Acute and chronic effects of molsidomine on pulmonary artery pressure and work capacity in patients with coronary heart disease.
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.
Jansen
W
W
Medizinische Klinik I, Städtisches Krankenhaus Leverkusen, F.R.G.
Eggeling
T
T
Meyer
L
L
Tauchert
M
M
Hilger
H H
HH
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
D008981:Molsidomine