Plasma matrix metalloproteinases in neonates having surgery for congenital heart disease

Overview

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.

Keywords

Cardiopulmonary bypass, congenital heart disease, matrix metalloproteinases; neonate, pediatrics.

Correspondence

Ari R. Joffe, Department of Pediatrics, 3A3.07 Walter C Mackenzie Center, 8440-112 Street, Edmonton, Alberta, T6G 2B7 Canada. E-mail: ajoffe@cha.ab.ca

Acknowledgements

We thank the Pediatric
Intensive Care Research Team for help with
patient enrolment, and data and sample collection.
We also thank Yuanyuan Liang and Quili
Duan for assistance in statistical analyses. This
project was supported by a grant from the
University Hospital Foundation (AJ and PYC) and
operating grants from the Canadian Institutes of
Health Research (RS and PYC). RR, RS, and P-YC
are researchers supported by the Alberta
Heritage Foundation for Medical Research.

Received

2009-03-24T00:00:00