[Hemodynamic and humoral effects of parenteral therapy with intravenously administered ACE inhibitor quinaprilat in patients with advanced heart failure].
The hemodynamic and neurohumoral effects of single and multiple doses of intravenous quinaprilat were assessed and compared with placebo in a double-blind design. The study group included 50 patients aged between 33 and 76 years with NYHA Class III and IV heart failure. The patients were randomized into three treatment groups to receive low (0.5 and 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) intravenous doses of quinaprilat or placebo on day 1, and, based on the responses, q6h on two further days. The hemodynamic parameters were determined by right-heart catheterization. Quinaprilat is the active metabolite of quinapril, an ACE inhibitor with high affinity for the angiotensin converting enzyme, which is formulated for oral application. Compared with placebo, single and multiple doses of quinaprilat increased cardiac index by 25% (p < 0.05) and simultaneously decreased both peripheral vascular resistance by 25% (p < 0.05) and left ventricular filling pressures by 33% (p < 0.05). There was a dose-related decrease in mean right atrial pressure by 47% (p < 0.05) without significant heart rate changes (-3-5 bpm). The mean artery pressure showed a dose-related maximum decrease of 4-9 mm Hg 45-60 min after single-dose quinaprilat and of 7-10 mm Hg (p < 0.05) after repetitive dosing. Maximum changes were observed 15-90 min after drug application. The hemodynamic changes after multiple-dose quinaprilat were similar to those observed following single doses and generally persisted during the total observation period of 6 h. Compared with placebo, quinaprilat reduced ACE activity and angiotensin II and aldosterone concentrations, and increased plasma renin activity. There were no significant changes with regard to plasma catecholamines and the atrial natriuretic factor, although a slight decrease could be observed. The study results obtained in patients with advanced heart failure support both the safety and favorable hemodynamic and neurohumoral effects of intravenous quinaprilat over an observation period of 3 days.
Mitrovic
V
V
Kerckhoff-Klinik, Bad Nauheim.
Mudra
H
H
Bonzel
T
T
Schmidt
W
W
Schlepper
M
M
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D009320:Atrial Natriuretic Factor / Q000097:blood; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012083:Renin / Q000097:blood; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D002395:Catecholamines; D006728:Hormones; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; C054501:quinaprilat; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D007703:Peptidyl-Dipeptidase A; D012083:Renin
Hämodynamische und humorale Auswirkungen einer parenteralen Therapie mit dem intravenös verabreichbaren ACE-Hemmer Quinaprilat bei Patienten mit fortgeschrittener Herzinsuffizienz.