Effects of Aprotinin or Tranexamic Acid on Proteolytic/cytokine Profiles in Infants After Cardiac Surgery

Background: After cardiopulmonary bypass (CPB), elaboration of cytokines, and subsequent induction of interstitial proteases, such as matrix metalloproteinases (MMPs), can result in a complex postoperative course. The serine protease inhibitor, aprotinin, which has been used in congenital heart surgery putatively for modulating fibrinolysis is now unavailable, necessitating the use of lysine analogues such as tranexamic acid (TXA). The present study tested the hypothesis that distinctly different plasma profiles of signaling molecules and proteases would be differentially affected after the administration of aprotinin or TXA in the context of congenital cardiac surgery and CPB.

Methods: Thirty-seven patients (age, 4.8 +/- 0.3 months) undergoing corrective surgery for ventricular septal defect and tetralogy of Fallot received either aprotinin (n = 22) or TXA (n = 15). Using a high throughput multiplex suspension immunoassay, plasma was serially quantified for cytokines and MMPs: before aprotinin or TXA (baseline), after separation from CPB, and 4, 12, 24, and 48 hours post-CPB.

Results: Tumor necrosis factor-alpha increased initially after CPB in both the aprotinin and TXA groups, but at 24 and 48 hours post-CPB was approximately 50% lower in the aprotinin group (p < 0.05). The IL-10 levels were threefold higher in the TXA group compared with the aprotinin group immediately post-CBP (p < 0.05). Plasma levels of MMP types associated with inflammation, MMP-8, and MMP-9, were twofold higher in the late post-CPB period in the TXA group when compared with the aprotinin group.

Conclusions: After ventricular septal defect or tetralogy of Fallot repair in children, cytokine induction occurs, which is temporally related to the emergence of a specific MMP profile. Moreover, these unique findings demonstrated differential effects between the serine protease inhibitor aprotinin and the lysine analogue TXA with respect to cytokine and MMP induction in the early postoperative period. The different cytokine-proteolytic profile between these antifibrinolytics may in turn influence biologic processes in the postoperative period.