title: The effect of a peptide-containing synthetic lung surfactant on gas exchange and lung mechanics in a rabbit model of surfactant depletion.
abstract: BACKGROUND
  Currently, a new generation of synthetic pulmonary surfactants is being developed that may eventually replace animal-derived surfactants used in the treatment of respiratory distress syndrome. Enlightened by this, we prepared a synthetic peptide-containing surfactant (Synsurf) consisting of phospholipids and poly-l-lysine electrostatically bonded to poly-l-glutamic acid. Our objective in this study was to investigate if bronchoalveolar lavage (BAL)-induced acute lung injury and surfactant deficiency with accompanying hypoxemia and increased alveolar and physiological dead space is restored to its prelavage condition by surfactant replacement with Synsurf, a generic prepared Exosurf, and a generic Exosurf containing Ca(2+).
  
  
  METHODS
  Twelve adult New Zealand white rabbits receiving conventional mechanical ventilation underwent repeated BAL to create acute lung injury and surfactant-deficient lung disease. Synthetic surfactants were then administered and their effects assessed at specified time points over 5 hours. The variables assessed before and after lavage and surfactant treatment included alveolar and physiological dead space, dead space/tidal volume ratio, arterial end-tidal carbon dioxide tension (PCO2) difference (mainstream capnography), arterial blood gas analysis, calculated shunt, and oxygen ratios.
  
  
  RESULTS
  BAL led to acute lung injury characterized by an increasing arterial PCO2 and a simultaneous increase of alveolar and physiological dead space/tidal volume ratio with no intergroup differences. Arterial end-tidal PCO2 and dead space/tidal volume ratio correlated in the Synsurf, generic Exosurf and generic Exosurf containing Ca(2+) groups. A significant and sustained improvement in systemic oxygenation occurred from time point 180 minutes onward in animals treated with Synsurf compared to the other two groups (P < 0.001). A statistically significant decrease in pulmonary shunt (P < 0.001) was found for the Synsurf-treated group of animals, as well as radiographic improvement in three out of four animals in that group.
  
  
  CONCLUSIONS
  In general, surfactant-replacement therapy in the animals did not fully restore the lung to its prelavage condition. However, our data show that the formulated surfactant Synsurf improves oxygenation by lowering pulmonary shunt.
authors.affiliation: Division of Pharmacology, Cape Town, South Africa. jmvzyl@sun.ac.za
authors.forename: Johann M
authors.initials: JM
authors.lastname: van Zyl
authors.forename: Johan
authors.initials: J
authors.lastname: Smith
authors.forename: Arthur
authors.initials: A
authors.lastname: Hawtrey
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002118:Calcium / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010767:Phosphorylcholine / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D012126:Respiratory Dead Space / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D013997:Time Factors
chemical_list: D004338:Drug Combinations; D005233:Fatty Alcohols; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D010100:Oxygen; D002118:Calcium
keywords: capnometry; oxygenation; pulmonary gas exchange; pulmonary surfactant; respiratory dead space; synthetic peptides