title: Inhaled prostacyclin reduces cardiopulmonary bypass-induced pulmonary endothelial dysfunction via increased cyclic adenosine monophosphate levels.
abstract: OBJECTIVE
  Cardiopulmonary bypass triggers a systemic inflammatory response that alters pulmonary endothelial function, which can contribute to pulmonary hypertension. This study was designed to demonstrate that inhaled prostacyclin, a selective pulmonary vasodilator prostaglandin, prevents pulmonary arterial endothelial dysfunction induced by cardiopulmonary bypass.
  
  
  METHODS
  Three groups of Landrace swine were compared: control without cardiopulmonary bypass (control group); 90 minutes of normothermic cardiopulmonary bypass (bypass group); 90 minutes of cardiopulmonary bypass and treated with prostacyclin during cardiopulmonary bypass (continuous nebulization with continuous positive airway pressure until the end of the cardiopulmonary bypass; prostacyclin group). After 60 minutes of reperfusion, swine were put to death and pulmonary arteries harvested. After contraction to phenylephrine, endothelium-dependent relaxation to bradykinin and acetylcholine was studied in standard organ chamber experiments. The pulmonary artery intravascular cyclic adenosine monophosphate content was compared between the 3 groups (post-cardiopulmonary bypass).
  
  
  RESULTS
  There was a statistically significant improvement of the endothelium-dependent relaxation to bradykinin in the prostacyclin group when compared with the bypass group (P <.05). There was no statistically significant difference for endothelium-dependent relaxation to acetylcholine (P >.05) between the prostacyclin and the bypass groups. There was a statistically significant decrease in the cyclic adenosine monophosphate content and a statistically significant increase of the mean pulmonary artery pressure in the bypass group only (P <.05).
  
  
  CONCLUSIONS
  Prophylactic use of inhaled prostacyclin has a favorable impact on the pulmonary endothelial dysfunction induced by cardiopulmonary bypass associated with preservation of pulmonary intravascular cyclic adenosine monophosphate content and the pulmonary vascular tone.
authors.affiliation: Research Center and Department of Surgery, Montreal Heart Institute, Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Fortier
authors.forename: R G
authors.initials: RG
authors.lastname: DeMaria
authors.forename: Y
authors.initials: Y
authors.lastname: Lamarche
authors.forename: O
authors.initials: O
authors.lastname: Malo
authors.forename: A
authors.initials: A
authors.lastname: Denault
authors.forename: F
authors.initials: F
authors.lastname: Desjardins
authors.forename: M
authors.initials: M
authors.lastname: Carrier
authors.forename: L P
authors.initials: LP
authors.lastname: Perrault
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002317:Cardiovascular Agents / Q000008:administration & dosage; D000242:Cyclic AMP / Q000097:blood*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D011464:Epoprostenol / Q000008:administration & dosage*; D005260:Female; D007211:Indoles / Q000008:administration & dosage; D008168:Lung / Q000098:blood supply* / Q000378:metabolism*; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008955:Models, Cardiovascular; D010656:Phenylephrine / Q000008:administration & dosage; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D015415:Biomarkers; D002317:Cardiovascular Agents; D007211:Indoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; C008121:indolylheptylamine; D000249:Adenosine Monophosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D000109:Acetylcholine