Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method

Kim, Chong S., S. C. Hu, P. DeWitt, and T. R. Gerrity.Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method. J. Appl.Physiol. 81(5): 2203-2213, 1996.Detailedregional deposition of inhaled particles was investigated in youngadults (n = 11) by use of aserial bolus aerosol delivery technique. A small bolus (45 mlhalf-width) of monodisperse aerosols [1-, 3-, and5-µm particle diameter(D_p)] wasdelivered sequentially to a specific volumetric depth of the lung(100-500 ml in 50-ml increments), while the subject inhaled cleanair via a laser aerosol photometer (25-ml dead volume) with a constantflow rate ( = 150, 250, and 500 ml/s) andexhaled with the same without a pause to theresidual volume. Deposition efficiency (LDE) and deposition fraction in10 local volumetric regions and total deposition fraction of the lungwere obtained. LDE increased monotonically with increasing lung depthfor all three D_p.LDE was greater with smaller values in all lungregions. Deposition was distributed fairly evenly throughout the lungregions with a tendency for an enhancement in the distal lung regions for D_p = 1 µm.Deposition distribution was highly uneven forD_p = 3 and 5 µm, and the region of the peak deposition shifted toward the proximalregions with increasingD_p. Surface dosewas 1-5 times greater in the small airway regions and 2-17times greater in the large airway regions than in the alveolar regions.The results suggest that local or regional enhancement of deposition occurs in healthy subjects and that the local enhancement can be animportant factor in health risk assessment of inhaled particles.

     

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.

     

Effect of stochastic heterogeneity on lung impedance during acute bronchoconstriction: a model analysis

Thorpe, C. William, and Jason H. T. Bates. Effect ofstochastic heterogeneity on lung impedance during acutebronchoconstriction: a model analysis. J. Appl.Physiol. 82(5): 1616-1625, 1997.In a previousstudy (J. H. T. Bates, A. M. Lauzon, G. S. Dechman, G. N. Maksym, and T. F. Schuessler. J. Appl.Physiol. 76: 616-626, 1994), we investigated theacute changes in isovolume lung mechanics immediately after a bolusinjection of histamine. We found that dynamic resistance and elastanceincreased progressively in the 80-s period after injection, whereas theestimated tissue hysteresivity reached a stable plateau after ~25 s.In the present study, we developed a computer model of the lung toinvestigate the mechanisms responsible for these observations. Themodel conforms to Horsfield's morphometry, with the addition ofcompliant airways and structural damping tissue units. Using thismodel, we simulated the time course of acute bronchoconstriction afterintravenous administration of a bolus of bronchial agonist.Heterogeneity was induced by randomly varying the values of the maximalairway smooth muscle contraction and the tissue response to theagonist. Our results demonstrate that much of the increase in lungimpedance observed in our previous study can be produced purely by theeffects of airway heterogeneity. However, we were only able toreproduce the plateauing of hysteresivity by assigning a minimum radius to each airway, beyond which it would immediately snap completely shut.We propose that airway closure played an important role in ourexperimental observations.

     

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.

     

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.

     

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).

     

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.

     

Vagal stimulation induces expiratory lengthening in the in vitro neonate rat

Mellen, Nicholas M., and Jack L. Feldman.Vagal stimulation induces expiratory lengthening in the in vitroneonate rat. J. Appl. Physiol. 83(5):1607-1611, 1997.Respiration is modulated by lung mechanoreceptorfeedback in vivo on a cycle-to-cycle basis. We replicated thismodulation in vitro and tested four stimulus protocols to identifywhich of these most closely replicated in vivo responses to lungmechanoreceptor activation in mammals. We activated pulmonary vagalafferent pathways by electrical stimulation or by lung inflation,applied during expiration, which produces expiratory lengthening invivo. In each modality, transient and tonic stimuli were applied.Stimuli were applied over a range of delays following inspiratorytermination. Tonic stimuli were maintained until subsequent inspiratoryonset. All stimulus modalities prolonged expiration(P < 0.05). These results indicatethat the neural circuitry mediating pulmonary afferent modulation ofexpiratory duration is retained in vitro.

     

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.

     

Calibration of Pd-porphyrin phosphorescence for oxygen concentration measurements in vivo

Sinaasappel, M., and C. Ince. Calibration ofPd-porphyrin phosphorescence for oxygen concentration measurements in vivo. J. Appl. Physiol. 81(5):2297-2303, 1996.Quantitative measurement of oxygenconcentrations in the microvasculature is of prime importance in issuesrelated to oxygen transport to tissue. The introduction of thequenching of the Pd-porphyrin phosphorescence as oxygen sensor in vivoby Wilson et al. (J. Appl. Physiol.74: 580-589, 1993) has provided in this context a major advance inthis area of research. For in vivo application, the dye is coupled toalbumin to restrict the dye to the circulation and to measure oxygen in the physiological range. In this study a phosphorimeter with a gatedphotomultiplier is presented and validated. Furthermore, anonlinear-fit method using the Marquardt-Levenberg algorithm is used tocalculate the decay time. With this new phosphorimeter, calibrationmeasurements were performed to investigate the effects of pH,temperature, and diffusivity. The results present a preparation methodfor albumin coupling of the dye that eliminates the pH dependency ofthe quenching kinetics. Furthermore, the decreased oxygen diffusivityof serum was compared with that of water, and it was shown thatcalibration constants measured in water can be extrapolated to serum.

     

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion

Simon, Brett A., Koichi Tsuzaki, and Jose G. Venegas.Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion. J. Appl.Physiol. 82(3): 882-891, 1997.Regionalpneumoconstriction induced by alveolar hypocapnia is an importanthomeostatic mechanism for optimization of ventilation-perfusionmatching. We used positron imaging of ¹³NN-equilibrated lungs to measurethe distribution of regional tidal volume(VT), lung volume(VL), and lung impedance(Z) before and after left (L)pulmonary artery occlusion (PAO) in eight anesthetized, open-chestdogs. Measurements were made during eucapnic sinusoidal ventilation at0.2 Hz with 4-cmH₂O positive end expiratory pressure. Right(R) and L lung impedances(ZRandZL)were determined from carinal pressure and positron imaging of dynamicregional VL. LPAO caused anincrease in|ZL|relative to|ZR|,resulting in a shift in VT awayfrom the PAO side, with a L/R|Z| ratio changing from 1.20 ± 0.07 (mean ± SE) to 2.79 ± 0.85 after LPAO(P < 0.05). Although mean L lungVL decreased slightly, theVL normalized parametersspecific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% totallung capacity also increased after PAO. We conclude that PAO results inan increase in regional lung Z thatshifts ventilation away from the affected area at normal breathingfrequencies and that this effect is not due to a change inVL but reflects mechanicalconstriction at the tissue level.

     

Effects of transverse fiber stiffness and central tendon on displacement and shape of a simple diaphragm model

Boriek, Aladin M., and Joseph R. Rodarte. Effects oftransverse fiber stiffness and central tendon on displacement and shapeof a simple diaphragm model. J. Appl. Physiol. 82(5): 1626-1636, 1997.Our previous experimental results (A. M. Boriek, S. Lui, and J. R. Rodarte. J. Appl. Physiol. 75:527-533, 1993 and A. M. Boriek, T. A. Wilson, and J. R. Rodarte.J. Appl. Physiol. 76: 223-229, 1994) showed that1) costal diaphragm shape is similar at functional residualcapacity and end inspiration regardless of whether the diaphragm muscleshortens actively (increased tension) or passively (decreased tension);2) diaphragmatic muscle length changes minimally in thedirection transverse to the muscle fibers, suggesting the diaphragm maybe inextensible in that direction; and 3) the central tendon isnot stretched by physiological stresses. A two-dimensional orthotropicmaterial has two different stiffnesses in orthogonal directions. In theplane tangent to the muscle surface, these directions are along thefibers and transverse to the fibers. We wondered whether orthotropicmaterial properties in the muscular region of the diaphragm andinextensibility of the central tendon might contribute to the constancyof diaphragm shape. Therefore, in the present study, we examined theeffects of stiffness transverse to muscle fibers and inextensibility ofthe central tendon on diaphragmatic displacement and shape. Finiteelement hemispherical models of the diaphragm were developed by usingpressurized isotropic and orthotropic membranes with a wide range ofstiffness ratios. We also tested heterogeneous models, in which themuscle sheet was an orthotropic material, having transverse fiberstiffness greater than that along the fibers, with the central tendonbeing an inextensible isotropic cap. These models revealed thatincreased transverse stiffness limits the shape change of thediaphragm. Furthermore, an inextensible cap simulating the centraltendon dramatically limits the change in shape as well as the membrane displacement in response to pressure. These findings provide a plausible mechanism by which the diaphragm maintains similar shapes despite different physiological loads. This study suggests that changesof diaphragm shape are restricted because the central tendon isessentially inextensible and stiffness in the direction transverse tothe muscle fibers is greater than stiffness along the fibers.

     

Extended models of the ventilatory response to sustained isocapnic hypoxia in humans

Liang, Pei-Ji, Daphne A. Bascom, and Peter A. Robbins.Extended models of the ventilatory response to sustained isocapnic hypoxia in humans. J. Appl. Physiol. 82(2): 667-677, 1997.The purpose of this study was to examine extensions of a modelof hypoxic ventilatory decline (HVD) in humans. In the original model (model I) devised by R. Painter, S. Khamnei, and P. Robbins(J. Appl. Physiol. 74: 2007-2015, 1993), HVD is modeledentirely by a modulation of peripheral chemoreflex sensitivity. In thefirst extension (model II), a more complicated dynamic is usedfor the change in peripheral chemoreflex sensitivity. In the secondextension (model III), HVD is modeled as a combination ofboth the mechanism of Painter et al. and a component that isindependent of peripheral chemoreflex sensitivity. In all cases, aparallel noise structure was incorporated to describe the stochasticproperties of the ventilatory behavior to remove the correlation of theresiduals. Data came from six subjects from a study by D. A. Bascom, J. J. Pandit, I. D. Clement, and P. A. Robbins (Respir. Physiol.88: 299-312, 1992). For model II, there was a significantimprovement in fit for two out of six subjects. The reasons for thiswere not entirely clear. For model III, the fit was againsignificantly improved in two subjects, but in this case the subjectswere those who had the most marked undershoot and recovery ofventilation at the relief of hypoxia. In these two subjects, thechemoreflex-independent component contributed ~50% to total HVD.In the other four subjects, the chemoreflex-independent componentcontributed ~10% to total HVD. It is concluded that in somesubjects, but not in others, there may be a component of HVD thatis independent of peripheral chemoreflex sensitivity.

     

Surfactant inhibition by plasma: gestational age and surfactant treatment effects in preterm lambs

Ikegami, Machiko, Celso M. Rebello, and Alan H. Jobe.Surfactant inhibition by plasma: gestational age and surfactant treatment effects in preterm lambs. J. Appl.Physiol. 81(6): 2517-2522, 1996.The preterminfant with respiratory distress syndrome has edematous lungs and smallamounts of surfactant that do not function normally. We reported thatsurfactant recovered from preterm lambs after surfactant treatment canhave decreased sensitivity to inhibition of surface tension by plasma.We asked whether this augmented resistance to inhibition was dependenton lung development (gestational age) by testing sensitivity to plasmainhibition of 1) endogenous surfactant from preterm lambs and 2)surfactant from preterm lambs after treatment with an organicsolvent-extracted natural sheep surfactant. Surfactant recovered aftersurfactant treatment of 121- or 128-days-gestation lambs had the samesensitivity to plasma inhibition as did the surfactant used to treatthe lambs. Surfactant recovered from 134-days-gestation lambs haddecreased sensitivity to inhibition. Lung maturation is a variableinfluencing surfactant inhibition by plasma.

     

Nonlinear systems identification: autocorrelation vs. autoskewness

Sammon, Michel, and Frederick Curley. Nonlinear systemsidentification: autocorrelation vs. autoskewness. J. Appl. Physiol. 83(3): 975-993, 1997.Autocorrelation function(C¹) orautoregressive model parameters are often estimated for temporal analysis of physiological measurements. However, statisticalapproximations truncated at linear terms are unlikely to be ofsufficient accuracy for patients whose homeostatic control systemscannot be presumed to be stable local to a single equilibrium. Thus aquadratic variant ofC¹[autoskewness function(C²)] isintroduced to detect nonlinearities in an output signal as a functionof time delays. By use of simulations of nonlinear autoregressivemodels, C² isshown to identify only those nonlinearities that "break" the symmetry of a system, altering the mean and skewness of its outputs. Case studies of patients with cardiopulmonary dysfunction demonstrate arange of ventilatory patterns seen in the clinical environment; whereastesting of C¹reveals their breath-by-breath minute ventilation to be significantly autocorrelated, theC² test concludesthat the correlation is nonlinear and asymmetrically distributed.Higher-order functionals [e.g., autokurtosis(C³)] arenecessary for global analysis of metastable systems that continuously"switch" between multiple equilibrium states and unstable systemsexhibiting nonequilibrium dynamics.

     

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.

     

Respiratory-related neurons of the fastigial nucleus in response to chemical and mechanical challenges

Xu, Fadi, and Donald T. Frazier. Respiratory-relatedneurons of the fastigial nucleus in response to chemical and mechanical challenges. J. Appl. Physiol. 82(4):1177-1184, 1997.Responses of cerebellar respiratory-relatedneurons (CRRNs) within the rostral fastigial nucleus and the phrenicneurogram to activation of respiratory mechano- and chemoreceptors wererecorded in anesthetized, paralyzed, and ventilated cats. Respiratorychallenges included the following: 1) cessation of the ventilator for asingle breath at the end of inspiration (lung inflation) or atfunctional residual capacity, 2)cessation of the ventilator for multiple breaths, and3) exposure to hypercapnia. NineteenCRRNs having spontaneous activity during control conditions werecharacterized as either independent (basic, n = 14) or dependent (pump,n = 5) on the ventilator movement. Thirteen recruited CRRNs showed no respiratory-related activity untilbreathing was stressed. Burst durations of expiratory CRRNs wereprolonged by sustained lung inflation but were inhibited when thevolume was sustained at functional residual capacity; it was vice versafor inspiratory CRRNs. Multiple-breath cessation of the ventilator andhypercapnia significantly increased the firing rate and/orburst duration concomitant with changes noted in the phrenic neurogram.We conclude that CRRNs respond to respiratory inputs fromCO₂ chemo- and pulmonarymechanoreceptors in the absence of skeletal muscle contraction.

     

Nitric oxide-endothelin-1 interaction in humans

Ahlborg, Gunvor, and Jan M. Lundberg. Nitricoxide-endothelin-1 interaction in humans. J. Appl.Physiol. 82(5): 1593-1600, 1997.Healthy menreceived N^G-monomethyl-L-arginine(L-NMMA) intravenously to studycardiovascular and metabolic effects of nitric oxide synthase blockadeand whether this alters the response to endothelin-1 (ET-1) infusion.Controls only received ET-1.L-NMMA effects were that heartrate (17%), cardiac output (17%), and splanchnic and renal blood flow(both 33%) fell promptly (all P < 0.01). Mean arterial blood pressure (6%), and systemic (28%) andpulmonary (40%) vascular resistances increased(P < 0.05 to 0.001). Arterial ET-1levels (21%) increased due to a pulmonary net ET-1 release(P < 0.05 to 0.01). Splanchnic glucose output (SGO) fell (26%, P < 0.01). Arterial insulin and glucagon were unchanged. Subsequent ET-1infusion caused no change in mean arterial pressure, heart rate, orcardiac output, as found in the present controls, or in splanchnic andrenal blood flow or splanchnic glucose output as previously found withET-1 infusion (G. Ahlborg, E. Weitzberg, and J. M. Lundberg.J. Appl. Physiol. 79: 141-145,1995). In conclusion, L-NMMAlike ET-1, induces prolonged cardiovascular effects and suppresses SGO.L-NMMA causes pulmonary ET-1release and blocks responses to ET-1 infusion. The results indicatethat nitric oxide inhibits ET-1 production and thereby interacts withET-1 regarding increase in vascular tone and reduction of SGO inhumans.

     

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.

     

Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis

Hsia, C. C. W., C. J. C. Chuong, and R. L. Johnson, Jr.Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis. J. Appl.Physiol. 83(4): 1397-1404, 1997.To understandthe effects of dynamic shape distortion of red blood cells (RBCs) as itdevelops under high-flow conditions on the standard physiological andmorphometric methods of estimating pulmonary diffusing capacity, wecomputed the uptake of CO across a two-dimensional geometric capillarymodel containing a variable number of equally spaced RBCs. RBCs arecircular or parachute shaped, with the same perimeter length. Total COdiffusing capacity (DL_CO)and membrane diffusing capacity(DM_CO)were calculated by a finite element method.DL_COcalculated at two levels of alveolar PO₂ were used to estimateDM_CO by theRoughton-Forster (RF) technique. The same capillary model was subjectedto morphometric analysis by the random linear intercept method toobtain morphometric estimates ofDM_CO. Results show thatshape distortion of RBCs significantly reduces capillary diffusive gasuptake. Shape distortion exaggerates the conceptual errors inherent inthe RF technique (J. Appl. Physiol.79: 1039-1047, 1995); errors are exaggerated at a high capillaryhematocrit. Shape distortion also introduces additional error inmorphometric estimates ofDM_CO causedby a biased sampling distribution of random linear intercepts; errors are exaggerated at a low capillary hematocrit.