Systemic, pulmonary, brachial, renal and hepato-splanchnic hemodynamic effects of spirapril in severe congestive heart failure.
The effects of a single oral dose (6 mg) of the angiotensin-I converting enzyme inhibitor, spirapril, on systemic, pulmonary and regional (brachial, renal, hepato-splanchnic) hemodynamics as well as on biological parameters investigating the renin-angiotensin-aldosterone and sympathetic nervous systems were studied over a 24-hour period in eight patients with severe congestive heart failure (CHF). As compared to pretreatment values, spirapril significantly decreased mean arterial (-19%, peak effect), right atrial (-42%), mean pulmonary arterial (-38%) and pulmonary capillary wedge (-46%) pressures. Spirapril significantly decreased heart rate (-14%) and increased stroke volume index (+43%) thus resulting in a slight increase in cardiac index. All these effects were maximal between 2.5 and 4 h. Brachial artery diameter (+12%) and brachial (+41%) and renal (+36%) blood flows increased significantly whereas brachial (-41%) and renal (-36%) vascular resistances decreased significantly. All these effects were usually maximal between 1 and 2.5 h. Hepato-splanchnic hemodynamics were not drug-affected. Spirapril significantly inhibited plasma converting enzyme activity (-96% at 4 h), increased plasma renin activity (+505% at 4 h), and decreased plasma aldosterone (-46% at 24 h), norepinephrine (-31% at 24 h) and atrial natriuretic factor (-33% at 7 h). Thus, in severe CHF, acute administration of spirapril, 6 mg orally, exerts both arterial and venous vasodilating properties and improves both the systemic and regional hemodynamics and the biological status of the patients.
Bellissant
E
E
Service de Pharmacologie Clinique, Centre Hospitalier de Bicêtre, Le Kremlin-Bicêtre, France.
Annane
D
D
Pussard
E
E
Thuillez
C
C
Giudicelli
J F
JF
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D004656:Enalapril / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril