Vernakalant does not alter early repolarization or contractility in normal and electrically remodelled atria

Arne van Hunnik, Hussein Nasrallah, Dennis H. Lau, Marion Kuiper, Sander Verheule, Ulrich Schotten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)
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Abstract

Besides the inhibition of the sodium inward current, vernakalant also inhibits the ultra rapid rectifier (I-Kur) and transient outward current (I-to). Inhibition of these currents increases contractility in canine atrial myocytes and goat atria. We investigated the effect of vernakalant on early repolarization and contractility in normal and electrically remodelled atria. Goats were implanted a pressure catheter, piezoelectric crystals, and electrodes to obtain atrial contractility and effective refractory period (ERP). The active component in pressure distance loops was used to compute the atrial work index (AWI). Experiments were performed in normal and electrically remodelled atria at clinically relevant plasma levels of vernakalant. As a positive control, the I-to/I-Kur blocker AVE0118 was investigated. Monophasic action potentials were recorded in anaesthetized goats and in explanted hearts to determine changes in action potential morphology. Vernakalant did not affect atrial work loops during sinus rhythm. Likewise vernakalant did not increase atrial fractional shortening or AWI during pacing with fixed heart rate and AV-delay. In contrast, AVE0118 did increase AWI, with a positive force frequency relation. Both in normal and remodelled atria, vernakalant strongly increased ERP but did not prolong early repolarization. In goat atria, vernakalant does not have an atrial positive inotropic effect and does not affect early repolarization. At high rates vernakalant may even have a negative inotropic effect.
Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalEP Europace
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Vernakalant
  • Atrial fibrillation
  • Ion current
  • Action potential
  • Repolarization
  • Remodeling
  • Contractility
  • CURRENT I-TO
  • POTASSIUM CURRENT
  • SINUS RHYTHM
  • FIBRILLATION
  • CARDIOVERSION
  • INCREASES
  • TISSUE
  • GOAT
  • KUR

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