Effect of radiation and radioprotection on small intestinal function in canines

Radiation with doses > 7.5 Gy damages the canine intestinal mucosa, and pretreatment with WR2721 reduces this damage. However, the effects of radiation and of WR2721 on in vivo intestinal transport are unclear. Therefore, we determined canine survival, intestinal transport, and mucosal histology following unilateral abdominal irradiation. Isoperistaltic ileostomies were prepared in 23 dogs under general anesthesia and aseptic conditions. After a three-week recovery period, animals were given either placebo or WR2721, 150 mg/kg intravenously, 30 min prior to 10 Gy cobalt-60 abdominal irradiation. Ileal transport and histology were determined in both groups before exposure and one, four, and seven days after irradiation. Seven-day survival was significantly improved by pretreatment with WR2721 (91% vs 33%, P < 0.02). On day 4, both mucosal integrity and net intestinal absorption were significantly better (P < 0.05) after WR2721 than after placebo. Thus, radiation-induced damage to the ileal mucosa is accompanied by a reduction in net ileal absorption of water and electrolytes in vivo. In addition, pretreatment with WR2721 improves animal survival while reducing ileal damage and improving intestinal absorption.