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Cardiac Ultrastructural and Electrophysiological Abnormalities in Postweanling Copper-Restricted and Copper-Repleted Rats in the Absence of Hypertrophy^1,2,

Department of Human Nutrition and Food Management ^* Department of Veterinary Physiology and Pharmacology, The Ohio State University, Columbus, OH 43210-1295

Cardiac ultrastructural and functional characteristics were determined in copper-depleted and copper-repleted rats. Male weanling rats were randomized into five groups that were fed either copper-adequate or copper-deficient diets. After 5 wk, one group fed each diet was studied to obtain baseline values. At this time, one copper-adequate postweanling group continued to receive the adequate diet as control, one deficient postweanling group was fed the adequate diet to evaluate the effect of copper repletion and one postweanling adequate group was fed the deficient diet to evaluate copper depletion in relatively older rats. These dietary treatments were continued for six additional weeks. Copper-depleted rats of both ages exhibited significant cardiac ultrastructural pathology and electrocardiogram abnormalities and the postweanling copper-depleted rats exhibited these abnormalities in the absence of hypertrophy and anemia. Increased mitochondrial volume density, disarranged cristae, and nonaligned myofibrils with disturbances at Z-bands were displayed. Additionally, all copper-depleted rats demonstrated fragmented basal laminae at capillary-myocyte interface. Increased QRS amplitude and notching and greater QT intervals were displayed. Copper-repleted rats exhibited some, but not total, reversal of these abnormalities. These results suggest that capillary-myocyte interface changes may play an important role in the developing pathology of copper depletion.

KEY WORDS: • copper deficiency • electrocardiogram • mitochondria • ultrastructure • rats

¹ Supported by the National Heart, Lung and Blood Institute, National Institutes of Health, Grant No. 5 R01 HL43286, to D. M. Medeiros.

² This study was conducted in partial fulfillment of the requirements of the Doctor of Philosophy degree for Jeannette Davidson.

³ To whom correspondence and reprint requests should be addressed.

Manuscript received 18 November 1991. Revision accepted 18 February 1992.