Can Infarct Size Be Limited? Prospects for “Injury-Delaying” Therapy

  • D. J. Hearse
Conference paper

Abstract

An assessment of our methods for protecting the ischaemic myocardium leads to the conclusion that we are faced with a situation of surgical success versus clinical failure. Thus, while the development and application of cardioplegia has revolutionized cardiac surgery, clinical cardiologists have failed conspicuously in their quest for “anti-infarct” drugs to limit the size of an evolving infarct. Despite more than 15 years of intensive research, and the expenditure of many hundreds of millions of dollars, we have to conclude that no single anti-infarct agent has achieved widespread and sustained clinical use. Surprising though it may seem, cardiologists are only just beginning to acknowledge the axiom that in the absence of early re- flow, severely ischaemic tissue must eventually die and no drug can prevent this.

Keywords

Magnesium Ischemia Chloride Sodium Superoxide Explosive 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hearse DJ, Yellon DM (1981) The border zone in evolving myocardial infarction: controversy or confusion? Am J Cardiol 47: 1321–1334PubMedCrossRefGoogle Scholar
  2. 2.
    Hearse DJ (1983) Critical distinctions in the modification of myocardial cell injury. In: Opie LH (ed) Calcium antagonists and cardiovascular disease. Raven, New York, pp 129–145Google Scholar
  3. 3.
    Hearse DJ, Yellon DM (1984) Why are we still in doubt about infarct size limitation? The experimentalist’s viewpoint. In: Hearse DJ, Yellon DM (eds) Therapeutic approaches to myocardial infarct size limitation. Raven, New York, pp 17–41Google Scholar
  4. 4.
    Hearse DJ (1987) The protection of the ischemic myocardium: surgical success versus clinical failure. Progress in cardiovascular disease (In press)Google Scholar
  5. 5.
    Newman PE (1981) The coronary collateral circulation: determination and functional significance in ischemic heart disease. Am Heart J 102: 431–445PubMedCrossRefGoogle Scholar
  6. 6.
    Brazier J, Hottenrott C, Buckberg GD (1975) Non coronary collateral blood flow. Ann Thorac Surg 19: 426–435PubMedCrossRefGoogle Scholar
  7. 7.
    Schaper W (1971) The collateral circulation of the heart. Elsevier, AmsterdamGoogle Scholar
  8. 8.
    Schaper W (1984) Experimental infarcts and the microcirculation. In: Hearse DJ, Yellon DM (eds) Therapeutic approaches to myocardial infarct size limitation. Raven, New York, pp 79–90Google Scholar
  9. 9.
    Downey JM (1984) Why the endocardium? In: Hearse DJ, Yellon DM (eds) Therapeutic approaches to myocardial infarct size limitation. Raven, New York, pp 125–138Google Scholar
  10. 10.
    Maxwell MP, Hearse DJ, Yellon DM (1987) The species variation in the coronary collateral circulation during regional myocardial ischaemia: a critical determinant of the rate of evolution and extent of myocardial infarction. Cardiovasc Res 21: 737–746PubMedCrossRefGoogle Scholar
  11. 11.
    Hearse D J, Crome R, Yellon DM, Wyse RKH (1983) Metabolic and flow correlates of myocardial ischaemia. Cardiovasc Res 17: 452–458PubMedCrossRefGoogle Scholar
  12. 12.
    Kudoh Y, Hearse DJ, Maxwell MP, Yoshida S, Downey JM, Yellon DM (1986) Calcium antagonists and evolving myocardial infarction: studies of the effect of nifedipine on tissue ATP, collateral flow and infarct size in the closed chest dog. J Mol Cell Cardiol 18 (Suppl 4): 77–92PubMedCrossRefGoogle Scholar
  13. 13.
    Chambers DE, Yellon DM, Hearse DJ, Downer JM (1983) Effects of flurbiprofen in altering the size of myocardial infarcts in dogs: reduction or delay? Am J Cardiol 51: 884–890PubMedCrossRefGoogle Scholar
  14. 14.
    Yoshida S, Downey JM, Friedman FR, Chambers DE, Hearse DJ, Yellon DM (1985) Nifedipine limits infarct size for 24 hours in closed chest coronary embolized dogs. Basic Res Cardiol 80: 76–87PubMedCrossRefGoogle Scholar
  15. 15.
    Yellon DM, Hearse DJ, Maxwell MP, Chambers DE, Downey JM (1983) Sustained limitation of myocardial necrosis 24 hours after coronary artery occlusion: verapamil infusion in dogs with small infarcts. Am J Cardiol 51: 1409–1413PubMedCrossRefGoogle Scholar
  16. 16.
    Hearse DJ, Yellon DM, Downey JM (1987) Can beta blockers limit infarct size? Eur Heart J 7: 925–930Google Scholar
  17. 17.
    Hearse DJ, Braimbridge MV, Jynge P (1981) Protection of the ischemic myocardium: cardioplegia. Raven, New YorkGoogle Scholar
  18. 18.
    Smith HJ, Briscoe MG (1985) The relative sensitization by acidosis of five calcium blockers in cat papillary muscles. J Mol Cell Cardiol 17: 709–716PubMedCrossRefGoogle Scholar
  19. 19.
    Hearse DJ, Humphrey SM, Chain EB (1973) Abrupt reoxygenation of the anoxic potassium arrested perfused rat heart. A study of myocardial enzyme release. J Mol Cell Cardiol 5:395– 407Google Scholar
  20. 20.
    Hearse DJ (1971) Reperfusion of the ischaemic myocardium. J Mol Cell Cardiol 9: 605–616CrossRefGoogle Scholar
  21. 21.
    Braunwald E, Kloner RA (1985) Myocardial reperfusion: a double-edged sword? J Clin Invest 76: 1713–1719PubMedCrossRefGoogle Scholar
  22. 22.
    Hearse DJ, Humphrey SM, Bullock GR (1978) The oxygen paradox and the calcium paradox: two facets of the same problem? J Mol Cell Cardiol 10: 641–668PubMedCrossRefGoogle Scholar
  23. 23.
    Hearse DJ (1984) Reperfusion of the ischaemic myocardium. Clin Res Rev 4: 58–61Google Scholar
  24. 24.
    Kuroda H, Ishiguro S, Mori T (1986) Optimal calcium concentration in the initial reperfu- sate for post-ischemic myocardial performance (calcium concentration during reperfusion). J Mol Cell Cardiol 18: 625–633PubMedCrossRefGoogle Scholar
  25. 25.
    Braunwald E, Kloner RA (1982) The stunned myocardium: prolonged postischemic ventricular dysfunction. Circulation 66: 1146–1147PubMedCrossRefGoogle Scholar
  26. 26.
    Reimer KA, Hill ML, Jennings RB (1981) Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. J Mol Cell Cardiol 13: 229–239PubMedCrossRefGoogle Scholar
  27. 27.
    Jolly SR, Kane WJ, Bailie MB, Adams GD, Lucchesi BR (1984) Canine myocardial reperfusion injury: its reduction by the combined administration of superoxide dismutase and catalase. Circ Res 54: 277–285PubMedGoogle Scholar
  28. 28.
    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: 331–340PubMedGoogle Scholar
  29. 29.
    Manning AS, Coltart DJ, Hearse DJ (1984) Ischemia- and reperfusion-induced arrhythmias in the rat: effects of xanthine oxidase inhibition with allopurinol. Circ Res 55: 545–550PubMedGoogle Scholar
  30. 30.
    Lazar HL, Buckberg GD, Manganaro AM, Becker A (1980) Myocardial energy replenishment and reversal of ischemic damage by substrate enhancement of secondary blood cardioplegia with amino acids during reperfusion. J Thorac Cardiovasc Surg 80: 350–359PubMedGoogle Scholar
  31. 31.
    Follette DM, Buckberg GD (1984) Reducing post-ischemic myocardial injury during cardiopulmonary bypass by temporary initial reperfusate modification. Clin Res Rev 4: 25–28Google Scholar
  32. 32.
    Rau EE, Shine KI, Gervais A, Douglas AM, Amos EC (1979) Enhanced mechanical recovery of anoxic and ischemic myocardium by amino acid perfusion. Am J Physiol 236: 873–879Google Scholar
  33. 33.
    Shine KI, Douglas AM (1983) Low calcium reperfusion of ischemic myocardium. J Mol Cell Cardiol 15: 251–260PubMedCrossRefGoogle Scholar
  34. 34.
    Follette DM, Fey K, Buckberg GD, Heley JJ, Steed DL, Foglia RP, Maloney JV (1981) Reducing post-ischemic damage by temporary modification of reperfusate calcium, potassium, pH and osmolality. J Thorac Cardiovasc Surg 82: 221–238PubMedGoogle Scholar
  35. 35.
    Manning AS, Hearse DJ (1984) Reperfusion-induced arrhythmias: mechanisms and prevention. J Mol Cell Cardiol 16: 497–517PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • D. J. Hearse

There are no affiliations available

Personalised recommendations