Repetitive coxsackievirus infection induces cardiac dilatation in post-myocarditic mice

The relation between mycarditis and dilated cardiomyopathy (DCM) is controv ersial. To clarify the pathogenic mechanism of these diseases, the present study examined the effect of repetitive inoculation with coxsackievirus B3 (CVB3) in post-myocarditic mice. Inbred 3-week-old A/J mice were inoculated intraperitoneally with CVB3 (Nancy strain; 2x10(4) plaque-forming units) a nd reinfected in the same manner with CVB3 at 40 weeks (3W+/40W+). All mice were killed at 42 weeks old. The weight of the hearts of the 3W+/40W+ grou p were significantly increased compared with those of the 3W-/40W+ group, a nd both the heart weight/body weight and lung weight/body weight ratios of the 3W+/40W+ group were also significantly increased over those of the 3W-/ 40W- group, although the levels of serum neutralizing antibody titers were significantly increased in the 3W+/40W+ group over the level of the other g roups. No increase in inflammatory cell infiltration or fibrosis progressio n was observed in the 3W+/40W+ group relative to the 3W+/40W- group, but th e second inoculation resulted in a significant left ventricular dilatation and in left and right ventricular free wall thinning (3.31+/-0.20 mm vs 2.6 1+/-0.19mm, p<0.05; 0.54+/-0.09mm vs 0.72+/-0.16mm, p<0.05, respectively). The sarcomere length was also significantly increased in the 3W+/40W+ group compared with that of the other groups, as determined by electron microsco py. Degenerative or necrotic areas in the infected hearts were not stained with anti-mouse IgG antibody, but were stained, only in 3W+/40W+ mice, with anti-mouse IgM antibody. The concentrations of INF-alpha in the hearts of the 3W+/40W+ group were increased significantly over those of the 3W+/40W- group. Repetitive CVB3 infection produced cardiac dilatation without inflam matory cell infiltration in post- myocarditic mice. Autoimmunity mediated b y the circulation of certain antibodies (eg, antibodies against the CVB3 ge nome or a CVB3-related protein) may be part of the pathogenic mechanism for this phenomenon. Thus, repetitive virus infection might contribute to the pathogenesis of cardiac dilatation.