Skip to main content
SpringerLink
Log in

Ionic and metabolic progenitors of reperfusion arrhythmias

  • Chapter
Myocardial Ischemia and Arrhythmia

  • 781 Accesses

Summary

Experimental studies have shown that reperfusion of transiently ischaemic myocardium can result in the induction of severe ventricular arrhythmias such as ventricular fibrillation (VF). Incidences of such arrhythmias have been documented in man also; however, their clinical importance remains unclear. Although several mechanisms have been proposed for reperfusion arrhythmogenesis, current experimental evidence suggests that the intracellular accumulation of Ca2+ (Ca2+ overload) may be the final trigger responsible for the induction of VF. Intracellular Ca2+ accumulation itself may be induced or exacerbated by a number of components associated with reperfusion. Among these are the generation of free oxygen radicals and associated oxidant stress, and activation of the sarcolemmal Na +/H+ exchanger; these components may act in a synergistic manner to disrupt Ca2+ homeostasis and thereby induce VF.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson SE, Murphy E, Steenbergen C, London RE, Cala PM (1990) Na-H exchange in myocardium: effects of hypoxia acidification on Na and Ca. Am J Physiol 259: C940 - C948

    PubMed  CAS  Google Scholar 

  2. Avkiran M, Curtis MJ (1991) Independent dual perfusion of left and right coronary arteries in isolated rat hearts. Am J Physiol 261: H2082 - H2090

    PubMed  CAS  Google Scholar 

  3. Avkiran M, Ibuki C (1992) Reperfusion-induced arrhythmias: a role for washout of extracellular protons? Circ Res 71: 1429–1440

    PubMed  CAS  Google Scholar 

  4. Bernier M, Curtis MJ, Hearse DJ (1989) Ischemia-induced reperfusion-induced arrhythmias: importance of heart rate. Am J Physiol 256: H21 - H31

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  6. Carmeliet E (1992) A fuzzy subsarcolemmal space for intracellular Na+ in cardiac cells? Cardiovasc Res 26: 433–422

    Article  PubMed  CAS  Google Scholar 

  7. Coetzee WA, Owen P, Dennis SC, Saman S, Opie LH (1990) Reperfusion damage: free radicals mediate delayed membrane changes rather than early ventricular arrhythmias. Cardiovasc Res 24: 156–164

    Article  PubMed  CAS  Google Scholar 

  8. Corr PB, Witkowski FX (1984) Arrhythmias associated with reperfusion: basic insights and clinical relevance. J Cardiovasc Pharmacol 6 Suppl 6: 5903–5909

    Google Scholar 

  9. Corr PB, Yamada KA, Datorre SD (1990) Modulation of a-adrenergic receptors and their intracellular coupling in the ischemic heart, Basic Res Cardiol 85 (sup1): 31–45

    PubMed  Google Scholar 

  10. Curtis MJ (1991) The rabbit dual coronary perfusion model: a new method for assessing the pathological relevance of individual products of the ischaemic milieu: role of potassium in arrhythmogenesis. Cardiovasc Res 25: 1010–1022

    Article  PubMed  CAS  Google Scholar 

  11. Curtis MJ, Hearse DJ (1989) Reperfusion-induced arrhythmias are critically dependent tipon occluded zone size: relevance to the mechanism of arrhythmogenesis. J Mol Cell Cardiol 21: 625–637

    Article  PubMed  CAS  Google Scholar 

  12. Curtis MJ, Hearse DJ (1989) Ischaemia-induced and reperfusion-induced arrhythmias differ in their sensitivity to potassium: implications for mechanisms of initiation and maintenance of ventricular fibrilation. J Mol Cell Cardiol 21: 21–40

    Article  PubMed  CAS  Google Scholar 

  13. Curtis MJ, Pugsley MK, Walker MJA (1993) Endogenous chemical mediators of ventricular arrhythmias in ischaemic heart disease. Cardiovasc Res 27: 703–719

    Article  PubMed  CAS  Google Scholar 

  14. Dennis SC, Coetzee WA, Cragoe EJ Jr, Opie LH (1990) Effects of proton buffering and of amiloride derivatives on reperfusion arrhythmias in isolated rat hearts: possible evidence for an arrhythmogenic role of Na+-H+ exchange. Circ Res 66: 1156–1159

    PubMed  CAS  Google Scholar 

  15. Dennis SC, Gevers W, Opie LH (1991) Protons in ischemia: where do they come from; where do they go to? J Mol Cell Cardiol 23: 1077–1086

    Article  PubMed  CAS  Google Scholar 

  16. Gambassi G, Spurgeon HA, Lakatta EG, Blank PS, Capogrossi MC (1992) Different effects of a-and ß-adrenergic stimulation on cytosolic pH and myofilament responsiveness to Ca’ in cardiac myocytes. Circ Res 71: 870–882

    PubMed  CAS  Google Scholar 

  17. Garlick PB, Davies MJ, Hearse DJ, Slater TF (1987) Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ Res 61: 757–760

    PubMed  CAS  Google Scholar 

  18. Hagar JM, Kloner RA (1990) Reperfusion arrhythmias: experimental and clinical aspects. The Age of Reperfusion 2: 1–5

    Google Scholar 

  19. Hearse DJ (1990) Ischemia, reperfusion, and the determinants of tissue injury. Cardiovasc Drug Ther 4: 767–776

    Article  Google Scholar 

  20. Hearse DJ (1991) Stunning-a radical review. Cardiovasc Drug Ther 5: 853–876

    Article  CAS  Google Scholar 

  21. Hearse DJ, Kusama Y, Bernier M (1989) Rapid electrophysiological changes leading to arrhythmias in the aerobic rat heart. Photosensitization studies with rose bengal-derived reactive oxygen intermediates. Circ Res 65: 146–153

    PubMed  CAS  Google Scholar 

  22. Holmberg SR, Cumming DV, Kusama Y, Hearse DJ, Wilson Poole PA, Shattock MJ, Williams AJ (1991) Reactive oxygen species modify the structure and function of the cardiac sarcoplasmic reticulum calcium-release channel. Cardioscience 2: 19–25

    PubMed  CAS  Google Scholar 

  23. Ibuki C, Hearse DJ, Avkiran M (1992) Rate of reflow and reperfusion induced arrhythmias: studies with dual coronary perfusion. Cardiovasc Res 26: 316–323

    Article  PubMed  CAS  Google Scholar 

  24. Ibuki C, Hearse DJ, Avkiran M (1993) Mechanisms of antifibrillatory effect of acidic reperfusion: role of perfusate bicarbonate concentration. Am J Physiol 264: H783 - H790

    PubMed  CAS  Google Scholar 

  25. January CT, Fozzard HA (1988) Delayed afterdepolarizations in heart muscle: mechanisms and relevance Pharm Rev 40: 219–227

    CAS  Google Scholar 

  26. Kihara Y, Morgan JP (1991) Intracellular calcium and ventricular fibrillation: studies in the aequorin-loaded isovolumic ferret heart. Circ Res 68: 1378–1389

    PubMed  CAS  Google Scholar 

  27. Kinoshita K, Mitani A, Tsuruhara Y, Kanegae Y, Tokunaga K (1992) Analysis of determinants of ventricular fibrillation induced by reperfusion: dissociation between electrical instability and myocardial damage. Ann Thorac Surg 53: 999–1005

    Article  PubMed  CAS  Google Scholar 

  28. Knopf H, Theising R, Moon CH, Hirche H (1990) Continuous determination of extracellular space and changes of K+, Na+, Ca2+, and H+ during global ischaemia in isolated rat hearts. J Mol Cell Cardiol 22: 1259–1272

    Article  PubMed  CAS  Google Scholar 

  29. Kusama Y, Bernier M, Hearse DJ (1989) Singlet oxygen-induced arrhythmias. Dose-and light-response studies for photoactivation of rose bengal in the rat heart. Circulation 80: 1432–1448

    Article  PubMed  CAS  Google Scholar 

  30. Lazdunski M, Frelin C, Vigne P (1985) The sodium/hydrogen exchange system in cardiac cells: its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH. J Mol Cell Cardiol 17: 1029–1042

    Article  PubMed  CAS  Google Scholar 

  31. Macleod KT (1991) Regulation interaction of intracellular calcium, sodium and hydrogen ions in cardiac muscle. Cardioscience 2: 71–85

    PubMed  CAS  Google Scholar 

  32. Manning AS, Hearse DJ (1984) Reperfusion-induced arrhythmias: mechanisms and prevention. J Mol Cell Cardiol 16: 497–518

    Article  PubMed  CAS  Google Scholar 

  33. Matsuura H, Shattock MJ (1991) Membrane potential fluctuations and transient inward currents induced by reactive oxygen intermediates in isolated rabbit ventricular cells. Circ Res 68: 319–329

    PubMed  CAS  Google Scholar 

  34. Meng H, Pierce GN (1991) Involvement of sodium in the protective effect of 5-(N, Ndimethyl)-amiloride on ischemia-reperfusion injury in isolated rat ventricular wall. J Pharmacol Exp Ther 256: 1094–1100

    PubMed  CAS  Google Scholar 

  35. Molina-Viamonte V, Anyukhovsky EP, Rosen MR (1991) An α1-adrenergic receptor subtype is responsible for delayed afterdepolarizations and triggered activity during simulated ischemia and reperfusion of isolated canine purkinje fibers. Circulation 84: 1732–1740

    PubMed  CAS  Google Scholar 

  36. Myerburg RJ, Kessler KM, Mallon SM, Cox MM, Demarchena E, Interian A Jr., Castellanos A (1992) Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm. New Eng J Med 326: 1451–1455

    Article  PubMed  CAS  Google Scholar 

  37. Nakanishi T, Seguchi M, Tsuchiya T, Cragoe EJ Jr, Takao A, Momma K (1991) Effect of partial Na pump and Na-H exchange inhibition on [Ca]i during acidosis in cardiac cells. Am J Physiol 261: C758 - C766

    PubMed  CAS  Google Scholar 

  38. Nakata T, Hearse DJ, Curtis MJ (1990) Are reperfusion-induced arrhythmias caused by disinhibition of an arrhythmogenic component of ischemia? J Mol Cell Cardiol 22: 843–858

    Article  PubMed  CAS  Google Scholar 

  39. Opie LH, Coetzee WA (1988) Role of calcium ions in reperfusion arrhythmias: relevance to pharmacologic intervention. Cardiovasc Drug Ther 2: 623–636

    Article  CAS  Google Scholar 

  40. Piwnica-Worms D, Jacob R, Shigeto N, Horres CR, Lieberman M (1986) Na/H exchange in cultured chick heart cells: secondary stimulation of electrogenic transport during recovery from intracellular acidosis. J Mol Cell Cardiol 18: 1109–1116

    Article  PubMed  CAS  Google Scholar 

  41. Podzuweit T, Binz KH, Nennstiel P, Flaig W (1989) The anti-arrhythmic effects of myocardial ischaemia. Relation to reperfusion arrhythmias? Cardiovasc Res 23: 81–90

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  43. Rasmussen HH, Cragoe EJ Jr, Ten Eick RE (1989) Na+-dependent activation of Na+-K+ pump in human myocardium during recovery from acidosis. Am J Physiol 256: H256 - H264

    PubMed  CAS  Google Scholar 

  44. Reeves JP, Bailey CA, Hale CC (1986) Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. J Biol Chem 261: 4945–4955

    Google Scholar 

  45. Schömig A, Richardt G (1990) Cardiac sympathetic activity in myocardial ischaemia: release and effects of noradrenaline. Basic Res Cardiol 85 Suppl 1: 9–30

    Google Scholar 

  46. Shattock MJ, Matsuura H (1993) Measurement of Na+-K+ pump current in isolated rabbit ventricular myocytes using the whole-cell voltage-clamp technique: inhibition of the pump by oxidant stress. Circ Res 72: 91–101

    PubMed  CAS  Google Scholar 

  47. Shattock MJ, Matsuura H, Hearse DJ (1991) Functional and electrophysiological effects of oxidant stress on isolated ventricular muscle: a role for oscillatory calcium release from sarcoplasmic reticulum in arrhythmogenesis? Cardiovasc Res 25: 645–651

    Article  PubMed  CAS  Google Scholar 

  48. Sheridan DJ (1987) Reperfusion-induced arrhythmias: an experimental observation awaiting clinical discovery? In: Life Threatening Arrhythmias During Ischemia and Infarction, edited by Hearse DJ, Manning AS and Janse MJ. New York: Raven Press, p. 49–62

    Google Scholar 

  49. Sheridan DJ, Penkoske PA, Sobel BE, Corr PB (1980) Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats. J Clin Invest 65: 161–171

    Article  PubMed  CAS  Google Scholar 

  50. Tanaka K, Hearse DJ (1988) Reperfusion-induced arrhythmias in the isolated rabbit heart: characterization of the influence of the duration of regional ischemia and the extracellular potassium concentration. J Mol Cell Cardiol 20: 201–211

    Article  PubMed  CAS  Google Scholar 

  51. Tani M (1990) Mechanisms of Ca2+ overload in reperfused ischemic myocardium. Annu Rev Physiol 52: 543–559

    Article  PubMed  CAS  Google Scholar 

  52. Tani M, Neely JR (1991) Deleterious effects of digitalis on reperfusion-induced arrhythmias and myocardial injury in ischemic rat hearts: possible involvements of myocardial Na+ and Ca2+ imbalance. Basic Res Cardiol 86: 340–354

    Article  PubMed  CAS  Google Scholar 

  53. Terzic A, Pucéat M, Clément O, Scamps F, Vassort G (1992) α l-adrenergic effects on intracellular pH and calcium and on myofilaments in single rat cardiac cells. J Physiol 447: 275–292

    PubMed  CAS  Google Scholar 

  54. Thandroyen FT, McCarthy J, Burton KP, Opie LH (1988) Ryanodine and caffeine prevent ventricular arrhythmias during acute myocardial ischemia and reperfusion in rat heart. Circ Res 62: 306–314

    PubMed  CAS  Google Scholar 

  55. Thandroyen FT, Morris AC, Hagler HK, Ziman B, Pai L, Willerson JT, Buja LM (1991) Intracellular calcium transients and arrhythmia in isolated heart cells. Circ Res 69: 810–819

    PubMed  CAS  Google Scholar 

  56. Tzivoni D, Keren A, Granot H, Gottlieb S, Benhorin J, Stern S (1983) Ventricular fibrillation caused by myocardial reperfusion in Prinzmetal’s angina. Am Heart J 105: 323–325

    Article  PubMed  CAS  Google Scholar 

  57. Vaughan-Jones RD, Wu ML (1990) Extracellular H+ inactivation of Na+-H+ exchange in the sheet cardiac purkinje fibre. J Physiol 428: 441–466

    PubMed  CAS  Google Scholar 

  58. Wallert MA, Fröhlich O (1989) Na+-H+ exchange in isolated myocytes from adult rat heart. Am J Physiol 257: C207 - C213

    PubMed  CAS  Google Scholar 

  59. Winston DC, Spinale FG, Crawford FA, Schulte BA (1990) Immunocytochemical and enzyme histochemical localization of Na+/K+-ATPase in normal and ischemic porcine myocardium. J Mol Cell Cardiol 22: 1071–1082

    Article  PubMed  CAS  Google Scholar 

  60. Woodward B, Zakaria MN (1985) Effect of some free radical scavengers on reperfusion induced arrhythmias in the isolated rat heart. J Mol Cell Cardiol 17: 485–493

    Article  PubMed  CAS  Google Scholar 

  61. Yamada M, Hearse DJ, Curtis MJ (1990) Reperfusion and readmission of oxygen. Pathophysiological relevance of oxygen-derived free radicals to arrhythmogenesis. Circ Res 67: 1211–1224

    PubMed  CAS  Google Scholar 

  62. Yan GX, Kléber AG (1992) Changes in extracellular and intracellular pH in ischemic rabbit papillary muscle. Circ Res 71: 460–470

    PubMed  CAS  Google Scholar 

  63. Yasutake M, Ibuki C, Hearse DJ, Avkiran M (1993) Role of Na+/H+ exchange in reperfusion arrhythmogenesis. Eur Heart J 14 (abstr. suppl.): 86

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular Research The Rayne Institute, St Thomas’ Hospital, Lambeth Palace Road, London, SE1 7EH, UK

    Dr. Metin Avkiran

Authors
  1. Dr. Metin Avkiran
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abt. Innere Medizin III, Medizinische Universitätsklinik, Hugstetter Straße 55, 79106, Freiburg, Germany

    M. Zehender  & H. Just  & 

  2. Innere Medizin, Universitätskrankenhaus Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    T. Meinertz

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt

About this chapter

Cite this chapter

Avkiran, M. (1994). Ionic and metabolic progenitors of reperfusion arrhythmias. In: Zehender, M., Meinertz, T., Just, H. (eds) Myocardial Ischemia and Arrhythmia. Steinkopff. https://doi.org/10.1007/978-3-642-72505-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-72505-0_6

  • Publisher Name: Steinkopff

  • Print ISBN: 978-3-642-72507-4

  • Online ISBN: 978-3-642-72505-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation