J Clin Pharmacol
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Cardiac excitability and antiarrhythmic drugs: a different perspective

MF Arnsdorf

A matrix of active and passive cellular properties determines net cardiac excitability. The hypothesis of altered excitability suggests that for cardiac arrhythmias to arise, the normal matrix must be perturbed by arrhythmogenic influences to produce a proarrhythmic matrical configuration to permit rhythm disturbances caused by abnormalities of propagation, abnormal automaticity, or altered excitability. Antiarrhythmic drugs may act with one or more components of the normal or proarrhythmic matrix to normalize or to create new antiarrhythmic or, perhaps, proarrhythmic matrices. Traditionally, antiarrhythmic drug classifications have been based on predominant drug actions. These classifications have clinical and some experimental utility but fail to consider the complicated effects that pathophysiologic influences and pharmacologic actions may have on active and passive cellular properties. Cluster analysis may allow the development of new classifications of arrhythmogenesis and antiarrhythmic drugs. The matrical concept has important clinical implications and suggest strategies for treating patients with cardiac rhythm disturbances.
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