Summary
Male Wistar rats were treated with high cortisol doses for 1 week. The dose administered daily was 15 mg per animal in group 1 (7 animals) and 30 mg in group 2 (7 animals). 7 rats served as control group. After cortisol treatment the body weights decreased due to skeletal muscle catabolism and the heart weights increased. Morphometric analysis of the left ventricular posterior papillary muscles gave evidence that the increased heart weights resulted from an increased number of mitochondria and an increased volume of the cytoplasm, whereas the myofibrillar mass was not affected. The surface area of inner mitochondrial membranes (+cristae mitochondriales) per myofibrillar unit volume increased from 15.7 μ2/μ3 to 21.3 μ2/μ3 in group 1 and 21.4 μ2/μ3 in group 2. Ultrastructural changes indicating myocardial cell damage were absent. Similar quantitative results have been reported to occur in the early phase of cardiac overload. For elucidating the hemodynamic effects of glucocorticoid a second experiment was performed: 7 Wistar rats were treated with cortisol in the same way as group 1, 7 others of the same body weight served as control. The systolic arterial pressure was significantly elevated in the cortisol group. Though myocardial tissue is known to be able to accumulate large quantities of glucocorticoids our results indicate that the application of high cortisol doses for a short time does not produce myocardial cell damage and does not suppress the myocardial adaption to the glucocorticoid-induced hypertension, i.e. hypertrophy. On the contrary, it seems to be possible that the adaption process is itself facilitated or accelerated by the presence of high cortisol concentrations in the heart. This thesis is supported by the considerably higher relative heart weights in the cortisol groups and is in agreement with observations reported by other authors.
Similar content being viewed by others
References
Albert, R.E., Smith, W.W., Eichna, L.W.: Hemodynamic changes associated with fluid retention induced in noncardiac subjects by corticotropin (ACTH) and cortisone ; comparison with hemodynamic changes of congestive heart failure. Circulation 12, 1047–1056 (1955)
Anversa, P., Vitali-Mazza, L., Visioli, O., Marchetti, G.: Experimental cardiac hypertrophy: a quantitative ultrastructural study in the compensatory stage. J. Mol. Cell. Cardiol. 3, 213–228 (1971)
Beardsley, A.C., Okuda, M., Lefer, A.M.: Factors influencing nonspecific binding of glucocorticoids in myocardial tissue. Proc. Soc. Exp. Biol. Med. 151, 457–461 (1976)
Berson, G., Swynghedauw, B.: Myofibrillar ATPase in rats experimental heart failure produced by a two steps mechanical overloading. Cardiovasc. Res. 7, 464–469 (1973)
Beznák, M.: The behaviour of the weight of the heart and the blood pressure of albino rats under different conditions. J. Physiol. 124, 44–63 (1954)
Bózner, A., Meesen, H.: Die Feinstruktur des Herzmuskels der Ratte nach einmaligem und nach wiederholtem Schwimmtraining. Virchows Arch. Abt. B Zellpath. 3, 248–269 (1969)
Bózner, A., Knieriem, H.J., Meesen, H., Reinauer, H.: Die Ultrastruktur und Biochemie des Herzmuskels der Ratte im Thiaminmangel und nach einer Gabe von Thiamin. Virchows Arch. Abt. B Zellpath. 2, 125–143 (1969)
Bullock, G.R., Carter, E.E., Elliot, P., Peters, R.F., Simpson, P., White, A.M.: Relative changes in the function of muscle ribosomes and mitochondria during the early phase of steroid-induced catabolism. Biochem. J. 127, 881–892 (1972)
Busuttil, R.W., George, W.J.: Myocardial ischemia, cyclic nucleotides, and lysosomal enzymes. Advances in Cyclic Nucleotides Research, Vol 9, 629–645, W. J. George and L. J. Ignarro (eds). New York: Raven Press 1978
D'Agostino, A.N.: An electron microscopic study of cardial necrosis produced by a fluorocortisol and sodium phosphate. Am. J. Pathol. 45, 633–644 (1964)
Delcayre, C., Swynghedauw, B.: A comparative study of heart myosin. ATPase and light subunits from different species. Pflügers Arch. 355, 39–47 (1975)
Fizel, A., Fizelova, A.: Participation of catecholamine and cortical hormones in the myocardial metabolic adaption to mechanical overload of the heart. Recent Adv. Cardiac Struct. Metab. 1, 814–829 (1972)
Friedman, S.M., Friedman, C.L., Nakashima, M.: The hypertensive effect of compound F acetate (17-OH-corticosterone-21-acetate) in the rat. Endocrinology 51, 401–405 (1952)
Funder, J.W., Duval, D., Meyer, P.: Cardiac glucocorticoid receptors: the binding of tritiated dexamethasone in rat and dog heart. Endocrinology 93, 1300–1308 (1973)
Hatt, P.Y.: Cellular changes in mechanically overloaded heart. Basic Res. Cardiol. 72, 198–202 (1977)
Hatt, P.Y., Jouannot, P., Moravec J., Perennec, J., Laplace, M.: Development and reversal of pressure-induced cardiac hypertrophy. Basic Res. Cardiology 73, 406–421 (1978)
Hofmann, V.G., Emmrich, J.: Kreislaufwirkungen der Nebennierenrindenhormone. Verhandl. dtsch. Ges. Kreislaufforsch. 25, 108–111 (1959)
Jacob, R., Ebrecht, G., Kämmereit, A., Medugorac, I., Wendt-Gallitelli, M.F.: Myocardial function in different models of cardiac hypertrophy. An attempt of correlating mechanical, biochemical, and morphological parameters. Basic Res. Cardiol. 72, 160–167 (1977)
Ketelsen, U.P., Freund-Mölbert, E., Struck, E.: Zur Pathomorphologie der Corticoidmyopathie. Ultrastrukturelle Veränderungen des Plasmalemm der Skelett- und Herzmuskelzelle im Vergleich zur intrazellulären Reaktion. Beitr. Path. 153, 133–164 (1974)
Kloner, R.A., Fishbein, M.C., Lew, H., Maroko, P.R., Braunwald, E.: Mummification of the infarcted myocardium by high dose corticosteroids. Circulation 57, 56–63 (1978)
Kolanowski, J., Lammert, J.: Rate of uptake of endogenous cortisol by the left ventricle of the anaesthetized dog during ventilation with ambient air and during hypoxia. J. Physiol. 233, 519–527 (1973)
Kuegelgen, B. von, Rich, W., Koch, E.: Hydrocortisonwirkungen auf Kreislauf- und Lungenfunktion. Verh. Dtsch. Ges. Kreislaufforsch. 25, 112–116 (1959)
Leclerq, J.F., Swynghedauw, B.: Myofibrillar ATPase, DNA and OH pro content of human hypertrophied heart. Europ. J. Clin. Invest. 6, 27–30 (1976)
Libby, P., Maroko, P.R., Bloor, C.M., Sobel, B.E., Braunwald, E.: Reduction of experimental myocardial infarct size by corticosteroid administration. J. Clin. Invest. 52, 599–607 (1973)
Mall, G., Kayser, K., Rossner, J.A.: The loss of membrane images from oblique sectioning of biological membranes and the availability of morphometric principles — demonstrated by the examination of heart muscle mitochondria. Mikroskopie 33, 246–254 (1977)
Mall, G., Reinhard, H.: Morphometrische Untersuchungen am Rattenherzen nach hochdosierter Gabe von Cortisol. Verh. Dtsch. Ges. Path. 61, 445 (1977)
Mall, G., Reinhard, H., Kayser, K., Rossner, J.A.: An effective morphometric method for electron microscopic studies on papillary muscles. Virchows Arch. A Path. Anat and Histol. 379, 219–228 (1978)
Mayer, M., Shafrier, E., Kaiser, N., Milholland, R.J., Rosen, F.: Interaction of glucocorticoid hormones with rat skeletal muscle catabolic effects and hormone binding. Metabolism 25, 157–167 (1976)
McCallister, L.P., Page, E.: Effects of thyroxin on ultrastructure of rat myocardial cells: a stereological study. J. Ultrastruct. Res. 42, 136–155 (1973)
Meerson, F.Z., Zaletayeva, T.A., Lagutchev, S.S., Pshennikova, M.G.: Structure and mass of mitochondria in the process of compensatory hyperfunction and hypertrophy of the heart. Exp. Cell Res. 36, 568–578 (1964)
Metzler, A. von: Über die hormonale Ursache der Herzhypertrophie. Archiv Kreislaufforsch. 18, 359–395 (1952)
Mueller, E.A., Griffin, W.S.T., Wildenthal, K.: Isoproterenol — induced cardiomyopathy: Changes in cardiac enzymes and protection by methylprednisolone. J. Moll. Cell. Cardiol. 9, 565–578 (1977)
Nienhaus, H., Poche, R., Reimold, E.: Elektrolytverschiebungen, histologische Veränderungen der Organe und Ultrastruktur des Herzmuskels nach Belastung mit Cortisol, Aldosteron und primärem Natriumphosphat bei der Ratte. Virchows Arch. Path. Anat. 337, 245–269 (1963)
Okuda, M., Young, K.R., Lefer, A.M.: Localization of glucocorticoid uptake in normal and ischemic myocardial tissue of isolated perfused cat hearts. Circulation Res. 39, 640–646 (1976)
Page, E., Polimeni, P.I., Zak, R., Early, J., Johnson, M.: Myofibrillar mass in rat and rabbit heart muscle. Circulation Res. 30, 430–439 (1972)
Page, E., McCallister, L.P.: Quantitative electron microscopic description of heart muscle cells. Am. J. Cardiol. 31, 172–181 (1973)
Poche, R., De Mello Mattos, C.M., Rembarz, H.W., Stoepel, K.: Über das Verhältnis Mitochondrien: Myofibrillen in den Herzmuskelzellen der Ratte bei Druckhypertrophie des Herzens. Virchows Arch. Abt. A Path. Anat. 344, 100–110 (1968)
Sambhi, M.P., Weil, M.H., Udhoji, V.N.: Acute pharmacodynamic effects of glucocorticoids. Circulation 31, 523–530 (1965)
Seleznev, Yu. M., Danilov, S.M., Preobradjensky, S.N., Volkova, N.G., Kuznetsova, L.A., Smirnov, V.N., Volchek, A.G.: Glucocorticoid-binding proteins of rat heart cytosol and their possible role in the transfer of glucocorticoids into nuclei. J. Mol. Cell. Cardiol. 10, 877–891 (1978)
Selye, H.: The pluricausal cardiopathies. Springfield, III.: Charles C. Thomas 1961
Selye, H., Somogyi, A., Côté, G.: Sensitization by corn oil for the production of cardiac necroses by various steroids and sodium salts. Am. J. Cardiol. 23, 719–722 (1969)
Shoji, S., Pennington, R.J.T.: The effect of cortisone on protein breakdown and synthesis in rat skeletal muscle. Mol. Cell. Endocrinol. 7, 159–169 (1977)
Smith, H.E., Page, E.: Morphometry of rat mitochondrial subcompartiments and membranes: application to myocardial cell atrophy after hypophysectomy. J. Ultrastruct. Res. 55, 31–41 (1976)
Spath, J.A. Jr., Lane, D.L., Lefer, A.M.: Protective action of methylprednisolone on the myocardium during experimental myocardial ischemia in the rat. Circ. Res. 35, 44–51, (1974)
Spath, J.A., Lefer, A.M.: Effects of dexamethasone on myocardial cells in the early phase of acute myocardial infarction. Am. Heart J. 90, 50–55 (1975)
Swynghedauw, B., Schwartz, K., Léger, J.J.: Cardiac myosin. Phylogenic and pathological changes. Basic Res. Cardiol. 72, 254–260 (1977)
Tate, E.L., Herbener, G.H.: A morphometric study of the density of mitochondrial cristae in heart and liver of aging mice. J. Gerontol. 31, 129–134 (1975)
Warmuth, H., Fleischer, M., Themann, H., Achatzky, R.S., Dittrich, H.: Feinstrukturell-morphometrische Befunde an der Kammerwand hypertrophierter menschlicher Ventrikel. Virchows Arch. A Path. Anat. and Histol. 380, 135–147 (1978)
Weibel, E.R.: Stereological principles for morphometry in electron microscopic cytology. Int. Rev. Cytol. 26, 235–302 (1969)
Wollenberger, A., Schulze, W.: Über das Volumenverhältnis von Mitochondrien im chronisch überlasteten, hypertrophierten Herzen. Naturwissenschaften 49, 161–162 (1962)
Author information
Authors and Affiliations
Additional information
Dedicated to Professor Dr. W. Doerr on the occasion of his 65th birthday
The results have been partially reported in 1977 (cf. G. Mall and H. Reinhard, Verh. Dtsch. Ges. Path. 61, 445)
This investigation was supported by the “Sonderforschungsbereich 90” of the “Deutsche Forschungsgemeinschaft.”
Rights and permissions
About this article
Cite this article
Mall, G., Reinhard, H., Stopp, D. et al. Morphometric observations on the rat heart after high-dose treatment with cortisol. Virchows Arch. A Path. Anat. and Histol. 385, 169–180 (1980). https://doi.org/10.1007/BF00427402
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00427402