Changes in myocardial cell size and number during the development and reversal of hyperthyroidism in neonatal rats

Increased workload was produced in newborn rats to study myocyte structure during conversion from hyperplastic to hypertrophic growth. Newborn rats were given L-thyroxine (T4) for 12 days and killed at that time or 20 days after discontinuing T4 treatment. Myocytes were isolated by a perfusion technique with collagenase. Cellular dimensions were determined with a sonic digitizer. Mean cell volumes were also determined with a Coulter counter for comparison with values obtained with the digitizer. Heart weight to body weight ratios were increased 30% in 12-day-old hyperthyroid rats. Cell length increased 22%, and cell volume increased 31% after 12 days of treatment with T4. The calculated number of ventricular myocytes indicated that T4 inhibited rather than stimulated hyperplastic myocyte growth. Twenty days after discontinuing T4 treatment, heart weight to body weight ratio and mean cell volume of treated animals were similar to control values. Cell length, however, remained significantly increased (14%), and cell width was significantly reduced (8%) after reversal of hyperthyroidism. We conclude that excess T4 inhibits hyperplastic myocyte growth in neonatal rats while stimulating hypertrophy of existing myocytes primarily by increasing cell length. Myocytes remained significantly longer after reversal of hyperthyroidism, indicating that structural changes may persist.