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(Circulation. 1997;95:1745-1748.)
© 1997 American Heart Association, Inc.

Articles

Electrophysiological Remodeling of the Heart Owing to Rate

Douglas P. Zipes, MD

the Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, and the Roudebush Veterans Administration Medical Center, Indianapolis, Ind.

Correspondence to Douglas P. Zipes, MD, Krannert Institute of Cardiology, 1111 W 10th St, Indianapolis, IN 46202-4800.

Key Words: Editorials • atrium • ventricles • arrhythmia • fibrillation

	Introduction

 
Although damage to the heart from inflammation and infarction are well-established stimuli that trigger major cardiac remodeling, it has been known since 1954 that a persistent supraventricular tachycardia also can alter cardiac structure and function.¹ This clinical observation was exploited 8 years later when it was demonstrated that rapid stimulation of the normal heart could produce reversible congestive heart failure.² Since then, rapid pacing has been used frequently to create an investigational animal model of heart failure.

	Effects of Prolonged Tachycardia on Ventricular Electrophysiology

 
The effects of prolonged pacing-induced tachycardia, in the range of 250 bpm for 3 or 4 weeks, has been studied in depth in several animal species and has been shown to cause extensive myocardial remodeling. Biventricular enlargement with reduced wall thickness and no increase in muscle mass, reduced cross-sectional myocyte area and increased length, disarray of myofibril alignment and cytoarchitecture, increases in contractile protein degradation, and destruction of the supporting myocardial collagen matrix represent some of the structural changes contributing to reduced ventricular function.³ Diminished responsiveness to ß-adrenoceptor stimulation caused by a reduction in ß-receptor density and a variety of alterations in the adrenergic signaling processes also occur.⁴ Replacement fibrosis, loss of cells, and reactive hypertrophy of the remaining cells have been noted recently.⁵ mRNA levels for specific cytoskeletal proteins increase, along with alterations in cytoskeletal architecture⁶ and abnormalities in phospholamban.⁷

In pigs subjected to 3 weeks of a tachycardia-induced cardiomyopathy, myocyte action potential showed reduced membrane resting potential, reduced amplitude and upstroke velocity, and prolonged duration at 90% repolarization. Peak L-type Ca²⁺ . . . [Full Text of this Article]

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