Calcium-dependent changes of the myocardial contractile function at chronic adriamycin treatment

• Autorzy: Kapelko V.I. , Veksler V.I. , Gorina M.S. , Golikov M.A.
• Języki publikacji: EN

Abstrakty

EN

Kapelko, V. I., Veksler, V. L, Gorina, M. S. and Golikov, M. A.: Calcium-dependent changes of the myocardial contractile function at chronic adriamycin treatment. Acta physiol, pol., 1988, 39 (3): 106-174. The contractile function of hearts and atria isolated from rats treated with adriamycin (ADM, total cumulative dose 16-20 mg/kg for 8-10 weeks) was moderately lower as compared to control ipreparations. However, the former exhibited a relatively higher positive inotropic response to an elevation of Ca⁺⁺ concentration in the perfusate of isolated hearts or paired pulse stimulation of atria so that maximally attainable values were similar in both groups. On the contrary, the depression of ADM-treated atrial contractile amplitude became even more prominent at moderate increase in stimulation rate and was associated with the apparent incomplete re- laxation. Chemically skinned fibers from ADM-treated hearts began to develop force at lower Ca⁺⁺ concentration and exhibited higher Ca⁺⁺ - -sensitdvity in pCa range 5.8-5.4. Results suggest that long-term ADM- -treatment may he associated with a functional deficiency of Ca⁺⁺ -trans- porting mechanisms in myocardial cells which may contribute to the depression of the cardiac contractile function.

• Wydawca: -
• Czasopismo: Acta Physiologica Polonica
• Rocznik: 1988
• Tom: 39
• Numer: 3
• Opis fizyczny: p.166-174,fig.,ref.

Twórcy

autor

Kapelko V.I.

• Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow, USSR

autor

Veksler V.I.

• Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow, USSR

autor

Gorina M.S.

• Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow, USSR

autor

Golikov M.A.

• Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow, USSR

Bibliografia

• 1. Caroni P., Villani, F., Carafoli, E. (1981) The cardiotoxic antibiotic doxorubicin inhibits the Na⁺/Ca²⁺ exchange of dog heart sarcolemmal vesicles. FEBS Lett. 130. 184-186.
• 2. Ditchey, R. V., LeWinter, M. M., Higgins, С. B. (1984) Acute effects of doxorubicin (adriamycin) on left ventricular function in dogs. Int. J. Cardiol. 6. 341-350.
• 3. Fabiato, A. (1985) Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J. gen. Physiol. 85. 291-320.
• 4. Fabiato, A., Fabiato, F. (1979) Calculator programs for computing the conposition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J. Physiol. (Paris) 75. 463-505.
• 5. Gibbs, C. L., Woolley, G., Kotsanas, G., Gibson, W. R. (1984) Cardiac energetics in daunorubicin-induced cardiomyopathy. J. Moi. Cell. Cardiol. 16. 953-962.
• 6. Henderson, I. C., Frei, E. (1979) Adriamycin and the heart. New Engl. J. Nied. 300. 310-312.
• 7. Hilgemann, D. W. (1986) Extracellular calcium transients at single excitations in rabbit atrium measured with tetramethylmurexide. J. gen. Physiol. 87. 707-735.
• 8. Jensen, R. A., Acton, E. M., Peters J. H. (1984) Doxorubicin cardiotoxicity in the rat: comparison of electrocardiogram, transmembrane potential, and structural effects. J. Cardiovasc. Pharmacol. 6. 186-200.
• 9. Kapelko, V. I., Popovich, M. I., Golikov, M. A., Shulzhenko, V. S., Gorina, M. S. (1937) Myocardial diastolic stiffness in chronic adriamycin treatment. Bull. Exp. Biol. Med. (USSR) 103. 1. 17-19.
• 10. Langer, G. A. (1983) The "sodium pump lag" revisited. J. Mol. Cell. Cardiol. 15. 647-651.
• 11. Lefrak, E. A., Pitha, J., Rozenheim, S., Gottlieb, J. (1973) A clinicopathological analysis of adriamycin cardiotoxicity. Cancer 32. 302-314.
• 12. Lorell, Ł H., Grossman, W. (1987) Cardiac hypertrophy: the Consequences for diastole. J. Amer. Coli, Cardiol. 9. 1189-1193.
• 13. McClellan, G. B., Winegrad, S. (1978) The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle. J. Gen. Physiol. 72. 737- 764.
• 14. McFalls, E. O., Paulson, D. J., Gilbert, E. F., Ehug, A. L. (1986) Carnitine protection against adrdamycin-induced cardiomyopathy in rats, life Sci. 38. 497-505.
• 15. Meerson, F, Z., Kapelko, V. I., Nourmatov, A. A. (1971) Physiological evaluation of the capacity of the diastole mechanism. Acta Cardiol. 26. 547-567.
• 16. Mettler, F. P., Young, D. M., Ward, J. M. (1977, Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats. Cancer Res. 37. 2705-2713.
• 17. Mitchell, M. R., Powell, T., Terrar, D. A., Twist, V. W. (1985) Influence of a change in stimulation rate on action potentials, currents and contractions in rat ventricular cells. J. Physiol. 364. 113-130.
• 18. Morgan, J, P., Blinks, J. R. (1982) Intracellular Ca²⁺ transients in the cat papillary muscle. Can. J. Physiol. Pharmacol. 60. 524-528.
• 19. Olson, H. M., Young, D. M., Prieur, D. J., Le Roy, A. F., Reagan, R. L. (1974) Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits. Amer. J. Pathol. 77. 439-454.
• 20. Olson, H. M., Capen, С. C. (1978) Chronic cardiotoxicity of doxorubicin (adriamycin) in the rat: morphologic and biochemical investigations. Toxicol. Appl. Pharmacol. 44. 605-616.
• 21. Pelikan, P. C. D,, Weisfeldt, M. L., Jacobus, W. E., Miceli, M. V., Bulkley, B. H„ Gerstenblith, G. (1986) Acute doxorubicin cardiotoxicity: functional, metabolic and morphologic alterations in the isolated, perfused rat heart. J. Cardiovasc. Pharmacol. 8. 1058-1066.
• 22. Rabkin, S. W., (1983) Interaction of external calcium concentration and verapamil on the effects of doxorubicin (adriamycin) in the isolated heart preparation. J. Cardiov, Pharmacol. 5. 848-855.
• 23. ReVis, N., Marusic, N. (1979) Sequestration of ⁴⁵Ca²⁺ by mitochondria from rabbit heart, liver, and kidney after doxorubicin от digoxin/doxorubicin treatment. Exp. Mol. Pathol. 31. 440-451.
• 24. Singal, P. K., Pierce, G. N. (1986) Adriamycin stimulates low-affinity Ca²⁺ binding and lipid peroxidation but depresses myocardial function. Amer. J. Physiol. 250 (Heart Circ. Physiol. 19). H419-H425.
• 25. Veksler, V. I., Elizarova, E. P., Kapelko, V. I. (1985) Effects of phosphate and acidosis on calcium sensitivity of cardiac myofibrils. Bull. Exp. Biol. Med. 99. 2. 133-135.
• 26. Wier, W. G. (1980) Calcium transients during excitation contraction coupling in mammalian heart: aequorin signals of canine Purkinje fibers. Science 207. 1085- 1087.
• 27. Wildt, D. J. de, Jong, Y. de, Hillen, F. C., Steerenberg, P. A., Hoesel, Q. G. С. M. van (1985) Cardiovascular effects of doxorubicin-induced cardiotoxiCity in the intact Lou/M Wsl rat and in isolated heart preparations. J. Pharmacol. Exptl. The- rap. 235. 234-240.