Skip to main content
SpringerLink
Log in

Pathophysiology of superoxide radical as potential mediator of reperfusion injury in pig heart

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

Summary

The role of oxygen0derived free radicals in myocardial reperfusion injury was studied using the isolated in situ pig heart model. The free radical scavengers, superoxide dismutase (SOD) and catalase, protected the ischemic pig heart subjected to one hour of normothermic regional ischemia followed by one hour of global hypothermic arrest and one hour normothermic reperfusion. A significant increase in thiobarbituric acid reactive material and oxidized glutathione appeared in the perfusate demonstrating free radical-mediated lipid peroxidation during reperfusion, and this was prevented by the addition of SOD plus catalase. The values of three important antioxidative enzymes, SOD, catalase, and glutathione peroxidase, showed reduced activities after 2 hours of ischemia. These values did not change significantly after 60 minutes of reperfusion following the 2 hours ischemic insult. The concentrations of high-energy phosphate compounds including creatine phosphate (CP), adenosine triphosphate (ATP), and total adenine nucleotide were reduced significantly during ischemia and reperfusion in hearts which were not protected by SOD and catalase. The plasma creatine phosphokinase levels were lowered appreciably as a result of SOD and catalase treatment. It may be concluded from these experiments that oxygen-derived free radicals are present during reperfusion and SOD and catalase play a significant role in the protection of ischemic myocardium from reperfusion injury.

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

Similar content being viewed by others

References

  1. Atkinson DE (1968) The energy charge of the adenylate pool as a regulatory parameter. Biochemistry 7:4030–4034

    PubMed  Google Scholar 

  2. Badwey JA, Karnovsky ML (1980) Active oxygen species and the functions of phagocytic leukocytes. Ann Rev Biochem 49:695–737

    PubMed  Google Scholar 

  3. Bromberg Y and Pick E (1983) Unsaturated fatty acids as second messengers of superoxide generation by macrophages. Cell Immunol 79:240–252

    PubMed  Google Scholar 

  4. Bulkley BH, Hutchins GM (1977) Myocardial consequences of coronary artery bypass graft surgery. The paradox of necrosis in areas of revascularization. Circulation 56:906–913.

    PubMed  Google Scholar 

  5. Chien KJR, Han A, Sen A, Buja LM, Willerson JT (1984) Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Circ Res 54:313–322

    PubMed  Google Scholar 

  6. Curnulte JT, Badwey JA, Robinson JM, Karnovsky MJ, Karnovsky ML (1984) Studies on the mechanism of superoxide release from human neutrophils stimulated with arachidonate. J Biol Chem 259:11851–11857

    PubMed  Google Scholar 

  7. Das DK, Aryomlooi J, Neogi A (1983) Effect of ischemia on fatty acid metabolism in fetal lung. Life Sci 33:569–576

    PubMed  Google Scholar 

  8. Das DK, Neogi A (1984) Effects of superoxide anions on the (Na+K) ATPase system in ratlung. Clin Physiol Biochem 2:32–38

    PubMed  Google Scholar 

  9. Dobbs WA, Engelman RM, Rousou JH, Douglas DM, Lemeshow S, Avrunin JS (1983) Performance of pig heart after 30 o 120 minutes hypothermic arrest. J Surg Res 35:132–141

    PubMed  Google Scholar 

  10. Dobbs WA, Engelman RM, Rousou JH, Pels MA, Alvarez J (1981) Residual metabolism of the hypothermci arrested pig heart. J Surg Res 31:319–323

    PubMed  Google Scholar 

  11. Engelman RM, Dobbs WA, Rousou JH, Meeran MK (1981) Myocardial high-energy phosphate replenishment during ischemic arrest: aerobic versu anaerobic metabolism. Ann Thorac Surg 33:453–458

    Google Scholar 

  12. Engelman RM, Rousou JH, Dobbs WA, Pels MA, Longo F (1980) The superiority of blood cardioplegia in myocardial preservation. Circulation (Suppl 1) 62:162–166

    Google Scholar 

  13. Engelman RM, Rousou JH, Longo R, Auvil J, Vertrees RA (1979) The time course of myocardial high-energy phosphate degradation during potassium cardioplegic arrest. Surgery 86:138–147

    PubMed  Google Scholar 

  14. Fee JA, Valentine JS (1977) Chemical and physical properties of superoxide. In: Michelson AM, McCord JM, Fridovich I (eds) Superoxide and superoxide dismutases. Academic Press, New York, 19

    Google Scholar 

  15. Fong K, McCoy P, Poyer J (1973) Evidence that peorxidation of lysosomal membranes is initiated by hydroxyl free radicals produced during flavin enzyme activity. J Biol Chem 248:7792–7797

    PubMed  Google Scholar 

  16. Ganote CE, Seabra GR, Nayley WG, Jennings RB (1975) Irreversible myocardial injury in anoxic perfused rat hearts. Am J Pathol 80:419–450

    PubMed  Google Scholar 

  17. Guarnieri C, Flamigni F, Caldarera CM (1980) Role of oxygen in the cellular damage induced by reoxygenation of hypoxic heart. J Mol Cell Cardiol 12:797–808

    PubMed  Google Scholar 

  18. Hearse DJ, Stewart DA, Chien EB (1974) Recovery from cardiac bypass and elective cardiac arrest. The metabolic consequences of various cardioplegic procedures in the isolated rat heart. Circ Res 35:448–457

    PubMed  Google Scholar 

  19. Jolly SR, Kane WJ, Bailie MB, Abrams GD, Lucchesi BR (1984) Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ Res 54:277–285

    PubMed  Google Scholar 

  20. Juengling E, Kammermeier H (1979) Rapid assay of adenine nucleotides or creatine compounds in extracts of cardiac tissue by paired ion reverse-phase high performance liquid chromatography. Ann Biochem 102:358–361

    Google Scholar 

  21. Meerson FZ, Kagan VE, Arkhipenko RV, Belkina LM, Rozhitskaya II (1981) Prevention of activation of lipid peroxidation and myocardial antioxidative system damages in stress and experimental myocardial infarction. Kardiologia 12:55–60

    Google Scholar 

  22. Meerson FZ, Kagan VE, Kozlov YP, Belkina LM, Arkhipenko YV (1982) The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart. Basic Res Cardiol 77:465–485

    PubMed  Google Scholar 

  23. Mowbary J, Bates DJ, Perrett D (1981) Inversely related oscillations in the content of cyclic GMP and the total adenine nucleotides in steady-state perfused rat hearts. FEBS Lett 131:55–59

    PubMed  Google Scholar 

  24. Otani H, Tanaka H, Inove T, Umemoto M, Omoto K, Tanaka K, Sato T, Osako T, Mosuda A, Nonoyama A, Kagawa T (1984) In vitro study on contribution of oxidative metabolism of isolated rabbit heart mitochondria to myocardial reperfusion injury. Circ Res 55:168–175

    PubMed  Google Scholar 

  25. Reidel DK, Rovetto MJ (1978) Myocardial ATP synthesis and mechanical function following oxygen deficiency. Am J Physiol 234:11620–11624

    Google Scholar 

  26. Reimer KA, Jennings RB (1985) Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusiion in dogs. Circulation 71:1059–1075

    Google Scholar 

  27. Reimer KA, Nennings RB, Cobb FR, Murdock RH, Greenfield DC, Baker LC, Buckley BH, Hutchins GM, Schwartz RB, Bailey KR, Passamani ER (1985) Animal models for protecting ischemic myocardium. results of the NHEI Cooperative Studies. Comparison of unconscious and conscious dogs. Circ Res 56:651–665.

    PubMed  Google Scholar 

  28. Romson JL, Hook BG, Rigot VH, Schork MA, Swanson DP, Lucchesi BR (1982) The effect of ibuprofen on accumulation of indium III-labeled platelets and leukocytes in experimental myocardial infarction. Circulation 66:1002–1011

    PubMed  Google Scholar 

  29. Rousou JH, Dobbs WA, Meeran MK, Engelman RM (1982) The temperature dependence of recovery of metabolic function following hypothermic potassium cardioplegic arrest. J Thorac Cardiovasc Surg 83:117–121

    PubMed  Google Scholar 

  30. Shlafer M, Kane PF, Wiggins VY (1982) Possible role for cytotoxic osygen metabolites in the pathogenesis of cardiac ischemic injury. Circulation (Suppl) 66:85–95

    Google Scholar 

  31. Shlafer M, Kane PF, Dirsh MM (1982) Superoxide dismutase plus catalase enhances the efficacy of hypothermic cardioplegia to protect the globally ischemic reperfused heart. J Thorac Cardiovasc Surg 83:830–839

    PubMed  Google Scholar 

  32. Slater RF (1984) Overview of methods used for detecting lipid peroxidation. Methods Enzymol 105:283–293

    PubMed  Google Scholar 

  33. Smith HJ, Kent KM, Epstein SE (1978) Contractile damage from reperfusion after transient ischemia in the dog. J Thorac Cardiovasc Surg 75:452–457

    PubMed  Google Scholar 

  34. Steinberg H, Greenwald RA, Moak SA, Das DK (1983) The effect of oxygen adaptation on oxyradical injury to pulmonary endothelium. Am Rev Respir Dis 128:94–97

    PubMed  Google Scholar 

  35. Steinberg H, Greenwald RA, Sciubba J, Das DK (1982) The effect of oxygen-derived free-radicals on pulmonary endothelial cell function in the isolated perfused rat lung. Exp Lung Res 3:163–173

    PubMed  Google Scholar 

  36. Steward JR, Crute SL, Loughlin V, Hes ML, Greenfield LJ (1983) Allpurinol prevents free radical mediated myocardial reperfusion injury. Surg Forum 34:325–326

    Google Scholar 

  37. Takahashi K, Kako KJ (1983) The effect of a calcium channel antagonist, Nisoldipine, on the ischemic-induced change of canine sarcolemmal membrane. Basic Res Cardiol 78:326–337

    PubMed  Google Scholar 

  38. Tanaka J, Tominaga R, Yoshitoshi M, Matski K, Komori M, Sese A, Yasiu H, Tokunaga K (1981) Coenzyme Q10: the prophylactic effect on low cardiac output following cardiac valve replacement. Ann Thorac Surg 33:145–151

    Google Scholar 

  39. Vary TC, Angelakos ET, Schaffer SW (1979) Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart. Circ Res 45:218–225

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. D. K. Das

    Present address: Departments of Surgery, The University of Connecticut Health Center, 263 Farmington Avenue, 06032, Farmington, Connecticut

Authors and Affiliations

  1. Departments of Surgery, The University of Connecticut Health Center, 263 Farmington Avenue, 06032, Farmington, Connecticut

    R. M. Engelman, J. A. Rousou, R. H. Breyer, H. Otani & S. Lemeshow

  2. Baystate Medical Center, Springfield, Massachusetts

    D. K. Das, R. M. Engelman, J. A. Rousou, R. H. Breyer, H. Otani & S. Lemeshow

  3. The University of Massachusetts School of Public Health, Amherst, Massachusetts, (USA)

    D. K. Das, R. M. Engelman, J. A. Rousou, R. H. Breyer, H. Otani & S. Lemeshow

Authors
  1. D. K. Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. M. Engelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. A. Rousou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. H. Breyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Otani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Lemeshow
    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

Das, D.K., Engelman, R.M., Rousou, J.A. et al. Pathophysiology of superoxide radical as potential mediator of reperfusion injury in pig heart. Basic Res Cardiol 81, 155–166 (1986). https://doi.org/10.1007/BF01907380

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01907380

Key words

Search

Navigation