Tidal volume effects on surfactant treatment responses with the initiation of ventilation in preterm lambs

Wada, Kazuko, Alan H. Jobe, and Machiko Ikegami. Tidalvolume effects on surfactant treatment responses with the initiation ofventilation in preterm lambs. J. Appl.Physiol. 83(4): 1054-1061, 1997.We hypothesizedthat initiation of ventilation in preterm lambs with high volumes wouldcause lung injury and decrease the subsequent response to surfactanttreatment. Preterm lambs were randomized to ventilation for 30 minafter birth with 5 ml/kg (VT5),10 ml/kg (VT10), or 20 ml/kg(VT20) tidal volumes and then ventilated with ~10 ml/kg tidal volumes to achieve arterialPCO₂ values of ~50 Torr to 6 h ofage. VT20 lambs had lowercompliances, lower ventilatory efficiencies, higher recoveries ofprotein, and lower recoveries of surfactant in alveolar lavages and in surfactant that had decreased compliances when tested in preterm rabbits than VT5 orVT10 lambs. Other lambsrandomized to treatment with surfactant at birth and ventilation with6, 12, or 20 ml/kg tidal volumes for 30 min had no indicators of lunginjury. An initial tidal volume of 20 ml/kg decreased the subsequentresponse to surfactant treatment, an effect that was prevented withsurfactant treatment at birth.

     

Continuous non-invasive monitoring of tidal volumes by measurement of tidal impedance in neonatal piglets

Background

Electrical Impedance measurements can be used to estimate the content of intra-thoracic air and thereby give information on pulmonary ventilation. Conventional Impedance measurements mainly indicate relative changes, but no information concerning air-volume is given. The study was performed to test whether a 3-point-calibration with known tidal volumes (VT) during conventional mechanical ventilation (CMV) allows subsequent calculation of VT from total Tidal-Impedance (tTI) measurements using Quadrant Impedance Measurement (QIM). In addition the distribution of TI in different regions of the thorax was examined.

Methodology and Principal Findings

QIM was performed in five neonatal piglets during volume-controlled CMV. tTI values at three different VT (4, 6, 8 ml/kg) were used to establish individual calibration curves. Subsequently, each animal was ventilated with different patterns of varying VT (2–10 ml/kg) at different PEEP levels (0, 3, 6, 9, 12 cmH₂O). VT variation was repeated after surfactant depletion by bronchoalveolar lavage. VT was calculated from tTI values (VT_calc) and compared to the VT delivered by the ventilator (VT_PNT). Bland-Altman analysis revealed good agreement between VT_calc and VT_PNT before (bias −0.08 ml; limits of agreement −1.18 to 1.02 ml at PEEP = 3 cmH₂O) and after surfactant depletion (bias −0.17 ml; limits of agreement −1.57 to 1.22 ml at PEEP = 3 cmH₂O). At higher PEEP levels VT_calc was lower than VT_PNT, when only one fixed calibration curve (at PEEP 3 cmH₂O) was used. With a new calibration curve at each PEEP level the method showed similar accuracy at each PEEP level. TI showed a homogeneous distribution over the four assessed quadrants with a shift toward caudal regions of the thorax with increasing VT.

Conclusion

Tidal Impedance values could be used for precise and accurate calculation of VT during CMV in this animal study, when calibrated at each PEEP level.     

Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs

To determine theinitial signaling event in the vascular permeability increase afterhigh airway pressure injury, we compared groups of lungs ventilated atdifferent peak inflation pressures (PIPs) with (gadolinium group) andwithout (control group) infusion of 20 µM gadolinium chloride, aninhibitor of endothelial stretch-activated cationchannels. Microvascular permeability was assessed by using the capillary filtration coefficient(K_fc), ameasure of capillary hydraulic conductivity.K_fc was measuredafter ventilation for 30-min periods with 7, 20, and 30 cmH₂O PIP with 3 cmH₂O positive end-expiratorypressure and with 35 cmH₂O PIPwith 8 cmH₂O positive end-expiratory pressure. In control lungs,K_fc increasedsignificantly to 1.8 and 3.7 times baseline after 30 and 35 cmH₂O PIP, respectively. In thegadolinium group,K_fc was unchangedfrom baseline (0.060 ± 0.010 ml · min¹ · cmH₂O¹ · 100 g¹) after any PIPventilation period. Pulmonary vascular resistance increasedsignificantly from baseline in both groups before the lastK_fc measurementbut was not different between groups. These results suggest thatmicrovascular permeability is actively modulated by a cellular responseto mechanical injury and that stretch-activated cation channels mayinitiate this response through increases in intracellular calciumconcentration.

     

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.

     

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.

     

Effect of PEEP and Tidal Volume on Ventilation Distribution and End-Expiratory Lung Volume: A Prospective Experimental Animal and Pilot Clinical Study

Introduction

Lung-protective ventilation aims at using low tidal volumes (V_T) at optimum positive end-expiratory pressures (PEEP). Optimum PEEP should recruit atelectatic lung regions and avoid tidal recruitment and end-inspiratory overinflation. We examined the effect of V_T and PEEP on ventilation distribution, regional respiratory system compliance (C_RS), and end-expiratory lung volume (EELV) in an animal model of acute lung injury (ALI) and patients with ARDS by using electrical impedance tomography (EIT) with the aim to assess tidal recruitment and overinflation.

Methods

EIT examinations were performed in 10 anaesthetized pigs with normal lungs ventilated at 5 and 10 ml/kg body weight V_T and 5 cmH₂O PEEP. After ALI induction, 10 ml/kg V_T and 10 cmH₂O PEEP were applied. Afterwards, PEEP was set according to the pressure-volume curve. Animals were randomized to either low or high V_T ventilation changed after 30 minutes in a crossover design. Ventilation distribution, regional C_RS and changes in EELV were analyzed. The same measures were determined in five ARDS patients examined during low and high V_T ventilation (6 and 10 (8) ml/kg) at three PEEP levels.

Results

In healthy animals, high compared to low V_T increased C_RS and ventilation in dependent lung regions implying tidal recruitment. ALI reduced C_RS and EELV in all regions without changing ventilation distribution. Pressure-volume curve-derived PEEP of 21±4 cmH₂O (mean±SD) resulted in comparable increase in C_RS in dependent and decrease in non-dependent regions at both V_T. This implied that tidal recruitment was avoided but end-inspiratory overinflation was present irrespective of V_T. In patients, regional C_RS differences between low and high V_T revealed high degree of tidal recruitment and low overinflation at 3±1 cmH₂O PEEP. Tidal recruitment decreased at 10±1 cmH₂O and was further reduced at 15±2 cmH₂O PEEP.

Conclusions

Tidal recruitment and end-inspiratory overinflation can be assessed by EIT-based analysis of regional C_RS.     

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.

     

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.

     

Phosphotyrosine phosphatase and tyrosine kinase inhibition modulate airway pressure-induced lung injury

We determinedwhether drugs which modulate the state of protein tyrosinephosphorylation could alter the threshold for high airwaypressure-induced microvascular injury in isolated perfused rat lungs.Lungs were ventilated for successive 30-min periods with peak inflationpressures (PIP) of 7, 20, 30, and 35 cmH₂O followed by measurement ofthe capillary filtration coefficient (K_fc), asensitive index of hydraulic conductance. In untreated control lungs,K_fc increased by1.3- and 3.3-fold relative to baseline (7 cmH₂O PIP) after ventilation with30 and 35 cmH₂O PIP. However, inlungs treated with 100 µM phenylarsine oxide (a phosphotyrosinephosphatase inhibitor),K_fc increased by4.7- and 16.4-fold relative to baseline at these PIP values. In lungs treated with 50 µM genistein (a tyrosine kinase inhibitor),K_fc increasedsignificantly only at 35 cmH₂OPIP, and the three groups were significantly different from each other.Thus phosphotyrosine phosphatase inhibition increased thesusceptibility of rat lungs to high-PIP injury, and tyrosine kinaseinhibition attenuated the injury relative to the high-PIP control lungs.

     

Effects of surfactant proteins SP-B and SP-C on dynamic and static mechanics of immature lungs

Kobayashi, Tsutomu, Katsumi Tashiro, Ken Yamamoto, ShunichiNitta, Shigeo Ohmura, and Yasuhiro Suzuki. Effects of surfactant proteins SP-B and SP-C on dynamic and static mechanics of immature lungs. J. Appl. Physiol. 83(6):1849-1856, 1997.To investigate the effects of surfactantproteins B (SP-B) and C (SP-C) on lung mechanics, we compared tidal andstatic lung volumes of immature rabbits anesthetized with pentobarbitalsodium and given reconstituted test surfactants (RTS).With a series of RTS having various SP-B concentrations (0-0.7%)but a fixed SP-C concentration (1.4%), both the tidal volume with25-cmH₂O insufflation pressure and the static volume deflated to5-cmH₂O airway pressure increased, significantly correlating with the SP-B concentration: the former increased from 6.5 to 26.0 ml/kg (mean), and the latter increased from6.4 to 31.8 ml/kg. With another series of RTS having afixed SP-B concentration (0.7%) but various SP-C concentrations(0-1.4%), the tidal volume increased from 5.1 to 24.8 ml/kg,significantly correlating with the SP-C concentration, whereas thestatic volume increased from 3.4 to 32.0 ml/kg, the ceiling value, inthe presence of a minimal concentration of SP-C (0.18%). Inconclusion, certain doses of SP-B and SP-C were indispensable foroptimizing dynamic lung mechanics; the static mechanics, however,required significantly less SP-C.

     

Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency

Wolfson, Marla R., Nancy E. Kechner, Robert F. Roache,Jean-Pierre DeChadarevian, Helena E. Friss, S. David Rubenstein, andThomas H. Shaffer. Perfluorochemical rescue after surfactant treatment: effect of perflubron dose and ventilatory frequency. J. Appl. Physiol. 84(2): 624-640, 1998.To test the hypotheses that perfluorochemical (PFC) liquidrescue after natural surfactant (SF) treatment would improve pulmonaryfunction and histology and that this profile would be influenced by PFCdose or ventilator strategy, anesthetized preterm lambs(n = 31) with respiratory distresswere studied using nonpreoxygenated perflubron. All animals received SFat 1 h and were randomized at 2 h as follows and studied to 4 h postnatal age: 1) conventionalmechanical gas ventilation (n = 8),2) 30 ml/kg perflubron with gasventilation [partial liquid ventilation (PLV)] at 60 breaths/min (n = 8),3) 10 ml/kg perflubron with PLV at60 breaths/min (n = 7), and4) 10 ml/kg perflubron with PLV at30 breaths/min (n = 8). All animalstolerated instillation without additional cardiopulmonary instability.All perflubron-rescued groups demonstrated sustained improvement in gasexchange, respiratory compliance, and reduction in pressure requirements relative to animals receiving SF alone. Improvement wasdirectly related to perflubron dose and breathing frequency; peakinspiratory pressure required to achieve physiological gas exchange waslower in the higher-dose and -frequency groups, and mean airwaypressure was lower in the lower-frequency group. Lung expansion wasgreater and evidence of barotrauma was less in the higher-dose and-frequency group; regional differences in expansion were not differentas a function of dose but were greater in the lower-frequency group.Regional differences in lung perflubron content were reduced in thehigher-dose and -frequency groups and greatest in the lower-dose and-frequency group. The results suggest that, whereas PLV of theSF-treated lung improves gas exchange and lung mechanics, theprotective benefits of perflubron in the lung may depend on dose andventilator strategy to optimize PFC distribution and minimize exposureof the alveolar-capillary membrane to a gas-liquid interface.

     

Different ventilation strategies alter surfactant responses in preterm rabbits.

The effect of ventilation strategy on in vivo function of different surfactants was evaluated in preterm rabbits delivered at 27 days gestational age and ventilated with either 0 cmH2O positive end-expiratory pressure (PEEP) at tidal volumes of 10-11 ml/kg or 3 cmH2O PEEP at tidal volumes of 7-8 ml/kg after treatment with one of four different surfactants: sheep surfactant, the lipids of sheep surfactant stripped of protein (LH-20 lipid), Exosurf, and Survanta. The use of 3 cmH2O PEEP decreased pneumothoraces in all groups except for the sheep surfactant group where pneumothoraces increased (P < 0.01). Ventilatory pressures (peak pressures - PEEP) decreased more with the 3 cmH2O PEEP, low-tidal-volume ventilation strategy for Exosurf-, Survanta-, and sheep surfactant-treated rabbits (P < 0.05), whereas ventilation efficiency indexes (VEI) improved only for Survanta- and sheep surfactant-treated rabbits with 3 cmH2O PEEP (P < 0.01). Pressure-volume curves for sheep surfactant-treated rabbits were better than for all other treated groups (P < 0.01), although Exosurf and Survanta increased lung volumes above those in control rabbits (P < 0.05). The recovery of intravascular radiolabeled albumin in the lungs and alveolar washes was used as an indicator of pulmonary edema. Only Survanta and sheep surfactant decreased protein leaks in the absence of PEEP, whereas all treatments decreased labeled albumin recoveries when 3 cmH2O PEEP was used (P < 0.05). These experiments demonstrate that ventilation style will alter a number of measurements of surfactant function, and the effects differ for different surfactants.     

Respiratory impedances and acinar gas transfer in a canine model for emphysema

Barnas, George M., Paul A. Delaney, Ileana Gheorghiu,Srinivas Mandava, Robert G. Russell, Renée Kahn, and Colin F. Mackenzie. Respiratory impedances and acinar gas transfer in acanine model for emphysema. J. Appl.Physiol. 83(1): 179-188, 1997.We examined howthe changes in the acini caused by emphysema affected gas transfer outof the acinus (T_aci) and lungand chest wall mechanical properties. Measurements were taken from fivedogs before and 3 mo after induction of severe bilateral emphysema byexposure to papain aerosol (170-350 mg/dose) for 4 consecutive wk.With the dogs anesthetized, paralyzed, and mechanically ventilated at0.2 Hz and 20 ml/kg, we measuredT_aci by the rate of washout of¹³³Xe from an area of the lungwith occluded blood flow. Measurements were repeated at positiveend-expiratory pressures (PEEP) of 10, 5, 15, 0, and 20 cmH₂O. We also measured dynamicelastances and resistances of the lungs(EL andRL, respectively) and chest wall at the different PEEP and during sinusoidal forcing in the normal rangeof breathing frequency and tidal volume. After final measurements, tissue sections from five randomly selected areas of the lung eachshowed indications of emphysema.T_aci during emphysema was similarto that in control dogs. ELdecreased by ~50% during emphysema (P < 0.05) but did not change itsdependence on frequency or tidal volume.RL did not change(P > 0.05) at the lowest frequencystudied (0.2 Hz), but in some dogs it increased compared with control at the higher frequencies. Chest wall properties were not changed byemphysema (P > 0.05). We suggestthat although large changes in acinar structure andEL occur during uncomplicatedbilateral emphysema, secondary complications must be present to causeseveral of the characteristic dysfunctions seen in patients withemphysema.

     

Elastic moduli of excised constricted rat lungs

When airways constrict, the surrounding parenchyma undergoesstretch and distortion. Because of the mechanical interdependence between airways and parenchyma, the material properties of the parenchyma are important factors that modulate the degree ofbronchoconstriction. The purpose of this study was to investigate theeffect of changes in transpulmonary pressure (Ptp) and inducedconstriction on parenchymal bulk (k)and shear (µ) moduli. In excised rat lungs, pressure was measured atthe airway opening, and pressure-volume curves were obtained byimposing step decreases in volume with a calibrated syringe from totallung inflation. Calculation was made ofk during small-volume oscillations (1 Hz). Absolute lung volume at 0 cmH₂O Ptp was obtained bysaline displacement. To calculate µ, a lung-indentation test wasperformed. The lung surface was deformed with a cylindrical punch(diameter = 0.45 cm) in 0.25-mm increments, and the force required toeffect this displacement was measured by a weight balance. Measurementsof k and µ were obtained at 4 and 10 cmH₂O Ptp, and again at 4 cmH₂O Ptp, after delivery ofmethacholine aerosol (100 mg/ml) into the trachea. Values ofk and µ in rat lungs were similar tothose reported in other species. In addition, k and µ were dependent on Ptp. Afterinduced constriction, k and µ increased significantly. That k and µ can increase after induced constriction has important implicationsvis a vis the factors modulating airway narrowing.

     

Positive end-expiratory pressure and surfactant decrease lung injury during initiation of ventilation in fetal sheep

The initiation of ventilation in preterm, surfactant-deficient sheep without positive end-expiratory pressure (PEEP) causes airway injury and lung inflammation. We hypothesized that PEEP and surfactant treatment would decrease the lung injury from initiation of ventilation with high tidal volumes. Fetal sheep at 128-day gestational age were randomized to ventilation with: 1) no PEEP, no surfactant; 2) 8-cmH(2)O PEEP, no surfactant; 3) no PEEP + surfactant; 4) 8-cmH(2)O PEEP + surfactant; or 5) control (2-cmH(2)O continuous positive airway pressure) (n = 6-7/group). After maternal anesthesia and hysterotomy, the head and chest were exteriorized, and the fetus was intubated. While maintaining placental circulation, the fetus was ventilated for 15 min with a tidal volume escalating to 15 ml/kg using heated, humidified, 100% nitrogen. The fetus then was returned to the uterus, and tissue was collected after 30 min for evaluation of early markers of lung injury. Lambs receiving both surfactant and PEEP had increased dynamic compliance, increased static lung volumes, and decreased total protein and heat shock proteins 70 and 60 in bronchoalveolar lavage fluid compared with other groups. Ventilation, independent of PEEP or surfactant, increased mRNA expression of acute phase response genes and proinflammatory cytokine mRNA in the lung tissue compared with controls. PEEP decreased mRNA for cytokines (2-fold) compared with groups receiving no PEEP. Surfactant administration further decreased some cytokine mRNAs and changed the distribution of early growth response protein-1 expression. The use of PEEP during initiation of ventilation at birth decreased early mediators of lung injury. Surfactant administration changed the distribution of injury and had a moderate additive protective effect.     

Lung resistance and elastance in spontaneously breathing preterm infants: effects of breathing pattern and demographics

Reported values of lung resistance(RL) and elastance (EL) in spontaneouslybreathing preterm neonates vary widely. We hypothesized that thisvariability in lung properties can be largely explained by both inter-and intrasubject variability in breathing pattern and demographics.Thirty-three neonates receiving nasal continuous positive airwaypressure [weight 606-1,792 g, gestational age (GA) of25-33 wk, 2-49 days old] were studied. Transpulmonary pressure was measured by esophageal manometry and airway flow by facemask pneumotachography. Breath-to-breath changes in RL andEL in each infant were estimated by Fourier analysis ofimpedance (Z) and by multiple linear regression (MLR).RL_MLR (RL_MLR = 0.85 × RL_Z 0.43; r² = 0.95) and EL_MLR(EL_MLR = 0.97 × EL_Z + 8.4; r² = 0.98) werehighly correlated to RL_Z andEL_Z, respectively. Both RL(mean ± SD; RL_Z = 70 ± 38, RL_MLR = 59 ± 36 cmH₂O · s · l¹)and EL (EL_Z = 434 ± 212, EL_MLR = 436 ± 210 cmH₂O/l)exhibited wide intra- and intersubject variability.Regardless of computation method, RL was found to decreaseas a function of weight, age, respiratory rate (RR), and tidal volume(VT) whereas it increased as a function ofRR · VT and inspiratory-to-expiratorytime ratio (TI/TE). EL decreasedwith increasing weight, age, VT and female gender andincreased as RR and TI/TE increased. Weconclude that accounting for the effects of breathing patternvariability and demographic parameters on estimates of RLand EL is essential if they are to be of clinical value.Multivariate statistical models of RL and ELmay facilitate the interpretation of lung mechanics measurements inspontaneously breathing infants.

     

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.

     

Reliability of Single-Use PEEP-Valves Attached to Self-Inflating Bags during Manual Ventilation of Neonates – An In Vitro Study

Introduction

International resuscitation guidelines suggest to use positive end-expiratory pressure (PEEP) during manual ventilation of neonates. Aim of our study was to test the reliability of self-inflating bags (SIB) with single-use PEEP valves regarding PEEP delivery and the effect of different peak inflation pressures (PIP) and ventilation rates (VR) on the delivered PEEP.

Methods

Ten new single-use PEEP valves from 5 manufacturers were tested by ventilating an intubated 1kg neonatal manikin containing a lung model with a SIB that was actuated by an electromechanical plunger device. Standard settings: PIP 20cmH₂O, VR 60/min, flow 8L/min. PEEP settings of 5 and 10cmH₂O were studied. A second test was conducted with settings of PIP 40cmH₂O and VR 40/min. The delivered PEEP was measured by a respiratory function monitor (CO₂SMO⁺).

Results

Valves from one manufacturer delivered no relevant PEEP and were excluded. The remaining valves showed a continuous decay of the delivered pressure during expiration. The median (25^th and 75^th percentile) delivered PEEP with standard settings was 3.4(2.7–3.8)cmH₂O when set to 5cmH₂O and 6.1(4.9–7.1)cmH₂O when set to 10cmH₂O. Increasing the PIP from 20 to 40 cmH₂O led to a median (25^th and 75^th percentile) decrease in PEEP to 2.3(1.8–2.7)cmH₂O and 4.3(3.2–4.8)cmH₂O; changing VR from 60 to 40/min led to a PEEP decrease to 2.8(2.1–3.3)cmH₂O and 5.0(3.5–6.2)cmH₂O for both PEEP settings.

Conclusion

Single-use PEEP valves do not reliably deliver the set PEEP. PIP and VR have an effect on the delivered PEEP. Operators should be aware of these limitations when manually ventilating neonates.     

ET-1-induced bronchoconstriction is mediated via ETB receptor in mice

Nagase, Takahide, Tomoko Aoki, Teruaki Oka, YoshinosukeFukuchi, and Yasuyoshi Ouchi. ET-1-induced bronchoconstriction ismediated via ET_B receptor in mice.J. Appl. Physiol. 83(1): 46-51, 1997.Endothelin (ET)-1 is one of the most potent agonists of airwaysmooth muscle and can act via two different ET receptor subtypes, i.e.,ET_A andET_B. To determine the effects ofET-1 on in vivo pulmonary function and which ET receptors are involved in murine lungs, we investigated 1)the effects of ET and sarafotoxin S6c (S6c), a selectiveET_B agonist, on pulmonary functionand 2) the effects of BQ-123 andBQ-788, specific ET_A- andET_B-receptor antagonists, onET-1-induced bronchoconstriction. ICR mice were anesthetized and mechanically ventilated (frequency = 2.5 Hz, tidalvolume = 8 ml/kg, positive end-expiratory pressure = 3 cmH₂O). Intravenous ET-1, ET-2,and ET-3 increased lung resistance similarly and equipotently, whereasS6c elicited a greater degree of bronchoconstriction. Mice were thenpretreated with saline (Sal), BQ-123 (0.2, 1, and 5 mg/kg), or BQ-788(0.2, 1, and 5 mg/kg) before administration of ET-1(10⁷ mol/kg iv). No dose ofBQ-123 blocked ET-1-induced constriction, whereas pretreatment witheach dose of BQ-788 significantly inhibited ET-1-induced responses.There were significant differences in morphometrically assessed airwayconstriction between Sal and BQ-788 and between BQ-123 and BQ-788,whereas no significant difference was observed between Sal and BQ-123.There were no significant morphometric differences in the airway wallarea among the three groups. These observations suggest that theET_B- but notET_A-receptor subtype may mediatethe changes in murine pulmonary function in response to ET-1. Inaddition, the ET_B-receptorantagonist reduces ET-1-induced airway narrowing by affecting airwaysmooth muscle contraction in mice.

     

Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier

Jerome, E. Heidi, Keiji Enzan, Dominique Douguet, DachuanLei, Gary Jesmok, Carol W. Johnson, Maritza Neuburger, and Norman C. Staub. Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier.J. Appl. Physiol. 81(4):1730-1738, 1996.Interleukin-2 (IL-2) is reputed tocause a "vascular leak syndrome." We studied pulmonaryhemodynamics and lymph dynamics in six sheep treated for 7 days withIL-2 (1.8 million IU/kg twice daily or 1.8 million IU/kg each day as acontinuous infusion). Lung lymph flow increased from 4.8 ± 2 ml/15min pre-IL-2 to 14.4 ± 6.8 ml/15 min on the seventh day of IL-2.The lymph-to-plasma protein concentration ratio was unchanged (0.70 ± 0.06 vs. 0.63 ± 0.13). The plasma-to-lymph equilibrationhalf-time of radiolabeled albumin was 2.0 ± 0.6 h pre-IL-2 and 1.0 ± 0.7 h on day 7 of IL-2. Pulmonary arterial pressure was 24 ± 7 cmH₂O pre-IL-2, increased to 32 ± 4 cmH₂O on the fourth day ofIL-2, and returned to 29 ± 5 cmH₂O on the seventh day of IL-2.Extravascular lung water was normal (4.07 ± 0.25 g/g dry lung). Toclearly determine whether the increase in lung lymph flow was due tohemodynamic changes or to increased leakiness of the microvascularbarrier, we volume loaded six sheep with lactated Ringer solutionbefore and after 3 days of IL-2 treatment (1.8 million IU/kg twicedaily). Lung lymph flows increased fivefold during 4 h of crystalloidinfusion compared with baseline and were higher after 3 days of IL-2.However, lymph-to-plasma protein concentration ratios decreased to the same low levels pre- and post-IL-2 (0.39 ± 0.06 vs. 0.41 ± 0.10), indicating an intact microvascular barrier. Extravascular lung water was elevated (5.56 ± 0.39 g/g dry lung) but was not different from lung water in three volume-loaded control sheep (4.87 ± 0.53 g/g dry lung). We conclude that IL-2 causes minimal or no injury to thepulmonary microvascular barrier and that volume expansion during IL-2treatment can cause hydrostatic pulmonary edema.