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A Novel Approach to Reducing Postoperative Intraperitoneal Adhesions Through the Inhibition of Insulinlike Growth Factor I Activity
Michael L. Gimbel, MD;
Dirk Chelius, PhD;
Thomas K. Hunt, MD;
E. Martin Spencer, MD,PhD
Arch Surg. 2001;136:311-317.
Hypothesis Interference with insulinlike growth factor I (IGF-I) activity, both systemically and intraperitoneally, reduces postoperative intraperitoneal adhesion severity.
Setting Experimental animal model.
Design, Interventions, and Main Outcome Measures: Adult female rats were subjected to hypophysectomy, sham hypophysectomy (control), IGF binding protein 4 (IGFBP-4) treatment, or albumin treatment (control). All rats underwent laparotomy and uterine horn abrasion with adjacent parietal peritoneal trauma for the purpose of creating postoperative intraperitoneal adhesions. Glucocorticoids and thyroid hormone were replaced in the hypophysectomy group. On postoperative day 10, rats were weighed, subjected to phlebotomy, and killed. Postmortem laparotomies were performed and blinded observers scored uterine-peritoneal adhesions on a 0 to 3 scoring system. Plasma IGFBP-4 levels and organ weights were measured in the IGFBP-4 and albu-min treatment groups. Blood samples in all rats were analyzed for IGF-I levels.
Results Rats with low IGF-I levels (hypophysectomy) and inhibited IGF-I activity (IGFBP-4 treatment) formed significantly less severe adhesions than their control counterparts. As expected, rats in the hypophysectomy group displayed greater weight loss and lower plasma IGF-I levels than sham-treated rats. Rats treated with IGFBP-4 and those treated with albumin demonstrated no differences in body weight, organ weights, IGF-I levels, and IGFBP-4 levels.
Conclusions Both the reduction of systemic IGF-I levels via hypophysectomy and the inhibition of local intraperitoneal IGF-I activity via IGFBP-4 treatment resulted in diminished postoperative adhesion severity. Treatment with IGFBP-4 may play a role in postoperative adhesion prophylaxis in the future.
From the Wound Healing Laboratory at the University of California, San Francisco. Dr Gimbel is now with the Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa; Drs Chelius and Spencer, with the Laboratory of Growth and Development, California Pacific Medical Center Research Institute, San Francisco; and Dr Hunt, with the Department of Surgery, University of California, San Francisco.
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