Developmental changes in ventricular action potential properties in guinea-pigs are modulated by age-related changes...

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 T4 (TT4) 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 APD50 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 less than 0.001). TT4 decreased exponentially with age with a time constant of 4.8 days, from 3.9 +/- 0.4 micrograms/dl in newborns to less than 1.0 microgram/dl in adults. In the age range studied, APD50 and TT4 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 Vmax only slightly increased with age. Alterations in the thyroid state in newborns affected ventricular action potentials as predicted by the hypothesis. In euthyroid (TT4 = 3.9 +/- 0.4 micrograms/dl), hypothyroid (TT4 = 1.6 +/- 0.4 micrograms/dl) and hyperthyroid (TT4 = 39.8 +/- 10.8 micrograms/dl) newborns, APD50 was: 100.6 +/- 3.4 ms, 117.7 +/- 4.2 ms and 63.7 +/- 7.4 ms, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)