Skip to main content
ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #77179
Title: COPPER DEFICIENCY ENHANCES THE TOXICITY OF OUABAIN TO HEARTS PERFUSED BY THE LANGENDORFF METHOD

Author
item MCLEAN, S - MEDICAL COLLEGE OF OHIO
item ONWOCHEI, M - MEDICAL COLLEGE OF OHIO
item ASKARI, A - MEDICAL COLLEGE OF OHIO
item Klevay, Leslie

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 4/6/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Copper deficiency induces cardiac hypertrophy and is proposed as an etiologic factor in ischemic heart disease. As the alpha 2 isoform of Na/ K-ATPase decreases 50 to 80% in copper deficiency (Huang, et al., Cardio- vasc Res 29:563, 1995) and the therapeutic and toxic effects of ouabain are mediated by ATPase, we tested the hypothesis that copper deficiency increases sensitivity to ouabain toxicity. Male weanling rats of the Sprague-Dawley strain were fed a purified diet (Klevay, Am J Clin Nutr 26:1060, 1973) based on corn oil (10%), egg white protein (20%) and sucrose (62%) supplemented with zinc, with or without extra copper. After verification of deficiency, rats were shipped rapidly from Grand Forks to Toledo, where hearts were perfused under conditions of constant flow rate (6.5 ml/min/g heart) and preload (15 mmHg). After baseline measurements during 20 min equilibration, doses of ouabain were infused for 15 min each h at 25, 50, and 100 uM. Only at 100uM were there differences between groups. Left ventricular developed pressure, rate of increase of developed pressure, and rate of relaxation were decreased by 30%, 33%, and 24%, respecitvely (P<0.005) in deficiency. Deficient hearts also had an increased incidence of ventricular tachycardia (P<0.05). The deficient rat heart contracts normally under basal conditions but is more prone to ouabain toxicity which may reflect altered intracellular ions (as we found in Physiol & Behavior 49:309, 1991) from decreased ATPase expression. Perhaps people low in copper are more likely to become intoxicated with digitalis than those who benefit from the medicine, as U.S. diets often are low in copper.