Hemodynamic Effects of Nicorandil, Isosorbide Dinitrate, and Dihydralazine in Healthy Volunteers

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Abstract
In this randomized, double-blind, crossover, single-dose study with 12 healthy subjects, we determined the hemodynamic changes and their time kinetics after administration of the mononitrate nicorandil (60 mg s.l.) and compared these effects with changes after administration of isosorbide dinitrate (ISDN: 20 mg s.l.), dihydralazine (10 mg i.v.), and placebo. Mechanocardiography, electrical impedence cardiography, and M-mode echocardiography measured drug effects. Dihydralazine increased heart rate, systolic pressure, and ventricular ejection time, and it decreased peripheral resistance, diastolic pressure, preejection period, end-systolic diameter and wall stress; these changes indicate an intense, pure afterload reduction. ISDN decreased systolic pressure, peripheral resistance, end-diastolic and systolic diameters and wall stress, shorted the ejection time, and prolonged the preejection period. The responses suggest ISDN causes a notable preload reduction accompanied by some afterload reduction. Nicorandil''s effects were similar to those of ISDN in that the reductions in preload were equal, although the afterload reduction was more intense. Nicorandil''s effects reached significance within 10 min, reached a maximum by 60 min, and had not vanished at 4 h. A drug with this profile and time kinetics should be tested further in situations requiring pre- and afterload reductions.