What is the clinical evidence from this study?

Study design: Other. Population: Healthy and myocardial infarction (animal model). Intervention: Propranolol or Metoprolol vs. Saline. Primary outcome: Ventricular sympathetic axon density (p=<0.05).

What does this research mean for the field?

Chronic administration of beta-blockers, such as propranolol and metoprolol, increases ventricular sympathetic axon density by inhibiting beta-1 autoreceptor suppression of axon growth, which likely contributes to beta-blocker withdrawal syndrome. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine whether beta-adrenoceptor antagonists alter myocardial sympathetic innervation and identify the cellular mechanisms underlying beta-blocker withdrawal syndrome.

September 15, 2010Journal of NeuroscienceOpen Access

β-Adrenoceptor Blockers Increase Cardiac Sympathetic Innervation by Inhibiting Autoreceptor Suppression of Axon Growth

Q: What are the key findings of this study?

Chronic administration of the beta-blockers propranolol and metoprolol increased ventricular sympathetic axon density by 48% and 44%, respectively, compared to saline in rats.

Q: What does this research mean for the field?

Chronic administration of beta-blockers, such as propranolol and metoprolol, increases ventricular sympathetic axon density by inhibiting beta-1 autoreceptor suppression of axon growth, which likely contributes to beta-blocker withdrawal syndrome. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether beta-adrenoceptor antagonists alter myocardial sympathetic innervation and identify the cellular mechanisms underlying beta-blocker withdrawal syndrome.

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Key result

Chronic administration of the beta-blockers propranolol and metoprolol increased ventricular sympathetic axon density by 48% and 44%, respectively, compared to saline in rats.

Why the study?

Does beta-adrenoceptor blockade increase cardiac sympathetic innervation in rats and sympathetic neuronal cell cultures?

Population

Female Sprague Dawley rats aged 60 days, neonatal rat superior cervical ganglion neurons, and rat pup…

Comparison

Beta-blocker infusions via minipump for 1 week… vs Saline infusion or control medium.

Design

Preclinical, Neurite outgrowth was measured blindly

Follow-up

1 week (infusion), 48 hours (post-discontinuation/in vitro)

Authors

GCGwenaëlle L. ClarkeUniversity of Kansas Medical Center ABAritra BhattacherjeeBoston Children's Hospital STSarah E. TagueUniversity of Kansas Medical Center

Discussion

Member takes

Implication

May contribute to beta-blocker withdrawal syndrome; leaves open relevance to human cardiac sympathetic innervation.

Key Points

To determine whether beta-adrenoceptor antagonists alter myocardial sympathetic innervation and identify the cellular mechanisms underlying beta-blocker withdrawal syndrome.
Infused rats with propranolol, metoprolol, or saline for 1 week and assessed cardiovascular reactivity and ventricular contractility 2 days after drug discontinuation.
Measured neurite outgrowth in cultured sympathetic neurons treated with selective beta-antagonists, beta-agonists, or norepinephrine synthesis inhibitors.
Assessed ventricular sympathetic axon density via immunohistochemistry in naive rats and in a coronary artery ligation model of heart failure.
Both propranolol and metoprolol increased myocardial sympathetic axon density in vivo and stimulated axon outgrowth in culture via beta-1 adrenoceptor inhibition.
Propranolol discontinuation caused hyperresponsive ventricular contractility to tyramine and exaggerated blood pressure surges during stress tests despite normalized beta-receptor sensitivity.
Propranolol reversed heart failure-induced ventricular sympathetic axon depletion in coronary artery-ligated rats without altering infarct-associated hyperinnervation.

Structured PICO

Does beta-adrenoceptor blockade increase cardiac sympathetic innervation in rats and sympathetic neuronal cell cultures?

Population

Female Sprague Dawley rats aged 60 days, neonatal rat superior cervical ganglion (SCG) neurons, and rat pup cardiomyocytes. Includes a model of myocardial infarction via coronary artery ligation.

Intervention

Beta-blocker infusions (propranolol 13.2 mg/kg/d, metoprolol 36 mg/kg/d, or phentolamine 1 mg/kg/d) via minipump for 1 week; in vitro exposure to propranolol, metoprolol, ICI 118551, dobutamine, or alpha-methyl-p-tyrosine.

Comparator

Saline infusion (in vivo) or control medium (in vitro).

Outcome

Ventricular sympathetic innervation density (percentage of field area occupied by DBH-immunoreactive axons) and neurite outgrowth in vitro.surrogate

Main Result

p-value: p=<0.05

Chronic beta-blockade increases ventricular sympathetic axon proliferation by disrupting beta1-autoreceptor negative feedback, providing a potential mechanism for beta-blocker withdrawal syndrome.

Cite This Study

Clarke et al. (2010) studied Healthy and myocardial infarction (animal model). Propranolol or Metoprolol vs. Saline was evaluated on Ventricular sympathetic axon density (p=<0.05). Chronic administration of the beta-blockers propranolol and metoprolol increased ventricular sympathetic axon density by 48% and 44%, respectively, compared to saline in rats.

synapsesocial.com/papers/6a1c4ddf01af05bf0da92efe https://doi.org/10.1523/jneurosci.1667-10.2010

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β-Adrenoceptor Blockers Increase Cardiac Sympathetic Innervation by Inhibiting Autoreceptor Suppression of Axon Growth

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

β-Adrenoceptor Blockers Increase Cardiac Sympathetic Innervation by Inhibiting Autoreceptor Suppression of Axon Growth

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider