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 cardiovascular 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 was administered intravenously to rabbits at single doses of 4, 20, and 100 mg/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 continuously monitored during a 6-h interval after injection of CaNa2-EDTA. Immediately before administration (-1 min) and at 3 and 6 h over the period of the experiment, the plasma cytokine response (tumor necrosis factor-alpha) and trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg, Pb) were measured. Regardless of dose, blood pressure was found to decrease, but no corresponding changes 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 cardiovascular 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-dependent increase in Mn that was equally pronounced at all time-points after the 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 trace elements, no or inconsistent effects were observed. This model allows the study of concomitant cardiovascular and trace element changes during treatment with drugs and chelating agents preceding a possible lethal end point and associated pathophysiologic changes.
Ilbäck
N G
NG
Toxicology Division, National Food Administration, Uppsala, Sweden.
Stålhandske
T
T
Lindh
U
U
D000758:Anesthesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D004492:Edetic Acid / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D014131:Trace Elements / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002614:Chelating Agents; D016207:Cytokines; D014131:Trace Elements; D014409:Tumor Necrosis Factor-alpha; D004492:Edetic Acid