Action potential duration restitution and ventricular fibrillation due to rapid focal excitation

Moshe Swissa, Zhilin Qu, Toshihiko Ohara, Moon Hyoung Lee, Shien Fong Lin, Alan Garfinkel, Hrayr S. Karagueuzian, James N. Weiss, Peng Sheng Chen

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The focal source hypothesis of ventricular fibrillation (VF) posits that rapid activation from a focal source, rather than action potential duration (APD) restitution properties, is responsible for the maintenance of VF. We injected aconitine (100 μg) into normal isolated perfused swine right ventricles (RVs) stained with 4-{β-[2-(di-n-butylamino)-6-naphthyl]vinyl}pyridinium (di-4-ANEPPS) for optical mapping studies. Within 97 ± 163 s, aconitine induced ventricular tachycardia (VT) with a mean cycle length 268 ± 37 ms, which accelerated before converting to VF. Drugs that flatten the APD restitution slope, including diacetyl monoxime (10-20 mM, n = 6), bretylium (10-20 μg/ml, n = 3), and verapamil (2-4 μg/ml, n = 3), reversibly converted VF to VT in all cases. In two RVs, VF persisted despite of the excision of the aconitine site. Simulations in two-dimensional cardiac tissue showed that once VF was initiated, it remained sustained even after the "aconitine" site was eliminated. In this model of focal source VF, the VT-to-VF transition occurred due to a wave break outside the aconitine site, and drugs that flattened the APD restitution slope converted VF to VT despite continuous activation from aconitine site.

Original languageEnglish (US)
Pages (from-to)H1915-H1923
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number5 51-5
StatePublished - Jun 29 2002
Externally publishedYes

Keywords

  • Arrhythmia
  • Mapping
  • Pacing
  • Tachyarrhythmias

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Swissa, M., Qu, Z., Ohara, T., Lee, M. H., Lin, S. F., Garfinkel, A., Karagueuzian, H. S., Weiss, J. N., & Chen, P. S. (2002). Action potential duration restitution and ventricular fibrillation due to rapid focal excitation. American Journal of Physiology - Heart and Circulatory Physiology, 282(5 51-5), H1915-H1923.