Alternative pathway of complement is activated during in vitro ventricular assist.
BACKGROUND
Although ventricular assist devices (VAD) have improved survival in selected patients, their use continues to be complicated by thromboembolism and end-organ failure. Complement activation may play a role in the pathogenesis of these complications. Previous studies have found that the complement common terminal pathway is activated during VAD circulation. C3a levels rise dramatically during VAD use. Because the C3a fragment is generated by either the alternative or classical pathway, the purpose of this study is to determine the relative importance of the respective pathways in complement activation during in vitro VAD circulation.


METHODS
Six in vitro VAD circuits were simulated for 3 days using 450 mL of human blood. Temperature, activated clotting time, pH, pCO2, pO2, Ca2+, and glucose were maintained at physiologic levels. Enzyme immunoassays were used to measure concentrations of fragment Bb to indicate alternative pathway activation and fragment C4d to indicate classical pathway activation.


RESULTS
Fragment Bb concentrations rise from 1.92 to 10.77 micrograms/mL during the first 6 hours of circulation. Thereafter, Bb levels plateau. C4d concentrations slowly rise from a baseline of 1.49 to 6.84 micrograms/mL in 72 hours.


CONCLUSIONS
These findings suggest that both the alternative and classical pathways of complement are activated during VAD circulation. Alternative pathway activation precedes classical pathway activation during in vitro VAD circulation and may be of greater clinical importance during clinical VAD circulation.
Chen
J C
JC
Department of Surgery, University of California, Irvine Medical Center, Orange 92868, USA.
Huynh
T N
TN
Serna
D L
DL
Sun
C P
CP
Ha
H
H
Steward
E
E
Webster
S
S
Brenner
M
M
D001243:Assisted Circulation; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b; D003170:Complement Pathway, Alternative; D006333:Heart Failure / Q000097:blood* / Q000628:therapy; D006353:Heart-Assist Devices; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood
D015415:Biomarkers; D003181:Complement C4; D010446:Peptide Fragments; D011994:Recombinant Proteins; D003179:Complement C3b; D015935:Complement C4b; C032261:complement C4d; D051561:Complement C3 Convertase, Alternative Pathway