Circulation, Vol 85, 1743-1750, Copyright © 1992 by American Heart Association
LA Mulieri, G Hasenfuss, B Leavitt, PD Allen and NR Alpert
BACKGROUND. In congestive heart failure (idiopathic dilated
cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease
in end-diastolic left ventricular volume, depressed peak rates of left
ventricular pressure rise and fall, and depressed heart-rate- dependent
potentiation of contractility (bowditch treppe). We studied contractile
function of isolated left ventricular myocardium from New York Heart
Association class IV-failing and nonfailing hearts at physiological
temperature and heart rates in order to identify and quantitate
abnormalities in myocardial function that underlie abnormal ventricular
function. METHODS AND RESULTS. The isometric tension- generating ability of
isolated left ventricular strips from nonfailing and failing human hearts
was investigated at 37 degrees C and contraction frequencies ranging from
12 to 240 per minute (min-1). Strips were dissected using a new method of
protection against cutting injury with 2,3-butanedione monoxime (BDM) as a
cardioplegic agent. In nonfailing myocardium the twitch tension-frequency
relation is bell- shaped developing 25 +/- 2 mN/mm2 at a contraction
frequency of 72 min- 1 and peaking at 44 +/- 3.7 mN/mm2 at a contraction
frequency of 174 +/- 4 min-1. In failing myocardium the peak of the curve
occurs at lower frequencies between 6 and 120 min-1 averaging 81 +/- 22
min-1, and it develops 48% (p less than 0.001) and 80% (p less than 0.001)
less tension than in nonfailing myocardium at 72 and 174 min-1,
respectively. Between 60 and 150 min-1 tension increases by 107% in
nonfailing myocardium, but it does not change significantly in failing
myocardium. Peak rates of rise and fall of isometric twitch tension vary in
parallel with twitch tension as stimulation frequency rises in nonfailing
myocardium but not in failing myocardium. CONCLUSIONS. The quantitative
agreement between these results from isolated myocardium and those from
catheterization laboratory measurements on intact humans suggest that
alterations of myocardial origin, independent of systemic factors, may
contribute to the above mentioned abnormalities in left ventricular
function seen in dilated cardiomyopathy.
ARTICLES
Altered myocardial force-frequency relation in human heart failure
Department of Physiology and Biophysics, University of Vermont College of Medicine, Medical Center Hospital of Vermont, Burlington 05405.
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