title: The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits.
abstract: 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.
  
  
  OBJECTIVE
  To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency.
  
  
  METHODS
  30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO2 = 0.8, PEEP = 7cmH2O) and randomized into three groups: Normoventilation-Normocapnia (NN)-group: tidal volume (Vt) = 7.5 ml/kg, target PaCO2 = 40 mmHg; Normoventilation-Hypercapnia (NH)-group: Vt = 7.5 ml/kg, target PaCO2 = 80 mmHg by increasing FiCO2; and a Hypoventilation-Hypercapnia (HH)-group: Vt = 4.5 ml/kg, target PaCO2 = 80 mmHg. Plasma lactate and interleukin (IL)-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL), to measure lung wet-to-dry weight, lung tissue IL-8, and to obtain lung histology.
  
  
  RESULTS
  PaO2 was significantly higher in the HH-group compared to the NN-group (p<0.05), with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8) resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH-group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group.
  
  
  CONCLUSIONS
  Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO2 tensions and pH alone.
authors: Division of Neonatology and Pediatric Critical Care, Department of Pediatrics, Children's Hospital, Ulm University, 89070 Ulm, Germany.
authors: Helmut D
authors: HD
authors: Hummler
authors: Division of Neonatology and Pediatric Critical Care, Department of Pediatrics, Children's Hospital, Ulm University, 89070 Ulm, Germany.
authors: Katharina
authors: K
authors: Banke
authors: Departments of Physiology, Medicine and Pediatrics, CENTRe: Collaborative for Environmental and Neonatal Therapeutics Research; Temple Lung Center; Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors: Marla R
authors: MR
authors: Wolfson
authors: Pediatric Neonatology Unit, Department of Molecular and Developmental Medicine, University Hospital of Siena, Siena, Italy.
authors: Giuseppe
authors: G
authors: Buonocore
authors: Institute for Pathology, Medizinisches Versorgungszentrum, Staedtisches Krankenhaus Kiel, Germany.
authors: Michael
authors: M
authors: Ebsen
authors: Department of Neonatology, Children's Hospital, University of Tuebingen, Tuebingen, Germany.
authors: Wolfgang
authors: W
authors: Bernhard
authors: Centre of Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany.
authors: Dimitrios
authors: D
authors: Tsikas
authors: Division of Neonatology and Pediatric Critical Care, Department of Pediatrics, Children's Hospital, Ulm University, 89070 Ulm, Germany.
authors: Hans
authors: H
authors: Fuchs
mesh_terms: D000142:Acidosis, Respiratory / Q000209:etiology* / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D006439:Hemodynamics; D006935:Hypercapnia / Q000150:complications*; D055370:Lung Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D011663:Pulmonary Surfactants; D011817:Rabbits; D012121:Respiration, Artificial / Q000379:methods; D013990:Tidal Volume
chemical_list: D015415:Biomarkers; D011663:Pulmonary Surfactants