A Neurokinin 1 Receptor Antagonist (NK-1ra) Decreases Adhesion Reformation After Laparoscopic Lysis of Adhesions (Loa) in a Rat Model
Scott G. Prushik*1, Cary B. Aarons1, Ronald Matteotti1, Karen L. Reed1, ADAM C. Gower1, Arthur F. Stucchi1, Susan E. Leeman2, James M. Becker1
1Surgery, Boston University, Boston, MA; 2Pharmacology, Boston University, Boston, MA
Introduction: Up to 94% of patients develop fibrous adhesions following abdominal surgery and a significant number of these patients will require a second operation for LOA. We have previously shown that inhibition of binding of the proinflammatory peptide, substance P, to its receptor using the NK-1RA CJ-12,255 (Pfizer) decreased primary adhesion formation and upregulated the peritoneal fibrinolytic system in a rat model. While most studies have focused on the prevention of primary adhesions, few have addressed adhesion reformation following LOA. The aim of this study was to determine the effects of NK-1RA administration on adhesion reformation and peritoneal fibrinolytic activity following LOA.
Methods: Adhesions were induced in 31 rats by our previously described ischemic button model. Seven days later, rats underwent laparoscopy during which adhesions were scored, lysed, and the NK-1RA or saline was administered. Seven days after LOA, 23 rats were sacrificed and adhesions were scored. Eight rats were also sacrificed 24 hours after the LOA to obtain peritoneal tissue and fluid which were analyzed for tissue plasminogen activator (tPA) mRNA expression and peritoneal fibrinolytic activity by RT-PCR and bioassay, respectively.
Results: At laparoscopy, 79±3.0% of buttons formed adhesions. In controls, 42±3.2% of buttons reformed adhesions after LOA (p<0.05), while in the NK-1RA animals 18.2±3.5% of buttons reformed adhesions (p<0.05). Compared with controls, NK-1RA administration increased tPA mRNA levels by 27% and fibrinolytic activity by 6-fold (p<0.05) (7.0 ±2.1U/ml vs. 1.2±0.54U/ml).
Conclusions: When administered during laparoscopic LOA, a NK-1RA significantly decreases adhesion reformation and upregulates peritoneal fibrinolytic activity.
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