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Circulation, Vol 90, 12-16, Copyright © 1994 by American Heart Association
SD Katz, R Rao, JW Berman, M Schwarz, L Demopoulos, R Bijou and TH LeJemtel
BACKGROUND: Tumor necrosis factor-alpha (TNF alpha), which we and others
have shown to be elevated in patients with severe congestive heart failure
(CHF), is involved in the regulation of nitric oxide metabolism. Whether
increased concentrations of TNF alpha affect nitric oxide-mediated
vasodilation in patients with CHF has not been studied previously. METHODS
AND RESULTS: Serum concentrations of TNF alpha, interleukin-1 (IL-1),
interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined in venous
blood (pg/mL) from 17 patients with stable New York Heart Association
classes II and III CHF (mean age, 58 +/- 11 years; mean left ventricular
ejection fraction, 19.5 +/- 7.3) and 17 age-matched normal subjects with
enzyme-linked immunosorbent assays (detection limit of assays, 20 pg/mL).
Forearm blood flows were determined with plethysmography (mL/min per 100
mL) in 17 patients and 7 normal subjects in response to brachial artery
administration of graded concentrations of acetylcholine (10(-6) mol/L and
10(-5) mol/L) and nitroglycerin (10(-7) mol/L and 10(-6) mol/L). Serum
concentrations of TNF alpha were above the detection limits of the assay in
10 of 17 patients with CHF (mean serum concentration, 39.4 +/- 3.8 pg/mL).
Forearm blood flow responses to acetylcholine and nitroglycerin were
significantly greater in these 10 patients than in the 7 patients without
detectable serum TNF alpha and were closely correlated with TNF alpha serum
concentrations (r > or = .81, P < .01 and r > or = .65, P < .05
respectively). In 1 of 17 normal subjects, the serum concentration of TNF
alpha was just above the detection limit of the assay. Serum concentrations
of IL-2 were above the detection limit of the assay in 14 of 17 patients
with CHF (mean serum concentration, 112 +/- 19 pg/mL). IL-2 was not
detected in the serum of normal subjects. Serum concentrations of IL-1 and
IL-6 were below the detection limit of the assays in all patients and
normal subjects assayed. CONCLUSIONS: Increased TNF alpha concentrations
are closely correlated with forearm blood flow responses to regional
administration of acetylcholine and nitroglycerin. The significant
correlation between serum concentrations of TNF alpha and forearm blood
flow responses to acetylcholine and nitroglycerin suggests that both the
inducible and the constitutive forms of nitric oxide synthase are involved
in the regulation of peripheral vasomotor tone in patients with CHF.
ARTICLES
Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure. Relation to nitric oxide- dependent vasodilation in the forearm circulation
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
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