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

Athena Soulika, Mohammad M. Khan, Takashi Hattori, Frank W. Bowen, Bradford A. Richardson, C. Erik Hack, Arvind Sahu, L. Henry Edmunds, John D. Lambris

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)212-221
Number of pages10
JournalClinical Immunology
Volume96
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

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Keywords

  • Anticoagulant
  • Cardiopulmonary bypass
  • Complement inhibitors
  • Compstatin
  • Cyclic peptides
  • Heparin/protamine complexes
  • Primates

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pathology and Forensic Medicine

Cite this

Soulika, A., Khan, M. M., Hattori, T., Bowen, F. W., Richardson, B. A., Hack, C. E., Sahu, A., Edmunds, L. H., & Lambris, J. D. (2000). Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons. Clinical Immunology, 96(3), 212-221. https://doi.org/10.1006/clim.2000.4903