Pharmacodynamic Effects of Beta-Adrenergic Receptor Blockade in Patients with Hyperthyroidism *

Adequate oral or intravenous doses of a betaadrenergic receptor-blocking drug, nethalide,' produce no significant changes in the resting oxygen consumption, heart rate, cardiac output, and systemic mean arterial or mean right atrial pressures of patients with spontaneous hyperthyroidism (1). These findings do not support the concept that the hemodynamic changes in hyperthyroidism are mediated through adrenergic stimulation of betaadrenergic receptors. The work of Brewster, Isaacs, Osgood, and King, however, supported the hypothesis that the sympathetic nervous system may be responsible for the metabolic and hemodynamic changes associated with the hypermetabolic state, since the alterations induced by thyroid feeding to dogs could be abolished by epidural blockade (2). The possibility exists that spontaneous hyperthyroidism and drug-induced hypermetabolism may have similar hemodynamic findings but different mechanisms. This study was designed to test the effects of beta-adrenergic blockade in normal subjects before, during, and after the induction of hypermetabolism with triio-

Section: Discussioncontrasting

confidence: 49%

Effects of beta-adrenergic receptor blockade in normal subjects before, during, and after triiodothyronine-induced hypermetabolism.

Wilson¹,

Theilen²,

Hege³

et al. 1966

“…On the other hand, Van der Schoot and Moran (42) recently reported that hyperthyroidism does not potentiate, but tends to depress, the positive inotropic and chronotropic responses to catecholamines both in vivo (dogs) and in vitro (rat atria and ventricle strips); and Margolius and Gaffney found that pressor and chronotropic responses to endogenously released or exogenously administered norepinephrine in dogs were not affected by pretreatment with thyroid hormone or '-"I (43). Similarly, Wilson, Theilen, Hege, and Valenca showed that isoproterenol produced similar increments in heart rate and cardiac index in normal human subjects before and after triiodothyronineinduced hypermetabolism (44) and Wilson, Theilen, and Fletcher found that propranolol, in doses sufficient to block the effects of isoproterenol, did not alter the hemodynamic effects produced by triiodothyronine administration (45).…”

Section: Mals (Figs 4 and 5)mentioning

confidence: 89%

Influence of the Thyroid State on the Intrinsic Contractile Properties and Energy Stores of the Myocardium*

Buccino¹,

Spann²,

Pool³

et al. 1967

377

100

Abstract. The intrinsic contractile properties of isolated cat papillary muscles and myocardial high energy phosphate stores were examined at three levels of thyroid activity and correlated with hemodynamic measurements in the intact animal. In addition, the relationship of thyroid state to endogenous norepinephrine stores and myocardial responsiveness to certain inotropic in-.terventions were studied. In muscles from hyperthyroid cats, the velocity of shortening and the rate of tension development were markedly augmented, while duration of active state was decreased, compared to euthyroid muscles. These findings occurred in the presence and absence of intact norepinephrine stores and over a wide range of temperature and contraction frequency. The opposite changes occurred in muscles from hypothyroid cats. Isometric tension was slightly higher in muscles from hyperthyroid and lower in muscles from hypothyroid cats. The inotropic response to both norepinephrine and strophanthidin varied inversely with the level of thyroid state and allowed all three groups of muscles to reach a common ceiling of isometric tension regardless of thyroid state. Creatine phosphate and adenosine triphosphate stores were intact at all three levels of thyroid state. Thus, the level of thyroid activity profoundly affects the intrinsic contractile state of cardiac muscle, independent of both norepinephrine stores and alterations in high energy phosphate stores, and, in addition, modifies the responsiveness of cardiac muscle to inotropic agents.

“…In contrast, the influence of thyroid state on the mechanics of contraction of isolated cardiac muscle has been completely documented only recently (5). In the intact experimental animal, and in man, the effects of altered thyroid state upon heart rate, total body or organ blood flow and metabolism (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), heart size, and the electrocardiogram have been investigated (19)(20)(21)(22). However, there is little information on the manner in which hyper-and hypothyroidism affect the characteristics of contraction of the intact, in situ left ventricle.…”

Section: Introductionmentioning

confidence: 99%

Influence of the thyroid state on left ventricular tension-velocity relations in the intact, sedated dog

Taylor¹,

Covell²,

Ross³

1969

108

The mechanical properties of left ventricular contraction were described in terms of tension, velocity, length, and time in closed-chest, sedated normal, hypothyroid, and hyperthyroid dogs. Heart rate was controlled at 150 beats/min, and instantaneous contractile element velocity was calculated from left ventricular pressure and its first derivative during isovolumic left ventricular contractions, produced by sudden balloon occlusion of the ascending aorta during diastole. Wall tension was derived from ventricular pressure and volume, the latter being obtained from the pressure-volume relation of the arrested ventricle, and tension-velocity relations were analyzed over a range of ventricular enddiastolic volumes. At any level of ventricular volume, the hypothyroid state was associated with a displacement of the tension-velocity relation of the left ventricle downwards and to the left, and the time to peak tension was prolonged (154 msec, normal 139 msec). In the hyperthyroid state, the tension-velocity relation of the left ventricle was displaced upwards and to the right, and the time to peak tension was reduced (80 msec). The changes in the tension-velocity relations indicate that the inotropic state of the left ventricle in the intact dog varies directly with the animal's thyroid state. This influence on myocardial contractility necessarily constitutes an important and integral part of the response of the intact circulation to altered thyroid state.