Methylmercury removal in the dog during infusion of 2,3-dimercaptosuccinic acid (Dmsa)

T,3-Dimercaptosuccinic acid (DMSA) has been utilized in chelation therapy and in extracorporal compiexing hemodialysis therapy for experimental methyimercury intoxi-cation. In the latter application, substantial excretion of methyimercury occurred by the urinary route. This prompted the current study of the effects of continuous intravenous DMSA infusion therapy on methyimercury kinetics in the dog. A nimals previously dosed with 203 Hg-iabeied methyimercury at 2.5 mg Hg/kg received a priming dose of DMSA, followed by a continuous iv infusion at dose rates that resulted in DMSA concentrations in plasma similar to those observed during DMSA compiexing hemodialysis therapy. The kinetics of 203Hg removal in DMSA-infused dogs was compared with both saline-infused controls and DMSA compiexing hemodialysis treated dogs.DMSA infusion therapy resulted in a shift in 203 Hg binding within systemic blood from the red-ceii fraction into plasma. This was consistent with an observed association of DMSA with the plasma fraction. The shift in 203 Hg from red cells into plasma was paralleled by an increase in urinary clearance of 203 Hg during the DMSA infusion period, in four dogs treated in this fashion, an average of 6.5 pg of mercury was removed by the urinary route over the 5-h treatment period, compared to 0.007 pg in the saline-infused dogs. Although a simitar magnitude of mercury output into urine was observed during DMSA compiexing hemodialysis, an additional 5 pg was removed by the dialyzer, making that technique 7.5 times as effective as infusion therapy. Comparing 203 Hg tissue concentration after DMSA infusion therapy with the saline- treated controls revealed a 6.5-fold decrease in liver, a 3-foid reduction in kidney, and a 27% reduction in cerebrum. No significant differences were observed in medulla or cerebellum. Histopathoiogy revealed no consistent differences between DMSA-treated and saline-treated animals.The DMSA infusion therapy was effective in causing a rapid removal of 203 Hg from animals previously dosed with 203 Hg-iabeied methyimercury. DMSA infusion therapy may provide a useful therapeutic alternative for methyimercury poisoning when rapid removal of the intoxicant is desired and hemodialysis equipment and expertise are not readily available.