Persistent Pulmonary Hypertension of the Newborn: Therapeutical Approach

Division of Neonatology, Perrino Hospital, s.s. 7 per Mesagne, 72100 Brindisi, Italy.
Mini Reviews in Medicinal Chemistry (Impact Factor: 2.9). 01/2009; 8(14):1507-13. DOI: 10.2174/138955708786786507
Source: PubMed


Persistent pulmonary hypertension of the newborn (PPHN), is defined as a failure of the pulmonary vasculature to relax at birth and consequently of the normal adaptation to extra uterine life of the fetal heart/lung system, resulting in hypoxemia. This condition, occurs in about 1-2 newborns per 1000 live births and despite significant improvements in treatment it is associated with substantial infant mortality and morbidity. Over the years wider application of inhaled nitric oxide (iNO) therapy and improved ventilation strategies including surfactant, high-frequency oscillatory ventilation has led to a decrease in the need for invasive life-sustaining therapies such as extracorporeal membrane oxygenation (ECMO). Mortality rate varies from 10 to 20 % of affected newborns in developed countries, but it is much higher when PPHN is refractory to the above reported therapies or when they are not available. As a consequence, development of new therapeutic strategies for severe PPHN is crucial. In particular, recent studies seem to show that sildenafil, a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance may be a useful therapeutic adjunct to critically ill neonates with PPHN.

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    • "Hypoxia contributes significantly to the pathophysiology of some common diseases at the beginning of life, including persistent pulmonary arterial hypertension (PPHN) and cyanotic congenital heart disease (CCHD) [1] [2]. PPHN reflects a failure of the pulmonary vasculature to relax at birth, resulting in severe hypoxemia shortly after birth, marked pulmonary hypertension, and vasoreactivity with extrapulmonary right-to-left shunting of blood across the ductus arteriosus and/or foramen ovale, as well as the absence of cyanotic congenital heart disease [3] [4]. The incidence of PPHN is around 0.2% [5] [6] and it can occur either as a primary condition or it may develop secondary to meconium aspiration, respiratory distress syndrome, infection, or congenital diaphragmatic hernia [7] [8]. "
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    ABSTRACT: HIF-1 alpha (hypoxia-inducible factor-1 alpha) mediates the responses of mammalian cells to hypoxia/ischemia by inducing the expression of adaptive gene products (e.g., vascular endothelial growth factor (VEGF) and erythropoietin (EPO)). Persistent pulmonary hypertension of the newborn (PPHN) and cyanotic congenital heart disease (CCHD) are common neonatal diseases considered as paradigms of hypoxemia. Since the expression HIF-1 alpha, VEGF and EPO in newborns diagnosed with these diseases has yet to be studied, we set out to define the expression of these genes in peripheral blood from newborn infants diagnosed with PPHN and CCHD. The mRNA transcripts encoding HIF-1 alpha, VEGF and EPO were measured by RT-PCR in healthy newborn infants and infants diagnosed with PPHN and CCHD. An important increase in HIF-1 alpha expression was observed in both pathological conditions, accompanied by significant increases in VEGF and EPO expression when compared to healthy infants. HIF-1 alpha mRNA expression increases in newborn infants with PPHN or CCHD, as does the expression of its target genes VEGF and EPO.
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    ABSTRACT: Sildenafil is a phosphodiesterase type 5 inhibitor used as a therapeutic adjunct in critically ill neonates with persistent pulmonary hypertension. Sildenafil is associated with several ocular complications in adults and is suspected to exacerbate retinopathy of prematurity (ROP). The risk of ocular complication in sildenafil-treated newborns, not otherwise at risk for the development of ROP, is unknown. Twenty-two neonates with birth gestational age greater than 34 weeks and birth weight over 2,100 g who received oral sildenafil for more than 2 weeks were assessed by a pediatric ophthalmologist for potential ocular complications. Four patients had ocular findings: 2 had bacterial conjunctivitis; 1 had optic nerve hypoplasia, choroidal coloboma, and nystagmus; 1 had previously suffered from a hypotensive episode and had a documented cortical injury accompanied by bilateral optic disk atrophy and nystagmus. All cases seemed unrelated to sildenafil use and improved despite continued use of the drug. Our results do not support the need for a routine ophthalmologic examination in term and near-term neonates receiving sildenafil.
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