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

Fertil Steril. 2003 Sep:80 Suppl 2:795-802. doi: 10.1016/s0015-0282(03)00779-9.

Abstract

Objective: To evaluate the role of hypoxia inducible factors (HIFs) 1alpha and 2alpha in adhesion formation after laparoscopic surgery.

Design: Prospective, randomized study.

Setting: Academic research center.

Animal(s): 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(+/-)).

Intervention(s): 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.

Main outcome measure(s): Adhesions were blindly scored after 7 days.

Result(s): 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.

Conclusion(s): 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Carbon Dioxide / adverse effects
  • DNA-Binding Proteins / physiology*
  • Female
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Laparoscopy / adverse effects
  • Laparoscopy / methods
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins / physiology*
  • Peritoneum / surgery*
  • Pneumoperitoneum, Artificial / adverse effects*
  • Postoperative Complications
  • Prospective Studies
  • Random Allocation
  • Tissue Adhesions / etiology*
  • Trans-Activators / physiology*
  • Transcription Factors*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • Carbon Dioxide
  • endothelial PAS domain-containing protein 1