Persistent pulmonary hypertension of the newborn (PPHN) is a serious and potentially fatal condition, characterized by hypoxemia
due to increased pulmonary vascular resistance (PVR) with resultant shunting of pulmonary blood to the systemic circulation.
Inhaled nitric oxide (iNO) has been considered a revolutionary treatment of PPHN. Data show that the use of iNO has reduced the need
of ECMO in neonates with severe PPHN, while in moderate PPHN, iNO administration has been associated with a significant decrease in
ventilatory support and prevented progression to severe PPHN.
Not all neonates respond to iNO therapy though, and phosphodiesterase (PDE) inhibitors with their potent vasodilator properties have
evolved as an alternative therapy or as an adjunct to the treatment of PPHN with iNO. There are ten families of PDE isoenzymes. PDE 5
is particularly prevalent in vascular smooth muscle (VSM) and PDE 5 inhibitors, such as sildenafil, have been used in clinical practice.
This review provides a comprehensive account of existing data in the literature, from animal and clinical studies, on the use of sildenafil
for the treatment of PPHN. Sildenafil may also have a role as a single mode of therapy, since in resource-limited settings the cost of iNO
is a serious concern.
Keywords: Persistent pulmonary hypertension of newborn, sildenafil, hypoxemia, pulmonary vascular resistance (PVR), pulmonary blood, systemic circulation, Inhaled nitric oxide (iNO), phosphodiesterase (PDE) inhibitors, vasodilator, vascular smooth muscle (VSM)
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