Role of Thyroid State in Age-Dependent Cardiac Effects of Ouabain in Guinea Pigs

Abstract

We tested the hypothesis that the decrease in the thyroid state, with age, contributes to the age-related increase in myocardial responsiveness to cardiac glycosides. Thyroid hormone levels (reflecting the thyroid state): total T(4) (μg/dl) and total T(3) (ng/dl) in the 3 groups of guinea pigs were (mean ± SEM): adults (3 months old): < 1.0 and 22.6 ± 1.1; euthyroid newborns (0-5 days old): 3.9 ± 0.4 and 56.5 ± 11.9; hypothyroid newborns, (0-5 days old): 1.5 ± 0.3 and 26.5 ± 9.8. In euthyroid newborns, T(4 and T(3) levels were significantly higher than in adults (p < 0.01 for T(4) and p < 0.05 for T(3)) and in hypothyroid newborns (p < 0.05). Isometric twitch was recorded from right ventricular papillary muscles by means of a force transducer. Ouabain 1O^-6 M increased isometric twitch tension in adults (tension = 0.66 ± 0.18 g/mm^2) by 123.6 ± 18.2%, in euthyroid newborns (tension = 0.19 ± 0.04 g/mm^2) by 83.6 ± 14.5%, and in hypothyroid newborns (tension = 0.12 ± 0.01 g/mm^2) by 170.9 ± 33.8% (p < 0.01). Ouabain dose-response curve in the range of 10^-7 M — 0.5 × 10^-5 M was significantly different (compared by two-way ANOVA) between euthyroid newborns and hypothyroid newborns (p < 0.01), and between euthyroid newborns and adults (p < 0.01). Toxic effects of ouabain reflected by the generation of aftercontractions were also age related and were augmented by hypothyroidism in newborns. Aftercontraction amplitude was 105.0 ± 9.5 mg/mm^2/s in adults, 23.8 ± 5.0 mg/mm^2/s in euthyroid newborns and 89.5 ± 15.3 mg/mm^2/s in hypothyroid newborns, p < 0.001 euthyroid newborns versus hypothyroid newborns and adults. These results suggest that the age-related alterations in the thyroid state may contribute to changes in the inotropic and toxic effects of cardiac glycosides.