Intrasphincteric nitric oxide reduces sphincter of Oddi motility in an endoscopic porcine model.

Abstract

Nitric oxide (NO), a potent nonadrenergic, noncholinergic mediator of gastrointestinal smooth muscle, causes relaxation of the category I pump like sphincter of Oddi (SO) (eg, opossum, rabbit) and category II resistor like SO (eg, pig, human). Topical administration of a NO donor induces SO relaxation in humans, and parenteral administration of sodium nitroprusside (SNP) decreases sphincter contractility in pig SO. The aim of this study is to evaluate the effect of intrasphincteric SNP injection on pig SO. Under general anesthesia, two pigs received intrasphincteric saline injection (1 ml) and six pigs received intrasphincteric SNP (0.5 microg/ml) injection into the SO. All injections were administered into the major papilla using a 5-mm sclerotherapy needle through the duodenoscope. Endoscopic biliary manometry was performed using the standard station pull-through technique and SO pressures were recorded before and after injection. Intrasphincteric saline injection did not significantly change the mean SO motility index (MI) (197 vs 198). However, intrasphincteric SNP reduced both the mean SO basal pressure (P = 0.002) and the mean SO MI (226 vs 109; P = 0.002). The effect of intrasphincteric SNP lasted up to 45 min and did not cause significant lowering of systemic blood pressure. This is the first study to demonstrate that intrasphincteric SNP results in significant reduction in both SO basal pressure and SO MI in the porcine model. The endoscopic intrasphincteric administration of NO donor drugs is technically feasible and without observed systemic side effects.