Hemodynamic effects of molsidomine, isosorbide dinitrate, and nifedipine at rest and during exercise

Abstract

In the first study the hemodynamic effects of standard doses of molsidomine (2 mg intravenously), isosorbide dinitrate (ISDN) (5 mg sublingually), and nifedipine (20 mg sublingually) were assessed at rest and under exercise conditions in a group of 30 patients with coronary heart disease. With the patients at rest both molsidomine and ISDN were associated with prompt reductions in left ventricular end-diastolic pressure and mean pulmonary artery pressure, whereas nifedipine was associated with slight reductions in left ventricular end-diastolic pressure and mean pulmonary artery pressure that did not attain statistical significance. Nifedipine and ISDN caused a decrease in mean aortic blood pressure, which resulted in a reactive increase in heart rate that was only significant with nifedipine. After administration of molsidomine, there was no significant change in mean aortic pressure at rest. There were reductions in stroke volume index and cardiac index after administration of molsidomine and ISDN. Nifedipine, however, was associated with significant increases in stroke volume index and cardiac index. None of the three test substances caused changes of contractility parameters. Under exercise conditions reductions in left ventricular end-diastolic pressure, mean pulmonary pressure, and mean aortic pressure were documented following administration of molsidomine, ISDN, and nifedipine. There were no major changes in maximum heart rate or stroke volume index during exercise with any of the three drugs. However, nifedipine was associated with a significant increase in cardiac index, whereas molsidomine and ISDN produced no major changes. In a second clinical study the short-term effects of oral administration of 2 mg of molsidomine before and after a 2-week course of therapy with 2 mg of molsidomine four times daily were determined in 10 patients with the diagnosis of coronary artery disease. There was no significant difference in hemodynamic parameters at rest and during exercise between initial findings on the first and fourteenth days of the study. Comparisons of the results with the first study show that oral and intravenous administration of molsidomine is followed by comparable changes in hemodynamic parameters. Our results demonstrate that molsidomine, ISDN, and nifedipine influence preload and afterload but that their effects on venous and arterial resistance differ in degree. At standard therapeutic doses molsidomine and ISDN reduce the hemodynamic parameters of preload, whereas nifedipine is associated primarily with afterload reduction. These effects are also demonstrable under exercise conditions. All three substances limit the increase in pulmonary artery pressure caused by exercise-induced ischemia. There was no significant loss of hemodynamic effects after a 2-week course of treatment with molsidomine.