Evidence of increased matrix metalloproteinase-9 concentration in patients following cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response, which can result in acute lung injury known as "postperfusion syndrome." Neutrophil activation with concomitant serine protease release has been implicated in the pathogenesis of "postperfusion syndrome." Increased plasma levels of neutrophil elastase (NE) have been demonstrated in patients undergoing CPB, and it is well documented that both NE and matrix metalloproteinase-9 (MMP-9) have a synergistic role in pulmonary injury. We, therefore, hypothesized that plasma levels of MMP-9 would be elevated in patients after CPB. Human plasma was obtained after informed consent from eight patients undergoing CPB. Plasma was collected at the start of CPB, 5 minutes after the initiation of CPB, and at the termination of CPB (156 +/- 17 min). All samples were analyzed by both standard enzyme-linked immunosorbent assay (ELISA) and gelatin zymography for MMP-9 (free and total enzyme) concentration. Data were expressed as means +/-SE and assessed by analysis of variance (ANOVA). Plasma MMP-9 concentration was significantly increased at the end of CPB (191 +/- 30.4 ng/mL; p <.05) as compared to both the start of CPB (28.3 +/- 13.2 ng/mL) and 5 minutes after the initiation of CPB (44.3 +/- 15.4 ng/mL). Patients undergoing CPB show an increase in serum MMP-9 levels. Prior studies utilizing an animal model of "postperfusion syndrome" have shown that inhibition of MMP-9 and NE prevented pulmonary injury following CPB. The results of the current study suggest that such an approach may also have merit in the clinical setting of cardiopulmonary bypass.