Inhibition of postsurgical adhesions in a standardized rabbit model: intraperitoneal treatment with tissue plasminogen activator.

The direct effects of tissue plasminogen activators (TPA) delivered locally into the peritoneal cavity at the site of injury on the subsequent formation of postsurgical adhesions in rabbits were studied. A 3 x 5 cm flap of parietal peritoneum (approximately 1 mm thick) was sharply dissected from the right lateral peritoneal sidewall. The serosal surface of the adjacent small bowel was abraded with a scalpel until punctate bleeding developed. Alzet minipumps containing varying doses of TPA were sewn into the subcutaneous space with their polyethylene catheter tips leading from the pump into the peritoneal cavity, 2-3 mm over the injury test site. Within 7 days after the implantation of the pumps, the rabbits were killed and the extent of adhesions was determined. The threshold dosage at which significant beneficial antiadhesion properties are obtained was between 0.015 and 0.05 mg TPA/mL of buffer at 6 x 10(-4) mg/kg/day. Effective adhesion prevention occurred with only two days of treatment beginning the day of surgery.