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 medica l 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 c helation 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 hyperi nsulinemia and hypertriglyceridemia, and is unique in the spontaneous devel opment of atherosclerosis and ischemic myocardial lesions. Experimental protocol: Eight-month-old, obese, male JCR:LA-cp rats were fit ted with indwelling venous cannulae and infused over 4 weeks with ethylened iaminetetraacetic acid (EDTA) 5 days a week at a daily dose of 40 mg/kg bod y 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 sacrific ed and perfusion-fixed for scanning electron microscopy of the aortic arch. Results: Plasma cholesterol concentrations were not changed by the EDTA tre atment. Tn contrast, plasma triglyceride concentrations were raised signifi cantly (74%, p < 0.05). Lean control rats showed minimal abnormality of the aortic arch, whereas the obese control rats had raised intimal lesions, fr equent 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 hone contents of calcium and magnesium wer e not significantly reduced. Conclusions: Chelation therapy using intravenous EDTA has no beneficial eff ects on the arterial lesions in the atherosclerotic JCR:LA-cp rat. The incr ease in plasma triglyceride concentrations would be grounds for concern in human patients.