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Persistent pulmonary hypertension of the newborn, or PPHN, represents a challenging condition associated with high morbidity and mortality. Management is complicated by complex pathophysiology and limited neonatal specific evidence-based literature, leading to a lack of universal contemporary clinical guidelines for the care of these patients. To address this need and to provide consistent high-quality clinical care for this challenging population in our neonatal intensive care unit, we sought to develop a comprehensive clinical guideline for the acute stabilization and management of neonates with PPHN. Utilizing cross-disciplinary expertise and incorporating an extensive literature search to guide best practice, we present an approachable, pragmatic, and clinically relevant guide for the bedside management of acute PPHN. Key Points PPHN is associated with several unique diagnoses; the associated pathophysiology is different for each unique diagnosis. PPHN is a challenging, dynamic, and labile process for which optimal care requires frequent reassessment. Key management goals are adequate tissue oxygen delivery, avoiding harm. [ABSTRACT FROM AUTHOR]

Administration of 1,3-bis(2-chloroethyl)-N-nitrosourea (BCNU) inhibits hepatic activities of glutathione reductase (GR) comparably in both adult male Fischer-344 (F344) and Sprague–Dawley (SD) rats in vivo. BCNU pretreatment greatly exacerbates the hepatic necrosis caused by diquat in F344 rats, but does not similarly potentiate liver injury in SD rats. The primary purpose of the present studies was to test the hypothesis that BCNU pretreatment would exhibit differences between the two strains in inhibition of GR activities in hepatic subcellular compartments that would correlate with the differing effects on diquat-induced hepatic necrosis. In the present studies, 16 h after administration of 80 mg/kg of BCNU, GR activities in the hepatic homogenates were 20–30% of activities in vehicle-treated controls. Neither the extents of inhibition nor the GR activities in hepatic cytosol, microsomes, mitochondria, or purified nuclei isolated by differential centrifugation were different between SD and F344 rats treated with BCNU. The results indicate that differences between SD and F344 rats in the effects of BCNU on susceptibilities to diquat-induced hepatic necrosis are not readily attributable to compartmentally selective inhibition of GR. In addition, hepatic O6-alkylguanine-DNA alkyltransferase (AGT, MGMT) levels were almost completely depleted in BCNU-treated rats of both strains, thus indicating that MGMT-dependent pathways are unlikely to be critical determinants of the effects of BCNU on this model of acute cell death mediated by reactive oxygen species in vivo. [Copyright &y& Elsevier]