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Tight Glycemic Control Protects the Myocardium and Reduces Inflammation in Neonatal Heart Surgery

Dirk Vlasselaers, Dieter Mesotten, Lies Langouche, Ilse Vanhorebeek, Ingeborg Van den Heuvel, Ilse Milants, Pieters Wouters, Patrick Wouters UGent, Bart Meyns, Mette Bjerre, et al. (2010) ANNALS OF THORACIC SURGERY. 90(1). p.22-30
abstract
Neonatal cardiac surgery evokes hyperglycemia and a systemic inflammatory response. Hyperglycemia is associated with intensified inflammation and adverse outcome in critically ill children and in pediatric cardiac surgery. Recently we demonstrated that tight glycemic control (TGC) reduced morbidity and mortality of critically ill children. Experimental data suggest that insulin protects the myocardium in the setting of ischemia-reperfusion injury, but this benefit could be blunted by coinciding hyperglycemia. We hypothesized that insulin-titrated TGC, initiated prior to myocardial ischemia and reperfusion, protects the myocardium and attenuates the inflammatory response after neonatal cardiac surgery. Methods This is a prospective randomized study at a university hospital. Fourteen neonates were randomized to intraoperative and postoperative conventional insulin therapy or TGC. Study endpoints were effects on myocardial damage and function; inflammation, endothelial activation, and clinical outcome parameters. Results Tight glycemic control significantly reduced circulating levels of cardiac troponin-I (p = 0.009), heart fatty acid-binding protein (p = 0.01), B-type natriuretic peptide (p = 0.002), and the need for vasoactive support (p = 0.008). The TGC suppressed the rise of the proinflammatory cytokines interleukin-6 (p = 0.02) and interleukin-8 (p = 0.05), and reduced the postoperative increase in C-reactive protein (p = 0.04). Myocardial concentrations of Akt, endothelial nitric-oxide synthase, and their phosphorylated forms were not different between groups. Conclusions In neonates undergoing cardiac surgery, intraoperative and postoperative TGC protects the myocardium and reduces the inflammatory response. This appears not to be mediated by an early, direct insulin signaling effect, but may rather be due to independent effects of preventing hyperglycemia during reperfusion
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
Heart, surgery, neonate, Glucose, INTENSIVE INSULIN THERAPY, Myocardium, HYPERGLYCEMIA, TROPONIN-I, NITRIC-OXIDE, CARDIOPULMONARY BYPASS, GLUCOSE CONTROL, NATRIURETIC PEPTIDE, PEDIATRIC CARDIAC-SURGERY, CRITICALLY-ILL PATIENTS, ARTERIAL SWITCH OPERATION
journal title
ANNALS OF THORACIC SURGERY
Ann. Thorac. Surg.
volume
90
issue
1
pages
22 - 30
publisher
Elsevier Inc
Web of Science type
Article
Web of Science id
000278998400004
JCR category
SURGERY
JCR impact factor
3.558 (2010)
JCR rank
13/186 (2010)
JCR quartile
1 (2010)
ISSN
0003-4975
DOI
10.1016/j.athoracsur.2010.03.093
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1006614
handle
http://hdl.handle.net/1854/LU-1006614
date created
2010-07-08 13:49:44
date last changed
2016-12-19 15:42:12
@article{1006614,
  abstract     = {Neonatal cardiac surgery evokes hyperglycemia and a systemic inflammatory response. Hyperglycemia is associated with intensified inflammation and adverse outcome in critically ill children and in pediatric cardiac surgery. Recently we demonstrated that tight glycemic control (TGC) reduced morbidity and mortality of critically ill children. Experimental data suggest that insulin protects the myocardium in the setting of ischemia-reperfusion injury, but this benefit could be blunted by coinciding hyperglycemia. We hypothesized that insulin-titrated TGC, initiated prior to myocardial ischemia and reperfusion, protects the myocardium and attenuates the inflammatory response after neonatal cardiac surgery.

Methods
This is a prospective randomized study at a university hospital. Fourteen neonates were randomized to intraoperative and postoperative conventional insulin therapy or TGC. Study endpoints were effects on myocardial damage and function; inflammation, endothelial activation, and clinical outcome parameters.
Results
Tight glycemic control significantly reduced circulating levels of cardiac troponin-I (p = 0.009), heart fatty acid-binding protein (p = 0.01), B-type natriuretic peptide (p = 0.002), and the need for vasoactive support (p = 0.008). The TGC suppressed the rise of the proinflammatory cytokines interleukin-6 (p = 0.02) and interleukin-8 (p = 0.05), and reduced the postoperative increase in C-reactive protein (p = 0.04). Myocardial concentrations of Akt, endothelial nitric-oxide synthase, and their phosphorylated forms were not different between groups.
Conclusions
In neonates undergoing cardiac surgery, intraoperative and postoperative TGC protects the myocardium and reduces the inflammatory response. This appears not to be mediated by an early, direct insulin signaling effect, but may rather be due to independent effects of preventing hyperglycemia during reperfusion},
  author       = {Vlasselaers, Dirk  and Mesotten, Dieter  and Langouche, Lies  and Vanhorebeek, Ilse  and Van den Heuvel, Ingeborg  and Milants, Ilse  and Wouters, Pieters  and Wouters, Patrick and Meyns, Bart  and Bjerre, Mette  and Hansen, Troels Krarup and Van den Berghe, Greet },
  issn         = {0003-4975},
  journal      = {ANNALS OF THORACIC SURGERY},
  keyword      = {Heart,surgery,neonate,Glucose,INTENSIVE INSULIN THERAPY,Myocardium,HYPERGLYCEMIA,TROPONIN-I,NITRIC-OXIDE,CARDIOPULMONARY BYPASS,GLUCOSE CONTROL,NATRIURETIC PEPTIDE,PEDIATRIC CARDIAC-SURGERY,CRITICALLY-ILL PATIENTS,ARTERIAL SWITCH OPERATION},
  language     = {eng},
  number       = {1},
  pages        = {22--30},
  publisher    = {Elsevier Inc},
  title        = {Tight Glycemic Control Protects the Myocardium and Reduces Inflammation in Neonatal Heart Surgery},
  url          = {http://dx.doi.org/10.1016/j.athoracsur.2010.03.093},
  volume       = {90},
  year         = {2010},
}

Chicago
Vlasselaers, Dirk , Dieter Mesotten, Lies Langouche, Ilse Vanhorebeek, Ingeborg Van den Heuvel, Ilse Milants, Pieters Wouters, et al. 2010. “Tight Glycemic Control Protects the Myocardium and Reduces Inflammation in Neonatal Heart Surgery.” Annals of Thoracic Surgery 90 (1): 22–30.
APA
Vlasselaers, D., Mesotten, D., Langouche, L., Vanhorebeek, I., Van den Heuvel, I., Milants, I., Wouters, P., et al. (2010). Tight Glycemic Control Protects the Myocardium and Reduces Inflammation in Neonatal Heart Surgery. ANNALS OF THORACIC SURGERY, 90(1), 22–30.
Vancouver
1.
Vlasselaers D, Mesotten D, Langouche L, Vanhorebeek I, Van den Heuvel I, Milants I, et al. Tight Glycemic Control Protects the Myocardium and Reduces Inflammation in Neonatal Heart Surgery. ANNALS OF THORACIC SURGERY. Elsevier Inc; 2010;90(1):22–30.
MLA
Vlasselaers, Dirk , Dieter Mesotten, Lies Langouche, et al. “Tight Glycemic Control Protects the Myocardium and Reduces Inflammation in Neonatal Heart Surgery.” ANNALS OF THORACIC SURGERY 90.1 (2010): 22–30. Print.