Hyperoxia and prevention of adhesion formation: a laparoscopic mouse model for open surgery.

ABSTRACT

OBJECTIVE: CO(2) pneumoperitoneum with more than 10% oxygen enhances adhesions. As during open surgery the peritoneum is exposed to air (20% oxygen), in this hyperoxia-enhanced adhesion model we evaluated the effect of hypothermia and products with known effectiveness in hypoxia (pure CO(2) pneumoperitoneum) and normoxia (CO(2) pneumoperitoneum plus 3-4% oxygen) models. Results were expected to be important for adhesion prevention in open surgery, and, moreover, similarities and differences between the three models would be important to identify differences in pathways of adhesion formation between laparoscopy and laparotomy. DESIGN: Two experiments were performed in which the effect of hypothermia (32 degrees C), a surfactant (phospholipids), a barrier (Hyalobarrier gel), reactive oxygen species scavengers (superoxide dismutase, SOD, and ascorbic acid, AA), anti-inflammatory agents (dexamethasone and nimesulide), a calcium channel blocker (diltiazem) and recombinant plasminogen activator (r-PA) were evaluated upon adhesions. SETTING: University Hospital. POPULATION BALB/c mice. METHODS: Hyperoxia-enhanced adhesions were induced by performing laparoscopically bipolar lesions during 60 minutes of CO(2) pneumoperitoneum plus 12% oxygen at 37 degrees C body temperature. MAIN OUTCOME MEASURES: Adhesions were scored after 7 days. RESULTS: In this model, adhesions were reduced by hypothermia (P < 0.02; Wilcoxon), phospholipids (P = 0.03), Hyalobarrier gel (P < 0.004), dexamethasone (P < 0.005) and diltiazem (P < 0.01). A significant but quantitatively borderline effect was seen for AA (P < 0.002) and r-PA (P = 0.0005), whereas SOD and nimesulide did not have any effect. CONCLUSIONS: Hyperoxia-enhanced adhesions were prevented by hypothermia, dexamethasone, phospholipids, Hyalobarrier gel, diltiazem, r-PA and AA. All effects were similar to those in the hypoxia-enhanced adhesion model, suggesting that the underlying mechanisms are similar.