Circulation, Vol 79, 491-502, Copyright © 1989 by American Heart Association
H Drexler, U Banhardt, T Meinertz, H Wollschlager, M Lehmann and H Just
To discover the underlying mechanisms involved in the beneficial long- term
effects of angiotensin converting enzyme (ACE) inhibitors, we investigated
the systemic and peripheral effects of short- and long- term ACE inhibition
in patients with chronic heart failure. After assessing the short-term
effects and dose titration with cilazapril, a new long-acting ACE
inhibitor, 21 patients were randomized to receive either placebo or the ACE
inhibitor. Seventeen patients completed the 3- month treatment. Central
hemodynamic output, femoral blood flow (measured by thermodilution), oxygen
saturation, and lactate and norepinephrine levels were determined
simultaneously in the femoral vein and radial artery during treatment and
after a 3-month rest and during symptom-limited bicycle exercise.
Short-term ACE inhibition improved rest and exercise hemodynamic output,
but it did not alter peak femoral blood flow, calculated leg oxygen
consumption, or systemic oxygen uptake during exercise, despite significant
reduction in femoral norepinephrine extraction and arterial angiotensin
levels during exercise. In contrast, long-term ACE inhibition further
improved exercise cardiac output and increased leg blood flow (from 2.3 to
2.9 l/min, p less than 0.05), leg oxygen consumption (from 277 to 403
ml/min, p less than 0.05), and systemic oxygen uptake (from 1,133 to 1,453
ml/min, p less than 0.05), whereas these variables remained unchanged with
placebo treatment (p less than 0.02 between groups). Moreover, a moderate
but significant increase in femoral oxygen extraction occurred after
long-term therapy (ACE inhibitor: from 76% to 83%, p less than 0.05;
placebo: from 75% to 74%, NS; p less than 0.01 between groups). We conclude
that long-term ACE inhibition is clinically beneficial in that it improves
blood flow to skeletal muscle during exercise over time. The long-term
effects of ACE inhibition are, in part, probably related to peripheral
(vascular) mechanisms, for example, by reversing the inability of
peripheral vessels to dilate and by improving oxygen utilization.
ARTICLES
Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure. A double- blind, placebo-controlled trial
Medizinische Klinik III, University of Freiburg, FRG.
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