Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure

Abstract

We investigated the extent and duration of the haemodynamic effects of two regimens of molsidomine, i.e. two tablets of a standard regimen consisting of 4 mg given 6 h apart and one tablet of 16 mg in sustained-release form once daily in 13 patients with chronic congestive heart failure using a placebo-controlled, randomized, double-blind and crossover protocol over a period of 12 h. Both regimens significantly affected systolic, mean and diastolic pulmonary arterial pressure (reductions of up to 15%), right atrial pressure (reductions of up to 35%) and total pulmonary resistance (reductions of up to 18%). The lower dose achieved its maximum action after about 1 h and remained effective for 2 h, whereas the higher dose in sustained-release form showed maximal efficacy at 2 h and remained active even at 12 h. In contrast, only minor changes in arterial blood pressure, systemic vascular resistance and cardiac output were observed on both regimens, almost exclusively at 2 h. Heart rate was not affected by either of the regimens tested. Neither regimen led to any untoward adverse effects. Thus, molsidomine is a potent vasodilating agent which, apart from its effects on preload, also acts on pulmonary arterial and right atrial pressures, leaving systemic circulation largely unaffected on the regimens tested. Administered on its own, it is therefore suitable for treatment of congestive heart failure.

l-Arginine is unlikely to exert neuroendocrine effects in humans via the generation of nitric oxide

“…However, contrary to expectation, no evidence was found to justify this speculation. In the first instance, molsido¬ mine alone had no effect on any hormone tested, although it was used at a dose that is known to be pharmacologically effective in the periphery in the human (17). L-arginine was also shown in the present study to have no effect on the basal or hypoglycaemiastimulated release of vasopressin.…”