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.
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.
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
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