Circulation, Vol 88, 136-145, Copyright © 1993 by American Heart Association
IT Meredith, G Eisenhofer, GW Lambert, EM Dewar, GL Jennings and MD Esler
BACKGROUND. Increased concentrations of norepinephrine in coronary sinus
plasma reported in congestive heart failure (CHF) could result from
increased cardiac sympathetic nerve firing and norepinephrine release or
from failure of neuronal uptake mechanisms to recapture released
norepinephrine. We have applied neurochemical indexes of cardiac
sympathetic nerve function in heart failure patients to delineate the
underlying neural pathophysiology. METHODS AND RESULTS. Cardiac
norepinephrine synthesis, assessed from the cardiac overflow of the
norepinephrine precursor dihydroxyphenylalanine (DOPA), intraneuronal
metabolism estimated from the overflow of the intraneuronal metabolite
dihydroxyphenylglycol (DHPG), neuronal norepinephrine reuptake assessed
from the fractional extraction of plasma-tritiated norepinephrine and
production of tritiated DHPG across the heart, and norepinephrine spillover
to plasma were examined in eight patients with CHF caused by coronary
artery disease (left ventricular ejection fraction of 26 +/- 5%, mean +/-
SEM) and 14 age- matched healthy subjects. Cardiac norepinephrine spillover
was increased eightfold in CHF subjects (127 ng/min versus 14 ng/min in
healthy subjects; standard error of the difference [SED], 8 ng/min; P <
.002), and cardiac DOPA was increased twofold (P < .02). The fractional
extraction of tritiated norepinephrine across the heart was marginally less
in CHF subjects (0.63 versus 0.73 in normal subjects; SED, 0.02), but the
extent to which pharmacological neuronal uptake blockade with desipramine
reduced the cardiac extraction of tritiated norepinephrine (by 71% versus
73% in normal subjects) and reduced the production of tritiated DHPG
derived from uptake and intraneuronal metabolism of tritiated
norepinephrine was similar in CHF patients and healthy subjects.
CONCLUSIONS. The marked increase in norepinephrine spillover from the heart
in CHF attributable to coronary artery disease results primarily from an
increase in sympathetic nerve firing and neuronal release of
norepinephrine, not from faulty neuronal reuptake of norepinephrine.
ARTICLES
Cardiac sympathetic nervous activity in congestive heart failure. Evidence for increased neuronal norepinephrine release and preserved neuronal uptake
Alfred and Baker Medical Unit, Baker Medical Research Institute, Melbourne, Victoria, Australia.
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