1999 Fiscal Year Final Research Report Summary
Enteroviral Replication and Cardiocyte Injury in the Myocardium from patients with Dilated Cardiomyopathy and Perforin Knockout Mice with Viral Myocarditis
| Project/Area Number |
10670681
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka Medical College |
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Principal Investigator |
DEGUCHI Hirofumi Faculty of Medicine, Osaka Medical College, Assistant Professor, 医学部, 助教授 (90131341)
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| Co-Investigator(Kenkyū-buntansha) |
KITAURA Akira Faculty of Medicine,Osaka Medical College,Research Associate, 医学部, 助手 (50257862)
KITAURA Yasushi Faculty of Medicine,Osaka Medical College,Professor, 医学部, 教授 (50084950)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Myocarditis / Dilated cardiomyopath / Enterovirus / Viral genome / Coxsackie virus / in situ hybridization / Perforin / Knockout mouse |
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| Research Abstract |
(1)Experimental Coxsackievirus B3 Myocarditis in Perforin Knockout (pfk) Mice.
We examined light and (LM) electron-microscopic (EM) changes of the myocardium obtained from pfk and wild(C57BL/6) mice with Coxsackievirus B3(CVB3) myocarditis. The mice were sacrificed on days 5-28 after virus inoculation. On days 8 and 14 many cardiocytes underwent necrosis with infiltration of lymphocytes and macrophages. By immuno-EM perforin were often observed in the granules of lymphocytes. The lymphocytes were sometimes in close contact with plasma membrane of cardiocytes. In pfk mice, cardiocyte necrosis was less than in wild mice, although significant number of lymphocytes infiltrated in the myocardium. These findings suggest that perforin plays an important role in the development of lymphcyte-mediated cardiocyte injury.
(2)Enteroviral RNA Replicatin in 26 Cases of Dilated Cardiomyopathy (DCM) with Refractory Heart Failure
We performed light microscopic in situ hybridization (ISH) and virological analyses of myocardial specimens obtained by partial left ventriculectomy. Myocardial specimens were tested for the presence and localization of enteroviral RNA in the myocardium by PCR and ISH. In PCR studies, both sense and antisense viral RNA were detected in the myocardium of seven patients(38%). The presence of these RNAs indicates active viral replication in the myocardium. On ISH, 3 patients had evidence of active replication of enteroviral genomes. Viral signals were found in degenerating cardiocytes, interstitial inflammatory cells and endothelial cells of small vessels. We detected both sense and antisense enteroviral RNA in various myhocardial lesions. Our results suggest that active viral replication plays a role in the development of myocardial lesions in DCM patients.
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[Publications] Terasaki T, Okabe M, Hayashi T, Fujioka S, Suwa M, Hirota Y, Kitaura Y, Kawamura K, Isomura T, Suma H: "Myocardial inflammatory cell infiltrates in cases of dilated cardiomyopathy : Light microscopic, immuno-histochemical, and virological analyses of myocardium specimens obtained by partial left ventriculectomy"J Card Surg. 14. 141-146 (1999)
Description
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