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March 21, 2013Circulation Arrhythmia and ElectrophysiologyOpen Access

Combined Na + /Ca 2+ Exchanger and L-Type Calcium Channel Block as a Potential Strategy to Suppress Arrhythmias and Maintain Ventricular Function

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Why the study?

Does combined NCX and LTCC inhibition with SEA-0400 suppress dofetilide-induced TdP without compromising hemodynamics in a dog model of chronic AV block?

Population

Dog model with chronic atrioventricular block and isolated ventricular myocytes

Comparison

SEA-0400 at 0.4 and 0.8 mg/kg in vivo, and 1… vs Verapamil (0.3 mg/kg and 0.06 mg/kg)

Design

Preclinical

Authors

VBVincent J.A. BourgonjeNetherlands Institute for Innovative Ocular SurgeryMVMarc A. VosElectrophysiologySÖSemir ÖzdemirAkdeniz University

Discussion

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Implication

Preclinical data suggest hemodynamic safety for NCX inhibition in TdP; leaves open clinical translation from this animal model.

Structured PICO

Does combined NCX and LTCC inhibition with SEA-0400 suppress dofetilide-induced TdP without compromising hemodynamics in a dog model of chronic AV block?

P
Population
Dog model with chronic atrioventricular block and isolated ventricular myocytes
I
Intervention
SEA-0400 (combined NCX and LTCC inhibitor) at 0.4 and 0.8 mg/kg in vivo, and 1 μmol/L in vitro
C
Comparator
Verapamil (0.3 mg/kg and 0.06 mg/kg)
O
Outcome
Suppression of dofetilide-induced torsade de pointes arrhythmias (TdP) and effect on left ventricular pressure (LVP)surrogate

Combined NCX and LTCC inhibition with SEA-0400 effectively suppresses dofetilide-induced TdP arrhythmias without the negative inotropic effects seen with specific LTCC inhibition in a preclinical model.

Cite This Study

Bourgonje et al. (2013) studied this question.

synapsesocial.com/papers/6a72acd331a3df82432a35b9https://doi.org/10.1161/circep.113.000322
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Selective inhibition of sodium–calcium exchanger by SEA‐0400 decreases early and delayed afterdepolarization in canine heart2004 · 99 citations
  2. 2The Na+/Ca2+ exchange blocker SEA0400 fails to enhance cytosolic Ca2+ transient and contractility in canine ventricular cardiomyocytes2008 · 34 citations
  3. 3Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells1985 · 41 citations
  4. 4Enhanced Ca <sup>2+</sup> Release and Na/Ca Exchange Activity in Hypertrophied Canine Ventricular Myocytes2000 · 263 citations
  5. 5Window Ca<sup>2+</sup> current and its modulation by Ca<sup>2+</sup> release in hypertrophied cardiac myocytes from dogs with chronic atrioventricular block2006 · 62 citations