A conscious mouse model of gastric ileus using clinically relevant endpoints

BACKGROUND: Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. METHODS: Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. RESULTS: Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. CONCLUSION: Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of stomach function appears to be simultaneous to colonic recovery

Chronic lactose intake modifies the gastric emptying of monosaccharides but not of disaccharides in weanling rats

Ninety-six weanling male Wistar rats were fed for four weeks one of two different chows: a normal rat chow containing 55.5% (w/w) starch (control group, N = 48) or a rat chow in which starch was partially replaced by lactose, in such away that the experimental group (N = 48) received 35.5% (w/w) starch and 20% (w/w) lactose. The gastric emptying of fluid was then studied by measuring the gastric retention of four test meals containing lactose (5% or 10%, w/v) or glucose + galactose (5% or 10%, w/v). Homogenates of the small intestine were assayed for lactase activity. The gastric retention values were obtained 15 min after orogastric infusion of the liquid meals. The median values for gastric retention of the 5% lactose solutions were 37.7% for the control group and 37.0% for the experimental group (P>0.02). For the 10% lactose solution the median values were 51.2% and 47.9% (P>0.02) for the control and experimental groups, respectively. However, for the 2.5% glucose + 2.5% galactose meal the median gastric retention was lower (P0.05). These results suggest that the prolonged ingestion of lactose by young adult rats changes the gastric emptying of a solution containing 5% monosaccharides. This adaptation may reflect the desensitization of intestinal nutrient receptors, possibly by an osmotic effect of lactose present in the chow.30672372

Effect of Phoneutria nigriventer spider venom on gastric emptying in rats

The effect of Phoneutria nigriventer spider venom (PNV) on the gastric emptying of liquids was studied in 240 young adult Wistar rats (2-3 months of age) divided into subgroups of 8 animals each, The study was performed in 3 stages. Initially, PNV was injected into rats at doses of 0, 19, 0.38 or 0.76 mg/kg and the effect on gastric emptying was assessed 30 min later. In the second stage, a time-course study was performed by injecting 0.76 mg PNV/kg and measuring the effect on gastric emptying 15, 60 and 120 min post-venom In the last stage, in order to investigate the possible mechanisms of PNV influence on gastric emptying, one group of rats underwent subdiaphragmatic vagotomy and then received 0.76 mg PNV/kg while three other groups were pretreated iv with either prazosin (0.4 mg/kg), domperidone (1.0 mg/kg) or propranolol (0.6 mg/kg) and then given 0.38 or 0.76 mg PNV/kg. In this last stage, gastric retention was measured 30 min post-venom. Each animal received a saline test meal solution containing phenol red as a marker (60 mu g/ml). Ten min after administering the test meal by gavage, gastric retention was determined by measuring the residual test meal marker concentration and the animals were sacrified. PNV (0.76 mg/kg) provoked a significant delay in gastric emptying of liquids 15, 30 and 60 min after its administration, Propranolol partially interfered with gastric emptying in rats that had received 0.38 and 0.76 mg PNV/kg. Vagotomy and pretreatment of the rats with prazosin and domperidone had no effect. We conclude that the delay in the liquid gastric emptying observed in severely envenomed rats was probably due, at least in part, to a venom-stimulated release of catecholamines which inhibited gastric motility by activating smooth muscle beta-adrenergic receptors.29220521

Gastric emptying in premature newborns with acute respiratory distress

Objectives: The authors hypothesized that acute respiratory distress (ARD) delays gastric emptying. The objective was to test this hypothesis by assessing gastric emptying on the second and seventh days of life in premature infants with ARD resulting from pulmonary disease. Methods: Thirty-nine newborns with ARD starting on the first day of life were selected and paired with 39 healthy control newborns matched by weight (within 250 g). Gestational age was <= 35 weeks and birth weight was <= 1750 g for all subjects. Gastric emptying was assessed at 48.0 +/- 24.0 hours and at 168.0 +/- 24.0 hours of life. A test meal consisting of 3 mL/kg of 5% glucose in water labeled with phenol red was administered by gastric tube over 1 minute and gastric retention was determined as percent test meal remaining in the stomach 30 minutes after administration. Results: Gastric retention at 30 minutes varied considerably in both groups and was significantly higher (P < 0.01) in newborns with ARD (61.4%) than controls (51.8%) at 48.0 +/- 24.0 hours, decreasing significantly after partial or full remission of ARD at 168 +/- 24 hours of life. Gastric retention was 60.2% in newborns with feeding intolerance and 36.8% in tolerant newborns (P < 0.001) at 168 hours. ARD and periventricular or intraventricular hemorrhage were predictors of gastric retention at 48 +/- 24 hours of life, whereas feeding intolerance and gestational age were predictors of gastric retention at 168 +/- 24 hours. Gastric retention was inversely correlated with gestational age. Conclusion: Gastric emptying is delayed in premature infants with ARD during the first 72 hours of life and may impair the initiation of enteral feeding.40333934