Kutaura Y
Jpn Circ J. 1981 Jul;45(7):747-62.
In a series of experimental studies to test the hypothesis that idiopathic cardiomyopathy in man represents a sequela of virus myocarditis, coxsackie B 1, 3 or 5 virus was inoculated into ICR mice with two different amounts, that is, a small amount (0.1 ml of 10(5.5) TCID50/ml) and a large amount (0.1 ml of 10(7.5) TCID50/ml). Histopathological and immunofluorescent studies of the heart, analysis of the antibody titers in sera and evaluation of the virus concentration in various organs including the heart were carried out in an acute (up to the 21st day) and chronic phase (up to the 18th month) of the experiment. A small amount of coxsackie B 1 or 5 virus did not cause myocarditis, while a large amount of either virus rarely induced mild myocarditis. A small amount of coxsackie B 3 virus frequently caused mild myocarditis without obvious residual pathologic changes of the heart, while a large amount of the same virus always caused acute and severe myocarditis. In these animals, acute myocardial changes are almost in agreement with those in previous investigations except for capillary thrombi. The virus was isolated from the heart with higher titers than from other organs and identified in some cardiocytes by immunofluorescent study until the 14th day. Neutralizing antibody in sera appeared on the 7th day and remained for several months. Approximately two thirds of these mice left no significant myocardial lesions, whereas about one third of them which probably had extensive myocardial lesions in the acute phase developed significant myocardial fibrosis with calcification in the chronic phase. These lesions appeared to become larger after the 6th month. In and around the fibrotic lesions, atrophy, hypertrophy and/or disarray of myocardial fibers were observed. These hearts did not show hypertrophy or dilatation but their histologic findings resembled those seen in some cases of congestive cardiomyopathy except for severe calcification in the myocardium.
在一系列实验研究中，为了验证人类特发性心肌病是病毒性心肌炎后遗症这一假说，将柯萨奇B1、3或5型病毒以两种不同剂量接种到ICR小鼠体内，即小剂量（0.1 ml，10(5.5) TCID50/ml）和大剂量（0.1 ml，10(7.5) TCID50/ml）。在实验的急性期（直至第21天）和慢性期（直至第18个月），对心脏进行了组织病理学和免疫荧光研究，分析了血清中的抗体滴度，并评估了包括心脏在内的各个器官中的病毒浓度。小剂量的柯萨奇B1或5型病毒未引起心肌炎，而大剂量的这两种病毒很少诱发轻度心肌炎。小剂量的柯萨奇B3型病毒经常引起轻度心肌炎，心脏无明显残留病理改变，而大剂量的同型病毒总是引起急性重症心肌炎。在这些动物中，除了毛细血管血栓外，急性心肌变化与先前研究的结果几乎一致。直到第14天，从心脏分离出的病毒滴度高于其他器官，并通过免疫荧光研究在一些心肌细胞中得以鉴定。血清中的中和抗体在第7天出现并持续数月。大约三分之二的这些小鼠没有明显的心肌病变，而大约三分之一在急性期可能有广泛心肌病变的小鼠在慢性期出现了显著的心肌纤维化并伴有钙化。这些病变在第6个月后似乎变得更大。在纤维化病变及其周围，观察到心肌纤维萎缩、肥大和/或排列紊乱。这些心脏未表现出肥大或扩张，但其组织学表现类似于某些充血性心肌病病例，只是心肌中有严重钙化。
