Coronary microvascular response to intracoronary administration of nicorandil

Nicorandil is an antianginal drug that causes potent coronary vasodilation of both epicardial and resistance vessels. To measure the dose-response kinetics of bolus injections of intracoronary nicorandil and to compare the vasodilatory response to nicorandil with that of intracoronary papaverine in humans, coronary blood flow velocity was measured in 30 patients using a 3Fr intravascular Doppler catheter. Continuous intravenous nitroglycerin 6 to 8 micrograms/min was infused to achieve maximal vasodilation of the epicardial vessels. Bolus doses of nicorandil dissolved in warmed saline solution were injected into the left (0.1, 0.2, 0.5, 1.0, 1.5, and 2.0 mg) and right (0.1, 0.2, 0.4, 0.8, 1.0, and 1.5 mg) coronary arteries. Intracoronary nicorandil caused a dose-dependent increase in coronary flow velocity and a decrease in coronary vascular resistance. Maximal vasodilatory effects equivalent to those obtained with 12 +/- 2 mg of intracoronary papaverine were induced with nicorandil 1.5 mg in the left coronary artery, and effects similar to those of 10 +/- 2 mg of papaverine were produced with nicorandil 1.0 mg in the right coronary artery. The time from injection of nicorandil to the onset of maximal hyperemia and duration of hyperemia were significantly shorter after nicorandil than after papaverine in both coronary arteries. Each dose of nicorandil produced no clinical symptoms and fewer changes in systemic hemodynamics and electrocardiographic QT intervals than did papaverine. These results suggest that a bolus administration of intracoronary nicorandil can safely, quickly, and reliably induce maximal coronary hyperemia comparable to that achieved with intracoronary papaverine in humans.