Modulation of Inflammatory Response in Cardiopulmonary Bypass

Chapter

Abstract

Cardiac surgery and cardiopulmonary bypass initiate a systemic inflammatory response largely determined by blood contact with foreign surfaces and the activation of complement. It is generally accepted that cardiopulmonary bypass initiates a whole-body inflammatory reaction varies, but the persistence of any degree of inflammation may be considered potentially harmful to the cardiac patient. The development of strategies to control the inflammatory following cardiac surgery is currently the focus of considerable research efforts. Diverse techniques including maintenance of hemodynamic stability, minimization of exposure to cardiopulmonary bypass circuitry, and pharmacologic and immunomodulatory agents have been examined in clinical studies. This chapter provides a brief overview of the various therapeutic strategies being used to modulate the inflammatory response initiated by cardiopulmonary bypass.

Keywords

Convection Ischemia Corticosteroid Aspirin Adenosine 

References

  1. 1.
    Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg. 2002;21:232–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Raja SG, Dreyfus GD. Modulation of systemic inflammatory response after cardiac surgery. Asian Cardiovasc Thorac Ann. 2005;13:382–95.PubMedCrossRefGoogle Scholar
  3. 3.
    Raja SG, Berg GA. Impact of off-pump coronary artery bypass surgery on systemic inflammation: current best available evidence. J Card Surg. 2007;22(5):445–55.PubMedCrossRefGoogle Scholar
  4. 4.
    CEBM. Oxford centre for evidence based medicine. Available at http://www.cebm.net/index.aspx?o=1025. Accessed 7 Oct 2011.
  5. 5.
    Lin CY, Yang TL, Hong GJ, Li CY, Lin FY, Tsai CS. Enhanced intracellular heat shock protein 70 expression of leukocytes and serum interleukins release: comparison of on-pump and off-pump coronary artery surgery. World J Surg. 2010;34:675–81.PubMedCrossRefGoogle Scholar
  6. 6.
    Onorati F, Rubino AS, Nucera S, Foti D, Sica V, Santini F, et al. Off-pump coronary artery bypass surgery versus standard linear or pulsatile cardiopulmonary bypass: endothelial activation and inflammatory response. Eur J Cardiothorac Surg. 2010;37:897–904.PubMedCrossRefGoogle Scholar
  7. 7.
    Serrano Jr CV, Souza JA, Lopes NH, Fernandes JL, Nicolau JC, Blotta MH, et al. Reduced expression of systemic proinflammatory and myocardial biomarkers after off-pump versus on-pump coronary artery bypass surgery: a prospective randomized study. J Crit Care. 2010;25:305–12.PubMedCrossRefGoogle Scholar
  8. 8.
    Rasmussen BS, Laugesen H, Sollid J, Grønlund J, Rees SE, Toft E, et al. Oxygenation and release of inflammatory mediators after ­off-pump compared with after on-pump coronary artery bypass surgery. Acta Anaesthesiol Scand. 2007;51:1202–10.PubMedCrossRefGoogle Scholar
  9. 9.
    Parolari A, Camera M, Alamanni F, Naliato M, Polvani GL, Agrifoglio M, et al. Systemic inflammation after on-pump and off-pump coronary bypass surgery: a one-month follow-up. Ann Thorac Surg. 2007;84:823–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Tatoulis J, Rice S, Davis P, Goldblatt JC, Marasco S. Patterns of postoperative systemic vascular resistance in a randomized trial of conventional on-pump versus off-pump coronary artery bypass graft surgery. Ann Thorac Surg. 2006;82:1436–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Cavalca V, Sisillo E, Veglia F, et al. Isoprostanes and oxidative stress in off-pump and on-pump coronary bypass surgery. Ann Thorac Surg. 2006;81:562–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Wehlin L, Vedin J, Vaage J, Lundahl J. Peripheral blood monocyte activation during coronary artery bypass grafting with or without cardiopulmonary bypass. Scand Cardiovasc J. 2005;39:78–86.PubMedCrossRefGoogle Scholar
  13. 13.
    Wan IY, Arifi AA, Wan S, et al. Beating heart revascularization with or without cardiopulmonary bypass: evaluation of inflammatory response in a prospective randomized study. J Thorac Cardiovasc Surg. 2004;127:1624–31.PubMedCrossRefGoogle Scholar
  14. 14.
    Wehlin L, Vedin J, Vaage J, Lundahl J. Activation of complement and leukocyte receptors during on- and off pump coronary artery bypass surgery. Eur J Cardiothorac Surg. 2004;25:35–42.PubMedCrossRefGoogle Scholar
  15. 15.
    Dorman BH, Kratz JM, Multani MM, et al. A prospective, randomized study of endothelin and postoperative recovery in off-pump versus conventional coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2004;18:25–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Al-Ruzzeh S, Hoare G, Marczin N, et al. Off-pump coronary artery bypass surgery is associated with reduced neutrophil activation as measured by the expression of CD11b: a prospective randomized study. Heart Surg Forum. 2003;6:89–93.PubMedGoogle Scholar
  17. 17.
    Møller CH, Steinbrüchel DA. Platelet function after coronary artery bypass grafting: is there a procoagulant activity after off-pump compared with on-pump surgery? Scand Cardiovasc J. 2003;37:149–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Jemielity MM, Perek B, Buczkowski P, Lesniewska K, Wiktorowicz K, Dyszkiewicz W. Inflammatory response following off-pump and on-pump coronary artery bypass grafting. Heart Surg Forum. 2003;6 Suppl 1:S40–1.Google Scholar
  19. 19.
    Okubo N, Hatori N, Ochi M, Tanaka S. Comparison of m-RNA expression for inflammatory mediators in leukocytes between on-pump and off-pump coronary artery bypass grafting. Ann Thorac Cardiovasc Surg. 2003;9:43–9.PubMedGoogle Scholar
  20. 20.
    Wildhirt SM, Schulze C, Schulz C, et al. Reduction of systemic and cardiac adhesion molecule expression after off-pump versus conventional coronary artery bypass grafting. Shock. 2001;16 Suppl 1:55–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Schulze C, Conrad N, Schutz A, et al. Reduced expression of systemic proinflammatory cytokines after off-pump versus conventional coronary artery bypass grafting. Thorac Cardiovasc Surg. 2000;48:364–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Wildhirt SM, Schulze C, Conrad N, et al. Reduced myocardial cellular damage and lipid peroxidation in off-pump versus conventional coronary artery bypass grafting. Eur J Med Res. 2000;5:222–8.PubMedGoogle Scholar
  23. 23.
    Gulielmos V, Menschikowski M, Dill H, et al. Interleukin-1, interleukin-6 and myocardial enzyme response after coronary artery bypass grafting – a prospective randomized comparison of the conventional and three minimally invasive surgical techniques. Eur J Cardiothorac Surg. 2000;18:594–601.PubMedCrossRefGoogle Scholar
  24. 24.
    Czerny M, Baumer H, Kilo J, et al. Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass. Eur J Cardiothorac Surg. 2000;17:737–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Ascione R, Lloyd CT, Underwood MJ, Lotto AA, Pitsis AA, Angelini GD. Inflammatory response after coronary revascularization with or without cardiopulmonary bypass. Ann Thorac Surg. 2000;69:1198–204.PubMedCrossRefGoogle Scholar
  26. 26.
    Diegeler A, Doll N, Rauch T. Humoral immune response during coronary artery bypass grafting: a comparison of limited approach, “off-pump” technique, and conventional cardiopulmonary bypass. Circulation. 2000;102(19 Suppl 3):III95–100.PubMedGoogle Scholar
  27. 27.
    Matata BM, Sosnowski AW, Galinanes M. Off-pump bypass graft operation significantly reduces oxidative stress and inflammation. Ann Thorac Surg. 2000;69:785–91.PubMedCrossRefGoogle Scholar
  28. 28.
    Gu YJ, Mariani MA, van Oeveren W, Grandjean JG, Boonstra PW. Reduction of the inflammatory response in patients undergoing minimally invasive coronary artery bypass grafting. Ann Thorac Surg. 1998;65:420–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Fromes Y, Gaillard D, Ponzio O, et al. Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation. Eur J Cardiothorac Surg. 2002;22:527–33.PubMedCrossRefGoogle Scholar
  30. 30.
    Gott VL, Whiffen JD, Dutton RC. Heparin bonding on colloidal graphite surfaces. Science. 1963;142:1297–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Gott VL, Daggett RL. Serendipity and the development of heparin and carbon surfaces. Ann Thorac Surg. 1999;68(3 Suppl):S19–22.PubMedCrossRefGoogle Scholar
  32. 32.
    Warren OJ, Watret AL, de Wit KL, et al. The inflammatory response to cardiopulmonary bypass: part 2-anti-inflammatory therapeutic strategies. J Cardiothorac Vasc Anesth. 2009;23:384–93.PubMedCrossRefGoogle Scholar
  33. 33.
    Ranucci M, Mazzucco A, Pessotto R, et al. Heparin-coated circuits for high-risk patients: a multicenter, prospective, randomized trial. Ann Thorac Surg. 1999;67:994–1000.PubMedCrossRefGoogle Scholar
  34. 34.
    te Velthuis H, Baufreton C, Jansen PG, et al. Heparin coating of extracorporeal circuits inhibits contact activation during cardiac operations. J Thorac Cardiovasc Surg. 1997;114:117–22.CrossRefGoogle Scholar
  35. 35.
    Baufreton C, Moczar M, Intrator L, et al. Inflammatory response to cardiopulmonary bypass using two different types of heparin-coated extracorporeal circuits. Perfusion. 1998;13:419–27.PubMedCrossRefGoogle Scholar
  36. 36.
    Lundblad R, Moen O, Fosse E. Endothelin-1 and neutrophil activation during heparin-coated cardiopulmonary bypass. Ann Thorac Surg. 1997;63:1361–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Fosse E, Thelin S, Svennevig JL, et al. Duraflo II coating of cardiopulmonary bypass circuits reduces complement activation, but does not affect the release of granulocyte enzymes: a European multicentre study. Eur J Cardiothorac Surg. 1997;11:320–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Boonstra PW, Gu YJ, Akkerman C, et al. Heparin coating of an extracorporeal circuit partly improves hemostasis after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1994;107:289–92.PubMedGoogle Scholar
  39. 39.
    Mangoush O, Purkayastha S, Haj-Yahia S, et al. Heparin-bonded circuits versus nonheparin-bonded circuits: an evaluation of their effect on clinical outcomes. Eur J Cardiothorac Surg. 2007;31:1058–69.PubMedCrossRefGoogle Scholar
  40. 40.
    Baker RA, Willcox TW. Australian and New Zealand perfusion survey: equipment and monitoring. J Extra Corpor Technol. 2006;38:220–9.PubMedGoogle Scholar
  41. 41.
    Raja SG, Yousufuddin S, Rasool F, Nubi A, Danton M, Pollock J. Impact of modified ultrafiltration on morbidity after pediatric cardiac surgery. Impact of modified ultrafiltration on morbidity after pediatric cardiac surgery. Asian Cardiovasc Thorac Ann. 2006;14:341–50.PubMedCrossRefGoogle Scholar
  42. 42.
    Hiramatsu T, Imai Y, Kurosawa H, et al. Effects of dilutional and modified ultrafiltration in plasma endothelin-1 and pulmonary vascular resistance after the Fontan procedure. Ann Thorac Surg. 2002;73:861–5.PubMedGoogle Scholar
  43. 43.
    Chew MS, Brix-Christensen V, Ravn HB, et al. Effect of modified ultrafiltration on the inflammatory response in paediatric open-heart surgery: a prospective, randomized study. Perfusion. 2002;17:327–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Pearl JM, Manning PB, McNamara JL, Saucier MM, Thomas DW. Effect of modified ultrafiltration on plasma thromboxane B2, leukotriene B4, and endothelin-1 in infants undergoing cardiopulmonary bypass. Ann Thorac Surg. 1999;68:1369–75.PubMedCrossRefGoogle Scholar
  45. 45.
    Portela F, Espanol R, Quintans J. Combined perioperative ultrafiltration in pediatric cardiac surgery. The preliminary results. Rev Esp Cardiol. 1999;52:1075–82.PubMedCrossRefGoogle Scholar
  46. 46.
    Wang W, Huang HM, Zhu DM, Chen H, Su ZK, Ding WX. Modified ultrafiltration in paediatric cardiopulmonary bypass. Perfusion. 1998;13:304–10.PubMedCrossRefGoogle Scholar
  47. 47.
    Journois D, Israel-Biet D, Pouard P, et al. High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children. Anesthesiology. 1996;85:965–76.PubMedCrossRefGoogle Scholar
  48. 48.
    Journois D, Pouard P, Greeley WJ. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Effects on hemostasis, cytokines, and complement components. Anesthesiology. 1994;81:1181–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Saatvedt K, Lindberg H, Geiran OR, et al. Ultrafiltration after cardiopulmonary bypass in children: effects on hemodynamics, cytokines and complement. Cardiovasc Res. 1996;31:596–602.PubMedGoogle Scholar
  50. 50.
    Luciani GB, Menon T, Vecchi B, et al. Modified ultrafiltration reduces morbidity after adult cardiac operations: a prospective, randomized clinical trial. Circulation. 2001;104(12 Suppl 1):I253–9.PubMedGoogle Scholar
  51. 51.
    Grünenfelder J, Zünd G, Schoeberlein A, et al. Modified ultrafiltration lowers adhesion molecule and cytokine levels after cardiopulmonary bypass without clinical relevance in adults. Eur J Cardiothorac Surg. 2000;17:77–83.PubMedCrossRefGoogle Scholar
  52. 52.
    Boodhwani M, Williams K, Babaev A, et al. Ultrafiltration reduces blood transfusions following cardiac surgery: a meta-analysis. Eur J Cardiothorac Surg. 2006;30:892–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Williams GD, Ramamoorthy C, Chu L, et al. Modified and conventional ultrafiltration during pediatric cardiac surgery: clinical outcomes compared. J Thorac Cardiovasc Surg. 2006;132:1291–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Gu YJ, de Vries AJ, Boonstra PW, van Oeveren W. Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery. J Thorac Cardiovasc Surg. 1996;112:494–500.PubMedCrossRefGoogle Scholar
  55. 55.
    Gu YJ, de Vries AJ, Vos P, Boonstra PW, van Oeveren W. Leukocyte depletion during cardiac operation: a new approach through the venous bypass circuit. Ann Thorac Surg. 1999;67:604–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Johnson D, Thomson D, Mycyk T, Burbridge B, Mayers I. Depletion of neutrophils by filter during aortocoronary bypass surgery transiently improves postoperative cardiorespiratory status. Chest. 1995;107:1253–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Morioka K, Muraoka R, Chiba Y, et al. Leukocyte and platelet depletion with a blood cell separator: effects on lung injury after cardiac surgery with cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1996;111:45–54.PubMedCrossRefGoogle Scholar
  58. 58.
    Di Salvo C, Louca LL, Pattichis K, Hooper J, Walesby RK. Does activated neutrophil depletion on bypass by leukocyte filtration reduce myocardial damage? A preliminary report. J Cardiovasc Surg (Torino). 1996;37(6 Suppl 1):93–100.Google Scholar
  59. 59.
    Hurst T, Johnson D, Cujec B, et al. Depletion of activated neutrophils by a filter during cardiac valve surgery. Can J Anaesth. 1997;44:131–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Baksaas ST, Flom-Halvorsen HI, Ovrum E, et al. Leucocyte filtration during cardiopulmonary reperfusion in coronary artery bypass surgery. Perfusion. 1999;14:107–17.PubMedCrossRefGoogle Scholar
  61. 61.
    Roth M, Kraus B, Scheffold T, et al. The effect of leukocyte-depleted blood cardioplegia in patients with severe left ventricular dysfunction: a randomized, double-blind study. J Thorac Cardiovasc Surg. 2000;120:642–50.PubMedCrossRefGoogle Scholar
  62. 62.
    De Vecchi E, Paroni R, Pala MG, et al. Role of leucocytes in free radical production during myocardial revascularisation. Heart. 1997;77:449–55.PubMedGoogle Scholar
  63. 63.
    Sawa Y, Taniguchi K, Kadoba K, et al. Leukocyte depletion attenuates reperfusion injury in patients with left ventricular hypertrophy. Circulation. 1996;93:1640–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Andersen KS, Nygreen EL, Grong K, Leirvaag B, Holmsen H. Comparison of the centrifugal and roller pump in elective coronary artery bypass surgery – a prospective, randomized study with special emphasis upon platelet activation. Scand Cardiovasc J. 2003;37:356–62.PubMedCrossRefGoogle Scholar
  65. 65.
    Klein M, Dauben HP, Schulte HD, Gams E. Centrifugal pumping during routine open heart surgery improves clinical outcome. Artif Organs. 1998;22:326–36.PubMedCrossRefGoogle Scholar
  66. 66.
    Klein M, Mahoney CB, Probst C, Schulte HD, Gams E. Blood product use during routine open heart surgery: the impact of the centrifugal pump. Artif Organs. 2001;25:300–5.PubMedCrossRefGoogle Scholar
  67. 67.
    Menasché P, Peynet J, Haeffner-Cavaillon N. Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass. Circulation. 1995;92(9 Suppl):II334–40.PubMedGoogle Scholar
  68. 68.
    Birdi I, Caputo M, Underwood M, Bryan AJ, Angelini GD. The effects of cardiopulmonary bypass temperature on inflammatory response following cardiopulmonary bypass. Eur J Cardiothorac Surg. 1999;16:540–5.PubMedCrossRefGoogle Scholar
  69. 69.
    McLean RF, Wong BI. Normothermic versus hypothermic cardiopulmonary bypass: central nervous system outcomes. J Cardiothorac Vasc Anesth. 1996;10:45–52.PubMedCrossRefGoogle Scholar
  70. 70.
    Shann KG, Likosky DS, Murkin JM, et al. An evidence-based review of the practice of cardiopulmonary bypass in adults: a focus on neurologic injury, glycemic control, hemodilution, and the inflammatory response. J Thorac Cardiovasc Surg. 2006;132:283–90.PubMedCrossRefGoogle Scholar
  71. 71.
    Wan S, LeClerc JL, Huynh CH, et al. Does steroid pretreatment increase endotoxin release during clinical cardiopulmonary bypass? J Thorac Cardiovasc Surg. 1999;117:1004–8.PubMedCrossRefGoogle Scholar
  72. 72.
    Dernek S, Tunerir B, Sevin B, et al. The effects of methylprednisolone on complement, immunoglobulins and pulmonary neutrophil sequestration during cardiopulmonary bypass. Cardiovasc Surg. 1999;7:414–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Kawamura T, Inada K, Nara N, Wakusawa R, Endo S. Influence of methylprednisolone on cytokine balance during cardiac surgery. Crit Care Med. 1999;27:545–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Jansen NJ, van Oeveren W, van Vliet M, et al. The role of different types of corticosteroids on the inflammatory mediators in cardiopulmonary bypass. Eur J Cardiothorac Surg. 1991;5:211–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Tassani P, Richter JA, Barankay A, et al. Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures? J Cardiothorac Vasc Anesth. 1999;13:165–72.PubMedCrossRefGoogle Scholar
  76. 76.
    Kawamura T, Inada K, Okada H, Okada K, Wakusawa R. Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery. Can J Anaesth. 1995;42:399–403.PubMedCrossRefGoogle Scholar
  77. 77.
    Yilmaz M, Ener S, Akalin H, Sagdic K, Serdar OA, Cengiz M. Effect of low-dose methyl prednisolone on serum cytokine levels following extracorporeal circulation. Perfusion. 1999;14:201–6.PubMedCrossRefGoogle Scholar
  78. 78.
    van Overveld FJ, De Jongh R, Jorens PG, et al. Pretreatment with methylprednisolone in coronary artery bypass grafting influences the levels of histamine and tryptase in serum but not in bronchoalveolar lavage fluid. Clin Sci (Lond). 1994;86:49–53.Google Scholar
  79. 79.
    Lodge AJ, Chai PJ, Daggett CW, Ungerleider RM, Jaggers J. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal piglets: timing of dose is important. J Thorac Cardiovasc Surg. 1999;117:515–22.PubMedCrossRefGoogle Scholar
  80. 80.
    Robertson-Malt S, Afrane B, El Barbary M. Prophylactic steroids for pediatric open heart surgery. Cochrane Database Syst Rev. 2007;(4):CD005550.Google Scholar
  81. 81.
    Dieleman JM, van Paassen J, van Dijk D, et al. Prophylactic corticosteroids for cardiopulmonary bypass in adults. Cochrane Database Syst Rev. 2011;(5):CD005566.Google Scholar
  82. 82.
    Eagle KA, Guyton RA, Davidoff R, American College of Cardiology; American Heart Association. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation. 2004;110:e340–437.PubMedCrossRefGoogle Scholar
  83. 83.
    Castiglioni GC, Lojacono L, Tamborini G. Effects of trypsin and kallikrein inhibition in acute pancreatitis. Arch Ital Chir. 1965;91:365–76.PubMedGoogle Scholar
  84. 84.
    Royston D, Bidstrup BP, Taylor KM, Sapsford RN. Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet. 1987;2:1289–91.PubMedCrossRefGoogle Scholar
  85. 85.
    Poullis M, Manning R, Laffan M, et al. The antithrombotic effect of aprotinin: actions mediated via the proteaseactivated receptor 1. J Thorac Cardiovasc Surg. 2000;120:370–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Greilich PE, Brouse CF, Whitten CW, et al. Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: a randomized, double-blind, placebo-controlled study of epsilon-aminocaproic acid and aprotinin. J Thorac Cardiovasc Surg. 2003;126:1498–503.PubMedCrossRefGoogle Scholar
  87. 87.
    Hill GE, Pohorecki R, Alonso A, Rennard SI, Robbins RA. Aprotinin reduces interleukin-8 production and lung neutrophil accumulation after cardiopulmonary bypass. Anesth Analg. 1996;83:696–700.PubMedGoogle Scholar
  88. 88.
    Wendel HP, Heller W, Michel J, et al. Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage. J Thorac Cardiovasc Surg. 1995;109:1164–72.PubMedCrossRefGoogle Scholar
  89. 89.
    Levi M, Cromheecke ME, de Jonge E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet. 1999;354:1940–7.PubMedCrossRefGoogle Scholar
  90. 90.
    Mangano DT, Tudor IC, Dietzel C, Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006;354:353–65.PubMedCrossRefGoogle Scholar
  91. 91.
    Karkouti K, Beattie WS, Dattilo KM, et al. A propensity score case–control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion. 2006;46:327–38.PubMedCrossRefGoogle Scholar
  92. 92.
    Fergusson DA, Hébert PC, Mazer CD, BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358:2319–31.PubMedCrossRefGoogle Scholar
  93. 93.
    Ray WA, Stein CM. The aprotinin story – is BART the final chapter? N Engl J Med. 2008;358:2398–400.PubMedCrossRefGoogle Scholar
  94. 94.
    Sun SC, Appleyard R, Masetti P, et al. Improved recovery of heart transplants by combined use of oxygen-derived free radical scavengers and energy enhancement. J Thorac Cardiovasc Surg. 1992;104:830–7.PubMedGoogle Scholar
  95. 95.
    Julia PL, Buckberg GD, Acar C, Partington MT, Sherman MP. Studies of controlled reperfusion after ischemia. XXI. Reperfusate composition: superiority of blood cardioplegia over crystalloid cardioplegia in limiting reperfusion damage-importance of endogenous oxygen free radical scavengers in red blood cells. J Thorac Cardiovasc Surg. 1991;101:303–13.PubMedGoogle Scholar
  96. 96.
    Yau TM, Weisel RD, Mickle DA. Vitamin E for coronary bypass operations. A prospective, double-blind, randomized trial. J Thorac Cardiovasc Surg. 1994;108:302–10.PubMedGoogle Scholar
  97. 97.
    Sisto T, Paajanen H, Metsä-Ketelä T, et al. Pretreatment with antioxidants and allopurinol diminishes cardiac onset events in coronary artery bypass grafting. Ann Thorac Surg. 1995;59:1519–23.PubMedCrossRefGoogle Scholar
  98. 98.
    Fitch JC, Rollins S, Matis L, et al. Pharmacology and biological efficacy of a recombinant, humanized, single-chain antibody C5 complement inhibitor in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. Circulation. 1999;100:2499–506.PubMedCrossRefGoogle Scholar
  99. 99.
    Soulika AM, Khan MM, Hattori T, et al. Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons. Clin Immunol. 2000;96:212–21.PubMedCrossRefGoogle Scholar
  100. 100.
    Kirschfink M. Controlling the complement system in inflammation. Immunopharmacology. 1997;38:51–62.PubMedCrossRefGoogle Scholar
  101. 101.
    Takeuchi K, del Nido PJ, Ibrahim AE, et al. Vesnarinone and amrinone reduce the systemic inflammatory response syndrome. J Thorac Cardiovasc Surg. 1999;117:375–82.PubMedCrossRefGoogle Scholar
  102. 102.
    Mollhoff T, Loick HM, Van Aken H, Schmidt C, Rolf N, Tjan TD, et al. Milrinone modulates endotoxemia, systemic inflammation, and subsequent acute phase response after cardiopulmonary bypass (CPB). Anesthesiology. 1999;90:72–80.PubMedCrossRefGoogle Scholar
  103. 103.
    McNicol L, Andersen LW, Liu G, Doolan L, Baek L. Markers of splanchnic perfusion and intestinal translocation of endotoxins during cardiopulmonary bypass: effects of dopamine and milrinone. J Cardiothorac Vasc Anesth. 1999;13:292–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Berendes E, Mollhoff T, Van Aken H, et al. Effects of dopexamine on creatinine clearance, systemic inflammation, and splanchnic oxygenation in patients undergoing coronary artery bypass grafting. Anesth Analg. 1997;84:950–7.PubMedGoogle Scholar
  105. 105.
    Sinclair DG, Houldsworth PE, Keogh B, Pepper J, Evans TW. Gastrointestinal permeability following cardiopulmonary bypass: a randomised study comparing the effects of dopamine and dopexamine. Intensive Care Med. 1997;23:510–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Shafique T, Johnson RG, Dai HB, Weintraub RM, Sellke FW. Altered pulmonary microvascular reactivity after total cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1993;106:479–86.PubMedGoogle Scholar
  107. 107.
    Livelli Jr FD, Johnson RA, McEnany MT. Unexplained in-­hospital fever following cardiac surgery. Natural history, relationship to postpericardiotomy syndrome, and a prospective study of therapy with indomethacin versus placebo. Circulation. 1978;57:968–75.PubMedCrossRefGoogle Scholar
  108. 108.
    Mobert J, Becker BF. Cyclooxygenase inhibition aggravates ischemia-reperfusion injury in the perfused guinea pig heart: involvement of isoprostanes. J Am Coll Cardiol. 1998;31:1687–94.PubMedCrossRefGoogle Scholar
  109. 109.
    Hindman BJ, Moore SA, Cutkomp J, et al. Brain expression of inducible cyclooxygenase 2 messenger RNA in rats undergoing cardiopulmonary bypass. Anesthesiology. 2001;95:1380–8.PubMedCrossRefGoogle Scholar
  110. 110.
    Erez E, Erman A, Snir E, et al. Thromboxane production in human lung during cardiopulmonary bypass: beneficial effect of aspirin? Ann Thorac Surg. 1998;65:101–6.PubMedCrossRefGoogle Scholar
  111. 111.
    Sato K, Li J, Metais C, Bianchi C, Sellke F. Increased pulmonary vascular contraction to serotonin after cardiopulmonary bypass: role of cyclooxygenase. J Surg Res. 2000;90:138–43.PubMedCrossRefGoogle Scholar
  112. 112.
    Yang X, Ma N, Szabolcs MJ, Zhong J, Athan E, Sciacca RR, et al. Upregulation of COX-2 during cardiac allograft rejection. Circulation. 2000;101:430–8.PubMedCrossRefGoogle Scholar
  113. 113.
    Bouchard JF, Lamontagne D. Mechanisms of protection afforded by cyclooxygenase inhibitors to endothelial function against ischemic injury in rat isolated hearts. J Cardiovasc Pharmacol. 1999;34:755–63.PubMedCrossRefGoogle Scholar
  114. 114.
    Grandel U, Fink L, Blum A, et al. Endotoxin-induced myocardial tumor necrosis factor-alpha synthesis depresses contractility of isolated rat hearts: evidence for a role of sphingosine and cyclooxygenase-2-derived thromboxane production. Circulation. 2000;102:2758–64.PubMedCrossRefGoogle Scholar
  115. 115.
    Friedrich I, Silber RE, Baumann B, Fischer C, Holzheimer RG. IgM-enriched immunoglobulin preparation for immunoprophylaxis in cardiac surgery. Eur J Med Res. 2002;7:544–9.PubMedGoogle Scholar
  116. 116.
    Opal SM, Gluck T. Endotoxinas a drug target. Crit Care Med. 2003;31(1 Suppl):S57–64.PubMedCrossRefGoogle Scholar
  117. 117.
    Goldie AS, Fearon KC, Ross JA. Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group. JAMA. 1995;274:172–7.PubMedCrossRefGoogle Scholar
  118. 118.
    Martinez-Pellus AE, Merino P, Bru M. Endogenous endotoxemia of intestinal origin during cardiopulmonary bypass. Role of type of flow and protective effect of selective digestive decontamination. Intensive Care Med. 1997;23:1251–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence. Arch Surg. 1999;134:170–6.PubMedCrossRefGoogle Scholar
  120. 120.
    Engelman DT, Adams DH, Byrne JG, et al. Impact of body mass index and albumin on morbidity and mortality after cardiac surgery. J Thorac Cardiovasc Surg. 1999;118:866–73.PubMedCrossRefGoogle Scholar
  121. 121.
    Walesby RK, Goode AW, Bentall HH. Nutritional status of patients undergoing valve replacement by open heart surgery. Lancet. 1978;1:76–7.PubMedCrossRefGoogle Scholar
  122. 122.
    Abel RM, Grimes JB, Alonso D, Alonso M, Gay WA. Adverse hemodynamic and ultrastructural changes in dog hearts subjected to protein-calorie malnutrition. Am Heart J. 1979;97:733–44.PubMedCrossRefGoogle Scholar
  123. 123.
    Gianotti L, Braga M, Vignali A, et al. Effect of route of delivery and formulation of postoperative nutritional support in patients undergoing major operations for malignant neoplasms. Arch Surg. 1997;132:1222–30.PubMedCrossRefGoogle Scholar
  124. 124.
    Braga M, Gianotti L, Radaelli G, et al. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg. 1999;134:428–33.PubMedCrossRefGoogle Scholar
  125. 125.
    Griffiths RD. Outcome of critically ill patients after supplementation with glutamine. Nutrition. 1997;13:752–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of Cardiac SurgeryHarefield HospitalLondonUK

Personalised recommendations