Preventing ventricular fibrillation by flattening cardiac restitution

Alan Garfinkel, Young Hoon Kim, Olga Voroshilovsky, Zhilin Qu, Jong R. Kil, Moon Hyoung Lee, Hrayr S. Karagueuzian, James N. Weiss, Peng-Sheng Chen

Research output: Contribution to journalArticle

406 Citations (Scopus)

Abstract

Ventricular fibrillation is the leading cause of sudden cardiac death. In fibrillation, fragmented electrical waves meander erratically through the heart muscle, creating disordered and ineffective contraction. Theoretical and computer studies, as well as recent experimental evidence, have suggested that fibrillation is created and sustained by the property of restitution of the cardiac action potential duration (that is, its dependence on the previous diastolic interval). The restitution hypothesis states that steeply sloped restitution curves create unstable wave propagation that results in wave break, the event that is necessary for fibrillation. Here we present experimental evidence supporting this idea. In particular, we identify the action of the drug bretylium as a prototype for the future development of effective restitution-based antifibrillatory agents. We show that bretylium acts in accord with the restitution hypothesis: by flattening restitution curves, it prevents wave break and thus prevents fibrillation. It even converts existing fibrillation, either to a periodic state (ventricular tachycardia, which is much more easily controlled) or to quiescent healthy tissue.

Original languageEnglish (US)
Pages (from-to)6061-6066
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number11
DOIs
StatePublished - May 23 2000
Externally publishedYes

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Ventricular Fibrillation
Anti-Arrhythmia Agents
Sudden Cardiac Death
Ventricular Tachycardia
Action Potentials
Myocardium
Theoretical Models
Pharmaceutical Preparations
bretylium

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Preventing ventricular fibrillation by flattening cardiac restitution. / Garfinkel, Alan; Kim, Young Hoon; Voroshilovsky, Olga; Qu, Zhilin; Kil, Jong R.; Lee, Moon Hyoung; Karagueuzian, Hrayr S.; Weiss, James N.; Chen, Peng-Sheng.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 11, 23.05.2000, p. 6061-6066.

Research output: Contribution to journalArticle

Garfinkel, A, Kim, YH, Voroshilovsky, O, Qu, Z, Kil, JR, Lee, MH, Karagueuzian, HS, Weiss, JN & Chen, P-S 2000, 'Preventing ventricular fibrillation by flattening cardiac restitution', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 11, pp. 6061-6066. https://doi.org/10.1073/pnas.090492697
Garfinkel, Alan ; Kim, Young Hoon ; Voroshilovsky, Olga ; Qu, Zhilin ; Kil, Jong R. ; Lee, Moon Hyoung ; Karagueuzian, Hrayr S. ; Weiss, James N. ; Chen, Peng-Sheng. / Preventing ventricular fibrillation by flattening cardiac restitution. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 11. pp. 6061-6066.
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AU - Lee, Moon Hyoung

AU - Karagueuzian, Hrayr S.

AU - Weiss, James N.

AU - Chen, Peng-Sheng

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