Impact of NSAIDs and endurance exercise on myocardial fibrosis and arrhythmogenesis in murine coxsackieviral myocarditis

Abstract

Abstract Athletes often exhibit unexplained non-ischemic myocardial fibrosis, which is associated with malignant arrhythmias. Given the prevalent (over)use of NSAIDs among athletes and their harmful effects during viral myocarditis, this study examined the effects of combined NSAIDs and endurance exercise on the disease progression. To this end, male C57BL/6J mice underwent eight weeks of treadmill running (60 min/day; 18 cm/s) or no exercise. After two weeks, mice were implanted with mini-pumps delivering ibuprofen (70 mg/kg bw/day) or vehicle. Myocarditis was induced via intraperitoneal coxsackievirus inoculation. Mice were sacrificed six weeks post-inoculation for ventricular arrhythmogenicity evaluation and cardiac histopathological and molecular analysis. Exercising coxsackievirus-infected mice receiving ibuprofen recovered faster from weight loss. Mortality was low and similar across groups. Histopathology revealed abating inflammation and cell loss, without significant group differences. While exercise tended to increase extensive myocardial fibrosis, statistical analyses indicated no significant differences—with or without NSAIDs—in perivascular fibrosis, interstitial fibrosis, or myocardial scarring. NSAIDs—irrespective of exercise—did not increase arrhythmogenicity. In conclusion, ibuprofen in exercising mice with viral myocarditis resulted in faster weight loss recovery, without significant differences in inflammation, fibrosis, or arrhythmogenesis compared to exercise-only mice.