Inotropes in the beta-blocker era

B. D. Lowes, M. A. Simon, T. O. Tsvetkova, M. R. Bristow

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Beta-adrenergic blocking agents are now standard treatment for mild to moderate chronic heart failure (CHF). However, although many subjects improve on beta blockade, others do not, and some may even deteriorate. Even when subjects improve on beta blockade, they may subsequently decompensate and need acute treatment with a positive inotropic agent. In the presence of full beta blockade, a beta agonist such as dobutamine may have to be administered at very high (> 10 μg/kg/min) doses to increase cardiac output, and these doses may increase afterload. In contrast, phosphodiesterase inhibitors (PDEIs) such as milrinone or enoximone retain their full hemodynamic effects in the face of beta blockade. This is because the site of PDEI action is beyond the beta-adrenergic receptor, and because beta blockade reverses receptor pathway desensitization changes, which are detrimental to PDEI response. Moreover, when the combination of a PDEI and a beta-blocking agent is administered long term in CHF, their respective efficacies are additive and their adverse effects subtractive. The PDEI is administered first to increase the tolerability of beta-blocker initiation by counteracting the myocardial depressant effect of adrenergic withdrawal. With this combination, the signature effects of beta blockade (a substantial decrease in heart rate and an increase in left ventricular ejection fraction) are observed, the hemodynamic support conferred by the PDEI appears to be sustained, and clinical results are promising. However, large-scale placebo-controlled studies with PDEIs and beta blockers are needed to confirm these results.

Original languageEnglish (US)
Pages (from-to)III11-III16
JournalClinical Cardiology
Volume23
Issue number3 SUPPL.
StatePublished - Mar 1 2000

Fingerprint

Phosphodiesterase Inhibitors
Enoximone
Heart Failure
Hemodynamics
Milrinone
Adrenergic beta-Antagonists
Dobutamine
Anti-Arrhythmia Agents
Receptors, Adrenergic, beta
Cardiac Output
Stroke Volume
Adrenergic Agents
Heart Rate
Placebos
Therapeutics

Keywords

  • Beta blockers
  • Enoximone
  • Heart failure
  • Milrinone
  • Phosphodiesterase inhibitors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lowes, B. D., Simon, M. A., Tsvetkova, T. O., & Bristow, M. R. (2000). Inotropes in the beta-blocker era. Clinical Cardiology, 23(3 SUPPL.), III11-III16.

Inotropes in the beta-blocker era. / Lowes, B. D.; Simon, M. A.; Tsvetkova, T. O.; Bristow, M. R.

In: Clinical Cardiology, Vol. 23, No. 3 SUPPL., 01.03.2000, p. III11-III16.

Research output: Contribution to journalArticle

Lowes, BD, Simon, MA, Tsvetkova, TO & Bristow, MR 2000, 'Inotropes in the beta-blocker era', Clinical Cardiology, vol. 23, no. 3 SUPPL., pp. III11-III16.
Lowes BD, Simon MA, Tsvetkova TO, Bristow MR. Inotropes in the beta-blocker era. Clinical Cardiology. 2000 Mar 1;23(3 SUPPL.):III11-III16.
Lowes, B. D. ; Simon, M. A. ; Tsvetkova, T. O. ; Bristow, M. R. / Inotropes in the beta-blocker era. In: Clinical Cardiology. 2000 ; Vol. 23, No. 3 SUPPL. pp. III11-III16.
@article{2294d3a70cc24de2b70e7ef6504406cf,
title = "Inotropes in the beta-blocker era",
abstract = "Beta-adrenergic blocking agents are now standard treatment for mild to moderate chronic heart failure (CHF). However, although many subjects improve on beta blockade, others do not, and some may even deteriorate. Even when subjects improve on beta blockade, they may subsequently decompensate and need acute treatment with a positive inotropic agent. In the presence of full beta blockade, a beta agonist such as dobutamine may have to be administered at very high (> 10 μg/kg/min) doses to increase cardiac output, and these doses may increase afterload. In contrast, phosphodiesterase inhibitors (PDEIs) such as milrinone or enoximone retain their full hemodynamic effects in the face of beta blockade. This is because the site of PDEI action is beyond the beta-adrenergic receptor, and because beta blockade reverses receptor pathway desensitization changes, which are detrimental to PDEI response. Moreover, when the combination of a PDEI and a beta-blocking agent is administered long term in CHF, their respective efficacies are additive and their adverse effects subtractive. The PDEI is administered first to increase the tolerability of beta-blocker initiation by counteracting the myocardial depressant effect of adrenergic withdrawal. With this combination, the signature effects of beta blockade (a substantial decrease in heart rate and an increase in left ventricular ejection fraction) are observed, the hemodynamic support conferred by the PDEI appears to be sustained, and clinical results are promising. However, large-scale placebo-controlled studies with PDEIs and beta blockers are needed to confirm these results.",
keywords = "Beta blockers, Enoximone, Heart failure, Milrinone, Phosphodiesterase inhibitors",
author = "Lowes, {B. D.} and Simon, {M. A.} and Tsvetkova, {T. O.} and Bristow, {M. R.}",
year = "2000",
month = "3",
day = "1",
language = "English (US)",
volume = "23",
pages = "III11--III16",
journal = "Clinical Cardiology",
issn = "0160-9289",
publisher = "John Wiley and Sons Inc.",
number = "3 SUPPL.",

}

TY - JOUR

T1 - Inotropes in the beta-blocker era

AU - Lowes, B. D.

AU - Simon, M. A.

AU - Tsvetkova, T. O.

AU - Bristow, M. R.

PY - 2000/3/1

Y1 - 2000/3/1

N2 - Beta-adrenergic blocking agents are now standard treatment for mild to moderate chronic heart failure (CHF). However, although many subjects improve on beta blockade, others do not, and some may even deteriorate. Even when subjects improve on beta blockade, they may subsequently decompensate and need acute treatment with a positive inotropic agent. In the presence of full beta blockade, a beta agonist such as dobutamine may have to be administered at very high (> 10 μg/kg/min) doses to increase cardiac output, and these doses may increase afterload. In contrast, phosphodiesterase inhibitors (PDEIs) such as milrinone or enoximone retain their full hemodynamic effects in the face of beta blockade. This is because the site of PDEI action is beyond the beta-adrenergic receptor, and because beta blockade reverses receptor pathway desensitization changes, which are detrimental to PDEI response. Moreover, when the combination of a PDEI and a beta-blocking agent is administered long term in CHF, their respective efficacies are additive and their adverse effects subtractive. The PDEI is administered first to increase the tolerability of beta-blocker initiation by counteracting the myocardial depressant effect of adrenergic withdrawal. With this combination, the signature effects of beta blockade (a substantial decrease in heart rate and an increase in left ventricular ejection fraction) are observed, the hemodynamic support conferred by the PDEI appears to be sustained, and clinical results are promising. However, large-scale placebo-controlled studies with PDEIs and beta blockers are needed to confirm these results.

AB - Beta-adrenergic blocking agents are now standard treatment for mild to moderate chronic heart failure (CHF). However, although many subjects improve on beta blockade, others do not, and some may even deteriorate. Even when subjects improve on beta blockade, they may subsequently decompensate and need acute treatment with a positive inotropic agent. In the presence of full beta blockade, a beta agonist such as dobutamine may have to be administered at very high (> 10 μg/kg/min) doses to increase cardiac output, and these doses may increase afterload. In contrast, phosphodiesterase inhibitors (PDEIs) such as milrinone or enoximone retain their full hemodynamic effects in the face of beta blockade. This is because the site of PDEI action is beyond the beta-adrenergic receptor, and because beta blockade reverses receptor pathway desensitization changes, which are detrimental to PDEI response. Moreover, when the combination of a PDEI and a beta-blocking agent is administered long term in CHF, their respective efficacies are additive and their adverse effects subtractive. The PDEI is administered first to increase the tolerability of beta-blocker initiation by counteracting the myocardial depressant effect of adrenergic withdrawal. With this combination, the signature effects of beta blockade (a substantial decrease in heart rate and an increase in left ventricular ejection fraction) are observed, the hemodynamic support conferred by the PDEI appears to be sustained, and clinical results are promising. However, large-scale placebo-controlled studies with PDEIs and beta blockers are needed to confirm these results.

KW - Beta blockers

KW - Enoximone

KW - Heart failure

KW - Milrinone

KW - Phosphodiesterase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=0033995320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033995320&partnerID=8YFLogxK

M3 - Article

C2 - 10754776

AN - SCOPUS:0033995320

VL - 23

SP - III11-III16

JO - Clinical Cardiology

JF - Clinical Cardiology

SN - 0160-9289

IS - 3 SUPPL.

ER -