title: Right lung ischemia induces contralateral pulmonary vasculopathy in an animal model.
abstract: OBJECTIVE
  The study objective was to determine whether the vasculopathy seen in nonobstructed lung regions in chronic thromboembolic pulmonary hypertension is induced by the local blood flow increase or by factors released by the ischemic lung.
  
  
  METHODS
  Three groups of 10 piglets were studied 5 weeks after right pulmonary artery ligation, right pneumonectomy, or right pulmonary artery dissection (sham). Pulmonary vascular resistance, pulmonary arterial vasoreactivity, and morphometry were measured, and gene expressions of factors involved in vascular smooth muscle cell proliferation were quantified.
  
  
  RESULTS
  Left lung blood flow was similarly increased after right pneumonectomy and right pulmonary artery ligation. Compared with right pneumonectomy, right pulmonary artery ligation resulted in left lung vasculopathy with increased pulmonary vascular resistance (P = .0009), medial hypertrophy of the distal pulmonary artery (P < .0001), and decreases in maximal relaxation to acetylcholine (P = .013) and endothelial nitric oxide synthase gene expression (P = .041). These values were similar after sham and right pneumonectomy. In the left lung, right pulmonary artery ligation increased the gene expressions for insulin-like growth factor (P = .034), platelet-derived growth factor (P = .0006), and vascular endothelial growth factor (P = .0105) compared with right pneumonectomy and sham. Whereas endothelin-1 gene expression was not affected, expressions of endothelin-1 receptors A and B were downregulated after right pneumonectomy (P = .048 and P = .039, respectively) and right pulmonary artery ligation (P = .033 and P = .028, respectively).
  
  
  CONCLUSIONS
  Pulmonary vasculopathy was absent in the remaining lung 5 weeks after right pneumonectomy but developed in the nonobstructed lung regions 5 weeks after right pulmonary artery ligation, suggesting that factors released by the ischemic lung induced vascular remodeling in the contralateral lung. This endocrine process may involve the release of factors involved in vascular smooth muscle cell proliferation.
authors.affiliation: Laboratoire de Recherche Chirurgicale and INSERM U999, Hôpital Marie Lannelongue, Université Paris Sud, Le Plessis Robinson, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Sage
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
authors.forename: Philippe
authors.initials: P
authors.lastname: Herve
authors.forename: Ly
authors.initials: L
authors.lastname: Tu
authors.forename: Philippe
authors.initials: P
authors.lastname: Dartevelle
authors.forename: Saadia
authors.initials: S
authors.lastname: Eddahibi
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000235:genetics; D005786:Gene Expression Regulation; D006984:Hypertrophy; D007511:Ischemia / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008026:Ligation; D008168:Lung / Q000098:blood supply*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011013:Pneumonectomy; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D011652:Pulmonary Circulation; D012333:RNA, Messenger / Q000378:metabolism; D017466:Receptors, Endothelin / Q000235:genetics; D012039:Regional Blood Flow; D013002:Somatomedins / Q000235:genetics; D013552:Swine; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014655:Vascular Resistance; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D013002:Somatomedins; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III