Effects of EDTA on trace elements and cardiovascular function in the anesthetised rabbit

The present study was undertaken in order to study the effects of the broad -acting chelating agent CaNa2-EDTA on plasma trace elements and cardiovascu lar function in anesthetised New Zealand White rabbits. Trace elements are important for cardiovascular and immune functions and the rabbit is a well- accepted species in cardiovascular studies. The test compound CaNa2-EDTA wa s administered intravenously to rabbits at single doses of 4, 20, and 100 m g/kg. In addition, at 20 mg/kg, the effects of a second dose after 3 h were also investigated. Heart rate, blood pressure and body temperature were co ntinuously monitored during a 6-h interval after injection of CaNa2-EDTA. I mmediately before administration (-1 min) and at 3 and 6 h over the period of the experiment, the plasma cytokine response (humor necrosis factor-alph a) and trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg, Pb) were measured. Regar dless of dose, blood pressure was found to decrease, but no corresponding c hanges in heart rate were observed. Both a repeated administration of 20 mg /kg and a single dose of 100 mg/kg were detrimental and caused severe cardi ovascular effects and lethality. alpha-TNF tended to increase, though only at 100 mg/kg. The electrocardiogram and body temperature were not affected by the treatment. The most pronounced trace element change was a dose-depen dent increase in Mn that was equally pronounced at all time-points after th e dose. There was an initial decrease in Cd at low dose levels (4 and 20 mg /kg) that turned into an increase after 6 h at 20 mg/kg and from 2 h at 100 mg/kg. A similar pattern with pronounced decreases at low dose levels was observed for Zn. Cu decreased similarly at all dose levels. For the other t race elements, no or inconsistent effects were observed. This model allows the study of concomitant cardiovascular and trace element changes during tr eatment with drugs and chelating agents preceding a possible lethal end poi nt and associated pathophysiologic changes.