title: Role of hypoxia inducible factors 1alpha and 2alpha in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.
abstract: OBJECTIVE
  To evaluate the role of hypoxia inducible factors (HIFs) 1alpha and 2alpha in adhesion formation after laparoscopic surgery.
  
  
  METHODS
  Prospective, randomized study.
  
  
  METHODS
  Academic research center.
  
  
  METHODS
  Forty Swiss/129SvJ wild-type mice and transgenic mice partially deficient for the genes encoding for HIF-1alpha (HIF-1alpha(+/-)) or HIF-2alpha (HIF-2alpha(+/-)).
  
  
  METHODS
  Adhesions were induced by standardized lesions during laparoscopy. To evaluate "basal adhesions" and "pneumoperitoneum-enhanced adhesions," the pneumoperitoneum was maintained for a minimum (10 minutes) or prolonged (60 minutes) period, respectively.
  
  
  METHODS
  Adhesions were blindly scored after 7 days.
  
  
  RESULTS
  In both HIF-1alpha and HIF-2alpha wild-type mice, pneumoperitoneum enhanced adhesion formation. In comparison with wild-type mice, basal adhesions were lower in HIF-1alpha(+/-) and similar in HIF-2alpha(+/-) mice. Pneumoperitoneum did not enhance adhesion formation in HIF-1alpha(+/-) or in HIF-2alpha(+/-) mice. Therefore, in comparison with the correspondent wild-type mice, pneumoperitoneum-enhanced adhesions were lower in HIF-1alpha(+/-) and HIF-2alpha(+/-) mice.
  
  
  CONCLUSIONS
  These data confirm that CO(2) pneumoperitoneum enhances adhesion formation and indicate that this effect is mediated, at least in part, by an up-regulation of HIF-1alpha and HIF-2alpha.
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002245:Carbon Dioxide / Q000009:adverse effects; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010535:Laparoscopy / Q000009:adverse effects / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000502:physiology*; D010537:Peritoneum / Q000601:surgery*; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects*; D011183:Postoperative Complications; D011446:Prospective Studies; D011897:Random Allocation; D000267:Tissue Adhesions / Q000209:etiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002245:Carbon Dioxide; D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497443:Hif1a protein, mouse