What question did this study set out to answer?

To determine whether beta-adrenergic receptor blockade improves cardiac muscle performance by restoring normal ryanodine receptor calcium release channel function in patients with heart failure.

May 19, 2003Circulation

β-Blockers Restore Calcium Release Channel Function and Improve Cardiac Muscle Performance in Human Heart Failure

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Why the study?

Does beta-blocker therapy restore normal RyR2 channel function and improve cardiac muscle performance in patients with heart failure?

Population

24 human hearts

Comparison

Beta-blocker therapy vs Heart failure without beta-blocker treatment…

Design

Preclinical

Authors

SRSteven ReikenElectrophysiology XWXander H.T. WehrensElectrophysiology ABAlessandro BarboneIRCCS Humanitas Research Hospital

Discussion

Member takes

Implication

Beta-blockers may improve HF via RyR2 restoration; leaves open prospective in vivo confirmation.

Key Points

To determine whether beta-adrenergic receptor blockade improves cardiac muscle performance by restoring normal ryanodine receptor calcium release channel function in patients with heart failure.
Examined 24 explanted human hearts from patients undergoing transplantation or normal donors: 10 heart failure patients treated with beta-blockers (carvedilol, metoprolol, or atenolol), 9 untreated heart failure patients, and 5 normal controls.
Assessed left ventricular volume using isolated perfused hearts and tested beta-agonist responsiveness in isolated myocardial muscle strips.
Evaluated ryanodine receptor (RyR2) protein kinase A phosphorylation via back-phosphorylation, FKBP12.6 binding by coimmunoprecipitation, and channel function using planar lipid bilayers.
Beta-blocker treatment reduced left ventricular volume (indicating reverse remodeling) and restored contractile responsiveness to beta-agonists in failing human myocardium.
Improved cardiac function was directly associated with the restoration of normal FKBP12.6 levels in the RyR2 macromolecular complex and the normalization of RyR2 calcium channel function.

Structured PICO

Does beta-blocker therapy restore normal RyR2 channel function and improve cardiac muscle performance in patients with heart failure?

Population

24 human hearts (10 from patients with heart failure treated with beta-blockers, 9 from patients with heart failure without beta-blocker treatment, and 5 normal hearts)

Intervention

Beta-blocker therapy (carvedilol, metoprolol, or atenolol)

Comparator

Heart failure without beta-blocker treatment, and normal hearts

Outcome

Left ventricular volume, beta-agonist responsiveness, RyR2 PKA phosphorylation, FKBP12.6 levels in the RyR2 macromolecular complex, and RyR2 channel functionsurrogate

Beta-blocker therapy in heart failure improves cardiac muscle function by restoring normal FKBP12.6 levels and RyR2 calcium release channel function.

Cite This Study

Reiken et al. (2003) studied this question.

synapsesocial.com/papers/6a7f52868b768b9c059d3048 https://doi.org/10.1161/01.cir.0000068316.53218.49

Topics

Heart transplantation Heart failure HFrEF treatment

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β-Blockers Restore Calcium Release Channel Function and Improve Cardiac Muscle Performance in Human Heart Failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

β-Blockers Restore Calcium Release Channel Function and Improve Cardiac Muscle Performance in Human Heart Failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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