APT070 inhibits complement activation during in vitro cardiopulmonary bypass.
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.


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 microg/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).


CONCLUSIONS
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.
De Silva
Ravi J
RJ
Papworth Hospital NHS Trust, Papworth Everard, Cambridgeshire CB3 8RE, UK. ravijdesilva@doctors.org.uk
Vuylsteke
Alain
A
Fritchley
Sarah J
SJ
Trull
Andrew K
AK
Dunning
John J
JJ
Wallwork
John
J
D039481:CD11b Antigen / Q000097:blood; D002315:Cardiopulmonary Bypass; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D039481:CD11b Antigen; D051056:Complement Inactivating Agents; D015938:Complement Membrane Attack Complex; D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015926:Complement C3a