Phospholipid Alterations and Membrane Injury during Myocardial Ischemia

  • Kenneth R. Chien
  • James T. Willerson
  • L. Maximilian Buja
Part of the Advances in Myocardiology book series (ADMY)


Several independent studies have demonstrated that there is a degradation of membrane phospholipids during myocardial ischemia. At present, most of the data support the initial activation of a phospholipase A pathway of phospholipid degradation. The extent of total phospholipid degradation is in the nanomole per gram wet weight quantity, as opposed to ischemic liver, in which the extent of phospholipid depletion approaches the micromole per gram wet weight level. However, in vitro studies suggest that calcium permeability properties and other myocardial cell membrane functions are sensitive to nanomole levels of phospholipid degradation. Clearly, further work is necessary in intact cell and heart preparations to correlate the degradation of phospholipid with the development of irreversible membrane injury during ATP depletion and hypoxia.


Myocardial Ischemia Membrane Phospholipid Membrane Injury Permeability Defect Ischemic Liver 
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  1. 1.
    Chien, K. R., Abrams, J., Serroni, A., Martin, J. T., and Farber, J. L. 1978. Accelerated phospholipid degradation and associated membrane dysfunction in irreversible ischemic liver cell injury. J. Biol. Chem. 253:4809–4817.PubMedGoogle Scholar
  2. 2.
    Chien, K. R., Abrams, J., Pfau, R. G., and Farber, J. L. 1977. Prevention by chlorpromazine of ischemic liver cell death. Am. J. Pathol. 88:539–558.PubMedGoogle Scholar
  3. 3.
    Chien, K. R., Sherman, C., Mittnacht, S., and Farber, J. L. 1980. Microsomal membrane structure and function consequent to calcium activation of an endogenous phospholipase. Arch. Biochem. Biophys. 205:614–622.PubMedCrossRefGoogle Scholar
  4. 4.
    Farber, J. L., Chien, K. R., and Mittnacht, S. 1982. The pathogenesis of irreversible cell injury in ischemia. Am. J. Pathol. 102:271–278.Google Scholar
  5. 5.
    Wattiaux, R., and Wattiaux-De Coninck, S. 1980. Reversible and irreversible alterations of lysosomes in ischemic rat liver: Effects of chlorpromazine. Biochem. Pharmacol. 29:963–966.PubMedCrossRefGoogle Scholar
  6. 6.
    Matsumoto, J., Tanaka, T., Gamo, M., Saito, K., and Honjo, I. 1981. Phospholipid metabolism of dog liver under hypoxic conditions induced by ligation of the hepatic artery. Biochim. Biophys. Acta 664:527–537.PubMedCrossRefGoogle Scholar
  7. 7.
    Patel, Y., Stewart, J., Matthys, E., and Venkatacham, M. A. 1982. Renal cortical free fatty acid and 1,2 diglyceride in renal ischemic injury. Clin. Res. 30:541A.Google Scholar
  8. 8.
    Smith, M. W., Collan, Y., Kaling, M., and Trump, B. F. 1980. Changes in mitochondrial lipids of rat kidney during ischemia. Biochim. Biophys. Acta. 618:192–201.PubMedCrossRefGoogle Scholar
  9. 9.
    Bazan, N. G. 1970. Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim. Biophys. Acta 218:1–14.PubMedCrossRefGoogle Scholar
  10. 10.
    Van der Vusse, G. I., Roeman, T.H. M., Prinzen, F. W., Coumans, W. A., and Reneman, R. S. 1982. Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischemic conditions. Circ. Res. 50:538–546.PubMedCrossRefGoogle Scholar
  11. 11.
    Corr, P. D., Snyder, D. W., Lee, B. I., Gross, R. W., Keim, C. R., and Sobel, B. E. 1982. Pathophysiological concentrations of lysophosphatides and the slow response. Am. J. Physiol. 243 : H187–H195.PubMedGoogle Scholar
  12. 12.
    Hsueh, W., Isaksan, P. C., and Needleman, P. 1977. Hormone selective lipase activation in the isolated rabbit heart. Prostaglandins 13:1073–1090.PubMedGoogle Scholar
  13. 13.
    Vasdev, S. C., Kako, K. J., and Biro, G. P. 1979. Phospholipid composition of cardiac mitochondria and lysosomes in experimental myocardial ischemia in the dog. J. Mol. Cell. Cardiol. 11:1195–1200.PubMedCrossRefGoogle Scholar
  14. 14.
    Shaikh, N. A., and Downar, E. 1981. Time course of changes in porcine myocardial phospholipid levels during ischemia: A reassessment of the lysolipid hypothesis. Circ. Res. 49:316–325.PubMedCrossRefGoogle Scholar
  15. 15.
    Chien, K. R., Reeves, J. P., Buja, L. M., Bonte, F., Parkey, R. W., and Willerson, J. T. 1981. Phospholipid alterations in canine ischemic myocardium: Temporal and topographical correlations with Tc-99m-PPi accumulation and an in vitro sarcolemmal Ca + 2 permeability defect. Circ. Res. 48:711–719.PubMedCrossRefGoogle Scholar
  16. 16.
    Hostetler, K. Y., and Hall, L. B. 1980. Phospholipase C activity of rat tissues. Biochem. Biophys. Res. Commun. 96:388–393.PubMedCrossRefGoogle Scholar
  17. 17.
    Weglicki, W. B. 1980. Degradation of phospholipids of myocardial membranes. In: Wildenthal, K. (ed.), Degradative Processes in Heart and Skeletal Muscle. pp. 377–388. Elsevier/North-Holland, Amsterdam.Google Scholar
  18. 18.
    Prescott, S. M., and Majerus, P. W. 1981. The fatty acid composition of phosphatidylinositol from thrombin-stimulated human platelets. J. Biol. Chem. 256:579–582.PubMedGoogle Scholar
  19. 19.
    Gross, R. E., and Sobel, B. E. 1982. Lysophosphatidylcholine metabolism in the rabbit heart. J. Biol. Chem. 257:6702–6708.PubMedGoogle Scholar
  20. 20.
    Sobel, B. E., Corr, P. B., Robison, A. K., Goldstein, R. A., Witkowski, F. X., and Klein, M. S. 1978. Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium. J. Clin. Invest. 62:546–553.PubMedCrossRefGoogle Scholar
  21. 21.
    Mogelson, S., Wilson, G. E., and Sobel, B. E. 1980. Characterization of rabbit myocardial phospholipids with 31P nuclear magnetic resonance. Biochim. Biophys. Acta 619:688.Google Scholar
  22. 22.
    Shaikh, N. A., and Downar, E. 1983. Ischemic induced phospholipase(s) activation in isolated perfused cat hearts. J. Mol. Cell. Cardiol. 15:171.Google Scholar
  23. 23.
    Chien, H. R., Han, A., Bush, L. R., Buja, L. M., and Willerson, J. T. 1984. Accumulation of unesterified arachidonate in ischemic canine myocardium: Relationship to a phosphatioylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids. Circ. Res. 54:313–322.PubMedCrossRefGoogle Scholar
  24. 24.
    Gunn, M. D., Sen, H., Kim, Y. M., Revtyak, G., Buja, L. M., Campbell, W. B., and Chien, K. R. Arachidonate metabolism of cultured myocardial cells during ATP depletion: Deacylation of arachidonate without conversion to prostaglandins. Submitted.Google Scholar
  25. 25.
    Prinzen, F. W., van der Vusse, G. J., Coumans, W. A., Roemen, T. H. M., and Reneman, R. S. 1983. Accumulation of non-esterified fatty acids in ischemic myocardium in relation to residual blood flow and ATP content. J. Mol. Cell. Cardiol. 15:370.CrossRefGoogle Scholar
  26. 26.
    Bakardjieva, A., Galla, H. J., and Helmreich, E. J. M. 1979. Modulation of the ß-receptor adenylate cyclase interactions in cultured Chang liver cells by phospholipid enrichment. Biochem. 18:3016–3023.CrossRefGoogle Scholar
  27. 27.
    Hasin, Y., Sapoznikov, D., Stein, O., and Stein, Y. 1982. Effect of fatty acid composition of rat heart myocytes on their electrical activity. J. Mol. Cell. Cardiol. 14:163–171.PubMedCrossRefGoogle Scholar
  28. 28.
    Langer, G. A., Frank, J. S., and Philipson, K. D. 1981. Correlation of alterations in cation exchange and sarcolemmal ultrastructure produced by neuraminidase and phospholipases in cardiac cell tissue culture. Circ Res. 49:1289–1299.PubMedCrossRefGoogle Scholar
  29. 29.
    Higgins, T. J. C., Bailey, P. J., and Allsopp, D. 1982. Interrelationship between cellular metabolic status and susceptibility of heart cells to attack by phospholipase. J. Mol. Cell. Cardiol. 14:645–654.PubMedCrossRefGoogle Scholar
  30. 30.
    Shaikh, N. A., and Downar, E. 1983. Effects of exogenous and endogenous lysophospholipids on the excitability of cardiac muscle and Purkinje fibres of sheep heart. J. Mol. Cell. Cardiol . 15:170.Google Scholar
  31. 31.
    Sedlis, S. P., Corr, P. B., Sobel, B. E., and Ahumada, G. G. 1983. Lysophosphatidylcholine potentiates Ca+ + accumulation in rat cardiac myocytes. Am. J. Physiol. 13:H32–H38.Google Scholar
  32. 32.
    Katz, A. M. 1982. Membrane derived lipids and the pathogenesis of ischemic myocardial damage. J. Mol. Cell. Cardiol. 14:627–632.PubMedCrossRefGoogle Scholar
  33. 33.
    Ashavaid, T. F., Colvin, R. A., Mac Alister, T., Messineo, F. C., and Katz, A. M. 1983. Fatty acid effects on Na/Ca exchange in sarcolemmal vesicles. J. Mol. Cell. Cardiol. 15:362.Google Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Kenneth R. Chien
    • 1
  • James T. Willerson
    • 1
  • L. Maximilian Buja
    • 2
  1. 1.Department of Internal Medicine (Cardiology Division)University of Texas Health Science CenterDallasUSA
  2. 2.Department of PathologyUniversity of Texas Health Science CenterDallasUSA

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