Prevention of intra-abdominal adhesions using the antiangiogenic COX-2 inhibitor celecoxib.
OBJECTIVE
To determine the effects of COX-2 specific inhibitors on postoperative adhesion formation.


BACKGROUND
Intra-abdominal adhesions are the major cause of intestinal obstruction and secondary infertility after surgical procedures. Because adhesion synthesis requires angiogenesis, and cyclooxygenase-2 enzyme (COX-2) inhibitors have antiendothelial activity, we tested COX-2 inhibitors in a murine model of intra-abdominal adhesion formation.


METHODS
A silicone patch was secured to the lateral abdominal wall of groups of C57BL/6 mice, followed by cecal abrasion to promote adhesion formation. Beginning on the day of surgery, mice were treated with the selective COX-2 agents, celecoxib or rofecoxib, and the nonspecific COX inhibitors, aspirin, naproxen, ibuprofen, or indomethacin. Animals were treated for 10 days and killed. A second group (celecoxib, rofecoxib, aspirin) was treated for 10 days and observed for an additional 25 days. After treatment, intra-abdominal adhesions were scored using a standard method. The patch was subjected to immunohistochemistry with the endothelial-specific marker, CD31.


RESULTS
Animals treated with selective and nonselective COX-2 inhibitors, except aspirin, had significantly fewer adhesions than control animals. Celecoxib produced a maximal reduction in adhesion formation compared with rofecoxib and the nonselective COX-2 inhibitors at 10 days. After 25 days, celecoxib and rofecoxib, but not aspirin, had fewer adhesions than control mice. Adhesions from mice treated with celecoxib had reduced microvessel density compared with rofecoxib, the nonselective COX inhibitors, and control animals.


CONCLUSIONS
Selective COX-2 inhibitors, in particular celecoxib, provide durable inhibition of intra-abdominal adhesions through an antiangiogenic mechanism.
Department of Surgery, Children's Hospital and Harvard Medical School, Boston, MA, USA.
Arin K
AK
Greene
Ian P J
IP
Alwayn
Vania
V
Nose
Evelyn
E
Flynn
David
D
Sampson
David
D
Zurakowski
Judah
J
Folkman
Mark
M
Puder
D000818:Animals; D001707:Biopsy, Needle; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007415:Intestinal Obstruction / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D011720:Pyrazoles / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000494:pharmacology*; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib