[Effect of recombinant human superoxide dismutase (r-h-SOD) on reperfusion-induced irreversible arrhythmia in...

Using anesthetized rats, we performed a dose-response study of the ability of r-h-SOD to reduce the mortality caused by reperfusion-induced irreversible arrhythmia. The hearts were subjected to regional ischemia by the occlusion of the left coronary artery for 4 min followed by reperfusion for 7 min. First, the relation between the anti-arrhythmic effect of r-h-SOD and the size of the ischemic zone was examined. The protective effect of r-h-SOD was easily detected in rats with an ischemic zone size of 40-55% of the total heart weight, but not in rats with other zone sizes. Intravenous infusion of r-h-SOD at rates of 430 to 130,000 U/kg/min beginning 1 min after regional ischemia significantly reduced the mortality after reperfusion. R-h-SOD at the doses used did not affect the blood pressure, heart rate or arrhythmia during the ischemic period. R-h-SOD at rates of 130 to 130,000 U/kg/min was intravenously infused into anesthetized rats, and its plasma level was measured at 3 min after the beginning of the infusion. The plasma level of r-h-SOD increased dose-dependently (8.5 to 6,600 U/ml). In conclusion, r-h-SOD reduced mortality after reperfusion over a wide range of doses and its effective plasma level was estimated to be 28 to 6,600 U/ml in this model.