Abstract 108 Poster Session III, Monday, 5/3 (poster 133)

Background: Over the last several years we have demonstrated that adenovirus is an important etiologic agent of myocarditis and its sequela dilated cardiomyopathy (DCM) in children. Adenovirus can be detected in the myocardium as frequently as the enteroviruses, which previously were implicated as the primary agent of acquired myocarditis/DCM. In order to investigate the cellular and molecular events involved in this disorder we are developing an animal model of adenovirus-induced myocarditis, analogous to the murine enterovirus myocarditis models. For these purposes we are using the cotton rat, a non-primate species which supports adenovirus replication.

Methods: Initially the optimal route of virus administration was determined. Cotton rats (6 per group) were administered with 107 plaque forming units (pfu) of adenovirus type 5 by intranasal (IN), intraperitoneal (IP), or intracardiac (IC) injection. Two animals per group were sacrificed after 4, 14 and 28 days. Viral titers in the lungs were determined at day 4 to confirm adenovirus administration. Adenoviral DNA in heart and lung samples was detected by polymerase chain reaction (PCR). The hearts were examined for evidence of pathology by H/E and T cell-specific immunostaining.

Results: Adenoviral DNA was detected in the lungs of all animals at days 4 and 14, except for one animal receiving virus by IP injection which was negative. At day 28 only the animals administered virus by IN or IC (one animal) were positive for adenovirus.

Adenoviral DNA was detected in the hearts of all animals inoculated by IC injection, whereas by IP and IN inoculation virus was detectable only at day 4. None of the control animals (sham injected) had evidence of pathology nor did any of the animals inoculated IN. In contrast all of the animals inoculated IP had some grade of myocarditis, although at day 4 both were borderline. The animals injected IC had diffuse epicarditis at day 4, but this was healed at the later time points. Myocarditis/borderline myocarditis, however, had developed at days 14 and 28 in these IC injected animals.

Conclusions: These preliminary data suggest that we have the basis of an animal model of adenovirus-induced myocarditis. The hearts are currently being analyzed by in situ hybridization to localize the types of cells infected by adenovirus. We are currently analyzing this model for the underlying biology responsible for acute and chronic cardiac dysfunction in this acquired disease.