Energetic consequences of thyroid-modulated shifts in ventricular isomyosin distribution in the rat

Heat production (measured myothermically), force development and isomyosin distribution were measured in left ventricular papillary muscles from adult male rats in three thyroid states: hyperthyroid (T3), euthyroid (C) and hypothyroid (Tx). Rats were rendered hyperthyroid by daily injections of tri-iodothyronine and hypothyroid by radioisotopic thyroidectomy. Papillary muscle performance was measured both for trains of isometric twitches and for brief (2 s) tetani achieved by increasing the Ca2+ concentration and adding caffeine to the bathing solution. Resting metabolic rate was uninfluenced by thyroid state. Heat-stress relations were determined for both twitches and tetani by altering muscle length. Tx muscles showed an elevated stress-independent or activation heat (intercept of the heat-stress relation), a depressed stress-dependent heat (slope of the heat-stress relation), and greatly enhanced peak twitch and tetanic (Smax) stresses. When normalized for Smax, the maximal rates of tetanic stress development and heat production were depressed in the Tx group. In the T3 group, only the normalized maximal rate of tetanic stress development was significantly increased. The lack of significant effects on other mechanical and energetic parameters probably reflects an under-dosing of animals in this tri-iodothyronine-treated group, an interpretation supported by the modest change in isomyosin distribution resulting from the treatment regimen used. Separate isomyosin analyses of papillary muscles and their associated ventricles yielded excellent correlation demonstrating the suitability of papillary muscles as a model of ventricular wall tissue. By experimentally manipulating the thyroid state, the distribution of the three ventricular isomyosins were correspondingly altered with a shift toward a greater and lesser proportion of high activity myosin ATPase in the hyperthyroid and hypothyroid groups respectively. The average proportions of the myosin heavy chain associated with high actin-activated myosin ATPase were 86, 74 and 6% for groups T3, C and Tx respectively. The measured changes in papillary muscle energetics correlate well with these thyroid-induced changes in isomyosin distribution and can be explained in terms of altered crossbridge dynamics.