ROLE OF THYROID STATE IN AGE-DEPENDENT CARDIAC EFFECTS OF OUABAIN IN GUINEA-PIGS

We tested the hypothesis that the decrease in the thyroid state, with age, contributes to the age-related increase in myocardial responsiven ess to cardiac glycosides. Thyroid hormone levels (reflecting the thyr oid state): total T4 (mu-g/dl) and total T3 (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, T4 and T3 levels were significantly higher than in adults (p < 0.01 for T4 and p < 0.05 for T3) and in hypothyro id newborns (p < 0.05). Isometric twitch was recorded from right ventr icular papillary muscles by means of a force transducer. Ouabain 10(-6 ) M increased isometric twitch tension in adults (tension = 0.66 +/- 0 .18 g/mm2) by 123.6 +/- 18.2%, in euthyroid newborns (tension = 0.19 /- 0.04 g/mm2) by 83.6 +/- 14.5%, and in hypothyroid newborns (tension = 0.12 +/- 0.01 g/mm2) by 170.9 +/- 33.8% (p < 0.01). Ouabain dose-re sponse curve in the range of 10(-7) M - 0.5 X 10(-5) M was significant ly different (compared by two-way ANOVA) between euthyroid newborns an d hypothyroid newborns (p < 0.01), and between euthyroid newborns and adults (p < 0.01). Toxic effects of ouabain reflected by the generatio n of aftercontractions were also age related and were augmented by hyp othyroidism in newborns. Aftercontraction amplitude was 105.0 +/- 9.5 mg/mm2/s in adults, 23.8 +/- 5.0 mg/mm2/s in euthyroid newborns and 89 .5 +/- 15.3 mg/mm2/s in hypothyroid newborns, p < 0.001 euthyroid newb orns versus hypothyroid newborns and adults. These results suggest tha t the age-related alterations in the thyroid state may contribute to c hanges in the inotropic and toxic effects of cardiac glycosides.