Skip to main content
SpringerLink
Log in

Reversible and Irreversible Damage of the Myocardium: New Ischemic Syndromes, Ischemia/Reperfusion Injury, and Cardioprotection

  • Chapter
  • First Online:
Handbook of Cardiac Anatomy, Physiology, and Devices

Abstract

Ischemia and reperfusion injuries can lead to major compromises in cardiac function. While the intent of many of the past cardioprotective therapies was to protect the myocardium from ischemic necrosis, it may be that reperfusion injury following ischemia may occur despite such preventative attempts. There are continued efforts to identify improvements in myocardial protective strategies, and their ultimate goals are to minimize the risk of cellular injuries to all types of patients undergoing cardiovascular therapies, treatments, or surgeries. The goal of this chapter is to provide the reader with a general review of the physiology and pathophysiology of “myocardial ischemia.”

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

References

  1. Edmunds LH, ed. Cardiac surgery in the adult. New York, NY: McGraw-Hill, 1997:295–318.

    Google Scholar 

  2. Yellon DM, Rahimtoola SH, Opie LH, et al. New ischemic syndromes: Beyond angina and infarction. New York, NY/Philadelphia, PA: Lippincott-Raven Publishers, 1997:10–20, 106–14.

    Google Scholar 

  3. Opie LH. The heart: Physiology, from cell to circulation. Philadelphia, PA: Lippincott-Raven, 1998:515–89.

    Google Scholar 

  4. Shen YT, Vatner SF. Mechanism of impaired myocardial function during progressive coronary stenosis in conscious pigs. Hibernation versus stunning? Circ Res 1995;76:479–88.

    CAS  Google Scholar 

  5. Bolli R, Marban E. Molecular and cellular mechanisms of myocardial stunning. Physiol Rev 1999;79:609–34.

    PubMed  CAS  Google Scholar 

  6. Karmazyn M, Moffat MP. Role of Na+/H+ exchange in cardiac physiology and pathophysiology: Mediation of myocardial reperfusion injury by the pH paradox. Cardiovasc Res 1993;27:915–24.

    Article  PubMed  CAS  Google Scholar 

  7. Miller WP, McDonald KS, Moss RL. Onset of reduced Ca2+ sensitivity of tension during stunning in porcine myocardium. J Mol Cell Cardiol 1996;28:689–97.

    Article  PubMed  CAS  Google Scholar 

  8. Kusuoka H, Koretsune Y, Chacko VP, et al. Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning? Circ Res 1990;66:1268–76.

    CAS  Google Scholar 

  9. McDonough JL, Labugger R, Pickett W, et al. Cardiac troponin I is modified in the myocardium of bypass patients. Circulation 2001;103:58–64.

    PubMed  CAS  Google Scholar 

  10. Opie LH, du Toit EF. Postischemic stunning: The two-phase model for the role of calcium as pathogen. J Cardiovasc Pharmacol 1992;20:S1–4.

    PubMed  CAS  Google Scholar 

  11. Aguilera IM, Vaughan RS. Calcium and the anaesthetist. Anaesthesia 2000;55:779–90.

    Article  PubMed  CAS  Google Scholar 

  12. Robertie PG, Butterworth JF, Royster RL, et al. Normal parathyroid hormone responses to hypocalcemia during cardiopulmonary bypass. Anesthesiology 1991;75:43–8.

    Article  PubMed  CAS  Google Scholar 

  13. Bolli R, Patel BS, Jeroudi MO, et al. 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 1988;82:476–85.

    Article  PubMed  CAS  Google Scholar 

  14. Heusch G, Schulz R. Myocardial hibernation. Ital Heart J 2002;3:282–4.

    PubMed  Google Scholar 

  15. Boden WE, Brooks WW, Conrad CH, et al. Incomplete, delayed functional recovery late after reperfusion following acute myocardial infarction: “Maimed myocardium”. Am Heart J 1995;130:922–32.

    Article  PubMed  CAS  Google Scholar 

  16. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124–36.

    Article  PubMed  CAS  Google Scholar 

  17. Lawson CS, Coltart DJ, Hearse DJ. “Dose”-dependency and temporal characteristics of protection by ischaemic preconditioning against ischaemia-induced arrhythmias in rat hearts. J Mol Cell Cardiol 1993;25:1391–402.

    Article  PubMed  CAS  Google Scholar 

  18. Schultz JE, Rose E, Yao Z, et al. Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol 1995;268:H2157–61.

    PubMed  CAS  Google Scholar 

  19. Coles JA, Jr., Sigg DC, Iaizzo PA. Role of kappa-opioid receptor activation in pharmacological preconditioning in swine. Am J Physiol Heart Circ Physiol 2003;284:2091–9.

    Google Scholar 

  20. Sigg DC, Coles JA, Jr., Gallagher WJ, et al. Opioid cardioprotection: Myocardial function and energy metabolism. Ann Thorac Surg 2001;72:1576–82.

    Article  PubMed  CAS  Google Scholar 

  21. Yellon DM, Downey JM. Preconditioning the myocardium: From cellular physiology to clinical cardiology. Physiol Rev 2003;83:1113–51.

    PubMed  CAS  Google Scholar 

  22. Gross GJ. Role of opioids in acute and delayed preconditioning. J Mol Cell Cardiol 2003;35:709–18.

    Article  PubMed  CAS  Google Scholar 

  23. Cohn PF, Fox KM. Silent myocardial ischemia. Circulation 2003;108:1263–77.

    Article  PubMed  Google Scholar 

  24. Leaf A, Kang JX, Xiao YF. Fish oil fatty acids as cardiovascular drugs. Curr Vasc Pharmacol 2008;6:1–12. Review.

    Article  PubMed  CAS  Google Scholar 

  25. Xiao YF, Sigg DC, Ujhelyi MR, Wilhelm JJ, Richardson ES, Iaizzo PA. Pericardial delivery of Omega-3 fatty acid: A novel approach to reduce myocardial infarct sizes and arrhythmias. Am J Phyisol Heart Circ Physiol 2008;294:H2212–8

    Article  CAS  Google Scholar 

  26. Fliss H, Gattinger D. Apoptosis in ischemic and reperfused rat myocardium. Circ Res 1996;79:949–56.

    PubMed  CAS  Google Scholar 

  27. Opie LH, Coetzee WA. Role of calcium ions in reperfusion arrhythmias: Relevance to pharmacologic intervention. Cardiovasc Drugs Ther 1988;2:623–36.

    Article  PubMed  CAS  Google Scholar 

  28. Manning AS, Hearse DJ. Reperfusion-induced arrhythmias: Mechanisms and prevention. J Mol Cell Cardiol 1984;16:497–518.

    Article  PubMed  CAS  Google Scholar 

  29. Wehrens XH, Doevendans PA, Ophuis TJ, et al. A comparison of electrocardiographic changes during reperfusion of acute myocardial infarction by thrombolysis or percutaneous transluminal coronary angioplasty. Am Heart J 2000;139:430–6.

    Article  PubMed  CAS  Google Scholar 

  30. Maes A, Van de Werf F, Nuyts J, et al. Impaired myocardial tissue perfusion early after successful thrombolysis. Impact on myocardial flow, metabolism, and function at late follow-up. Circulation 1995;92:2072–8.

    PubMed  CAS  Google Scholar 

  31. Forde RC, Fitzgerald DJ. Reactive oxygen species and platelet activation in reperfusion injury. Circulation 1997;95:787–9.

    PubMed  CAS  Google Scholar 

  32. Menasche P, Peynet J, Haeffner-Cavaillon N, et al. Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass. Circulation 1995;92:II334–40.

    PubMed  CAS  Google Scholar 

  33. Anderson RE, Li TQ, Hindmarsh T, et al. Increased extracellular brain water after coronary artery bypass grafting is avoided by off-pump surgery. J Cardiothorac Vasc Anesth 1999;13:698–702.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  35. Inserte J, Garcia-Dorado D, Ruiz-Meana M, et al. The role of the Na+–H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema. J Mol Cell Cardiol 1997;29:1167–75.

    Article  PubMed  CAS  Google Scholar 

  36. Garcia-Dorado D, Gonzalez MA, Barrabes JA, et al. Prevention of ischemic rigor contracture during coronary occlusion by inhibition of Na(+)–H(+) exchange. Cardiovasc Res 1997;35:80–9.

    Article  PubMed  CAS  Google Scholar 

  37. Klein HH, Bohle RM, Pich S, et al. Time delay of cell death by Na+/H+ exchange inhibition in regionally ischemic, reperfused porcine hearts. J Cardiovasc Pharmacol 1997;30:235–40.

    Article  PubMed  CAS  Google Scholar 

  38. Shipolini AR, Yokoyama H, Galinanes M, et al. Na+/H+ exchanger activity does not contribute to protection by ischemic preconditioning in the isolated rat heart. Circulation 1997;96:3617–25.

    PubMed  CAS  Google Scholar 

  39. Yoshida H, Karmazyn M. Na(+)/H(+) exchange inhibition attenuates hypertrophy and heart failure in 1-wk postinfarction rat myocardium. Am J Physiol Heart Circ Physiol 2000;278:H300–4.

    PubMed  CAS  Google Scholar 

  40. Myers ML, Farhangkhoee P, Karmazyn M. Hydrogen peroxide induced impairment of post-ischemic ventricular function is prevented by the sodium–hydrogen exchange inhibitor HOE 642 (cariporide). Cardiovasc Res 1998;40:290–6.

    Article  PubMed  CAS  Google Scholar 

  41. Mathur S, Karmazyn M. Interaction between anesthetics and the sodium–hydrogen exchange inhibitor HOE 642 (cariporide) in ischemic and reperfused rat hearts. Anesthesiology 1997;87:1460–9.

    Article  PubMed  CAS  Google Scholar 

  42. Hartmann M, Decking UK. Blocking Na(+)–H(+) exchange by cariporide reduces Na(+)-overload in ischemia and is cardioprotective. J Mol Cell Cardiol 1999;31:1985–95.

    Article  PubMed  CAS  Google Scholar 

  43. Theroux P, Chaitman BR, Danchin N, et al. 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 2000;102:3032–8.

    PubMed  CAS  Google Scholar 

  44. Myers ML, Karmazyn M. Improved cardiac function after prolonged hypothermic ischemia with the Na+/H+ exchange inhibitor HOE 694. Ann Thorac Surg 1996;61:1400–6.

    Article  PubMed  CAS  Google Scholar 

  45. Zeymer U, Suryapranata H, Monassier JP, et al. The Na+/H+ exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. J Am Coll Cardiol 2001;38:1644–50.

    Article  PubMed  CAS  Google Scholar 

  46. Bugge E, Yterhus K. Inhibition of sodium–hydrogen exchange reduces infarct size in the isolated rat heart-A protective additive to ischaemic preconditioning. Cardiovasc Res 1995;29:269–74.

    PubMed  CAS  Google Scholar 

  47. Dhalla NS, Elmoselhi AB, Hata T, et al. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res 2000;47:446–56.

    Article  PubMed  CAS  Google Scholar 

  48. Khaper N, Rigatto C, Seneviratne C, et al. Chronic treatment with propranolol induces antioxidant changes and protects against ischemia-reperfusion injury. J Mol Cell Cardiol 1997;29:3335–44.

    Article  PubMed  CAS  Google Scholar 

  49. Kalaycioglu S, Sinci V, Imren Y, et al. Metoprolol prevents ischemia-reperfusion injury by reducing lipid peroxidation. Jpn Circ J 1999;63:718–21.

    Article  PubMed  CAS  Google Scholar 

  50. Feuerstein GZ, Yue TL, Cheng HY, et al. Myocardial protection by the novel vasodilating beta-blocker, carvedilol: Potential relevance of anti-oxidant activity. J Hypertens 1993;11:S41–8.

    Article  CAS  Google Scholar 

  51. Iyengar SR, Charrette EJ, Iyengar CK, et al. Myocardial glycogen in prevention of perioperative ischemic injury of the heart: A preliminary report. Can J Surg 1976;19:246–51.

    PubMed  CAS  Google Scholar 

  52. Yellon DM, Baxter GF. Reperfusion injury revisited: Is there a role for growth factor signaling in limiting lethal reperfusion injury? Trends Cardiovasc Med 1999;9:245–9.

    Article  PubMed  CAS  Google Scholar 

  53. Saraste A, Pulkki K, Kallajoki M, et al. Apoptosis in human acute myocardial infarction. Circulation 1997;95:320–3.

    PubMed  CAS  Google Scholar 

  54. Baxter GFM., Brar BK, Latchman DS, Yellon DM. Infarct-limiting action of transforming growth factor beta-1 in isolated rat heart is abolished. Circulation 1998;100:1–9.

    Google Scholar 

  55. Baines CP, Wang L, Cohen MV, et al. 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 1999;94:188–98.

    Article  PubMed  CAS  Google Scholar 

  56. Buerke M, Murohara T, Skurk C, et al. Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci USA 1995;92:8031–5.

    Article  PubMed  CAS  Google Scholar 

  57. Cuevas P, Carceller F, Martinez-Coso V, et al. Cardioprotection from ischemia by fibroblast growth factor: Role of inducible nitric oxide synthase. Eur J Med Res 1999;4:517–24.

    PubMed  CAS  Google Scholar 

  58. Stephanou A, Brar B, Heads R, et al. Cardiotrophin-1 induces heat shock protein accumulation in cultured cardiac cells and protects them from stressful stimuli. J Mol Cell Cardiol 1998;30:849–55.

    Article  PubMed  CAS  Google Scholar 

  59. Morita K, Ihnken K, Buckberg GD, et al. Studies of hypoxemic/reoxygenation injury without aortic clamping. VIII. Counteraction of oxidant damage by exogenous glutamate and aspartate. J Thorac Cardiovasc Surg 1995;110:1228–34.

    Article  PubMed  CAS  Google Scholar 

  60. Drinkwater DC Jr., Cushen CK, Laks H, et al. The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations. J Thorac Cardiovasc Surg 1992;104:1349–55.

    PubMed  Google Scholar 

  61. Nakanishi K, Zhao ZQ, Vinten-Johansen J, et al. Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction. J Thorac Cardiovasc Surg 1995;109:1146–54.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medtronic, Inc., 8200 Coral Sea St, MNV 41, Mounds View, MN 55112, USA

    James A. Coles & Daniel C. Sigg

  2. Department of Surgery, University of Minnesota, B172Mayo, MMC107, 420 Delaware St. SE, Minneapolis, MN 55455, USA

    Paul A. Iaizzo

Authors
  1. James A. Coles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel C. Sigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul A. Iaizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James A. Coles .

Editor information

Editors and Affiliations

  1. Dept. Surgery, University of Minnesota, Delaware St. SE., 420, Minneapolis, 55455, U.S.A.

    Paul A. Iaizzo

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Coles, J.A., Sigg, D.C., Iaizzo, P.A. (2009). Reversible and Irreversible Damage of the Myocardium: New Ischemic Syndromes, Ischemia/Reperfusion Injury, and Cardioprotection. In: Iaizzo, P. (eds) Handbook of Cardiac Anatomy, Physiology, and Devices. Humana Press. https://doi.org/10.1007/978-1-60327-372-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-372-5_14

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-371-8

  • Online ISBN: 978-1-60327-372-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation