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Regional differences of superoxide dismutase activity enhance the superoxide–induced electrical heterogeneity in rabbit hearts

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Abstract

During myocardial ischemia and the subsequent reperfusion, free radicals are important intermediates of the cellular damage and rhythm disturbances. We examined the effects of superoxide radicals or hydrogen peroxide (H2O2) on the action potentials in isolated rabbit Purkinje fibers, atrial muscle and ventricular muscle. Reactive oxygen species (ROS) donors such as adriamycin, xanthine/xanthine oxidase and menadione induced prolongation of APD90 in Purkinje fibers. Menadione (30 µM), the most specific superoxide radical donor, prolonged the action potential duration at 90% repolarization (APD90) by 17% in Purkinje fibers, whereas it shortened the APD by 57% in ventricular muscle, and it did not affect the atrial APD. All these menadione–induced effects were completely blocked by 2,2,6,6–tetramethyl– 1–peperadinyloxy, a superoxide radical scavenger. Superoxide dismutase (SOD) activity was lowest in Purkinje fibers, it was moderate in atrial muscle and highest in ventricular muscle. H2O2 shortened the APDs of all three cardiac tissues in a concentration–dependent manner. These results suggest that the different electrical responses to O2●– in different cardiac regions may result from the regional differences in the SOD activity, thereby enhancing the regional electrical heterogeneity.

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References

  1. Akaike T, Maeda H (1996) Quantitation of nitric oxide using 2-phenyl-4, 4, 5, 5- tetramethylimidazoline-1-oxyl 3-oxide (PTIO). Methods Enzymol 268:211–221

    CAS  PubMed  Google Scholar 

  2. Ames BN, Shigenaga MK (1992) Oxidants are a major contributor to aging. Ann NY Acad Sci 663:85–96

    CAS  PubMed  Google Scholar 

  3. Barrington PL (1994) Interactions of H2O2, EGTA and patch pipette recording methods in feline ventricular myocytes. J Mol Cell Cardiol 26:557–568

    CAS  PubMed  Google Scholar 

  4. Beresewicz A, Horackova M (1991) Alterations in electrical and contractile behavior of isolated cardiomyocytes by hydrogen peroxide: possible ionic mechanisms. J Mol Cell Cardiol 23:899–918

    Article  CAS  PubMed  Google Scholar 

  5. Bernier M, Hearse DJ, Manning AS (1986) Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with “anti-free radical” interventions and a free radical-generating system in the isolated perfused rat heart. Circ Res 58:331–340

    CAS  PubMed  Google Scholar 

  6. Bhatnagar A, Srivastava SK, Szabo G (1990) Oxidative stress alters specific membrane currents in isolated cardiac myocytes. Circ Res 67:535–549

    CAS  PubMed  Google Scholar 

  7. Bolli R, Zughaib M, Li XY, Tang XL, Sun JZ, Triana JF, McCay PB (1995) Recurrent ischemia in the canine heart causes recurrent bursts of free radical production that have a cumulative effect on contractile function. A pathophysiological basis for chronic myocardial “stunning”. J Clin Invest 96:1066–1084

    CAS  PubMed  Google Scholar 

  8. Bryant SM, Shipsey SJ, Hart G (1997) Regional differences in electrical and mechanical properties of myocytes from guinea-pig hearts with mild left ventricular hypertrophy. Cardiovasc Res 35:315–323

    Article  CAS  PubMed  Google Scholar 

  9. Casis O, Iriarte M, Gallego M, Sanchez- Chapula JA (1998) Differences in regional distribution of K+ current densities in rat ventricle. Life Sci 63:391–400

    Article  CAS  PubMed  Google Scholar 

  10. Cerbai E, Ambrosio G. , Porciatti F, Chlariello M, Giotti A, Mugelli A (1991) Cellular electrophysiological basis for oxygen radical-induced arrhythmias. A patch-clamp study in guinea pig ventricular myocytes. Circulation 84:1773–1782

    CAS  PubMed  Google Scholar 

  11. Chung SH, Chung SM, Lee JY, Kim SR, Park KS, Chung JH (1999) The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma. FEBS Lett 449:235–240

    Article  CAS  PubMed  Google Scholar 

  12. Cole WC, McPherson CD, Sontag D (1991) ATP-regulated K+ channels protect the myocardium against ischemia/ reperfusion damage. Circ Res 69:571–581

    CAS  PubMed  Google Scholar 

  13. Corbisier P, Houbion A, Remacle J (1987) A new technique for highly sensitive detection of superoxide dismutase activity by chemiluminescence. Anal Biochem 164:240–247

    Article  CAS  PubMed  Google Scholar 

  14. Das DK, Maulik N (1994) Antioxidant effectiveness in ischemia-reperfusion tissue injury. Methods Enzymol 233:601–610

    CAS  PubMed  Google Scholar 

  15. den Hartog GJ, Haenen GR, Boven E, van der Vijgh WJ, Bast A (2004) Lecithinized copper, zinc-superoxide dismutase as a protector against doxorubicin-induced cardiotoxicity in mice. Toxicol Appl Pharmacol 194:180–188

    CAS  PubMed  Google Scholar 

  16. Elsasser A, Suzuki K, Lorenz-Meyer S, Bode C, Schaper J (2001) The role of apoptosis in myocardial ischemia: a critical appraisal. Basic Res Cardiol 96:219–226

    Article  CAS  PubMed  Google Scholar 

  17. Ferrari R, Ceconi C, Curello S, Guarnieri C, Caldarera CM, Albertini A, Visioli O (1985) Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity. J Mol Cell Cardiol 17:937–945

    CAS  PubMed  Google Scholar 

  18. Fridovich I (1986) Superoxide dismutases. Adv Enzymol Relat Areas Mol Biol 58:61–97

    CAS  PubMed  Google Scholar 

  19. Fridovich I (1989) Superoxide dismutases. An adaptation to a paramagnetic gas. J Biol Chem 264:7761–7764

    CAS  PubMed  Google Scholar 

  20. Gelvan D, Saltman P, Powell SR (1991) Cardiac reperfusion damage prevented by a nitroxide free radical. Proc Natl Acad Sci USA 88:4680–4684

    CAS  PubMed  Google Scholar 

  21. Gill JS, McKenna WJ, Camm AJ (1995) Free radicals irreversibly decrease Ca2+ currents in isolated guinea-pig ventricular myocytes. Eur J Pharmacol 292:337–340

    CAS  PubMed  Google Scholar 

  22. Goldhaber JI, Ji S, Lamp ST, Weiss JN (1989) Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle. Implications for ischemia and reperfusion injury. J Clin Invest 83:1800–1809

    CAS  PubMed  Google Scholar 

  23. Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186:1–85

    CAS  Google Scholar 

  24. Halliwell B, Gutteridge JM, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119:598–620

    CAS  PubMed  Google Scholar 

  25. Han H, Kaiser R, Hu K, Laser M, Ertl G, Bauersachs J (2003) Selective modulation of endogenous nitric oxide formation in ischemia/reperfusion injury in isolated rat hearts-effects on regional myocardial flow and enzyme release. Basic Res Cardiol 98:165–174

    CAS  PubMed  Google Scholar 

  26. Hayashi H, Ponnambalam C, Mcdonald TF (1987) Arrhythmic activity in reoxygenated guinea pig papillary muscles and ventricular cells. Circ Res 61:124–133

    CAS  PubMed  Google Scholar 

  27. Josephson RA, Silverman HS, Lakatta EG, Stern MD, Zweier JL (1991) Study of the mechanisms of hydrogen peroxide and hydroxyl free radical-induced cellular injury and calcium overload in cardiac myocytes. J Biol Chem 266:2354–2361

    CAS  PubMed  Google Scholar 

  28. Keynes RG, Griffiths C, Garthwaite J (2003) Superoxide-dependent consumption of nitric oxide in biological media may confound in vitro experiments. Biochem J 369:399–406

    Article  CAS  PubMed  Google Scholar 

  29. Kim YS, Jhon DY, Lee KY (2004) Involvement of ROS and JNK1 in seleniteinduced apoptosis in Chang liver cells. Exp Mol Med 36:157–164

    CAS  PubMed  Google Scholar 

  30. Kobara M, Tatsumi T, Takeda M, Mano A, Yamanaka S, Shiraishi J, Keira N, Matoba S, Asayama J, Nakagawa M (2003) The dual effects of nitric oxide synthase inhibitors on ischemia-reperfusion injury in rat hearts. Basic Res Cardiol 98:319–328

    Article  CAS  PubMed  Google Scholar 

  31. Kourie JI (1998) Interaction of reactive oxygen species with ion transport mechanisms. Am J Physiol 275:C1–C24

    CAS  PubMed  Google Scholar 

  32. Kramer JH, Misik V, Weglicki WB (1994) Lipid peroxidation-derived free radical production and postischemic myocardial reperfusion injury. Ann NY Acad Sci 723:180–196

    CAS  PubMed  Google Scholar 

  33. Lehninger AL (1982) Principles of Biochemistry. Worth Publishers, Inc. , New York

  34. Leichtweis S, Ji LL (1997) Exercise and oxidative stress: sources of free radicals and their impact on antioxidant systems. Age 20:91–106

    Google Scholar 

  35. Maxwell SR (2000) Coronary artery disease- free radical damage, antioxidant protection and the role of homocysteine. Basic Res Cardiol 95 (Suppl 1):I65–I71

    Article  PubMed  Google Scholar 

  36. Miyoshi S, Miyazaki T, Moritani K, Ogawa S (1996) Different responses of epicardium and endocardium to KATP channel modulators during regional ischemia. Am J Physiol 271:H140–H147

    CAS  PubMed  Google Scholar 

  37. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136

    CAS  PubMed  Google Scholar 

  38. Nakaya H, Takeda Y, Tohse N, Kanno M (1992) Mechanism of the membrane depolarization induced by oxidative stress in guinea-pig ventricular cells. J Mol Cell Cardiol 24:523–534

    CAS  PubMed  Google Scholar 

  39. Nakaya H, Tohse N, Kanno M (1987) Electrophysiological derangements induced by lipid peroxidation in cardiac tissue. Am J Physiol 253:H1089–H1097

    CAS  PubMed  Google Scholar 

  40. Nebot C, Moutet M, Huet P, Xu JZ, Yadan JC, Chaudiere J (1993) Spectrophotometric assay of superoxide dismutase activity based on the activated autoxidation of a tetracyclic catechol. Anal Biochem 214:442–451

    Article  CAS  PubMed  Google Scholar 

  41. Pallandi RT, Perry MA, Campbell TJ (1987) Proarrhythmic effects of an oxygen- derived free radical generating system on action potentials recorded from guinea pig ventricular myocardium: a possible cause of reperfusion-induced arrhythmias. Circ Res 61:50–54

    CAS  PubMed  Google Scholar 

  42. Pfeiffer S, Leopold E, Hemmens B, Schmidt K, Werner ER, Mayer B (1997) Interference of carboxy-PTIO with nitric oxide- and peroxynitrite-mediated reactions. Free Radic Biol Med 22:787–794

    Article  CAS  PubMed  Google Scholar 

  43. Pogwizd SM, Corr PB (1987) Electrophysiologic mechanisms underlying arrhythmias due to reperfusion of ischemic myocardium. Circulation 76:404–426

    CAS  PubMed  Google Scholar 

  44. Samuni A, Krishna CM, Mitchell JB, Collins CR, Russo A (1990) Superoxide reaction with nitroxides. Free Radic Res Commun 9:241–249

    CAS  PubMed  Google Scholar 

  45. Sato N, Nishimura M, Tanaka H, Homma N, Watanabe Y (1989) Augmentation and subsequent attenuation of Ca2+ current due to lipid peroxidation of the membrane caused by t-butyl hydroperoxide in the rabbit sinoatrial node. Br J Pharmacol 98:721–723

    CAS  PubMed  Google Scholar 

  46. Schrader J (1985) Mechanisms of ischemic injury in the heart. Basic Res Cardiol 80 Suppl 2:135–139

    Google Scholar 

  47. Sies H (1991) Oxidative stress: from basic research to clinical application. Am J Med 91:31S–38S

    Article  CAS  Google Scholar 

  48. Surawicz B (1992) Role of potassium channels in cycle length dependent regulation of action potential duration in mammalian cardiac Purkinje and ventricular muscle fibres. Cardiovasc Res 26:1021–1029

    CAS  PubMed  Google Scholar 

  49. Tokube K, Kiyosue T, Arita M (1996) Openings of cardiac KATP channel by oxygen free radicals produced by xanthine oxidase reaction. Am J Physiol 271:H478–H489

    CAS  PubMed  Google Scholar 

  50. Unterberg C, Buchwald AB, Mindel L, Kreuzer H (1992) Oxygen free radical damage of isolated cardiomyocytes: comparative protective effect of radical scavengers and calcium antagonists. Basic Res Cardiol 87:148–160

    CAS  PubMed  Google Scholar 

  51. Yu BP (1994) Cellular defenses against damage from reactive oxygen species. Physiol Rev 74:139–162

    CAS  PubMed  Google Scholar 

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Correspondence to Y.–G. Kwak.

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Drs. B. H. Choi and K.–Ch. Ha contributed equally to this study.

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Choi, B.H., Ha, KC., Park, J. et al. Regional differences of superoxide dismutase activity enhance the superoxide–induced electrical heterogeneity in rabbit hearts. Basic Res Cardiol 100, 355–364 (2005). https://doi.org/10.1007/s00395-005-0531-x

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