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(Circulation. 1996;93:1667-1676.)
© 1996 American Heart Association, Inc.
Articles |
Cardiac Sympathetic Nerve Function in Congestive Heart Failure
From the Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke (G.E., I.J.K., D.S.G.), Bethesda, Md; the Cardiology Branch, National Heart, Lung, and Blood Institute (A.A.Q.), National Institutes of Health, Bethesda, Md; the Departments of Cardiology and Clinical Physiology, University of Göteborg, Göteborg, Sweden (P.F., B.R.); and the Baker Medical Research Institute, Prahran, Victoria, Australia (G.L., D.M.K., M.D.E.).
Correspondence to Graeme Eisenhofer, Bldg 10, Room 5N-214, 10 Center Dr MSC 1424, National Institutes of Health, Bethesda, MD 20892-1424. E-mail ge@box-g.nih.gov.
Background Increased availability of norepinephrine (NE) for activation of cardiac adrenoceptors (increased cardiac adrenergic drive) and depletion of myocardial NE stores may contribute to the pathophysiology and progression of congestive heart failure. This study used a comprehensive neurochemical approach to examine the mechanisms responsible for these abnormalities.
Methods and Results Subjects with and without congestive heart failure received intravenous infusions of [3H]NE. Cardiac spillover, reuptake, vesicular-axoplasmic exchange, and tissue stores of NE were assessed from arterial and coronary venous plasma concentrations of endogenous and [3H]-labeled NE and dihydroxyphenylglycol. Tyrosine hydroxylase activity was assessed from plasma dopa, and NE turnover was assessed from measurements of NE metabolites. NE release and reuptake were both increased in the failing heart; however, the efficiency of NE reuptake was reduced such that cardiac spillover of NE was increased disproportionately more than neuronal release of NE. Cardiac NE stores were 47% lower and the rate of vesicular leakage of NE was 42% lower in the failing than in the normal heart. Cardiac spillover of dopa and NE turnover were increased similarly in congestive heart failure.
Conclusions Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrenergic drive in congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increase in cardiac NE turnover in CHF. Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.
Key Words: norepinephrine • heart failure • nervous system, autonomic • radioisotopes
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