Complement activation and cytokine generation after modified Fontan procedure

The modified Fontan procedure separates the systemic and pulmonary circulations in patients born with a functional single ventricle. Delayed recovery is frequently observed after this procedure. It was our hypothesis that complement activation or cytokine generation may contribute to the pathophysiology of this problem.

We measured activated complement C3, thromboxane B2, interleukin-6, and tumor necrosis factor-alpha levels by immunoassay in 16 patients undergoing Fontan procedure. Patient plasma samples were obtained preoperatively, on initiation of cardiopulmonary bypass, after administration of protamine, and 1, 4, 8, and 24 hours postoperatively.

There was no early or late mortality in this cohort of patients. Low cardiac output developed in 3 of 16 patients, and pleural effusions developed in 5. The median length of hospital stay was 9 days. Activated complement C3 levels increased from a baseline of 1,486 +/- 564 to 4,600 +/- 454 ng/mL after cardiopulmonary bypass and administration of protamine, and returned to baseline by 24 hours. The level of interleukin-6 increased from 42 +/- 32 to 176 +/- 22 pg/mL and at 24 hours remained elevated at 71 +/- 15 pg/mL. Neither thromboxane B2 nor tumor necrosis factor-alpha levels increased significantly.

The data demonstrate threefold to four-fold increases in activated complement C3 and interleukin-6, indicating that both humoral and cellular systems are affected. It is our conclusion that complement and cytokine activation may contribute to the delayed recovery observed after Fontan procedure.