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(Circulation. 1999;99:1091-1100.)
© 1999 American Heart Association, Inc.
Current Perspective |
From Myocarditis to Cardiomyopathy: Mechanisms of Inflammation and Cell Death
Learning From the Past for the Future
Presented in part as a State-of-the-Art lecture at the Featured Research Sessions: Myocarditis—Mechanisms of Inflammation and Cell Death at the 69th Scientific Sessions of the American Heart Association, New Orleans, La, November 13, 1996.
From Kyoto University and Kyoto Regional Study Center, University of the Air.
Correspondence to Chuichi Kawai, MD, Nishiiru Karasuma Shimochojamachi-dori, Kamikyoku, Kyoto 602-8002, Japan.
Abstract—A progression from
viral myocarditis to dilated cardiomyopathy has
long been hypothesized, but the actual extent of this progression has
been uncertain. However, a causal link between viral myocarditis and
dilated cardiomyopathy has become more evident than
before with the tremendous developments in the molecular
analyses of autopsy and endomyocardial
biopsy specimens, new techniques of viral gene amplification, and
modern immunology. The persistence of viral RNA in the
myocardium beyond 90 days after inoculation, confirmed by
the method of polymerase chain reaction, has given us new insights into
the pathogenesis of dilated cardiomyopathy.
Moreover, new knowledge of T-cell–mediated immune responses in murine
viral myocarditis has contributed a great deal to the understanding of
the mechanisms of ongoing disease processes. Apoptotic cell
death may provide the third concept to explain the pathogenesis of
dilated cardiomyopathy, in addition to persistent
viral RNA in the heart tissue and an immune system–mediated mechanism.
Beneficial effects of 
1-adrenergic blocking agents,
carteolol, verapamil, and ACE inhibitors have
been shown clinically and experimentally in the treatment of viral
myocarditis and dilated cardiomyopathy. Antiviral
agents should be more extensively investigated for clinical use. The
rather discouraging results obtained to date with immunosuppressive
agents in the treatment of viral myocarditis indicated the importance
of sparing neutralizing antibody production, which may be
controlled by B cells, and raised the possibility of promising
developments in immunomodulating therapy.
Key Words: viruses • myocarditis • cardiomyopathy • immune system • apoptosis
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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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|
|
|
|
|
|
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|
|
|
|
 |
|
 M T Kearney, J M Cotton, P J Richardson, and A M Shah Viral myocarditis and dilated cardiomyopathy: mechanisms, manifestations, and management Postgrad. Med. J., January 1, 2001; 77(903): 4 - 10. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
 |
|
 A. M. Feldman and D. McNamara Myocarditis N. Engl. J. Med., November 9, 2000; 343(19): 1388 - 1398. [Full Text] [PDF]
|
|
|
|
|
|
C. M Oakley GENERAL CARDIOLOGY: Myocarditis, pericarditis and other pericardial diseases Heart, October 1, 2000; 84(4): 449 - 454. [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
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