Acute intracranial hypertension-induced inhibition of gastric emptying: evaluation in conscious rats

Abstract

To study the effect of raised intracranial pressure (ICP)-induced alterations in gastric emptying, and their modulation by pharmacological interventions, an experimental model was standardized in rats. A test meal of methylcellulose and phenol red was administered intragastrically. ICP was raised to 40, 60 and 80 mmHg by connecting a buffered saline pressure head to an intracerebroventricular (i.c.v.) cannula. Gastric emptying was estimated after killing the animals, from the residual stomach phenol red content. Inhibition of gastric emptying was observed when ICP was raised, the maximum being at 80 mmHg ICP (percent gastric emptying 26.5%±2.8 vs. 83.4±4.7 in sham-ICP). Pretreatment with clonidine, prazosin or ondansetron did not modify the raised ICP-induced inhibition of gastric emptying. Cisapride was ineffective at 1 mg/kg but caused a partial reversal at the 5- and 10-mg/kg doses (46.9±3.1% and 42.6±4.0%, respectively). Carbachol at a lower dose of 0.1 mg/kg i.p., produced a greater reversal (78.3±6.0%) than did the high dose (52.8±4.1). Bretylium partially reversed the inhibition of gastric emptying (45.7±4.3%). The protective effect of carbachol and cisapride suggests that suppression of vagal activity due to increased ICP may play an important role in the inhibition of gastric emptying due to intracranial hypertension.