title: Discordant effects of alkalosis on elevated pulmonary vascular resistance and vascular reactivity in lamb lungs.
abstract: OBJECTIVE
  After an initial vasodilator response to alkalosis, many children with pulmonary hypertension exhibit marked pulmonary vascular reactivity despite continued alkalosis therapy. This study sought to a) identify the mediator of alkalosis-induced pulmonary vasodilation in isolated lamb lungs; b) determine whether alkalosis-induced pulmonary vasodilation decreases over time in this model; and c) determine whether alkalosis enhanced vascular reactivity to subsequent pressor stimuli.
  
  
  METHODS
  Prospective, interventional study.
  
  
  METHODS
  Isolated perfused lungs from 1-month-old lambs.
  
  
  METHODS
  Hypocarbic alkalosis, hypoxia, and infusion of the thromboxane mimetic agent U46619
  
  
  RESULTS
  Pulmonary artery pressure was measured at constant flow, so a change in pressure reflects change in resistance. Hypoxic pulmonary artery pressure was compared after 20 and 100 mins of hypocarbic alkalosis or normocarbia in control and cyclooxygenase-inhibited lungs. Pulmonary artery dose responses to U46619 were then measured in control lungs. Responses to hypoxia and U46619 were also compared after 60-80 mins of hypocarbic or normocarbic normoxia. Hypocarbic alkalosis acutely reduced hypoxic pulmonary vascular resistance, and this was sustained for at least 100 mins. Cyclooxygenase inhibition blocked this vasodilation, suggesting that it was mediated by dilator prostaglandins. However, subsequent reactivity to U46619 was enhanced in hypoxic alkalotic lungs, and both hypoxia and U46619 caused significant vasoconstriction in normoxic alkalotic lungs.
  
  
  CONCLUSIONS
  Alkalosis caused sustained vasodilation when pulmonary vascular resistance was high but either failed to attenuate or enhanced vascular reactivity to subsequent pressor stimuli.
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine, Baltimore, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Moreira
authors.forename: D C
authors.initials: DC
authors.lastname: O'Donnell
authors.forename: M L
authors.initials: ML
authors.lastname: Tod
authors.forename: J A
authors.initials: JA
authors.lastname: Madden
authors.forename: J B
authors.initials: JB
authors.lastname: Gordon
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000472:Alkalosis, Respiratory / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D011897:Random Allocation; D012756:Sheep; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007213:Indomethacin