Portal-Systemic Shunting and the Hemodynamic Effects of Nitroglycerin in the Rat

Abstract

A hemodynamic response to oral nitroglycerin has been used recently to estimate the extent of portal systemic shunts in humans. We studied the hemodynamic effects of this drug in the rat with partial portal vein ligation, a model in which portal hypertension develops and the extent of portal-systemic collaterals can be measured. Two to ten days after the initial procedure, shunted and sham-operated controls received a continuous infusion of nitroglycerin into a jugular vein, the ileocolic vein, or intrajejunally. The response of systolic arterial pressure to intravenous nitroglycerin was similar in shunted and sham animals. The cumulative dose-response curve showed an earlier and more pronounced response in shunted rats receiving nitroglycerin intraportally, suggesting a marked increase in bioavailability. When the arterial response to nitroglycerin, infused intraportally at 1 microgram/kg X min, was compared to the extent of ileocolic shunting, measured with radioactive microspheres, a close correlation (r = 0.84) was seen; shunting values ranged from 0% (sham) to 97%. Additionally, in shunted rats a more pronounced response to intraportal, compared to intrajejunal, infusion suggested a contribution of the intestine to the first-pass elimination of the drug. The bioavailability of intraportal and intrajejunal nitroglycerin is influenced by the extent of portal systemic collaterals. A significant reduction in portal vein pressure in response to nitroglycerin seen in this animal model supports its testing as a therapeutic agent in portal hypertension.