Effects of continuous intravenous infusion of isosorbide dinitrate on development of tolerance to vasodilating action in human epicardial coronary arteries

Abstract

This study was performed to determine the effects of long-term intravenous infusion on the coronary vasodilating actions of continuous intravenous and bolus intracoronary administration of isosorbide dinitrate (ISDN). With quantitative coronary angiography, the coronary diameter and the vasodilating response to intracoronary ISDN (1 mg) at angiographically normal segments were studied before and after intravenous administration of ISDN, 10 to 60 μg/min for 1 hour, 2 days, or 5 days. The vasodilating effects of intravenous ISDN were 72% ± 13%, 65% ± 21%, and 6% ± 11% of the response to intracoronary ISDN in the baseline study in each group. Irrespective of the duration of intravenous infusion, subsequent intracoronary ISDN dilated coronary arteries to extent similar to that observed in each baseline study. In conclusion, significant coronary vasodilating effects of intravenous ISDN were observed after a 2-day infusion, whereas tolerance to the vasodilating effects apparently developed within 5 days of infusion. The vasodilating response to bolus intracoronary ISDN was preserved even when the vasodilating effects of intravenous ISDN were no longer present.