(Circulation. 1996;94:2285-2296.)
© 1996 American Heart Association, Inc.
Articles |
Medical Therapy Can Improve the Biological Properties of the Chronically Failing Heart
A New Era in the Treatment of Heart Failure
the Department of Internal Medicine (Cardiology Division) (E.J.E.), The University of Texas Southwestern and Dallas VA Medical Centers; and the Division of Cardiology (M.R.B.), University of Colorado Health Science Center (Denver).
Abstract Myocardial failure has been considered to be an irreversible and progressive process characterized by ventricular enlargement, chamber geometric alterations, and diminished pump performance. However, more recent evidence has suggested that certain types of medical therapy may lead to retardation and even reversal of the cardiomyopathic process. In the failing heart, long-term neurohormonal/autocrine-paracrine activation results in abnormalities in myocyte growth, energy production and utilization, calcium flux, and receptor regulation that produce a progressively dysfunctional, mechanically inefficient heart. Interventions such as ACE inhibition and ß-blockade result in a reduction in the harmful long-term consequences of neurohormonal/autocrine-paracrine effects and retard the progression of left ventricular dysfunction or ventricular remodeling. Furthermore, in subjects with idiopathic dilated or ischemic cardiomyopathy, antiadrenergic therapy with ß-blocking agents appears to be able to partially reverse systolic dysfunction and ventricular remodeling. Although the precise mechanisms underlying this latter effect have not yet been elucidated, the general mechanism appears to be via improvement in the biological function of the cardiac myocyte. Such an improvement in the intrinsic defect(s) responsible for myocardial failure will likely translate into important clinical benefits.
Key Words: heart failure • remodeling • myocardial contraction
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|
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|
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|
|
|
|
|
|
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|
|
|
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|
|
|
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|
|
|
|
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|
|
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|
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|
|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
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|
|
|
|
 |
|
 Y.-Y. Zhou, D. Yang, W.-Z. Zhu, S.-J. Zhang, D.-J. Wang, D. K. Rohrer, E. Devic, B. K. Kobilka, E. G. Lakatta, H. Cheng, et al. Spontaneous Activation of beta 2- but Not beta 1-Adrenoceptors Expressed in Cardiac Myocytes from beta 1beta 2 Double Knockout Mice Mol. Pharmacol., November 1, 2000; 58(5): 887 - 894. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
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|
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|
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|
S. H. Dunlap, C. A. Sueta, L. Tomasko, and K. F. Adams Jr. Association of body mass, gender and race with heart failure primarily due to hypertension J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1602 - 1608. [Abstract] [Full Text] [PDF]
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