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Updated: Jun 12, 2026
Neonatal Cardiac Scaffolds: Novel Matrices for Regenerative Studies
Published on: November 5, 2016
Circulating matrix metalloproteinase levels after ventricular septal defect repair in infants
Tim C McQuinn1, Rachael L Deardorff, Rupak Mukherjee
1Department of Pediatrics Cardiology, Medical University of South Carolina and the Ralph H Johnson VA Medical Center, Charleston, SC, USA.
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.
Methods And Results:
Using a low-volume (50-60 microL), 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.
Insights
This study reveals that tracking inflammatory molecules after congenital heart surgery can predict patient recovery. Specific patterns of cytokines and matrix metalloproteinases indicate early postoperative outcomes.
Area of Science:
- Biochemistry
- Immunology
- Cardiovascular Surgery
Background:
- Congenital heart disease surgery triggers significant inflammatory responses.
- The interplay between cytokines and matrix metalloproteinases (MMPs) in postoperative outcomes is not fully understood.
Purpose of the Study:
- To investigate the serial changes in a broad panel of cytokines and MMPs after congenital heart defect repair.
- To correlate these molecular changes with early postoperative clinical outcomes.
Main Methods:
- A high-sensitivity multiplex assay was used to measure 8 cytokines and 9 MMPs in 9 patients preoperatively and post-VSD repair.
- Serial plasma samples were collected and analyzed.
- Results were correlated with clinical data including inotropic support, oxygenation, and fluid balance.
Main Results:
- Distinct temporal profiles were observed for cytokines and MMPs, with some peaking early (e.g., IL-2, IL-8, IL-10, MMP-9) and others remaining elevated longer (e.g., MMP-3, MMP-8).
- Early IL-10 levels inversely correlated with inotropic requirement (r=-0.85, P<.005).
- Late MMP-7 levels inversely correlated with fluid balance (r=-0.90, P<.001).
Conclusions:
- Serial profiling of cytokines and MMPs provides valuable insights into the relationship between molecular changes and early postoperative outcomes in congenital heart surgery.
- Specific patterns of these biomarkers may serve as predictors for managing the postoperative course.
