A UNIFIED PERSPECTIVE ON COPPER DEFICIENCY AND CARDIOMYOPATHY

Dietary copper restriction in rats results in cardiomyopathy. In rats fed copper-restricted diets from weaning for 5 to 8 weeks, a concentri c hypertrophy is apparent, whereas postweaning copper restriction does produce cardiomyopathy without apparent hypertrophy. Both sets of cir cumstances appear to affect the integrity of the basal laminae of card iac myocytes and capillaries. In rats fed copper-restricted diets from weaning, decreases in cytochrome c oxidase are related not only to co pper's role as a coenzyme, but also to a marked decrease in the nuclea r encoded subunits of the enzyme complex. Decreased levels of the delt a-subunit of ATP synthase have been observed. However, such aberration s in mitochondrial enzymes, as well as morphologic alterations, appare ntly do not affect cardiac levels of ATP. This review suggests mechani sms of cardiac adaptation and initiation factors leading to cardiac hy pertrophy. We present a hypothetical working model explaining the even ts leading to cardiac failure in the copper-deficient rat heart based on the present body of knowledge, and compare the pathology with other models of cardiomyopathies.