During cardiopulmonary-bypass matrixmetalloproteinases released may contribute to ventricular dysfunction. This study was to determine plasma matrix-metalloproteinases in neonates after cardiopulmonary-bypass and their relation to post-operative course. A prospective observational study included 18 neonates having cardiac surgery. Plasma matrix-metalloproteinases-2 and 9 activities were measured by gelatin-zymography preoperatively, on starting cardiopulmonarybypass, 7-8 min after aortic cross-clamp release, and 1h, 4h, 24h, and 3d after cardiopulmonary- bypass. Plasma concentrations of their tissue inhibitors 1 and 2 were determined by enzyme-linked immunosorbent assay. Cardiac function was assessed by serial echocardiography. Paired t-tests and Wilcoxon tests were used to assess temporal changes, and linear correlation with simultaneous clinical and cardiac function parameters were assessed using Pearson’s product-moment correlation coefficient. Plasma matrix-metalloproteinases activities and their tissue inhibitor concentrations decreased during cardiopulmonary-bypass. Matrix-metalloproteinase- 2 plasma activity increased progressively starting 1h after cardiopulmonarybypass and returned to pre-operative levels at 24h. Matrix-metalloproteinase-9 plasma activity increased significantly after release of aortic cross-clamp, peaked 7-8min later, and returned to baseline at 24h. Plasma tissueinhibitor 1 and 2 concentrations increased 1h after cardiopulmonary-bypass. Cardiac function improved from 4h to 3d after surgery (p<0.05). There was no evidence of significant correlations between matrix-metalloproteinases or their inhibitors and cardiac function, inotrope scores, organ dysfunction scores, ventilation days, or hospital days. The temporal profile of plasma matrix-metalloproteinases and their inhibitors after cardiopulmonary- bypass in neonates are similar to adults. In neonates, further study should determine whether circulating matrix-metalloproteinases are useful biomarkers of disease activity locally within the myocardium, and hence of clinical outcomes.
Cardiopulmonary bypass, congenital heart disease, matrix metalloproteinases; neonate, pediatrics.
Ari R. Joffe, Department of Pediatrics, 3A3.07 Walter C Mackenzie Center, 8440-112 Street, Edmonton, Alberta, T6G 2B7 Canada. E-mail: email@example.com
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