Chelation therapy in the JCR:LA-cp rat: experimental assessment of a putative antiatherosclerotic treatment.

OBJECTIVE

To test the efficacy of chelation therapy, an alternative medical treatment, as an antiatherosclerotic procedure, using an animal model of insulin resistance and vascular disease.

DESIGN

A prospective animal experiment with procedures modelled on human chelation treatments.

SUBJECTS

The JCR:LA-cp rat, a strain that, if homozygous for the autosomal recessive cp gene, becomes obese and insulin resistant, with marked hyperinsulinemia and hypertriglyceridemia, and is unique in the spontaneous development of atherosclerosis and ischemic myocardial lesions.

EXPERIMENTAL PROTOCOL

Eight-month-old, obese, male JCR:LA-cp rats were fitted with indwelling venous cannulae and infused over 4 weeks with ethylenediaminetetraacetic acid (EDTA) 5 days a week at a daily dose of 40 mg/kg body weight. At the end of the treatment period, samples were taken for assay of blood parameters and for mineral content of bone. The rats were sacrificed and perfusion-fixed for scanning electron microscopy of the aortic arch.

RESULTS

Plasma cholesterol concentrations were not changed by the EDTA treatment. In contrast, plasma triglyceride concentrations were raised significantly (74%, p < 0.05). Lean control rats showed minimal abnormality of the aortic arch, whereas the obese control rats had raised intimal lesions, frequent adherent macrophages and endothelial damage. The frequency of these vascular abnormalities in the EDTA-treated rats was not different from that seen in the obese controls. The bone contents of calcium and magnesium were not significantly reduced.

CONCLUSIONS

Chelation therapy using intravenous EDTA has no beneficial effects on the arterial lesions in the atherosclerotic JCR:LA-cp rat. The increase in plasma triglyceride concentrations would be grounds for concern in human patients.