Circulation, Vol 84, 1589-1596, Copyright © 1991 by American Heart Association
SH Kubo, TS Rector, AJ Bank, RE Williams and SM Heifetz
BACKGROUND. Endothelial cells produce a number of substances, collectively
termed endothelium-derived relaxing factor (EDRF), that promote local
relaxation of vascular smooth muscle. Although studies have demonstrated
defects in endothelium-dependent vasodilation in animal models of
hypertension, atherosclerosis, and heart failure, there are only limited
data from human subjects because of the difficulty in obtaining fresh
vascular segments. METHODS AND RESULTS. To address the hypothesis that
endothelium-dependent vasodilation is attenuated in patients with heart
failure, we measured forearm blood flow responses to the intra-arterial
administration of methacholine, a known stimulus of EDRF release through
muscarinic receptors. In 14 normal subjects, a dosage range of methacholine
increased forearm blood flow by 5.26 +/- 0.63, 10.50 +/- 0.63, and 13.22
+/- 0.86 ml/min/100 ml forearm volume (FAV); these responses were 1.98 +/-
0.46, 5.48 +/- 0.79, and 8.50 +/- 1.53 ml/min/100 ml FAV in 14 patients
with heart failure. When pooled over all doses, the responses were
strikingly less in the patients with heart failure (5.32 +/- 0.31 versus
9.52 +/- 0.60 ml/min/100 ml FAV; p = 0.0003). In a second study, the
average difference in forearm blood flow responses between patients with
heart failure and normal subjects with methacholine was significantly
greater than the average difference between the groups with nitroprusside
(4.04 +/- 1.10 versus 2.20 +/- 0.71 ml/min/100 ml FAV; p = 0.04). The
decreased methacholine responses in the patients with heart failure were
not related to age (r = 0.39; p = NS) or etiology because there was no
difference in the responses between patients with ischemic heart disease
and those with idiopathic cardiomyopathy. CONCLUSIONS. These data suggest
that endothelium-dependent vasodilation is attenuated in patients with
heart failure. Although the mechanisms of the decreased
endothelium-dependent responses in heart failure are not known, this
impaired local vasodilation may contribute to abnormalities in
vasoconstriction that are characteristic of heart failure.
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Endothelium-dependent vasodilation is attenuated in patients with heart failure
Cardiovascular Division, University of Minnesota, Minneapolis 55455.
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