[Hemodynamic effect of molsidomine in coronary patients with heart failure with clinically manifest nitrate tolerance].
Objective of the present study was to investigate the hemodynamic response to molsidomine in nitrate tolerance state. In 13 out of 16 patients (5 women, 11 men, 62 [53/71] years [median, 25%/75%-percentiles]) with chronic heart failure (NYHA stage II-III; median angiographic ejection fraction (EF) 55%) and coronary artery disease (stenosis of at least 75%) the development of tolerance under the continuous infusion of high doses of nitroglycerin (10 mg/h) was observed. Tolerance was defined as a benefit loss of at least 50% of the initial nitroglycerin effect with respect to the pulmonary capillary wedge pressure. Compared to the state of tolerance to nitroglycerin the infusion of 10 mg molsidomine over 15 minutes resulted in significant changes of the median values (25%/75%-percentiles) of mean right atrial pressure from 16 (12/21) to 9 (5/12) mmHg (p < 0.01), mean pulmonary artery pressure from 37 (30/40) to 24 (20/30) mmHg (p < 0.001), mean pulmonary capillary wedge pressure from 22 (18/25) to 15 (10/22) mmHg (p < 0.01) and cardiac output from 4.1 (3.5/4.7) to 5.2 (4.2/5.6) l/min (p < 0.01). This action of molsidomine corresponded to a complete overcoming (> 100%) of the benefit loss observed during the development of nitrate tolerance with respect to all above-mentioned hemodynamic parameters. Under parallel maintainance of nitroglycerin infusion (10 mg/h) these hemodynamic effects of molsidomine, i.e. at least 90% of the peak effect, lasted for 147 (130/182) minutes (median, 25%/75%-percentiles). Baseline values, i.e. a loss of at least 75% of the molsidomine effect, were only reached after 363 (319/412) minutes (median, 25%/75%-percentiles).(ABSTRACT TRUNCATED AT 250 WORDS)
Störk
T
T
Kardiologie/Intensivmedizin, Universitätsklinikum Rudolf Virchow, FU Berlin.
Möckel
M
M
Störk
S
S
Piske
G
G
Danne
O
O
Bodemann
T
T
Müller
R
R
Eichstädt
H
H
Hochrein
H
H
D000368:Aged; D003327:Coronary Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000009:adverse effects / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000627:therapeutic use*
D008981:Molsidomine; D005996:Nitroglycerin
Hämodynamische Wirkung von Molsidomin bei herzinsuffizienten Koronarkranken mit klinisch manifester Nitrattoleranz.