Silymarin and vitamin E do not attenuate and vitamin E might even enhance the antiarrhythmic activity of amiodarone in a rat reperfusion arrhythmia model

Oxidative stress and lysosomal phospholipoidosis, which also might be partl y attributed to free radicals induced by amiodarone (AM), may be involved i n AM toxicity, which can be prevented by antioxidants. Our aim was to study if vitamin E (E) or silymarin (S), a lipid and a water-soluble antioxidant , modified the antiarrhythmic efficacy of AM in a rat reperfusion arrhythmi a test. The following groups of male Sprague-Dawley rats (15 rats/group) we re treated by gavage once a day for 4 weeks: 1. methylcellulose (MC, 0.4%), 2. sunflower seed oil (SSO), 3. AM, suspended in MC (30 mg/kg), 4. E, diss olved in SSO (100 mg/kg), 5. AM + E, 6. S, suspended in MC (80 mg/kg), 7. A M + S. The mean duration of ventricular tachycardia + fibrillation (MDVT VF) and sinus rhythm (MDSR) the incidence of ventricular fibrillation (VF) and ventricular tachycardia (VT) and mortality were measured during a 10-mi n reperfusion after a 5-min coronary artery occlusion in anaesthetized rats . An arrhythmia score, representing the combined incidence and duration of different types of ventricular arrhythmia, was calculated. Compared with th e MC group, MDSR was longer and MDVT + VF was shorter in all drug treated g roups and in the SSO group. In the AM + E treated group MDSR was prolonged more and MDVT + VF was shortened more than in the AM, E or SSO groups. Comp ared with the MC group, the incidence of VF and mortality was similarly dec reased in the SSO group and in most drug treated groups. No significant dif ference in the incidence of VT was found among all groups. The arrhythmia s core was reduced by all drug treatments. Combined treatment with AM + E dec reased arrhythmia score more than treatment with AM or SSO alone, but arrhy thmia score was similar in the AM + E and E groups. In conclusion, both AM and antioxidant treatments alone or together resulted in a marked reduction of reperfusion arrhythmias in this model. SSO also exerted a moderate anti arrhythmic effect. Antioxidants administered together with AM did not atten uate and E might have even enhanced the antiarrhythmic effect of AM, theref ore the combination of antioxidants with AM may be advantageous to reduce A M toxicity.