High-dose digoxin (10 mg/kg/day) significantly increased 14-day mortality and worsened myocardial necrosis and cellular infiltration in a murine model of viral myocarditis.
Does digoxin improve survival and reduce myocardial injury in a murine model of viral myocarditis?
High-dose digoxin worsens survival and increases myocardial inflammation in a murine model of viral myocarditis, suggesting it should be avoided in patients with heart failure due to viral myocarditis.
Results of recent studies suggest that proinflammatory cytokines cause myocardial contractile dysfunction, and that the drugs used to treat heart failure modulate the production of cytokines. This study was designed to examine the effects of digoxin in a murine model of heart failure induced by viral myocarditis. Four-week-old inbred DBA/2 mice were inoculated intraperitoneally with encephalomyocarditis virus (EMCV). Digoxin was given orally in doses of 0.1, 1 or 10 mg/kg daily from the day of virus inoculation. Interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha production in the heart were measured on day 5 after EMCV inoculation by enzyme-linked immunosorbent assay. The 14-day mortality tended to be increased in mice treated with 1 mg/kg, and was significantly increased in the group treated with 10 mg/kg per day. Myocardial necrosis and cellular infiltration on day 6 were significantly more severe in the high-dose digoxin group than in the control group. In the animals treated with 1 mg/kg digoxin, IL-1beta was significantly higher than in the control group. Intracardiac TNF-alpha levels were increased in a dose-dependent manner. These results suggest that digoxin worsens viral myocarditis, and that its use in high doses should be avoided in patients suffering from heart failure due to viral myocarditis.
Matsumori et al. (Fri,) conducted a other in Viral myocarditis. Digoxin vs. Control group was evaluated on 14-day mortality, myocardial necrosis, cellular infiltration, and cytokine production. High-dose digoxin (10 mg/kg/day) significantly increased 14-day mortality and worsened myocardial necrosis and cellular infiltration in a murine model of viral myocarditis.