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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #142014
Title: CONGESTIVE HEART FAILURE IN COPPER-DEFICIENT MICE

Author
item ELSHERIF, LAILA - UNIV OF LOUISVILLE
item ORTINES, RAYMOND - UNIV OF LOUISVILLE
item Saari, Jack
item KANG, Y - UNIV OF LOUISVILLE

Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2003
Publication Date: 8/1/2003
Citation: Elsherif, L., Ortines, R.V., Saari, J.T., Kang, Y.J. 2003. Coongestive heart failure in copper-deficient mice. Experimental Biology and Medicine. 228:811-817.

Interpretive Summary: Dietary copper deficiency leads to a variety of detrimental changes in the heart, including structural, molecular and functional changes. The purpose of this study was to examine functional characteristics of the copper-deficient heart that may determine whether the heart is beginning to fail. Mice were fed adequate or copper-deficient diet for 5 weeks. By using a method of measuring pressure within hearts of anesthetized rats we showed that hearts from copper-deficient rats were not able to develop as high a maximum pressure, had an elevated pressure during relaxation, were not able to contract and relax as fast and exhibited a blunted response to an adrenalin-like compound as compared to copper-adequate hearts. These are all characteristics associated with heart failure and illustrate that adequate copper nutrition is required for proper heart function.

Technical Abstract: Copper deficiency (CuD) leads to hypertrophic cardiomyopathy in various experimental models. The morphological, electrophysiological and molecular aspects of this hypertrophy have been under investigation for a long time. However, the transition from compensated hypertrophy to decompensated heart failure has not been investigated in the study of CuD. We set out to investigate the contractile and hemodynamic parameters of the CuD mouse heart and to determine whether heart failure follows hypertrophy in the CuD heart. Dams of FVB mice were fed CuD or copper-adequate (CuA) diet starting from the third day post delivery and the weanling pups were fed the same diet for a total period of up to 5 wks (pre- and post- weanling). Beginning at wk 4, female mice were used for the analysis of the functional parameters of the heart using a surgical technique for catheterizing the left ventricle. A significant decrease in left ventricle systolic pressure was observed with no significant change in heart rate, and more importantly contractility as measured by the maximal rate of left ventricular pressure rise (+dP/dt) and decline (-dP/dt) were significantly depressed in the CuD mice. On the other hand, left ventricle end diastolic pressure was elevated, and relaxation was impaired in the CuD animals; the duration of relaxation was prolonged. In addition to significant changes in the basal level of cardiac function, CuD hearts had a blunted response to the stimulation of the ß-adrenergic agonist isoproterenol. This study shows that CuD leads to systolic and diastolic dysfunction, which are indices commonly used to diagnose congestive heart failure (CHF).