Lack of effect of antioxidant therapy during renal ischemia and reperfusion in dogs

Abstract

Acute ischemic renal failure is of great clinical importance because of its frequent occurrence and the high mortality it causes. Recent observations indicate that reperfusion has its own dangers because of oxygenderived free radicals. To study this problem, ischemia was evoked in dogs in one kidney, by clamping the left renal artery for 45 min. This was followed by a 90-min period of reperfusion when diuresis, GFR, PAH clearance and sodium and potassium excretion were studied. Besides a control group (n=6), the following treatment groups were investigated. Allopurinol (n=7): 50 mg/kg for two days p.o. and 50 mg/kg in physiological saline infusion during the experiment; a small dose of SOD (n=6): 0.5 mg/kg in infusion, started 1 min before reperfusion and given continuously for 10 min; and a high dose of SOD (n=7): 5 mg/kg as above. In the first 15 min following reperfusion, the renal functions significantly worsened in all groups. Later on, the renal functions gradually improved and in the last period after reperfusion, GFR in the ischemic kidney was 64%, cPAH 59%, diuresis 60% and sodium and potassium excretion were 65% and 76%, respectively, of the basal values in the control group.

Treatment with free radical scavengers did not cause any considerable changes in the renal functions. In some respects, the worst results were observed with low-level SOD treatment (cPAH, diuresis, as well as sodium and potassium excretion).

At the end of reperfusion, there was a significant drop in sodium excretion by the right (intact circulation) kidney of the treated animals.