title: Role of poly-(ADP-ribose) synthetase in lipopolysaccharide-induced vascular failure and acute lung injury in pigs.
abstract: OBJECTIVE
  To assess the contribution of poly (adenosine 5'-diphosphate ribose) synthetase (PARS) to the development of bacterial lipopolysaccharide (LPS)-induced acute lung injury and vascular failure in pigs.
  
  
  METHODS
  Four groups of anesthetized, paralyzed, and mechanically ventilated domestic white pigs. Group 1 served as control, whereas Escherichia coli LPS (20 microg/kg/h) was continuously infused in group 2. Group 3 received 20 mg/kg injection of 3-aminobenzamide (a selective inhibitor of PARS activity) 15 minutes before LPS infusion. Only 3-aminobenzamide and not LPS was injected in group 4. All animals were examined for 180 minutes. Systemic and pulmonary hemodynamics and lung mechanics were measured during the experimental period. Lung wet/dry ratio, bronchoalveolar lavage (BAL) protein levels and cell counts and lung nitrotyrosine (footprint of peroxynitrite) immunostaining were also measured in a few animals.
  
  
  RESULTS
  LPS infusion evoked a progressive decline in systemic arterial pressure, a small increase in cardiac output, and biphasic elevation of pulmonary arterial pressure. Lung compliance declined progressively, whereas lung and total respiratory resistance rose significantly after LPS infusion. Prominent nitrotyrosine immunostaining was detected around small airways and pulmonary endothelium of LPS-infused animals. No significant changes in lung wet/dry ratio and BAL protein levels and cell counts were produced by LPS infusion. Pretreatment with 3-aminobenzamide did not alter the systemic and pulmonary hemodynamic responses to LPS infusion but eliminated the rise in pulmonary and total respiratory resistance.
  
  
  CONCLUSIONS
  We concluded that PARS activation plays an important role in the changes of lung mechanics associated with LPS-induced acute lung injury but had no role in vascular failure.
authors.affiliation: Istituto di Fisiologia Veterinaria e Biochemica, Università degli Studi di Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Albertini
authors.forename: M G
authors.initials: MG
authors.lastname: Clement
authors.forename: C L
authors.initials: CL
authors.lastname: Lafortuna
authors.forename: M
authors.initials: M
authors.lastname: Caniatti
authors.forename: S
authors.initials: S
authors.lastname: Magder
authors.forename: K
authors.initials: K
authors.lastname: Abdulmalek
authors.forename: S N
authors.initials: SN
authors.lastname: Hussain
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D011506:Proteins / Q000032:analysis; D011652:Pulmonary Circulation / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000201:enzymology* / Q000382:microbiology* / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects; D012772:Shock, Septic / Q000150:complications* / Q000201:enzymology* / Q000503:physiopathology; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011506:Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases