Independent mechanisms for the chronotropic and inotropic responses in hyperthyroidism

Abstract

We established a hyperthyroid rat model and compared the hemodynamic responses of the hypertrophied rat heartin vivo andin vitro. Heart rate (557±26 beats/min), systolic blood pressure (162±5 mm Hg) and dry heart mass (230±11 mg) in hyperthyroid rats were significantly greater than in control animals (408±12 beats/min, 140±5 mm Hg and 193±4 mg respectively).In vitro studies were performed in order to eliminate neurohumoral and peripheral circulatory factors which are presentin vivo. In thein vitro “working” heart preparation, there was no significant difference between the heart rates of L-thyroxine-treated (263±9 beats/min) and control (258±10 beats/min) animals, implying that the tachycardia of hyperthyroidism is partly mediated byin vivo factors. Consistent with this hypothesis was the observation that the hyperthyroid heart was more sensitive to the chronotropic effects of physiological concentrations of the synthetic catecholamine, isoproterenol (10⁻⁸M, 10⁻⁷ M) than the control heart. The maximum rate of left ventricular pressure rise (dP/dt_max) was used as an index of myocardial contractility.In vitro values for dP/dt_max were significantly greater in hearts from hyperthyroid rats (5338±228 mm Hg/s) than in control hearts (4583±158 mm Hg/s), suggesting that the increased contractile response of hyperthyroidism is intrinsic to the heart itself. Although persistence of the inotropic response of the hyperthyroid heartin vitro was associated with an increase in heart mass, this factor alone did not account entirely for the enhanced contractility. It appears that intrinsicfunctional changes also contribute to the inotropic response of the hyperthyroid heart.