Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons

Copyright 2000 Academic Press.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 96(2000), 3 vom: 01. Sept., Seite 212-21
1. Verfasser: Soulika, A M (VerfasserIn)
Weitere Verfasser: Khan, M M, Hattori, T, Bowen, F W, Richardson, B A, Hack, C E, Sahu, A, Edmunds, L H Jr, Lambris, J D
Format: Aufsatz
Sprache:English
Veröffentlicht: 2000
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, U.S. Gov't, P.H.S. Complement Inactivator Proteins Hemoglobins Peptides, Cyclic Protamines compstatin protamine heparin aggregate Heparin 9005-49-6
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245 1 0 |a Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons 
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520 |a Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug 
650 4 |a Journal Article 
650 4 |a Research Support, U.S. Gov't, P.H.S. 
650 7 |a Complement Inactivator Proteins  |2 NLM 
650 7 |a Hemoglobins  |2 NLM 
650 7 |a Peptides, Cyclic  |2 NLM 
650 7 |a Protamines  |2 NLM 
650 7 |a compstatin  |2 NLM 
650 7 |a protamine heparin aggregate  |2 NLM 
650 7 |a Heparin  |2 NLM 
650 7 |a 9005-49-6  |2 NLM 
700 1 |a Khan, M M  |e verfasserin  |4 aut 
700 1 |a Hattori, T  |e verfasserin  |4 aut 
700 1 |a Bowen, F W  |e verfasserin  |4 aut 
700 1 |a Richardson, B A  |e verfasserin  |4 aut 
700 1 |a Hack, C E  |e verfasserin  |4 aut 
700 1 |a Sahu, A  |e verfasserin  |4 aut 
700 1 |a Edmunds, L H  |c Jr  |e verfasserin  |4 aut 
700 1 |a Lambris, J D  |e verfasserin  |4 aut 
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