Back to 2008 Program and Abstracts
A Neurokinin-1 Receptor Antagonist (Nk1ra) That Reduces Intraabdominal Adhesions Augments the Anti-Adhesive Effects of a Hyaluronic Acid/Carboxymethylcellulose (Ha/Cmc) Adhesion Barrier in Rats
Rizal Lim*1, Jonathan M. Morrill1,2, Karen L. Reed1,2, Adam C. Gower1, Bilaal Mccloud1, Susan E. Leeman2,1, Arthur F. Stucchi1,2, James M. Becker1
1Surgery, Boston University Medical Center, Boston, MA; 2Pharmacology, Boston University Medical Center, Boston, MA
Introduction: Intraabdominal adhesions can be a significant cause of postoperative morbidity. Previous work from this laboratory has shown that an NK1RA significantly reduces adhesion formation in a rat model. HA/CMC (Seprafilm Adhesion Barrier® Genzyme), proven to reduce the incidence of adhesions in patients undergoing laparotomy, may have its efficacy limited to the location of the film, typically under the midline incision. The purpose of this study was to evaluate the anti-adhesion efficacy of the NK1RA (CJ-12,255; Pfizer) when administered in combination with HA/CMC in a rat model of adhesion formation.
Methods: Adhesions were created via a midline laparotomy by placing 3 ischemic buttons, 1 cm apart on each side of the peritoneum. Rats received no treatment (n=6), NK1RA (25 mg/kg) (n=5), HA/CMC and saline (n=12), or HA/CMC and NK1RA (25 mg/kg) (n=12) administered intraperitoneally at the time of surgery. HA/CMC was applied unilaterally over half the ischemic buttons and the NK1RA was administered in a 1ml saline lavage. The rats were sacrificed at 7 days and adhesions scored as percent of buttons with formed adhesions. To evaluate peritoneal fibrinolytic activity, ischemic buttons were created as above and randomized to receive NK1RA alone (n=6), bilateral HA/CMC and saline lavage (n=6), or bilateral HA/CMC and NK1RA lavage (n=6). Animals were sacrificed at 24 hours, and peritoneal tissue and fluid collected for tissue plasminogen activator (tPA) activity assay, a measure of fibrinolytic activity.
Results: Rats treated with NK1RA had significantly fewer adhesions compared with controls (80 ± 8% vs. 20 ± 4%; p <0.05). HA/CMC also significantly decreased adhesions from 75 ± 8.3% to 44 ± 10.3% (p<0.05); however, adhesion reduction was limited to buttons over which HA/CMC was placed. The combination of the NK1RA and HA/CMC increased the efficacy of HA/CMC, further reducing adhesions to 11 ± 4.7%, a 75% reduction compared to HA/CMC alone (p<0.05). In these same animals the adhesions were reduced by 45% on the non- HA/CMC side (p<0.05). Administration of the NK1RA alone increased peritoneal tPA activity more than 137% compared with HA/CMC alone (26.7 ± 3.5 vs. 11.2 ± 2.2 U/ml, p<0.05); however, this increase was attenuated when NK1RA was administered in the presence of HA/CMC (14.6 ± 3.5U/ml, p<0.05 compared with NK1RA alone).
Conclusions: The efficacy of HA/CMC was significantly augmented by the addition of an NK1RA suggesting that further research is warranted to develop a biodegradable, barrier-based delivery system for more effective prevention of adhesions.
