Surg Endosc. 2007 Mar 14; [Epub ahead of print]
A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation.
Prushik SG, Aarons CB, Matteotti R, Reed KL, Gower AC, Leeman SE, Stucchi AF, Becker JM.
Department of Surgery, Boston University School of Medicine, 88 East Newton street, C500, Boston, MA, 02118, USA, scott.prushik@bmc.org.
BACKGROUND: Up to 94% of patients experience fibrous adhesions after abdominal surgery, and a significant number of these patients require a second operation for open or laparoscopic lysis of adhesions (LOA). The authors have previously shown that inhibition of the binding of tachykinin ligands to the neurokinin 1 receptor (NK-1R) using the neurokinin 1 receptor antagonist (NK-1RA) CJ-12,255 decreases primary adhesion formation and upregulates the peritoneal fibrinolytic system in a rat model. Whereas most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation after LOA. This study aimed to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity after laparoscopic LOA. METHODS: Adhesions were induced in 31 rats using our previously described ischemic button model. The rats underwent laparoscopy 7 days later, during which adhesions were scored and lysed followed by administration of the NK-1RA or saline. Then 7 days after LOA, 23 rats were killed and adhesions were scored. Eight rats also were killed 24 h after the LOA to obtain peritoneal tissue and fluid, which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and bioassay, respectively. RESULTS: At laparoscopy, 79% +/- 3% of the buttons formed adhesions. In the saline-administered control animals, 42% +/- 3.2% of the buttons reformed adhesions after LOA (p < 0.05), whereas in the animals that received the NK-1RA, 18.2% +/- 3.5% of the buttons reformed adhesions (p < 0.05). As compared with control animals, NK-1RA administration increased tPA mRNA levels by 38% and fibrinolytic activity sixfold (p < 0.05; 7.0 +/- 2.1 U/ml vs 1.2 +/- 0.54 U/ml). CONCLUSIONS: When administered during laparoscopic LOA, an NK-1RA significantly upregulates peritoneal fibrinolytic activity and decreases adhesion reformation. |
