Electrocardiographic Changes Are Strongly Correlated With The Extent Of Cardiac Inflammation In Mice With Coxsackievirus B3-Induced Viral Myocarditis *

Objective: Viral myocarditis (VM) can induce changes in myocardial electrical conduction and arrhythmia. However, their relationship with myocarditis-associated arrhythmic substrates in the heart such as inflammation and fibrosis is relatively unknown. This we have analyzed in the present study. Methods: C3H mice were infected with 1 x10 5 plaque-forming units Coxsackievirus B3 (CVB3, n = 68) and were compared with uninfected control mice (n = 10). Electrocardiograms (ECGs) were recorded in all conscious mice shortly before sacrifice and included heart rate; P-R interval; QRS duration; QTc interval and R-peak amplitude of lead II and aVF. Mice were sacrificed at 4, 7, 10, 21, 35 or 49 days postinfection. Cardiac lesion size, calcification, fibrosis and cellular infiltration of CD45 + lymphocytes, MAC3 + macrophages, Ly6G + neutrophils and mast cells were quantitatively determined in cross-sections of the ventricles. Putative relations between ECG changes and lesion size and/or cardiac inflammation were then analyzed. Results: Significant transient reductions in QRS duration and R-peak amplitude occurred between 4 and 14 days post-infection and returned to baseline values thereafter. The magnitude of these ECG changes strongly correlated to the extent of lymphocyte (days 7 and 14), macrophage (days 7 and 10) and neutrophil (days 7) infiltration. The ECG changes did not significantly correlate with lesion size and fibrosis. Conclusion: VM induces transient changes in myocardial electrical conduction that are strongly related to cellular inflammation of the heart. These data show that even in mild VM, with relatively little cardiac damage, the inflammatory infiltrate can form an important arrhythmogenic substrate. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )