Local Release of Fibrinolytic Agents for Adhesion Prevention

• Published in: The Journal of surgical research Vol. 59; no. 6; pp. 759 - 763
• Main Authors: Hill-West, Jennifer L., Dunn, Randall C., Hubbell, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-1995; Elsevier
• Subjects: Animals; Biological and medical sciences; Digestive system; Drug Implants; Female; Hydrogel, Polyethylene Glycol Dimethacrylate; Injections, Intraperitoneal; Medical sciences; Pharmacology. Drug treatments; Polyethylene Glycols; Postoperative Complications - prevention & control; Rats; Rats, Sprague-Dawley; Streptokinase - administration & dosage; Streptokinase - pharmacology; Tissue Adhesions - prevention & control; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - pharmacology; Urokinase-Type Plasminogen Activator - administration & dosage; Urokinase-Type Plasminogen Activator - pharmacology; Uterine Diseases - prevention & control; Uterus - surgery; Intraperitoneal administration; Rat; Rodentia; Controlled therapeutic trial; Route of administration; Adhesion; Prevention; In vivo; Chemotherapy; Vertebrata; Mammalia; Animal; Surgery; Fibrinolytic
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1995.1236

Tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and streptokinase were evaluated for their ability to reduce postsurgical adhesion formation in a rat uterine horn devascularization and serosal injury model in a blinded, randomized study. Small doses of tPA, uPA, or streptokinase were delivered over approximately a 4-day period either from a biodegradable hydrogel matrix or as four daily intraperitoneal injections. The hydrogel was formed upon the uterine horns by photopolymerization of an aqueous precursor solution containing dissolved drug. A control group that received no treatment had an average extent of adhesion formation of 72 ± 15% (mean ± SEM, percentage of the length of the uterine horns involved in adhesions). Application of this formulation of the hydrogel alone reduced the extent of adhesion formation to 22 ± 10% by functioning as a mechanical barrier. When tPA was released from the hydrogel, adhesion formation was reduced to 4 ± 3%, while when tPA was given by intraperitoneal injection, adhesion formation was only reduced to 49 ± 8%. Local delivery of urokinase reduced adhesion formation to 6 ± 6%, but intraperitoneal injection of urokinase did not reduce adhesion formation. Streptokinase did not reduce adhesion formation when administered by intraperitoneal injection and increased adhesion formation to 45 ± 9% when locally released relative to the hydrogel alone. These results suggest that both tPA and uPA may be used to prevent adhesion formation when delivered locally.