What question did this study set out to answer?

To resolve the distinct roles of early afterdepolarizations and transmural repolarization gradients in ventricular arrhythmogenesis under hypokalaemic conditions using calcium homeostasis inhibitors.

May 25, 2007Acta PhysiologicaOpen Access

Separation of early afterdepolarizations from arrhythmogenic substrate in the isolated perfused hypokalaemic murine heart through modifiers of calcium homeostasis

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Population

Langendorff-perfused hypokalaemic murine hearts paced from the right ventricular epicardium (n=6)

Comparison

Nifedipine (10 nm - 1 microm) or KN-93 (2 microm) vs Absence of nifedipine and KN-93

Design

Preclinical

Authors

MKMatthew J. KilleenAdventHealth Tampa IGIman S. GurungUniversity of Cambridge GTGlyn ThomasNIHR Bristol Cardiovascular Biomedical Research Unit

Discussion

Member takes

Implication

Supports calcium modulation of EADs in hypokalemic models; hypothesis-generating with no immediate clinical implications.

Key Points

To resolve the distinct roles of early afterdepolarizations and transmural repolarization gradients in ventricular arrhythmogenesis under hypokalaemic conditions using calcium homeostasis inhibitors.
Langendorff-perfused hypokalaemic mouse hearts (n = 6) paced from the right ventricular epicardium were evaluated with the L-type Ca2+ channel blocker nifedipine (10 nM–1 µM) and the CaMKII inhibitor KN-93 (2 µM).
Epicardial and endocardial monophasic action potentials were recorded to assess action potential duration (APD90), early afterdepolarizations, triggered beats, and arrhythmogenesis during spontaneous rhythm and programmed electrical stimulation.
In spontaneous rhythm, 100 nM nifedipine reduced early afterdepolarizations and triggered beats from 66.9 ± 15.7% to 28.3 ± 8.7% and ventricular tachycardia episodes from 10.8 ± 6.3% to 1.2 ± 0.7% (n = 6, P < 0.05), whereas 1 µM nifedipine abolished all spontaneous arrhythmic events.
Programmed electrical stimulation still triggered ventricular tachycardia in 6 of 6 hearts exposed to 0, 10, and 100 nM nifedipine, but 1 µM nifedipine suppressed inducible tachycardia while shifting transmural repolarization gradients (ΔAPD90) from -5.9 ± 2.5 to 15.5 ± 3.2 ms.
KN-93 (2 µM) similarly decreased early afterdepolarizations and triggered beats to 29.6 ± 8.9% and spontaneous ventricular tachycardia to 1.7 ± 1.1% (n = 6), but permitted stimulation-induced tachycardia amid a persistently negative ΔAPD90.

Structured PICO

Population

Langendorff-perfused hypokalaemic murine hearts paced from the right ventricular epicardium (n=6)

Intervention

Nifedipine (10 nm - 1 microm) or KN-93 (2 microm)

Comparator

Absence of nifedipine and KN-93

Outcome

Incidence of early afterdepolarizations (EADs), triggered beats, ventricular tachycardia (VT), and monophasic action potentials (MAPs)surrogate

In a hypokalaemic murine heart model, modifying calcium homeostasis with nifedipine or KN-93 separates the roles of early afterdepolarizations and repolarization gradients in ventricular tachycardia pathogenesis.

Cite This Study

Killeen et al. (2007) studied this question.

synapsesocial.com/papers/6a72c2f122b3175134db7b7f https://doi.org/10.1111/j.1748-1716.2007.01715.x

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Separation of early afterdepolarizations from arrhythmogenic substrate in the isolated perfused hypokalaemic murine heart through modifiers of calcium homeostasis

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Separation of early afterdepolarizations from arrhythmogenic substrate in the isolated perfused hypokalaemic murine heart through modifiers of calcium homeostasis

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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