What is the clinical evidence from this study?

Population: Heart failure (rabbit model) (n=30). Intervention: Dantrolene vs. Control conditions (untreated). Primary outcome: Diastolic Ca2+ spark frequency and intra-SR Ca2+ wave threshold (p=<0.001).

What question did this study set out to answer?

To assess the effects of dantrolene on calcium handling in ventricular myocytes from heart failure and normal rabbits.

December 17, 2011AJP Heart and Circulatory Physiology

Dantrolene prevents arrhythmogenic Ca²⁺release in heart failure

Q: What are the key findings of this study?

Dantrolene exerted antiarrhythmic effects in heart failure cardiomyocytes by significantly decreasing the frequency of diastolic Ca2+ sparks and increasing the intra-SR Ca2+ wave threshold without compromising inotropy.

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

To assess the effects of dantrolene on calcium handling in ventricular myocytes from heart failure and normal rabbits.

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Key result

Dantrolene exerted antiarrhythmic effects in heart failure cardiomyocytes by significantly decreasing the frequency of diastolic Ca2+ sparks and increasing the intra-SR Ca2+ wave threshold without compromising inotropy.

Why the study?

Does dantrolene improve intracellular Ca2+ handling and exert antiarrhythmic effects in ventricular myocytes from failing rabbit hearts?

Population

Ventricular myocytes from normal and failing rabbit hearts

Comparison

Dantrolene (1 μM) vs Untreated normal and failing rabbit myocytes

Design

Preclinical

Authors

JMJoshua T. MaxwellWake Forest University TDTimothy L. DomeierUniversity of Missouri LBLothar A. BlatterElectrophysiology

Discussion

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Implication

Dantrolene may stabilize RyR2 and reduce Ca2+ leak in HF models; leaves open clinical antiarrhythmic utility.

Key Points

To assess the effects of dantrolene on calcium handling in ventricular myocytes from heart failure and normal rabbits.
Examined intracellular calcium handling of ventricular myocytes in heart failure and normal conditions.
Measured cytosolic and intra-sarcoplasmic reticulum calcium concentrations using a specific calcium indicator.
Assessed postrest decay, wave initiation threshold, and spark frequency in response to dantrolene treatment.
Dantrolene treatment in heart failure myocytes increased intra-SR calcium threshold and decreased calcium spark frequency.
In heart failure myocytes, dantrolene improved postrest decay and SR calcium content.
Dantrolene exhibited antiarrhythmic effects while preserving inotropy in heart failure cardiomyocytes.

Structured PICO

Does dantrolene improve intracellular Ca2+ handling and exert antiarrhythmic effects in ventricular myocytes from failing rabbit hearts?

Population

Ventricular myocytes isolated from 30 New Zealand White rabbits, including 5 with induced nonischemic heart failure, to evaluate intracellular calcium handling.

Intervention

Dantrolene (1 μM)

Comparator

Untreated normal and failing rabbit myocytes

Outcome

Intracellular Ca(2+) handling (SR Ca(2+) load, postrest decay of SR Ca(2+) content, threshold for spontaneous Ca(2+) wave initiation, and Ca(2+) spark frequency)surrogate

Main Result

p-value: p=<0.001

Dantrolene exerts antiarrhythmic effects and preserves inotropy in heart failure cardiomyocytes by stabilizing ryanodine receptor function and improving sarcoplasmic reticulum calcium handling.

Limitations

In vitro study using isolated animal cardiomyocytes, which may not fully translate to in vivo human heart failure.

Cite This Study

Maxwell et al. (2011) studied Heart failure (rabbit model) (n=30). Dantrolene vs. Control conditions (untreated) was evaluated on Diastolic Ca2+ spark frequency and intra-SR Ca2+ wave threshold (p=<0.001). Dantrolene exerted antiarrhythmic effects in heart failure cardiomyocytes by significantly decreasing the frequency of diastolic Ca2+ sparks and increasing the intra-SR Ca2+ wave threshold without compromising inotropy.

synapsesocial.com/papers/6a63aa1ba8b6909d49095daa https://doi.org/10.1152/ajpheart.00936.2011

Topics

HFrEF treatment Heart failure

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Dantrolene prevents arrhythmogenic Ca²⁺release in heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Topics

Dantrolene prevents arrhythmogenic Ca²⁺release in heart failure

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Topics

Also Consider