Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Martinho, S (Author) Other; Adao, R (Author) FMUP; Leite-Moreira AF (Author) FMUP; Brás-Silva C (Author) FMUP

Journal

Title: Frontiers in Pediatrics

Vol. 8

Publisher: Frontiers Media

Indexing

ISI Web of Knowledge - 32 Citations

Scopus - 35 Citations

Other information

Authenticus ID: P-00S-K3P

DOI: 10.3389/fped.2020.00342

Abstract (EN): Persistent pulmonary hypertension of the newborn (PPHN) is one of the main causes of neonatal morbidity and mortality. It is characterized by sustained elevation of pulmonary vascular resistance (PVR), preventing an increase in pulmonary blood flow after birth. The affected neonates fail to establish blood oxygenation, precipitating severe respiratory distress, hypoxemia, and eventually death. Inhaled nitric oxide (iNO), the only approved pulmonary vasodilator for PPHN, constitutes, alongside supportive therapy, the basis of its treatment. However, nearly 40% of infants are iNO resistant. The cornerstones of increased PVR in PPHN are pulmonary vasoconstriction and vascular remodeling. A better understanding of PPHN pathophysiology may enlighten targeted and more effective therapies. Sildenafil, prostaglandins, milrinone, and bosentan, acting as vasodilators, besides glucocorticoids, playing a role on reducing inflammation, have all shown potential beneficial effects on newborns with PPHN. Furthermore, experimental evidence in PPHN animal models supports prospective use of emergent therapies, such as soluble guanylyl cyclase (sGC) activators/stimulators,l-citrulline, Rho-kinase inhibitors, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, recombinant superoxide dismutase (rhSOD), tetrahydrobiopterin (BH4) analogs, omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), 5-HT2A receptor antagonists, and recombinant human vascular endothelial growth factor (rhVEGF). This review focuses on current knowledge on alternative and novel pathways involved in PPHN pathogenesis, as well as recent progress regarding experimental and clinical evidence on potential therapeutic approaches for PPHN.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 23