RESEARCH ARTICLEThe Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits Helmut D.Hummler 1*,Katharina Banke 1,Marla R.Wolfson 2,Giuseppe Buonocore 3,Michael Ebsen 4,Wolfgang Bernhard 5,Dimitrios Tsikas 6,Hans Fuchs 11Division of Neonatology and Pediatric Critical Care,Department of Pediatrics,Children ’s Hospital,Ulm University,89070Ulm,Germany,2Departments of Physiology,Medicine and Pediatrics,CENTRe :Collaborative for Environmental and Neonatal Therapeutics Research;Temple Lung Center;Center forInflammation,Translational and Clinical Lung Research,Temple University School of Medicine,Philadelphia,Pennsylvania,United States of America,3Pediatric Neonatology Unit,Department of Molecular andDevelopmental Medicine,University Hospital of Siena,Siena,Italy,4Institute for Pathology,Medizinisches Versorgungszentrum,Staedtisches Krankenhaus Kiel,Germany,5Department of Neonatology,Children ’s Hospital,University of Tuebingen,Tuebingen,Germany,6Centre of Pharmacology and Toxicology,Hannover Medical School,Hannover,Germany*helmut.hummler@uni-ulm.deAbstract Background Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency.Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor.Objectives To study the differential effects of a lung protective ventilatory strategy or hypercapnic aci-dosis on gas exchange,hemodynamics and lung injury in an animal model of surfactant deficiency.Methods 30anesthetized,surfactant-depleted rabbits were mechanically ventilated (FiO 2=0.8,PEEP =7cmH 2O)and randomized into three groups:Normoventilation-Normocapnia (NN)-group:tidal volume (Vt)=7.5ml/kg,target PaCO 2=40mmHg;Normoventilation-Hypercap-nia (NH)-group:Vt =7.5ml/kg,target PaCO 2=80mmHg by increasing FiCO 2;and a Hypo-ventilation-Hypercapnia (HH)-group:Vt =4.5ml/kg,target PaCO 2=80mmHg.Plasma lactate and interleukin (IL)-8were measured every 2h.Animals were sacrificed after 6h to perform bronchoalveolar lavage (BAL),to measure lung wet-to-dry weight,lung tissue IL-8,and to obtain lunghistology.PLOS ONE |DOI:10.1371/journal.pone.0147807February 3,20161/16OPEN ACCESSCitation:Hummler HD,Banke K,Wolfson MR,Buonocore G,Ebsen M,Bernhard W,et al.(2016)The Effects of Lung Protective Ventilation orHypercapnic Acidosis on Gas Exchange and LungInjury in Surfactant Deficient Rabbits.PLoS ONE 11(2):e0147807.doi:10.1371/journal.pone.0147807Editor:Edgardo Szyld,Icahn School of Medicine atMount Sinai,ARGENTINAReceived:June 23,2015Accepted:January 8,2016Published:February 3,2016Copyright:©2016Hummler et al.This is an openaccess article distributed under the terms of theCreative Commons Attribution License ,which permitsunrestricted use,distribution,and reproduction in anymedium,provided the original author and source arecredited.Data Availability Statement:All relevant data arewithin the paper and its Supporting Information file.Funding:Work performed in this study wassupported in part by the Department of Defense/Office of Naval Research N000141210597andN000141210810(MRW).Competing Interests:The authors have declaredthat no competing interests exist.
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