Adrenergic and cholinergic contributions to decreased gastric emptying,small intestinal transit,and colonic transit in the postoperative ileus rat

The depression of gastric emptying (GE), small intestinal transit (SIT), and colonic transit (CT) was studied in laparotomized rats 45 min after surgery to systematically determine neuronal contributions to postoperative ileus in this species. Chemical sympathectomy by intravenous 6-hydroxydopamine (100 mg/kg) 48 hr prior to surgery normalized CT and increased GE and SIT. If GE was measured 5 hr instead of 45 min after laparotomy, sympathectomized values were normal, but those of vehicle-treated controls were still depressed. Subcutaneous atropine (6 mg/ kg) administered 20 min prior to laparotomy prevented the augmentation of GE and CT by prior sympathectomy. Intraperitoneal phentolamine (0.25 mg/kg) but not propranolol (0.25 mg/kg) 20 min prior to surgery mimicked the effects of 6-hydroxydopamine pretreatment. Subcutaneous bethanechol (0.05, 0.1, or 1.0 mg/kg), neostigmine (0.01, 0.05, or 0.1 mg/kg), or guanethidine (1.0, 5.0, or 10.0 mg/kg) 20 min prior to laparotomy normalized CT and increased GE as compared to vehicle-treated controls. SIT was slightly augmented by neostigmine or bethanechol treatment. Combining chemical sympathectomy with carbachol (0.03 mg/kg) or neostigmine (0.03 mg/kg) normalized GE and increased CT and SIT more than with either compound alone. Subcutaneous methysergide (20 mg/kg) or naloxone (0.5 mg/kg) 20 min prior to surgery had no effect on transit. Subcutaneous indomethacin (10 mg/kg) 3 hr prior to laparotomy was likewise ineffective in increasing propulsion. These results suggest that postoperative ileus is caused both by increased α, but not β sympathetic activity in the stomach, small intestine, and possibly the colon, as well as depression of propulsive stimuli in stomach, small intestine, and the colon. Recovery of propulsive stimuli occurred prior to diminution of sympathetic activity in the stomach. Combination therapy with compounds to reverse both these phenomena appear to normalize propulsion most effectively. Some discrepancies in past reports on this subject were resolved.