Dose-Response Curve of Angiographically Smooth Human Epicardial Vessel Segments to Intracoronary Injections of Isosorbide Dinitrate

The coronary vasodilator properties of isosorbide dinitrate are well established but the doses generally used (1,000–2,000 μg) are still empirical. We studied, with the use of quantitative coronary arteriography (CAESAR System), the response of smooth vessel segments (>1.85 mm diameter), preconstricted with methylergometrine (400 μg i.v.), to intracoronary injections of graded doses (5–100 μg) of isosorbide dinitrate and the effects of these injections on systemic hemodynamic parameters in 10 patients undergoing diagnostic coronary angiography. Six further patients, in whom the injections of isosorbide dinitrate were replaced by equivalent volumes of normal saline, served as controls. Relative to the diameter 5 min after injection of methylergometrine, the diameter increased by a mean ± SD of 9 ± 7, 26 ± 12, 33 ± 15, 38 ± 14, and 39 ± 16% after injections of 5, 15, 60, 240, and 1,000 μg, respectively, of isosorbide dinitrate. After a cumulative dose of 80 μg, subsequent doses did not cause further significant increases in diameter. Injection of saline in the control group did not alter the coronary diameter. A significant fall in systolic arterial pressure, compared to the control group, occurred at a cumulative dose of 320 μg. The mean arterial pressure and heart rate were unchanged. Significant coronary vasodilation occurs with intracoronary doses of isosorbide much smaller than those currently employed. Cumulative doses of 320 μg or more cause systemic hemodynamic changes without producing additional coronary vasodilation. During interventional cardiac procedures, where systemic hypotension is undesirable, the use of smaller doses of intracoronary isosorbide dinitrate than currently employed may be feasible and should be investigated further.