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


METHODS
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.


METHODS
University Hospital.


METHODS
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.


METHODS
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.
Binda
M M
MM
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. mercedes.binda@gmail.com
Koninckx
P R
PR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004110:Diltiazem / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005782:Gels; D006820:Hyaluronic Acid / Q000627:therapeutic use; D018496:Hyperoxia / Q000150:complications*; D007036:Hypothermia, Induced; D010535:Laparoscopy / Q000009:adverse effects* / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010743:Phospholipids / Q000627:therapeutic use; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects; D000267:Tissue Adhesions / Q000209:etiology / Q000517:prevention & control*
D000893:Anti-Inflammatory Agents; D002121:Calcium Channel Blockers; D005782:Gels; D010743:Phospholipids; D003907:Dexamethasone; D006820:Hyaluronic Acid; D004110:Diltiazem