Circulation, Vol 85, 2132-2139, Copyright © 1992 by American Heart Association
EJ Eichhorn, JE Willard, L Alvarez, AS Kim, DB Glamann, RC Risser and PA Grayburn
BACKGROUND. Although changes in contractility are often accompanied by
changes in relaxation, a mathematical model of ventricular coupling has not
been described. A model we examined suggests a hyperbolic relation between
measurements of contraction and relaxation. We thus tested the hypothesis
that relatively load-independent measurements of contractility
(end-systolic elastance [Ees]) and relaxation (the slope of the
tau-to-end-systolic pressure relation [R]) were coupled. METHODS AND
RESULTS. To establish the validity of the model, an assessment of Ees and R
was made in 30 subjects who underwent sequential digital ventriculography
and micromanometer pressure measurements during atrial pacing (93 +/- 10
min-1) before and after graded doses of nitroprusside. To establish if a
cyclic AMP (cAMP)-mediated intervention alters coupling, seven of the 30
subjects were studied before and after 3 months of beta-blockade. To
determine if a non-cAMP- mediated intervention alters coupling, 12 other
patients were studied before and after deslanoside. Nonlinear regression
analysis for the initial 30 patients suggested a hyperbolic relation: (Ees)
(R) = 1.05 (r = 0.79, p less than 0.001) with an inflection point near Ees
= 1.02 mm Hg/ml. Thus, with normal or near-normal contractility, relaxation
is normal and not load dependent (R is close to 0). With systolic
dysfunction, relaxation becomes very afterload dependent and so must be
normalized for load. After long-term beta-blockade in patients with severe
left ventricular dysfunction, small improvements in contractility
(elastance) occurred with larger changes in relaxation, but the curve
describing the relation was not displaced. Acute administration of
deslanoside resulted in a large increase in elastance and a smaller change
in relaxation but did not alter coupling. However, the magnitude of the
change in R was dependent on the predrug R value. CONCLUSIONS. These data
suggest contraction and relaxation may be physiologically coupled with
relaxation relatively preserved in early heart failure and more rapid
deterioration in relaxation as elastance falls under 1.02 mm Hg/ml. Both
beta-blockers (which may act through cAMP) and digitalis (which is cAMP
independent) improve contraction and relaxation, but both mechanisms appear
to maintain coupling. The hyperbolic relation between contraction and
relaxation may have important implications regarding therapeutic response
and selection of patients for clinical trials in heart failure.
ARTICLES
Are contraction and relaxation coupled in patients with and without congestive heart failure?
Cardiac Catheterization Laboratory, Dallas Veterans Administration Hospital, Tex.
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