Commentary: Nitric oxide: An important contributor to neuroprotection during pediatric cardiac surgery

Abstract

Microglia are the resident immune cells of the brain. They play a central role in neural immune function in reacting to a wide variety of brain insults. In addition, recent findings in developmental neuroscience highlight the importance of microglia for maturation and normal function of the central nervous system. 1 We have previously shown that cardiopulmonary bypass (CPB) and hypothermic circulatory arrest cause prolonged microglia expansion. 2 The article by Kajimoto and colleagues 3 from Seattle Children's Hospital in this issue of the Journal describes an interesting laboratory study using a translational piglet model. Study animals were ventilated with 20 parts per million of nitric oxide during reperfusion for approximately 3 hours before sacrifice. Subsequent morphologic analysis suggests that inhaled nitric oxide reduced microglial activation after CPB in the hippocampus.Nitric oxide use during infant and pediatric CPB has become increasingly popular clinically following publication of a large prospective randomized clinical trial. 4 The beneficial effects of nitric oxide were particularly apparent in patients younger than 6 weeks of age, who had significantly reduced length of intensive care unit stay and low cardiac output syndrome. In another clinical study, 5 there was improved myocardial protection, improved fluid balance, and improved postoperative intensive care unit course consistent with a general anti-inflammatory effect of nitric oxide that mitigates the systemic inflammatory response to CPB. We have also demonstrated a neuroprotective effect of nitric oxide during CPB and deep hypothermic circulatory arrest using magnetic resonance spectroscopy. 6 The present report further supports the notion that nitric oxide can be an important contributor to protect neurons and glial cells from insults associated with CPB and deep hypothermic circulatory arrest.It is now clear that the etiology of neurologic deficits in children with congenital heart disease (CHD) is cumulative and multifactorial. 7 Alterations in fetal cerebral oxygen delivery cause immature and delayed brain development before birth and before surgery. Lawrence and colleagues 8 recently demonstrated with a unique ''artificial womb'' system that prenatal and preoperative chronic hypoxemia result in similar alterations in microglial morphology in fetal sheep. Several clinical studies demonstrate that further brain damage commonly occurs postoperatively in the individual who has brain immaturity due to fetal hypoxia. Therefore, future studies will be required to determine the effects of cardiac surgery on the brain that contains microglia that are already activated and toxic to develop the optimal regimen of nitric oxide for neuroprotection.