Dose- and time-related vasodilator response of conduit coronary arteries to intracoronary isosorbide dinitrate in human beings

Abstract

The time course of the vasodilation of different segments of the epicardial coronary vasculature after three different doses of intracoronary isosorbide dinitrate (ISDN) was investigated in angiographically normal coronary arteries in 10 patients with quantitative coronary angiography. In five patients, 0.1 mg and 0.3 mg ISDN were injected intracoronary 30 minutes apart, and the effect of each dose was assessed at 1, 5, 10, and 15 minutes after the administration by serial angiograms. In five additional patients, a single dose of 3 mg was injected and coronary vasodilation was assessed at 1, 5, 10, 15, and 20 minutes. After each dose, dilation of epicardial coronary arteries occurred within 1 minute, peaked at 5 minutes and progressively decreased thereafter. Relative to control, peak percent diameter increase was (mean ± SEM) 10% ± 0.9% ( p < 0.01), 18.5% ± 1.5% ( p < 0.01), and 26% ± 2.1% ( p < 0.01) after 0.1, 0.3, and 3.0 mg, respectively. When small (1 to 2 mm), medium (2 to 3 mm), and large (>3 mm) vessels were separately analyzed, peak response was respectively 12% ± 1.3% ( p < 0.01), 9% ± 1.9% ( p < 0.01), and 7% ± 1% ( p < 0.05) after 0.1 mg ISDN; 22% ± 1.3% ( p < 0.01), 16% ± 1.3% ( p < 0.01), and 12% ± 0.8% ( p < 0.01) after 0.3 mg; and 38% ± 2.4% ( p < 0.01), 22% ± 2.1% ( p < 0.01), and 17% ± 2% ( p < 0.01) after 3.0 mg. The duration of the response increased with the dose, but was inversely related to the size of the vessel. In small vessels (<2 mm diameter), a significant dilation was found up to 10 minutes after 0.1 mg and up to 15 and 20 minutes after 0.3 and 3.0 mg, respectively. Medium vessels (2 to 3 mm diameter) dilated significantly up to 5 minutes after 0.1 mg, up to 10 minutes after 0.3 mg, and up to 20 minutes after 3.0 mg. Large vessels (>3 mm diameter) were found significantly dilated at 5 minutes after 0.1 mg, at 1 and 5 minutes after 0.3 mg, and up to 10 minutes after 3.0 mg. Thus, epicardial coronary vasodilation after the intracoronary injection of isosorbide dinitrate appears to be a function of both the dose injected and the vessel size.