Catecholamine excretion and cardiac stores of norepinephrine in congestive heart failure

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      The role of the sympathetic nervous system in congestive heart failure was studied by determining the urinary excretion of norepinephrine and its concentration in cardiac tissue. Norepinephrine excretion averaged 22.5 μg. per day in normal subjects and 22.4 μg. per day in class I or II cardiac patients. It was increased in patients with heart failure, averaging 46.4 μg. per day in class III patients and 58.1 μg. per day in class IV patients. No significant increase in urinary excretion of epinephrine or vanilmandelic acid was observed in the patients with heart failure. The norepinephrine excretion was substantially increased in all patients by the stress of a corrective cardiac operation.
      The concentration of norepinephrine in atrial tissue was found to be reduced in patients with heart failure, averaging 0.49 μg. per gm. compared to 1.77 μg. per gm. in cardiac patients without failure. A reduction of norepinephrine was also observed in the left ventricle, and the concentrations in the ventricle were found to be lowest in the patients with the lowest atrial norepinephrine concentrations. Increased urinary excretion of norepinephrine was observed in patients with markedly depressed cardiac concentrations of the neurotransmitter substance.
      It is concluded that heart failure is associated with augmented activity of the sympathetic nervous system, reflected in increased norepinephrine excretion and often associated with a deficit of cardiac norepinephrine. It is suggested that in patients in whom depletion of neurotransmitter in the heart is most pronounced, there may be a relative deficiency of sympathetic function which in turn adversely affects the contractile state of the myocardium.
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        • Starling E.H.
        Points on pathology of heart disease.
        Lancet. 1897; 1: 569
        • Altschule M.D.
        Physiology in Diseases of the Heart and Lungs.
        in: Harvard University Press, Cambridge, Mass1949: 32
        • Anzola J.
        • Rushmer R.F.
        Cardiac response to sympathetic stimulation.
        Circulation Res. 1956; 4: 302
        • Sarnoff S.J.
        • Brockman S.K.
        • Gilmore J.P.
        • Linden R.J.
        • Mitchell J.H.
        Regulation of ventricular contraction: influence of cardiac sympathetic and vagal nerve stimulation on atrial and ventricular dynamics.
        Circulation Res. 1960; 8: 1108
        • Braunwald E.
        • Chidsey C.A.
        • Harrison D.C.
        • Gaffney T.E.
        • Kahler R.L.
        Studies on the function of the adrenergic nerve endings in the heart.
        Circulation. 1963; 28: 958
        • von Euler U.S.
        Quantitation of stress by catecholamine analysis.
        Clin. Pharmacol. & Therap. 1964; 5: 398
        • Raab W.
        • Gigee W.
        Total urinary catechol excretion in cardiovascular and other clinical conditions.
        Circulation. 1954; 9: 592
        • Pekarrinen A.
        • Tisalo E.
        • Kasanen A.
        • Laihinen A.
        • Thomasson B.
        Adrenosympathetic and adrenocortical function in cardiac insufficiency.
        Am. J. Cardiol. 1960; 5: 604
      1. Nomenclature and criteria for diagnosis of diseases of the heart and blood vessels. New York Heart Association, Inc, New York1963
        • Anton A.H.
        • Sayre D.
        A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines.
        J. Pharmacol. & Exper. Therap. 1962; 138: 360
        • Crout J.R.
        Standard Methods in Clinical Chemistry. vol. 3. Academic Press, New York1960: 62
        • Bertler A.
        • Carlsson A.
        • Rosengren E.
        A method for the fluorimetric determination of adrenaline and noradrenaline in tissues.
        Acta physiol. scandinav. 1958; 44: 273
        • Pisano J.J.
        • Crout J.R.
        • Abraham D.
        Determination of 3-methoxy-4-hydroxymandelic acid in urine.
        Clin. chim. acta. 1962; 7: 285
        • Chidsey C.A.
        • Braunwald E.
        • Morrow A.G.
        • Mason D.T.
        Myocardial norepinephrine concentration in man: effects of reserpine and congestive heart failure.
        New England J. Med. 1963; 269: 633
        • Bray G.A.
        A simple efficient liquid scintillator for counting aqueous solutions in a liquid scintillation counter.
        Anal. Biochem. 1960; 1: 279
        • Chidsey C.A.
        • Harrison D.C.
        • Braunwald E.
        The augmentation of plasma norepinephrine response to exercise in patients with congestive heart failure.
        New England J. Med. 1962; 267: 650
        • Merrill A.J.
        Edema and decreased renal blood flow in patients with chronic congestive heart failure: evidence of “forward failure” as a primary cause of edema.
        J. Clin. Invest. 1948; 27: 272
        • Myers J.D.
        • Hickam J.B.
        Estimation of hepatic blood flow and splanchnic oxygen consumption in heart failure.
        J. Clin. Invest. 1948; 27: 620
        • Muth H.A.V.
        • Wormald P.N.
        • Bishop J.M.
        • Donald K.W.
        Further studies of blood flow in the resting arm during supine leg exercise.
        Clin. Sc. 1958; 17: 603
        • Wood J.E.
        • Litter J.
        • Wilkins R.W.
        Peripheral venoconstriction in human congestive heart failure.
        Circulation. 1956; 13: 524
        • Burch G.E.
        Evidence for increased venous tone in chronic congestive heart failure.
        Arch. Int. Med. 1956; 98: 750
        • Tomomatsu T.
        • Ueba Y.
        • Matsumoto T.
        • Ikoma T.
        • Kondo Y.
        Catecholamine in congestive heart failure.
        Jap. Heart J. 1963; 4: 13
        • Goodall McC.
        • Rosen L.
        Urinary excretion of noradrenaline and its metabolites at 10 minute intervals after intravenous injection of dl-noradrenaline-2-C14.
        J. Clin. Invest. 1963; 42: 1578
        • Kopin I.J.
        • Gordon E.K.
        Metabolism of administered and drug-released norepinephrine-7-H3 in the rat.
        J. Pharmacol. & Exper. Therap. 1963; 140: 207
        • Franksson C.
        • Gemzell C.A.
        • von Euler U.S.
        Cortical and medullary adrenal activity in surgical and allied conditions.
        J. Clin. Endocrinol. 1954; 14: 608
        • Brodie B.
        • Beaven M.A.
        Neurochemical transducer systems.
        Med. exp. 1963; 8: 320
        • Kopin I.J.
        Storage and metabolism of catecholamines: the role of monoamine oxidase.
        Pharmacol. Rev. 1964; 16: 179
        • Udenfriend S.
        Fluorescence Assay in Biology and Medicine.
        in: Academic Press, New York1962: 158
        • Shore P.A.
        • Cohn V.H.
        • Highman B.
        • Maling H.M.
        Distribution of norepinephrine in heart.
        Nature. 1958; 181: 848
        • Spann J.F.
        • Chidsey C.A.
        • Braunwald E.
        Reduction of cardiac stores of norepinephrine in experimental heart failure.
        Science. 1964; 145: 1439
        • Chidsey C.A.
        • Kaiser G.A.
        • Sonnenblick E.H.
        • Spann J.F.
        • Braunwald E.
        Cardiac norepinephrine Stores in experimental heart failure in the dog.
        J. Clin. Invest. 1965; 43: 2386