Proinflammatory cytokines, including tumor necrosis factor (TNF) α and the interieukins, are important in the metabolic response to injury or infection. Although the importance of cytokine release during cardiopulmonary bypass (CPB) is not fully appreciated, increasing num bers of publications present evidence that cytokine release during CPB is detrimental. In addition, endoge nous inhibitors of cytokine function, including TNF-sol uble receptor and interleukin 1 receptor antagonist, are released in response to elevated proinflammatory cyto kine levels during and after CPB. The involvement of these endogenous inhibitors in the pathophysiology of proinflammatory cytokine-induced solid organ injury after CPB remains to be defined.
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References
1.
Billiau A., Vandederckhove F.: Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock. Eur J Clin Invest21:559-73, 1991
2.
Jansen Njg, van Oeveren W., Gu YJ, et al: Endotoxin release and tumor necrosis factor formation during cardiopulmonary bypass. Ann Thorac Surg54:744-748, 1992
3.
Bennett-Guerrero E., Ayuso L., Hamilton-Davies C., et al: Relationship of preoperative antiendotoxin core antibodies and adverse outcomes following cardiac surgery. JAMA277:646-650, 1997
4.
Andersen LW, Landow L., Baek L., et al: Association between gastric intramucosal pH and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor-a concentrations in patients undergoing cardiopulmonary bypass. Crit Care Med21:210-217, 1993
5.
Tao W., Zwishchenberger JB, Nguyen TT, et al: Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand. J Thorac Cardiovasc Surg110:819-828, 1995
6.
Oudemans-van Straaten HM, Jansen Pgm, Hoek FJ, et al: Intestinal permeability, circulating endotoxin, and postoperative systemic responses in cardiac surgery patients . J Cardiothorac Vasc Anesth10:287-294, 1996
7.
Martinez-Pellus AE, Merino P., Bru M., et al: Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass ?Crit Care Med21:1684-1691, 1993
8.
Dinarello CA , Cannon JG, Wolff SM, et al: Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin-1. J Exp Med163: 1433-1450, 1986
9.
Lowry SF: Cytokine mediators of immunity and inflammation. Arch Surg128:1235-1241, 1993
10.
Hall RI, Smith MS, Rocker G.: The systemic inflammatory response to cardiopulmonary bypass: Pathophysiologic, therapeutic, and pharmacological considerations. Anesth Analg85:766-782, 1997
11.
Tulla H., Takala J., Alhava E., et al: Hypermetabolism after coronary artery bypass. J Thorac Cardiovasc Surg101: 598-600, 1991
12.
Hennein HA, Ebba H., Rodriguez JL, et al: Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. J Thorac Cardiovasc Surg108:626-635, 1994
13.
Cremer J., Martin M., Redl H., et al: Systemic inflammatory response syndrome after cardiac operations . Ann Thorac Surg61:1714-1720, 1996
14.
Deng MC, Dasch B., Erren M., et al: Impact of left ventricular dysfunction on cytokines, hemodynamics, and outcome in bypass grafting. Ann Thorac Surg62:184-190, 1996
15.
Whitten CW, Hill GE, Ivy R., et al: Does the duration of cardiopulmonary bypass or aortic cross-clamp, in the absence of blood and/or blood product administration, influence the IL-6 response to cardiac surgery? Anesth Analg86:28-33, 1998
16.
Torre-Amione G., Kapadia S., Lee J., et al: Tumor necrosis factor-α and tumor necrosis factor receptors in the failing human heart. Circulation93:704-711, 1996
17.
Seghaye MC, Grabitz RG, Duchateau J., et al: Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations. J Thorac Cardiovasc Surg112:687-697, 1996
18.
Kumar A., Thota V., Dee L., et al: Tumor necrosis factor α and interleukin 1β are responsible for in vitro myocardial cell depression induced by human septic shock serum . J Exp Med183:949-958, 1996
19.
Emala CW, Kuhl J., Hungerford CL, et al: TNF inhibits isoproterenol-stimulated adenylate cyclase activity in cultured airway smooth muscle cells. Am J Physiol272: L644-L650, 1997
20.
Yamamoto S. , Tsutsui H., Tagawa H., et al: Role of myocyte nitric oxide in β-adrenergic hyporesponsiveness in heart failure. Circulation95:1111-1114, 1997
21.
Schwinn DA, Leone BJ, Spahn DR, et al: Desensitization of myocardial β-adrenergic receptors during cardiopulmonary bypass. Circulation84:2559-2567, 1997
22.
Avall A., Hyllner M., Bengtson JP, et al: Postoperative inflammatory response after autologous and allogeneic blood transfusion. Anesthesiology87:511-516, 1997
23.
Arnaout MA: Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood75:1037-1050, 1990
24.
Kukielka GL , Smith CW, Manning AM, et al: Induction of interleukin-6 synthesis in the myocardium. Circulation92:1866-1875, 1995
25.
Kilbride PM , Mayer JE, Newberger JW, et al: Induction of intercellular adhesion molecule-1 and E-selectin mRNA in heart and skeletal muscle of pediatric patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg107:1183-1192, 1994
26.
Wilson I., Gillinov AM, Curtis WE, et al: Inhibition of neutrophil adherence improves postischemic ventricular performance of the neonatal heart. Circulation88: 372-379, 1993
27.
Entman ML, Youker KA, Shojit T., et al: Neutrophil-induced oxidative injury of cardiac myocytes: A compartmented system requiring CD11b/CD18-ICANI-I adherence. J Clin Invest90:1335-1345, 1992
28.
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 Surg111:45-54, 1996
29.
Chiba Y., Morioka K., Muraoka R., et al: Effects of depletion of leukocytes and platelets on cardiac dysfunction after cardiopulmonary bypass. Ann Thorac Surg65:107-114, 1998
30.
Mocada S., Higgs A.: The L-arginine-nitric oxide pathway. N Engl J Med329:2002-2012, 1993
31.
Radi R., Beckman JS, Bush KM, et al: Peroxynitrite oxidation of sulfhydryls. J Biol Chem266:4244-4250, 1991
32.
Depre C., Vanoverschelde J.Goudemant J., et al: Protection against ischemic injury by nonvasoactive concentrations of nitric oxide synthase inhibitors in the perfused rabbit heart. Circulation92:1911-1918, 1995
33.
Szabo C., Southan GJ, Thiemermann C.: Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase. Proc Natl Acad Sci USA91:12471-12476, 1994
34.
Finkel MS, Oddis CV, Jacob TD, et al: Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science257:387-389, 1992
35.
Ruvolo G., Greco E., Speziale G., et al: Nitric oxide formation during cardiopulmonary bypass. Ann Thorac Surg57:1055-1056, 1994
36.
Hill GE, Snider S., Galbraith T., et al: Glucocorticoids reduce bronchial epithelial inflammation during cardiopulmonary bypass. Am J Respir Crit Care Med152:1791-1795, 1995
37.
Delgado R., Rojas A., Glaria LA, et al: CA2+-independent nitric oxide synthase activity in human lung after cardiopulmonary bypass. Thorax50:403-404, 1995
38.
De Graaf JC , Banga JD, Moncada S., et al: Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation85:2284-2290, 1992
39.
Szabolcs M. , Michler RE, Yang X., et al: Apoptosis of cardiac myocytes during cardiac allograft rejection. Circulation94:1665-1673, 1996
40.
Haywood GA, Tsao PS, von der Leyen HE, et al: Expression of inducible nitric oxide synthase in human heart failure. Circulation93:1087-1094, 1996
41.
Brady Ajb, Warren JB, Poole-Wilson PA, et al: Nitric oxide attenuates cardiac myocyte contraction. Am J Physiol265:H176-H182, 1993
42.
Ungureanu-Longrois D., Balligand JL, Kelly RA, et al: Myocardial contractile dysfunction in the systemic inflammatory response syndrome: Role of a cytokine-inducible nitric oxide synthase in cardiac myocytes. J Mol Cell Cardiol27:155-167, 1995
43.
Tseng EE, Brock MV, Lange MS, et al: Neuronal nitric oxide synthase inhibition reduces neuronal apoptosis after hypothermic circulatory arrest. Ann Thorac Surg64:1639-1647, 1997
44.
Kelly RA, Smith TW: Cytokines and cardiac contractile function. Circulation95:778-781, 1997
45.
Niazi Z., Flodin P., Joyce L., et al: Effect of glucocorticosteroids in patients undergoing coronary artery bypass surgery. Chest76:262-268, 1979
46.
Fecht DC, Magovern GJ, Park SB, et al: Beneficial effects of methylprednisolone in patients on cardiopulmonary bypass. Circ Shock5:415-422, 1978
47.
Teoh Kht, Bradley CA, Gauldie J., et al: Steroid inhibition of cytokine-mediated vasodilation after warm heart surgery. Circulation92:1137-1153, 1995 (suppl II)
48.
Waage A., Slupphaug G., Shalaby R.Glucocorticoids inhibit the production of IL-6 from monocytes, endothelial cells, and fibroblasts. Eur J Immunol20:2439-2943, 1990
49.
Tabardel Y. , Duchateau J., Schmartz D., et al: Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men. Surgery119:76-80, 1996
50.
Cronstein BN , Kimmel SC, Levin RI, et al: A mechanism for the antiinflammatory effects of corticosteroids: The glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Proc Natl Acad Sci USA89:9991-9995, 1992
51.
Hill GE, Alonso A., Thiele GM, et al: Glucocorticoids blunt neutrophil CD11b surface glycoprotein upregulation during cardiopulmonary bypass in humans. Anesth Analg79:23-27, 1994
52.
Radomski MW , Palmer Rmj, Moncada S.: Glucocorticoids inhibit the expression of an inducible, but not the contitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA87:10043-10047, 1990
53.
Butler J., Chong GL, Baigrie RJ, et al: Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg53:833-838, 1992
54.
Steinberg BM , Grossi EA, Schwartz DS, et al: Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass. Ann Thorac Surg60:525-529, 1995
55.
Redmond JM, Gillinov AM, Stuart RS, et al: Heparin-coated bypass circuits reduce pulmonary injury. Ann Thorac Surg56:474-479, 1993
56.
Journois D. , Pouard P.Greeley WJ, et al: Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Anesthesiology81:1181-1189, 1994
57.
Millar AB, Armstrong L., van der Linden J., et al: Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass. Ann Thorac Surg56:1499-1502, 1993
58.
Menasche P. , Haydar S., Peynet J., et al: A potential mechanism of vasodilation after warm heart surgery. J Thorac Cardiovasc Surg107:292-299, 1994
59.
Le Deist F. , Menasche P., Kucharski C., et al: Hypothermia during cardiopulmonary bypass delays but does not prevent neutrophil-endothelial cell adhesion. Circulation92:11345-11348, 1995 (suppl II)
60.
Roytblat L. , Talmor D., Rachinsky M., et al: Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass. Anesth Analg87:266-271, 1998
61.
Larsen B., Hoff G., Wilhelm W., et al: Effect of intravenous anesthetics on spontaneous and endotoxin-stimulated cytokine response in cultured human whole blood. Anesthesiology89:1218-1227, 1998
62.
Shimaoka M. , Iida T., Ohara A., et al: Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells. Br J Anaesth77:238-242, 1996
63.
Kim KU, Kwon OF, Jue DM: Pro-tumour necrosis factor cleavage enzyme in macrophage membrane/particulate . Immunology80:134-139, 1993
64.
Kim H., Lee HS, Change KT, et al: Chloromethyl ketones block induction of nitric oxide synthase in murine macrophages by preventing activation of nuclear factor-kB. J Immunol154:4741-4748, 1995
65.
Hill GE, Taylor JA, Robbins RA: Differing effects of aprotinin and e-aminocaproic acid on cytokine-induced inducible nitric oxide synthase expression. Ann Thorac Surg63:74-77, 1997
66.
Hill GE, Alonso A., Spurzem JR, et al: Aprotinin and methylpredisolone equally blunt cardiopulmonary bypass-induced inflammation in humans. J Thorac Cardiovasc Surg110:1658-1662, 1995
67.
Hill GE, Springall DR, Robbins RA: Aprotinin is associated with a decrease in nitric oxide production during cardiopulmonary bypass. Surgery121:449-455, 1997
68.
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 Surg109:1164-1172, 1995
69.
Aoki M., Jonas RA, Nomura F., et al: Effects of aprotinin on acute recovery of cerebral metabolism in piglets after hypothermic circulatory arrest. Ann Thorac Surg58:146-153, 1994
70.
Becket MA, Brannan J., Fleming J., et al: The effect of high dose aprotonin therapy on the systemic inflammatory response in a porcine model of cardiopulmonary bypass. Perfusion11:278-280, 1996
71.
Mollhoff T. , Loick HM, Van Aken H., et al: Milrinone modulates endotoxemia, systemic inflammation, and subsequent acute phase response after cardiopulmonary bypass (CPB). Anesthesiology90:72-80, 1999
