Ion channel blockers in the treatment of Chronic heart failure

Abstract

Strategies for pharmacological treatment of chronic congestive heart failure (CHF) arediscussed from the viewpoint of cardiac ion channel modulations. It remains controversial as to whether Na channel blockers, which are the most effective drugs to suppress ventricular arrhythmias, can improve the prognosis of chronic CHF. As far as recent knowledge of interactions between the Na channel and its blocker is concerned, lidocaine-like agents such as mexiletine, which inhibit the Na channel current by binding to the channel in the inactivated state, are recommended because they can suppress premature ventricular contractions without prolongation of QRS complexes of sinus beats. To develop a new agent for the treatment of chronic CHF, we extracted the common features of electropharmacologic actions shared by amiodarone and vesnarinone, both of which have been reported to reduce the mortality of patients with chronic CHF. It is concluded that increases in the action potential duration (APD) of ventricular muscle mediated through an inhibition of the delayed rectifier K channel (I K channel) and a reduction of sinus node firing through an inhibition of L type Ca channel in addition to I K channel inhibition, are essential for the treatment of chronic CHF.