Apoptosis during cardiac surgery

  • Hermann Aebert
  • Joachim P. Schmitt
  • Heribert Schunkert
Part of the Basic Science for the Cardiologist book series (BASC, volume 5)


Open heart surgery involves substantial stress for cardiac myocytes and thus the risk of cellular damage. Particularly, open heart surgery implies cardiac arrest for a quiet and bloodless surgical field. The physiological blood flow via the coronary arteries is interrupted by cross-clamping of the ascending aorta and the heart is perfused temporarily with some type of cardioplegic solution. These solutions contain non-physiologic ion concentrations to arrest electromechanic coupling. Together with hypothermia, cardioplegia results in reduction of the energy requirements of the heart by up to 97% (1,2). Nevertheless, a distinct depression of cardiac contractility is observed early in the postoperative period (3). The extent of this depression is directly related to patient survival (4). The reasons for the delayed recovery of the heart are poorly understood but cellular trauma or potentially apoptosis may be involved (5). Given this background information, a better understanding and further improvements of cardioplegic strategies are certainly needed.


Heat Shock Protein Open Heart Surgery Cardioplegic Solution Cardioplegic Arrest Physiological Blood Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Buckberg DG. Myocardial protection, an overview. Semin Thorac Cardiovasc Surg. 1993;5:98–106.PubMedGoogle Scholar
  2. 2.
    Bretschneider HJ, Gebhard MM, Preusse CJ. „Cardioplegia. Principles and problems.“ In Physiology and pathophysiology of the heart, N. Sperrlohn, ed. Boston: M. Nijhoff Publishers, 1984;605–616.Google Scholar
  3. 3.
    Breisblatt WM, Stein KL, Wolfe CJ, Follansbee WP, Capozzi J, Armitage JM, Hardesty RL. Acute myocardial dysfunction and recovery: a common occurence after coronary bypass surgery. J Am Coll Cardiol. 1990; 15:1261–1269.PubMedGoogle Scholar
  4. 4.
    Kirklin JW and Barrat-Boyes BG. „Myocardial management during cardiac surgery with cardiopulmonary bypass.“ In Cardiac Surgery, 2nd edn., JW Kirklin and BG Barrat-Boyes, eds. New York, London, Tokyo: Churchill Livingston, 1993;133–165.Google Scholar
  5. 5.
    Aebert H, Cornelius T, Birnbaum DE, Siegel AV, Riegger GA, Schunkert H. Induction of immediate early genes and programmed cell death following cardioplegic arrest in human hearts. Eur J Cardio-thorac Surg. 1997; 12:261–267.CrossRefGoogle Scholar
  6. 6.
    Demmy TL, Haggerty SP, Boley TM, Curtis JJ. Lack of cardioplegia uniformity in clinical myocardial preservation. Ann-Thorac-Surg. 1994;57:648–51.PubMedGoogle Scholar
  7. 7.
    Izumo S, Nadal-Ginard B, Mahdavi V. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA. 1988;85:339–343.PubMedCrossRefGoogle Scholar
  8. 8.
    Currie RW, Tanguay RM, Kingma JG Jr. Heat-shock response and limitation of tissue necrosis during occlusion/reperfusion in rabbit hearts. Circulation, 1993;87:963–971.PubMedGoogle Scholar
  9. 9.
    Amrani M, Corbett J, Boateng SY, Dunn MJ, Yacoub MH. Kinetics of induction and protective effect of heat-shock proteins after cardioplegic arrest. Ann Thorac Surg. 1996;61:1407–1412.PubMedCrossRefGoogle Scholar
  10. 10.
    Currie RW, Karmazyn M, Kloc M, Mailer K. Heat-shock response is associated with enhanced postischemic ventricular recovery. Cire Res. 1988;63:543–549.Google Scholar
  11. 11.
    Hutter MM, Sievers RE, Barbosa V, Wolfe CL. Heat shock protein induction in rat hearts. A direct correlation between the amount of heat shock protein induced and the degree of myocardial protection. Circulation 1994;89:355–360.PubMedGoogle Scholar
  12. 12.
    Plumier JC, Ross BM, Currie RW. Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery. J Clin Invest. 1995;95:1854–1860.PubMedGoogle Scholar
  13. 13.
    Kwak HJ, Jun CD, Pae HO, Yoo JC, Park YC, Choi BM, Na YG, Park RK, Chung HT, Chung HY, Park WY, Seo JS. The role of inducible 70-kDa heat shock protein in cell cycle control, differentiation, and apoptotic cell death of the human myeloid leukemic HL-60 cells. Cell Immunol. 1998;187:1–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Buzzard KA, Giaccia AJ, Killender M, Anderson RL. Heat shock protein 72 modulates pathways of stress-induced apoptosis. J Biol Chem. 1998;273; 17147–17153.PubMedCrossRefGoogle Scholar
  15. 15.
    Aebert H, Cornelius T, Ehr T, Holmer SR, Birnbaum DE, Riegger GA, Schunkert H. Expression of immediate early genes after cardioplegic arrest and reperfusion. Ann Thorac Surg. 1997;63:1669–1675.PubMedCrossRefGoogle Scholar
  16. 16.
    Preston GA, Lyon TT, Yin Y, Lang JE, Solomon G, Annab L, Srinivasan DG, Alcorta DA, Barrett JC. Induction of apoptosis by c-Fos protein. Mol Cell Biol. 1996; 16:211–218.PubMedGoogle Scholar
  17. 17.
    Smyne RJ, Vendrell M, Hayward M, Baker SJ, Miao GG, Schilling K, Robertson ML, Curran T, Morgan JI. Continous c-fos expression preceeds programmed cell death in vivo. Mature 1993;363:166–169.Google Scholar
  18. 18.
    Steller H. Mechanisms and genes of cellular suicide. Science 1995;267:1445–1449.PubMedCrossRefGoogle Scholar
  19. 19.
    Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R. In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology 1995;21:1465–1468.PubMedCrossRefGoogle Scholar
  20. 20.
    Majno G, and Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am JPathol 1995, 146:3–15.Google Scholar
  21. 21.
    Martin SJ and Green DR. Protease activation during apoptosis: death by a thousand cuts? Cell 1995;82:349–352.PubMedCrossRefGoogle Scholar
  22. 22.
    Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 1997;275:1129–1132.PubMedCrossRefGoogle Scholar
  23. 23.
    Vander Heiden MG, Chandel NS, Williamson EK, Schumacker PT, Thompson CB. Bcl-xl regulates the membrane potential and volume homeostasis of mitochondria. Cell 1997;91:627–637.CrossRefGoogle Scholar
  24. 24.
    Green DR and Reed JC. Mitochondria and Apoptosis. Science 1998;281:1309–1312.PubMedCrossRefGoogle Scholar
  25. 25.
    Robinson Jr. JB, Brent LG, Sumegi B, Srere PA. In Mitochondria, a practical approach, VM Darley-Usmar, D Rickwood, MT Wilson, eds. Oxford, Washington DC: IRL Press, 1987;160, 161.Google Scholar
  26. 26.
    Freude B, Masters TN, Kostin S, Robicsek F, Schaper J. Cardiomyocyte apoptosis in acute and chronic conditions. Basic Res Cardiol. 1998;93:85–89.PubMedCrossRefGoogle Scholar
  27. 27.
    Birdi I, Angelini GD, Bryan AJ. Biochemical markers of myocardial injury during cardiac operations. Ann Thorac Surg. 1997;63:879–884.PubMedCrossRefGoogle Scholar
  28. 28.
    Prasad K, Kalra J, Bharadwaj B, Chaudhary AK. Increased oxygen free radical activity in patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. Am Heart J. 1992;123:37–45.PubMedCrossRefGoogle Scholar
  29. 29.
    Cheng W, Li B, Kajstura J, Li P, Wolin MS, Sonnenblick EH, Hintze TH, Olivetti G, Anversa P. Stretch-induced programmed myocyte cell death. J Clin Invest. 1995;96:2247–2259.PubMedGoogle Scholar
  30. 30.
    Milano CA, White WD, Smith LR, Jones RH, Lowe JE, Smith PK, Van-Trigt P. Coronary artery bypass in patients with severely depressed ventricular function. Ann Thorac Surg. 1993;56:487–493.PubMedGoogle Scholar
  31. 31.
    Hosenpud, J.D., Bennet, L.E., Keck, B.M., Fiol, B., Novick, RJ. The Registry of the International Society for Heart and Lung Transplantation: fourteenth official report-1997. J Heart Lung Transplant. 1997;16:691–712.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Hermann Aebert
    • 1
  • Joachim P. Schmitt
    • 1
  • Heribert Schunkert
    • 1
  1. 1.Universität RegensburgRegensburgGermany

Personalised recommendations