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(Circulation Research. 2001;88:1095.)
© 2001 American Heart Association, Inc.

Editorial

New Era for Translational Research in Cardiac Arrhythmias

Satomi Adachi-Akahane, Yoshihisa Kurachi

From the Laboratory of Pharmacology and Toxicology (S.A.-A.), Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan, and Department of Pharmacology II (Y.K.), Graduate School of Medicine, Osaka University, Osaka, Japan.

Correspondence to Yoshihisa Kurachi, MD, PhD, Department of Pharmacology II, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. E-mail ykurachi@pharma2.med.osaka-u.ac.jp

Key Words: heart failure • arrhythmogenesis • Na⁺-Ca²⁺ exchanger • inwardly rectifying K⁺ channels • ß-adrenergic receptor

Heart failure is a multifactorial syndrome of hemodynamic decompensation that is a final common pathway for a variety of cardiovascular disorders. More than 40% of patients with heart failure lose their lives because of sudden cardiac death. Thus, the prevention of life-threatening cardiac arrhythmia is one of the major goals in the treatment of heart failure. The Cardiac Arrhythmia Suppression Trial (CAST) study has shown that class I antiarrhythmic agents are not clinically beneficial for long-term treatment of arrhythmias in patients with previous myocardial infarction. Although ß-adrenergic blockers and amiodarone are effective in reducing arrhythmic mortality,¹ the underlying mechanisms are not fully understood. Thus, development of the experimental animal models and comprehensive studies for elucidation of pathophysiological characteristics of life-threatening cardiac arrhythmias in heart failure is of fundamental importance.

The electrophysiological substrates associated with life-threatening cardiac arrhythmias are varied and include impairment of conduction attributable to structural alterations, spatial and temporal inhomogeneity of action potential duration attributable to remodeling of ionic channels, and triggered activity.² There are several studies describing changes in the functional expression of various ion channels and Ca²⁺-handling proteins/systems in cardiac myocytes isolated from failing hearts.^{3 4} In human and some animal models of heart failure, the protein level of the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA) is reduced and that of Na⁺-Ca²⁺ exchanger (NCX) is increased.⁴ It has also been reported that the reduced SR Ca²⁺ uptake activity and enhanced Ca²⁺ extrusion via NCX results in a decrease of the Ca²⁺ content in the SR . . . [Full Text of this Article]

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