Temporal dynamics of acute isovolume bronchoconstriction in the rat

Bates, Jason H. T., Thomas F. Schuessler, Carrie Dolman, andDavid H. Eidelman. Temporal dynamics of acute isovolume bronchoconstriction in the rat. J. Appl.Physiol. 82(1): 55-62, 1997.The time course oflung impedance changes after intravenous injection of bronchial agonisthave produced significant insights into the mechanisms ofbronchoconstriction in the dog (J. H. T. Bates, A.-M. Lauzon, G. S. Dechman, G. N. Maksym, and T. F. Shuessler. J. Appl.Physiol. 76: 616-626, 1994). We studied the timecourse of acute induced bronchoconstriction in five anesthetizedparalyzed open-chest rats injected intravenously with a bolus ofmethacholine. For the 16 s immediately after injection, we held thelung volume constant while applying small-amplitude flow oscillationsat 1.48, 5.45, and 19.69 Hz simultaneously, which provided us withcontinuous estimates of lung resistance(RL) and elastance(EL) at eachfrequency. This procedure was repeated at initial lung inflationpressures of 0.2, 0.4, and 0.6 kPa. BothRL andEL increased progressively aftermethacholine administration; however, the rate of change ofEL increased dramatically asfrequency was increased, whereas RL remained relativelyindependent of frequency. We interpret these findings in terms of athree-compartment model of the rat lung, featuring two parallelalveolar compartments feeding into a central airway compartment. Modelsimulations support the notions that both central airway shunting andregional ventilation inhomogeneity developed to a significant degree inour constricted rats. We also found that the rates of increase in bothRL andEL were greatly enhanced as theinitial lung inflation pressure was reduced, in accord with the notionthat parenchymal tethering is an important mechanism limiting theextent to which airways can narrow when their smooth muscle isstimulated to contract.

     

Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening

Suki, Béla, Huichin Yuan, Qin Zhang, and Kenneth R. Lutchen. Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening. J. Appl.Physiol. 82(4): 1349-1359, 1997.During abronchial challenge, much of the observed response of lung tissues isan artifactual consequence of inhomogeneous airway constriction.Inhomogeneities, in the sense of time constant inequalities, are aninherently linear phenomenon. Conversely, if lung tissues respond to abronchoagonist, they become more nonlinear. On the basis of thesedistinct responses, we present an approach to separate real tissuechanges from airway inhomogeneities. We developed a lung model thatincludes airway inhomogeneities in the form of a continuousdistribution of airway resistances and nonlinear viscoelastic tissues.Because time domain data are dominated by nonlinearities, whereasfrequency domain data are most sensitive to inhomogeneities, we apply acombined time-frequency domain identification scheme. This model wastested with simulated data from a morphometrically based airway modelmimicking gross peripheral airway inhomogeneities and shown capable ofrecovering all tissue parameters to within 15% error. Application toour previously measured data suggests that in dogs during histamine infusion 1) the distribution ofairway resistances increases widely and2) lung tissues do respond but lessso than previously reported. This approach, then, is unique in itsability to differentiate between airway and tissue responses to anagonist from a single broadband measurement made at the airway opening.

     

Greater airway narrowing in immature than in mature rabbits during methacholine challenge

Shen, X., V. Bhargava, G. R. Wodicka, C. M. Doerschuk, S. J. Gunst, and R. S. Tepper. Greater airway narrowing in immature thanin mature rabbits during methacholine challenge. J. Appl. Physiol. 81(6): 2637-2643, 1996.It hasbeen demonstrated that methacholine (MCh) challenge produces a greaterincrease in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst.J. Appl. Physiol. 79: 1190-1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01-5.0 mg/kg). Airway narrowing was determined frommeasurements of Raw in vivo and from morphometric measurements on lungsections obtained after rapidly freezing the lung after the MChchallenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greaterfor 1- and 2-mo-old animals than for 6-mo-old animals. The foldincrease in Raw was highly correlated with the degree of airwaynarrowing assessed morphometrically(r² = 0.82, P < 0.001). We conclude that thematurational difference in the effect of MCh on lung resistance isprimarily caused by greater airway narrowing in the immature rabbits.

     

Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation

Shen, X., M. F. Wu, R. S. Tepper, and S. J. Gunst. Pharmacological modulation of the mechanicalresponse of airway smooth muscle to length oscillation.J. Appl. Physiol. 83(3): 739-745, 1997.Stretch and retraction of the airways caused by changes in lungvolume may play an important role in regulating airway reactivity. Westudied the effects of different pharmacological stimuli on airwaysmooth muscle to determine whether the muscle behavior during lengthoscillation can be modulated pharmacologically and to evaluate the roleof different activation mechanisms in determining its behavior duringthe oscillation. Active force decreased below the static isometricforce during the shortening phase of length oscillation, resulting inan overall depression of force during the length oscillation cycle.This pattern of response was unaffected by the contractile stimulus orlevel of activation, suggesting that it was caused by a mechanism that is independent of the level of activation of cross bridges. The normalized area of the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects ofdifferent stimuli on hysteresivity were not correlated with theireffects on isotonic shortening velocity or isometric force, suggestingthat the pharmacological modulation of the behavior of airway smoothmuscle during length oscillation at these amplitudes cannot beaccounted for by the effects on the cross-bridge cycling rate.

     

A distributed nonlinear model of lung tissue elasticity

Maksym, Geoffrey N., and Jason H. T. Bates. Adistributed nonlinear model of lung tissue elasticity.J. Appl. Physiol. 82(1): 32-41, 1997.- We present a theory relating the static stress-strainproperties of lung tissue strips to the stress-bearing constituents,collagen and elastin. The fiber pair is modeled as a Hookean spring(elastin) in parallel with a nonlinear string element (collagen), whichextends to a maximum stop length. Based on a series of fiber pairs, wedevelop both analytical and numerical models with distributedconstituent properties that account for nonlinear tissue elasticity.The models were fit to measured stretched stress-strain curves of fiveuniaxially stretched tissue strips, each from a different dog lung. Wefound that the distributions of stop length and spring stiffness followinverse power laws, and we hypothesize that this results from thecomplex fractal-like structure of the constituent fiber matrices inlung tissue. We applied the models to representative pressure-volume(PV) curves from patients with normal, emphysematous,and fibrotic lungs. The PV curves were fit to theequation V = A  Bexp(KP),where V is volume, P is transpulmonary pressure, andA, B, andK are constants. Our models lead to apossible mechanistic explanation of the shape factorK in terms of the structuralorganization of collagen and elastin fibers.

     

Effects of lung volume on lung and chest wall mechanics in rats

To investigate the effect of lung volume onchest wall and lung mechanics in the rats, we measured theimpedance (Z) under closed- and open-chest conditions at variouspositive end-expiratory pressures (0-0.9 kPa) by using acomputer-controlled small-animal ventilator (T. F. Schuessler andJ. H. T. Bates. IEEE Trans. Biomed. Eng. 42: 860-866, 1995) that we have developed fordetermining accurately the respiratory Z in small animals. The Z oftotal respiratory system and lungs was measured with small-volumeoscillations between 0.25 and 9.125 Hz. The measured Z was fitted to amodel that featured a constant-phase tissue compartment (withdissipation and elastance characterized by constantsG andH, respectively) and a constant airwayresistance (Z. Hantos, B. Daroczy, B. Suki, S. Nagy, and J. J. Fredberg. J. Appl.Physiol. 72: 168-178, 1992). We matched the lungvolume between the closed- and open-chest conditions by using thequasi-static pressure-volume relationship of the lungs to calculate Zas a function of lung volume. Resistance decreased with lung volume andwas not significantly different between total respiratory system andlungs. However, G andH of the respiratory system weresignificantly higher than those of the lungs. We conclude that chestwall in rats has a significant influence on tissue mechanics of thetotal respiratory system.

     

Airway-parenchymal interdependence after airway contraction in rat lung explants

The constrictionof pulmonary airways is limited by the tethering effect exerted byparenchymal attachments. To characterize this tethering effect at thescale of intraparenchymal airways, we studied the pattern ofparenchymal distortion due to bronchoconstriction in a rat lung explantsystem. First, we measured the elastic modulus under tension for 2%(wt/vol) agarose alone (37.6 ± 1.5 kPa) and for agarose-filled lung(5.7 ± 1.3 kPa). The latter is similar to the elastic modulus ofair-filled lung at total lung capacity (4.5-6 kPa) (S. J. Lai-Fook, T. A. Wilson, R. E. Hyatt, and J. R. Rodarte.J. Appl. Physiol. 40: 508-513,1976), suggesting that explants can be used as a model of lung tissuedistortion. Subsequently, confocal microscopic images of fluorescentlylabeled 0.5-mm-thick explants prepared from agarose-filled rat lungsinflated to total lung capacity (48 ml/kg) were acquired. Images weretaken before and after airway constriction was induced by directapplication of 10 mM methacholine, and the pattern of parenchymaldistortion was measured from the displacement of tissue landmarksidentified in each image for 14 explants. The magnitude of the radialcomponent of tissue displacement was calculated as a function ofdistance from the airway wall and characterized by a parameter,b, describing the rate at which tissuemovement decreased with radial distance. The parameterb was 0.994 ± 0.19 (SE), which isclose to the prediction of b = 1 ofmicromechanical modeling (T. A. Wilson. J. Appl.Physiol. 33: 472-478, 1972). There was significantvariability in b, however, which wascorrelated with the fractional reduction in airway diameter (r = 0.496). Additionally, parenchymaldistortion showed significant torsion with respect to the radialdirection. This torsion was similar in concentric zones around theairway, suggesting that it originates from inhomogeneity in theparenchyma rather than inhomogeneous airway constriction. Our resultsdemonstrate the significance of the nonlinear mechanical properties ofalveolar walls and the anisotropy of the parenchyma in determining the nature of airway-parenchymal interdependence.

     

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.

     

Strain-induced growth of the immature lung

Zhang, Shaoping, Vicki Garbutt, and John T. McBride.Strain-induced growth of the immature lung. J. Appl. Physiol. 81(4): 1471-1476, 1996.Toinvestigate the relationship between strain and postnatal lung growth,two groups of weanling ferrets were tracheotomized: the study group wasexposed for 2 wk to a continuous positive airway pressure (CPAP) of 6 cmH₂O and the other group wasexposed to atmospheric pressure (control). Total lung capacity after 2 wk was ~40% higher in the CPAP-exposed animals than in the controlanimals (n = 19 for the control groupand 18 for the study group; P < 0.01). CPAP exposure was also associated with increases in lung weightand total lung protein and DNA contents. Lung recoil, measured in asubgroup of animals, was characterized by air-filled and saline-filledstatic expiratory pressure-volume curves. Neither in the air-filledlungs nor in the saline-filled lungs was there a significant differencebetween CPAP-exposed and control animals in lung recoil at equalfractions of total lung capacity. These data indicate that mechanicalstrain was associated with an acceleration of lung growth in immatureferrets. The preservation of volume-corrected lung recoil and theexpected contribution of surface forces and tissue forces to lungrecoil in CPAP-exposed animals suggest that this response did notinvolve simple lung distension but included a remodeling of the lungparenchyma.

     

Kinematics and mechanics of midcostal diaphragm of dog

Boriek, Aladin M., Joseph R. Rodarte, and Theodore A. Wilson. Kinematics and mechanics of midcostal diaphragm of dog. J. Appl. Physiol. 83(4):1068-1075, 1997.Radiopaque markers were attached to theperitoneal surface of three neighboring muscle bundles in the midcostaldiaphragm of four dogs, and the locations of the markers were trackedby biplanar video fluoroscopy during quiet spontaneous breathing andduring inspiratory efforts against an occluded airway at three lungvolumes from functional residual capacity to total lung capacity inboth the prone and supine postures. Length and curvature of the musclebundles were determined from the data on marker location. Musclelengths for the inspiratory states, as a fraction of length atfunctional residual capacity, ranged from 0.89 ± 0.04 at endinspiration during spontaneous breathing down to 0.68 ± 0.07 duringinspiratory efforts at total lung capacity. The muscle bundles werefound to have the shape of circular arcs, with the three bundlesforming a section of a right circular cylinder. With increasing lungvolume and diaphragm displacement, the circular arcs rotate around theline of insertion on the chest wall, the arcs shorten, but the radiusof curvature remains nearly constant. Maximal transdiaphragmaticpressure was calculated from muscle curvature and maximaltension-length data from the literature. The calculated maximaltransdiaphragmatic pressure-length curve agrees well with the data ofRoad et al. (J. Appl. Physiol. 60:63-67, 1986).

     

Effects of hypoxic pulmonary vasoconstriction on pulmonary gas exchange

Brimioulle, Serge, Philippe Lejeune, and Robert Naeije.Effects of hypoxic pulmonary vasoconstriction on pulmonary gasexchange. J. Appl. Physiol. 81(4):1535-1543, 1996.Several reports have suggested that hypoxicpulmonary vasoconstriction (HPV) might result in deterioration ofpulmonary gas exchange in severe hypoxia. We therefore investigated theeffects of HPV on gas exchange in normal and diseased lungs. Weincorporated a biphasic HPV stimulus-response curve observed in intactdogs (S. Brimioulle, P. Lejeune, J. L. Vachièry, M. Delcroix, R. Hallemans, and R. Naeije, J. Appl.Physiol. 77: 476-480, 1994) into a 50-compartment lung model (J. B. West, Respir.Physiol. 7: 88-110, 1969) to control the amount ofblood flow directed to each lung compartment according to the localhypoxic stimulus. The resulting model accurately reproduced the bloodgas modifications caused by HPV changes in dogs with acute lung injury.In single lung units, HPV had a moderate protective effect on alveolaroxygenation, which was maximal at near-normal alveolarPO₂ (75-80 Torr), mixed venousPO₂ (35 Torr), andPO₂ at which hemoglobin is 50%saturated (24 Torr). In simulated diseased lungs associated with40-60 Torr arterial PO₂,however, HPV increased arterial PO₂ by 15-20 Torr. We conclude that HPV can improve arterialoxygenation substantially in respiratory failure.

     

Friction in airway smooth muscle: mechanism, latch, and implications in asthma

Fredberg, J. J., K. A. Jones, M. Nathan, S. Raboudi,Y. S. Prakash, S. A. Shore, J. P. Butler, and G. C. Sieck. Friction in airway smooth muscle: mechanism, latch, andimplications in asthma. J. Appl.Physiol. 81(6): 2703-2712, 1996.In muscle,active force and stiffness reflect numbers of actin-myosin interactions and shortening velocity reflects their turnover rates, but the molecular basis of mechanical friction is somewhat less clear. Tobetter characterize molecular mechanisms that govern mechanical friction, we measured the rate of mechanical energy dissipation and therate of actomyosin ATP utilization simultaneously in activated canineairway smooth muscle subjected to small periodic stretches as occur inbreathing. The amplitude of the frictional stress is proportional toE, where E is the tissue stiffness defined by the slope of theresulting force vs. displacement loop and  is the hysteresivitydefined by the fatness of that loop. From contractile stimulus onset,the time course of frictional stress amplitude followed a biphasicpattern that tracked that of the rate of actomyosin ATP consumption.The time course of hysteresivity, however, followed a differentbiphasic pattern that tracked that of shortening velocity. Takentogether with an analysis of mechanical energy storage and dissipationin the cross-bridge cycle, these results indicate, first, that likeshortening velocity and the rate of actomyosin ATP utilization,mechanical friction in airway smooth muscle is also governed by therate of cross-bridge cycling; second, that changes in cycling rateassociated with conversion of rapidly cycling cross bridges to slowlycycling latch bridges can be assessed from changes of hysteresivity ofthe force vs. displacement loop; and third, that steady-state forcemaintenance (latch) is a low-friction contractile state. This lastfinding may account for the unique inability of asthmatic patients to reverse spontaneous airways obstruction with a deep inspiration.

     

Aerosol dispersion in human lung: comparison between numerical simulations and experiments for bolus tests

Darquenne, Chantal, Peter Brand, Joachim Heyder, and ManuelPaiva. Aerosol dispersion in human lung: comparison between numerical simulations and experiments for bolus tests.J. Appl. Physiol. 83(3): 966-974, 1997.Bolus inhalations of 0.87-µm-diameter particles wereadministered to 10 healthy subjects, and data were compared withnumerical simulations based on a one-dimensional model of aerosoltransport and deposition in the human lung (J. Appl.Physiol. 77: 2889-2898, 1994). Aerosol boluseswere inhaled at a constant flow rate into various volumetric lungdepths up to 1,500 ml. Parameters such as bolus half-width, mode shift, skewness, and deposition were used to characterize the bolus and todisplay convective mixing. The simulations described the experimental results reasonably well. The sensitivity of the simulations to different parameters was tested. Simulated half-width appeared to beinsensitive to altered values of the deposition term, whereas it wasgreatly affected by modified values of the apparent diffusion in thealveolar zone of the lung. Finally, further simulations were comparedin experiments with a fixed penetration volume and various flow rates.Comparison showed good agreement, which may be explained by the factthat half-width, mode shift, and skewness were little affected by theflow rate.

     

Three-dimensional reconstruction of human diaphragm with the use of spiral computed tomography

Pettiaux, Nicolas, Marie Cassart, Manuel Paiva, and MarcEstenne. Three-dimensional reconstruction of human diaphragm withthe use of spiral computed tomography. J. Appl.Physiol. 82(3): 998-1002, 1997.We developed atechnique of diaphragm imaging by using spiral computed tomography, andwe studied four normal subjects who had been previously investigatedwith magnetic resonance imaging (A. P. Gauthier, S. Verbanck,M. Estenne, C. Segebarth, P. T. Macklem, and M. Paiva.J. Appl. Physiol. 76: 495-506,1994). One acquisition of 15- to 25-s duration was performed atresidual volume, functional residual capacity, functional residualcapacity plus one-half inspiratory capacity, and total lung capacitywith the subject holding his breath and relaxing. From theseacquisitions, 20 coronal and 30 sagittal images were reconstructed ateach lung volume; on each image, diaphragm contour in the zone ofapposition and in the dome was digitized with the software Osiris, andthe digitized silhouettes were used for three-dimensionalreconstruction with Matlab. Values of length and surface area for thediaphragm, the dome, and the zone of apposition were very similar tothose obtained with magnetic resonance imaging. We conclude thatsatisfactory three-dimensional reconstruction of the in vivo diaphragmmay be obtained with spiral computed tomography, allowing accurate measurements of muscle length, surface area, and shape.

     

Determination of airway and tissue resistances after antigen and methacholine in nonhuman primates

Madwed, Jeffrey B., and Andrew C. Jackson.Determination of airway and tissue resistances after antigen andmethacholine in nonhuman primates. J. Appl.Physiol. 83(5): 1690-1696, 1997.Antigen challenge of Ascaris suum-sensitiveanimals has been used as a model of asthma in humans. However, noreports have separated total respiratory resistance into airway (Raw)and tissue (Rti) components. We compared input impedance (Zin) andtransfer impedance (Ztr) to determine Raw and Rti in anesthetizedcynomolgus monkeys under control and bronchoconstricted conditions. Zindata between 1 and 64 Hz are frequency dependent during baselineconditions, and this frequency dependence shifts in response toA. suum or methacholine. Thus itcannot be modeled with the DuBois model, and estimates of Raw and Rticannot be determined. With Ztr, baseline data were much less variablethan Zin in all monkeys. After bronchial challenge withA. suum or methacholine, the absoluteamplitude of the resistive component of Ztr increased and its zerocrossing shifted to higher frequencies. These data can estimate Raw and Rti with the six-element DuBois model. Therefore, in monkeys, Ztr hasadvantages over other measures of lung function, since it provides amethodology to separate estimates of Raw and Rti. In conclusion, Ztrshows spectral features similar to those reported in healthy andasthmatic humans.

     

Effects of surface tension and intraluminal fluid on mechanics of small airways

Hill, Mark J., Theodore A. Wilson, and Rodney K. Lambert.Effects of surface tension and intraluminal fluid on the mechanicsof small airways. J. Appl. Physiol.82(1): 233-239, 1997.Airway constriction is accompanied byfolding of the mucosa to form ridges that run axially along the innersurface of the airways. The muscosa has been modeled (R. K. Lambert.J. Appl. Physiol. 71: 666-673,1991) as a thin elastic layer with a finite bending stiffness, and thecontribution of its bending stiffness to airway elastance has beencomputed. In this study, we extend that work by including surfacetension and intraluminal fluid in the model. With surface tension, thepressure on the inner surface of the elastic mucosa is modified by thepressure difference across the air-liquid interface. As folds form inthe mucosa, intraluminal fluid collects in pools in the depressionsformed by the folds, and the curvature of the air-liquid interfacebecomes nonuniform. If the amount of intraluminal fluid is small,<2% of luminal volume, the pools of intraluminal fluid are small, the air-liquid interface nearly coincides with the surface of themucosa, and the area of the air-liquid interface remains constant asairway cross-sectional area decreases. In that case, surface energy isindependent of airway area, and surface tension has no effect on airwaymechanics. If the amount of intraluminal fluid is >2%, the area ofthe air-liquid interface decreases as airway cross-sectional areadecreases, and surface tension contributes to airway compression. Themodel predicts that surface tension plus intraluminal fluid can causean instability in the area-pressure curve of small airways. Thisinstability provides a mechanism for abrupt airway closure and abruptreopening at a higher opening pressure.

     

A model of the spontaneously breathing patient: applications to intrinsic PEEP and work of breathing

Schuessler, Thomas F., Stewart B. Gottfried, and Jason H. T. Bates. A model of the spontaneously breathing patient: applications to intrinsic PEEP and work of breathing.J. Appl. Physiol. 82(5):1694-1703, 1997.Intrinsic positive end-expiratory pressure(PEEP_i) and inspiratory work ofbreathing (WI) are important factors in the management of severe obstructive respiratory disease. Weused a computer model of spontaneously breathing patients with chronicobstructive pulmonary disease to assess the sensitivity of measurementtechniques for dynamic PEEP_i(PEEP_{i dyn}) andWI to expiratory muscle activity(EMA) and cardiogenic oscillations (CGO) on esophageal pressure.Without EMA and CGO, bothPEEP_{i dyn} andWI were accurately estimated(r = 0.999 and 0.95, respectively). Addition of moderate EMA causedPEEP_{i dyn} andWI to be systematically overestimated by 141 and 52%, respectively. Furthermore, CGOintroduced large random errors, obliterating the correlation betweenthe true and estimated values for bothPEEP_{i dyn}(r = 0.29) andWI (r = 0.38). Thus the accurateestimation of PEEP_{i dyn} andWI requires steps to be taken toameliorate the adverse effects of both EMA and CGO. Taking advantage ofour simulations, we also investigated the relationship betweenPEEP_{i dyn} and staticPEEP_i(PEEP_{i stat}). ThePEEP_{i dyn}/PEEP_{i stat}ratio decreased as stress adaptation in the lung was increased,suggesting that heterogeneity of expiratory flow limitation isresponsible for the discrepancies betweenPEEP_{i dyn} andPEEP_{i stat} thathave been reported in patients with severe airwayobstruction.

     

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.

     

Long-term facilitation of upper airway muscle activities in vagotomized and vagally intact cats

Mateika, J. H., and R. F. Fregosi. Long-termfacilitation of upper airway muscle activities in vagotomized andvagally intact cats. J. Appl. Physiol.82(2): 419-425, 1997.The primary purpose of the presentinvestigation was to determine whether long-term facilitation (LTF) ofupper airway muscle activities occurs in vagotomized and vagally intactcats. Tidal volume and diaphragm, genioglossus, and nasal dilatormuscle activities were recorded before, during, and after one carotidsinus nerve was stimulated five times with 2-min trains of constantcurrent. Sixty minutes after stimulation, nasal dilator andgenioglossus muscle activities were significantly greater than controlin the vagotomized cats but not in the vagally intact cats. Tidalvolume recorded from the vagotomized and vagally intact cats wassignificantly greater than control during the poststimulation period.In contrast, diaphragm activities were not significantly elevated inthe poststimulation period in either group of animals. We conclude that1) LTF of genioglossus and nasaldilator muscle activities can be evoked in vagotomized cats;2) vagal mechanisms inhibit LTF inupper airway muscles; and 3) LTF canbe evoked in accessory inspiratory muscles because LTF of inspiredtidal volume was greater than LTF of diaphragm activity.

     

Effect of lung inflation in vivo on airways with smooth muscle tone or edema

Brown, Robert H., Wayne Mitzner, Yonca Bulut, and ElizabethM. Wagner. Effect of lung inflation in vivo on airways with smoothmuscle tone or edema. J. Appl.Physiol. 82(2): 491-499, 1997.Fibrousattachments to the airway wall and a subpleural surrounding pressurecan create an external load against which airway smooth muscle mustcontract. A decrease in this load has been proposed as a possible causeof increased airway narrowing in asthmatic individuals. To study theinteraction between the airways and the surrounding lung parenchyma, weinvestigated the effect of lung inflation on relaxed airways, airwayscontracted with methacholine, and airways made edematous by infusion ofbradykinin into the bronchial artery. Measurements were made inanesthetized sheep by using high-resolution computed tomography tovisualize changes in individual airways. During methacholine infusion,airway area was decreased but increased minimally with increases intranspulmonary pressure. Bradykinin infusion caused a 50% increase inairway wall area and a small decrease in airway luminal area. Incontrast to airways contracted with methacholine, the luminal areaafter bradykinin increased substantially with increases intranspulmonary pressure, reaching 99% of the relaxed area at totallung capacity. Thus airway edema by itself did not prevent fulldistension of the airway at lung volumes approaching total lungcapacity. Therefore, we speculate that if a deep inspiration fails torelieve airway narrowing in vivo, this must be a manifestation ofairway smooth muscle contraction and not airway wall edema.