Persistent pulmonary hypertension of newborn (PPHN) is associated with impaired pulmonary vasodilation at birth. Previous studies demonstrated that a decrease in angiogenesis contributes to this failure of postnatal adaptation. We investigated the hypothesis that oxidative stress from NADPH oxidase (Nox) contributes to impaired angiogenesis in PPHN. PPHN was induced in fetal lambs by ductus arteriosus ligation at 85% of term gestation. Pulmonary artery endothelial cells (PAEC) from fetal lambs with PPHN (HTFL-PAEC) or control lambs (NFL-PAEC) were compared for their angiogenic activities and superoxide production. HTFL-PAEC had decreased tube formation, cell proliferation, scratch recovery, and cell invasion and increased cell apoptosis. Superoxide (O(2)(-)) production, measured by dihydroethidium epifluorescence and HPLC, were increased in HTFL-PAEC compared with NFL-PAEC. The mRNA levels for Nox2, Rac1, p47(phox), and Nox4, protein levels of p67(phox) and Rac1, and NADPH oxidase activity were increased in HTFL-PAEC. NADPH oxidase inhibitor, apocynin (Apo), and antioxidant, N-acetyl-cysteine (NAC), improved angiogenic measures in HTFL-PAEC. Apo and NAC also reduced apoptosis in HTFL-PAEC. Our data suggest that PPHN is associated with increased O(2)(-) production from NADPH oxidase in PAEC. Increased oxidative stress from NADPH oxidase contributes to the impaired angiogenesis of PAEC in PPHN.

Newborn resuscitation requires a multidisciplinary team effort to deliver safe, effective and efficient care. California Perinatal Quality Care Collaborative’s Simulating Success program was designed to help hospitals implement on-site simulation-based neonatal resuscitation training programs. Partnering with the Center for Advanced Pediatric and Perinatal Education at Stanford, Simulating Success engaged hospitals over a 15 month period, including three months of preparatory training and 12 months of implementation. The experience of the first cohort (Children’s Hospital of Orange County (CHOC), Sharp Mary Birch Hospital for Women and Newborns (SMB) and Valley Children’s Hospital (VCH)), with their site-specific needs and aims, showed that a multidisciplinary approach with a sound understanding of simulation methodology can lead to a dynamic simulation program. All sites increased staff participation. CHOC reduced latent safety threats measured during team exercises from 4.5 to two per simulation while improving debriefing skills. SMB achieved 100% staff participation by identifying unit-specific hurdles within in situ simulation. VCH improved staff confidence level in responding to neonatal codes and proved feasibility of expanding simulation across their hospital system. A multidisciplinary approach to quality improvement in neonatal resuscitation fosters engagement, enables focus on patient safety rather than individual performance, and leads to identification of system issues.

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