[Alterations of metalloproteinases and their inhibitors concentrations in peripheral blood in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass]

Abstract

Cardiac surgery with cardiopulmonary bypass (CPB) in children with congenital heart disease induces neutrophil activation, degranulation and systemic inflammatory response. Matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) are enzymes involved in degranulation and leukocyte extravasation. These are secreted as a pro-enzyme in response to several inflammatory mediators and are inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2). To explore metalloproteinase activation during cardiac surgery we investigated MMP-9, MMP-2, TIMP-1 and TIPM-2 levels in young children during and after surgery. We measured the dynamics of these enzyme concentrations in peripheral blood. Additionally we measured CD11b and CD66b molecule expression on neutrophils. These investigations were carried out in 39 children, aged 5-38 months who were undergoing cardiacsurgery with cardiopulmonary bypass (CPB). Serum concentrations of MMPs and their inhibitors, CD11b and CD66b expression on neutrophils were sequentially measured before induction of anesthesia, at the initiation of CPB, after 30 minutes of CPB, at the end of CPB, 4 and 48 hours after CPB. MMP-9 concentration increased at the end of CPB and remained elevated for a period of 48 hours. The concentration of MMP-9 detected at the end of CPB positively correlated with time of CPB (r=0.68, p=0.0045). TIMP-1 concentration decreased significantly after 30 minutes of CPB, remained lowered to the end of CPB, and returned to the start of CPB level after 48 hours. CD11b and CD66b expression on neutrophils increased at the initiation of CPB. Our data confirm that MMPs play an important role in inflammatory complications after cardiac surgery in children. These findings suggest that kinetics of MMPs concentrations in serum after cardiac surgery appear to depend on many factors. We demonstrated the link between CPB duration and the MMP-9 concentration. Future studies will determine whether inhibition of MMPs activity diminishes morbidity in children after cardiac surgery.