Airway wall dimensions during carbachol-induced bronchoconstriction in rabbits

Sasaki, F., Y. Saitoh, L. Verburgt, and M. Okazawa.Airway wall dimensions during carbachol-inducedbronchoconstriction in rabbits. J. Appl.Physiol. 81(4): 1578-1583, 1996.Airway wall areais an important determinant of airway narrowing. We hypothesized thatin cross-sectioned peripheral airways, the wall area internal to theouter smooth muscle border (inner wall area) would decrease and theairway wall area external to the outer smooth the muscle layer(adventitial area) would increase during bronchoconstriction because ofthe relocation of blood and/or fluid between these compartments. To test this hypothesis, we used anesthetized open-chest rabbits and measured airway wall dimensions and smooth muscle shortening of membranous airways after carbachol-inducedbronchoconstriction using morphometric techniques. Acute (3-min) andsustained (40-min) bronchoconstriction was induced by aerosolnebulization of carbachol and compared with saline treatment. Afterphysiological measurements, the heart base was snared, and the lung andheart were excised en bloc and frozen by using liquid nitrogen while atranspulmonary pressure of 2 cmH₂Owas maintained. The lung was processed for light-microscopicexamination by using a freeze substitution technique. Results show thatadventitial area was significantly decreased aftersustained but not acute bronchoconstriction. The mechanism of thischange, which contradicts our hypothesis, is unclear. However, thedecrease of adventitial area could increase rather than decrease theeffect of lung parenchymal tethering and attenuate airwaynarrowing.

     

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.

     

Effects of edema on small airway narrowing

Wagner, Elizabeth M. Effects of edema on small airwaynarrowing. J. Appl. Physiol. 83(3):784-791, 1997.Numerous mediators of inflammation have beendemonstrated to cause airway microvascular fluid and proteinextravasation. That fluid extravasation results in airway wall edemaleading to airway narrowing and enhanced reactivity has not beenconfirmed. In anesthetized, ventilated sheep(n = 30), airway vascularfluid extravasation was induced by infusing bradykinin(10⁶ M) through acannulated, blood-perfused bronchial artery. Airway wall edema andluminal narrowing were determined morphometrically. Airway reactivityto methacholine (MCh; 10 µg/ml, intrabronchial artery) was determinedby measuring conducting airway resistance (Raw) by forced oscillation.Raw measurements were made and lung lobes were excised and quick frozenbefore or after a 1-h bradykinin infusion. In 10 airways per lobe(range 0.2- to 2.0-mm relaxed diameter), wall area occupied 32 ± 2% (SE) of the total normalized airway area(n = 9). Bradykinin infusion increasedwall area to 42 ± 5% (P = 0.02);luminal area decreased by <5%; and smooth muscle perimeter, ameasure of smooth muscle constriction, was not altered(n = 5). Raw showed nochange from baseline (1.4 ± 0.4 cmH₂O · l¹ · s)after bradykinin infusion (n = 10).During MCh challenge, Raw increased by 3.2 ± 04 cmH₂O · l¹ · s,and this change did not differ after administration of bradykinin. MChchallenge caused similar decreases in smooth muscle perimeter (10%)and luminal area (72 vs. 68%) before and after bradykinin infusion.However, the time constant of recovery of Raw from MCh constriction wasincreased from control (40 ± 3 s) to 57 ± 10 s after bradykinininfusion (P = 0.03). When lung lobeswere excised at the same time after MCh challenge was terminated(n = 5), luminal area was greaterbefore bradykinin infusion than after (86 vs. 78%;P = 0.007), as was smooth muscleperimeter. The results of this study demonstrate that airway wall edemalimits relaxation after induced constriction rather than enhancingconstriction.

     

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.

     

Airway smooth muscle orientation in intraparenchymal airways

Lei, M., H. Ghezzo, M. F. Chen, and D. H. Eidelman.Airway smooth muscle orientation in intraparenchymal airways.J. Appl. Physiol. 82(1): 70-77, 1997.Airway smooth muscle (ASM) shortening is the central eventleading to bronchoconstriction. The degree to which airway narrowingoccurs as a consequence of shortening is a function of both themechanical properties of the airway wall as well as the orientation ofthe muscle fibers. Although the latter is theoretically important, ithas not been systematically measured to date. The purpose of this studywas to determine the angle of orientation of ASM () in normal lungs by using a morphometric approach. We analyzed the airway tree of theleft lower lobes of four cats and one human. All material was fixedwith 10% buffered Formalin at a pressure of 25 cmH₂O for 48 h. The fixed materialwas dissected along the airway tree to permit isolation ofgenerations 4-18 in the cats andgenerations 5-22 in the humanspecimen. Each airway generation was individually embedded in paraffin.Five-micrometer-thick serial sections were cut parallel to the airwaylong axis and stained with hematoxylin-phloxine-saffron. Each blockyielded three to five sections containing ASM. To determine , wemeasured the orientation of ASM nuclei relative to the transverse axisof the airway by using a digitizing tablet and a light microscope (×250) equipped with a drawing tube attachment. Inspection of thesections revealed extensive ASM crisscrossing without a homogeneous orientation. The  was clustered between 20° and 20°in all airway generations and did not vary much between generations inany of the cats or in the human specimen. When  was expressedwithout regard to sign, the mean values were 13.2° in the cats and13.1° in the human. This magnitude of obliquity is not likely toresult in physiologically important changes in airway length duringbronchoconstriction.

     

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.

     

Mechanisms for the mechanical response of airway smooth muscle to length oscillation

Shen, X., M. F. Wu, R. S. Tepper, and S. J. Gunst. Mechanisms for the mechanical response ofairway smooth muscle to length oscillation. J. Appl.Physiol. 83(3): 731-738, 1997.Airway smoothmuscle tone in vitro is profoundly affected by oscillations in musclelength, suggesting that the effects of lung volume changes on airwaytone result from direct effects of stretch on the airway smooth muscle.We analyzed the effect of length oscillation on active force andlength-force hysteresis in canine tracheal smooth muscle at differentoscillation rates and amplitudes during contraction with acetylcholine.During the shortening phase of the length oscillation cycle, the activeforce generated by the smooth muscle decreased markedly below theisometric force but returned to isometric force as the muscle waslengthened. Results indicate that at rates comparable to those duringtidal breathing, active shortening and yielding of contractile elementscontributes to the modulation of force during length oscillation;however, the depression of force during shortening cannot be accountedfor by cross-bridge properties, shortening-induced cross-bridgedeactivation, or active relaxation. We conclude that the depression ofcontractility may be a function of the plasticity of the cellularorganization of contractile filaments, which enables contractileelement length to be reset in relation to smooth muscle cell length asa result of smooth muscle stretch.

     

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.

     

Relationship between airway microvascular leakage, edema, and baseline airway functions

Matheson, Melissa, Ann-Christine Rynell, Melissa McClean,and Norbert Berend. Relationship between airway microvascular leakage, edema, and baseline airway functions. J. Appl. Physiol. 84(1): 77-81, 1998.This study wasdesigned to examine the relationship among microvascular leakage,edema, and baseline airway function. Microvascular leakage was inducedin the airways of anesthetized, tracheostomized New Zealand Whiterabbits (n = 22) by using nebulized N-formyl-methionyl-leucyl-phenylalanine(10 mg) and was measured in the trachea by using the Evans blue dyetechnique. Airway wall thickness was assessed morphometrically in theright main bronchus after Formalin fixation at a pressure of 25 cmH₂O. Areas calculated includedthe mucosal wall area, the adventitial wall area, the total wall area,and the percentage of total wall area consisting of blood vessels. Aneutrophil count was also performed by analyzing numbers of cells inboth the mucosal wall area and the adventitial wall area. Airwayfunction was assessed before and 30 min after challenge withN-formyl-methionyl-leucyl-phenylalanineby determining airway resistance, functional residual capacity,specific airway resistance, and flow-volume and pressure-volume curves(after paralysis of the animals with suxamethonium). The concentration of Evans blue dye in tracheal tissue ranged from 31.3 to 131.2 µg.There was a significant correlation between this concentration and boththe adventitial wall area (P < 0.01)and mucosal neutrophil numbers (P < 0.005). There was no correlation between Evans blue concentration andeither blood vessel area or changes in respiratory physiologyparameters before and after challenge. There was no significantdifference between any respiratory physiology measurements before andafter challenge. We conclude that an increase in microvascular leakagecorrelates with airway edema in the adventitia; however, these airwaychanges have no significant effect on airway elastic or resistiveproperties.

     

Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo

Brown, Robert H., Wayne Mitzner, and Elizabeth M. Wagner.Interaction between airway edema and lung inflation onresponsiveness of individual airways in vivo. J. Appl.Physiol. 83(2): 366-370, 1997.Inflammatorychanges and airway wall thickening are suggested to cause increasedairway responsiveness in patients with asthma. In fivesheep, the dose-response relationships of individual airways weremeasured at different lung volumes to methacholine (MCh) before andafter wall thickening caused by the inflammatory mediator bradykininvia the bronchial artery. At 4 cmH₂O transpulmonary pressure(Ptp), 5 µg/ml MCh constricted the airways to a maximum of 18 ± 3%. At 30 cmH₂O Ptp, MCh resultedin less constriction (to 31 ± 5%). Bradykinin increased airwaywall area at 4 and 30 cmH₂O Ptp(159 ± 6 and 152 ± 4%, respectively;P < 0.0001). At 4 cmH₂O Ptp, bradykinin decreasedairway luminal area (13 ± 2%; P < 0.01), and the dose-response curve was significantly lower (P = 0.02). At 30 cmH₂O, postbradykinin, the maximalairway narrowing was not significantly different (26 ± 5%;P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation ofthe MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had no effecton the MCh-induced airway constriction. We conclude that inflammatoryfluid leakage in the airways cannot be a primary cause of airwayhyperresponsiveness.

     

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 tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits

Shen, X., S. J. Gunst, and R. S. Tepper. Effect oftidal volume and frequency on airway responsiveness in mechanically ventilated rabbits. J. Appl. Physiol.83(4): 1202-1208, 1997.We evaluated the effects of the rate andvolume of tidal ventilation on airway resistance (Raw) duringintravenous methacholine (MCh) challenge in mechanically ventilatedrabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions(0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge atfrequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg andalso under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions thanduring tidal ventilation at any frequency or volume. Increases in thevolume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression ofnarrowing in response to MCh increases as the magnitude of the volumeor the frequency of the tidal oscillations is increased. Our findingssuggest that the effect of lung volume changes on airway responsivenessin vivo is primarily related to the stretch of airway smooth muscle.

     

Decreased adenylyl cyclase protein and function in airway smooth muscle by chronic carbachol pretreatment

Cellular levels of cAMP arean important determinant of airway smooth muscle tone. We havepreviously shown that chronic (18 h) but not acute (30 min or 2 h)pretreatment with the muscarinic receptor agonist carbachol resulted indecreased adenylyl cyclase activity in response to GTP, isoproterenol,or forskolin via a pathway blocked by the protein kinase C inhibitorstaurosporine. The present study was designed to determine ifcarbachol-induced decreases in adenylyl cyclase activity were due toregulatory events at the level of either G_s or adenylylcyclase. Detergent-solubilized G_s from control orcarbachol-pretreated bovine airway smooth muscle had similar adenylylcyclase activity in response to either NaF or guanosine5'-O-(3-thiotriphosphate) (GTPS) when reconstituted intoS49 cyc membranes that lack endogenous G_s(carbachol pretreated: GTPS, 93 ± 13% of control;NaF/AlCl₃, 99 ± 8.6% of control; n = 4). Exogenous G_s solubilized from red blood cells failedto restore normal adenylyl cyclase activity when reconstituted intocarbachol-pretreated bovine airway smooth muscle (carbachol pretreated:GTP, 36 ± 10% of control; NaF/AlCl₃, 54 ± 11%of control; n = 4). [³H]forskolinradioligand saturation binding assays revealed a decreased quantity oftotal adenylyl cyclase protein after carbachol pretreatment (maximalbinding: 152 ± 40 and 107 ± 31 fmol/mg protein in control and carbachol-pretreated airway smooth muscle, respectively). Theseresults suggest that chronic activation of muscarinic receptors downregulates the expression of adenylyl cyclase protein in bovine airway smooth muscle.

     

NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle

Endogenous nitric oxide (NO) influences acetylcholine-inducedbronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural responsein several species. This study was designed to determine the importanceof NO as a neurally derived modulator of ovine airway and bronchialvascular smooth muscle. We measured the response of pulmonaryresistance (RL) and bronchialblood flow (br) to vagal stimulationin 14 anesthetized, ventilated, open-chest sheep duringthe following conditions: 1)control; 2) infusion of the -agonist phenylephrine to reduce baseline br bythe same amount as would be produced by infusion ofN-nitro-L-arginine(L-NNA), a NO synthaseinhibitor; 3) infusion ofL-NNA(10² M); and4) after administration of atropine(1.5 mg/kg). The results showed that vagal stimulation produced anincrease in RL andbr in periods 1, 2, and 3 (P < 0.01) that was not affected byL-NNA. Afteratropine was administered, there was no increase inbr or RL. Invitro experiments on trachealis smooth muscle contracted with carbachol showed no effect ofL-NNA on neural relaxation butshowed a complete blockade with propranolol(P < 0.01). In conclusion, thevagally induced airway smooth muscle contraction and bronchial vasculardilation are not influenced by NO, and the sheep's trachealis muscle,unlike that in several other species, does not have inhibitorynonadrenergic, noncholinergic innervation.

     

Lysophosphatidic acid enhances contractility of isolated airway smooth muscle

Toews, M. L., E. E. Ustinova, and H. D. Schultz.Lysophosphatidic acid enhances contractility of isolated airwaysmooth muscle. J. Appl. Physiol.83(4): 1216-1222, 1997.The effects of the simple phospholipidmediator lysophosphatidic acid (LPA) on the contractile responsivenessof isolated tracheal rings from rabbits and cats were assessed. In bothspecies, LPA increased the contractile response to the muscarinicagonist methacholine, but LPA did not induce contraction on its own.Conversely, LPA decreased the relaxation response to the-adrenergic-agonist isoproterenol in both species. Concentrations ofLPA as low as 10⁸ M wereeffective, and the effects of LPA were rapidly reversed on washing.Phosphatidic acid was much less effective, requiring higherconcentrations and producing only a minimal effect. Contractions induced by serotonin and by substance P also were enhanced by LPA, butKCl-induced contractions were unaffected. LPA inhibited theisoproterenol-induced relaxation of KCl-precontracted rings, similar toits effects on methacholine-precontracted rings, and relaxation inducedby the direct adenylyl cyclase activator forskolin was inhibited in amanner similar to that induced by isoproterenol. Epithelium removal didnot alter the contraction-enhancing effect of LPA. The ability of LPAto both enhance contraction and inhibit relaxation of airway smoothmuscle suggests that LPA could contribute to airway hypercontractilityin asthma, airway inflammation, or other types of lung injury.

     

Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs

Pisarri, Thomas E., and Gordon G. Giesbrecht. Reflextracheal smooth muscle contraction and bronchial vasodilation evoked byairway cooling in dogs. J. Appl.Physiol. 82(5): 1566-1572, 1997.Coolingintrathoracic airways by filling the pulmonary circulation with coldblood alters pulmonary mechanoreceptor discharge. To determine whetherthis initiates reflex changes that could contribute to airwayobstruction, we measured changes in tracheal smooth muscle tension andbronchial arterial flow evoked by cooling. In ninechloralose-anesthetized open-chest dogs, the right pulmonary artery wascannulated and perfused; the left lung, ventilated separately, providedgas exchange. With the right lung phasically ventilated, filling theright pulmonary circulation with 5°C blood increased smooth muscletension in an innervated upper tracheal segment by 23 ± 6 (SE) gfrom a baseline of 75 g. Contraction began within 10 s of injection andwas maximal at ~30s. The response was abolished by cervical vagotomy.Bronchial arterial flow increased from 8 ± 1 to 13 ± 2 ml/min, withlittle effect on arterial blood pressure. The time course wassimilar to that of the tracheal response. This response was greatlyattenuated after cervical vagotomy. Blood at 20°C also increasedtracheal smooth muscle tension and bronchial flow, whereas 37°Cblood had little effect. The results suggest that alteration ofairway mechanoreceptor discharge by cooling can initiate reflexes thatcontribute to airway obstruction.

     

Neural-mechanical coupling of breathing in REM sleep

Smith, C. A., K. S. Henderson, L. Xi, C.-M. Chow, P. R. Eastwood, and J. A. Dempsey. Neural-mechanical coupling of breathing in REM sleep. J. Appl.Physiol. 83(6): 1923-1932, 1997.During rapid-eye-movement (REM) sleep theventilatory response to airway occlusion is reduced. Possiblemechanisms are reduced chemosensitivity, mechanical impairment of thechest wall secondary to the atonia of REM sleep, or phasic REM eventsthat interrupt or fractionate ongoing diaphragm electromyogram (EMG)activity. To differentiate between these possibilities, we studiedthree chronically instrumented dogs before, during, and after15-20 s of airway occlusion during non-REM (NREM) and phasic REMsleep. We found that 1) for a given inspiratory time the integrated diaphragm EMG(Di) was similar or reduced in REM sleep relativeto NREM sleep; 2) for a givenDi in response to airway occlusion and thehyperpnea following occlusion, the mechanical output (flow or pressure)was similar or reduced during REM sleep relative to NREM sleep;3) for comparable durations ofairway occlusion the Di and integratedinspiratory tracheal pressure tended to be smaller and more variable inREM than in NREM sleep, and 4)significant fractionations (caused visible changes in trachealpressure) of the diaphragm EMG during airway occlusion inREM sleep occurred in ~40% of breathing efforts. Thus reducedand/or erratic mechanical output during and after airwayocclusion in REM sleep in terms of flow rate, tidal volume, and/or pressure generation is attributable largely to reduced neural activity of the diaphragm, which in turn is likely attributable to REM effects, causing reduced chemosensitivity at the level of theperipheral chemoreceptors or, more likely, at the central integrator.Chest wall distortion secondary to the atonia of REM sleep maycontribute to the reduced mechanical output following airway occlusionwhen ventilatory drive is highest.

     

Respiratory tissue properties derived from flow transfer function in healthy humans

Tomalak, W., R. Peslin, and C. Duvivier. Respiratorytissue properties derived from flow transfer function in healthy humans. J. Appl. Physiol. 82(4):1098-1106, 1997.Assuming homogeneity of alveolar pressure, therelationship between airway flow and flow at the chest during forcedoscillation at the airway opening [flow transfer function(FTF)] is related to lung and chest wall tissue impedance (Zti):FTF = 1 + Zti/Zg, where Zg is alveolar gas impedance, which isinversely proportional to thoracic gas volume. By using a flow-typebody plethysmograph to obtain flow rate at body surface, FTF has beenmeasured at oscillation frequencies (f_os) of 10, 20, 30 and 40 Hz in eight healthy subjects during both quiet and deepbreathing. The data were corrected for the flow shunted through upperairway walls and analyzed in terms of tissue resistance (Rti) andeffective elastance (Eti,eff) by using plethysmographically measuredthoracic gas volume values. In most subjects, Rti was seen to decreasewith increasingf_os and Eti,effto vary curvilinearly withf_os²,which is suggestive of mechanical inhomogeneity. Rti presented a weakvolume dependence during breathing, variable in sign according tof_os and amongsubjects. In contrast, Eti,eff usually exhibited a U-shaped patternwith a minimum located a little above or below functional residualcapacity and a steep increase with decreasing or increasing volume(30-80 hPa/l²) on eitherside. These variations are in excess of those expected from the sigmoidshape of the static pressure-volume curve and may reflect the effect ofrespiratory muscle activity. We conclude that FTF measurement is aninteresting tool to study Rti and Eti,eff and that these parametershave probably different physiological determinants.

     

Mechanical advantage of the canine triangularis sterni

De Troyer, André, and Alexandre Legrand.Mechanical advantage of the canine triangularis sterni.J. Appl. Physiol. 84(2): 562-568, 1998.Recent studies on the canine parasternal intercostal,sternomastoid, and scalene muscles have shown that the maximal changesin airway opening pressure (Pao) obtained per unit muscle mass(Pao/m) during isolatedcontraction are closely related to the fractional changes in musclelength per unit volume increase of the relaxed chest wall. In thepresent study, we have examined the validity of this relationship for the triangularis sterni, an important expiratory muscle of the rib cagein dogs. Passive inflation above functional residual capacity (FRC)induced a virtually linear increase in muscle length, such that, with a1.0-liter inflation, the muscle lengthened by 17.9 ± 1.6 (SE) % of its FRC length. When the muscle in one interspace wasmaximally stimulated at FRC, Pao increased by 0.84 ± 0.11 cmH₂O. However, in agreement withthe length-tension characteristics of the muscle, when lung volume wasincreased by 1.0 liter before stimulation, the rise in Pao amounted to1.75 ± 0.12 cmH₂O. At thehigher volume, Pao/m thereforeaveraged + 0.53 ± 0.05 cmH₂O/g, such that the coefficientof proportionality between the change in triangularis sterni lengthduring passive inflation and Pao/m was the same as that previously obtained for the parasternalintercostal and neck inspiratory muscles. These observations,therefore, confirm that there is a unique relationship between thefractional changes in length of the respiratory muscles, bothinspiratory and expiratory, during passive inflation and theirPao/m. Consequently, the maximal effect of a particular muscle on the lung can be predicted on the basisof its change in length during passive inflation and its mass. Ageometric analysis of the rib cage also established that thelengthening of the canine triangularis sterni during passive inflationis much greater than the shortening of the parasternal intercostalsbecause, in dogs, the costal cartilages slope downward from thesternum.

     

Wave-speed-determined flow limitation at peak flow in normal and asthmatic subjects

Pedersen, O. F., H. J. L. Brackel, J. M. Bogaard, and K. F. Kerrebijn. Wave-speed-determined flow limitation at peak flow innormal and asthmatic subjects. J. Appl.Physiol. 83(5): 1721-1732, 1997.The purpose ofthis study was to examine whether peak expiratory flow is determined bythe wave-speed flow-limiting mechanism. We examined 17 healthy subjectsand 11 subjects with stable asthma, the latter treated with inhaledbronchodilators and corticosteroids. We used an esophageal balloon anda Pitot-static probe positioned at five locations between the rightlower lobe and midtrachea to obtain dynamic area-transmural pressure(A-Ptm) curves as described (O. F. Pedersen, B. Thiessen, and S. Lyager. J. Appl.Physiol. 52: 357-369, 1982). From these curves weobtained cross-sectional area (A)and airway compliance (Caw = dA/dPtm) at PEF, calculated flow at wave speed {ws = A[A/(Caw*)^0.5],where  is density} and speed index is (SI = /ws). In 13 of 15 healthy andin 4 of 10 asthmatic subjects, who could produce satisfactory curves,SI at PEF was >0.9 at one or more measured positions. Alveolarpressure continued to increase after PEF was achieved, suggesting flowlimitation somewhere in the airway in all of these subjects. Weconclude that wave speed is reached in central airways at PEF in mostsubjects, but it cannot be excluded that wave speed is also reached inmore peripheral airways.