Superoxide dismutase and the reduction of reperfusion-induced arrhythmias: in vivo dose-response studies in the rat.

Using anesthetized rats we have investigated the dose-response characteristics for the ability of superoxide dismutase (SOD) to reduce the vulnerability of the rat heart to reperfusion-induced arrhythmias in vivo. Hearts (n = 15 in each group) were subjected to 7 min of regional ischemia followed by 10 min of reperfusion. In the control group (saline), 73% (11/15) of the hearts fibrillated during reperfusion, 20% (3/15) had atrioventricular block and 47% (7/15) died as a result of ventricular arrhythmias. Superoxide dismutase, administered as an intravenous bolus 2 min prior to reperfusion exerted a marked protective effect. At its most effective dose (10 mg/kg body wt i.e. 27,000 IU/kg body wt) reperfusion-induced ventricular fibrillation was reduced to 33% (5/15). Reperfusion-induced atrioventricular block was eliminated (0/15) and mortality was reduced to 7% (1/15, p less than 0.05). The protective effects were however very dose-dependent and at higher doses SOD exhibited no antiarrhythmic actions during reperfusion. These results, together with our previous findings in vitro, lend further support to our proposition that oxygen-derived free radicals may play a role in the induction of potentially lethal cardiac arrhythmias and that antifree radical interventions, even when given after the onset of ischemia, can be highly protective.