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.
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.