A decline of protective apolipoprotein J and complement factor H concomitant with increase in C5a 3 months after cardiac surgery-Evidence of long-term complement perturbations.

Background: Heart surgery results in complement activation with the potential for collateral end-organ damage, especially if the protective elements (complement factor H, Apolipoprotein J) are inadequate. Here, we have investigated if peri-operative stress results in an imbalance between complement activation and its protective mechanisms up to 3 months after heart surgery.

Methods: 101 patients scheduled for non-emergent cardiac surgery donated blood before the procedure (t), and 24 h (t ), 7 days (t ) and 3 months (t ) after. Complement activation was measured as a serum level of soluble activated component 5 (sC5a) and soluble terminal complement complex (sTCC). Simultaneously, protective complement factor H (CfH), and apolipoprotein J (ApoJ) were measured. Inflammatory responses were quantified using C-reactive protein (CRP) and interleukin-6 (IL-6). Details regarding anesthesia, intensive care unit (ICU) stay, pre-existing conditions, the incidence of postoperative complications, and mortality were collected from medical records.

Results: C5a declined at t to rebound at t and t . sTCC was significantly depressed at t and returned to baseline at later time points. In contrast, CfH and ApoJ were depressed at t . Milieu of complement factors aligned along two longitudinal patterns:cluster#1 (C5a/sTTC continuously increasing and CfH/ApoJ preserved at t) and cluster#2 (transient sC5a/sTTC increase and progressive decline of CfH). Most patients belonged to cluster #1 at t (68%), t (74%) and t (72%). sTCC correlated with APACHE ( =-0.25; < 0.031) and APACHE ( = 0.27; < 0.049). IL-6 correlated with C5a ( =-0.28; < 0.042) and sTTC ( =-0.28; < 0.015). Peri-operative administration of acetaminophen and aspirin altered the complement elements. Prolonged hospital stay correlated with elevated C5a [ (78) = 2.03; = 0.048] and sTTC serum levels [ (73) = 2.07; = 0.037]. Patients with stroke had a decreased serum level of C5a at t and t.

Conclusion: There is a significant decrease in complement protective factors 3 months after cardiac surgery, while C5a seems to be slightly elevated, suggesting that cardiac surgery affects complement milieu long into recovery.