Myocardial Protection in Adults

  • Francesco NicoliniEmail author
  • Tiziano Gherli


The use of cardioplegia solution has resulted in substantial improvements in safety and efficacy of cardiac surgery procedures. Its main aims are to protect the myocardium by inducing a cardioplegic diastolic arrest, reducing myocardial energy wasting, preventing cellular damage during the ischemia period and minimizing reperfusion injury after restoration of blood flow in the coronary arteries. This chapter provides an overview of the scientific evidence about cardioplegia as well as describes the daily practice of myocardial protection during cardiac operations. The basic principles of myocardial ischemia and reperfusion injury and how they impact on myocardial protection are discussed. Different types of cardioplegic methods, composition of cardioplegic solutions, strategies and timing of cardioplegic delivery along with adjuncts for cardioplegic solutions are also presented.


Cardioplegia Ischemia Myocardial injury Myocardial protection Reperfusion 



We thank Lois Clegg, English Language Teacher, University of Parma, for her assistance in the revision of the manuscript.


  1. 1.
    Edmunds LH. Cardiopulmonary bypass after 50 years. N Engl J Med. 2004;351:1603–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Daly RC, Dearani JA, McGregor CG, et al. Fifty years of open heart surgery at the Mayo Clinic. Mayo Clin Proc. 2005;80:636–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Baufreton C, Corbeau JJ, Pinaud F. Inflammatory response and haematological disorders in cardiac surgery: toward a more physiological cardiopulmonary bypass. Ann Fr Anesth Reanim. 2006;25:510–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Clermont G, Vergely C, Jazayeri S, et al. Systemic free radical activation is a major event involved in myocardial oxidative stress related to cardiopulmonary bypass. Anesthesiology. 2002;96:80–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Tavares-Murta BM, Cordeiro AO, Murta EF, Cunha Fde Q, Bisinotto FM. Effect of myocardial protection and perfusion temperature on production of cytokines and nitric oxide during cardiopulmonary bypass. Acta Cir Bras. 2007;22:243–50.PubMedCrossRefGoogle Scholar
  6. 6.
    Berg K, Haaverstad R, Astudillo R, et al. Oxidative stress during coronary artery bypass operations: Importance of surgical trauma and drug treatment. Scand Cardiovasc J. 2006;40:291–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Hearse DJ. Myocardial protection during open heart surgery: pre-ischemic, ischemic and post-ischemic considerations. In: Caldarera CM, Editrice HP, editors. Advances in studies on heart metabolism. Bologna: CLUEB; 1982. p. 329–44.Google Scholar
  8. 8.
    Collard CD, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology. 2001;94:1133–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Zaugg M, Lucchinetti E, Uecker M, Pasch T, Schaub MC. Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms. Br J Anaesth. 2003;91:551–65.PubMedCrossRefGoogle Scholar
  10. 10.
    Honda HM, Korge P, Weiss JN. Mitochondria and ischemia/reperfusion injury. Ann N Y Acad Sci. 2005;1047:248–58.PubMedCrossRefGoogle Scholar
  11. 11.
    Bigelow WG, Lindsay WK, Greenwood WF. Hypothermia; its possible role in cardiac surgery: An investigation of factors governing survival in dogs at low body temperatures. Ann Surg. 1950;132:849–66.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Melrose DG, Dieger DB, Bentall HH, Belzer FO. Elective cardiac arrest: preliminary communications. Lancet. 1955;2:21–2.CrossRefGoogle Scholar
  13. 13.
    Gaillard D, Bical O, Paumier D, Trivin F. A review of myocardial normothermia: Its theoretical basis and the potential clinical benefits in cardiac surgery. Cardiovasc Surg. 2000;8:198–203.PubMedCrossRefGoogle Scholar
  14. 14.
    Buckberg GD, Brazier JR, Nelson RL, Goldstein SM, McConnell DH, Cooper N. Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfused beating, fibrillating, and arrested heart. J Thorac Cardiovasc Surg. 1977;73:87–94.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Landymore RW, Marble AE. Effect of hypothermia and cardioplegia on intramyocardial voltage and myocardial oxygen consumption. Can J Surg. 1990;33:45–8.PubMedGoogle Scholar
  16. 16.
    Badak MI, Gurcun U, Discigil B, Boga M, Ozkisacik EA, Alayunt EA. Myocardium utilizes more oxygen and glucose during tepid blood cardioplegic infusion in arrested heart. Int Heart J. 2005;46:219–29.PubMedCrossRefGoogle Scholar
  17. 17.
    Kuniyoshi Y, Koja K, Miyagi K, Shimoji M, Uezu T, Yamashiro S, et al. Myocardial protective effect of hypothermia during extracorporeal circulation – By quantitative measurement of myocardial oxygen consumption. Ann Thorac Cardiovasc Surg. 2003;9:155–62.PubMedGoogle Scholar
  18. 18.
    Hearse DJ, Stewart DA, Braimbridge MV. The additive protective effects of hypothermia and chemical cardioplegia during ischemic cardiac arrest in the rat. J Thorac Cardiovasc Surg. 1980;79:39–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Grigore AM, Mathew J, Grocott HP, Reves JG, Blumenthal JA, White WD, et al. Prospective randomized trial of normothermic versus hypothermic cardiopulmonary bypass on cognitive function after coronary artery bypass graft surgery. Anesthesiology. 2001;95:1110–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Dobbs WA, Engelman RM, Rousou JH, Pels MA, Alvarez JM. Residual metabolism of the hypothermic-arrested pig heart. J Surg Res. 1981;31:319–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Lyons J, Raison J. A temperature-induced transition in mitochondrial oxidation: Contrasts between cold and warm blooded animals. Comp Biochem Physiol. 1970;37:405–11.CrossRefGoogle Scholar
  22. 22.
    Reissmann K, VanCitters R. Oxygen consumption and mechanical efficiency of the hypothermic heart. J Appl Phys. 1956;9:427–32.Google Scholar
  23. 23.
    Teoh KH, Christakis GT, Weisel RD, et al. Accelerated myocardial metabolic recovery with terminal warm blood cardioplegia. J Thorac Cardiovasc Surg. 1986;91:888–95.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Morita K, Ihnken K, Buckberg GD, Sherman MP, Young HH. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. IX. Importance of avoiding perioperative hyperoxemia in the setting of previous cyanosis. J Thorac Cardiovasc Surg. 1995;110(4 Pt 2):1235–44.PubMedCrossRefGoogle Scholar
  25. 25.
    Magovern GJ Jr, Flaherty JT, Gott VL, Bulkley BH, Gardner TJ. Failure of blood cardioplegia to protect myocardium at lower temperatures. Circulation. 1982;66(2 Pt 2):I60–7.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Jacob S, Kallikourdis A, Sellke F, Dunning J. Is blood cardioplegia superior to crystalloid cardioplegia? Interact Cardiovasc Thorac Surg. 2008;7:491–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Yeh CH, Wang YC, Wu YC, Chu JJ, Lin PJ. Continuous tepid blood cardioplegia can preserve coronary endothelium and ameliorate the occurrence of cardiomyocyte apoptosis. Chest. 2003;123:1647–54.PubMedCrossRefGoogle Scholar
  28. 28.
    Velez DA, Morris CD, Budde JM, Muraki S, Otto RN, Guyton RA, et al. All-blood (miniplegia) versus dilute cardioplegia in experimental surgical revascularization of evolving infarction. Circulation. 2001;104(12 Suppl 1):I296–302.PubMedCrossRefGoogle Scholar
  29. 29.
    Landymore RW, Marble AE, Eng P, MacAulay MA, Fris J. Myocardial oxygen consumption and lactate production during antegrade warm blood cardioplegia. Eur J Cardiothorac Surg. 1992;6:372–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Lichtenstein SV, el Dalati H, Panos A, Slutsky AS. Long cross-clamp time with warm heart surgery. Lancet. 1989;1:1443.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Lichtenstein SV, Ashe KA, el Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg. 1991;101:269–74.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Nesher N, Zisman E, Wolf T, et al. Strict thermoregulation attenuates myocardial injury during coronary artery bypass graft surgery as reflected by reduced levels of cardiac-specific troponin I. Anesth Analg. 2003;96:328–35.PubMedGoogle Scholar
  33. 33.
    Daniel S. Review on the multifactorial aspects of bioincompatibility in CPB. Perfusion. 1996;11:246–55.PubMedCrossRefGoogle Scholar
  34. 34.
    Kavanagh BP, Mazer CD, Panos A, Lichtenstein SV. Effect of warm heart surgery on perioperative management of patients undergoing urgent cardiac surgery. J Cardiothorac Vasc Anesth. 1992;6:127–31.PubMedCrossRefGoogle Scholar
  35. 35.
    Landymore RW, Marble AE, Fris J. Effect of intermittent delivery of warm blood cardioplegia on myocardial recovery. Ann Thorac Surg. 1994;57:1267–72.PubMedCrossRefGoogle Scholar
  36. 36.
    Isomura T, Hisatomi K, Sato T, Hayashida N, Ohishi K. Interrupted warm blood cardioplegia for coronary artery bypass grafting. Eur J Cardiothorac Surg. 1995;9:133–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Hayashida N, Isomura T, Sato T, Maruyama H, Higashi T, Arinaga K, et al. Minimally diluted tepid blood cardioplegia. Ann Thorac Surg. 1998;65:615–21.PubMedCrossRefGoogle Scholar
  38. 38.
    Guyton RA, Gott JP, Brown WM, Craver JM. Cold and warm myocardial protection techniques. Adv Card Surg. 1996;7:1–29.PubMedGoogle Scholar
  39. 39.
    Hayashida N, Weisel RD, Shirai T, et al. Tepid antegrade and retrograde cardioplegia. Ann Thorac Surg. 1995;59:723–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Menasché P, Subayi JB, Veyssié L, le Dref O, Chevret S, Piwnica A. Efficacy of coronary sinus cardioplegia in patients with complete coronary artery occlusions. Ann Thorac Surg. 1991;51:418–23.PubMedCrossRefGoogle Scholar
  41. 41.
    Crooke GA, Harris LH, Grossi EA, Baumann FG, Galloway AC, Colvin SB. Biventricular distribution of cold blood cardioplegic solution administered by different retrograde techniques. J Thorac Cardiovasc Surg. 1991;102:631–8.PubMedGoogle Scholar
  42. 42.
    Bezon E, Choplain JN, Khalifa AA, Numa H, Salley N, Barra JA. Continuous retrograde blood cardioplegia ensures prolonged aortic cross-clamping time without increasing the operative risk. Interact Cardiovasc Thorac Surg. 2006;5:403–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Gebhard MM, Preusse CJ, Schnabel PA, Bretschneider HJ. Different effects of cardioplegic solution HTK during single or intermittent administration. Thorac Cardiovasc Surg. 1984;32:271–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Bretschneider HJ. Myocardial protection. Thorac Cardiovasc Surg. 1980;28:295–302.PubMedCrossRefGoogle Scholar
  45. 45.
    Bretschneider HJ, Hübner G, Knoll D, Lohr B, Nordbeck H, Spieckermann PG. Myocardial resistance and tolerance to ischemia: physiological and biochemical basis. J Cardiovasc Surg. 1975;16:241–60.Google Scholar
  46. 46.
    Jin XY, Gibson DG, Pepper JR. Early changes in regional and global left ventricular function after aortic valve replacement. Comparison of crystalloid, cold blood, and warm blood cardioplegias. Circulation. 1995;92(9 Suppl):II155–62.PubMedCrossRefGoogle Scholar
  47. 47.
    Braathen B, Tonnessen T. Cold blood cardioplegia reduces the increase in cardiac enzyme levels compared with cold crystalloid cardioplegia in patients undergoing aortic valve replacement for isolated aortic stenosis. J Thorac Cardiovasc Surg. 2010;139:874–80.PubMedCrossRefGoogle Scholar
  48. 48.
    Calafiore AM, Teodori G, Mezzetti A, et al. Intermittent Antegrade Warm Blood Cardioplegia. Ann Thorac Surg. 1995;59:398–402.PubMedCrossRefGoogle Scholar
  49. 49.
    Salerno TA, Houck JP, Barrozo CAM, et al. Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection. Ann Thorac Surg. 1991;51:245–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Salerno TA, Charrette EJP, Chiong MA. Is cardioplegic re-arrest safe? Can J Surg. 1981;24:483–4.PubMedGoogle Scholar
  51. 51.
    Lichtenstein SV, Ashe KA, elDalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg. 1991;101:269–74.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Standeven JW, Jellinek M, Menz LJ, Kolata RJ, Barner HB. Cold blood potassium diltiazem cardioplegia. J Thorac Cardiovasc Surg. 1984;87:201–12.PubMedCrossRefGoogle Scholar
  53. 53.
    Duan L, Zhang C, Luo W, Gao Y, Chen R, Hu G. Does magnesium-supplemented cardioplegia reduce cardiac injury? A meta-analysis of randomized controlled trials. J Card Surg. 2015;30:338–45.PubMedCrossRefGoogle Scholar
  54. 54.
    Poveda-Jaramillo R, Monaco F, Zangrillo A, Landoni G. Ultra-short–acting β-blockers (Esmolol and Landiolol) in the perioperative period and in critically ill patients. J Cardiothorac Vasc Anesth. 2018;32:1415–25.PubMedCrossRefGoogle Scholar
  55. 55.
    Fiore AC, Naunheim KS, Taub J, et al. Myocardial preservation using lidocaine blood cardioplegia. Ann Thorac Surg. 1990;50:771–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Guerrero-Orriach JL, Escalona Belmonte JJ, Ramirez Fernandez A, Ramirez Aliaga M, Rubio Navarro M, Cruz MJ. Cardioprotection with halogenated gases: how does it occur? Drug Des Devel Ther. 2017;11:837–49.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Yeh CH, Chen TP, Lee CH, Wu YC, Lin YM, Lin PJ. Cardioplegia-induced cardiac arrest under cardiopulmonary bypass decreased nitric oxide production which induced cardiomyocytic apoptosis via nuclear factor kappa B activation. Shock. 2007;27:422–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Zeng J, He W, Qu Z, Tang Y, Zhou Q, Zhang B. Cold blood versus crystalloid cardioplegia for myocardial protection in adult cardiac surgery: A meta-analysis of randomized controlled studies. J Cardiothorac Vasc Anesth. 2014;28:674–81.PubMedCrossRefGoogle Scholar
  59. 59.
    Moghimian M, Faghihi M, Karimian SM, Imani A, Houshmand F, Azizi Y. Role of central oxytocin in stress-induced cardioprotection in ischemic-reperfused heart model. J Cardiol. 2013;61:79–86.PubMedCrossRefGoogle Scholar
  60. 60.
    Wu ZK, Laurikka J, Saraste A, Kytö V, Pehkonen EJ, Savunen T, et al. Cardiomyocyte apoptosis and ischemic preconditioning in open heart operations. Ann Thorac Surg. 2003;76:528–34.PubMedCrossRefGoogle Scholar
  61. 61.
    Ghosh S, Galiñanes M. Protection of the human heart with ischemic preconditioning during cardiac surgery: role of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2003;126:133–42.PubMedCrossRefGoogle Scholar
  62. 62.
    Perrault LP, Menasché P, Bel A, et al. Ischemic preconditioning in cardiac surgery: a word of caution. J Thorac Cardiovasc Surg. 1996;112:1378–86.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Cardiac Surgery Unit, Department of Medicine and SurgeryUniversity of ParmaParmaItaly

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