Active and passive changes in coronary diameter after vasodilation with SIN-1, the active metabolite of molsidomine

The vasodilating effects of intracoronary injections of 0.4 mg of SIN-1, the active metabolite of molsidomine, on epicardial coronary arteries and coronary stenoses were evaluated in 14 patients with coronary artery disease in a double-blind, randomized fashion vs placebo. Nine additional patients with well defined coronary stenoses received 0.4 mg of SIN-1 as well. Diameter changes of nonstenotic coronary arteries in proximal, medial, and distal coronary segments as well as changes of the residual luminal diameters within coronary stenoses were determined before (K), immediately after (M1), and 10 minutes after (M2) intracoronary administration of SIN-1. Aortic pressures and heart rate were monitored continuously. After administration of SIN-1, the diameters of nonstenotic coronary arteries increased in proximal segments by 9.4% (M1) and 11.7% (M2), in medial segments by 17.9% (M1) and 17.6% (M2), and in distal segments by 25.6% (M1) and 28.8% (M2). Within coronary stenoses the residual luminal diameters showed mean increases of 31.5% (M1) and 48.3% (M2). Placebo administration did not alter coronary diameters significantly. Aortic pressure and heart rate did not change after administration of SIN-1 or placebo. SIN-1 effectively dilates nonstenotic and stenotic coronary segments, as do nitrates and calcium channel blockers. By intracoronary injections, the direct effects on coronary vessels can be evaluated without interference with systemic effects. The increase in the residual luminal diameters within dynamic coronary stenoses after administration of SIN-1 is probably an important antianginal mechanism also for molsidomine.