Divergence of mucosal and motor effects of insulin-like growth factor (IGF)-I and LR(3)IGF-I on rat isolated ileum following abdominal irradiation

Background and Aims: In addition to its beneficial effects on small intesti nal mucosal development and repair, insulin-like growth factor (IGF)-I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to t he small intestinal dysmotility observed during and after abdominal radioth erapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of TGF-I (5 mg/kg per day) and the more potent analog LR(3)IGF-I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation. Methods: Intestinal motor activity was recorded from 6-8 cm segments of exp lanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 d ays after treatment with 10 Gy abdominal irradiation. At the time of irradi ation, all rats underwent implantation of an osmotic mini-pump that contain ed 100 mmol/L acetic acid vehicle (n = 8), IGF-I (n = 8) or LR(3)IGF-I (n = 7). For each experiment, the total number of pressure waves, high-amplitud e long-duration (defined as >20 mmHg, >6 s; HALD) pressure waves and long b ursts (>20) of pressure waves were determined. Ileal segments from 12 non-i rradiated rats were used as controls for manometric studies. In radiotherap y treated animals, the degree of mucosal damage was determined using a stan dardized histologic scoring system. Results: The HALD pressure waves were infrequent in non-irradiated rats but occurred in all irradiated animals. Insulin-like growth factor-I and LR(3) IGF-I had no effect on the frequency, amplitude or migration characteristic s of HALD pressure waves compared with vehicle. Histologic damage was reduc ed in animals that received IGF-I and LR(3)IGF-I compared with vehicle-trea ted animals. Conclusions: In radiation enteritis, IGF-I has no effect on neurally mediat ed small intestinal dysmotility while improving mucosal histology. The disp arity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis. (C) 2000 Blackwell Science Asia Pty Ltd.