compliance by 37%. Compared with the unanesthetized condition, the methacholine challenge (20 µg/kg) resulted in an increase incentral and peripheral airway resistance (69 and 319%, respectively) and a decrease in bronchial airway wall and tissue compliance (37 and79%, respectively). This technique is capable of measuring Ztr inanesthetized and awake guinea pigs. Analysis of these data with thiseight-element model provides reasonable estimates of airway and tissueparameters.

     

Rib cage mechanics during quiet breathing and exercise in humans

Kenyon, C. M., S. J. Cala, S. Yan, A. Aliverti, G. Scano, R. Duranti, A. Pedotti, and Peter T. Macklem. Rib cage mechanics during quiet breathing and exercise in humans. J. Appl. Physiol. 83(4): 1242-1255, 1997.Duringexercise, large pleural, abdominal, and transdiaphragmatic pressureswings might produce substantial rib cage (RC) distortions. We used athree-compartment chest wall model (J. Appl.Physiol. 72: 1338-1347, 1992) to measuredistortions of lung- and diaphragm-apposed RC compartments (RCp andRCa) along with pleural and abdominal pressures in five normal men. RCpand RCa volumes were calculated from three-dimensional locations of 86 markers on the chest wall, and the undistorted (relaxation) RCconfiguration was measured. Compliances of RCp and RCa measured duringphrenic stimulation against a closed airway were 20 and 0%,respectively, of their values during relaxation. There was marked RCdistortion. Thus nonuniform distribution of pressures distorts the RCand markedly stiffens it. However, during steady-state ergometerexercise at 0, 30, 50, and 70% of maximum workload, RC distortionswere small because of a coordinated action of respiratory muscles, sothat net pressures acting on RCp and RCa were nearly the samethroughout the respiratory cycle. This maximizes RC compliance andminimizes the work of RC displacement. During quiet breathing, plots ofRCa volume vs. abdominal pressure were to the right of the relaxationcurve, indicating an expiratory action on RCa. We attribute this topassive stretching of abdominal muscles, which more thancounterbalances the insertional component of transdiaphragmatic pressure.

     

An induced blood pressure rise does not alter upper airway resistance in sleeping humans

Wilson, Christine R., Shalini Manchanda, David Crabtree,James B. Skatrud, and Jerome A. Dempsey. An induced blood pressurerise does not alter upper airway resistance in sleeping humans.J. Appl. Physiol. 84(1): 269-276, 1998.Sleep apnea is associated with episodic increases in systemicblood pressure. We investigated whether transient increases in arterialpressure altered upper airway resistance and/or breathingpattern in nine sleeping humans (snorers and nonsnorers). Apressure-tipped catheter was placed below the base of the tongue, andflow was measured from a nose or face mask. Duringnon-rapid-eye-movement sleep, we injected 40- to 200-µg iv boluses ofphenylephrine. Parasympathetic blockade was used if bradycardia wasexcessive. Mean arterial pressure (MAP) rose by 20 ± 5 (mean ± SD) mmHg (range 12-37 mmHg) within 12 s and remained elevated for105 s. There were no significant changes in inspiratory or expiratorypharyngeal resistance (measured at peak flow, peak pressure, 0.2 l/s orby evaluating the dynamic pressure-flow relationship). Atpeak MAP, end-tidal CO₂ pressure fell by 1.5 Torr and remained low for 20-25 s. At 26 s after peak MAP, tidal volume fell by 19%, consistent with hypocapnic ventilatory inhibition. We conclude that transient increases in MAP of a magnitude commonly observed during non-rapid-eye-movement sleep-disordered breathing do not increase upper airway resistance and, therefore, willnot perpetuate subsequent obstructive events.

     

Respiratory-related pharyngeal constrictor muscle activity in decerebrate cats

Kuna, Samuel T., and Christi R. Vanoye.Respiratory-related pharyngeal constrictor muscle activity indecerebrate cats. J. Appl. Physiol.83(5): 1588-1594, 1997.Respiratory-related activity of thehyopharyngeus (middle pharyngeal constrictor) and thyropharyngeus(inferior pharyngeal constrictor) muscles was determined indecerebrate, tracheotomized adult cats and compared with theelectromyographic activity of the thyroarytenoid, a vocal cordadductor. During quiet breathing, the hyopharyngeus and usually thethyroarytenoid exhibited phasic activity during expiration and tonicactivity throughout the respiratory cycle. Respiratory-related thyropharyngeus activity was absent under these conditions. Progressive hyperoxic hypercapnia and progressive isocapnic hypoxia increased phasic expiratory activity in both pharyngeal constrictor (PC) musclesbut tended to suppress thyroarytenoid activity. Passively inducedhypocapnia and the central apnea that followed the cessation of themechanical hyperventilation were associated with tonic activation ofthe hyopharyngeus and thyroarytenoid but no recruitment inthyropharyngeus activity. The expiratory phase of a sigh and progressive pneumothorax were associated with an increase in phasic thyroarytenoid activity but no change in phasic PC activity. The results indicate that a variety of stimuli modulate respiratory-related PC activity, suggesting that the PC muscles may have a role in theregulation of upper airway patency during respiration.

     

A threshold lung volume for optimal mechanical effects on upper airway airflow dynamics: studies in an anesthetized rabbit model

Increasing lung volume improves upper airway airflow dynamics via passive mechanisms such as reducing upper airway extraluminal tissue pressures (ETP) and increasing longitudinal tension via tracheal displacement. We hypothesized a threshold lung volume for optimal mechanical effects on upper airway airflow dynamics. Seven supine, anesthetized, spontaneously breathing New Zealand White rabbits were studied. Extrathoracic pressure was altered, and lung volume change, airflow, pharyngeal pressure, ETP laterally (ETPlat) and anteriorly (ETPant), tracheal displacement, and sternohyoid muscle activity (EMG%max) monitored. Airflow dynamics were quantified via peak inspiratory airflow, flow limitation upper airway resistance, and conductance. Every 10-ml lung volume increase resulted in caudal tracheal displacement of 2.1 ± 0.4 mm (mean ± SE), decreased ETPlat by 0.7 ± 0.3 cmH(2)O, increased peak inspiratory airflow of 22.8 ± 2.6% baseline (all P < 0.02), and no significant change in ETPant or EMG%max. Flow limitation was present in most rabbits at baseline, and abolished 15.7 ± 10.5 ml above baseline. Every 10-ml lung volume decrease resulted in cranial tracheal displacement of 2.6 ± 0.4 mm, increased ETPant by 0.9 ± 0.2 cmH(2)O, ETPlat was unchanged, increased EMG%max of 11.1 ± 0.3%, and a reduction in peak inspiratory airflow of 10.8 ± 1.0%baseline (all P < 0.01). Lung volume, resistance, and conductance relationships were described by exponential functions. In conclusion, increasing lung volume displaced the trachea caudally, reduced ETP, abolished flow limitation, but had little effect on resistance or conductance, whereas decreasing lung volume resulted in cranial tracheal displacement, increased ETP and increased resistance, and reduced conductance, and flow limitation persisted despite increased muscle activity. We conclude that there is a threshold for lung volume influences on upper airway airflow dynamics.     

Effects of a synthetic lung surfactant on pharyngeal patency in awake human subjects

Van der Touw, T., A. B. H. Crawford, and J. R. Wheatley.Effects of a synthetic lung surfactant on pharyngeal patency inawake human subjects. J. Appl.Physiol. 82(1): 78-85, 1997.We examined theeffects of separate applications of saline and a synthetic lungsurfactant preparation (Surf; Exosurf Neonatal) into the supraglotticairway (SA) on the anteroposterior pharyngeal diameter(D_ap) and theairway pressures required to close (Pcl) and reopen (Pop) theSA in five awake normal supine subjects. D_ap, Pcl, and Popwere determined during lateral X-ray fluoroscopy and voluntary glotticclosure when pressure applied to the SA lumen was decreasedfrom 0 to 20 cmH₂O and thenincreased to +20 cmH₂O. After Surfapplication and relative to control,D_ap was largerfor most of the applied pressures, Pcl decreased (12.3 ± 1.9 to 18.7 ± 0.9 cmH₂O;P < 0.01), Pop decreased (13.4 ± 1.9 to 6.0 ± 3.4 cmH₂O;P < 0.01), and genioglossus electromyographic activity did not change (P > 0.05).Saline had no effect. These observations suggest that pharyngealintraluminal surface properties are important in maintaining pharyngealpatency. We propose that surfactants enhance pharyngeal patency byreducing surface tension and adhesive forces acting on intraluminal SAsurfaces.

     

Modulation of upper airway collapsibility during sleep: influence of respiratory phase and flow regimen.

We hypothesized that upper airway collapsibility is modulated dynamically throughout the respiratory cycle in sleeping humans by alterations in respiratory phase and/or airflow regimen. To test this hypothesis, critical pressures were derived from upper airway pressure-flow relationships in six tracheostomized patients with obstructive sleep apnea. Pressure-flow relationships were generated by varying the pressure at the trachea and nose during tracheostomy (inspiration and expiration) (comparison A) and nasal (inspiration only) breathing (comparison B), respectively. When a constant airflow regimen was maintained throughout the respiratory cycle (tracheostomy breathing), a small yet significant decrease in critical pressure was found at the inspiratory vs. end- and peak-expiratory time point [7.1 +/- 1.6 (SE) to 6.6 +/- 1.9 to 6.1 +/- 1.9 cmH(2)O, respectively; P < 0.05], indicating that phasic factors exerted only a modest influence on upper airway collapsibility. In contrast, we found that the inspiratory critical pressure fell markedly during nasal vs. tracheostomy breathing [1.1 +/- 1.5 (SE) vs. 6.1 +/- 1.9 cmH(2)O; P < 0.01], indicating that upper airway collapsibility is markedly influenced by differences in airflow regimen. Tracheostomy breathing was also associated with a reduction in both phasic and tonic genioglossal muscle activity during sleep. Our findings indicate that both phasic factors and airflow regimen modulate upper airway collapsibility dynamically and suggest that neuromuscular responses to alterations in airflow regimen can markedly lower upper airway collapsibility during inspiration.     

Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs

Matsumoto, Koichiro, Hisamichi Aizawa, Shohei Takata,Hiromasa Inoue, Naotsugu Takahashi, and Nobuyuki Hara.Nitric oxide derived from sympathetic nerves regulates airwayresponsiveness to histamine in guinea pigs. J. Appl.Physiol. 83(5): 1432-1437, 1997.Nitric oxide(NO), which can be derived from the nervous system or the epithelium ofthe airway, may modulate airway responsiveness. We investigated how NOderived from the airway nervous system would affect the airwayresponsiveness to histamine and acetylcholine in mechanicallyventilated guinea pigs. An NO synthase inhibitor N^G-nitro-L-argininemethyl ester (L-NAME) (1 mmol/kgip) significantly enhanced airway responsiveness to histamine but notto acetylcholine. Its enantiomerD-NAME (1 mmol/kg ip), incontrast, had no effect. TheL-NAME-induced airwayhyperresponsiveness was still observed in animals pretreated withpropranolol (1 mg/kg iv) and atropine (1 mg/kg iv). Pretreatment withthe ganglionic blocker hexamethonium (2 mg/kg iv) completely abolishedenhancing effect of L-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter theL-NAME-induced airwayhyperresponsiveness, whereas sympathetic stellatectomy completelyabolished it. Results suggest that NO that was presumably derived fromthe sympathetic nervous system regulates airway responsiveness tohistamine in guinea pigs.

     

Mechanical effects of pharyngeal constrictor activation on pharyngeal airway function

The mechanicaleffects of pharyngeal constrictor (PC) muscle activation on pharyngealairway function were determined in 20 decerebrate, tracheotomized cats.In 10 cats, a high-compliance balloon attached to a pressure transducerwas partially inflated to just occlude the pharyngeal airway. Duringprogressive hyperoxic hypercapnia, changes in pharyngeal balloonpressure were directly related to phasic expiratory hyopharyngeus(middle PC) activity. In two separate protocols in 10 additional cats,the following measurements were obtained with and without bilateralelectrical stimulation (0.2-ms duration, threshold voltage) of thedistal cut end of the vagus nerve's pharyngeal branch supplying PCmotor output: 1) pressure-volumerelationships in an isolated, sealed upper airway at a stimulationfrequency of 30 Hz and 2) rostrally directed axial force over a stimulation frequency range of 0-40 Hz. Airway compliance determined from the pressure-volume relationships decreased with PC stimulation at and below resting airway volume. Compared with the unstimulated condition, PC stimulation increased airway pressure at airway volumes at and above resting volume. Thisconstrictor effect progressively diminished as airway volume wasbrought below resting volume. At relatively low airway volumes belowresting volume, PC stimulation decreased airway pressure compared withthat without stimulation. PC stimulation generated a rostrally directedaxial force that was directly related to stimulation frequency. Theresults indicate that PC activation stiffens the pharyngeal airway,exerting both radial and axial effects. The radial effects aredependent on airway volume: constriction of the airway at relativelyhigh airway volumes, and dilation of the airway at relatively lowairway volumes. The results imply that, under certain conditions, PCmuscle activation may promote pharyngeal airway patency.

     

Upper airway extraluminal tissue pressure fluctuations during breathing in rabbits.

Transmural pressure at any level in the upper airway is dependent on the difference between intraluminal airway and extraluminal tissue pressure (ETP). We hypothesized that ETP would be influenced by topography, head and neck position, resistive loading, and stimulated breathing. Twenty-eight male, New Zealand White, anesthetized, spontaneously breathing rabbits breathed via a face mask with attached pneumotachograph to measure airflow and pressure transducer to monitor mask pressure. Tidal volume was measured via integration of the airflow signal. ETP was measured with a pressure transducer-tipped catheter inserted in the tissues of the lateral (ETPlat, n = 28) and anterior (ETPant, n = 21) pharyngeal wall. Head position was controlled at 30, 50, or 70 degrees, and the effect of addition of an external resistor, brief occlusion, or stimulated breathing was examined. Mean ETPlat was approximately 0.7 cmH2O greater than mean ETPant when adjusted for degree of head and neck flexion (P < 0.05). Mean, maximum, and minimum ETP values increased significantly by 0.7-0.8 cmH2O/20 degrees of head and neck flexion when adjusted for site of measurement (P < 0.0001). The main effect of resistive loading and occlusion was an increase in the change in ETPlat (maximum - minimum ETPlat) and change in ETPant at all head and neck positions (P < 0.05). Mean ETPlat and ETPant increased with increasing tidal volume at head and neck position of 30 degrees (all P < 0.05). In conclusion, ETP was nonhomogeneously distributed around the upper airway and increased with both increasing head and neck flexion and increasing tidal volume. Brief airway occlusion increased the size of respiratory-related ETP fluctuations in upper airway ETP.     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Phrenic motoneuron firing rates before, during, and after prolonged inspiratory resistive loading

Road, J. D., and A. M. Cairns. Phrenic motoneuronfiring rates before, during, and after prolonged inspiratory resistive loading. J. Appl. Physiol. 83(3):776-783, 1997.Phrenic motoneuron firing rates during briefinspiratory resistive loading (IRL) are high, and nearly all themotoneurons are recruited. Diaphragmatic fatigue has been difficult todemonstrate during IRL. Furthermore, evidence from studies in limbmuscles has shown variable motoneuron responses to prolongedhigh-intensity loads. We studied phrenic motoneuron firing ratesbefore, during, and after prolonged IRL in anesthetized rabbits. Of 117 phrenic axons, only 2 axons were not recruited; 41 axons were silentduring unloaded breathing but were recruited at higher loads. Silentaxons showed a more rapid increase in firing rate as the loadincreased. Phrenic motoneuron firing rates increased throughout theperiod of loading, whereas airway pressure swings did not. Afterprolonged IRL, higher motoneuron firing rates were needed during briefloads to produce the same airway pressure. No evidence of a decline inmotoneuron firing rates was seen at any point. We conclude that therespiratory muscles can be shown to demonstrate physiological responsesconsistent with fatigue during prolonged IRL, and activation rates arehigh and remain so throughout this prolonged loading.

     

Oxygen pulse in guinea pigs in hyperbaric helium and hydrogen

Kayar, Susan R., and Erich C. Parker. Oxygen pulse inguinea pigs in hyperbaric helium and hydrogen. J. Appl. Physiol. 82(3): 988-997, 1997.We analyzedO₂ pulse, the total volume of O₂ consumed per heart beat, inguinea pigs at pressures from 10 to 60 atmospheres. Animals were placedin a hyperbaric chamber and breathed 2%O₂ in either helium (heliox) orhydrogen (hydrox). Oxygen consumption rate(O₂) was measured by gaschromatographic analysis. Core temperature and heart rate were measuredby using surgically implanted radiotelemeters. TheO₂ was modulated over afourfold range by varying chamber temperature from 25 to 36°C. There was a direct correlation betweenO₂ and heartrate, which was significantly different for animals in heliox vs.hydrox (P = 0.003). By usingmultivariate regression analysis, we identified variables that weresignificant to O₂ pulse: bodysurface area, chamber temperature, core temperature, and pressure.After normalizing for all nonpressure variables, the residualO₂ pulse was found to decreasesignificantly (P = 0.02) with pressurefor animals in heliox but did not decrease significantly(P = 0.38) with pressure for animalsin hydrox over the range of pressures studied. This amounted to aroughly 25% lower O₂ pulse fornormothermic animals in 60 atmospheres heliox vs. hydrox. These resultssuggest that reduction of cardiovascular efficiency in a hyperbaricenvironment can be mitigated by the choice of breathing gas.

     

Lung parenchymal shear modulus, airway wall remodeling, and bronchial hyperresponsiveness

Lambert, Rodney K., and Peter D. Paré. Lungparenchymal shear modulus, airway wall remodeling, and bronchialhyperresponsiveness. J. Appl. Physiol.83(1): 140-147, 1997.When airways narrow, either through theaction of smooth muscle shortening or during forced expiration, thelung parenchyma is locally distorted and provides an increasedperibronchial stress that resists the narrowing. Although thisinterdependence has been well studied, the quantitative significance ofairway remodeling to interdependence has not been elucidated. We haveused an improved computational model of the bronchial response tosmooth muscle agonists to investigate the relationships between airwaynarrowing (as indicated by airway resistance), parenchymal shearmodulus, adventitial thickening, and inner wall thickening at lungrecoil pressures of 4, 5, and 8 cmH₂O. We have found that, at lowrecoil pressures, decreases in parenchymal shear modulus have asignificant effect that is comparable to that of moderate thickening ofthe airway wall. At higher lung recoil pressures, the effect isnegligible.

     

Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs

Bonham, A. C., K. S. Kott, and J. P. Joad. Sidestreamsmoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs. J. Appl.Physiol. 81(4): 1715-1722, 1996.We determinedthe effect of sidestream tobacco smoke (SS) exposure on responses oflung rapidly adapting receptors (RARs), peak tracheal pressure (Ptr),and arterial blood pressure (ABP) to substance P in young guinea pigs.Guinea pigs were exposed to SS or filtered air fromday 8 to days41-45 of life. They were then anesthetized andgiven three doses of intravenous substance P (1.56-4.94 nmol/kg).SS exposure augmented substance P-evoked increases in RAR activity(P = 0.029 by analysis of variance) but not substance P-evoked increases in peak Ptr or decreases in ABP.Neurokinin 1-receptor blockade (CP-96345, 400 nmol/kg) attenuatedsubstance P-evoked increases in RAR activity(P = 0.001) and ABP(P = 0.009) but not in peak Ptr(P = 0.06). Thus chronic exposure toSS in young guinea pigs exaggerates RAR responsiveness to substance P. The findings may help explain the increased incidence of airwayhyperresponsiveness and cough in children chronically exposed toenvironmental tobacco smoke.

     

Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction

Kaczka, David W., Edward P. Ingenito, Bela Suki, and KennethR. Lutchen. Partitioning airway and lung tissue resistances inhumans: effects of bronchoconstriction. J. Appl.Physiol. 82(5): 1531-1541, 1997.The contributionof airway resistance(Raw) and tissue resistance(Rti) to totallung resistance(RL)during breathing in humans is poorly understood. We have recentlydeveloped a method for separating Rawand Rti from measurements ofRLand lung elastance (EL)alone. In nine healthy, awake subjects, we applied a broad-band optimalventilator waveform (OVW) with energy between 0.156 and 8.1 Hz thatsimultaneously provides tidal ventilation. In four of the subjects,data were acquired before and during a methacholine (MCh)-bronchoconstricted challenge. TheRLandELdata were first analyzed by using a model with a homogeneous airwaycompartment leading to a viscoelastic tissue compartment consisting oftissue damping and elastance parameters. Our OVW-based estimates ofRaw correlated well with estimatesobtained by using standard plethysmography and were responsive toMCh-induced bronchoconstriction. Our data suggest thatRti comprises ~40% of totalRLat typical breathing frequencies, which corresponds to ~60% ofintrathoracic RL. During mildMCh-induced bronchoconstriction, Rawaccounts for most of the increase inRL. At high doses of MCh, therewas a substantial increase in RLat all frequencies and inEL athigher frequencies. Our analysis showed that bothRaw andRti increase, but most of the increaseis due to Raw. The data also suggestthat widespread peripheral constriction causes airway wall shunting toproduce additional frequency dependence inEL.

     

Inferior pharyngeal constrictor electromyographic activity during permeability pulmonary edema in lambs

Diaz, Véronique, Irenej Kianicka, PatrickLetourneau, and Jean-Paul Praud. Inferior pharyngealconstrictor electromyographic activity during permeability pulmonaryedema in lambs. J. Appl. Physiol. 81(4): 1598-1604, 1996.Newborn mammals exhibit an active expiratory upper airwayclosure during the first hours of extrauterine life. We have recentlyshown that permeability pulmonary edema led to active expiratoryglottic closure in awake newborn lambs while hypoxia (inspiredO₂ fraction 8%; 15 min) did not. In the presentstudy, we tested the hypothesis that expiratory glottic closure wasaccompanied by an increase in pharyngeal constrictor muscle expiratoryelectromyographic (EMG) activity. We studied seven awake nonsedatedlambs aged 8-20 days. Airflow (facial mask + pneumotachograph),blood gases (arterial catheter), and EMG activity of both thethyroarytenoid muscle (a glottic adductor) and the inferior pharyngealconstrictor muscle were recorded before and after intravenous injectionof halothane (0.05 ml/kg) to induce a permeability pulmonary edema. Acentral apnea (duration 15 s to 5 min) with continuous thyroarytenoidand inferior pharyngeal constrictor activity was observed withinseconds after halothane injection. One lamb died despite rescuingmaneuvers. An expiratory phasic thyroarytenoid and inferior pharyngealconstrictor muscle activity with simultaneous zero airflow graduallytook place and, by 30 min after halothane injection, was present ateach expiration in the six remaining lambs. Expiratory glottic andpharyngeal constrictor muscle EMG activity was subsequently presentduring the whole study period (1.5-5 h), even after correction ofthe initial hypoxia. Permeability lung edema was present at postmortem examination in all seven lambs. We conclude that a permeability pulmonary edema induced by intravenous halothane in nonsedated lambsenhances both glottic and pharyngeal constrictor muscle expiratory EMG.We hypothesize that expiratory contraction of the inferior pharyngealconstrictor muscle could participate in the active expiratory upperairway closure; this, in turn, might improve alveolocapillary gasexchange by increasing the end-expiratory lung volume.

     

Ventilatory response to helium-oxygen breathing during exercise: effect of airway anesthesia

Krishnan, Bharath S., Ron E. Clemens, Trevor A. Zintel,Martin J. Stockwell, and Charles G. Gallagher. Ventilatory response to helium-oxygen breathing during exercise: effect of airwayanesthesia. J. Appl. Physiol. 83(1):82-88, 1997.The substitution of a normoxic helium mixture(HeO₂) for room air (Air) during exercise results in a sustained hyperventilation, which is present evenin the first breath. We hypothesized that this response is dependent onintact airway afferents; if so, airway anesthesia (Anesthesia) shouldaffect this response. Anesthesia was administered to the upper airwaysby topical application and to lower central airways by aerosolinhalation and was confirmed to be effective for over 15 min. Subjectsperformed constant work-rate exercise (CWE) at 69 ± 2 (SE) % maximal work rate on a cycle ergometer on three separate days: twiceafter saline inhalation (days 1 and3) and once after Anesthesia(day 2). CWE commenced after a briefwarm-up, with subjects breathing Air for the first 5 min (Air-1),HeO₂ for the next 3 min, and Airagain until the end of CWE (Air-2). The resistance of the breathingcircuit was matched for Air andHeO₂. BreathingHeO₂ resulted in a small butsignificant increase in minute ventilation(I) anddecrease in alveolar PCO₂ in both theSaline (average of 2 saline tests; not significant) and Anesthesiatests. Although Anesthesia had no effect on the sustainedhyperventilatory response to HeO₂breathing, theI transientswithin the first six breaths ofHeO₂ were significantly attenuatedwith Anesthesia. We conclude that theI response to HeO₂ is not simply due to areduction in external tubing resistance and that, in humans, airwayafferents mediate the transient but not the sustained hyperventilatoryresponse to HeO₂ breathing duringexercise.