Abstract
Following ischemia — a condition characterized by oxygen depletion, acidosis, and retention of tissue metabolites (1) — severe oxidative damage to cardiovascular tissues occurs upon reperfusion. However, early reperfusion remains the major clinical method to salvage ischemic myocardium and further elucidation of the multiple injury mechanisms operative during ischemia/reperfusion is necessary to solve this paradoxical dilemma. In the process of ischemia/reperfusion, mounting evidence has confirmed that the generation of oxygen-derived free radicals participates in the injury process (2–4). At the whole organ level, the reported protection of cardiovascular tissues by antioxidant-type enzymes (eg. superoxide dismutase and catalase), antioxidant drugs (eg. deferoxamine) and vitamins (eg. vitamin E) suggest a role for free radicals in the reperfusion injury. In recent years studies employing electron spin resonance spectroscopy and spin-trapping agents have shown that increased production of free radicals occurs during ischemia and myocardial reperfusion (4–11). The specific cellular sites of generation of these toxic free radicals are not known. Certainly white cells migrating into ischemic/reperfused areas of myocardium are capable of generating significant amounts of superoxide anions (2,12–14); endothelial cells (15–17) and cardiomyocytes (18) have been reported to generate oxygen-derived free radicals as well. Nevertheless, the relative contribution of each of the various cell types to the overall process of injury of cardiovascular tissues remains an area of intense investigation. One significant challenge for this area of investigation is whether or not sufficient radicals accumulate to overwhelm the intrinsic cellular protective mechanisms.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Corr, P.B., Gross, R.W. and Sobel, B.E. Amphipathic metabolites and membrane dysfunction in ischemic myocardium. Circ. Res. 55:135–154, 1984.
Simpson, P.J., Fantone, J.C. and Lucchesi, B.R. Myocardial ischemia and reperfusion injury: oxygen radicals and the role of the neutrophil. In: Oxygen radicals and tissue injury, edited by Halliwell, B. Bethesda, MD: Federation of American Societies for Experimental Biology, 1988, p. 63–77.
McCord, J.M. Free radicals and myocardial ischemia: overview and outlook. Free Radical Biology Medicine 4:9–14, 1988.
Kramer, J.H., Arroyo, C.M., Dickens, B.F. and Weglicki, W.B. Spin-trapping evidence that graded myocardial ischemia alters post-ischemic superoxide production. Free Free Radical Biology Medicine 3:153–159, 1987.
Weglicki, W.B., Arroyo, C.M., Kramer, J.H., Mak, I.T., Leiboff, R.H, Mergner, G.W. and Dickens, B.F., Applications of spin trapping/ESR techniques in models of cardiovascular injury. In: Oxy-radicals in molecular biology and pathology (UCLA symposia on molecular and cellular biology; New series, volume 82), edited by Cerutti, P.A., Fridovich, I. and McCord, J.M. New York: Alan R. Liss, Inc., 1988, p. 357–364.
Monitini, J., Bagby, G.J. and Spitzer, J.J Importance of exogenous substrates for the energy production of adult rat heart myocytes. J. Mol. Cell. Cardiol. 13:903–611, 1981.
Arroyo, C.M., Kramer, J.H., Leiboff, R.H., Mergner, G.W., Dickens, B.F. and Weglicki, W.B. Spin trapping of oxygen and carbon-centered free radicals in ischemic canine myocardium. Free Radical Biology Medicine 3:313–316, 1987.
Bolli, R., Patel, B.S., Jeroudi, M.O., Lai, E.K. and McCay, P.B. Demonstration of free radical generation in “stunned” myocardium of intact dogs with the use of the spin trap alph-phenyl N-tert butyl nitrone. J. Clin. Invest. 82:476–485, 1988.
Garlick, P.B., Davies, M.J., Hearse, D.J. and Slater, T.F. Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ. Res. 61:757–760, 1987.
Blasig, I.E. and Ebert, B. Identification of free radicals trapped during myocardial ischemia. Studia Biophysica 116:35–41, 1986.
Bolli, R., Jeroudi, M.O., Patel, B.S., et al. Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog. Proc. Natl. Acad. Sci. USA 86:4695–4699, 1989.
Hess, M.L., Rowe, G.T., Caplan, M., Romson, J.L. and Lucchesi, B. Identification of hydrogen peroxide and hydroxyl radicals as mediators of leukocyte-induced myocardial dysfunction. Limitation of infarct size with neutrophil inhibition and depletion. Adv. Myocardiol. 5:159–175, 1985.
Menasch, P., Pasquier, C., Bellucci, S., Lorente, P., Jaillon, P. and Piwnica, A. Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man. J. Thor. Cardiovas. Surg. 96:582–589, 1988.
Engler, R.L. Free radical and granulocyte-mediated injury during myocardial ischemia and reperfusion. Am. J. Cardiol. 63:19E–23E, 1989.
Rosen, G.M. and Freeman, B.A. Detection of superoxide generated by endothelial cells. Proc. Natl. Acad. Sci.USA 81:7269–7273, 1984.
Ratych, R.E., Chuknyiska, R.S. and Bulkley, G.B. The primary localization of free radical generation after anoxia/reoxygenation in isolated endothelial cells. Surgery 102:122–131, 1987.
Zweier, J.L., Kuppusamy, P. and Lutty, G.A. Measurement of endothelial cell free radical generation: Evidence for a central mechanism of free radical injury in postischemic tissues. Proc. Natl. Acad. Sci. USA 85:4046–4050, 1988.
Blasig, I.E., Ebert, B., Wallukat, G. and Loewe, H. Spin trapping evidence for radical generation by isolated hearts and cultured heart cells. Free Radical Res. Comms. 1989.(In Press).
Okabe, E., Hess, M.L., Oyama, M. and Ito, H. Characterization of free radical-mediated damage of canine cardiac sarcoplasmic reticulum. Arch. Biochem. Biophys. 225:164–177, 1983.
Freeman, B.A. and Crapo, J.D. Biology of disease. Free radicals and tissue injury. Lab. Invest. 47:412–426, 1982.
Kramer, J.H., Mak, I.T. and Weglicki, W.B. Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical-induced lipid peroxidation. Circ. Res. 55:120–124, 1984.
Weglicki, W.B., Dickens, B.F., Mak, I.T. and Kramer, J.H. Free radical injury of myocardial membranes. Life Chemistry Reports 3:189–198, 1985.
Mak, I.T., Kramer, J.H. and Weglicki, W.B. Potentiation of free radical-induced lipid peroxidative injury to sarcolemmal membranes by lipid amphiphiles. J. Biol. Chem. 261:1153–1157, 1986.
Weglicki, W.B., Mak, I.T., Dickens, B.F. and Kramer, J.H. Models of injury of cardiovascular membranes by amphiphiles and free radicals. In: Myocardial ischemia. Advances in Myocardiology, vol. 8, edited by Dhalla, N.S., Innes, I.R. and Beamish, R.E. Boston, MA: Martinus Nijhoff Publishing, 1987, p. 113–122.
Mak, I.T. and Weglicki, W.B. Protection by beta-blocking agents against free radical-mediated sarcolemmal lipid peroxidation. Circ. Res. 63:262–266, 1988.
Mak, I.T., Arroyo, C.M. and Weglicki, W.B. Inhibition of sarcolemmal carbon-centered free radical formation by propranolol. Circ. Res. 65:1151–1156, 1989.
Zigler, J.S., Jr., Badaness, R.S., Gery, I. and Kinoshita, J.H. Effects of lipid peroxidation products on the rat lens in organ culture: A possible mechanism of cataract initiation in retinal degenerative disease. Arch. Biochem. Biophys. 225:149–156, 1983.
Bird, R.P., Basrur, P.K. and Alexander, J.C. Cytotoxicity of thermally oxidized fats. In Vitro 17:397–404, 1981.
Ito, T. and Yoden, K. Formation of fluorescent substances from degradation products of methyl linoleate hydroperoxides with amino compound. Lipids 23:1069–1072, 1988.
Hicks, M., Delbridge, L., Yue, D.K. and Reeve, T.S. Increase in crosslinking of nonenzymatically glycosylated collagen induced by products of lipid peroxidation. Arch. Biochem. Biophys. 268:249–254, 1989.
Vaca, C.E. and Harms-Ringdahl, M. Nuclear membrane lipid peroxidation products bind to nuclear macromolecules. Arch. Biochem. Biophys. 269:548–554, 1989.
Gutteridge, J.M.C. Lipid peroxidation: Some problems and concepts. In: Oxygen radicals and tissue injury, edited by Halliwell, B. Bethesda, Md: Federation of American Societies for Experimental Biology, 1988, p. 9–19.
van Deenen, L.L.M. Phospholipids in biomembranes. Progress in the chemistry of fats and other lipids vol 8 part 1:1–127, 1965.
Sevanian, A., Stein, R.A. and Mead, J.F. Metabolism of epoxidized phosphatidylcholine by phospholipase A2 and epoxide hydrolase. Lipids 16:781–789, 1981.
Yasuda, M. and Fujita, T. Effect of lipid peroxidation on phospholipase AZ activity of rat liver mitochondria. Japan J. Pharmacol. 27:429–435, 1977.
Itabe, H., Kudo, I. and Inoue, K. Preferential hydrolysis of oxidized phospholipids by peritoneal fluid of rats treated with casein. Biochim. Biophys. Acta 963:192–200, 1988.
Tan, K.H., Meyer, D.J., Belin, J. and Ketterer, B. Inhibition of microsomal lipid peroxidation by glutathione and glutathione transferases B and AA. Role of endogenous phospholipase A2. Biochem. J. 220:243–252, 1984.
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 1990 Kluwer Academic Publishers
About this chapter
Cite this chapter
Weglicki, W.B., Dickens, B.F., Kramer, J.H., Mak, I.T. (1990). Cardiovascular Membranes as Models for the Study of Free Radical Injury. In: Korecky, B., Dhalla, N.S. (eds) Subcellular Basis of Contractile Failure. Developments in Cardiovascular Medicine, vol 116. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1513-1_17
Download citation
DOI: https://doi.org/10.1007/978-1-4613-1513-1_17
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-8813-8
Online ISBN: 978-1-4613-1513-1
eBook Packages: Springer Book Archive