Sunitinib inhibits postoperative adhesions in a rabbit model

• Published in: Surgery 2011-07, Vol.150 (1), p.32-38
• Main Authors: Meisel, Jonathan A., MD, Fallon, Erica M., MD, Le, Hau D., MD, Nehra, Deepika, MD, de Meijer, Vincent E., MD, MSc, Rodig, Scott J., MD, Puder, Mark, MD, PhD
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Animals; Biological and medical sciences; Disease Models, Animal; Female; General aspects; Indoles - pharmacology; Medical sciences; Microvessels - drug effects; Microvessels - pathology; Protein Kinase Inhibitors - pharmacology; Pyrroles - pharmacology; Rabbits; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Surgery; Tensile Strength; Tissue Adhesions - pathology; Tissue Adhesions - physiopathology; Tissue Adhesions - prevention & control; Uterus - surgery; Wounds and Injuries - physiopathology
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2011.02.013

Background Postoperative abdominal adhesions are a major cause of morbidity and mortality. We previously demonstrated the inhibitory effect of sunitinib, a receptor tyrosine kinase inhibitor, on adhesion formation in a murine model, and now investigate its effects in a rabbit model. Methods Forty New Zealand White rabbits underwent a standard adhesion procedure. Preoperatively, animals were randomized to treatment with sunitinib or saline (control). Animals were treated with a total of 11 daily doses, 1 preoperative and 10 postoperative. One group of 20 animals (group 1) was humanely killed on postoperative day 10, and the other (group 2) on postoperative day 30. After killing, adhesions were scored and abdominal wounds were collected for tensile strength and microvessel density measurements. Results Sunitinib-treated animals in group 1 had a mean tenacity score of 1.67 ± 0.29 compared with 3.60 ± 0.16 in control animals ( P < .01). Similarly, the mean tenacity scores for sunitinib-treated and control animals in group 2 were 0.20 ± 0.20 and 2.70 ± 0.37, respectively ( P < .01). The mean uterine involvement scores for sunitinib-treated and control animals in group 1 were 1.44 ± 0.29 and 3.70 ± 0.15, respectively ( P < .01), and in group 2 were 0.10 ± 0.10 and 2.70 ± 0.45, respectively ( P < .01). There were no differences in ultimate or modular wound tensile strength between sunitinib-treated and control animals. Conclusion Sunitinib significantly reduces postoperative adhesions in a rabbit model. This therapy may improve postoperative adhesion-related morbidity and mortality.