Oxygen-derived free radicals related injury in the heart during ischemia and reperfusion.

Abstract

It has been suggested recently that oxygen-derived free radicals may play an important role in the genesis of reperfusion injury and arrhythmias. Free radicals have a very short half-life (ranging from mili- to microseconds), hence almost all the reports supporting the free radical hypothesis of reperfusion cell injury have been indirect. We have applied electrone spin resonance spectrometry to measure directly the amount of free radicals generated during ischemia and reperfusion. The concentration of free radicals in mitochondria increased significantly during ischemia (for 20 and 40 min). The concentration of free radicals after reperfusion was higher than that during ischemia, and a large amount of free radical generation occurred within the first 60 sec of reperfusion and returned to the level of prereperfusion at 5 min after reperfusion. The concentration of free radicals in the reperfusion-induced ventricular fibrillation group was significantly higher than that in the non-occurrence group. The administration of liposomal superoxide dismutase reduced the incidence of reperfusion-induced ventricular fibrillation and that prevented the free radical generation during reperfusion. This study showed that enhanced generation of free radicals occurred at the onset of ventricular fibrillation and that free radical scavenger prevented the development of arrhythmias and free radical generation during reperfusion. We have obtained more circumstantial evidence for an involvement of free radicals in the genesis of reperfusion injury and arrhythmias.