Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 μg/kg, to 22 patients with chronic congestive heart failure (ejection fraction < 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 μg/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 μg/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 μg/kg dose. The cardiac index was reduced by the 158 μg/kg dose, but increased after 251, 398, and 630 μg/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 μg/kg dose level. Thus, nicorandil displays a complex hemodynamic profile over the dose range tested, which most likely reflects variable systemic arterial and venous vasodilation in response to potassium channel activation and nitrate effects at the different doses. Nicorandil improves the hemodynamic abnormalities of heart failure without concomitant tachycardia or increase in plasma catecholamines; this interesting pharmacological profile suggests a possible role for nicorandil in the treatment of congestive heart failure.