Organotoxic effects of excessive doses of sodium nitroprusside in the rabbit

The simultaneous iv. infusion in conscious rabbits of 7.5 mg/kg.h sodium nitroprusside (SNP) plus sodium thiosulfate in the molar ratios 1:5 or 1:10, respectively, for 4 h produced perilobular necroses of liver cells. 21 days after the infusion, regeneration of the damaged cells was complete. No histological changes were found in various other organs after this high dose of SNP. No signs of liver toxicity were found in rabbits that had received 0.75 mg/kg.h SNP for 8 h daily during a period of 5 consecutive days. This dose was in the range of SNP doses recommended for clinical use in human patients. Nevertheless we suggest that apart from the thiocyanate plasma levels, also the GOT, GPT, and gamma-GT concentrations in blood be controlled, especially when high doses of SNP are to be given for prolonged periods in order to exclude possible hepatotoxic effects of SNP.