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Eur J Cardiothorac Surg 2006;30:72-76
© 2006 Elsevier Science NL

APT070 inhibits complement activation during in vitro cardiopulmonary bypass

^a Papworth Hospital NHS Trust, Papworth Everard, Cambridgeshire CB3 8RE, UK
^b Adprotech Ltd, Chesterford Research Park, Little Chesterford, Saffron Walden, Essex CB10 1XL, UK

Received 22 September 2005; received in revised form 20 February 2006; accepted 2 March 2006.

^_* Corresponding author. Address: Willow Cottage, 40 Green End, Landbeach, Cambridge, Cambridgeshire CB4 8RE, UK. Tel.: +44 1223 440341; fax: +44 1223 440341. (Email: ravijdesilva{at}doctors.org.uk).

Background: The proteins of the complement cascade play an important role in inflammation and the immune response. They have been shown to be activated during cardiopulmonary bypass (CPB), and may be responsible for the inflammatory response to CPB. We looked at the effect of APT070, an anti-complement agent, on human blood during in vitro CPB. Materials and methods: Four hundred millilitres of blood was venesected from healthy human volunteers and heparinised. To the blood was added either APT070 to a concentration of 50 µg/ml (n = 5) or vehicle control (n = 4). The blood was entered into an in vitro CPB circuit and circulated for 90 min. Results: Our results showed that after 90 min of in vitro bypass APT070 significantly inhibited the activation of compliment as demonstrated by C3a (p = 0.03) and sC5b-9 (p = 0.01) levels, and reduced neutrophil stimulation as measured by CD11b expression (p = 0.04 at 90 min). Conclusion: APT070 significantly inhibits complement and neutrophil activation. This result may have considerable implications, especially if it can be shown to decrease the inflammatory sequelae of CPB.

Key Words: Cardiopulmonary bypass • Inflammatory response • Cytokines