The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent.
BACKGROUND
Current methods to prevent intraabdominal adhesions are not uniformly effective. We recently showed in rats that a neurokinin-1 receptor (NK-1R) antagonist is capable of reducing adhesion formation. To determine the clinical feasibility of using an NK-1R antagonist to reduce adhesions, this study examined the time dependence for the effectiveness of NK-1R antagonist administration and its effects on wound healing.


METHODS
Adhesions were surgically induced in rats receiving a single intraperitoneal infusion of the NK-1R antagonist, CJ-12,255, during or 1, 5, 12, or 24 hours after surgery. Adhesion formation was assessed 7 days later. In a subset of animals, tissue plasminogen activator (tPA) activity, which is a measure of peritoneal fibrinolytic activity, was determined in peritoneal fluid 24 hours after surgery (48 hours for animals infused at 24 hours). The tPA activity was also determined in nonoperated animals 24 hours after peritoneal injection of the NK-1R antagonist. Colonic burst pressures were measured 7 days after creation of anastomoses in rats that were administered the antagonist at surgery.


RESULTS
The NK-1R antagonist significantly reduced (P=.003) intraabdominal adhesions when administered during or 1 hour after surgery, only moderately reduced (P=.08) adhesions when administered at 5 hours, and had no effect at 12 or 24 hours. Peritoneal tPA activity was significantly increased (P<.05) in peritoneal fluid 24 hours after administration of the NK-1R antagonist regardless of the surgical procedure. The NK-1R antagonist did not alter colonic anastomotic healing.


CONCLUSIONS
These data show that some of the events critical to adhesion formation occur within the first 5 hours following an abdominal operation in this model. The fact that the NK-1R antagonist does not impair colonic anastomotic healing enhances its usefulness as a therapeutic agent to inhibit adhesion formation.
Cohen
Philip A
PA
Department of Surgery, Boston University School of Medicine, Boston, MA 02118, USA.
Aarons
Cary B
CB
Gower
Adam C
AC
Stucchi
Arthur F
AF
Leeman
Susan E
SE
Becker
James M
JM
Reed
Karen L
KL
D000005:Abdomen; D000714:Anastomosis, Surgical; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003106:Colon / Q000601:surgery; D007263:Infusions, Parenteral; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D011183:Postoperative Complications / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D000267:Tissue Adhesions / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
C480026:6-diphenylmethyl-5-(5-isopropyl-2-methoxybenzylamino)-1-azabicyclo(2.2.2)octane-3-carboxylic acid; D019086:Bridged Bicyclo Compounds, Heterocyclic; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D010959:Tissue Plasminogen Activator