Billie Lou Short

NF-κB Activation Plays a Role in Superoxide-Mediated Cerebral Endothelial Dysfunction After Hypoxia/Reoxygenation

Background and Purpose— Cerebral vascular injury occurs in response to hypoxia/reoxygenation (H/R). However, the cellular signaling pathways that regulate this event remain unclear. The present study was designed to determine whether reactive oxygen species (ROS) mediate endothelial dysfunction after H/R in cerebral resistance arteries and, if so, the relative contribution of ROS, NADPH oxidase, and a nuclear factor-&kgr;B (NF-&kgr;B) pathway. Methods— Arterial diameter and intraluminal pressure were simultaneously measured on rat posterior cerebral arteries (PCA). Superoxide was measured by 5-&mgr;mol/L lucigenin-enhanced chemiluminescence. Results— Hypoxia/reoxygenation selectively inhibited cerebral vasodilation to the endothelium-dependent agonist acetylcholine (Ach) (0.01 to 10 &mgr;mol/L) by ≈50%. Impaired vasodilation after H/R was reversed by 2,2,6,6-tetramethylpiperidine-N-oxyl (Tempo) (100 &mgr;mol/L), a cell-permeable superoxide dismutase mimetic, and partially by ebselen (10 &mgr;mol/L), a peroxynitrite scavenger. H/R-impaired vasodilation to Ach was also preserved by apocynin (1 mmol/L), a specific inhibitor for NADPH oxidase. Correspondingly, H/R significantly increased lucigenin-detectable superoxide, which was reduced by either Tempo or apocynin, but not by allopurinol (10 &mgr;mol/L), an inhibitor of xanthine oxidase. Finally, the NF-&kgr;B inhibitors helenalin (10 &mgr;mol/L) and MG-132 (1 &mgr;mol/L) independently antagonized H/R-impaired Ach-induced vasodilation without affecting dilator response to sodium nitroprusside, an endothelium-independent vasodilator. Conclusions— These results indicate that superoxide mediates cerebral endothelial dysfunction after hypoxia/reoxygenation largely via activation of NADPH oxidase and possibly activation of NF-&kgr;B pathway.

Survival in congenital diaphragmatic hernia: use of predictive equations in the ECMO population.

Background: Equations have been proposed by the Wilford Hall/Santa Rosa (WHSR) and Congenital Diaphragmatic Hernia Study Group (CDHSG) for predicting survival in patients with CDH. The CDHSG stratifies risk based on a logistic regression equation incorporating birth weight and 5-min Apgar score, while the WHSR group uses the difference between maximum pO2 and maximum pCO2 as an index of risk. These models have not been applied specifically to the CDH ECMO (extracorporeal membrane oxygenation) population, a group at highest mortality risk. Objectives: To evaluate the WHSR and CDHSG predictive equations when applied to a population of patients with CDH requiring ECMO life support. Methods: A single-center retrospective review was conducted on infants with CDH treated with ECMO between 1993 and 2007. Predicted and actual outcomes were compared using receiver operating curve (ROC) analyses in which an area under the curve (AUC) of 1 denotes 100% agreement between predicted and actual outcomes. Kaplan-Meier analyses were also used to compare survival of patients who were risk-categorized according to each prediction model. Minimum pre-ECMO pCO2 was likewise evaluated as a predictor of survival. Results: Overall survival was 50% in 62 CDH patients treated with ECMO during the study period. The CDHSG equation did not discriminate between survivors and nonsurvivors (AUC 0.55, p = 0.499). The modified WHSR formula showed better discrimination of survival (AUC 0.71, p = 0.004). Lowest achievable pre-ECMO pCO2 had the highest AUC (0.723, p = 0.003). Patients with minimum pre-ECMO pCO2 <50 mm Hg had 56% survival, while those with >70 mm Hg had 0% survival. Conclusions: Equations proposed to predict survival in CDH patients may not discriminate survivors from nonsurvivors in the ECMO population. In this highest risk group, factors such as birth weight and Apgar score are less critical in estimating mortality risk than indicators of ventilation and oxygenation that reflect the degree of pulmonary hypoplasia.

Therapeutic Hypothermia for Neonatal Encephalopathy and Extracorporeal Membrane Oxygenation

This case series describes the clinical management of 5 infants who underwent whole-body cooling during extracorporeal membrane oxygenation (ECMO). In all 5 infants, systemic hypothermia was maintained during ECMO with acceptable clinical outcomes.

Intercenter Cost Variation for Perinatal Hypoxic-Ischemic Encephalopathy in the Era of Therapeutic Hypothermia.

OBJECTIVE To quantify intercenter cost variation for perinatal hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia across childrens hospitals. STUDY DESIGN Prospectively collected data from the Childrens Hospitals Neonatal Database and Pediatric Health Information Systems were linked to evaluate intercenter cost variation in total hospitalization costs after adjusting for HIE severity, mortality, length of stay, use of extracorporeal support or nitric oxide, and ventilator days. Secondarily, costs for intensive care unit bed, electroencephalography (EEG), and laboratory and neuroimaging testing were also evaluated. Costs were contextualized by frequency of favorable (survival with normal magnetic resonance imaging) and adverse (death or need for gastric tube feedings at discharge) outcomes to identify centers with relative low costs and favorable outcomes. RESULTS Of the 822 infants with HIE treated with therapeutic hypothermia at 19 regional neonatal intensive care units, 704 (86%) survived to discharge. The median cost/case for survivors was

Role of sensory C fibers in hypoxia/ reoxygenation-impaired myogenic constriction of cerebral arteries

58 552 (IQR

The impact of ethnic population dynamics on neonatal ECMO outcomes: a single urban institutional study.

32 476-

Critical Congenital Heart Disease Screening in NICU: Need for Revision and Standardization

130 203) and nonsurvivors

Contents Vol. 99, 2011

29 760 (IQR

Whole body cooling for treatment of and antecedents of neonatal encephalopathy: The Children's National Medical Center's experience May 2006–August 2009, –95 infants

16 897-

Plasticizer, Di(2-ethylhexyl)Phthalate (DEHP), exposure in neonatal ECMO vs. near-miss ECMO patients

61 399). Adjusting for illness severity and select interventions, intercenter differences explained 29% of the variation in total hospitalization costs. The widest cost variability across centers was EEG use, although low cost and favorable outcome centers ranked higher with regards to EEG costs. CONCLUSIONS There is marked intercenter cost variation associated with treating HIE across regional childrens hospitals. Our investigation may help establish references for cost and enhance quality improvement and resource utilization projects related to HIE.