A decline of protective apolipoprotein J and complement factor H concomitant with increase in C5a 3 months after...

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.

101 patients scheduled for non-emergent cardiac surgery donated blood before the procedure (t_baseline), and 24 h (t₂₄ ), 7 days (t₇ ) and 3 months (t₃ ) 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.

C5a declined at t₂₄ to rebound at t₇ and t₃ . sTCC was significantly depressed at t₂₄ and returned to baseline at later time points. In contrast, CfH and ApoJ were depressed at t₃ . Milieu of complement factors aligned along two longitudinal patterns:cluster#1 (C5a/sTTC continuously increasing and CfH/ApoJ preserved at t_baseline) and cluster#2 (transient sC5a/sTTC increase and progressive decline of CfH). Most patients belonged to cluster #1 at t₂₄ (68%), t_7d (74%) and t_3m (72%). sTCC correlated with APACHE₁ (r ² =-0.25; p < 0.031) and APACHE₂₄ (r ² = 0.27; p < 0.049). IL-6 correlated with C5a (r ² =-0.28; p < 0.042) and sTTC (r ² =-0.28; p < 0.015). Peri-operative administration of acetaminophen and aspirin altered the complement elements. Prolonged hospital stay correlated with elevated C5a [t (78) = 2.03; p = 0.048] and sTTC serum levels [U (73) = 2.07; p = 0.037]. Patients with stroke had a decreased serum level of C5a at t_7d and t_3m.

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.