Key result
Inoculation with coxsackievirus B3 and/or B4 induced histologically proven myocarditis in 84.6% (11 of 13) of cynomolgus monkeys, leaving chronic sequelae at 5 months.
This preclinical study demonstrates that coxsackievirus B3 and B4 inoculation in cynomolgus monkeys induces acute myocarditis with chronic histological sequelae and corresponding electrocardiographic changes.
Establishes a primate model for coxsackievirus myocarditis with chronic sequelae; leaves open human translation pending clinical data.
In 11 of 13 cynomolgus monkeys inoculated with coxsackievirus B3 and/or B4, myocarditis was proved histologically. Myocarditis was evident the first 10 days after inoculation and left chronic sequelae; moderate myocardial cellular hypertrophy with an increase of connective tissue with focal distribution, and some residual inflammatory foci were found 5 months after viral inoculation. Virus was recovered from the heart on the 4th day but not on the 10th day, while serum neutralizing antibody rose significantly over 2 or 3 weeks in most of the inoculated monkeys. Electrocardiographic abnormalities were found in all 11 monkeys in which the myocarditis was proved histologically. These abnormalities were usually transient and were detected most often in the ST-T segment of the right-side chest leads, corresponding to the anatomical distribution of the myocarditis.
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Hoshino et al. (1983) studied Coxsackie B viral myocarditis (n=13). Coxsackievirus B3 and/or B4 inoculation was evaluated on Histologically proved myocarditis. Inoculation with coxsackievirus B3 and/or B4 induced histologically proven myocarditis in 84.6% (11 of 13) of cynomolgus monkeys, leaving chronic sequelae at 5 months.
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