Developmental changes in ventricular action potential properties in guinea-pigs are modulated by age-related changes in the thyroid state

Abstract

Previous studies have demonstrated that in different cardiac preparations action potential duration (APD) increases with age. As in various species, thyroid hormone levels increase developmentally, and since hyperthyroidism shortens APD while hypothyroidism prolongs it, we hypothesized that developmental changes in APD result from age-related variations in the thyroid state. The hypothesis was tested by analysing ventricular action potentials and total T 4 (TT 4) levels in guinea-pigs in the age range of 0 days to 3 months (adult), and in hyperthyroid and hypothyroid newborns (0–5 days old). We found that APD 50 increased exponentially with age with a time constant of 6.7 days, from 100.6 ± 3.4 ms in newborns (0–5 days old) to 147.4 ± 5.2 ms in adults ( P<0.001). TT 4 decreased exponentially with age with a time constant of 4.8 days, from 3.9 ± 0.4 μg/dl in newborns to <1.0 μg/dl in adults. In the age range studied, APD 50 and TT 4 were linearly correlated: Y = −12.13X + 142, r − 0.865. In contrast to the marked changes in APD, resting potential and action potential amplitude were age-independent, and V ̇ max only slightly increased with age. Alterations in the thyroid state in newborns affected ventricular action potentials as predicted by the hypothesis. In euthyroid (TT 4 = 3.9 ± 0.4 μg/dl), hypothyroid (TT 4 = 1.6 ± 0.4 μg/dl) and hyperthyroid (TT 4 = 39.8 ± 10.8 μg/dl) newborns, APD 50 was: 100.6 ± 3.4 ms, 117.7 ± 4.2 ∗ ms,and 63.7 ± 7.4 ∗ ms, respectively ( ∗ P<0.01). The findings of this study suggest that the age-related alterations in the thyroid state may be responsible for the developmental changes in ventricular action potential duration.