Biochemistry of Serine Protease Inhibitors and Their Mechanisms of Action: A Review

Journal of Extra-Corporeal Technology

Volumn 35, Issue 4, 2003, Pages 326-338

  Wegner, Julie ^a  

^a UNIVERSITY OF ARIZONA   (United States)

Author keywords

Aprotinin; Cardiopulmonary bypass; Fibrinolysis; Hemostasis; Platelet; Serine protease inhibitor

Indexed keywords

ACTIVATED PROTEIN C; APROTININ; CYTOKINE; KALLIKREIN; NITRIC OXIDE; OXYGEN RADICAL; PLASMIN; SERINE PROTEINASE INHIBITOR;

ANTICOAGULATION; BIOCHEMISTRY; CARDIOPULMONARY BYPASS; DOSE RESPONSE; DRUG EFFICACY; DRUG MECHANISM; FIBRINOLYSIS; HEMOSTASIS; INFLAMMATION; POSTOPERATIVE HEMORRHAGE; REVIEW; THROMBOCYTE; VASCULAR ENDOTHELIUM;

EID: 0942298084     PISSN: 00221058     EISSN: 29698960     Source Type: Journal    
DOI: None     Document Type: Review

References (128)

1. Despotis GJ, Hogue CW. Pathophysiology, prevention, and treatment of bleeding after cardiac surgery: A primer for cardiologists and an update for the cardiothoracic team. Am J Cardiol. 1999;83: 15B-30B.
2. Levy JH. Hemostatic agents and their safety. J Cardiothorac Vasc Anesth. 1999;13(Suppl 4):6-11.
3. Laupacis A, Fergusson D. Drugs to minimize perioperative blood loss in cardiac surgery: Meta-analysis using perioperative blood transfusion as the outcome. Anesth Analg. 1997;85:1258-67.
4. Sato T, Tanaka K, Kondo C, et al. Nafamostat mesilate administration during cardiopulmonary bypass decreases postoperative bleeding after cardiac surgery. ASAIO Trans. 1991;37:M194-5.
5. Murase M, Usui A, Tomita Y, Maeda M, Koyama T, Abe T. Nafamostat mesilate reduces blood loss during open-heart surgery. Circulation. 1993;88(part 2):432-6.
6. Tanaka K, Kondo C, Takagi K, et al. Effects of nafamostat mesilate on platelets and coagulofibrinolysis during cardiopulmonary bypass surgery. ASAIO J. 1993;39:M545-9.
7. Fritz H, Wunderer G. Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. Arzneim Forsch. 1983; 33:479-94.
8. Peters DC, Noble S. Aprotinin. An update of its pharmacology and therapeutic use in open-heart surgery and coronary artery bypass surgery. Drugs. 1999;57:233-60.
9. Christensen V, Schiodt J. Effects of aprotinin on coagulation and fibrinolysis enzymes. Fibrinoly Proteoly. 1997;11:209-14.
10. Edmunds LH. Invited letter concerning: topical aprotinin. J Thorac Cardiovasc Surg. 1995;109:400-1.
11. Terrell MR, Walenga JM, Koza MJ, Pifarre R. Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass. Ann Thorac Surg. 1996;62:506-11.
12. Royston D. Aprotinin versus lysine analogues: The debate continues. Ann Thorac Surg. 1998;65:S9-19.
13. Dietrich W, Schopf K, Spannagl M, Jochum M, Braun SL, Meisner H. Influence of high- and low-dose aprotinin on activation of hemostasis in open-heart operations. Ann Thorac Surg. 1998;65: 70-8.
14. Beath SM, Nuttall GA, Fass DN, Oliver WC, Ereth MH, Oyen LJ. Plasma aprotinin concentrations during cardiac surgery: Full-versus half-dose regimens. Anesth Analg. 2000;91:257-64.
15. Smith PK, Muhlbaier LH. Aprotinin: Safe and effective only with the full-dose regimen. Ann Thorac Surg. 1996;62:1575-7.
16. Levy JH, Bailey JM, Salmenpera M. Pharmacokinetics of aprotinin in preoperative cardiac surgical patients. Anesthesiology. 1994;80: 1013-8.
17. Bennett-Guerrero E, Sorohan JG, Howell ST, et al. Maintenance of therapeutic plasma aprotinin levels during prolonged cardiopulmonary bypass using a large-dose regimen. Anesth Analg. 1996;83: 1189-92.
18. Hayashida N, Isomura T, Sato T, Maruyama H, Kosuga K, Aoyagi S. Effects of minimal-dose aprotinin on coronary artery bypass grafting. J Thorac Cardiovasc Surg. 1997;114:261-9.
19. Cicek S, Demirkilic U, Kuralay E, Ozal E, Tatar H. Postoperative aprotinin: Effect on blood loss and transfusion requirements in cardiac operations. Ann Thorac Surg. 1996;61:1372-6.
20. Boldt J, Knothe C, Zickman B, Bill S, Dapper F, Hempelmann G. Platelet function in cardiac surgery: Influence of temperature and aprotinin. Ann Thorac Surg. 1993;55:652-8.
21. Kawasuji M, Ueyama K, Sakakibara N, et al. Effect of low-dose aprotinin on coagulation and fibrinolysis in cardiopulmonary bypass. Ann Thorac Surg. 1993;55:1205-9.
22. Blauhut B, Harringer W, Bettelheim P, Doran JE, Spath P, Lundsgaard-Hansen P. Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1994;108:1083-91.
23. Royston D. Preventing the inflammatory response to open-heart surgery: The role of aprotinin and other protease inhibitors. Int J Cardiol. 1996;53(Suppl):S11-37.
24. Ray MJ, Marsh NA. Aprotinin reduces blood loss after cardiopulmonary bypass by direct inhibition of plasmin. Thromb Haemost. 1997;78:1021-6,
25. Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs. 1985;29:236-61.
26. 2-plasmin inhibitor deficiency. Am J Hematol. 1994;45:16-24.
27. 2-antiplasmin activity. Role in the evaluation and management of fibrinolytic states and other bleeding disorders. Arch Intern Med. 1989;149:1769-72.
28. Hill GE, Springall DR, Robbins RA. Aprotinin is associated with a decrease in nitric oxide production during cardiopulmonary bypass. Surgery. 1997;121:449-55.
29. Stoddart RW, Kiernan JA. Aprotinin, a carbohydrate-binding protein. Histochemie. 1973;34:275-80.
30. Thomson AW, Pugh-Humphreys RGP, Tweedie J, Horne CHW. Effects of the antiprotease Trasylol on peripheral blood leucocytes. Experimentia. 1977;34:528-30.
31. Spanier TB, Chen JM, Oz MC, et al. Selective anticoagulation with active site-blocked factor IXa suggests separate roles for intrinsic and extrinsic coagulation pathways in cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1998;116:860-9.
32. Burman JF, Chung HI, Lane DA, Philippou H, Adami A, Lincoln JCR. Role of factor XII in thrombin generation and fibrinolysis during cardiopulmonary bypass. Lancet. 1994;344:1192-3.
33. Salmenpera M, Rasi V, Mattila S. Cardiopulmonary bypass in a patient with factor XII deficiency. Anesthesiology. 1991;75:539-41.
34. Boisclair MD, Lane DA, Philippou H, et al. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood. 1993;82:3350-7.
35. Parratt R, Hunt BJ. Direct activation of factor X by monocyte occurs during cardiopulmonary bypass. Br J Haematol. 1998;101: 40-6.
36. Walsh PN. Platelets and factor XI bypass the contact system of blood coagulation. Thromb Haemost. 1999;82:234-42.
37. Minnema MC, TenCate H, Hack CE. The role of factor XI in coagulation: A matter of revision. Sem Thromb Hemost. 1999;25: 419-28.
38. Colman RW, Schmaier AH. Contact system: A vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood. 1997;90:3819-43.
39. Schmaier AH, Rojkjaer R, Shariat-Madar Z. Activation of the plasma kallikrein/kinin system on cells: A revised hypothesis. Thromb Haemost. 1999;82:226-33.
40. Sidelmann JJ, Gram J, Jespersen J, Kluft C. Fibrin clot formation and lysis: Basic mechanisms. Sem Thromb Hemost. 2000;26:605-18.
41. Wachtfogel YT, Kucich U, James HL, et al. Human plasma kallikrein releases neutrophil elastase during blood coagulation. J Clin Invest. 1983;72:1672-7.
42. Nagaoka H, Katori M. Inhibition of kinin formation by a kallikrein inhibitor during extracorporeal circulation in open-heart surgery. Circulation. 1975;52:325-32.
43. Blauhut B, Gross C, Necek S, Doran JE, Spath P, Lundsgaard-Hansen P. Effects of high-dose aprotinin on blood loss, platelet function, fibrinolysis, complement, and renal function after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1991;101:958-67.
44. Wachtfogel YT, Kucich U, Hack CE, et al. Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg. 1993;106: 1-9.
45. Misfeld M, Duppert S, Eleftheriadis S, Siemens H-J, Wagner T, Sieves H-H. Fibrinolysis-adjusted perioperative low-dose aprotinin reduces blood loss in bypass operations. Ann Thorac Surg. 1998;66: 792-9.
46. Liu B, Tengborn L, Larson G, et al. Half-dose aprotinin preserves hemostatic function in platelets undergoing bypass operations. Ann Thorac Surg. 1995;59:1534-40.
47. Kuliopulos A, Covic L, Seeley SK, Sheridan PJ, Helin J, Costello CE. Plasmin desensitization of the PAR 1 thrombin receptor: kinetics, sites of truncation, and implications for thrombolytic therapy. Biochemistry. 1999;38:4572-85.
48. Loscatzo J, Pasche B, Ouimet H, Freedman JE. Platelets and plasminogen activation. Thromb Haemost. 1995;74:291-3.
49. Michelson AD, Barnard MR. Plasmin-induced redistribution of platelet glycoprotein Ib. Blood. 1990;76:2005-10.
50. Cramer EM, Caen JP, Soria C, Berndt M, Tenza D. Differential distribution of platelet glycoproteins Ib and IIb-IIIa after plasmin stimulation. Blood. 1991;77:694-9.
51. Lu H, Soria C, Soria J, et al. Reversible translocation of glycoprotein Ib in plasmin-treated platelets: Consequences for platelet function. Eur J Clin Invest. 1993;23:785-93.
52. Kallis P, Tooze JA, Talbot S, Cowans D, Bevan DH, Treasure T. Aprotinin inhibits fibrinolysis, improves platelet adhesion, and reduces blood loss. Results of a double-blind randomized clinical trial. Eur J Cardiothorac Surg. 1994;8:315-23.
53. Hoffmann JJML, Janssen WCM. Interactions between thrombolytic agents and platelets: Effects of plasmin on platelet glycoproteins Ib and IIb/IIIa. Thromb Res. 1992;67:711-9.
54. Kimura M, Andersen TT, Fenton JW, Bahou WF, Aviv A. Plasmin-platelet interaction involves cleavage of functional thrombin receptor. Am J Physiol. 1996;271:C54-60.
55. Poullis M, Manning R, Laffan M, Haskard DO, Taylor KM, Landis RC. The antithrombotic effect of aprotinin: Actions mediated via the protease-activated receptor 1. J Thorac Cardiovasc Surg. 2000; 120:370-8.
56. Huang H, Ding W, Su Z, Zhang W. Mechanism of preserving the effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc Surg. 1993;106:11-88.
57. de Haan J, van Oeveren W. Platelets and soluble fibrin promote plasminogen activator causing down regulation of platelet glycoprotein lb/IX complexes: Protection by aprotinin. Thromb Res. 1998;92:171-9.
58. Kozek-Langenecker SA, Mohammad SF, Masaki T, Green W, Kamerath C, Cheung AK. The effects of aprotinin on platelets in vitro using whole blood flow cytometry. Anesth Analg. 2000;90:12-6.
59. John LCH, Rees GM, Kovacs IB. Reduction of heparin binding to and inhibition of platelets by aprotinin. Ann Thorac Surg. 1993;55: 1175-9.
60. Pintigny D, Dachary-Prigent J. Aprotinin can inhibit the proteolytic activity of thrombin. A fluorescence and an enzymatic study. Eur J Biochem. 1992;207:89-95.
61. Primack C, Walenga JM, Koza MJ, Shankey TV, Pifaree R. Aprotinin modulation of platelet activation in patients undergoing cardiopulmonary bypass. Ann Thorac Surg. 1996;61:1188-93.
62. van Oeveren W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CRH. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1990;99:788-97.
63. Shore-Lesserson L. Aprotinin has direct platelet protective properties. Fact or fiction? J Cardiothorac Vasc Anesth. 1999;13:379-81.
64. Basora M, Gumar C, Escolar G, Pacheco M, Fita G, Rodriguez E, Ordinas A. Platelet function during cardiac surgery and cardiopulmonary bypass with low-dose aprotinin. J Cardiothorac Vasc Anesth. 1999;13:382-7.
65. Ray MJ, Marsh NA, Just SJE, Perrin EJ, O'Brien MF, Hawson GAT. Preoperative platelet dysfunction increases the benefit of aprotinin in cardiopulmonary bypass. Ann Thorac Surg. 1997;63: 57-63.
66. Wahba A, Black G, Koksch M, et al. Aprotinin has no effect on platelet activation and adhesion during cardiopulmonary bypass. Thromb Haemost. 1996;75:844-8.
67. Zwaal RFA, Comfarius P, Bevers EM. Platelet procoagulant activity and microvesicle formation. Its putative role in hemostasis and thrombosis. Biochim Biophys Acta. 1992;1180:1-8.
68. Furman MI, Krueger LA, Frelinger AL, et al. GPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood. Thromb Haemost. 2000;84:492-8.
69. Thomas S, Metcalfe P, Goodall AH, Gray E. Monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa and Ib-alpha inhibit platelet dependent thrombin generation by different mechanisms. Thromb Haemost. 2000;84:98-101.
70. Pedicord DL, Thomas BE, Mousa SA, Dicker IB. Glycoprotein IIb/IIa receptor antagonists inhibit the development of platelet procoagulant activity. Thromb Res. 1998;90:247-58.
71. Chen HI, Wu YI, Hsieh YL, et al. Perturbation of platelet adhesion to endothelial cells by plasminogen activation in vitro. Thromb Haemost. 1997;78:914-8.
72. Okajima K, Abe H, Binder BR. Endothelial cell injury induced by plasmin in vitro. J Lab Clin Med. 1995;126:377-84.
73. Schafer AI, Rodriguez R, Loscalzo J, Gimbrone MA. Inhibition of vascular endothelial cell prostacyclin synthesis by plasmin. Blood. 1989;74:1015-20.
74. Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem. 1989;264:4743-6.
75. Espana F, Estelles A, Griffin JH, Aznar J, Gilabert J. Aprotinin (Trasylol) is a competitive inhibitor of activated protein C. Thromb Res. 1989;56:751-6.
76. Taby O, Chabbat J, Steinbuch M. Inhibition of activated protein C by aprotinin and the use of the insolublized inhibitor for its purification. Thromb Res. 1990;59:27-35.
77. Sweeney JD, Blair AJ, Dupuis MP, King TC, Moulton AL. Aprotinin, cardiac surgery, and factor V Leiden. Transfusion. 1997;37: 1173-8.
78. Robbins P, Forrest M, Fanning S, Royston D. Use of aprotinin therapy in a patient with factor V Leiden. Anesth Analg. 1997;84: 694-8.
79. Siebeck M, Fink E, Weipert J, et al. Inhibition of plasma kallikrein with aprotinin in porcine endotoxin shock. J Trauma. 1993;34:193-8.
80. de Smet AAEA, Joen MCN, van Oeveren W, et al. Increased anticoagulation during cardiopulmonary bypass by aprotinin. J Thorac Cardiovasc Surg. 1990;100:520-7.
81. Despotis GJ, Filos KS, Levine V, Alsoufieu A, Spitznagel E. Aprotinin prolongs activated and nonactivated whole blood clotting time and potentiates the effect of heparin in vitro. Anesth Analg. 1996; 82:1126-31.
82. Dietrich W, Dilthey G, Spannagl M, Jochum M, Braun SL, Richter JA. Influence of high-dose aprotinin on anticoagulation, heparin requirement, and celite- and kaolin-activated clotting time in heparin-pretreated patients undergoing open-heart surgery. Anesthesiology. 1995;83:679-89.
83. Spannagl M, Dietrich W, Beck A, Schramm W. High-dose aprotinin reduces prothrombin and fibrinogen conversion in patients undergoing extracorporeal circulation for myocardial revascularization. Thromb Haemost. 1994;72:159-60.
84. Boldt J, Schindler E, Knothe C, Hammermann H, Stertmann WA, Hempelmann G. Does aprotinin influence endothelial-associated coagulation in cardiac surgery? J Cardiothorac Vasc Anesth. 1994; 8:527-31.
85. Menichetti A, Tritapepe L, Ruvolo G, et al. Changes in coagulation patterns, blood loss, and blood use after cardiopulmonary bypass: Aprotinin vs. tranexamic acid vs. epsilon aminocaproic acid. J Cardiovasc Surg. 1996;37:401-7.
86. Barstad RM, Ovrum E, Ringdal MAL, et al. Induction of monocyte tissue factor procoagulant activity during coronary artery bypass is reduced with heparin-coated extracorporeal ciruit. Br J Haematol. 1996;94:517-25.
87. Lindmark E, Tenno T, Siegbahn A. Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression. Arterioscl Thromb Vasc Biol. 2000;20:2322-8.
88. Celi A, Pellegrini G, Lorenzet R, et al. P-selectin induces expression of tissue factor on monocytes. Proc Natl Acad Sci. 1994;91: 8767-71.
89. Polack B, Pernod G, Barro C, Doussiere J. Role of oxygen radicals in tissue factor induction by endotoxin in blood monocytes. Haemostasis. 1997;27:193-200.
90. Altieri DC. Inflammatory cell participation in coagulation. Sem Cell Biol. 1995;6:269-74.
91. Wilhelm CR, Ristich J, Kormos RL, Wagner WR. Monocyte tissue factor expression and ongoing complement generation in ventricular assist device patients. Ann Thorac Surg. 1998;65:1071-6.
92. Plescia J, Altieri DC. Activation of Mac-1 (CD11b/CD18)-bound factor X by released cathepsin G defines an alternative pathway of leukocyte initiation of coagulation. Biochem J. 1996;319:873-9.
93. Brinkman HJM, Mertens K, Holthius J, Zwart-Huinink LA, Grijm K, van Mourik JA. The activation of human blood coagulation factor X on the surface of endothelial cells: A comparison with various vascular cells, platelets, and monocytes. Br J Haematol. 1994;87:332-42.
94. Chabbat J, Porte P, Tellier M, Steinbuch M. Aprotinin is a competitive inhibitor of the factor VIIa-tissue factor complex. Thromb Res. 1993;71:205-15.
95. van den Besselaar AMHP, Dirven R, Bertina RM. Tissue factor-induced coagulation can be inhibited by aprotinin. Thromb Haemost. 1993;69:298-9.
96. Gilliland HE, Armstrong MA, Uprichard S, Clarke G, McMurray TJ. The effect of aprotinin on interleukin-8 concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system. Anaesthesia. 1999;54:427-33.
97. Khan MMH, Gikakis N, Miyamoto S, et al. Aprotinin inhibits thrombin formation and monocyte tissue factor in simulated cardiopulmonary bypass. Ann Thorac Surg. 1999;68:476-8.
98. Hill GE, Alonson A, Spurzem JR, Stammers AH, Robbins RA. Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass-induced inflammation in humans. J Thorac Cardiovasc Surg. 1995;110:1658-62.
99. Asimakopoulos G, Thompson R, Nourshargh S, Lidington EA, Mason JC, Ratnatunga CP, Haskard DO, Taylor KM, Landis RC. An anti-inflammatory property of aprotinin detected at the level of leukocyte extravascation. J Thorac Cardiovasc Surg. 2000;120:361-9.
100. Chen CC, Rosenbloom CL, Anderson DC, Manning AM. Selective inhibition of E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 expression by inhibitors of IKB-α phosphorylation. J Immunol. 1995;155:3538-45.
101. Boyle EM, Kerrier ED, Spiess BD. Endothelial cell injury in cardiovascular surgery: The procoagulant response. Ann Thorac Surg. 1996;62:1549-57.
102. 2 in cultured human umbilical vein endothelial cells. J Thorac Cardiovasc Surg. 1992;104:654-8.
103. Royston BD, Royston D, Coade SB, Morgan DML, Pearson JD. Aprotinin does not inhibit the release of PGI2 or vWF from cultured human endothelial cells. Thromb Haemost. 1992;67:172-5.
104. Allen S, Anastasiou N, Royston D, Paniagua R, Yacoub M. Effect of aprotinin on vascular reactivity of coronary artery vascular grafts. J Thorac Cardiovasc Surg. 1997;113:319-26.
105. Alonso A, Whitten CW, Hill GE. Pump prime only aprotinin inhibits cardiopulmonary bypass-induced neutrophil CD11b upregulation. Ann Thorac Surg. 1999;67:392-5.
106. Bannan S, Martin PG. Aprotinin complements heparin bonding in an in vitro model of cardiopulmonary bypass. Br J Haemost. 1998; 103:455-61.
107. Inui K, Shimazaki Y, Watanabe T, et al. Aprotinin reduces the expression of P-selectin on the surface of platelet and leukocyte-platelet conjugates. Artif Organs. 1998;22:1018-22.
108. Lord RA, Roath OS, Thompson JF, Chant ADB, Francis JL. Effect of aprotinin on neutrophil function after major vascular surgery. Br J Surg. 1992;79:517-21.
109. 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.
110. Hill GE, Diego RP, Stammers AH, Huffman SM, Pohorecki R. Aprotinin enhances the endogenous release of interleukin-10 after cardiac operations. Ann Thorac Surg. 1998;65:66-9.
111. Stefano GB, Rodriguez M, Glass R, Cesares F, Hughes TK, Bilfinger TV. Hyperstimulation of leukocytes by plasma from cardiopulmonary by-pass patients is diminished by morphine and IL-10 pretreatment. J Cardiovasc Surg. 1995;36:25-30.
112. Pajkrt D, van der Poll T, Levi M, et al. Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood. 1997;89:2701-5.
113. Ernofsson M, Tenno T, Siegbahn A. Inhibition of tissue factor surface expression in human peripheral blood monocytes exposed to cytokines. Br J Haematol. 1996;95:249-57.
114. Venturini G, Colasanti M, Ascenzi P. Aprotinin, the first competitive protein of NOS activity. Biochem Biophys Res Comm. 1998; 249:263-5.
115. Bruda NL, Hurlbert BJ, Hill GE. Aprotinin reduces nitric oxide production in vitro and in vivo in a dose-dependent manner. Clin Sci. 1998;94:505-9.
116. Broche VF, Suarez AR, Olembe E, et al. Aprotinin effects related to oxidative stress in cardiosurgery and mechanical cardiorespiratory support. Ann NY Acad Sci. 1996;793:721-4.
117. Rao SK, Palazzo RS, Metz HN, Wilson DW, Nikolic SD, Graver M, Rao PS. Redox potential measurements of plasma in patients undergoing coronary artery bypass graft and its clinical significance. J Pharmacol Toxicol Methods. 1997;38:151-6.
118. Hallett MB, Shandall A, Young HL. Mechanism of protection against "reperfusion injury" by aprotinin. Roles of polymorphonuclear leukocytes and oxygen radicals. Biochem Pharmacol. 1985; 34:1757-61.
119. Liu B, Belboul A, al-Khaja N, Dernevik L, Raberts D, William-Olsson G. High-dose aprotinin (trasylol) in reducing bleeding and protecting lung function in potential bleeders undergoing cardiopulmonary bypass. Chinese Med J. 1991;104:980-5.
120. Hirayama T, Roberts D, Allers M, Belboul A, Al-Khaja N, William-Olsson G. Association between bleeding and reduced red cell deformability following cardiopulmonary bypass. Scand J Thor Cardiovasc Surg. 1988;22:171-4.
121. Ashraf S, Tian Y, Cowan D, et al. "Low-dose" aprotinin modifies hemostasis but not proinflammatory cytokine release. Ann Thorac Surg. 1997;63:68-73.
122. Baufreton C, te Velthuis H, Jansen PGM, LeBesnerais P, Wildevuur CHR, Loisance DY. Reduction of blood activation in patients requiring aprotinin during cardiopulmonary bypass for coronary artery surgery. ASAIO J. 1996;42:M417-23.
123. Defraigne J-O, Pincemail J, Larbuisson R, Blaffart F, Limet R. Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration. Ann Thorac Surg. 2000;69:1084-91.
124. Boyle EM, Canty TG, Morgan EN, Yun W, Pohlman TH, Verrier ED. Treating myocardial ischemia-reperfusion injury by targeting endothelial cell transcription. Ann Thorac Surg. 1999;68:1949-53.
125. Canty TG, Boyle EM, Farr A, Morgan EN, Verrier ED, Pohlman TH. Oxidative stress induces NF-κB nuclear translocation without degradation of IκBa. Circulation. 1999;100(Suppl II):II-361-4.
126. Hill GE, Robbins RA. Aprotinin but not tranexamic acid inhibits cytokine-induced inducible nitric oxide synthase expression. Anesth Analg. 1997;84:1198-1202.
127. Hill GE, Taylor JA, Robbins RA. Differing effects of aprotinin and e-aminocaproic acid on cytokine-induced inducible nitric oxide synthase expression. Ann Thorac Surg. 1997;63:74-7.
128. Wang P, Wu P, Siegel MI, Egan RW, Billah MM. Interleukin (IL)-10 inhibits nuclear factorκαππαB (NFκB) activation in human monocytes. J Biol Chem. 1995;270:9558-63.