β-Adrenergic Receptor Blockade in Chronic Heart Failure

Bristow, Michael R.

doi:10.1161/01.cir.101.5.558

Cited by 920 publications

(639 citation statements)

References 125 publications

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“…Since the pioneering work in the 1970s [54], it took two decades until β-blockers turned from contraindication to standard treatment in heart failure [55] ( [58], respectively,) show a similar reduction in the risk of death by a third or more in patients with CHF who were already receiving ACE inhibitors and diuretics, a benefit greater than of any other drug used in heart M A N U S C R I P T…”

Section: β-Ar Blocking Drugsmentioning

confidence: 99%

Pharmacological modulation of β-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure

Matera

Martuscelli

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

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Section: β-Ar Blocking Drugsmentioning

confidence: 99%

Pharmacological modulation of β-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure

Matera

Martuscelli

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

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“…Carvedilol (Packer et al, 1996), bisoprolol (CIBIS II, 1999) and metoprolol (MERIT-HF Study Group, 1999) were shown to reduce mortality in patients with chronic heart failure. In contrast, xamoterol had adverse e ects on survival in patients with heart failure (Nicholas et al, 1990), and bucindolol failed to produce a bene®cial e ect compared to placebo (BEST, 1995;Bristow, 2000). Thus, di erences among b-adrenoceptor antagonists are likely to occur.…”

Section: Introductionmentioning

confidence: 99%

Different intrinsic activities of bucindolol, carvedilol and metoprolol in human failing myocardium

Maack

Cremers

Flesch

et al. 2000

British J Pharmacology

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1 Clinical studies have shown di erent e ects of b-blockers on the b-adrenergic system, tolerability and outcome in patients with heart failure. 2 The study examines b-adrenoceptor-G-protein coupling and intrinsic activity of bucindolol, carvedilol and metoprolol in human ventricular myocardium. 3 Radioligand binding studies ([ 125 I]-Iodocyanopindolol) were performed in membrane preparations of human failing and nonfailing myocardium. Functional experiments were carried out in isolated muscle preparations of human left ventricular myocardium from failing hearts. 4 Bucindolol and carvedilol bound non-selectively to b 1 -and b 2 -adrenoceptors and exerted guanine nucleotide modulatable binding. Metoprolol was 35-fold b 1 -selective and lacked guanine nucleotide modulatable binding. 5 All b-blockers antagonized isoprenaline-induced enhancement of contractility. 6 In preparations in which the coupling of the stimulatory G-protein to adenylate cyclase was facilitated by forskolin, bucindolol increased force of contraction in three and decreased it in ®ve experiments. Carvedilol increased force in one and decreased it in six experiments. Metoprolol decreased force in all experiments by 89.4+2.2% (P50.01 metoprolol vs carvedilol and bucindolol). The negative inotropic e ect of metoprolol was antagonized by bucindolol. 7 It is concluded that di erences in intrinsic activity can be detected in human myocardium and have an impact on cardiac contractility. In human ventricular myocardium, bucindolol displays substantially higher intrinsic activity than metoprolol and carvedilol. Bucindolol can behave as partial agonist or partial inverse agonist depending on the examined tissue. 8 Di erences in intrinsic activity may contribute to di erences in b-adrenoceptor regulation and possibly to di erences in tolerability and outcomes of patients with heart failure.

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“…Therapy with β-blockers has also been shown to consistently improve systolic function and reverse remodeling in patients with both ischemic and idiopathic cardiomyopathies. 22 The molecular basis for this improvement in cardiac function and reversal of remodeling by β-blocking agents remains incompletely understood, but partial reversal of a "fetal" pattern of gene expression appears to play a role.5 It is unclear, however, if β-blocking agents more generally alter gene expression and what additional regulators of contractile function and pathologic hypertrophy are affected by this type of treatment. The use of gene chip technology should allow for the extension of the initially reported paradigm of specific changes in gene expression that are associated with myocardial phenotypic change in patients treated with β-blocking agents.…”

Section: Discussionmentioning

confidence: 99%