Skip to main content
SpringerLink
Log in

The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart

  • Editorial
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

A working hypothesis on pathogenesis of ischemic heart damage has been proposed. According to this hypothesis, a crucial role in conversion of reversible damage into irreversible damage is played by cardiomyocyte membrane destruction caused by the so-called “lipid triad”. The latter comprises activation of lipid peroxidation, activation of phospholipases, and the degergentlike action of excessive amounts of free fatty acids and lysophospholipids. Marked activation of lipid peroxidation in experimental myocardial infarction, as well as reoxygenation following transitory ischemia, have been demonstrated. The proposed hypothesis and experimental data underly successful application of synthetic free radical scavengers (antioxidants) for heart protection against experimental myocardial infarction, transitory ischemia, and emotional, painful stress.

Zusammenfassung

In der vorliegenden Studie wird eine Arbeitshypothese zur Pathogenese der ischämischen Herzschädigung aufgestellt. Nach dieser Hypothese ist ein entscheidender Faktor für den Übergang von der reversiblen zur irreversiblen Schädigung eine Membrandestruktion der Herzmuskelzellen, welche durch sog. Lipid-Triaden verursacht wird. Letztere beinhaltet eine Aktivierung der Lipid-Peroxidation und der Phospholipase sowie eine Detergenz-ähnliche Wirkung exzessiver Mengen von freien Fettsäuren und Lysophospholipiden. Eine ausgepräge Aktivierung der Lipid-Peroxidation beim experimentellen Herzinfarkt sowie eine Reoxigenierung nach vorübergehender Ischämie wurden demonstriert. Die vorgelegte Hypothese und die experimentellen Daten legen eine Anwendung von Radialfängern (Antioxidantien) nahe für die Protektion des Herzens gegen experimentellen Myokardinfarkt, vorübergehende Ischämie und emotionalen Streß bei Schmerzsituationen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Abstracts of the Meeting of the American Section of the International Society for Heart Research. J. Mol. Cell. Cardiol. 9, suppl. (1977).

  2. Abstracts for the Ninth Congress of the International Society for Heart Research. J. Mol. Cell. Cardiol.10, suppl. 1 (1978).

    Google Scholar 

  3. Abstracts for the Tenth Hearth Congress of the International Society for Heart Research. J. Mol. Cell. Cardiol.12, suppl. 1 (1980).

    Google Scholar 

  4. Arkhipenko, Yu. V., A. K. Gazdarov, V. E. Kagan, Yu. P. Kozlov, V. B. Spirichev: Lipid peroxidation and impaired transport of Ca2+ through sarcoplasmic reticulum membranes in vitamin E deficiency. Biokhimiya (Rus.)41, 1898–1902 (1976).

    Google Scholar 

  5. Baba, A., E. Lee, A. Ohta, T. Tatsuno, H. Iwata: Activation of adenylate cyclase of rat brain by lipid peroxidation. J. Biol. Chem.256, 3679–3684 (1981).

    PubMed  Google Scholar 

  6. Babior, B. M., J. T. Curnutte, R. S. Kipness: Pyridine nucleotide-dependent superoxide production by a cell-free system from human granulocytes. J. Clin. Invest.56, 1035–1042 (1975).

    PubMed  Google Scholar 

  7. Bogdanova, E. D., V. E. Kagan, I. Ya. Kuliev, F. Z. Meerson, L. L. Prilipko: Activation of lipid peroxidation in the brain and appearance of antibodies against brain antigenes upon stress. Immunologia (Rus.)2, 65–66 (1981).

    Google Scholar 

  8. Bors, W., C. Michel, M. Saran, E. Lengfelder: The involvement of oxygen radicals during the autooxidation of adrenaline. Biochem. Biophys. Acta540, No. 1, 162–172 (1978).

    PubMed  Google Scholar 

  9. Burlakova, E. B.: Molecular mechanisms of action of free radical scavengers in therapy of cardio-vascular diseases. Kardiologia (Rus.)8, 48–52 (1980).

    Google Scholar 

  10. Burlakova, E. B., A. V. Alesenko, E. M. Molochkina, N. P. Palmina, N. G. Khrapova: Bioantioxidants in X-ray damage and malignant growth. “Nauka” Publishers (Moscow 1975).

    Google Scholar 

  11. Chazov, E. I.: Emotional stress and cardio-vascular diseases. Vestnik AMN SSSR (Russ.)8, 3–8 (1975).

    Google Scholar 

  12. Chien, R., G. Richard, B. Pfow, I. Farber: Ischemic myocardial cell injury. Am. J. Pathol.97, No. 3, 215–219 (1979).

    Google Scholar 

  13. Clavines, J., F. Christensen, G. Sylven: Interstinal absorption and in vivo formation of lipoperoxides in vitamin E deficient rats. Acta Chem. Scand.25, No. 12, 3220–3226 (1971).

    PubMed  Google Scholar 

  14. Cooley, D. A., G. Reul, D. Wukasch: Ischaemic contracture of the heart: “stone heart”. Am. J. Cardiol.29, 575–577 (1972).

    PubMed  Google Scholar 

  15. Devyatkina, T. A.: Effect of ionol on development of experimental atherosclerosis, DAN SSSR (Rus.)242, No. 2, 449–452 (1978).

    Google Scholar 

  16. Fridovich, I.: Superoxide dismutases. Ann. Rev. Biochem.44, 147–159 (1975).

    PubMed  Google Scholar 

  17. Guarniery, G., F. Flamigni, C. M. Caldarera: Role of the oxygen in the cellular damage induced by re-oxygenation of the hypoxic heart. J. Mol. Cell. Cardiol.12, No. 8, 797–808 (1980).

    PubMed  Google Scholar 

  18. Guarniery, G., F. Flamigni, C. Rossoni-Caldarera: Glutathione-peroxidase activity and release of glutathione from oxygen-deficient perfused rat heart. Biochem. Biophys. Res. Communs.89, No. 2, 678–684 (1979).

    Google Scholar 

  19. Gudbjarnason, S., J. Hallgrimsson: Cardiac lipids myocardial ischemia. Proc. of the VIIIth World Congress of Cardiology (Tokyo 1978).

  20. Hearse, D. J., S. M. Humphrey, E. B. Chain: Abrupt reoxygenation of the anoxic potassium-arrested perfused rat heart: a study of myocardial enzyme release. J. Mol. Cell. Cardiol.5, 395–407 (1973).

    PubMed  Google Scholar 

  21. Hearse, D. J., S. M. Humphrey, W. G. Nayler, A. Slade, D. Border: Ultrastructural damage associated with reoxygenation of the anoxic myocardium. J. Mol. Cell. Cardiol.7, 315–324 (1975).

    PubMed  Google Scholar 

  22. Hugnson, M., J. D. Balentine, H. B. Daniell: The ultrastructural pathology of hyperbaric oxygen exposure observations on the heart. Lab. Invest.37, 516–523 (1977).

    PubMed  Google Scholar 

  23. Jain, S. K., S. B. Shonet: Calcium potentiates the peroxidation of erythrocyte membrane lipids. Biochem. Biophys. Acta642, 46–54 (1981).

    PubMed  Google Scholar 

  24. Kagan, V. E., Yu. V. Arkhipenko, V. A. Pisarev, L. V. Belousova, Yu. P. Kozlov: Lipid peroxidation-induced damages of sarcoplasmic reticulum membranes and the role of LPO in the development of muscle pathology. In: Biophysics of Membranes. “Nauka” Publishers (Moscow 1981).

    Google Scholar 

  25. Kagan, V. E., O. A. Azizova, Yu. V. Arkhipenko, N. K. Klaan, Yu. P. Kozlov, Yu. A. Vladimirov: Interrelationship between structural and functional conversions in sarcoplasmic reticulum membranes during lipid peroxidation. Biofizika (Rus.)22, No. 4, 625–630 (1974).

    Google Scholar 

  26. Kagan, V. E., S. V. Kotelevtsev, Yu. P. Kozlov: The role of enzymatic phospholipid peroxidation in the disassembly mechanism of endoplasmic reticulum membranes in vivo. DAN SSSR (Rus.)217, 213–216 (1974).

    Google Scholar 

  27. Kagan, V. E., A. A. Shvedova, K. N. Novikov: On phospholipase involvement in “reparation” of photoreceptor membranes subjected to peroxidation. Biofizika (Rus.)23, 279–284 (1978).

    Google Scholar 

  28. Kagan, V. E., M. V. Sitkovsky, V. S. Danilov, Yu. P. Kozlov: Peroxide formation in cell membrane phospholipids and its role in pathogenesis of malignant growth. DAN SSSR (Rus.)208, 733–735 (1973).

    Google Scholar 

  29. Katsanovich, E. R.: Study of interrelationship between various forms of ischemic heart disease and lipid peroxidation, antiradical activity and fatty acid content of blood serum lipids. Synopsis of Ph. D. Thesis (Moscow 1981).

  30. Katz, A., F. Messineo: Lipid-membrane interactions and the pathogenesis of ischemic damage of the myocardium. Circul. Res.48, No. 1, 1–20 (1981).

    Google Scholar 

  31. Kogan, A. Kh., A. N. Kudrin, S. M. Nikolaev: Free radical lipid peroxidation and pathogenesis of coronary-occulusional myocardial infarction. In: “Free radical oxidation in normalcy and under pathology” (Moscow 1976).

  32. Kogan, A. Kh., V. I. Kulitskaya: Effect of permanent magnetic field on various models of cancerogenesis. Patofiziol. i eksperiment. terapia (Rus.)2, 63–68 (1977).

    Google Scholar 

  33. Korchagin, V. P., L. B. Bratkovskaya, A. A. Shvedova, Yu. V. Arkhipenko, V. E. Kagan, S. A. Shukolyukov: Oligomerization of intrinsic membrane proteins during lipid peroxidation. Biokhimiya (Rus.)45, 1767–1772 (1980).

    Google Scholar 

  34. Kozlov, Yu. P., V. S. Danilov, V. E. Kagan, M. V. Sitkovsky: Free radical lipid oxidation in the membranes. MGU Publishers (Moscow 1972).

    Google Scholar 

  35. Kozlov, Yu. P., V. B. Ritov, V. E. Kagan: Transport of Ca2+ and free radical oxidation of lipids in sarcoplasmic reticulum membranes. DAN SSSR (Rus.)212, 1239–1242 (1973).

    Google Scholar 

  36. Kudrin, A. N., A. Kh. Kogan, V. V. Korolev, S. M. Nikolaev, N. N. Beskrovnov: Free radical oxidation of lipids in pathogenesis of myocardial infarction and therapeutico-preventive role of the free radical scavenger, sodium selenite, and its combination with vitamin E. Kardiologia (Rus.)2, 115–118 (1978).

    Google Scholar 

  37. Kudrin, A. N., V. P. Nuzhny, S. M. Nikolaev: Effects of sodium selenite,-tocopherol and their combination on some parameters of functional state of the adrenergic and cholinergic systems of heart in experimental myocardial infarction. Farmakol. i toksikol. (Rus.)6, 706–710 (1977).

    Google Scholar 

  38. Lebedev, A. V., D. O. Levitsky, V. A. Loginov: Oxygen as inducer of Ca2+ transfer across lipid bilayer membranes. DAN SSSR (Rus.)252, No. 6, 1494–1497 (1980).

    Google Scholar 

  39. Litvitsky, P. F., A. Kh. Kogan, A. N. Kudrin, L. O. Lukyanova: Pathogenetic role of LPO activation and a protective effect of sodium selenite in ischemia and reperfusion of the myocardium. Bull. eksper. biol. i meditsini (Rus.)3, 271–274 (1981).

    Google Scholar 

  40. Meerson, F. Z.: Adaptation, stress and prophylaxis. “Nauka” Publishers (Moscow 1981).

    Google Scholar 

  41. Meerson, F. Z., Yu. V. Arkhipenko, I. I. Rozhitskaya, V. E. Kagan: Damage of the Ca2+ transporting system of sarcoplasmic reticulum of the heart in emotionalpain stress. Bull. eksper. biol. i meditsini (Rus.)4, 405–406 (1981).

    Google Scholar 

  42. Meerson, F. Z., L. M. Belkina, A. A. Ugolove, L. Yu. Golubeva, N. A. Abdikaliev, E. S. Solomatina: The use of free radical scavengers for prevention of experimental myocardial infarction and reoxygenation damages of heart function. Kardiologia (Rus.)20, No. 10, 81–86 (1980).

    Google Scholar 

  43. Meerson, F. Z., V. E. Kagan, Yu. V. Arkhipenko, L. M. Belkina, I. I. Rozhitskaya: Prevention of activation of lipid peroxidation and myocardial antioxidative system damages in stress and experimental myocardial infarction. Kardiologia12, 55–60 (1981).

    Google Scholar 

  44. Meerson, F. Z., V. E. Kagan, L. Yu. Golubeva, A. A. Ugolev, M. V. Shimkovich, L. M. Giber, I. I. Rozhitskaya: Prevention of stressory and hypoxic damages of the heart using the free radical scavenger BHT. Kardiologia (Rus.)8, 108–111 (1979).

    Google Scholar 

  45. Meerson, F. Z., V. E. Kagan, L. L. Prilipko, I. I. Rozhitskaya, L. M. Giber, Yu. P. Kozlov: Activation of lipid peroxidation in emotional-pain stress. Bull. eksper. biol. i meditsini (Rus.)10, 404–406 (1979).

    Google Scholar 

  46. Meerson, F. Z., V. V. Malyshev, N. S. Popova, G. I. Markovskaya: Suppression of stressory response and gastric ulceration by GOBA administration. Bull. esper. biol. i meditsini (Rus.)12, 659–661 (1979).

    Google Scholar 

  47. Meerson, F. Z., V. A. Pavlova, E. N. Korobejnikova: Prevention of stressory damages by the free radical scavenger and beta-adrenoblocking agent inderal. Voprosy meditsinskoi khimii (Rus.)26, No. 6, 827–832 (1980).

    Google Scholar 

  48. Player, T. J., H.-O. Hultin: The effect of lipid peroxidation on the calcium-accumulating ability of the microsomal fraction isolated from chicken breast muscle. Biochem. J.174, 17–22 (1978).

    PubMed  Google Scholar 

  49. Programme and Abstracts of the First Meeting of the Japanese Section of the International Society for Heart Research, Osaka, Japan. J. Mol. Cell. Cardiol.9, suppl. 1 (1977).

    Google Scholar 

  50. Programme and Abstracts of the Second Meeting of the Japanese Section of the International Society for Heart Research, Tokyo, Japan. J. Mol. Cell. Cardiol.11, suppl. 3 (1979).

    Google Scholar 

  51. Ruda, M. Ya.: On a reduction of a damage locus in myocardial infarction. Kardiologia (Rus.)1, 5–8 (1981).

    Google Scholar 

  52. Samuelsson, B.: The leukotrienes: a new group of biologically active compounds including SRS-A. Trends in Pharmacol. Sci.1, 227–230 (1980).

    Google Scholar 

  53. Shvedova, A. A., V. E. Kagan, K. N. Novikov, Kh. A. Ulmasov, Yu. P. Kozlov, M. A. Ostrovsky: Conformational sensitivity of free radical oxidation of phospholipids in photoreceptor membranes. In: “Structural lability of membranes and its role in regulation of functional activity of cells” (Minsk 1974).

  54. Shvedova, A. A., A. S. Sidorov, K. N. Novikov, I. V. Galushchenko, V. E. Kagan: Lipid peroxidation and electric activity of the retina. Vision Res.19, 49–55 (1979).

    PubMed  Google Scholar 

  55. Tarusov, B. N.: Primary process of X-radiation. “Gosatomizdat” Publishers (Moscow, 1957).

    Google Scholar 

  56. Vasdev, S. C., K. I. Kako, I. P. Biro: Phospholipid composition of cardiac mitochondria and lysosomes in experimental myocardial ischemia in the dog. J. Mol. Cell. Cardiol.11, 1195–1200 (1979).

    PubMed  Google Scholar 

  57. Vladimirov, Yu. A., A. I. Archakov: Lipid peroxidation in biological membranes. “Nauka” Publishers (Moscow 1972).

    Google Scholar 

  58. Voskresensky, O. N., A. N. Borisenko, T. A. Devyatkina, V. V. Brechko, T. I. Goloborodko: Search into antisclerotic drugs of the free radical scavenger type and their effects on the free radical mechanisms of atherogenesis. In: “Pharmacology—to Public Health” (Proc. of the IVth Federal Congress of Pharmacologists) (Leningrad 1976).

Download references

Author information

Author notes

  1. F. Z. Meerson

    Present address: Laboratory of Heart Pathophysiology, Institute of General Pathology and Pathological Physiology of the USSR Academy of Medical Sciences, Baltijskaya ul. 8, 125 315, Moscow, U.S.S.R.

  2. V. E. Kagan

    Present address: Laboratory of Physico-Chemistry of Biomembranes, School of Biology, Moscow State University, 117 234, Moscow, U.S.S.R.

Authors and Affiliations

  1. Laboratory of Heart Pathophysiology, Institute of General Pathology and Pathological Physiology of the USSR Academy of Medical Sciences, Baltijskaya ul. 8, 125 315, Moscow, U.S.S.R.

    V. E. Kagan, Yu. P. Kozlov, L. M. Belkina & Yu. V. Arkhipenko

  2. Laboratory of Physico-Chemistry of Biomembranes, School of Biology, Moscow State University, 117 234, Moscow, U.S.S.R.

    F. Z. Meerson, Yu. P. Kozlov, L. M. Belkina & Yu. V. Arkhipenko

Authors
  1. F. Z. Meerson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. E. Kagan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu. P. Kozlov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. M. Belkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu. V. Arkhipenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meerson, F.Z., Kagan, V.E., Kozlov, Y.P. et al. The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart. Basic Res Cardiol 77, 465–485 (1982). https://doi.org/10.1007/BF01907940

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01907940

Key words

Search

Navigation