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Preventing ventricular fibrillation by flattening cardiac restitution

Authors
 Alan Garfinkel  ;  Young-Hoon Kim  ;  Olga Voroshilovsky  ;  Zhilin Qu  ;  Jong R. Kil  ;  Moon-Hyoung Lee  ;  Hrayr S. Karagueuzian  ;  James N. Weiss  ;  Peng-Sheng Chen 
Citation
 Proceedings of the National Academy of Sciences of the United States of America, Vol.97(11) : 6061-6066, 2000 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2000
MeSH
Action Potentials/drug effects ; Animals ; Anti-Arrhythmia Agents/pharmacology ; Anti-Arrhythmia Agents/therapeutic use* ; Bretylium Compounds/pharmacology ; Bretylium Compounds/therapeutic use* ; Cardiac Pacing, Artificial ; Computer Simulation ; Cromakalim/pharmacology ; Cromakalim/therapeutic use ; Diastole/physiology ; Drug Design ; Drug Evaluation, Preclinical ; Fluorescent Dyes ; Heart Conduction System/drug effects* ; Heart Conduction System/physiopathology ; Models, Biological ; Pyridinium Compounds ; Swine ; Ventricular Fibrillation/drug therapy ; Ventricular Fibrillation/physiopathology ; Ventricular Fibrillation/prevention & control*
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.
Files in This Item:
T200002441.pdf Download
DOI
10.1073/pnas.090492697
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Moon-Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171844
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