Alternative pathway of complement is activated during in vitro ventricularassist

Background: Although ventricular assist devices (VAD) have improved surviva l in selected patients, their use continues to be complicated by thromboemb olism and end-organ failure. Complement activation may play a role in the p athogenesis of these complications. Previous studies have found that the co mplement common terminal pathway is activated during VAD circulation. C3a l evels rise dramatically during VAD use. Because the C3a fragment is generat ed by either the alternative or classical pathway, the purpose of this stud y is to determine the relative importance of the respective pathways in com plement activation during in vitro VAD circulation. Methods: Six in vitro VAD circuits were simulated for 3 days using 450 mt o f human blood. Temperature, activated clotting time, pH, pCO(2), pO(2), Ca2 +, and glucose were maintained at physiologic levels. Enzyme immunoassays w ere used to measure concentrations of fragment Bb to indicate alternative p athway activation and fragment C4d to indicate classical pathway activation . Results: Fragment Bb concentrations rise from 1.92 to 10.77 mu g/mL during the first 6 hours of circulation. Thereafter, Bb levels plateau, C4d concen trations slowly rise from a baseline of 1.49 to 6.84 mu g/mL in 72 hours. Conclusions: These findings suggest that both the alternative and classical pathways of complement are activated during VAD circulation. Alternative p athway activation precedes classical pathway activation during In vitro VAD circulation and may be of greater clinical importance during clinical VAD circulation.