Skip to main content
SpringerLink
Log in

Reversible and Irreversible Damage of the Myocardium

New Ischemic Syndromes, Ischemia/Reperfusion Injury, and Cardioprotection

  • Chapter
Handbook of Cardiac Anatomy, Physiology, and Devices

Abstract

The goal of this chapter is to provide a review of the physiology and pathophysiology of myocardial ischemia. In the past, it was thought that a lack of blood flow to the heart resulted in irreversible myocardial damage and necrosis (infarction). However, more recent evidence has suggested that there are several clinical scenarios, in presentation falling between the basic definitions of ischemia and infarction, in which the heart may recover a variable degree of preischemic function even though some degree of necrosis has occurred. Furthermore, with technological advances that allow intentional cardiac arrest during cardiac surgery, as well as noninvasive cardiac angioplasty (opening) of occluded coronary arteries, the phenomenon of reperfusion injury has at the same time been added as a sometimes-debilitating clinical syndrome. This chapter explores these new ischemic syndromes and describes up-to-date means for protecting the heart from these conditions (cardioprotection).

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

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Rao, V. and Weisel R. D., (1997) Intraoperative protection of organs: Hhypothermia, cardioplegia, and cerebroplegia, Chapter 10, in Cardiac Surgery in the Adult. Edmunds, L.H. (ed.), McGraw-Hill, New York, NY, pp. 295–318.

    Google Scholar 

  2. Yellon, D.M., Rahimtoola, S.H., Opie, L.H., et al. (eds.). (1997) Ischemic injury and myocardial protection: evolving concepts, Jennings, R. B., and Ischemic diastolic dysfunction and postischemic diastolic stunning, Apstein, C. S., Varma, N., and Eberli, F. R., in New Ischemic Syndromes: Beyond Angina and Infarction. Lippincott-Raven, New York, NY, pp. 10–20, 106–114.

    Google Scholar 

  3. Opie, L.H. (1998) The Heart: Physiology, from Cell to Circulation. Lippincott-Raven, New York, NY, 515–589

    Google Scholar 

  4. Shen, Y.T. and Vatner, S.F. (1995) Mechanism of impaired myocardial funtion during progressive coronary stenosis in conscious pigs. Hibernation versus stunning? Circ Res. 76, 479–88.

    PubMed  CAS  Google Scholar 

  5. Bolli, R. and Marban, E. (1999) Molecular and cellular mechanisms of myocardial stunning. Physiol Rev. 79, 609–634.

    PubMed  CAS  Google Scholar 

  6. Karmazyn, M. and Moffat, M.P. (1993) Role of Na+/H+ exchange in cardiac physiology and pathophysiology: mediation of myocardial reperfusion injury by the pH paradox. Cardiovasc Res. 27, 915–924.

    PubMed  CAS  Google Scholar 

  7. Miller, W.P., McDonald, K.S., and Moss, R.L. (1996) Onset of reduced Ca2+ sensitivity of tension during stunning in porcine myocardium. J Mol Cell Cardiol. 28, 689–697.

    Article  PubMed  CAS  Google Scholar 

  8. Kusuoka, H., Koretsune, Y., Chacko, V.P., et al. (1990) Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning? Circ Res. 66, 1268–1276.

    PubMed  CAS  Google Scholar 

  9. McDonough, J.L., Labugger, R., Pickett, W., et al. (2001) Cardiac troponin I is modified in the myocardium of bypass patients. Circulation. 103, 58–64.

    PubMed  CAS  Google Scholar 

  10. Opie, L.H. and du Toit, E.F. (1992) Postischemic stunning: the two-phase model for the role of calcium as pathogen. J Cardiovasc Pharmacol. 20, S1–S4.

    Article  PubMed  CAS  Google Scholar 

  11. Aguilera, I.M. and Vaughan, R.S. (2000) Calcium and the anaesthetist. Anaesthesia. 55, 779–790.

    Article  PubMed  CAS  Google Scholar 

  12. Robertie, P.G., Butterworth, J.F., Royster, R.L., et al. (1991) Normal parathyroid hormone responses to hypocalcemia during cardiopulmonary bypass. Anesthesiology. 75, 43–48.

    Article  PubMed  CAS  Google Scholar 

  13. Bolli, R., Patel, B.S., Jeroudi, M.O., et al. (1988) Demonstration of free radical generation in “stunned” myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone. J Clin Invest. 82, 476–485.

    Article  PubMed  CAS  Google Scholar 

  14. Heusch, G., and Schulz, R. (2002) Myocardial hibernation. Ital Heart J. 3, 282–284.

    PubMed  Google Scholar 

  15. Boden, W.E., Brooks, W.W., Conrad, C.H., et al. (1995) Incomplete, delayed functional recovery late after reperfusion following acute myocardial infarction: “maimed myocardium”. Am Heart J. 130, 922–932.

    Article  PubMed  CAS  Google Scholar 

  16. Murry, C.E., Jennings, R.B., and Reimer, K.A. (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 74, 1124–1136.

    PubMed  CAS  Google Scholar 

  17. Lawson, C.S., Coltart, D.J., and Hearse, D.J. (1993) “Dose”-dependency and temporal characteristics of protection by ischemic preconditioning against ischaemia-induced arrhythmias in rat hearts. J Mol Cell Cardiol. 25, 1391–1402.

    Article  PubMed  CAS  Google Scholar 

  18. Schultz, J.E., Rose, E., Yao, Z., et al. (1995) Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol. 268, H2157–H2161.

    PubMed  CAS  Google Scholar 

  19. Coles, J.A., Jr., Sigg, D.C., and Iaizzo, P.A. (2003) Role of kappaopioid receptor activation in pharmacological preconditioning in swine. Am Journal Physiol Heart Circ Physiol. 284, 2091–2099.

    Google Scholar 

  20. Sigg, D.C., Coles, J.A., Jr., Gallagher, W.J., et al. (2001) Opioid cardioprotection: myocardial function and energy metabolism. Ann Thorac Surg. 72, 1576–1582.

    Article  PubMed  CAS  Google Scholar 

  21. Yellon, D.M. and Downey, J.M. (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev. 83, 1113–1151.

    PubMed  CAS  Google Scholar 

  22. Gross, G.J. (2003) Role of opioids in acute and delayed preconditioning. J Mol Cell Cardiol. 35, 709–718.

    Article  PubMed  CAS  Google Scholar 

  23. Cohn, P.F., Fox, K.M., and Daly, C. (2003) Silent myocardial ischemia. Circulation. 108, 1263–1277.

    Article  PubMed  Google Scholar 

  24. Fliss, H. and Gattinger, D. (1996) Apoptosis in ischemic and reperfused rat myocardium. Circ Res. 79, 949–956.

    PubMed  CAS  Google Scholar 

  25. Opie, L.H. and Coetzee, W.A. (1988) Role of calcium ions in reperfusion arrhythmias: relevance to pharmacologic intervention. Cardiovasc Drugs Ther. 2, 623–636.

    Article  PubMed  CAS  Google Scholar 

  26. Manning, A.S. and Hearse, D.J. (1984) Reperfusion-induced arrhythmias: mechanisms and prevention. J Mol Cell Cardiol. 16, 497–518.

    Article  PubMed  CAS  Google Scholar 

  27. Wehrens, X.H., Doevendans, P.A., Ophuis, T.J., et al. (2000) A comparison of electrocardiographic changes during reperfusion of acute myocardial infarction by thrombolysis or percutaneous transluminal coronary angioplasty. Am Heart J. 139, 430–436.

    Article  PubMed  CAS  Google Scholar 

  28. Maes, A., Van de Werf, F., Nuyts, J., et al. (1995) Impaired myocardial tissue perfusion early after successful thrombolysis. Impact on myocardial flow, metabolism, and function at late follow-up. Circulation. 92, 2072–2078.

    PubMed  CAS  Google Scholar 

  29. Forde, R.C. and Fitzgerald, D.J. (1997) Reactive oxygen species and platelet activation in reperfusion injury. Circulation. 95, 787–789.

    PubMed  CAS  Google Scholar 

  30. Menasche, P., Peynet, J., Haeffner-Cavaillon, N., et al. (1995) Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass. Circulation. 92, II334–II340.

    PubMed  CAS  Google Scholar 

  31. Anderson, R.E., Li, T.Q., Hindmarsh, T., et al. (1999) Increased extracellular brain water after coronary artery bypass grafting is avoided by off-pump surgery. J Cardiothorac Vasc Anesth. 13, 698–702.

    Article  PubMed  CAS  Google Scholar 

  32. Karmazyn, M. (1998) The myocardial sodium-hydrogen exchanger (NHE) and its role in mediating ischemic and reperfusion injury. Keio J Med. 47, 65–72.

    PubMed  CAS  Google Scholar 

  33. Inserte, J., Garcia-Dorado, D., Ruiz-Meana, M., et al. (1997) The role of the Na+-H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema. J Mol Cell Cardiol. 29, 1167–1175.

    Article  PubMed  CAS  Google Scholar 

  34. Garcia-Dorado, D., Gonzalez, M.A., Barrabes, J.A., et al. (1997) Prevention of ischemic rigor contracture during coronary occlusion by inhibition of Na(+)-H(+) exchange. Cardiovasc Res. 35, 80–89.

    Article  PubMed  CAS  Google Scholar 

  35. Klein, H.H., Bohle, R.M., Pich, S., et al. (1997) Time delay of cell death by Na+/H+ exchange inhibition in regionally ischemic, reperfused porcine hearts. J Cardiovasc Pharmacol. 30, 235–240.

    Article  PubMed  CAS  Google Scholar 

  36. Shipolini, A.R., Yokoyama, H., Galinanes, M., et al. (1997) Na+/H+ exchanger activity does not contribute to protection by ischemic preconditioning in the isolated rat heart. Circulation. 96, 3617–3625.

    PubMed  CAS  Google Scholar 

  37. Yoshida, H. and Karmazyn, M. (2000) Na(+)/H(+) exchange inhibition attenuates hypertrophy and heart failure in 1-week post-infarction rat myocardium. Am J Physiol Heart Circ Physiol. 278, H300–H304.

    PubMed  CAS  Google Scholar 

  38. Myers, M.L., Farhangkhoee, P., and Karmazyn, M. (1998) Hydrogen peroxide induced impairment of post-ischemic ventricular function is prevented by the sodium-hydrogen exchange inhibitor HOE 642 (cariporide). Cardiovasc Res. 40, 290–296.

    Article  PubMed  CAS  Google Scholar 

  39. Mathur, S. and Karmazyn, M. (1997) Interaction between anesthetics and the sodium-hydrogen exchange inhibitor HOE 642 (cariporide) in ischemic and reperfused rat hearts. Anesthesiology. 87, 1460–1469.

    Article  PubMed  CAS  Google Scholar 

  40. Hartmann, M. and Decking, U.K. (1999) Blocking Na(+)-H(+) exchange by cariporide reduces Na(+)-overload in ischemia and is cardioprotective. J Mol Cell Cardiol. 31, 1985–1995.

    Article  PubMed  CAS  Google Scholar 

  41. Theroux, P., Chaitman, B.R., Danchin, N., et al. (2000) Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. Main results of the GUARDIAN trial. Guard During Ischemia Against Necrosis (Guardian) Investigators. Circulation. 102, 3032–3038.

    PubMed  CAS  Google Scholar 

  42. Myers, M.L. and Karmazyn, M. (1996) Improved cardiac function after prolonged hypothermic ischemia with the Na+/H+ exchange inhibitor HOE 694. Ann Thorac Surg. 61, 1400–1406.

    Article  PubMed  CAS  Google Scholar 

  43. Zeymer, U., Suryapranata, H., Monassier, J.P., et al. (2001) The Na+/H+ exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. J Am Coll Cardiol. 38, 1644–1650.

    Article  PubMed  CAS  Google Scholar 

  44. Bugge, E. and Yterhus, K. (1995) Inhibition of sodium-hydrogen exchange reduces infarct size in the isolated rat heart-a protective additive to ischaemic preconditioning. Cardiovasc Res. 29, 269–274.

    Article  PubMed  CAS  Google Scholar 

  45. Dhalla, N.S., Elmoselhi, A.B., Hata, T., et al. (2000) Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res. 47, 446–456.

    Article  PubMed  CAS  Google Scholar 

  46. Khaper, N., Rigatto, C., Seneviratne, C., et al. (1997) Chronic treatment with propranolol induces antioxidant changes and protects against ischemia-reperfusion injury. J Mol Cell Cardiol. 29, 3335–3344.

    Article  PubMed  CAS  Google Scholar 

  47. Kalaycioglu, S., Sinci, V., Imren, Y., et al. (1999) Metoprolol prevents ischemia-reperfusion injury by reducing lipid peroxidation. Jpn Circ J. 63, 718–721.

    Article  PubMed  CAS  Google Scholar 

  48. Feuerstein, G.Z., Yue, T.L., Cheng, H.Y., et al. (1993) Myocardial protection by the novel vasodilating beta-blocker, carvedilol: potential relevance of anti-oxidant activity. J Hypertens. 11, S41–S48.

    Article  CAS  Google Scholar 

  49. Iyengar, S.R., Charrette, E.J., Iyengar, C.K., et al. (1976) Myocardial glycogen in prevention of perioperative ischemic injury of the heart: a preliminary report. Can J Surg. 19, 246–251.

    PubMed  CAS  Google Scholar 

  50. Yellon, D.M. and Baxter, G.F. (1999) Reperfusion injury revisited: is there a role for growth factor signaling in limiting lethal reperfusion injury? Trends Cardiovasc Med. 9, 245–249.

    Article  PubMed  CAS  Google Scholar 

  51. Saraste, A., Pulkki, K., Kallajoki, M., et al. (1997) Apoptosis in human acute myocardial infarction. Circulation. 95, 320–323.

    PubMed  CAS  Google Scholar 

  52. Baxter, G.F.M., Brar, B.K., Latchman, D.S., Yellon, D.M. (1998) Infarct-limiting action of transforming growth factor beta-1 in isolated rat heart is abolished. Circulation. 100, 1–9.

    Google Scholar 

  53. Baines, C.P., Wang, L., Cohen, M.V., et al. (1999) Myocardial protection by insulin is dependent on phospatidylinositol 3-kinase but not protein kinase C or KATP channels in the isolated rabbit heart. Basic Res Cardiol. 94, 188–198.

    Article  PubMed  CAS  Google Scholar 

  54. Buerke, M., Murohara, T., Skurk, C., et al. (1995) Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci USA. 92, 8031–8035.

    Article  PubMed  CAS  Google Scholar 

  55. Cuevas, P., Carceller, F., Martinez-Coso, V., et al. (1999) Cardioprotection from ischemia by fibroblast growth factor: role of inducible nitric oxide synthase. Eur J Med Res. 4, 517–524.

    PubMed  CAS  Google Scholar 

  56. Stephanou, A., Brar, B., Heads, R., et al. (1998) Cardiotrophin-1 induces heat shock protein accumulation in cultured cardiac cells and protects them from stressful stimuli. J Mol Cell Cardiol. 30, 849–855.

    Article  PubMed  CAS  Google Scholar 

  57. Morita, K., Ihnken, K., Buckberg, G.D., et al. (1995) Studies of hypoxemic/reoxygenation injury: without aortic clamping. VIII. Counteraction of oxidant damage by exogenous glutamate and aspartate. J Thorac Cardiovasc Surg. 110, 1228–1234.

    Article  PubMed  CAS  Google Scholar 

  58. Drinkwater, D.C., Jr., Cushen, C.K., Laks, H., et al. (1992) The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations. J Thorac Cardiovasc Surg. 104, 1349–1355.

    PubMed  Google Scholar 

  59. Nakanishi, K., Zhao, Z.Q., Vinten-Johansen, J., et al. (1995) Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. J Thorac Cardiovasc Surg. 109, 1146–1154.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medtronic, Inc., Minneapolis, MN

    James A. Coles Jr. PhD & Daniel C. Sigg MD, PhD

  2. Departments of Surgery, Physiology, and Anesthesiology, Director of Education for the Lillehei Heart Institute, University of Minnesota, Minneapolis, MN

    Paul A. Iaizzo PhD

Authors
  1. James A. Coles Jr. PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel C. Sigg MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul A. Iaizzo PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgery, University of Minnesota, Minneapolis, MN

    Paul A. Iaizzo PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Coles, J.A., Sigg, D.C., Iaizzo, P.A. (2005). Reversible and Irreversible Damage of the Myocardium. In: Iaizzo, P.A. (eds) Handbook of Cardiac Anatomy, Physiology, and Devices. Humana Press. https://doi.org/10.1007/978-1-59259-835-9_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-835-9_12

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-443-2

  • Online ISBN: 978-1-59259-835-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation