A Molecular Biologic Approach to Cardiac Toxicology
Molecular biology seeks to depict biological function in terms of discrete events, individually accessible to biochemical study. With the myocardial cell this approach has had some success. The affinity of receptors for a variety of drugs, the ionic basis for signal transmission across the sarcolemmal membrane, and the enzymatic components of the various membranes that control internal calcium, have been studied and provide a rationale for at least some of the reversible, pharmacologically induced dysfunctions that represent the side effects of conventional drugs on this cell. This symposium, however, deals largely with chemical agents which initiate sequences of incompletely understood events that lead ultimately to irreversible tissue damage and cell death. Among these effects, the myocardial necrosis produced by suprapharmacological concentrations of isoproterenol has been of special interest because its production may have some elements in common with infarction or ischemic damage and because it induces resistance to further chemical damage.
KeywordsXanthine Oxidase Myocardial Necrosis Free Radical Damage Spin Trapping Sarcolemmal Membrane
Unable to display preview. Download preview PDF.
- 2.BLOOM, S. Reversible and irreversible injury; Calcium as a major determinant. In Cardiac Toxicology, Vol. 1, T. Balazs, Ed., pp. 179–201. Boca Raton: CRC Press (1981).Google Scholar
- 9.EVANS, C.A. Spin trapping. Aldrichimica Acta12, 23–29 (1979).Google Scholar
- 12.HERMAN, E. Cardiotoxicity of anti-neoplastic drugs. In Cardiac Toxicology, Vol. 2, T. Balazs, Ed., pp. 165–189. Boca Raton: CRC Press (1981).Google Scholar
- 14.JANZEN, E.G. A critical review of spin trapping in biological systems. In Free Radicals in Biology, Vol. 4, W.A. Pryor, Ed., pp. 115–154. New York: Academic Press (1980).Google Scholar
- 17.KLUGMANN, S., BARTOLI KLÜGMANN, F., DECORTI, G., GORI, D., SYLVESTRI, F. & CAMERINI, F. Adriamycin experimental cardiomyopathy in Swiss mice. Different effects of two calcium antagonistic drugs on ADM-induced cardiomyopathy. Pharmacological Research Communications13, 769–776 (1981).PubMedCrossRefGoogle Scholar
- 19.LEHR, D. Studies on the cardiotoxicity of alpha and beta adrenergic amines. In Cardiac Toxicology, Vol. 2, T. Balazs, Ed., pp. 75–113. Boca Raton: CRC Press (1981).Google Scholar
- 22.McCORD, J.M. Superoxide, superoxide dismutase and oxygen toxicity. In Reviews in Biochemical Toxicology, Vol. 1., E. Hodgson, J.R. Bend & R.M. Philpot, Eds., pp. 109–124. New York: Elsevier/North Holland (1979).Google Scholar
- 30.ROY, R.S. & McCORD, J.M. Ischemic-induced conversion of xanthine dehydrogenase to xanthine oxidase. Federation Proceedings 41, 767 (1982).Google Scholar
- 31.SELYE, H. The Chemical Prevention of Necrosis. New York: Ronald Press (1958).Google Scholar