Circulation, Vol 88, 2700-2704, Copyright © 1993 by American Heart Association
LA Mulieri, BJ Leavitt, BJ Martin, JR Haeberle and NR Alpert
BACKGROUND. Postoperative ejection phase parameters and patient survival
rates for mitral valve replacement surgery are considerably lower than for
similar aortic valve surgery. While chordal transection probably is the
major contributor to the lowered values, there is also evidence for
decreased preoperative myocardial contractile reserve in mitral
regurgitation patients. This study characterizes abnormalities in the
force-frequency relation that may underlie impaired function of myocardium
isolated from mitral regurgitation patients with New York Heart Association
class II-III heart failure. METHODS AND RESULTS. Left ventricular
epicardial myocardium was obtained by surgical biopsy during mitral valve
replacement surgery in patients with mitral regurgitation heart failure
(left ventricular ejection fraction, 0.64 +/- 0.05) and during coronary
artery bypass surgery in patients with normal ventricular function. The
steady-state twitch tension versus frequency relation was measured in
myocardial strip preparations (37 degree C, 12 to 228 min-1) in the absence
and presence of forskolin. Relative to normal function, peak isometric
twitch tension in mitral regurgitation is depressed by 50% (P < .02) and
74% (P < .003) at contraction frequencies of 60 min-1 and 168 min-1,
respectively. The slope of the tension-frequency curve is blunted and its
peak is shifted to a lower frequency (mitral regurgitation: 134 min-1;
normal function: 173 min-1; P < .02). The myosin heavy chain
concentration did not differ between mitral regurgitation and normal
function strips (53 +/- 4 versus 54 +/- 4 nmol/g blotted wt). Forskolin
(0.5 mumol/L) completely reversed the tension depression, blunting, and the
lowered peak frequency in the mitral regurgitation preparations.
CONCLUSIONS. Preoperatively, myocardial tension generation in mitral
regurgitation patients is severely depressed, and the force-frequency curve
is blunted and has a negative slope in the exercise range of heart rates.
The reversal of these defects by forskolin suggests that abnormal
excitation-contraction coupling may underlie the decreased contractile
reserve in mitral regurgitation patients.
ARTICLES
Myocardial force-frequency defect in mitral regurgitation heart failure is reversed by forskolin
Department of Molecular Physiology and Biophysics, University of Vermont, Burlington 05405-0068.
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