Systemic and regional hemodynamic effects of perindopril in congestive heart failure.
The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right atrial pressure (-60%), and mean pulmonary capillary wedge pressure (-28%), whereas it significantly increased cardiac index (+ 12%). Brachial (+ 130%, pulsed Doppler technique) and renal (+ 34%) blood flows were also significantly increased whereas hepatic blood flow remained unchanged. Brachial flow/cardiac output and renal flow/cardiac output ratios increased significantly from 0.8 to 1.6 and from 13.2 to 16.5, respectively. The maximal decreases in forearm and renal (but not in systemic) vascular resistances were correlated with the basal plasma norepinephrine concentrations but not plasma epinephrine concentrations or plasma renin activity. We conclude that in severe heart failure (a) perindopril considerably improves systemic hemodynamics and exerts an inhomogeneous vasodilating effect, resulting in a redistribution of flows toward the forearm and renal territories, (b) norepinephrine is a major determinant of the arteriolar tone in these two vascular beds, and (c) the pulsed Doppler is a particularly suitable method to non-invasively detect and assess hemodynamic improvements in heart failure patients.
Department of Clinical Pharmacology, Hôpital de Bicêtre, France.
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C
Thuillez
C
C
Richard
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Loueslati
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Auzepy
J F
JF
Giudicelli
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D020913:Perindopril
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D020913:Perindopril