title: Circulating matrix metalloproteinase levels after ventricular septal defect repair in infants.
abstract: BACKGROUND
  Surgery for congenital heart disease initiates a complex inflammatory response that can influence the postoperative course. However, broad integration of the cytokine and proteolytic cascades (matrix metalloproteinases: MMPs), which may contribute to postoperative outcomes, has not been performed.
  
  
  RESULTS
  Using a low-volume (50-60 μL), high-sensitivity, multiplex approach, we serially measured a panel of cytokines (interleukins 2, 4, 6, 8, and 10, tumor necrosis factor alpha, interleukin 1β, and granulocyte-macrophage colony stimulating factor) and matrix metalloproteinases (matrix metalloproteinases 2, 3, 7, 8, 9, 12, and 13) in patients (n = 9) preoperatively and after repair of ventricular septal defect. Results were correlated with outcomes such as inotropic requirement, oxygenation, and fluid balance. Serial changes in perioperative plasma levels of the cytokines and matrix metalloproteinases exhibited distinct temporal profiles. Plasma levels of interleukins 2, 8, and 10 and matrix metalloproteinase 9 peaked within 4 hours, whereas levels of matrix metalloproteinase 3 and 8 remained elevated at 24 and 48 hours after crossclamp removal. Area-under-the-curve analysis of early cytokine levels were associated with major clinical variables, including inverse correlations between early interleukin 10 levels and cumulative inotrope requirement at 48 hours (r: -0.85; P < .005) and late matrix metalloproteinase 7 levels and cumulative fluid balance (r: -0.90; P < .001).
  
  
  CONCLUSIONS
  The unique findings of this study were that serial profiling a large array of cytokines and proteolytic enzymes after surgery for congenital heart disease can provide insight into relationships between changes in bioactive molecules to early postoperative outcomes. Specific patterns of cytokine and matrix metalloproteinase release may hold significance as biomarkers for predicting and managing the postoperative course after surgery for congenital heart disease.
authors.affiliation: Department of Pediatrics Cardiology, Medical University of South Carolina and the Ralph H Johnson VA Medical Center, Charleston, SC, USA.
authors.forename: Tim C
authors.initials: TC
authors.lastname: McQuinn
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Deardorff
authors.forename: Rupak
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Anna Greta B
authors.initials: AG
authors.lastname: Taylor
authors.forename: Eric M
authors.initials: EM
authors.lastname: Graham
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Atz
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Forbus
authors.forename: Stacia M
authors.initials: SM
authors.lastname: DeSantis
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Young
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: Fred A
authors.initials: FA
authors.lastname: Crawford
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bradley
authors.forename: Scott T
authors.initials: ST
authors.lastname: Reeves
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D016207:Cytokines / Q000097:blood; D005260:Female; D006343:Heart Septal Defects / Q000201:enzymology* / Q000601:surgery*; D006801:Humans; D007223:Infant; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D016207:Cytokines; D020782:Matrix Metalloproteinases