Pharmacologic Therapy of Arrhythmias

Abstract

Disturbances of cardiac rhythm are often debilitating, recurrent and not uncommonly life threatening. The importance of an accurate diagnosis of arrhythmias and an understanding of the cellular mechanisms of arrhythmogenesis are crucial to successful treatment. Misdiagnosis of tachyarrhythmias can prove to be fatal. Over the last two decades we have refined our understanding of the mechanisms underlying cardiac arrhythmias. It no longer suffices to think of depolarization and repolarization of cardiac cells as a simple change in membrane resistance. The cardiac action potential is now understood in terms of the structural proteins which make up ion channels, which, in turn, control ion fluxes across the plasma membrane. Ideally, such a sophisticated understanding of arrhythmogenesis would lead to a more effective therapy. Unfortunately, our current knowledge of ion fluxes responsible for the cardiac action potential are based on normal tissue studies mostly in animal models. Correlating these results to abnormal tissue may not just be a simple extrapolation. Tissue abnormalities are essential for the initiation and propagation of various tachyarrhythmias. In addition, derangements in tissue structure, e.g. post infarction, alter the properties of the ion channels.