Tight glycemic control protects the myocardium and reduces inflammation in neonatal heart surgery.

Abstract

BACKGROUND:

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.

• Authors: Dirk Vlasselaers, Dieter Mesotten, Lies Langouche, Ilse Vanhorebeek, Ingeborg van den Heuvel, Ilse Milants, Pieter Wouters, Patrick Wouters, Bart Meyns, Mette Bjerre, Troels Krarup Hansen, Greet Van den Berghe
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 90 Issue 1 Pg. 22-9 (Jul 2010) ISSN: 1552-6259 [Electronic] Netherlands
• PMID: 20609741 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin

Topics

• Blood Glucose (metabolism)
• Cardiac Surgical Procedures (adverse effects)
• Critical Illness (therapy)
• Heart Defects, Congenital (blood, surgery)
• Humans
• Hyperglycemia (etiology, metabolism)
• Hypoglycemic Agents (administration & dosage)
• Infant, Newborn
• Insulin (administration & dosage)
• Myocardial Reperfusion Injury (blood, metabolism, prevention & control)
• Myocardium (metabolism)
• Prospective Studies
• Systemic Inflammatory Response Syndrome (etiology, metabolism, prevention & control)