title: Acute and chronic effects of molsidomine on pulmonary artery pressure and work capacity in patients with coronary heart disease.
abstract: To test the clinically supposed development of tolerance during chronic molsidomine therapy we studied a total of 11 patients with angiographically-proven coronary heart disease at rest and during ergometric exercise (supine position; submaximal, i.e. 50 W for 3 min, and maximal exercise). Pulmonary arterial pressure (PAPmean, floating catheter), arterial blood pressure (RR, cuff method), work capacity (W x min) and duration of exercise loading (sec) were measured at rest and on exercise before and during chronic (4 weeks) oral therapy with 3 x 4 mg day-1 of molsidomine. Acute administration of 4 mg molsidomine reduced the mean arterial resting pressure by 12% and under submaximal exercise loading by 8%. After molsidomine, the PAPmean was reduced by 35% at rest; following a period of treatment of 4 weeks no significant decrease in efficacy could be discerned (PAPmean reduction by 31%). Under submaximal and maximal exercise the PAPmean dropped by 44% and 37%, respectively (35.5 +/- 6.7 cf. 19.9 +/- 4.5 mmHg; 39.2 +/- 6.5 cf. 24.8 +/- 7.0 mmHg), whilst simultaneously the work capacity increased by 93% (281 +/- 108 cf. 545 +/- 254 W x min). After 4 weeks treatment with 12 mg day-1 of molsidomine, the PAPmean of 22.4 +/- 6.6 mmHg and 30.1 +/- 9.9 mmHg under identical exercise loading conditions, remained significantly below the exercise load value prior to the onset of medication. The molsidomine-induced increase in the exercise tolerance was maintained throughout the long-term medication (537 +/- 268 W x min). With a four-week treatment with daily doses of molsidomine there was a persistent effect on the pulmonary arterial pressure and the work capacity. Thus development of tolerance during high dose, long-term molsidomine therapy is not to be expected.
authors: Medizinische Klinik I, Städtisches Krankenhaus Leverkusen, F.R.G.
authors: W
authors: W
authors: Jansen
authors: T
authors: T
authors: Eggeling
authors: L
authors: L
authors: Meyer
authors: M
authors: M
authors: Tauchert
authors: H H
authors: HH
authors: Hilger
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004361:Drug Tolerance; D005080:Exercise Test; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000503:physiopathology
chemical_list: D008981:Molsidomine