title: Pulmonary vascular dysfunction induced by high tidal volume mechanical ventilation.
abstract: OBJECTIVE
  Acute lung injury and acute respiratory distress syndrome are characterized by increased pulmonary artery pressure and ventilation-perfusion mismatch. We analyzed the changes in the pulmonary vascular function in a model of ventilator-induced acute lung injury.
  
  
  METHODS
  Controlled in vivo laboratory study.
  
  
  METHODS
  Animal research laboratory.
  
  
  METHODS
  Anesthetized male Sprague-Dawley rats.
  
  
  METHODS
  Rats were ventilated for 120 minutes using low tidal volume ventilation (control group, tidal volume 9 mL/kg, positive end-expiratory pressure 5 cm H2O, n = 15), high tidal volume ventilation (high tidal volume group, tidal volume 25 mL/kg, zero positive end-expiratory pressure, n = 14), or high tidal volume ventilation plus the poly-(adenosine diphosphate-ribose) polymerase inhibitor 3-aminobenzamide (10 mg/kg IP, high tidal volume group + 3-aminobenzamide group, n = 7). Vascular rings from small pulmonary arteries were mounted in a myograph for isometric tension recording. Lung messenger RNA and protein expression were analyzed by reverse transcriptase-polymerase chain reaction and Western blot, respectively.
  
  
  RESULTS
  High tidal volume ventilation impaired phenylephrine- and acetylcholine-induced responses in pulmonary arteries in vitro, which were accompanied by induction of inducible nitric oxide synthase messenger RNA and protein. These effects, as well as hypoxemia and hypotension, were prevented by 3-aminobenzamide. Hypoxic pulmonary vasoconstriction and responses to exogenous sphingomyelinase were increased, whereas the responses to serotonin, Kv current density, and inhibition of Kv currents by hypoxia were unaffected by high tidal volume.
  
  
  CONCLUSIONS
  High tidal volume ventilation-induced pulmonary vascular dysfunction was characterized by reduced alpha-adrenergic-induced vasoconstriction, reduced endothelium-dependent vasodilatation, and enhanced hypoxic pulmonary vasoconstriction.
authors.affiliation: Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Menendez
authors.forename: Leticia
authors.initials: L
authors.lastname: Martinez-Caro
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nin
authors.forename: Javier
authors.initials: J
authors.lastname: Moral-Sanz
authors.forename: Daniel
authors.initials: D
authors.lastname: Morales
authors.forename: Angel
authors.initials: A
authors.lastname: Cogolludo
authors.forename: Andres
authors.initials: A
authors.lastname: Esteban
authors.forename: Jose A
authors.initials: JA
authors.lastname: Lorente
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007022:Hypotension / Q000503:physiopathology / Q000517:prevention & control; D000860:Hypoxia / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D009213:Myography; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods; D011651:Pulmonary Artery / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013990:Tidal Volume / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D055397:Ventilator-Induced Lung Injury / Q000503:physiopathology*
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; C025160:3-aminobenzamide; D019001:Nitric Oxide Synthase