Arrhythmogenic ionic remodeling - Adaptive responses with maladaptive consequences

Compensatory changes in ion transport mechanisms occur in response to a variety of cardiac disease processes. Recent work has demonstrated that these adaptive responses can produce the arrhythmogenic substrate for a variety of important cardiac rhythm disorders. Two important paradigms are atrial tachycardia-induced remodeling and ionic remodeling caused by congestive heart failure. Atrial tachycardia promotes cellular Ca2+ loading and downregulates a variety of ion channels, particularly L-type Ca2+ channels, thereby promoting the occurrence and maintenance of atrial fibrillation. Congestive heart failure alters the expression and function of a variety of membrane transport processes, including several K+-channels and key Ca2+-transport systems, favoring the occurrence of arrhythmogenic afterdepolarizations. An improved understanding of the mechanisms and consequences of arrhythmogenic ionic remodeling promises to lead to novel and improved therapeutic approaches. (Trends Cardiovasc Med 2001; 11:295-301). (C) 2001, Elsevier Science Inc.