Myocardial Preservation during Cardiopulmonary Resuscitation

  • T. Pellis
  • W. Tang
Conference paper


Sudden cardiac death accounts for 300,000 to 400,000 deaths annually in the United States, it is the most common and often first manifestation of coronary heart disease and is responsible for approximately 50% of mortality for cardiovascular diseases in the United States and other developed countries [1, 2]. Sudden cardiac death describes the unexpected natural death from a cardiac cause within a short period, generally ≤ 1 hour from onset of symptoms, in a person without any prior condition that would appear fatal [1]. Cardiopulmonary resuscitation (CPR) effectively restores haemodynamic stability and return to spontaneous circulation (ROSC) in 40% to 60% of arrests. Prolonged survival is significantly lower because of an underlying illness and postresuscitation syndrome, specifically central nervous system injury and left ventricular stunning after resuscitation [3].


Cardiopulmonary Resuscitation KATP Channel Ischemic Precondition Myocardial Stunning Ischaemic Precondition 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Zipes DP, Wellens HJJ (1998) Sudden cardiac death. Circulation 98:2334–2351PubMedCrossRefGoogle Scholar
  2. 2.
    American Heart Association (1991) Heart and Stroke Facts. Dallas: American Heart AssociationGoogle Scholar
  3. 3.
    Thel MC, O’Connor CM, Durham ( 1999) Cardiopulmonary resuscitation: Historical prespective to recent investigations. Am Heart J 137:39–48PubMedCrossRefGoogle Scholar
  4. 4.
    Liberthson RR, Nagel EL, Hirschman JC (1974) Prehospital ventricular fibrillation. Prognosis and follow-up course. N Engl J Med 291:317–321PubMedCrossRefGoogle Scholar
  5. 5.
    Brain Resuscitation Clinical Trial II Study Group (1991) A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. N Engl J Med 324:1125–1231Google Scholar
  6. 6.
    Becker LB, Ostrander MP, Barrett J et al (1991) CPR Chicago: outcome of cardiopulmonary resuscitation in a large metropolitan area-where are the survivors? Ann Emerg Med 20:355–361PubMedCrossRefGoogle Scholar
  7. 7.
    Brown CG, Martin DR, Pepe PE (1992) A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. N Engl J Med 327:1051–1055PubMedCrossRefGoogle Scholar
  8. 8.
    Stiell IG, Herbert PC, Weitzman BN (1992) High-dose epinephrine in adult cardiac arres.t N Engl J Med 327:1045–1050CrossRefGoogle Scholar
  9. 9.
    Lombardi G, Gallagher J, Gennis P (1994) Outcome of out-of-hospital cardiac arrest in New York city: the Pre-hospital Arrest Survival Evaluation (PHASE) study. JAMA 271:678–683PubMedCrossRefGoogle Scholar
  10. 10.
    Tang W, Weil MH, Sun S et al (1993) Progressive myocardial dysfunction after cardiac resuscitation. Crit Care Med 21:1046–1050PubMedCrossRefGoogle Scholar
  11. 11.
    Gazmuri RJ, Weil MH, Bisera J et al (1996) Myocardial dysfunction after successful resuscitation from cardiac arrest. Crit Care Med 24:992–1000PubMedCrossRefGoogle Scholar
  12. 12.
    Brain Resuscitation Clinical Trial I Study Group (1986) A randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. N Engl J Med 314:397–403CrossRefGoogle Scholar
  13. 13.
    Gray WA, Capone RJ, Most AS (1991) Unsuccessful emergency medical resuscitation-are continued efforts in the emergency department justified? N Engl J Med 325:1393–1398PubMedCrossRefGoogle Scholar
  14. 14.
    Tang Z, Weil MH, Sun S et al (1997) High energy countershocks increase ventricular ectopy after successful CPR [abstract]. Crit Care Med 25:A57Google Scholar
  15. 15.
    Tang W, Weil MH, Sun S et al (1995) Epinephrine increases the severity of post-resuscitation myocardial dysfunction. Circulation 92:3089–3093PubMedCrossRefGoogle Scholar
  16. 16.
    Sun SJ, Weil MH, Tang W et al (1996) Effects of buffer agents on post-resuscitation myocardial dysfunction. Crit Care Med 24:2035–2041PubMedCrossRefGoogle Scholar
  17. 17.
    Xie J, Weil MH, Sun SJ et al (1997) High power defibrillation increases the severity of post-resuscitation myocardial dysfunction. Circulation 96:683–688PubMedCrossRefGoogle Scholar
  18. 18.
    De Antonio HJ, Kaul S, Lerman BB (1990) Reversible myocardial depression survivors of cardiac arrest. Pacing Clin Electrophysiol 13:982–985CrossRefGoogle Scholar
  19. 19.
    Lewes SJ, Holmberg S, Quinn E (1993) Out-of-hospital resuscitation in EastSussex: 1981-1989. Br Heart J 70:568–573CrossRefGoogle Scholar
  20. 20.
    United States Statistical Abstract 116th Edition, 1994Google Scholar
  21. 21.
    Steenbergen C, Murphy E, Watts JA et al (1990) Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart. Circ Res 66:135–146PubMedCrossRefGoogle Scholar
  22. 22.
    Murry CE, Richard VJ, Jennings RB et al (1991) Myocardial protection is lost before contractile function recovers from preconditioning. Am J Physiol 260:H796-H804Google Scholar
  23. 23.
    Johnson BA, Weil MH, Tang W et al (1995) Mechanisms of myocardial acidosis during arrest J Appl Physiol 78:1579–1584PubMedGoogle Scholar
  24. 24.
    Hoffmeister HM, Mauser M, Schaper W (1985) Effects of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium. Basic Res Cardiol 80:445–458PubMedCrossRefGoogle Scholar
  25. 25.
    Kusuoka H, Porterfield JK, Weisman HF et al (1987) Pathophysiology and pathogenesis of stunned myocardium: depressed Ca2+ activation overload in ferret hearts. J Clin Invest 79:950–961PubMedCrossRefGoogle Scholar
  26. 26.
    Schafer S, Heusch G (1990) Recruitment of a time-dependent inotropic reserve by postextrasystolic potentiation in normal and reperfused myocardium. Basic Res Cardiol 85:257–269PubMedCrossRefGoogle Scholar
  27. 27.
    Kida M, Fujiwara H, Uegaito T et al (1993) Dobutamine prevents both myocardial stunning and phosphocreatine overshoot without affecting ATP level. J Mol Cell Cardiol 25:875–8135PubMedCrossRefGoogle Scholar
  28. 28.
    Marban E (1991) Myocardial stunning and hibernation. The physiology behind the colloquialisms. Circulation 83:681–688PubMedCrossRefGoogle Scholar
  29. 29.
    Li XY, McCay PB, Zughaib M et al (1993) Demonstration of free radical generation in the “stunned” myocardial in the conscious dog and identification of major differences between conscious and open-chest dogs. J Clin Invest 92:1025–1041PubMedCrossRefGoogle Scholar
  30. 30.
    Ehring T, Bohm M, Heusch G (1992) The calcium antagonist shows the functional recovery of reperfused myocardium only when given before ischemia. J Cardiovasc Pharmacol 20:63–74PubMedGoogle Scholar
  31. 31.
    Du Toit EF, Opie LH (1992) Modulation of severity of reperfusion stunning in the isolated rat heart by agents altering calcium flux at the onset of reperfusion. Circ Res 70:960–967CrossRefGoogle Scholar
  32. 32.
    Ehring T, Heusch G (1995) Stunned myocardium and the attenuation of stunning by calcium antagonists. Am J Cardiol 75:61E–67EPubMedCrossRefGoogle Scholar
  33. 33.
    Schwartz A (1992) Molecular and cellular aspects of calcium channel antagonism. Am J Cardiol 70(suppl):6F–8FPubMedCrossRefGoogle Scholar
  34. 34.
    Ferrari R, Visioli O (1994) How do calcium antagonists differ in clinical practice? Cardiovasc Drug Ther 8:565–575CrossRefGoogle Scholar
  35. 35.
    Tanskela JS, Shoubridge EA (1996) Intercellular calcium dynamics and cellular energetics in ischemic cells studied by concurrent and doublequantum filtered spectroscopy. J Neurochem 66:266–276CrossRefGoogle Scholar
  36. 36.
    Reimer KA, Murry CE, Yamasawa I et al (1986) Four brief periods of ischemia cause no cumulative ATP loss or necrosis. Am J Physiol 251:H1306-H1305Google Scholar
  37. 37.
    Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136PubMedCrossRefGoogle Scholar
  38. 38.
    Schott RJ, Rohmann S, Braun ER et al(1990) Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66:1133–1142PubMedCrossRefGoogle Scholar
  39. 39.
    Iwamoto T, Miura T, Adachi T et al (1991) Myocardial infarct size-limiting effect if ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit. Circulation 83:1015–1022PubMedCrossRefGoogle Scholar
  40. 40.
    Yellon DM, Alkhulaifi AM, Browne EE et al (1992) Ischemic preconditioning limits infarct size in the rat heart. Cardiovasc Res 26:983–987PubMedCrossRefGoogle Scholar
  41. 41.
    Menasche P, Kevelaitis E, Mouuas C et al (1995) Preconditioning with potassium channel openers: a new concept for enhancing cardioplegic protection? J Thorac Cardiovasc Surg 110:1606–1614PubMedCrossRefGoogle Scholar
  42. 42.
    Takeda S, Satoh T, Osada M et al (1995) Protective effect of pacing on reperfusion-induced ventricular arrhythmias in isolated rat hearts. Can J Cardiol 11:573–579PubMedGoogle Scholar
  43. 43.
    Shiki K, Hearse DJ (1987) Preconditioning of ischemic myocardium: reperfusion-induced arrhythmias. Am J Physiol 253:H1470-H1476Google Scholar
  44. 44.
    Cohen MV, Liu GS, Downey JM (1991) Preconditioning causes improved wall motion as well as smaller infarcts after transient coronary occlusion in rabbits. Circulation 84:341–349PubMedCrossRefGoogle Scholar
  45. 45.
    Sun JZ, Tang XL, Park SW et al (1996) Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs. J Clin Invest 97:562–576PubMedCrossRefGoogle Scholar
  46. 46.
    Xu C, Chen Y, Lu M (1995) A clinical study on limitation of infarct size ischemic preconditioning in 100 cases of acute myocardial infraction. Chung Hua Nei Ko Tsa Chih 34:16–18PubMedGoogle Scholar
  47. 47.
    Pasceri V, Lanza GA, Parti G (1996) Preconditioning by transient myocardial ischemia confers protection against ischemia-induced ventricular arrhythmias in variant angina. Circulation 94:1850–1856PubMedCrossRefGoogle Scholar
  48. 48.
    Mei DA, Gross GJ (1995) Evidence for the involvement of the ATP-sensitive potassium channel in a novel model of hypoxic preconditioning in dogs. Cardiovasc Res 30:222–230PubMedGoogle Scholar
  49. 49.
    Koning MM, Gho BC, van Klaarwater E et al (1996) Rapid ventricular pacing produces myocardial protection by nonischemic activation of KATP channels. Circulation 93:178–186PubMedCrossRefGoogle Scholar
  50. 50.
    Murphy E, Penman M, London RE et al (1991) Amiloride delays the ischemic-induced rise in cytosolic free calcium. Circ Res 68:1250–1258PubMedCrossRefGoogle Scholar
  51. 51.
    Van Winkle DM, Thornton RB, Downey JM (1991) Cardioprotection from ischemic preconditioning is lost following prolonged reperfusion in the rabbit. Coron Artery Dis 2:613–619Google Scholar
  52. 52.
    Li YW, Whittaker P, Kloner RA (1992) The transient nature of the effect of ischemic preconditioning on myocardial infarct size and ventricular arrhythmia. Am Heart J 123:346–353PubMedCrossRefGoogle Scholar
  53. 53.
    Simkhovich BA, Whittaker P, Przyklenk K et al (1995) Transient preischemic acidosis protects the isolated rabbit heart subject to 30 minutes, but not 60 minutes, of global ischemia. Basic Res Cardiol 90:397–403PubMedCrossRefGoogle Scholar
  54. 54.
    Liu GS, Thornton J, Van Win et al (1991) Protection against infarction afforded by preconditioning is mediated by Al, adenosine receptors in the rabbit heart. Circulation 84:350–356PubMedCrossRefGoogle Scholar
  55. 55.
    Thornton JD, Liu GS, Downey JM (1993) Pretreatment with pertussis toxin blocks the protective effects of preconditioning: evidence for a Gprotein mechanism. J Mol Cell Cardiol 25:311–320PubMedCrossRefGoogle Scholar
  56. 56.
    Gross GJ, Auchampach JA (1992) Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. Circ Res 70:223–233PubMedCrossRefGoogle Scholar
  57. 57.
    Auchampach JA, Grover GJ, Gross GJ (1992) Blockade of ischemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate. Cardiovasc Res 26:1054–1062PubMedCrossRefGoogle Scholar
  58. 58.
    Behling RW, Malone HJ (1995) KATP-channel openers protect against increased cytosolic calcium during ischemia and reperfusion. J Mol Cell Cardiol 27:1809–1817PubMedCrossRefGoogle Scholar
  59. 59.
    Shigematsu S, Sato T, Abe T (1995) Pharmacological evidence for the persistent activation of ATP-sensitive K+ channels in early phase of reperfusion and its protective role against myocardial stunning. Circulation 92:2266–2275PubMedCrossRefGoogle Scholar
  60. 60.
    Mizumura T, Nithipatikom K, Gross GJ (1995) Bimakalin, an ATP-sensitive potassium channel opener, mimics the effects of ischemic preconditioning to reduce infarct size, adenosine release, and neutrophil function in dogs. Circulation 92:1236–1245PubMedCrossRefGoogle Scholar
  61. 61.
    Lawton JS, Sepic JD, Allen CT et al (1996) Myocardial protection with potassium-channel openers is as effective as St Thomas’ solution in the rabbit heart. Ann Thorac Surg 61:31–38CrossRefGoogle Scholar
  62. 62.
    Cleveland JC, Meldrum DR, Rowland RT et al (1997) Adenosine preconditioning of human myocardium is dependent upon the ATP-sensitive K channel. J Mol Cell Cardiol 29:175–182PubMedCrossRefGoogle Scholar
  63. 63.
    Liu Y, Gao WD, O’Rourke B (1996) Synergistic modulation of ATP-sensitive K+ currents by protein kinase C and adenosine. Implications for ischemic preconditioning. Circ Res 78:443–454PubMedCrossRefGoogle Scholar
  64. 64.
    Katsuda Y, Egashira K, Ueno H et al (1996) ATP-sensitive K+ channel opener pinacidil augments b1-adrenoceptor-induced coronary vasodilation in dogs. Am J Physiol 270:H2210-H2215Google Scholar
  65. 65.
    Vegh A, Papp JG, Parratt J (1994) Attenuation of the antiarrhythmic effects of ischemic preconditioning by blockage of bradykinin Bs receptors. Br J Pharmacol 113:1167–1172PubMedCrossRefGoogle Scholar
  66. 66.
    Parratt J, Vegh A, Papp JG (1995) Pronounced antiarrhythmic effects of ischemic preconditioning-are there possibilities for pharmacological exploitation? Pharmacol Res 31:225–234PubMedCrossRefGoogle Scholar
  67. 67.
    Gross GJ, Mei DA, Schultz JJ (1996) Criteria for a mediator or effector of myocardial preconditioning: do KATP channels meet the requirements? Basic Res Cardiol 91:31–34PubMedGoogle Scholar
  68. 68.
    Tang W, Weil MH, Sun SJ (1997) KATP channel activation improves post resuscitation myocardial function [abstract]. Circulation 96:1366Google Scholar
  69. 69.
    Tang W, Weil MH, Sun S et al (2000) K(ATP) channel activation reduces the severity of post resuscitation myocardial dysfunction. Am J Physiol Heart Circ Physiol 279: H1609-H1615Google Scholar

Copyright information

© Springer-Verlag Italia 2002

Authors and Affiliations

  • T. Pellis
    • 1
  • W. Tang
    • 2
  1. 1.Department of Clinical Sciences, Section of Anaesthesia, Intensive Care and Pain ClinicThe Institute of Critical Care MedicinePalm SpringsUSA
  2. 2.The University of Southern CaliforniaKeck School of MedicineLos AngelesUSA

Personalised recommendations