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The ‘Sicilian Gambit’
A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms

DOI: http://dx.doi.org/ 1112-1131 First published online: 2 October 1991

Abstract

The Queen's Gambit is an opening move in chess that provides a variety of aggressive options to the player electing it. This report represents a similar gambit (the ‘Sicilian Gambit’)on the part of a group of basic and clinical investigators who met in Taormina, Sicily, to consider the classification of antiarrhythmic drugs. Paramount to their considerations were (I) dissatisfaction with the options offered by existing classification systems for inspiring and directing research, development and therapy, (2) the disarray in the field of antiarrhythmic drug development and testing in this post-CAST era, and (3) the desire to provide an operational frame work for consideration of antiarrhythmic drugs that will both encourage advancement and have the plasticity to grow as a result of the advances that occur. The multifaceted approach suggested is, like the title of the manuscript, a gambit. It is an opening rather than a compendium, and is intended to challenge thought and in vestigation rather than to resolve issues. The manuscript incorporates first, a discussion of the shortcomings of the present system for drug classfication; second, a review of the molecular targets on which drugs act (including channels and receptors); third, a consideration of the mechanisms responsible for arrhythmias, including the identification of vulnerable para might be most accessible to drug effect; and finally, clinical considerations with respect to antiarrhythmic drugs. Information relating to the various levels of information is correlated across categories (i.e., clinical arrhythmias, cellular mechanisms and molecular targets), and a ‘spread sheet’ approach to antiarrhythmic action is presented that considers each drug as a unit, with similarities to and dissimilarities from other drugs being highlighted. A complete reference list for this work would require as many pages as the text itself For this reason, referencing is selective and incomplete. It is designed, infact, to provide sufficient background information to give the interested reader a starting frame of reference, rather than to recognize the complete body of literature that is the basis for this paper.

Footnotes

  • *This paper summarizes the outcome of a workshop held in Taormina, Sicily, 1–4 December. 1990. The need for the workshop was proposed by Peter J. Schwartz and Michiel J. Janse. It was organized by the Working Group on Arrhythmias of the European Society of Cardiology, with joint sponsorship by the Basic Science Council of the American Heart Association and the American College of Cardiology Its funding was administered by the European Society of Cardiology. The workshop was chaired by Michael R. Rosen. Participating in the workshop and coauthonng the paper are: J. Thomas Bigger Jr., Günter Breithardt. Arthur M Brown, A. John Camm. Edward Carmeliet, Harry A. Fozzard, Brian F. Hoffman, Michiel J. Janse. Ralph Lazzara. Alessandro Mugelli, Robert J. Myerburg, Dan M. Roden. Michael R. Rosen, Peter J. Schwartz, Harold C Strauss, Raymond L. Woosley, and Antonio Zaza. Not attending but acting as advisors were Ronald W. F. Campbell and Albert L. Waldo. The final preparation and organization of the manuscript were the responsibility of A. John Camm. Harry A. Fozzard, Michiel J. Janse, Ralph Lazzara, Michael R. Rosen. and Peter J. Schwartz.