open access

Vol 65, No 10 (2007)
Other
Published online: 2007-10-29
Submitted: 2012-12-28
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Original article
Proteolytic and cytokine balance abnormalities in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass

Jarosław Paśnik, Jadwiga Moll, Agnieszka Cywińska-Bernas, Jacek Moll, Andrzej Sysa, Krzysztof Zeman
Kardiol Pol 2007;65(10):1208-1214.

open access

Vol 65, No 10 (2007)
Other
Published online: 2007-10-29
Submitted: 2012-12-28

Abstract

Background: Cardiac surgery with cardiopulmonary bypass (CPB) in children with congenital heart disease induces a systemic inflammatory response. This inflammatory response is thought to be produced by exposing patients to proinflammatory factors. Aim: To explore the role of cytokines and proteolytic enzymes in inflammatory complications after cardiac surgery in children. Methods: We investigated the dynamics of concentrations of IL-6, IL-8 and IL-10, and metalloproteinases (MMPs) MMP-2 and MMP-9, and their inhibitors – tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2. These investigations were carried out in 28 children, aged 4-34 months, who underwent a cardiac operation with CPB. Serum concentrations of proteins were sequentially measured before induction of anaesthesia, at the initiation of CPB, after 30 minutes of CPB, at the end of CPB, and 4 and 48 hours after CPB. Results: The serum levels of IL-6 increased dramatically 4 hours after CPB compared with the level before anaesthesia (141.83±25.49 vs. 10.68±5.01 ng/ml, p=0.00004) and correlated with duration of CPB (r=0.74, p=0.00028). The serum levels of IL-8 increased 4 hours after CPB compared with the level before anaesthesia (267.1±41.3 vs. 8.5±6.3 ng/ml, p=0.00002). A significant increase of IL-10 concentration at the end of surgery and 4 hours after CPB was detected (95.12±23.57 vs. 10.34±6.45 ng/ml, p=0.000004 and 59.41±21.4 vs. 10.34±6.45 ng/ml, p=0.00004, respectively ). The MMP-9 concentration increased at the end of CPB and remained elevated for a period of 48 hours (44.40±13.95 vs. 19.53±7.58, p=0.000004 and 38.97±10.76 vs. 19.53±7.58, p=0.00004, respectively). The concentration of MMP-9 detected at the end of CPB positively correlated with duration of CPB (r=0.68, p=0.0045). The TIMP-1 concentration decreased significantly after 30 minutes of CPB, and remained lowered to the end of CPB (respectively 52.68±17.72 vs. 83.29±17.06 ng/ml, p=0.000006 and 34.94±10.58 vs. 83.29±17.06 ng/ml, p=0.00004,respectively). Conclusions: Cardiac surgery causes an increase of IL-6 and IL-8 concentrations in peripheral blood 4 hours after CPB termination. The concentration of anti-inflammatory IL-10 cytokine increases immediately after the end of CPB. We showed an increase of the MMP-2 and MMP-9 concentrations during and after CPB and simultaneous decrease of TIMP-1 inhibitor. We demonstrated a link between CPB duration and IL-6 and MMP-9 concentrations.

Abstract

Background: Cardiac surgery with cardiopulmonary bypass (CPB) in children with congenital heart disease induces a systemic inflammatory response. This inflammatory response is thought to be produced by exposing patients to proinflammatory factors. Aim: To explore the role of cytokines and proteolytic enzymes in inflammatory complications after cardiac surgery in children. Methods: We investigated the dynamics of concentrations of IL-6, IL-8 and IL-10, and metalloproteinases (MMPs) MMP-2 and MMP-9, and their inhibitors – tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2. These investigations were carried out in 28 children, aged 4-34 months, who underwent a cardiac operation with CPB. Serum concentrations of proteins were sequentially measured before induction of anaesthesia, at the initiation of CPB, after 30 minutes of CPB, at the end of CPB, and 4 and 48 hours after CPB. Results: The serum levels of IL-6 increased dramatically 4 hours after CPB compared with the level before anaesthesia (141.83±25.49 vs. 10.68±5.01 ng/ml, p=0.00004) and correlated with duration of CPB (r=0.74, p=0.00028). The serum levels of IL-8 increased 4 hours after CPB compared with the level before anaesthesia (267.1±41.3 vs. 8.5±6.3 ng/ml, p=0.00002). A significant increase of IL-10 concentration at the end of surgery and 4 hours after CPB was detected (95.12±23.57 vs. 10.34±6.45 ng/ml, p=0.000004 and 59.41±21.4 vs. 10.34±6.45 ng/ml, p=0.00004, respectively ). The MMP-9 concentration increased at the end of CPB and remained elevated for a period of 48 hours (44.40±13.95 vs. 19.53±7.58, p=0.000004 and 38.97±10.76 vs. 19.53±7.58, p=0.00004, respectively). The concentration of MMP-9 detected at the end of CPB positively correlated with duration of CPB (r=0.68, p=0.0045). The TIMP-1 concentration decreased significantly after 30 minutes of CPB, and remained lowered to the end of CPB (respectively 52.68±17.72 vs. 83.29±17.06 ng/ml, p=0.000006 and 34.94±10.58 vs. 83.29±17.06 ng/ml, p=0.00004,respectively). Conclusions: Cardiac surgery causes an increase of IL-6 and IL-8 concentrations in peripheral blood 4 hours after CPB termination. The concentration of anti-inflammatory IL-10 cytokine increases immediately after the end of CPB. We showed an increase of the MMP-2 and MMP-9 concentrations during and after CPB and simultaneous decrease of TIMP-1 inhibitor. We demonstrated a link between CPB duration and IL-6 and MMP-9 concentrations.
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Keywords

cardiopulmonary bypass; cardiac surgery; congenital heart disease; cytokines; metalloproteinases

About this article
Title

Original article
Proteolytic and cytokine balance abnormalities in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 65, No 10 (2007)

Pages

1208-1214

Published online

2007-10-29

Bibliographic record

Kardiol Pol 2007;65(10):1208-1214.

Keywords

cardiopulmonary bypass
cardiac surgery
congenital heart disease
cytokines
metalloproteinases

Authors

Jarosław Paśnik
Jadwiga Moll
Agnieszka Cywińska-Bernas
Jacek Moll
Andrzej Sysa
Krzysztof Zeman

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