Effects of molsidomine on left ventricular dimensions and cardiac function in patients with chronic heart failure.

The effects of molsidomine were studied in seven patients with refractory congestive heart failure by means of two-dimensional echocardiography. Four milligrams of molsidomine or placebo was sublingually administered in a double-blind crossover manner. End-diastolic dimension, end-systolic dimension, and mean velocity of circumferential fiber shortening were measured just below the mitral valve before drug or placebo administration and 1 hour later. No significant changes were observed with placebo. Heart rate and mean arterial pressure were not significantly modified with Molsidomine (80 to 83 bpm and 100 to 97 mm Hg, respectively). The reduction in end-diastolic dimension (67 to 61 mm; 9%; P less than 0.01) was slightly greater than the decline in end-systolic dimension (59 to 54 mm; 8%; p less than 0.01). The mean velocity of circumferential fiber shortening increased from 0.4 to 0.5 sec-1 but did not achieve statistical significance. Thus sublingual administration of molsidomine in patients with chronic heart failure reduces end-diastolic more than end-systolic dimension without effect on blood pressure, suggesting a predominant action on cardiac preload.

Effect of oral sustained-release nitroglycerin on exercise capacity in angina pectoris: dose-response relation and duration of action during double-blind crossover randomized acute therapy.

Ten men with documented coronary artery disease and stable exertional angina underwent a double-blind crossover study to examine the benefit and the duration of action on their symptom-limited exercise capacity of 2 doses (2.5 and 6.5 mg) of sustained-release nitroglycerin (SRNG). A multistage bicycle test was performed in the sitting position by steps of 30 W each 3 minutes until the onset of typical angina pectoris. It was performed 24 hours before the start of the study; 1 and 5 hours after administration of placebo, and repeated after 2.5 and 6.5 mg of SRNG administered in a double-blind crossover study according to a 4 successive days protocol. No differences appeared between administration of placebo (1 and 5 hours) and the results obtained at the first exercise test. The dose of 2.5 mg of SRNG was effective on the symptom-limited working capacity but only at 1 hour (+9%; p less than 0.01). The dose of 6.5 mg was more effective both at 1 hour (+25%; p less than 0.001) and at 5 hours (+27%; p less than 0.001). All patients had angina at a higher heart rate (+5 to 8%; p = NS [not significant] and p less than 0.01), whereas systolic blood pressure and double product tended to be slightly but insignificantly increased. S-T depression at the onset of angina was insignificantly changed with placebo, and 2.5 and 6.5 mg of SRNG. It is concluded that 6.5 mg of orally administered SRNG is effective during at least 5 hours, and that the magnitude of the benefit and its duration are dose-related.