White Matter Protection in Congenital Heart Surgery
Background—Neurodevelopmental delays in motor skills and white matter (WM) injury have been documented in congenital heart disease (CHD) and after pediatric cardiac surgery. The lack of a suitable animal model has hampered our understanding of the cellular mechanisms underlying WM injury in these patients. Our aim is to identify an optimal surgical strategy for WM protection to reduce neurological injury in CHD patients.
Methods and Results—We developed a porcine cardiopulmonary bypass (CPB) model, which displays area dependent WM maturation. In this model, WM injury was identified following CPB-induced ischemia-reperfusion injury. The degree of injury was inversely correlated with the maturation stage, indicating maturation-dependent vulnerability of WM. Within different oligodendrocyte (OL) developmental stages, we show selective vulnerability of O4+ pre-OLs, while OL progenitor cells (OPCs) were resistant to insults. This indicates that immature WM is vulnerable to CPB-induced injury, but has an intrinsic potential for recovery mediated by endogenous OPCs. OPC number decreased with age, suggesting that earlier repair allows successful WM development. OPC proliferation was observed within a few days after CPB-induced ischemia-reperfusion injury; however by four weeks arrested OL maturation and delayed myelination were detected. Logistic model confirmed that maintaining higher oxygenation and reducing inflammation were effective in minimizing the risk of injury at immature stages of WM development.
Conclusions—Primary repair in neonates and young infants potentially provides successful WM development in CHD patients. Cardiac surgery during this susceptible period should avoid ischemia-reperfusion injury and minimize inflammation to prevent long-term WM-related neurological impairment.
- Received June 7, 2011.
- Accepted January 4, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited