Independent mechanisms for the chronotropic and inotropic responses in hyperthyroidism.
We established a hyperthyroid rat model and compared the hemodynamic responses of the hypertrophied rat heart in vivo and in vitro. Heart rate (557 +/- 26 beats/min), systolic blood pressure (162 +/- 5 mmHg) and dry heart mass (230 +/- 11 mg) in hyperthyroid rats were significantly greater than in control animals (408 +/- 12 beats/min, 140 +/- 5 mmHg and 193 +/- 4 mg respectively). In vitro studies were performed in order to eliminate neurohumoral and peripheral circulatory factors which are present in vivo. In the in 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 by in 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(-8) M, 10(-7) M) than the control heart. The maximum rate of left ventricular pressure rise (dP/dtmax) was used as an index of myocardial contractility. In vitro values for dP/dtmax were significantly greater in hearts from hyperthyroid rats (5338 +/- 228 mmHg/s) than in control hearts (4583 +/- 158 mmHg/s), suggesting that the increased contractile response of hyperthyroidism is intrinsic to the heart itself. Although persistence of the inotropic response of the hyperthyroid heart in vitro was associated with an increase in heart mass, this factor alone did not account entirely for the enhanced contractility. It appears that intrinsic functional changes also contribute to the inotropic response of the hyperthyroid heart.
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics; D006980:Hyperthyroidism / Q000150:complications / Q000503:physiopathology*; D007545:Isoproterenol; D008297:Male; D009200:Myocardial Contraction; D051381:Rats; D011919:Rats, Inbred Strains
D007545:Isoproterenol