Refining a preclinical model of viral myocarditis in accordance with biotech standards

Viral myocarditis is a clinically relevant inflammatory heart disease that can progress to dilated cardiomyopathy and heart failure. However, preclinical models often suffer from limited translational relevance and high animal burden.

This study aimed to refine a murine model of Coxsackievirus B3 (CVB3)-induced myocarditis by integrating dietary and imaging innovations to improve animal welfare, data quality, and clinical applicability. BALB/cJ mice were infected with heart-passaged CVB3 and monitored for up to 56 days. A hydrolyzed amino acid diet was introduced to mitigate CVB3-induced pancreatitis and associated weight loss. Cardiac function was assessed using 1D, 2D, and 4D echocardiography, including speckle-tracking strain analysis.

The refined diet significantly reduced animal health burden, reduced weight loss, and stabilized blood glucose, during development of cardiac inflammation and fibrosis. 4D echocardiography provided a highly sensitive and reproducible detection of systolic dysfunction, while strain analysis revealed early and regional myocardial impairment, closely mirroring clinical myocarditis phenotypes. Histopathological and AI-based analyses confirmed dose- and time-dependent inflammation and fibrosis, with peak inflammation at day 7 and persistent abnormalities through day 56.

In summary, this model offers a robust and ethically optimized platform for translational research and therapeutic development in inflammatory cardiomyopathies, aligned with the principles of the 3Rs.