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The Journal of Thoracic and Cardiovascular Surgery, Vol 106, 1-9, Copyright © 1993 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
YT Wachtfogel, U Kucich, CE Hack, P Gluszko, S Niewiarowski, RW Colman and LH Edmunds Jr
Aprotinin reduces blood loss after cardiac operations and decreases the
bleeding time. The mechanism of action of aprotinin that produces these
effects is not clear. During simulated extracorporeal circulation the
contact and complement systems, platelets, and neutrophils are activated.
We investigated the effect of aprotinin on kallikrein-C1- inhibitor complex
and C1-C1-inhibitor complex formation, neutrophil degranulation, and
platelet release and aggregation during simulated extracorporeal
circulation. Fresh heparinized human blood was recirculated at 37 degrees C
for 2 hours in a spiral coil membrane oxygenator-roller pump perfusion
circuit. Changes in platelet count, leukocyte count, platelet response to
adenosine diphosphate, and plasma levels of beta-thromboglobulin,
kallikrein-C1-inhibitor complexes, C1- C1-inhibitor complexes, and
neutrophil elastase were measured before and at 5, 30, 60, and 120 minutes
of recirculation at 0, 0.015, 0.03, 0.06, and 0.12 mg/ml doses of
aprotinin. Platelet counts decreased to 36% +/- 12% of control values at 5
minutes and increased to 56% +/- 13% at 120 minutes without aprotinin.
Aprotinin did not affect platelet counts, but it did prevent the decrease
in sensitivity of platelets to adenosine diphosphate and it attenuated
beta-thromboglobulin release. In the absence of aprotinin,
kallikrein-C1-inhibitor and C1-C1- inhibitor complexes increased
progressively to 0.53 +/- 0.14 U/ml and 2.38 +/- 0.33 U/ml, respectively,
at 120 minutes. Kallikrein-C1- inhibitor complexes were completely
inhibited and C1-C1-inhibitor complexes were partially inhibited at
aprotinin concentrations of 0.03 mg/ml or greater. Release of neutrophil
elastase was partially but not completely inhibited at the highest dose of
aprotinin and was 50% inhibited at a dose of 0.03 mg/ml. Because activation
of the fibrinolytic system does not occur in this system, the changes were
independent of the inhibition of plasmin. We conclude that aprotinin in
high doses completely inhibited kallikrein-induced activation of
neutrophils and partially inhibited complement-induced activation.
Aprotinin did not directly affect platelet adhesion or aggregation, but it
indirectly preserved platelet sensitivity to agonists and also attenuated
release of alpha-granule contents. The data indicate that in the presence
of aprotinin platelet function was partially preserved, kallikrein
production was totally inhibited, complement activation was partially
inhibited, and neutrophil release was partially inhibited, thus attenuating
the "whole body inflammatory response" associated with cardiopulmonary
bypass.
ARTICLES
Aprotinin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa.
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M. R. Terrell, J. M. Walenga, M. J. Koza, and R. Pifarre Efficacy of Aprotinin With Various Anticoagulant Agents in Cardiopulmonary Bypass Ann. Thorac. Surg., August 1, 1996; 62(2): 506 - 511. [Abstract] [Full Text]
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D. Royston Systemic inflammatory responses to surgery with cardiopulmonary bypass Perfusion, May 1, 1996; 11(3): 177 - 189. [PDF]
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M. Yii, T. Gourlay, J. Fleming, B. Matata, and K. Taylor Evaluation of Carmeda(R) Bioactive Surface (CBAS(R)), Duraflo II and a novel nonspecific protease-modified surface using a new in vitro model simulating cardiopulmonary bypass Perfusion, May 1, 1996; 11(3): 229 - 240. [PDF]
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M.-C. Seghaye, MD, J. Duchateau, R. G. Grabitz, T. Wolffb, C. Marcus, W. Engelhardt, H. Hornchen, B. J. Messmer, and G. von Bernuth EFFECT OF SODIUM NITROPRUSSIDE ON COMPLEMENT ACTIVATION INDUCED BY CARDIOPULMONARY BYPASS: A CLINICAL AND EXPERIMENTAL STUDY J. Thorac. Cardiovasc. Surg., April 1, 1996; 111(4): 882 - 892. [Abstract] [Full Text]
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