[en] Background. The serine protease inhibitor aprotinin inhibits trypsin, kallikrein, and plasmin and enhances the complement hemolytic activity of the first complement component C1. We tested whether low-dose aprotinin influences the inflammatory reaction related to cardiopulmonary bypass. Methods. In an open, randomized study, 25 children undergoing cardiac operations were investigated prospectively. The treated group comprised 11 patients receiving low-dose aprotinin (20,000 kIU/kg [2.8 mg/kg]), and the control group included 14 patients. Complement activation, cytokine production, and leukocyte stimulation were analyzed before, during, and after cardiopulmonary bypass. Results. In all children, significant C3 conversion and C5a generation, interleukin-6 synthesis, and myeloperoxidase, eosinophil cationic protein, and histamine liberation occurred in relation to cardiopulmonary bypass. This was not influenced by aprotinin treatment. In contrast, neutrophil kinetic studies at the end of cardiopulmonary bypass showed a significantly lower increase in the aprotinin as compared with the control group. Conclusions. Our results suggest that low-dose aprotinin has little influence on the inflammatory reaction induced by cardiopulmonary bypass. Aprotinin affects neutrophil mobilization but not white blood cell degranulation related to cardiopulmonary bypass, and has no influence on complement activation and interleukin-6 synthesis.
Disciplines :
Pediatrics Cardiovascular & respiratory systems
Author, co-author :
Seghaye, Marie-Christine ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie cardiologique et pneumologique
Duchateau, J.; Centre Hospitalier Universitaire Brugmann, Brussels > Laboratory of Immunology
Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:552-9.
Moat NE, Rebuck N, Shore DF, Evans TW, Finn AHR. Humoral and cellular activation in a simulated extracorporeal circuit. Ann Thorac Surg 1993;56:1509-14.
Bidstrup BP, Harrison J, Royston D, Taylor KM, Treasure T. Aprotinin therapy in cardiac operations: a report on use in 41 cardiac centers in the United Kingdom. Ann Thorac Surg 1993;55:971-6.
Westaby S. Aprotinin in perspective. Ann Thorac Surg 1993;55:1033-41.
Van Oeveren W, Jansen NJG, Bidstrup BP, et al. Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass. Ann Thorac Surg 1987;44:640-5.
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.
Fritz H, Wunderer G. Biochemistry and applications of aprotinin, the kallikrein inhibitor from bovine organs. Arzneimittelforschung 1983;33:479-94.
Laurel M-TP, Ratnoff OD, Everson B. Inhibition of the activation of Hageman factor (factor XII) by aprotinin (Trasylol). J Lab Clin Med 1992;119:580-5.
Delage JM, Simard J, Lehner-Netsch G. The enhancement of the haemolytic activity of the first component of complement by Trasylol. Immunology 1976;31:601-6.
Blauhut B, Gross C, Necek S, Doran JE, Späth 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.
Law SKA, Reid KBM. Activation and control of the complement system. In: Male D, Rickwood D, eds. Complement. Oxford: IRL Press Limited, 1988:9-27.
Kozin F, Cochrane CG. The contact activation system of plasma: biochemistry and pathophysiology. In: Gallin JI, Goldstein IM, Snydermann R, eds. Inflammation: basic principles and clinical correlates. New York: Raven Press, 1988: 101-20.
Quiroga MM, Miyagishima R, Haendschen LC, Glovsky M, Martin BA, Hogg JC. The effect of body temperature on leukocyte kinetics during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1985;90:91-6.
Seghaye MC, Duchateau J, Grabitz RG, et al. Complement activation during cardiopulmonary bypass in infants and children: relation to postoperative multiple system organ failure. J Thorac Cardiovasc Surg 1993;106:978-87.
Boldt J, Osmer C, Schindler E, Linke LC, Stertmann WA, Hempelmann G. Circulating adhesion molecules in cardiac operations: influence of high-dose aprotinin. Ann Thorac Surg 1995;59:100-5.
Burden AC, Stacey RL, Wood RFM, Bell PR. The effect of protease inhibitors on leukocyte migration inhibition to tuberculin extract (PPD). Immunology 1978;34:217-21.
Seghaye MC, Duchateau J, Grabitz RG, et al. Histamine liberation related to cardiopulmonary bypass in children: possible relation to transient postoperative arrhythmias. J Thorac Cardiovasc Surg (in press).
Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J 1990;265:621-36.
Nijsten MWN, De Groot ER, Ten Duis HJ, Klasen HJ, Hack CE, Aarden LA. Serum levels of interleukin-6 and acute phase responses. Lancet 1987;II:921.
Dietrich W, Mössinger H, Spannagl M, et al. Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations. J Thorac Cardiovasc Surg 1993;105:712-20.
