What is the clinical evidence from this study?

Population: Drug-induced long QT type 2. Intervention: Dofetilide. Primary outcome: Ca2+-elevations and action potential depolarizations.

What question did this study set out to answer?

Investigate how stochastic sarcoplasmic reticulum calcium release synchronizes to overcome source-sink mismatch and initiate ventricular arrhythmias in drug-induced long QT type 2 syndrome.

February 27, 2015Circulation Arrhythmia and ElectrophysiologyOpen Access

Synchronous Systolic Subcellular Ca ²⁺ -Elevations Underlie Ventricular Arrhythmia in Drug-Induced Long QT Type 2

Q: What does this research mean for the field?

In drug-induced long QT type 2, synchronous systolic Ca2+-elevations precede voltage-depolarizations and overcome source-sink mismatch to trigger ventricular arrhythmias. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

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Key result

In drug-induced long QT type 2 rabbit hearts, synchronous systolic Ca2+-elevations preceded voltage-depolarizations by 9.2±5 ms, overcoming source-sink mismatch to trigger ventricular arrhythmias.

Key Points

Investigate how stochastic sarcoplasmic reticulum calcium release synchronizes to overcome source-sink mismatch and initiate ventricular arrhythmias in drug-induced long QT type 2 syndrome.
Performed dual optical mapping of action potentials and intracellular Ca2+ transients at low and high resolutions in Langendorff-perfused rabbit hearts.
Elicited long QT type 2 using the IKr channel blocker dofetilide and evaluated arrhythmia suppression using the ryanodine receptor stabilizer K201.
Dofetilide elicited synchronous systolic Ca2+ elevations 188±30 ms after action potential upstroke during 40% to 60% of peak Ca2+, preceding voltage depolarizations by 9.2±5 ms (n=5).
Systolic Ca2+ elevations emerged in focal 0.5×0.5 mm2 epicardial islands, creating steep action potential duration gradients where early afterdepolarizations propagated into arrhythmias.
Application of the ryanodine receptor stabilizer K201 fully eliminated abnormal Ca2+ elevations and abolished triggered ventricular arrhythmias.

Structured PICO

Population

Langendorff rabbit hearts

Intervention

Dofetilide (IKr inhibition) to induce long QT type 2, and K201 (ryanodine receptor stabilizer)

Comparator

Baseline (before arrhythmias)

Outcome

Optical maps of action potentials and Ca2+-transients at low and high resolutionsurrogate

Synchronous systolic Ca2+ elevations from the sarcoplasmic reticulum overcome source-sink mismatch to trigger ventricular arrhythmias in drug-induced long QT type 2, which can be prevented by ryanodine receptor stabilization.

Discussion

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Implication

Ryanodine receptor stabilization may suppress Ca2+-triggered arrhythmias in long QT type 2; leaves open translation from rabbit models to clinical practice.

Cite This Study

Kim et al. (2015) studied Drug-induced long QT type 2. Dofetilide was evaluated on Ca2+-elevations and action potential depolarizations. In drug-induced long QT type 2 rabbit hearts, synchronous systolic Ca2+-elevations preceded voltage-depolarizations by 9.2±5 ms, overcoming source-sink mismatch to trigger ventricular arrhythmias.

synapsesocial.com/papers/6a1d8ca6cc9f7df1b7059be1 https://doi.org/10.1161/circep.114.002214

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Implication

Ryanodine receptor stabilization may suppress Ca2+-triggered arrhythmias in long QT type 2; leaves open translation from rabbit models to clinical practice.

Synchronous Systolic Subcellular Ca ²⁺ -Elevations Underlie Ventricular Arrhythmia in Drug-Induced Long QT Type 2

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Synchronous Systolic Subcellular Ca ²⁺ -Elevations Underlie Ventricular Arrhythmia in Drug-Induced Long QT Type 2

Key Points

Structured PICO

Discussion

Implication

Cite This Study

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