Document Detail

A neurokinin 1 receptor antagonist decreases adhesion reformation after laparoscopic lysis of adhesions in a rat model of adhesion formation.
MedLine Citation:
PMID:  17356938     Owner:  NLM     Status:  MEDLINE    
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.
S G Prushik; C B Aarons; R Matteotti; K L Reed; A C Gower; S E Leeman; A F Stucchi; J M Becker
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Publication Detail:
Type:  Journal Article     Date:  2007-03-14
Journal Detail:
Title:  Surgical endoscopy     Volume:  21     ISSN:  1432-2218     ISO Abbreviation:  Surg Endosc     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-13     Completed Date:  2007-10-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8806653     Medline TA:  Surg Endosc     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1790-5     Citation Subset:  IM    
Department of Surgery, Boston University School of Medicine, 88 East Newton street, C500, Boston, MA 02118, USA.
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MeSH Terms
Bicyclo Compounds, Heterocyclic / therapeutic use*
Disease Models, Animal
Rats, Wistar
Receptors, Neurokinin-1 / antagonists & inhibitors*
Tissue Adhesions / prevention & control*,  surgery*
Reg. No./Substance:
0/6-diphenylmethyl-5-(5-isopropyl-2-methoxybenzylamino)-1-azabicyclo(2.2.2)octane-3-carboxylic acid; 0/Bicyclo Compounds, Heterocyclic; 0/Receptors, Neurokinin-1

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