From myocarditis to cardiomyopathy : Mechanisms of inflammation and cell death : Learning from the past for the future

• Published in: Circulation (New York, N.Y.) N.Y.), 1999-03, Vol.99 (8), p.1091-1100
• Main Author: KAWAI, C
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathy, Dilated - drug therapy; Cardiomyopathy, Dilated - etiology; Cell death; Heart; Humans; Immunity, Cellular; Immunosuppressive Agents - therapeutic use; Interferons - physiology; Killer Cells, Natural - immunology; Lymphocyte Depletion; Medical sciences; Membrane Glycoproteins - physiology; Mice; Myocarditis - drug therapy; Myocarditis - etiology; Myocarditis. Cardiomyopathies; Perforin; Pore Forming Cytotoxic Proteins; RNA, Viral - analysis; Virus Diseases - complications
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.99.8.1091

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 alpha1-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.