Acute Respiratory Distress Syndrome: Cellular and Molecular Mechanisms and Clinical Management PDF
Preview Acute Respiratory Distress Syndrome: Cellular and Molecular Mechanisms and Clinical Management
Acute Respiratory Distress Syndrome Cellular and Molecular Mechanisms and Clinical Management NATO ASI Series Advanced Science InstitutesSeries Aseriespresenting the results of activitiessponsoredby the NATOScience Committee, which aims at thedissemination ofadvanced scientificand technologicalknowledge, with a view tostrengthening links between scientificcommunities. The series is published by an internationalboardof publishersin conjunctionwith the NATOScientificAffairsDivision A LifeSciences Plenum PublishingCorporation B Physics NewYorkandLondon C Mathematical KluwerAcademic Publishers andPhysical Sciences Dordrecht,Boston,and London D BehavioralandSocialSciences E Applied Sciences F Computer andSystemsSciences Springer-Verlag G Ecological Sciences Berlin, Heidelberg,NewYork,London, H CellBiology Paris,Tokyo,HongKong,and Barcelona I GlobalEnvironmental Change PARTNERSHIPSUB-SERIES 1.DisarmamentTechnologies KluwerAcademic Publishers 2.Environment Springer-Verlag 3.High Technology KluwerAcademic Publishers 4.ScienceandTechnologyPolicy KluwerAcademic Publishers 5.ComputerNetworking KluwerAcademic Publishers ThePartnership Sub-Series incorporates activities undertaken incollaboration with NATO's Cooperation Partners, thecountries of the CISand Central and Eastern Europe, in PriorityAreas ofconcern to those countries. Recent Volumes in this Series: Volume295- PrionsandBrainDiseases inAnimalsandHumans editedbyDouglasR.O.Morrison Volume296- FreeRadicals, Oxidative Stress, andAntioxidants: Pathological and PhysiologicalSignificance editedbyTomrisOzben Volume297- AcuteRespiratory DistressSyndrome:CellularandMolecular MechanismsandClinicalManagement editedbySadisMatalon andJacoblashaSznajder Volume298- Angiogenesis:Models,Modulators, andClinicalApplications editedbyMichaelE.Maragoudakis SeriesA:LifeSciences Acute Respiratory Distress Syndrome Cellular and Molecular Mechanisms and Clinical Management Edited by Sadis Matalon The University ofAlabama at Birmingham Birmingham, Alabama and Jacob lasha Sznajder Universityof Illinois atChicago Chicago, Illinois Plenum Press NewYorkandLondon Published incooperation withNATO Scientific Affairs Division Proceedings ofaNATOAdvancedStudy Instituteon Acute Respiratory Distress Syndrome: Cellular and Molecular Mechanisms and Clinical Management, heldJune 15-25, 1997, inCorfu, Greece NATO-PCO-DATABASE The electronic index to the NATO ASI Series provides full bibliographical references (with keywords and/or abstracts) to about 50,000 contributions from international scientists published in all sections of the NATOASISeries.Accessto the NATO-PCO-DATA BASE is possible via a CD-ROM "NATO Science and Technology Disk" with user-friendly retrieval software inEnglish, French,andGerman (©WTVGmbHandDATAWARETechnologies, Inc. 1989).TheCD-ROMcontainstheAGARDAerospace Database. The CD-ROM can be ordered through any member of the Board of Publishers or through NATO-PCO,Overijse, Belgium. Ltbrary of Congress Catalogtng-tn-Pub1tcatton Olta Acute resp1ratoiY distress syndrole cellular and acIecutar- 119chan1SiS and c11n1ca1"Inage.ent I adtted by Sad1s Mata1on and Jacob lasha SznaJder. p. co. -- (NATOASI serIes. SerIes A. LIfe sciences : v, 297) "ProceedIngs of a NATOAdvanced Study InstItute on Acute RespIratory DIstress Syndroee, CeIlular and Molecular MechanIus and Cllntcal Manageeent. heId June 15-25. 1997. In Corfu. Greece"--T.p, verso. Inctudes btbfiographtea1references and Index. ISBN 0-306-45830-6 1. Rasp1ratory dIstress syndrole. Adu1t--Pathophys10logy -Congresses. 2. Respiratory dtstress syndrolle. Adult--Treatllent- -Congresses. I. Matalon. Sad1s. II. Sznajder, Jacob lasha. III. NATO Advanced Study Institute on Acute Resp1ratory Dtstress Syndrolle: Ce1'u'ar and MoJecuJar Meehan1SIiS and elln1caJManage.ent (1997 : Kerkyra. Greece) IV. Ser1es. [DllLM, 1. Resp1rotory 0Istress Syndrole. AduIt--physlopathology congresses. 2. Resp1ratory Distress Syndrolle. AduJt--drug therapy congresses. HF 140 A18347 19981 RC776.R38A2798 1998 616.2'4--dc21 DNLM/DLC for Library of Congress 98-17227 CIP ISBN 0-306-45830-6 ©1998Plenum Press,NewYork ADivision of Plenum PublishingCorporation 233SpringStreet, NewYork,N.Y.10013 http://www.plenum.com 10987654321 Allrights reserved Nopartofthis book maybereproduced, stored inaretrieval system,ortransmitted inany formorbyany means,electronic, mechanical,photocopying, microfilming, recording,or otherwise,without written permissionfromthePublisher FOREWORD Acute lunginjury,respiratoryfailure, andacute respiratorydistresssyndromeassoci atedwithsepsisandmultiorgandysfunctionisbecomingmorecommoninhospitalsthrough outtheworld. Althoughnewclassesofantimicrobialmedicationshavebeen introducedand aggressive intensive life supportsystemsare inuse inmany hospitals, mortality remains in therange of35to65percentineventhebestequippedmedicalfacilities. However,with new technologiesinphysiologyandcellularandmolecularbiology, wonderfulopportunitiesnow existforscientiststoexploremoreeffective approachestoidentificationofpatientsatrisk, to developbetterinsightstopathogenicmechanisms,tousenewtoolstofollow theprogression and natural historyofdisease,and to develop bettermodes oftherapies. The NATOAdvancedStudy InstituteonAcuteRespiratoryDistressSyndrome:Cel lularandMolecularMechanismsandClinicalManagementwasanoutstandingopportunity for laboratoryscientistsandclinical investigatorstodiscusstheir ownresearchapproaches, exploreopportunitiesforbringingnewdimensionstotheir laboratories,andworktogetherto identify possible clinical applications. The conference brought together investigators who have worked with patientsofall ages,includingthose who have sosuccessfullytreated in fants with respiratorydistresssyndrome. There isnodoubt that this stimulatingconference will bring newdimensions,newtechnologies,andnewinvestigatorsinto thescientificlabo ratoriesofeachparticipant.Thisprovideshopethatnewtherapeuticapproacheswilleventu ally be available. ItwasaspecialprivilegethattheNATOorganizersincludedrepresentativesfrom the National Heart, Lung, and Blood Institute, National InstitutesofHealth. Wewere most im pressedwith thepresentationsand thescientificinteractionsthat took place betweenthe at tendees. Claude Lenfant, M.D. Suzanne S.Hurd, Ph.D. Director, National Heart, Lung, and Blood Director, Division ofLung Diseases Institute National InstitutesofHealth National Heart, Lung,and Blood Institute Bethesda, Maryland National InstitutesofHealth Bethesda, Maryland v PREFACE Thismonographcontainsthecontributionsofinvited speakersandparticipantsatthe NATOAdvancedStudy InstituteonAcuteRespiratoryDistressSyndrome:CellularandMo lecular Mechanisms and Clinical Management, held in Corfu, Greece from June 15-25, 1997. The Advanced Study Institute provided a unique opportunity for internationally knownbasic scientistsandclinicianswithexpertiseinvariousaspectsoflunginjuryand re pair to exchange ideas on the pathophysiology and treatment ofAcute Lung Injury.There were25invitedspeakersand65studentsrepresenting 14countries.Someofthemostnotable contributionsofthis symposiumare outlinedbelow: Role ofNitric Oxide ("NO)in the treatmentofAcute Respiratory Distress Syn drome (ARDS). Currently, there is considerable controversy as to whether nitric oxide shouldbeadministeredtopatientswithARDS. Therewasalivelydebateontheuseof-NOin the treatmentofARDS with extensiveaudience participation.Several studies, mostly from European centers, summarized data on the use ofnitric oxide ("NO) in the treatment of ARDS.Althoughtheearlierreportswereencouraging,more recentdata fromseveralcenters show that administration of-NOdid not improve morbidity or mortality ofpatients with ARDS.Therewasconcernwith thethefactthatcessationof-NOtreatmentledtodramaticin creasesinthe pulmonarycirculationpressure,thus makingitdifficulttowean patientsfrom thistype oftherapy. Furthermore,anumberofpresentationsfrombasic scientistspointedout that reactive oxygen-nitrogen intermediates, produced by the reaction of-NO with oxygen free radicals, releasedby inflammatorycells,may damagethe pulmonarysurfactantsystem and alveolartype IIcells.It was agreed that although ashort course of-NO administration may prove beneficial in selective patients by improving oxygenation, its long-term use should be discouraged without additional data providing definitive evidence for decreased mortalityand morbidityand lack oftoxicity.On the otherhand,the use ofprostacyclinthat also has pulmonaryvasculardilationeffectsappears toshow beneficial effectsthat warrant further investigation inthis area. Importanceofactiveion transportacrossthe alveolarepithelium in enhancing theclearanceofalveolaredemain ARDS. Anumberofexcitingpresentationsfocusedon thecellularand molecularmechanismsofion transportacrossthealveolarepithelium.Dis cussionshelpedtoreconcileexistingcontroversieson thecontributionofvarioustransport ers influid clearanceacrossthealveolarepitheliumofanimalswith oxidantlung injury.One ofthe mostexcitingaspectsofthis meeting was the presentationofdata indicatingthat up regulationofiontransportacrossthealveolarepitheliumofpatientswith ARDS and inani mals with ARDS-type injury,using inotropic drugs such as isoproterenol, dobutamine and dopamine,decreasedtheamountofpulmonaryedemaand improvedoxygenation.Thisisan excitingdevelopmentand may have asignificant impact inthe treatmentofARDS. Drugdeliveryto theinjuredalveolarepithelium.Thereisconsiderableinterestin identifying agents that can improve the delivery ofvarious drugs (such as antioxidant en- vii zymes, anti-inflammatory compounds, etc.) to the alveolar epithelium of patients with ARDS.IthasbeenknownthatsurfactantdeficiencycontributestothedevelopmentofARDS andthat surfactantreplacementhasbeen efficaciousinimprovinglungmechanicsand oxy genationinboth animalsandpatientswithARDS.Excitingnewevidencefrom anumberof laboratoriesindicatethatsurfactantdeliverymixtures,alreadyusedforthecorrectionofsur factant deficiencyinneonates,greatlyimprove thedelivery ofanantioxidantenzymetothe alveolarepitheliumofnewbornanimals.Also, there were anumberofimportantpresenta tions discussing strategies for gene delivery to the alveolarepithelium.Evidence was pre sentedthatanewfamily ofpolycationicaminopolymercompoundsisextremelyefficientin transferringgenes toanumberofcelllines.Therewasconsiderableinterestintestingtheef ficacyofthese compoundsinanimals withlunginjuryresemblingARDS. Thesecompounds maycircumventsomeoftheproblemsassociatedwithadenoviruses,suchaslunginflamma tion, and may renderthe lung more resistanttooxidantinjury. Controversies in the clinical management of patients with ARDS. There was a lively debate on the advantages and disadvantages ofventilating patients with low versus high tidal volume. Large tidal volumes appear to compound the pre-existing lung injury, causingincreasedpermeabilityandpulmonaryedema. Inaddition,there were excitingpres entationsonventilatingbothanimalsandpatientswithARDSusingperfluorocarbons(liquid breathing).There were several suggestionsforadditionalexperimentstobetterdemonstrate theefficacyofthispotentiallyexcitingformoftreatmentinARDS.Plansweredevelopedfor anindustry-sponsoredmulticentertrialtosystematicallyexplore theabilitytopartiallyven tilate ARDS patientswithperfluorocarbonsanddeterminetheefficacyofthisform:ofventi lationbymeasuringphysiologicvariablesandchangesinmortality. Inaddition,studiesfrom several investigators summarized novel approaches to mechanical ventilation ofpatients with ARDS among which trachealgasinsufflationandprone positioning are being increas ingly utilizedwith encouragingresults.Severalpresentationsalso dealtwith thepotentially damagingeffects ofexcessivetidal volume ventilationon the lungs. Perhaps the best aspects ofthis symposiumwere the lively interactions among the participants and the fact that several newcollaborationswere establishedamong scientists and clinicians who previously knew each other only byreputation. The organizerswould liketotake thisopportunitytothank themembersofthe local organizing committee, Drs.Behrakis, Baltopoulos, and Chainis for all their hard work and encouragement.WewouldalsoliketothankHisExcellency, theGovernorofCorfu,Mr.An dreas Pagrates,His Excellency,the Mayor ofCorfu, Mr.Chrysanthos Sarles, His Holiness, theMetropolitanofCorfu, Mr.Timotheo,thePresidentoftheGeneralHospitalofCorfu,Dr. KostasAlexandropoulos,TheTownCouncilofCorfu, andthecitizensofCorfu fortheir gen erosityand hospitality.Special thanks toMr.Spyros Lychnos for working day andnight to ensurethat all participantsarrived inCorfu safe andsound and forhandlingthe myriadad ministrativedetails.Finally,wewould liketothank Ms.Nancy MatalonandMs.Mary Beth Campbell fortheir superbeditorial assistance inputting this volume together. Wewant tooffer special thanks toourcorporatesponsorslisted below.Theirgener ous contributionshelpedmaketheconferenceasuccessandprovidedsupportforadditional activities. • Alliance Pharmaceutical Corporation,San Diego, CA, USA • AmGen, Inc., Thousand Oaks, CA,USA • AmSouth Bank, Birmingham,AL,USA • Avanti PolarLipids, Inc.,Alabaster,AL,USA • Biotechnology General Corporation, Iselin, NJ, USA • Byk Gulden,LombergChemischeFabrik GmbH, Germany • Ciba-Geiga,Anthousaa, Greece • General Hospital ofCorfu, Greece viii • Glaxo-Wellcome, Halandri,Greece • Eli Lilly Pharmaceuticals, Athens,Greece • HewlettPackard,Andover, MA,USA • HoechstMarionRoussel, Bridgewater, NJ,USA • Rhone PoulenceRorer, Athens,Greece • Ross ProductsDivision,Abbott Laboratories, Columbus, OH, USA • SmithKlineBeechamPharmaceuticals,Lisle, IL,USA • Wyeth Hellas E.P.E.,Argyroupolis, Greece Dr.Sadis Matalon Dr.Jacob Iasha Sznajder ProfessorofAnesthesiology,Physiology ProfessorofMedicine Pulmonaryand and Biophysicsand Pediatrics Critical Care Medicine University ofAlabamaat Birmingham University ofIllinois atChicago and Birmingham,Alabama Columbia Michael Reese Hospital Chicago, Illinois ix CONTENTS SECTION 1:SODIUM(Na+)TRANSPORTANDFLUID CLEARANCE ACROSS THE NORMAL ANDINJURED LUNGS Regulation ofthe Sodium Pump in Hyperoxic Lung Injury . David H.Ingbar, Joseph M.Lasnier, O.Douglas Wangensteen, and Christine H.Wendt Lung Edema Clearance during Hyperoxic Lung Injury 13 Jacob Iasha Sznajderand Karen M.Ridge The Role ofLung Lymphatics in PulmonaryEdema Clearance " 19 Kyriakos D.Chainis,Karen M.Ridge,Jacob 1.Sznajder, and Dean Schraufnagel MolecularBiologyofLung Na+Absorption " 25 Pascal Barbry Regulation ofAlveolarSodium Transport byHypoxia " 36 Carole Planes and Christine Clerici Vectorial Movement ofSodiuminLung AlveolarEpithelium:Role and Regulation ofNa+,K-ATPase 45 Alejandro M.Bertorello,Karen Ridge,GoichiOgimoto,Guillermo Yudowski, Adrian I. Katz, and Jacob Iasha Sznajder The Premature Infant's Inability toClear Fetal Lung Liquid Results inRespiratory Distress Syndrome (RDS) 53 Hugh M.O'Brodovich Role ofMatrixMacromolecules inControlling Lung Fluid Balance: Transition from aDry Tissue toEdema** ......................................... 65 DanielaNegrini and Giuseppe Miserocchi Role ofthe Na+-K+-ATPase u Subunit inLung Liquid Clearance** 69 2 Karen M. Ridge, Walter Olivera,David H.Rutschmann,Stuart Horowitz, Phillip Factor,and Jacob Iasha Sznajder **indicates shortcommunicationfromparticipants. xi AveolarEpithelial Fluid Transportunder Normal and Pathological Conditions 71 Michael A. Matthay, Colleen Horan,Chun-Xue Bai,and Yibing Wang SECTION 2: ROLE OF THE PULMONARY SURFACTANTIN THE PATHOGENESIS ANDTREATMENTOF ARDS Host DefenseCapacitiesofPulmonary Surfactant 87 Ulrich Pison and Sylvia Pietschmann AlterationsofPulmonary Surfactant inARDS--Pathogenic Role and Therapeutic Perspectives ........................................................ 97 A. Gunther, D. Walrnrath,F.Grimminger,and W.Seeger SurfactantReplacement inPatientswith ARDS: ResultsofClinical Trials 107 Roger G.Spragg and Robert M. Smith Potential Role for Pulmonary SurfactantinLung Transplantation ................. 117 Fred Possmayer, RichardJ. Novick, Ruud A.W.Veldhuizen, John Lee, David Bjameson,and Jim F.Lewis PreparationofSurfactantand LipidVectorsforDelivery ofProteins and Genes to Tissue 125 Walter Shaw and Steve Burgess RecombinantSP-C Based SurfactantCan Improve Lung Function inSaline Lavaged Sheep** 133 Ruud Veldhuizen,Lynda McCaig,Li-Juan Yao,Carolyn Kerr,YushiIto, Jaret Malloy,and Jim Lewis SECTION3: MECHANISMS ANDMODIFICATION OF ACUTE AND CHRONIC LUNG INJURY Gene Therapy forthe Acute Respiratory Distress Syndrome 135 Philip Factor The Use ofRecombinantAntioxidants inNeonatalRespiratory Distress Syndrome .. 143 Jonathan M. Davis The Early InflammatoryResponse inAcute Respiratory Distress Syndrome (ARDS) 153 Nikhil Hirani and Seamas C.Donnelly The N-Nitroso-N-Methylurethane Induced Acute Lung Injury Animal Model for ARDS: Minireview " 159 Wilhelm S.Cruz and Michael A.Moxley Hyperoxia InducedFibrosis inARDS and Bpd:CurrentPathologyand Cytokine Profiles 165 JacquelineJ. Coalson,TheresaM.Siler-Khodr,VickiT.Winter,and BradleyA.Yoder xii
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