Comparison of the Action of Ouabain on the Heart in Hypothyroid, Euthyroid and Hyperthyroid Dogs

Rosén, Anders; Moran, Neil C.

doi:10.1161/01.res.12.5.479

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…In an earlier study from this laboratory it was observed that the percentage increase in contractile force of the right ventricle of intact hyperthyroid dogs was only slightly, though not significantly, lower than that observed in euthyroid animals (33). In a similar preparation, Rosen and Moran noted no difference between euthyroid and hyperthyroid dogs in their inotropic response to moderate doses of ouabain, but found that larger doses caused a smaller inotropic response in hyperthyroid than in euthyroid animals (34). Peacock and Moran reported that hyperthyroidism diminished the contractile force developed by strips of the right ventricle of rats and reduced the increment in force after the addition of ouabain to the bath (35).…”

Section: Mals (Figs 4 and 5)mentioning

confidence: 97%

“…Earlier investigators observed that hypothyroid dogs exhibited a normal increment of contractile force when ouabain was administered (34) and that the contractile force of right ventricular strips removed from hypothyroid rats, although greater than normal to begin with, showed reduced response after the addition of ouabain (35). The results of the present study are again not in concert with these findings, since we have noted that intrinsic contractile tension of muscles from hypothyroid cats tends to be reduced but that the increments of tension after the addition of strophanthidin were enhanced at every dose level studied.…”

Section: Mals (Figs 4 and 5)mentioning

confidence: 98%

“…All workers who have examined the problem agree that both hypoand hyperthyroid heart muscle respond to the glycoside (5, [33][34][35]; however, analysis of the problem in patients and intact experimental animals is complicated by the facts that the absorption and the turnover of the drug (36), as well as the fraction of the cardiac output which enters the coronary circulation (37,38), may all be influenced by alterations in the thyroid state, making it difficult to deliver a known concentration of drug to the myocardium. In an earlier study from this laboratory it was observed that the percentage increase in contractile force of the right ventricle of intact hyperthyroid dogs was only slightly, though not significantly, lower than that observed in euthyroid animals (33).…”

Section: Mals (Figs 4 and 5)mentioning

confidence: 99%

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

Buccino¹,

Spann²,

Pool³

et al. 1967

J. Clin. Invest.

377

100

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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.

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Section: Mals (Figs 4 and 5)mentioning

confidence: 97%

Section: Mals (Figs 4 and 5)mentioning

confidence: 98%

Section: Mals (Figs 4 and 5)mentioning

confidence: 99%

See 1 more Smart Citation

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

Buccino¹,

Spann²,

Pool³

et al. 1967

J. Clin. Invest.

377

100

View full text Add to dashboard Cite

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“…For many years it was believed that these alterations were entirely pharmacodynamic in nature due to alteration in the contractile state of myocardial muscle (Buccino et al, 1967;Morrow et al, 1963;Peacock and Moran, 1963;Rosen and Moran, 1963). The whole emphasis changed with the publication by Doherty and Perkins (1966) of a study of tritiated digoxin kinetics in hypo-and hyperthyroidism: plasma concentrations after intravenous injection were lower than control in the hyperthyroid group and higher than control in the hypothyroid group.…”

Section: Cardiac Glycosidesmentioning

confidence: 99%

Influence of Thyroid Dysfunction on Drug Pharmacokinetics

Shenfield

1981

Clinical Pharmacokinetics

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When thyroidfunction is altered there are a series of physiological changes which are likely to affect drug absorption, metabolism or excretion, and altered pharmacokinetics have been described for a variety of drugs in both hypothyroidism and hyperthyroidism.Absorption of riboflavine is increased in hypothyroidism and decreased in hyperthyroidism due to changes in gut motility. Opposite/in dings have been described for ethanol in rats, but remain to be confirmed in man. There is definite evidence of induction of hepatic metabolism in hyperthyroidism with reduced metabolism in hypothyroidism. A ntipyrine half-lives are therefore decreased in hyperthyroidism and prolonged in hypothyroidism. The same may be true for aminopyrine, but there do not appear to be any significant changes iin phenytoin kinetics. There is need for an increased dose of oral anticoagulants in hypothyroidism and a decreased dose in hyperthyroidism due to altered catabolism of vitamin K -dependent clotting factors in the absence of any alteration in the metabolism of the anticoagulant drugs themselves. A t present it is not possible to predict the effect of altered thyroid function on the metabolism of any individual drug.The antithyroid drug methimazole, which is also the active metabolite of carbimazole, has a shorter half-life in hyperthyroid patients than in normal controls. This probably accounts for the needforfrequent doses while hyperthyroidism is active and the effectiveness of a once daily dose once the disease is under control. Propylthiouracil has a shorter half-life than methimazole and there is litlle good evidence of any change in ha(f-I!fe with thyroid dysfunction.information about the ~-adrenoceptor blocking drugs in altered thyroid states is scanty, but there is a trend to a shortened propranolol ha(f-life and reduced area under the serum concentration-time curve in hyperthyroidism and a prolonged ha(f-life in hypothyroidism. The reasons for this will not be known untif propranolol metabolites are assayed in states of thyroid dysfunction. There is an increased clearance of practolol in hyperthyroidism, probably due to increased renal excretion.There are lower than normal plasma concentrations Qf cardiac glycosides in hyperthyroidism and, possibly, higher than normal concentrations in hypothyroidism. There appears to be an altered volume of distribution Qf digoxin in thyroid dysfunction -being increased in hyperthyroidism and decreased in hypothyroidism. This may be due to altered cardiac and skeletal muscle binding of digoxin in hyperthyroidism. Pharmacokinetic changes alone cannot

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“…A decreased left ventricular contractile response to calcium suggests that the effect of thyroid hormone on the myocardial contractile apparatus is not limited to adrenergic receptors. The decreased inotropic response to cardiac glycosides in hyperthyroid animals (6,12,13) also supports this concept. Thyroid hormone probably increases myocardial contractile ability by a direct effect.…”

Section: Discussionmentioning

confidence: 52%

Myocardial Contractile Response to Norepinephrine, Isoproterenol, and Calcium Chloride in Hyperthyroid Guinea Pigs

Goodkind

1969

Circulation Research

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Myocardial contractility, measured as the maximum left ventricular systolic pressure response to aortic constriction, is greater than normal in the hyperthyroid guinea pig. The effect of inotropic agents on this response was determined in anesthetized, open-chest, euthyroid, and hyperthyroid guinea pigs. Norepinephrine and isoproterenol in single doses, 1 |txg/kg, and isoproterenol infused intravenously, 1, 4 and 10 ^ig/kg/min, caused a smaller increase in myocardial contractile response to aortic constriction in hyperthyroid than in euthyroid animals. Hyperthyroid guinea pigs also responded to an infusion of calcium chloride, 11 mg/kg/min, with an increase in maximum systolic pressure which was less than normal. With each drug the maximum systolic pressure level attained during aortic constriction was greater in the euthyroid than in the hyperthyroid animals. Cardiac pacing of euthyroid guinea pigs at 430 beats/min, a rate similar to the spontaneous rate of the hyperthyroid guinea pig, did not alter the inotropic response to infused calcium, though single injections and intravenous infusions of isoproterenol had less of an effect than in the spontaneously beating normal heart. These results suggest that the increased myocardial contractility of the hyperthyroid guinea pig may have reached a near maximum level. As a result, the added inotropic effects of isoproterenol and calcium in these animals are less than in normal controls.ADDITIONAL KEY WORDS active inotropic agents tachycardia aortic constriction maximal systolic pressure cardiac pacing thyroxine pressure work afterload • Although early reports suggested that the cardiovascular system of thyroid-stimulated 18. CAIBOLI, V. J., AND CROUT, J. R. : Role of the autonomic nervous system in the resting tachycardia of experimental hyperthyroidism. J.

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Comparison of the Action of Ouabain on the Heart in Hypothyroid, Euthyroid and Hyperthyroid Dogs

Cited by 6 publications

References 19 publications

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

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

Influence of Thyroid Dysfunction on Drug Pharmacokinetics

Myocardial Contractile Response to Norepinephrine, Isoproterenol, and Calcium Chloride in Hyperthyroid Guinea Pigs

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