Inhibition of postsurgical adhesions in a standardized rabbit model: II. Intraperitoneal treatment with heparin.
The formation of adhesions after peritoneal trauma is thought to result from the deposition of fibrin and its subsequent organization by fibroblast ingrowth and, in some cases, neovascularization and reepithelialization. Since heparin is an effective anticoagulant, and clotting is a major contributor to postsurgical fibrin deposition, we studied the effects of heparin delivered locally into the peritoneal cavity at the site of the injury on the subsequent formation of postsurgical adhesions. A flap of parietal peritoneum (approximately 1 mm thick) was dissected from the right lateral peritoneal sidewall of New Zealand white female rabbits. The serosal surface of the adjacent small bowel was abraded with a scalpel to produce punctuate bleeding. This area between the excised parietal peritoneum and adjacent small bowel serosa was then used for evaluating the efficacy of heparin for adhesion prevention. Alzet minipumps containing phosphate-buffered saline with varying doses of heparin were sewn into the right dorsal subcutaneous space with Vicryl sutures. A polyethylene catheter tip leading from the pump into the peritoneal cavity was placed 2-3 mm over the injury test site. Within seven days after the implantation of the pumps, the rabbits were killed and the extent of adhesions determined, according to a qualitative grading system. The threshold dosage at which significantly beneficial antiadhesion properties were obtained was 1.5 x 10(-2) U/hour or 7.5 x 10(-3) U/kg/day. Effective adhesion prevention occurred with only two days of treatment beginning the day of surgery. At this dose, no postsurgical bleeding occurred. These findings suggest that local intraperitoneal administration of low-dose heparin throughout the immediate postoperative interval may result in adhesion-free healing.
Department of Obstetrics and Gynecology University of Southern California School of Medicine, Los Angeles.
M
M
Fukasawa
W
W
Girgis
G S
GS
diZerega
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D010537:Peritoneum / Q000601:surgery*; D011817:Rabbits; D000267:Tissue Adhesions; D014945:Wound Healing / Q000187:drug effects*
D006493:Heparin