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Effects of metoprolol on rest and exercise cardiac function and plasma catecholamines in chronic congestive heart failure secondary to ischemic or idiopathic cardiomyopathy

  • John W. Nemanich
    Correspondence
    Address for reprints: John W. Nemanich, MD, 4011 Talbot Road S, 500 Renton, Washington 98055.
    Affiliations
    From the Divisions of Cardiology, Gerontology and Geriatric Medicine, Department of Medicine and Department of Psychiatry and Behavioral Science and Geriatric Research, Education and Clinical Center, Seattle Veterans Administration Medical Center, Seattle, Washington, USA

    From the University of Washington, Seattle, Washington, USA
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  • Richard C. Veith
    Affiliations
    From the Divisions of Cardiology, Gerontology and Geriatric Medicine, Department of Medicine and Department of Psychiatry and Behavioral Science and Geriatric Research, Education and Clinical Center, Seattle Veterans Administration Medical Center, Seattle, Washington, USA

    From the University of Washington, Seattle, Washington, USA
    Search for articles by this author
  • Itamar B. Abrass
    Affiliations
    From the Divisions of Cardiology, Gerontology and Geriatric Medicine, Department of Medicine and Department of Psychiatry and Behavioral Science and Geriatric Research, Education and Clinical Center, Seattle Veterans Administration Medical Center, Seattle, Washington, USA

    From the University of Washington, Seattle, Washington, USA
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  • John R. Stratton
    Affiliations
    From the Divisions of Cardiology, Gerontology and Geriatric Medicine, Department of Medicine and Department of Psychiatry and Behavioral Science and Geriatric Research, Education and Clinical Center, Seattle Veterans Administration Medical Center, Seattle, Washington, USA

    From the University of Washington, Seattle, Washington, USA
    Search for articles by this author
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      Abstract

      To define the effects of 2 months of metoprolol therapy on cardiac function, aerobic performance and sympathetic nervous system activity, metoprolol (75 to 100 mg/day) was administered to 10 patients with chronic congestive heart failure (CHF). Metoprolol was discontinued in 2 patients because of worsening CHF. In the remaining 8 patients, peak oxygen uptake increased significantly (14.8 ± 3.0 to 16.1 ± 2.5 ml/kg/min, p < 0.05) as did the oxygen pulse (9.0 ± 2.2 to 12.6 ±1.8 ml/beat, p < 0.02). Resting heart rate (87 ± 18 to 62 ± 9 beats/min, p < 0.05) and peak exercise heart rate (133 ± 13 to 105 ± 30 beats/min, p < 0.02) were both reduced. Mean resting ejection fraction increased from 0.15 ± 0.06 to 0.25 ± 0.11 and peak exercise ejection fraction also tended to increase (0.19 ± 0.11 to 0.28 ± 0.15, difference not significant). Both resting plasma norepinephrine (613 ± 706 to 303 ± 142 pg/ml, p < 0.05) and epinephrine (71 ± 50 to 40 ± 21 pg/ml, p < 0.05) were reduced. Circulating lymphocyte β-adrenergic receptor number was unchanged (1,334 ± 292 to 1,344 ± 456 receptors/cell, difference not significant). It is concluded that metoprolol therapy is associated with improvements in rest and exercise ventricular performance and maximal aerobic capacity. These improvements are associated with a decline in resting sympathetic nervous system activity.
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      References

        • Swedberg K
        • Hjalmarson A
        • Waagstcin F
        • Wallentin I
        Beneficial effects of long-term beta-blockade in congestive cardiomyopathy.
        Br Heart J. 1980; 44: 117-133
        • Engelmeier RS
        • O'Connell JB
        • Walsh R
        • Rad N
        • Scanion PJ
        • Gunnar RM
        Improvement in symptoms and exercise tolerance with metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized placebo controlled trial.
        Circulation. 1985; 72: 536-546
        • Anderson JL
        • Lutz JR
        • Gilbert EM
        • Sorensen SG
        • Yanowitz FG
        • Mcnlove RL
        • Bartholomew M
        A randomized trial of low-dose beta-blockade therapy for idiopathic dilated cardiomyopathy.
        Am J Cardiol. 1985; 55: 471-475
        • Masking GJ
        • Esler MD
        • Jennings GL
        • Burton D
        • Johns JA
        • Korner PI
        Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorcnal sympathetic nervous activity.
        Circulation. 1986; 73: 615-621
        • Mann DL
        • Cooper G
        Neurohumoral activation in congestive heart failure: a double-edged sword?.
        Clin Cardiol. 1989; 12: 485-490
        • Fowler MB
        • Laser JA
        • Hopkins GL
        • Minobe W
        • Bristow MR
        Assessment of the bcta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response.
        Circulation. 1986; 74: 1290-1302
        • Veith RC
        • Best JD
        • Halter JB
        Dose-dependent suppression of norepinephrine appearance rate in plasma by clonidine in man.
        J Clin Endocrinol Metab. 1984; 59: 151-155
        • Esler M
        • Jackman G
        • Bobik A
        • Kelleher D
        • Jennings G
        • Leonard P
        • Skews H
        • Korner P
        Determination of norepinephrine appearance release rate and clearance in humans.
        Life Sci. 1979; 25: 1461-1470
        • Evans MR
        • Halter JB
        • Porte D
        Comparison of double- and single-isotope enzymatic derivative methods for measuring catecholamines in human plasma.
        Clin Chem. 1978; 24: 567-570
        • Abrass CK
        • O'Connor SW
        • Scarpace PI
        • Abrass IB
        Characterization of the B-adrenergic receptor of the rat peritoneal macrophage.
        J Immunol. 1985; 135: 1338-1341
        • Caldwell JH
        • Hamilton GW
        • Sorenson SG
        • Ritchie JL
        • Williams DL
        • Kennedy JW
        The detection of coronary artery disease with radionuclide techniques: a comparison of rest-exercise thallium imaging and ejection fraction responses.
        Circulation. 1980; 61: 610-619
        • Sorenson SG
        • Ritchie JL
        • Caldwell JC
        • Hamilton GW
        • Kennedy JW
        Serial exercise radionuclide angiography: validation of count derived changes in cardiac output and quantitation of maximal exercise ventricular volume change after nitroglycerin and propranolol in normal men.
        Circulation. 1980; 61: 600-609
        • Heilbrunn SM
        • Shah P
        • Bristow MR
        • Valentine HA
        • Ginsburg R
        • Fowler MD
        Increased beta receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy.
        Circulation. 1989; 79: 483-490
        • Archibald DG
        • Cohn JN
        • VA Cooperative Study Group
        A treatment-associated increase in ejection fraction predicts long-term survival in congestive heart failure (abstr).
        Circulation. 1986; 74: II-310
        • Wolfel EE
        • Hiatt WR
        • Brammell ML
        • Carry MR
        • Ringel SP
        • Travis V
        • Horwitz LD
        Effects of selective and nonselective beta-adrenergic blockade on mechanisms of exercise conditioning.
        Circulation. 1980; 74: 664-674
        • Esler M
        • Jennings G
        • Korner P
        • Blombery P
        • Sacharias N
        • Leonard P
        Measurement of total and organ-specific norepinephrine kinetics in humans.
        Am J Physiol. 1984; 247: E21-E28
        • Best JD
        • Halter JB
        Blood pressure and norepinephrine spillover during propranolol infusion in humans.
        Am J Physiol. 1985; 248: R400-R406
        • Man in 't Veld A
        • Schalenkamp MADH
        Effects of 10 different beta-adrenoceptor antagonists on hemodynamics, plasma renin activity, and plasma norepinephrine in hypertension: the key role of vascular resistance changes in relation to partial agonist activity.
        J Cardiovas Pharmacol. 1983; 5: S30-S45
        • Murray DP
        • Watson RDS
        • Zezulka AV
        • Murray RG
        • Littler WA
        Plasma catecholamine levels in acute myocardial infarction: influence of beta-adrenergic blockade and relation to central hemodynamics.
        Am Heart J. 1988; 115: 38-44
        • Esler M
        Assessment of sympathetic nervous function in humans from noradrenalin plasma kinetics.
        Clin Sc. 1982; 62: 247-254
        • Colucci WS
        • Deniss AR
        • Leatherman GF
        • Quigg RJ
        • Ludmer PL
        • Marsh JD
        • Gathier DF
        Intracoronary infusion of dobutamine to patients with and without severe congestive heart failure.
        J Clin Invest. 1988; 81: 1103-1110
        • Chatterjee K
        Effects of captopril and a combination of hydralazine and isosorbide dinitrate on myocardial sympathetic tone in patients with severe congestive heart failure.
        Br Heart J. 1986; 56: 152-157
        • Majid PA
        • Niznick J
        • Nishizaki S
        • Morris WM
        • Sole MJ
        Acute hemodynamic and neurohumoral effects of pindolol: a beta-receptor antagonist with high intrinsic sympathomimetic activity in patients with dilated cardiomyopathy.
        J Cardiovasc Pharmacol. 1987; 10: 309-314
        • Fowler MB
        • Bristow MR
        Rationale for beta-adrenergic blocking drugs in cardiomyopathy.
        Am J Cardiol. 1985; 55: 120D-124
        • Alderman J
        • Grossman W
        Are beta-adrenergic-blocking drugs useful in the treatment of dilated cardiomyopathy?.
        Circulation. 1985; 71: 854-858
        • Gallagher JJ
        Tachycardia and cardiomyopathy: the chicken-egg dilemma revisited.
        J Am Coll Cardiol. 1985; 6: 1172-1173
        • Brown MD
        • Hudlicka O
        Protective effects of long-term bradycardial pacing against catecholamine-induced myocardial damage in rabbit hearts.
        Circ Res. 1988; 62: 965-974
        • Franciosa JA
        • Wilen MM
        • Jordan RA
        Effects of enalapril, a new angiotensin-converting enzyme inhibitor, in a controlled trial in heart failure.
        J Am Coll Cardiol. 1985; 5: 101-107
        • The Captopril-Digoxin Multicenter Research Group
        Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure.
        JAMA. 1988; 259: 535-544