Acute thyrotoxicosis in the rabbit: Changes in cardiac myosin, contractility, and ultrastructure

Thomas C. Smitherman, Roger S. Johnson, Kathryn Taubert, Robert S. Decker, Kern Wildenthal, William Shapiro, Robert Butsch, E. Glen Richards

Research output: Contribution to journalArticle

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Abstract

Alterations in the activity of cardiac myosin ATPase are known to develop during hyperthyroidism. We have characterized some of the changes in the biochemical and structural properties of myosin from rabbits made severely hyperthyroid by injection of 1-thyroxine (200-250 μg/kg per day), and compared the development of these changes to development of abnormalities of cardiac contractility and ultrastructure. Ca2+-adenosine triphosphatase (ATPase) activity of thyrotoxic rabbit cardiac myosin was enhanced 1.9-2.4 times that of normal and had a greater alkali stability. Similar enhancement of cardiac myosin Mg2+-ATPase was found. The enhancement was specific to cardiac myosin and was not due to cachexia alone. K+ (EDTA)-ATPase of cardiac muscle was unaltered as were the α-helical content and the number and electrophoretic mobility of the light subunits. Myosin prepared from a mix of myocardium from normal and thyroxine-treated animals had Ca2+-ATPase activity intermediate to that of the normal and thyrotoxic rabbit myosins, consistent with the hypothesis that the enhanced enzymatic activity was due to a molecular change rather than the presence of activators in hearts of thyrotoxic animals or inhibitors in control animal hearts. A decrease in developed tension and maximum rate of tension development was found in papillary muscles from severely thyrotoxic rabbits (a change opposite to that which would be expected from enhanced myosin ATPase activity alone). Simultaneously, striking alterations of myofibrillar organization developed in the hearts of thyrotoxic animals as observed by electron microscopy of fixed sections, including disorganized deployment of thin filaments, as well as areas of muscle necrosis and repair. Thus, in this experimental model, severe hyperthyroidism is accompanied by major alterations in cardiac myosin that should tend to enhance contractility, but also by toxic changes that may damage the tissue directly and/or render it more susceptible to injury in vitro and thereby reduce its contractility. Experimentally induced thyrotoxicosis in rabbits may serve as a useful model for studying thyroid-induced cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)277-298
Number of pages22
JournalBiochemical Medicine
Volume21
Issue number3
DOIs
StatePublished - 1979

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Cardiac Myosins
Thyrotoxicosis
Myosins
Adenosine Triphosphatases
Rabbits
Animals
Hyperthyroidism
Muscle
Thyroxine
Myocardium
Electrophoretic mobility
Poisons
Alkalies
Cachexia
Papillary Muscles
Edetic Acid
Electron microscopy
Structural properties
Cardiomyopathies
Repair

ASJC Scopus subject areas

  • Biochemistry

Cite this

Smitherman, T. C., Johnson, R. S., Taubert, K., Decker, R. S., Wildenthal, K., Shapiro, W., ... Richards, E. G. (1979). Acute thyrotoxicosis in the rabbit: Changes in cardiac myosin, contractility, and ultrastructure. Biochemical Medicine, 21(3), 277-298. https://doi.org/10.1016/0006-2944(79)90083-8

Acute thyrotoxicosis in the rabbit : Changes in cardiac myosin, contractility, and ultrastructure. / Smitherman, Thomas C.; Johnson, Roger S.; Taubert, Kathryn; Decker, Robert S.; Wildenthal, Kern; Shapiro, William; Butsch, Robert; Richards, E. Glen.

In: Biochemical Medicine, Vol. 21, No. 3, 1979, p. 277-298.

Research output: Contribution to journalArticle

Smitherman, TC, Johnson, RS, Taubert, K, Decker, RS, Wildenthal, K, Shapiro, W, Butsch, R & Richards, EG 1979, 'Acute thyrotoxicosis in the rabbit: Changes in cardiac myosin, contractility, and ultrastructure', Biochemical Medicine, vol. 21, no. 3, pp. 277-298. https://doi.org/10.1016/0006-2944(79)90083-8
Smitherman, Thomas C. ; Johnson, Roger S. ; Taubert, Kathryn ; Decker, Robert S. ; Wildenthal, Kern ; Shapiro, William ; Butsch, Robert ; Richards, E. Glen. / Acute thyrotoxicosis in the rabbit : Changes in cardiac myosin, contractility, and ultrastructure. In: Biochemical Medicine. 1979 ; Vol. 21, No. 3. pp. 277-298.
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