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.

     

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

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

     

In vivo assessment of changes in air and tissue volumes after pneumonectomy

Takeda, S., E. Y. Wu, R. H. Epstein, A. S. Estrera, and C. C. W. Hsia. In vivo assessment of changes in air and tissue volumes after pneumonectomy. J. Appl.Physiol. 82(4): 1340-1348, 1997.We examined theprogression and topographical distribution of postpneumonectomy volumechanges in immature foxhounds undergoing right pneumonectomy (R-Pnx,n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequentlyraised to maturity. Volumes of lung air (Vair) and tissue(Vti) were estimated by computerized tomography (CT) scan at 7, 22, and52 wk after surgery at a transpulmonary pressure of 20 cmH₂O. Estimates of Vti by CT scanincluded both septal tissue as well as nonseptal tissue (small- andmedium-sized airways and blood vessels); these were compared withestimates of septal Vti by an acetylene rebreathing (Rb) method. Wefound significant correlations between these techniques(Vair_CT = 0.83 Vair_Rb + 275, R = 0.97;Vti_CT = 1.62 Vti_Rb  30, R = 0.81). Extravascular septal Vtireturned to normal 7 wk after R-Pnx and remained normal up to maturity.Nonseptal Vti remained significantly below normal. The greatestincrease in Vti occurred in the midlung region just cephalad and caudalto the heart. After an early period of accelerated tissue growth afterR-Pnx, the rate of septal tissue growth matched that of somatic growth,whereas nonseptal tissue growth lagged behind. Compensatory growth ofthe remaining left lung was not associated with selectivealterations in thoracic development.

     

In vitro bronchial responsiveness in two highly inbred rat strains

Wang, C. G., J. J. Almirall, C. S. Dolman, R. J. Dandurand,and D. H. Eidelman. In vitro bronchial responsiveness in twohighly inbred rat strains. J. Appl.Physiol. 82(5): 1445-1452, 1997.We investigatedmethacholine (MCh)-induced bronchoconstriction in explanted airwaysfrom Fischer and Lewis rats. Lung explants, 0.5- to 1.0-mm thick, wereprepared from agarose-inflated lungs of anesthetized 8- to 12-wk-oldmale rats. After overnight culture, videomicroscopy was used to recordbaseline images of the individual airways. Dose-response curves to MChwere then constructed by repeated administration of MCh; airways werereimaged 10 min after each MCh administration. Airway internal luminalarea(A_i)was measured at successive MCh concentrations from10⁹ to10¹ M. Inaddition to the effective concentration leading to 50% of the achievedmaximal response, we also determined the effective concentrationleading to a 40% reduction inA_i.Both the effective concentration leading to 50% of the achievedmaximal response and the concentration leading to a 40% reduction inA_iwere significantly lower among Fischer rat airways(P < 0.05). Airway closure was morecommon among Fischer rat airways (17%) than among those of Lewis rats(7.5%). Responsiveness of Fischer rat airways was more heterogeneousthan among Lewis airways; a larger number of Fischer rat airwaysexhibited high sensitivity to MCh. There was no relationship betweenresponsiveness and baselineA_iin either strain. In a second experiment, we measured the rate ofcontraction of explanted airways from lungs inflated to 50, 75, and100% of total lung capacity. The average rate of contraction in thefirst 15 s was higher in Fischer rat airways at each inflation volume.These data indicate that the hyperresponsiveness of the Fischer rat reflects the responsiveness of individual airways throughout the airwaytree and are consistent with the notion that in this model hyperresponsiveness is an intrinsic property of airway smooth muscle.

     

Effects of training duration on substrate turnover and oxidation during exercise

Phillips, S. M., H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, R. E. Hill, and S. M. Grant. Effects of training duration on substrate turnover and oxidation during exercise. J. Appl. Physiol. 81(5):2182-2191, 1996.Adaptations in fat and carbohydrate metabolismafter a prolonged endurance training program were examined using stableisotope tracers of glucose([6,6-²H₂]glucose),glycerol([²H₅]glycerol),and palmitate([²H₂]palmitate).Active, but untrained, males exercised on a cycle for 2 h/day[60% pretraining peak O₂consumption (O_{2 peak}) = 44.3 ± 2.4 ml ^· kg^{1 ·} min¹]for a total of 31 days. Three cycle tests (90 min at 60% pretraining O_{2 peak}) wereadministered before training (PRE) and after 5 (5D) and 31 (31D) daysof training. Exercise increased the rate of glucose production(R_a) and utilization(R_d) as well as the rate oflipolysis (glycerol R_a) and freefatty acid turnover (FFA R_a/R_d).At 5D, training induced a 10% (P < 0.05) increase in total fat oxidation because of an increase inintramuscular triglyceride oxidation (+63%,P < 0.05) and a decreased glycogenoxidation (16%, P < 0.05).At 31D, total fat oxidation during exercise increased a further 58%(P < 0.01). The pattern of fatutilization during exercise at 31D showed a reduced reliance on plasmaFFA oxidation (FFA R_d) and agreater dependence on oxidation of intramuscular triglyceride, whichincreased more than twofold (P < 0.001). In addition, glucose R_aand R_d were reduced at all timepoints during exercise at 31D compared with PRE and 5D. We concludethat long-term training induces a progressive increase in fatutilization mediated by a greater oxidation of fats from intramuscularsources and a reduction in glucose oxidation. Initial changes arepresent as early as 5D and occur before increases in muscle maximalmitochondrial enzyme activity [S. M. Phillips, H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, and S. M. Grant.Am. J. Physiol. 270 (Endocrinol. Metab. 33):E265-E272, 1996].

     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Kocis, Keith C., Peter J. Radell, Wayne I. Sternberger, JaneE. Benson, Richard J. Traystman, and David G. Nichols. Ultrasound evaluation of piglet diaphragm function before and after fatigue. J. Appl. Physiol. 83(5):1654-1659, 1997.Clinically, a noninvasive measure of diaphragmfunction is needed. The purpose of this study is to determine whetherultrasonography can be used to 1)quantify diaphragm function and 2)identify fatigue in a piglet model. Five piglets were anesthetized withpentobarbital sodium and halothane and studied during the followingconditions: 1) baseline (spontaneous breathing); 2) baseline + CO₂ [inhaledCO₂ to increase arterial PCO₂ to 50-60 Torr (6.6-8kPa)]; 3) fatigue + CO₂ (fatigue induced with 30 minof phrenic nerve pacing); and 4)recovery + CO₂ (recovery after 1 hof mechanical ventilation). Ultrasound measurements of the posteriordiaphragm were made (inspiratory mean velocity) in the transverseplane. Images were obtained from the midline, just inferior to thexiphoid process, and perpendicular to the abdomen. M-mode measures weremade of the right posterior hemidiaphragm in the plane just lateral tothe inferior vena cava. Abdominal and esophageal pressures weremeasured and transdiaphragmatic pressure (Pdi) was calculated duringspontaneous (Sp) and paced (Pace) breaths. Arterial blood gases werealso measured. Pdi(Sp) and Pdi(Pace)during baseline + CO₂ were 8 ± 0.7 and 49 ± 11 cmH₂O, respectively, anddecreased to 6 ± 1.0 and 27 ± 7 cmH₂O,respectively, during fatigue + CO₂. Mean inspiratory velocityalso decreased from 13 ± 2 to 8 ± 1 cm/s during theseconditions. All variables returned to baseline during recovery + CO₂. Ultrasonography can beused to quantify diaphragm function and identify piglet diaphragm fatigue.

     

Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs

Parker, James C., and Claire L. Ivey.Isoproterenol attenuates high vascular pressure-inducedpermeability increases in isolated rat lungs. J. Appl.Physiol. 83(6): 1962-1967, 1997.To separate thecontributions of cellular and basement membrane components of thealveolar capillary barrier to the increased microvascular permeabilityinduced by high pulmonary venous pressures (Ppv), we subjected isolatedrat lungs to increases in Ppv, which increased capillary filtrationcoefficient(K_fc) withoutsignificant hemorrhage (31 cmH₂O)and with obvious extravasation of red blood cells (43 cmH₂O). Isoproterenol (20 µM)was infused in one group (Iso) to identify a reversible cellularcomponent of injury, and residual blood volumes were measured to assessextravasation of red blood cells through ruptured basement membranes.In untreated lungs (High Ppv group),K_fc increased 6.2 ± 1.3 and 38.3 ± 15.2 times baseline during the 31 and 43 cmH₂O Ppv states. In Iso lungs, K_fc was 36.2%(P < 0.05) and 64.3% of that in theHigh Ppv group at these Ppv states. Residual blood volumes calculatedfrom tissue hemoglobin contents were significantly increased by53-66% in the high Ppv groups, compared with low vascularpressure controls, but there was no significant difference between HighPpv and Iso groups. Thus isoproterenol significantly attenuatedvascular pressure-induced K_fc increases atmoderate Ppv, possibly because of an endothelial effect, but it did notaffect red cell extravasation at higher vascular pressures.

     

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.

     

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.

     

Effects of chest wall counterpressures on lung mechanics under high levels of CPAP in humans

Beaumont, Maurice, Damien Lejeune, Henri Marotte, AlainHarf, and Frédéric Lofaso. Effects of chest wallcounterpressures on lung mechanics under high levels of CPAP in humans.J. Appl. Physiol. 83(2): 591-598, 1997.We assessed the respective effects of thoracic (TCP) andabdominal/lower limb (ACP) counterpressures on end-expiratory volume(EEV) and respiratory muscle activity in humans breathing at 40 cmH₂O of continuous positiveairway pressure (CPAP). Expiratory activity was evaluated on the basis of the inspiratory drop in gastric pressure (Pga) from its maximal end-expiratory level, whereas inspiratory activity was evaluated on thebasis of the transdiaphragmatic pressure-time product (PTPdi). CPAPinduced hyperventilation (+320%) and only a 28% increase in EEVbecause of a high level of expiratory activity (Pga = 24 ± 5 cmH₂O), contrasting with areduction in PTPdi from 17 ± 2 to 9 ± 7 cmH₂O · s¹ · cycle¹during 0 and 40 cmH₂O of CPAP,respectively. When ACP, TCP, or both were added, hyperventilationdecreased and PTPdi increased (19 ± 5, 21 ± 5, and 35 ± 7 cmH₂O · s¹ · cycle¹,respectively), whereas Pga decreased (19 ± 6, 9 ± 4, and 2 ± 2 cmH₂O, respectively). Weconcluded that during high-level CPAP, TCP and ACP limit lunghyperinflation and expiratory muscle activity and restore diaphragmaticactivity.

     

Letters to the Editor

The following are the abstracts of the articles discussed inthe subsequent letter:

  Huang, Yuh-Chin T., Aneysa C. Sane, Steven G. Simonson, Thomas A. Fawcett, Richard E. Moon,Philip J. Fracica, Margaret G. Menache, Claude A. Piantadosi, andStephen L. Young. Artificial surfactant attenuates hyperoxic lunginjury in primates. I. Physiology and biochemistry. J. Appl.Physiol. 78(5): 1816-1822, 1995.Prolonged exposure toO₂ causes diffuse alveolar damage and surfactantdysfunction that contribute to the pathophysiology of hyperoxic lunginjury. We hypothesized that exogenous surfactant would improve lungfunction during O₂ exposure in primates. Sixteen healthymale baboons (10-15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O₂(n = 6) or 100% O₂ plus aerosolized artificialsurfactant (Exosurf; n = 5). A third group of animals(n = 5) was ventilated with an inspired fraction ofO₂ of 0.21 to control for the effects of sedation andmechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution(_A/) was measureddaily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH₂O andwas intermittently raised to 10 cmH₂O for 30 minto obtain additional measurements of_A/. After theexperiments, lungs were obtained for biochemical and histologicalassessment of injury. O₂ exposures altered hemodynamics,progressively worsened_A/, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturatedphosphatidylcholine in lavage fluid and improved intrapulmonary shunt,arterial PO₂, and lung edema. Surfactant alsoenhanced the shunt-reducing effect of positive end-expiratory pressure.We conclude that an aerosolized protein-free surfactant decreased theprogression of pulmonary O₂ toxicity in baboons.

     

Upper airway muscle activity and upper airway resistance in young adults during sleep

Henke, Kathe G. Upper airway muscle activity and upperairway resistance in young adults during sleep. J. Appl. Physiol. 84(2): 486-491, 1998.To determinethe relationship between upper airway muscle activity and upper airwayresistance in nonsnoring and snoring young adults, 17 subjects werestudied during sleep. Genioglossus and alae nasi electromyogramactivity were recorded. Inspiratory and expiratory supraglotticresistance (Rinsp and Rexp, respectively) were measured at peak flow,and the coefficients of resistance(K_insp andK_exp,respectively) were calculated. Data were recorded during control,with continuous positive airway pressure (CPAP), and on the breathimmediately after termination of CPAP. Rinsp during control averaged 7 ± 1 and 10 ± 2 cmH₂O · l¹ · sand K_inspaveraged 26 ± 5 and 80 ± 27 cmH₂O · l¹ · s²in the nonsnorers and snorers, respectively(P = not significant). Onthe breath immediately after CPAP,K_insp did notincrease over control in snorers (80 ± 27 for control vs. 46 ± 6 cmH₂O · l¹ · s²for the breath after CPAP) or nonsnorers (26 ± 5 vs. 29 ± 6 cmH₂O · l¹ · s²).These findings held true for Rinsp.K_exp did notincrease in either group on the breath immediately after termination ofCPAP. Therefore, 1) increases inupper airway resistance do not occur, despite reductions inelectromyogram activity in young snorers and nonsnorers, and2) increases in Rexp and expiratoryflow limitation are not observed in young snorers.

     

Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity

Prisk, G. Kim, Ann R. Elliott, Harold J. B. Guy, SylviaVerbanck, Manuel Paiva, and John B. West. Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity.J. Appl. Physiol. 84(1): 244-252, 1998.We performed multiple-breath washouts ofN₂ and simultaneous washins of Heand SF₆ with fixed tidal volume(~1,250 ml) and preinspiratory lung volume (approximately thesubject's functional residual capacity in the standing position) infour normal subjects (mean age 40 yr) standing and supine in normalgravity (1 G) and during exposure to sustained microgravity (µG). Theprimary objective was to examine the influence of diffusive processeson the residual, nongravitational ventilatory inhomogeneity in the lungin µG. We calculated several indexes of convective ventilatoryinhomogeneity from each gas species. A normal degree of ventilatoryinhomogeneity was seen in the standing position at 1 G that was largelyunaltered in the supine position. When we compared the standingposition in 1 G with µG, there were reductions in phase III slope inall gases, consistent with a reduction in convection-dependentinhomogeneity in the lung in µG, although considerable convectiveinhomogeneity persisted in µG. The reductions in the indexes ofconvection-dependent inhomogeneity were greater for He than forSF₆, suggesting that the distancesbetween remaining nonuniformly ventilated compartments in µG wereshort enough for diffusion of He to be an effective mechanism to reducegas concentration differences between them.

     

Hyperpnea-induced bronchoconstriction is dependent on tachykinin-induced cysteinyl leukotriene synthesis

Yang, X. X., W. S. Powell, M. Hojo, and J. G. Martin.Hyperpnea-induced bronchoconstriction is dependent ontachykinin-induced cysteinyl leukotriene synthesis. J. Appl. Physiol. 82(2): 538-544, 1997.The purposeof the study was to test the hypothesis that tachykinins mediatehyperpnea-induced bronchoconstriction indirectly by triggeringcysteinyl leukotriene (LT) synthesis in the airways. Guinea pigs(350-600 g) were anesthetized with xylazine and pentobarbital sodium and received hyperpnea challenge (tidal volume 3.5-4.0 ml,frequency 150 breaths/min) with either humidified isocapnic gas(n = 6) or dry gas(n = 7). Dry gas challenge wasperformed on animals that received MK-571(LTD₄ antagonist; 2 mg/kg iv; n = 5), capsaicin(n = 4), neurokinin (NK) antagonists[NK₁ (CP-99994) + NK₂ (SR-48968) (1 mg/kg iv);n = 6], or theH₁ antihistamine pyrilamine (2 mg/kg iv; n = 5). We measured thetracheal pressure and collected bile for 1 h before and 2 h afterhyperpnea challenge. We examined the biliary excretion of cysteinylLTs; the recovery of radioactivity in bile after instillation of 1 µCi [³H]LTC₄intratracheally averaged 24% within 4 h(n = 2). The major cysteinyl LTidentified was LTD₄ (32% recoveryof radioactivity). Cysteinyl LTs were purified from bile of animalsundergoing hyperpnea challenge by using reverse-phase high-pressureliquid chromatography and quantified by radioimmunoassay. There was asignificant increase in the peak value of tracheal pressure afterchallenge, indicating bronchoconstriction in dry gas-challenged animalsbut not after humidified gas challenge. MK-571, capsaicin, and NKantagonists prevented the bronchoconstriction; pyrilamine didnot. Cysteinyl LT levels in the bile after challenge weresignificantly increased from baseline in dry gas-challenged animals(P < 0.05) and were higher than inthe animals challenged with humidified gas or dry gas-challengedanimals treated with capsaicin or NK antagonists (P < 0.01). The results indicatethat isocapnic dry gas hyperpnea-induced bronchoconstriction is LTmediated and the role of tachykinins in the response is indirectthrough release of LTs. Endogenous histamine does not contribute to theresponse.

     

Phrenic motoneuron discharge during sustained inspiratory resistive loading

Iscoe, Steve. Phrenic motoneuron discharge duringsustained inspiratory resistive loading. J. Appl.Physiol. 81(5): 2260-2266, 1996.I determinedwhether prolonged inspiratory resistive loading (IRL) affects phrenicmotoneuron discharge, independent of changes in chemical drive. Inseven decerebrate spontaneously breathing cats, the discharge patternsof eight phrenic motoneurons from filaments of one phrenic nerve weremonitored, along with the global activity of the contralateral phrenicnerve, transdiaphragmatic pressure, and fractional end-tidalCO₂ levels. Discharge patterns during hyperoxic CO₂ rebreathingand breathing against an IRL (2,500-4,000cmH₂O ^· l^{1 ·} s)were compared. During IRL, transdiaphragmatic pressure increased andthen either plateaued or decreased. At the highest fractional end-tidalCO₂ common to both runs,instantaneous discharge frequencies in six motoneurons were greaterduring sustained IRL than during rebreathing, when compared at the sametime after the onset of inspiration. These increased dischargefrequencies suggest the presence of a load-induced nonchemical drive tophrenic motoneurons from unidentified source(s).

     

Abdominal muscle fatigue after maximal ventilation in humans

Kyroussis, Dimitris, Gary H. Mills, Michael I. Polkey,Carl-Hugo Hamnegard, Nicholaos Koulouris, Malcolm Green, and John Moxham. Abdominal muscle fatigue after maximal ventilation inhumans. J. Appl. Physiol. 81(4):1477-1483, 1996.Abdominal muscles are the principal muscles ofactive expiration. To investigate the possibility of abdominal musclelow-frequency fatigue after maximal ventilation in humans, westimulated the nerve roots supplying the abdominal muscles. We used amagnetic stimulator (Magstim 200) powering a 90-mm circular coil andstudied six normal subjects. To assess the optimum level of stimulationand posture, we stimulated at each intervertebral level betweenT₇ andL₁ in the prone, supine, andseated positions. At T₁₀, we usedincreasing power outputs to assess the pressure-power relationship.Care was taken to avoid muscle potentiation. Twitch gastric pressure(Pga) was recorded with a balloon-tipped catheter. Mean (±SD)baseline twitch Pga measured with the subjects in the prone position atT₁₀ was 23.5 ± 5.4 cmH₂O. Within-occasion mean twitchPga coefficient of variation was 4.6 ± 1.1%. Twitch Pga wasmeasured with the subjects in the prone position with stimulation overT₁₀ before and after 2 min ofmaximal isocapnic ventilation (MIV). Twenty minutes after MIV, meantwitch Pga fell by 17 ± 9.1%(P = 0.03) and remained low 90 minafter MIV. We conclude that after maximal ventilation in humans thereis a reduction of twitch Pga and, therefore, of low-frequency fatiguein abdominal muscles.

     

Effect of the TI/TE ratio on mean intratracheal pressure in high-frequency oscillatory ventilation

In high-frequencyoscillatory ventilation (HFOV), an adequate mean airway pressure iscrucial for successful ventilation and optimal gas exchange, but airtrapping cannot be detected by the usual measurement at the y piece.Intratracheal pressures produced by the high-frequency oscillatorsHFV-Infantstar (IS), Babylog 8000 (BL), and the SensorMedics 3100A (SM)[the latter with either 30% (SM₃₀) or 50%(SM₅₀) inspiratory time] were investigated in fouranesthetized tracheotomized female piglets that were 1 day old andweighed 1.6-1.9 kg (mean 1.76 kg). The endotracheal tube wasrepeatedly clamped while the piglets were ventilated with anoscillation frequency of 10 Hz, and the airway pressure distal of theclamp was recorded as a measure of average intrapulmonary pressureduring oscillation. Clamping resulted in a significant decrease of meanairway pressure when the piglets were ventilated with SM₃₀(0.86 cmH₂O), BL (0.66 cmH₂O), and IS(0.71 cmH₂O), but airway pressure increased by a mean of0.76 cmH₂O with SM₅₀. Intratracheal pressure,when measured by a catheter pressure transducer at various oscillationfrequencies, was lower than at the y piece by 0.4-0.9cmH₂O (SM₃₀), 0.3-3 cmH₂O(BL), and 1-4.7 cmH₂O (IS) but was 0.4-0.7cmH₂O higher with SM₅₀. We conclude that theinspiratory-to-expiratory time(TI/TE) ratio influences theintratracheal and intrapulmonary pressures in HFOV and may sustain amean pressure gradient between the y piece and the trachea. ATI/TE ratio < 1:1 maybe useful to avoid air trapping when HFOV is used.

     

High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat lungs

Parker, James C., Ellen C. Breen, and John B. West.High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat lungs. J. Appl.Physiol. 83(5): 1697-1705, 1997.We hypothesizedthat wall stresses produced by high peak airway (Paw) and venous (Ppv)pressures would increase mRNA levels for structural proteins of theinterstitial matrix in isolated rat lungs. Groups of lungs(n = 6) were perfused for 4 h at apeak Paw of 35 cmH₂O (HiPaw),cyclical peak Ppv of 28 cmH₂O(HiPv), or baseline vascular and airway pressures (LoPress). In twoseparate groups, comparable peak pressures increased capillary filtration coefficient fourfold in each group. Northern blots wereprobed for mRNA of ₁(I),₁(III), and₂(IV) procollagen chains,laminin B chain, fibronectin, and transforming growth factor-₁, and densities werenormalized to 18S rRNA. mRNA was significantly higher in the HiPv groupfor type I (4.3-fold) and type III (3.8-fold) procollagen and laminin Bchain (4.8-fold) and in the HiPaw group for type I (2.4-fold) and typeIV (4.5-fold) procollagen and laminin B chain (2.3-fold) than in theLoPress group. Only fibronectin mRNA was significantly increased(3.9-fold) in the LoPress group relative to unperfused lungs. Estimatedwall stresses were highest for alveolar septa in the HiPaw group and for capillaries in the HiPv group. The different patterns of mRNA expression are attributed to different regional stresses or extent ofinjury.

     

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

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

     

Detection of expiratory flow limitation during exercise in COPD patients

Koulouris, Nickolaos G., Ioanna Dimopoulou, PäiviValta, Richard Finkelstein, Manuel G. Cosio, and J. Milic-Emili.Detection of expiratory flow limitation during exercise in COPDpatients. J. Appl. Physiol. 82(3):723-731, 1997.The negative expiratory pressure (NEP) method wasused to detect expiratory flow limitation at rest and at differentexercise levels in 4 normal subjects and 14 patients with chronicobstructive pulmonary disease (COPD). This method does not requireperformance of forced expirations, nor does it require use of bodyplethysmography. It consists in applying negative pressure (5cmH₂O) at the mouth during early expiration and comparing the flow-volume curve of the ensuing expiration with that of the preceding control breath. Subjects in whomapplication of NEP does not elicit an increase in flow during part orall of the tidal expiration are considered flow limited. The fournormal subjects were not flow limited up to 90% of maximal exercisepower output(_max).Five COPD patients were flow limited at rest, 9 were flow limited atone-third _max, and 12 were flow limited at two-thirds_max. Whereasin all patients who were flow limited at rest the maximalO₂ uptake was below the normallimits, this was not the case in most of the other patients. Inconclusion, NEP provides a rapid and reliable method to detectexpiratory flow limitation at rest and during exercise.