Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action

Background-Oxidative stress plays an important role in the pathophysiology of ischemic heart disease and heart failure, and antioxidants might be bene ficial in the treatment of these patients. This study was performed to dete rmine the scavenging effects of amiodarone on oxygen free radicals and its protective effects against oxygen radical-mediated injury in cardiac myocyt es. Methods and Results-The formation of the radical spin adduct with hydroxy r adical (. OH) in the presence of H2O2 (10 mmol/L) and Fe3+-nitrilotriacetat e (20 mu mol/L) was monitored by electron paramagnetic resonance spectrosco py combined with a spin trapping agent, 5,5-dimethyl pyrroline-N-oxide (DMP O). Amiodarone decreased the intensity of the DMPO-OH signals in a dose-dep endent manner (0.1 to 100 mu mol/L), whereas other antiarrhythmia drugs suc h as disopyramide and atenolol had no such effects. Furthermore, amiodarone (10 mu mol/L) protected intact adult canine cardiac myocytes against OH-me diated myocyte injury, as assessed by the degree of morphological change fr om rod shape to the irreversible hypercontracture state during the exposure of cells to H2O2 and Fe3+ in vitro, Conclusions-Amiodarone can protect cardiac myocytes against oxidative stres s-mediated injury by directly scavenging oxygen free radicals. Antioxidant action of amiodarone might potentially contribute to the beneficial effects of this drug in the treatment of patients with ischemic heart disease and congestive heart failure.