Combined Na+/Ca2+ Exchanger and L-Type Calcium Channel Block as a Potential Strategy to Suppress Arrhythmias and Maintain Ventricular Function

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Bourgonje V. J. A., Vos M. A., Ozdemir S., Doisne N., Acsai K., Varro A., ...More

CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, vol.6, no.2, pp.371-379, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 6 Issue: 2
  • Publication Date: 2013
  • Doi Number: 10.1161/circep.113.000322
  • Journal Name: CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.371-379
  • Keywords: antiarrhythmic drug, calcium channel, heart failure, long QT syndrome, Na+/Ca2+ exchange, Torsade de Pointes, TORSADES-DE-POINTES, IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR, CHRONIC ATRIOVENTRICULAR-BLOCK, EARLY AFTERDEPOLARIZATIONS, DIASTOLIC DYSFUNCTION, NA+-CA2+ EXCHANGER, HEART-FAILURE, CA2+ RELEASE, IN-VIVO, INHIBITION
  • Akdeniz University Affiliated: Yes

Abstract

Background-L-type calcium channel (LTCC) and Na+/Ca2+ exchanger (NCX) have been implicated in repolarization-dependent arrhythmias, but also modulate calcium and contractility. Although LTCC inhibition is negative inotropic, NCX inhibition has the opposite effect. Combined block may, therefore, offer an advantage for hemodynamics and antiarrhythmic efficiency, particularly in diseased hearts. In a model of proarrhythmia, the dog with chronic atrioventricular block, we investigated whether combined inhibition of NCX and LTCC with SEA-0400 is effective against dofetilide-induced torsade de pointes arrhythmias (TdP), while maintaining calcium homeostasis and hemodynamics.