Tim C. McQuinn, MD, Rachael L

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Circulating matrix metalloproteinase levels after ventricular septal defect repair in infants Tim C. McQuinn, MD, Rachael L. Deardorff, Rupak Mukherjee, PhD, Anna Greta B. Taylor, MD, Eric M. Graham, MD, Andrew M. Atz, MD, Geoffrey A. Forbus, MD, Stacia M. DeSantis, PhD, Jennifer B. Young, Robert E. Stroud, MS, Fred A. Crawford, MD, Scott M. Bradley, MD, Scott T. Reeves, MD, Francis G. Spinale, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 140, Issue 6, Pages 1257-1265 (December 2010) DOI: 10.1016/j.jtcvs.2010.05.014 Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Time course for perioperative and postoperative plasma levels (±SEM) of IL-6, IL-10, IL-2, and interferon gamma (INF-γ) in infants undergoing repair of a ventricular septal defect (VSD). The T-helper 1 cytokines (IL-2 and IFN-γ) never increase above baseline values. The shaded bars indicate the range of mean baseline values ± SEM. Baseline values were obtained before the incision, XC samples were obtained after modified ultrafiltration, and the other time points are measured from crossclamp removal. Note the variation in the Y-axis scale (all in pg/mL). #P < .05 vs baseline values, +P < .05 versus values after modified ultrafiltration (XC values). IL, Interleukin. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1257-1265DOI: (10.1016/j.jtcvs.2010.05.014) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Time course for perioperative and postoperative plasma levels of the cytokines TNF-α, GM-CSF, IL-8, and IL-1β in infants undergoing repair of a ventricular septal defect (VSD). TNF-α, GM-CSF, and IL-8 have similar time courses, peaking at 4 hours and declining rapidly. IL-1β increases from essentially undetectable levels to a peak at 24 hours before returning to generally undetectable levels at 48 hours. The shaded bars indicate the range of mean baseline values ± SEM. Baseline values were obtained before the incision, XC samples were obtained after modified ultrafiltration, and the other time points are measured from crossclamp removal. Note the variation in the Y-axis scale (all in pg/mL). #P < .05 versus baseline values, +P < .05 versus values after modified ultrafiltration (XC values). TNF-α, Tumor necrosis factor alpha; GM-CSF, granulocyte-macrophage colony stimulating factor; IL, interleukin. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1257-1265DOI: (10.1016/j.jtcvs.2010.05.014) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Time course for perioperative and postoperative plasma levels of MMP-2, MMP-3, MMP-7, MMP-8, and MMP-9 in infants undergoing repair of a ventricular septal defect (VSD). MMP-2 and MMP-7 values drop below baseline, whereas MMP-8 and MMP-9 values increase with dissimilar time courses. MMP-3 increases steadily through the period from 4 to 48 hours postoperatively. The shaded bars indicate the range of mean baseline values ± SEM. Baseline values were obtained before the incision, XC samples were obtained after modified ultrafiltration, and the other time points are measured from crossclamp removal. Note the variation in the Y-axis scale (all in pg/mL). #P < .05 versus baseline values, +P < .05 versus values after modified ultrafiltration (XC values). MMP, Matrix metalloproteinase. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1257-1265DOI: (10.1016/j.jtcvs.2010.05.014) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Top, Individual response plots for plasma IL-6 levels in the patients undergoing repair of a ventricular septal defect (VSD) at baseline and after crossclamp removal (XC) and modified ultrafiltration. Whereas the relative magnitude varied between patients, IL-6 levels increased at this early post-CPB time point. Bottom, Individual response plots for plasma MMP-9 levels in the VSD patients at baseline and at XC. Overall, a robust increase in plasma MMP-9 levels occurred at this early post-CPB time point. The darker solid lines indicate the mean baseline and XC values ± SEM. #P< .05 versus baseline values. IL, Interleukin; MMP, matrix metalloproteinase. The Journal of Thoracic and Cardiovascular Surgery 2010 140, 1257-1265DOI: (10.1016/j.jtcvs.2010.05.014) Copyright © 2010 The American Association for Thoracic Surgery Terms and Conditions