Effects of Leukocyte Depletion Filters on Matrix Metalloproteinase Activation in an Extracorporeal Circulation Circuit

Abstract

Matrix metalloproteinases (MMPs) are a family of endopeptidases that function to remodel tissue during both normal physiology and pathology. Research performed by the Medical University of South Carolina found an increased release of several MMP species during cardiopulmonary bypass (CPB), including the subtype MMP-9, but whether and to what degree the extracorporeal circulation circuit (ECC) induces the release of MMPs has yet to be determined. Human bank whole blood scheduled for discard was obtained and exposed to an ECC. The first set of studies (N = 8) was performed with a loop circuit using a standard arterial line filter. A leukoreduction filter was incorporated during the first 30 min of the pump run for the second set of trials; the leukoreduction filter was then bypassed and a standard arterial filter used for the remaining 60 minutes on pump (N = 8). Blood samples were drawn at four time points for analysis (baseline, 30, 60, and 90 min). Data were analyzed using repeated measures analysis of variance with betweensubjects factors, and a p value of less than .1 was considered statistically significant. The MMP-9 level increased by 130.44% at 90 min on pump in the standard arterial filter group and decreased by 34.62% at 90 min on pump in the leukoreduction group. There was a significant difference between the baseline MMP-9 level and the MMP-9 concentrations at 30, 60, and 90 min for both groups (p = .0348); there was a significant difference in MMP-9 levels between the two filter groups (p = .0611). The present study found a significant increase in MMP-9 levels when blood was exposed to an ECC with a standard arterial filter. The use of a leukoreduction filter significantly reduced MMP-9 concentrations as compared to baseline levels in this study. Leukocyte depletion filtration may serve to benefit CPB patients by attenuating the inflammatory response and disrupting pathways that govern such mediators as the MMPs.