This study was undertaken to test the hypothesis that a compensatory response of the heart to a chronic and continuous, metabolic and heart rate overload was an increase in the calcium sequestering activity of the myocardial sarcoplasmic reticulum. Calcium sequestering activity was estimated by determination of the calcium-dependent ATPase (Ca2+-ATPase) activity of isolated microsomes. Chronic rate overload was modelled by comparing: dysthyroid and control rats; control swine and swine with implanted cardiac pacemakers set at 180 beats/min; and different species of mammals with widely different heart rates. The myocardial sarcoplasmic reticulum Ca2+-ATPase pump activity was significantly increased by 39% for hyperthyroid rats compared to control rats and by 87% for control rats compared to thyroidectomized rats; by 63% for paced swine compared to control swine; and by 43% for rats compared to guinea pigs, by 140% for guinea pigs compared to dogs and by 120% for dogs compared to cows. These data indicate that calcium sequestering activity of myocardial sarcoplasmic reticulum increases in equivalent proportion to the chronotropic demand and that heart rate is a hemodynamic correlate of the sarcoplasmic reticulum Ca2+-ATPase activity.

It is well established that extreme dysthyroidism drastically alters the biochemical character of cardiac muscle. The purpose of this study was to determine if minor thyroid treatments would result in significant changes in the character of three major biochemical systems of muscle: metabolic; calcium regulating; and contractile systems. Different groups of New Zealand white rabbits had continuous time release propylthiouracil (PTU) pellets (500, 300, 200 and 100 mg) or triiodothyronine (T3) pellets (15 and 25 mg) subcutaneously implanted for 21 days. The ventricular myosin phenotypes shifted from 92% V3 myosin in the control rabbit hearts to 55% V3 and 10% V3 in the 15 mg and 25 mg T3 groups, respectively. PTU treatment resulted in a complete shift to the V3 myosin isoform. The sarcoplasmic reticulum Ca2+-ATPase activity increased with T3 and decreased with PTU treatments, except in the 500 mg PTU group. Ca2+-ATPase activity in the groups either side of the euthyroid group (100 mg PTU and 15 mg T3) did not change significantly. The glycolytic or aerobic potentials of the myocardium did not change with any of these minor thyroid treatments. It was concluded that the metabolic, enzymes, sarcoplasmic reticulum Ca2+-ATPase and myosin isozymes have different sensitivities to thyroid treatment and that minor thyroid treatments do result in significant changes in the biochemical character of the myocardium. These findings indicate that subclinical deviations in euthyroid status may affect myocardial biochemical character.