Acute hemodynamic effects of single-dose nicorandil in coronary artery disease

Fifteen patients undergoing routine cardiac catheterization for investigation of chest pain were given a single dose of 40 mg of nicorandil either sublingually (8 patients) or orally (7 patients). Fourteen patients had angina (11 effort, 3 atypical) and 1 had palpitations but all had normal left ventricular (LV) function (mean LV end-diastolic pressure 7.4 mm Hg). Hemodynamic evaluations and plasma drug concentrations were performed at baseline and 5, 15, 30, 45 and 60 minutes after dosing. In addition, venous compliance was determined at baseline, 15 and 45 minutes using forearm venous occlusion plethysmography. Significant (p <0.05) central and peripheral hemodynamic changes occurred within 15 minutes. A reduction in preload was apparent from a decrease in LV end-diastolic pressure (from 7.4 ± 1.7 to −2.6 ±1.5 mm Hg [p <0.05]) and a simultaneous decrease in mean pulmonary artery pressure (from 10.8 ± 0.7 to 5.1 ± 0.6 mm Hg [p <0.05]) at 60 minutes after dosing. This reduction in preload may reflect the venous vasodilatory activity of the drug as indicated by significant (p <0.05) increases in venous capacitance at 15 and 45 minutes. Total peripheral resistance decreased to a maximum of 19% (p <0.05) at 30 minutes and then began to return toward baseline. This effect in reducing afterload led to a substantial decrease (p <0.05) in systolic and diastolic aortic blood pressures, which was maximal at 45 minutes (34 and 21%, respectively). Transient increases in heart rate (p <0.05) and cardiac contractility indexes (p >0.05) were also observed. In addition, there was a gradual decrease in cardiac output that became significant (p <0.05) at 60 minutes. Severe hypotension that necessitated withdrawal from the study was observed in 2 patients and lower doses should be used for future investigation.