Metoprolol reduces sympathetic nerve hyperactivity in patients with heart failure

Rundqvist, Bengt; Bergmann-Sverrisdottir, Yrsa; Andersson, Bert; Elam, Mikael; Eisenhofer, Graeme; Waagstein, Finn; Friberg, Peter

doi:10.1016/s1053-2498(00)00573-8

Cited by 4 publications

(2 citation statements)

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“…Sympathetic hyperactivity is a hallmark of progressive heart failure, and it has been associated with a poor prognosis (4,12,35). It is well known that increased sympathetic activity leads to activation of RAS (9,36,37), which ultimately worsens cardiac function and remodeling.…”

Section: Discussionmentioning

confidence: 99%

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Ferreira

Bacurau²,

Evangelista³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C)ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.

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Section: Discussionmentioning

confidence: 99%

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Ferreira

Bacurau²,

Evangelista³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, we have preliminary data showing that nerve fibre recordings and evaluation of myocardial noradrenaline kinetics were capable of detecting a reduction in sympathetic activity during long term treatment with metoprolol. 24 β Blockers with intrinsic activity and a less negative inotropic effect have shown poor results and are useless in the treatment of heart failure. 25 26 On the other hand, there were small but non-significant positive findings in global left ventricular function already with the first dose of metoprolol, including a reduction in end systolic volumes in particular.…”

Section: Negative Inotropic Effects and Catecholaminesmentioning

confidence: 99%

Longitudinal myocardial contraction improves early during titration with metoprolol CR/XL in patients with heart failure

Andersson

Sveälv²,

Täng³

et al. 2002

Heart

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Objective: To investigate diastolic and systolic left ventricular recovery during titration with metoprolol CR/XL (controlled release/extended release). Design: Placebo run in, followed by an open study. Setting: University hospital. Patients: 14 patients with chronic heart failure. Interventions: Metoprolol CR/XL titrated from 12.5 mg once daily to 200 mg once daily. Main outcome measures: M mode recordings of atrioventricular (AV) plane displacement, Doppler measurement of transmitral flow and pulmonary venous flow, two dimensional ejection fraction, and measurement of venous plasma concentration of noradrenaline. Patients were investigated after 2, 4, 6, and 24 weeks of treatment.Results: A reduction of heart rate was observed on the first dose (12.5 mg once daily), from a mean (SD) of 74 (11) to 67 (11) beats/min, p < 0.05. This was accompanied by prominent effects on AV plane filling parameters, including an increase in early diastolic filling period from 87 (28) to 105 (33) ms (p < 0.05), and in the lateral AV plane fractional shortening from 8.7 (2.7)% to 10.2 (2.8)% (p < 0.05). An early trend towards improvement in global systolic left ventricular function was also seen, although this was not significant until six weeks. Ejection fraction increased from 33 (7.5)% to 38 (11)% (p < 0.05). Conclusions: First effects of left ventricular recovery during β blocker treatment were seen in recordings of longitudinal performance, as expressed by AV plane displacement. Doppler flow dynamics as well as global systolic recovery appeared several weeks later, emphasising the importance of longitudinal performance in evaluating left ventricular function.

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Roles of cardiac sympathetic neuroimaging in autonomic medicine

Goldstein

Cheshire

2018

Clin Auton Res

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Sympathetic neuroimaging is based on the injection of compounds that either radiolabel sites of the cell membrane norepinephrine transporter (NET) or that are taken up into sympathetic nerves via the NET and radiolabel intra-neuronal catecholamine storage sites. Detection of the radioactivity is by planar or tomographic radionuclide imaging. The heart stands out among body organs in terms of the intensity of radiolabeling of sympathetic nerves, and virtually all of sympathetic neuroimaging focuses on the left ventricular myocardium. The most common cardiac sympathetic neuroimaging method worldwide is I-metaiodobenzylguanidine (I-MIBG) scanning. I-MIBG scanning is used routinely in Europe and East Asia in the diagnostic evaluation of neurogenic orthostatic hypotension (nOH), to distinguish Lewy body diseases (e.g., Parkinson disease with orthostatic hypotension (OH), pure autonomic failure) from non-Lewy body diseases (e.g., multiple system atrophy) and to distinguish dementia with Lewy bodies from Alzheimer's disease. In the USA, I-MIBG scanning has been approved by the Food and Drug Administration for the evaluation of pheochromocytoma and some forms of heart failure-but not for the above-mentioned differential diagnoses. Positron emission tomographic methods based on imaging agents such asF-dopamine are categorized as research tools, despite more than a quarter century of clinical experience with these modalities. Considering that I-MIBG scanning is available at most academic medical centers in the USA, cardiac sympathetic neuroimaging by this methodology merits consideration as an autonomic test, especially in patients with nOH.

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Metoprolol reduces sympathetic nerve hyperactivity in patients with heart failure

Cited by 4 publications

References 0 publications

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Longitudinal myocardial contraction improves early during titration with metoprolol CR/XL in patients with heart failure

Roles of cardiac sympathetic neuroimaging in autonomic medicine

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