Consequences of the Sicilian Gambit.

The Sicilian Gambit states that arrhythmias are complex, having multiple causes. Further, any arrhythmia may be contributed to by a vulnerable parameter or parameters, the modification of which may prevent initiation, may terminate and/or may modify the rate of arrhythmia. It also states that the sites of the drug action include such diverse targets as channels, receptors, and second messenger systems. The Gambit is not a classification system. It stresses the complexity of drug molecules and their interactions with targets and arrhythmias, considering each drug as an individual molecule. Hence, it provides a data base of information that is readily accessible to the clinician or the investigator, thereby facilitating understanding and more enlightened decision-making with respect to therapy and drug development. The major obstacle to the Gambit's acceptance has resided in its complexity; however, this merely reflects what is a very complex field. Moreover, it is the investigators' belief that until we are ready to contend with the diverse mechanisms for arrhythmias and the ever more diverse targets for drug action we will not able to prevent and treat arrhythmias pharmacologically in consistently satisfactory fashion.