Intraperitoneal administration of adenosine inhibits formation of abdominal adhesions.
OBJECTIVE
Previously we demonstrated that peritoneal lavage with high concentrations of adenosine (1 mM) provides pharmacologic levels of adenosine in the intestines without elevating adenosine levels in the systemic circulation and without causing systemic hemodynamic effects (Alimentary Pharmacology & Therapeutics 2000; 14:1371-80). Because adenosine can be safely administered into the peritoneal cavity, and because it inhibits fibroblast proliferation and collagen production and inflammation and enhances angiogenesis, we tested the hypothesis that adenosine applied into the abdominal cavity safely and effectively reduces formation of abdominal adhesions.


METHODS
To test this hypothesis, in Sprague-Dawley rats, a window of right parietal peritoneum was removed and the cecum was brushed and placed next to the damaged peritoneum. After injury, rats received in the abdominal cavity either 20 ml of saline (n = 12, Saline Group) or 20 ml of 1 mM adenosine (n = 12, Adenosine 1X Group; and n = 12, Adenosine 4X Group). At 24, 48, and 72 hours after surgery, rats received by intraperitoneal injection either 10 ml of saline (Saline Group and Adenosine 1X Group) or 10 ml of 1 mM adenosine (Adenosine 4X Group).


RESULTS
After 14 days, the degree of adhesion formation was scored (0 to 4) by a blinded observer. Animals tolerated the adenosine treatments without signs of discomfort or distress. The adhesion scores were 2.6 +/- 0.34, 1.7 +/- 0.40, and 0.74 +/- 0.29 in the Saline, Adenosine 1X, and Adenosine 4X groups, respectively (P = 0.0035, Kruskal-Wallis analysis of variance).


CONCLUSIONS
Peritoneal administration of 1 mM adenosine safely and effectively reduces adhesion formation.
Center for Clinical Pharmacology, Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. edj+@pitt.edu
Edwin K
EK
Jackson
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D007410:Intestinal Diseases / Q000517:prevention & control* / Q000662:veterinary; D007415:Intestinal Obstruction / Q000517:prevention & control*; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000517:prevention & control
D000241:Adenosine