Pathophysiological mechanisms underlying the effects of β-adrenergic agonists and antagonists on functional capacity and survival in chronic heart failure

Milton Packer

Research output: Contribution to journalArticle

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Abstract

Recently completed controlled clinical trials suggest that the functional status and natural history of patients with chronic heart failure can be modified by drugs that enhance or interfere with the effects of the sympathetic nervous system. Long-term treatment with β-receptor agonists can produce clinical benefits in some patients by improving left ventricular diastolic function, even if tolerance develops to the effects of these drugs on cardiac output and left ventricular ejection fraction. β-Receptor stimulation, however, may also provoke ventricular arrhythmias by a direct effect on the failing heart or by promoting the development of hypokalemia. Similarly, long-term treatment with β-receptor antagonists may improve left ventricular systolic performance, ameliorate symptoms, and reduce mortality in chronic heart failure. β-Receptor blockade, however, may lead to worsening heart failure by interfering with the positive inotropic or the peripheral vasodilator actions of endogenous catecholamines. It is noteworthy that many of the benefits of β-adrenergic agonists and antagonists seem to be mediated by the effects of these drugs on the β1-receptor, whereas many of the deleterious responses to treatment appear to be related to the interaction of these agents with the β2-receptor. These observations support the concept that β1-receptors are the principal mediators of cardiac sympathetic nerve activity in states of circulatory stress, are most likely to be altered by the abnormal pathophysiological conditions of chronic heart failure, and consequently, provide a rational target for the development of novel therapeutic agents.

Original languageEnglish (US)
JournalCirculation
Volume82
Issue number2 SUPPL.
Publication statusPublished - Aug 1990

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Keywords

  • β-blockade
  • Heart failure
  • Receptors, β-adrenergic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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