EFFECT OF VARYING DAYS OF TISSUE PLASMINOGEN-ACTIVATOR THERAPY ON THE PREVENTION OF POSTSURGICAL ADHESIONS IN A RABBIT MODEL

The depression of focal fibrinolytic activity in mesothelial or serosal tissues which results from a surgical ischemic insult can lead to the formation of permanent fibrinous adhesions. To assess the time course for the prevention of adhesion formation by recombinant tissue plasminogen activator (rt-PA), infusions of rt-PA were administered to rabbits every 12 hr for a total of 1, 2, 4, or 8 days. Animals in each rt-PA treatment group received a total cumulative dose of 16 mg. Control animals received saline with the same corresponding dosing regimens as the treated groups. Prior to dosing, all animals had a devascularizing injury to the uterine horns performed bilaterally by bipolar cauterization of the uterine mesenteric vascular arcade below the horns. A catheter was then placed from a subcutaneous port to the intraperitoneal space. rt-PA, or saline, was instilled intraperitoneally via the subcutaneous port. Adhesions were scored at the second laparotomy by assessing the percentage of the involvement of the uterine horns in adhesions. Mean score for adhesion formation in each placebo group was 35 to 40%. Mean score (± standard error of the mean) for rt-PA after 1 day of therapy was 13.1% ± 3.89; after 2 days of therapy, 6.3% ± 1.57; after 4 days of therapy, 3.8% ± 1.57; and after 8 days of therapy, 6.9% ± 2.3 (P < 0.01 compared to the control grouped mean for each day of treatment). These results demonstrate that at the dose used in this study, increasing the availability of rt-PA from 1 to 4 days, results in a greater decrease in the formation of permanent adhesions. © 1993 Academic Press. All rights reserved.