oxadiazoles and Coronary-Vasospasm

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.

Topics: Coronary Angiography; Coronary Vasospasm; Coronary Vessels; Humans; Molsidomine; Oxadiazoles; Sydnones; Time Factors; Vasodilator Agents

We studied the effects of intracoronary injections of SIN-1 (0.8 mg), the active metabolite of molsidomine, on coronary artery diameters and coronary stenoses. In nine patients with abnormal angiograms measurements were made 4 and 8 minutes after SIN-1 administration. There was a statistically significant increase in coronary luminal diameter in proximal, medial, and distal segments as well as at the level of the stenoses. At 4 minutes after administration distal segments showed a mean increase in diameter of 50%, compared to a mean increase of 26% in proximal segments. In six patients with normal angiograms SIN-1 abolished three of four coronary spasms induced by ergonovine maleate. A protective effect of SIN-1 against the vasoconstrictor effects of ergonovine was still present at 8 minutes after administration. Heart rate and blood pressure remained unchanged throughout the study. We conclude that the vasodilation induced by SIN-1 in normal and stenotic coronary arteries is probably an important contribution to the antianginal efficacy of molsidomine and suggests that molsidomine may be effective in the prophylaxis of variant angina.

Topics: Coronary Angiography; Coronary Vasospasm; Coronary Vessels; Female; Humans; Male; Middle Aged; Molsidomine; Oxadiazoles; Sydnones; Vasodilator Agents

A provocative test of coronary artery spasm caused by alkalosis was used to evaluate a possible anti-coronary artery spasm effect of molsidomine. The rapid infusion of an alkaline buffer followed by maximal voluntary hyperventilation in 10 patients with angina at rest led to the appearance of anginal pain and significant, transient ischemic changes of the ST segment resulting from alkalosis-induced coronary spasm. A second provocative test was performed under the same conditions, 24 hours later, after the administration of 4 mg of molsidomine. Molsidomine prevented the development of coronary artery spasm in 8 of the 10 patients in the study group. These preliminary results justify further clinical evaluation of molsidomine in the treatment of vasospastic angina.

Topics: Alkalosis; Blood Pressure; Coronary Vasospasm; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Molsidomine; Oxadiazoles; Sydnones; Vasodilator Agents

A test provocation of coronary artery spasm by alkalosis was used to evaluate a possible anti-coronary artery spasm effect of molsidomine. The rapid infusion of an alkaline buffer followed by maximal voluntary hyperventilation in 10 patients with angina at rest led to the appearance of angina pain and significant, transient ischaemic changes of the ST segment, due to alkalosis induced coronary spasm. A second provocation test was performed under the same conditions, 24 hours later, after the prior administration of 4 mg of molsidomine. Molsidomine prevented the development of coronary artery spasm in 8 of the 10 patients in the study group. These preliminary results justify further clinical evaluation of molsidomine in the treatment of vasospastic angina.

Topics: Alkalosis; Coronary Vasospasm; Electrocardiography; Female; Humans; Male; Middle Aged; Molsidomine; Oxadiazoles; Sydnones