Enhanced myocardial contractility but not tachycardia persists in isolated working hyperthyroid rat hearts

It is generally believed that the increased contractility and tachycardia of the hyperthyroid heart are a result of thyroid hormone-induced alterations of the mechanical and electrical properties of the heart, respectively. We compared the contractility (dP/dt_max) and the spontaneous beating rate of hyperthyroid and euthyroid hearts perfused in vitro in either a non-working or a working mode. The dP/dt_max (4196±74 mm Hg s^-1) and beating rate (322±8 beats/min) of the non-working hyperthyroid hearts were significantly higher (p<0.001) than those of the euthyroid hearts (3267±115 mm Hg s^-1 and 260±6 beats/min at an external Ca²⁺ of 2.5 mM). At 2.5 mM Ca²⁺, the working hyperthyroid hearts again displayed enhanced contractility (5636±179 mm Hg s^-1 vs 4508±172 mm Hg s^-1; p<0.001) but the spontaneous beating rate (275±7 beats/min) was not significantly different from euthyroid (261±8 beats/min). When hearts were subjected to periods of alternate non-working and working perfusion, the beating rate of the hyperthyroid hearts was significantly higher than euthyroid during non-working (p<0.02) but not during working perfusion. Increasing the afterload on the non-working preparations in a stepwise fashion from 75 cm H₂O to 120 cm H₂O caused significant changes in left ventricular pressure and dP/dt_max in both heart types but the tachycardia in the hyperthyroid hearts persisted (at 120 cm H₂O; hyperthyroid, 294±9 beats/min; euthyroid, 224±10 beats/min; p<0.001). Alteration of the preload (10 to 25 cm H₂O) and afterload (75 to 105 cm H₂O) on working hyperthyroid and euthyroid hearts caused changes in both left ventricular pressure and dP/dt_max but the beating rates of both heart types were never significantly different. We conclude from our results that (i) the increased contractility of the hyperthyroid rat heart is due to thyroid hormone-induced alteration of the mechanical properties of the heart; (ii) the tachycardia of hyperthyroidism is not due to thyroid hormone-induced changes in the electrical properties of the heart, but probably involves some as yet unidentified chronotropic agent.