CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

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Cardiac hypertrophy is a classical copper deficiency symptom. The hypertrophy may be due to the anemia observed in copper deficiency. An alternative hypothesis to be tested is that the cardiac myocardium and valves may be altered in the copper deficient state. The objectives of the proposed research are to evaluate the hearts of copper deficient rats from three points-of-view: 1) structural, 2) functional, and 3) biochemical. Several studies will be performed. In all experiments rats will be fed a purified diet formulated after recommendations from the America: Institute of Nutrition with either 1) adequate copper (8mg/Kg feed) or 2) no added copper. Rats will be maintained on the diets from weaning until 9 wks thereafter. Indicators of copper deficiency (ie. hematocrit, liver copper) will be assessed along the course of the developing copper deficiency for all experiments. For experiment one, some rats will be sacrificed at weaning and at wk 3, 6, and 9 and have cardiac myocardium and valves processed for transmission electron microscopy and light microscopy observations. Other rats will be sampled at similar points in time and have cardiac function tests performed: cardiac output, heart rate, blood pressure, etc. In another experiment, using the above design, heart valves and myocardium will be analyzed separately for collagen crosslinking. Myocardium will be assayed for total crosslinking using thermal shrinkage of extracted collagen. Heart valves will be assayed using established techniques for 2 specific crosslinks synthesized as a result of copper dependent lysyl oxidase: dehydro-5, 5' dihydroxylysinonorleucine and hydroxypyridinium. These studies are designed to determine the relationships of structural and collagen maturity observed in hypertrophy among copper deficient rats with cardiac function states. Data will be evaluated by a 2-way analysis of variance with time and diet as main effects. Findings will be submitted to reviewed journals.