Biology Reference
In-Depth Information
Phosphodiesterases: Emerging Therapeutic
Targets for Neonatal Pulmonary Hypertension
Kathryn N. Farrow and Robin H. Steinhorn
Contents
1 Phosphodiesterases in the Pathophysiology of Neonatal Pulmonary Hypertension . . . . . . . 252
1.1 Normal Pulmonary Vascular Transition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
1.2 Pathophysiology of Persistent Pulmonary Hypertension of the Newborn . . . . . . . . . . . 255
1.3 Pathophysiology of Pulmonary Hypertension in the Older Infant . . . . . . . . . . . . . . . . . . . 261
2 PDE Inhibitors in Neonatal Pulmonary Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
2.1 PDE5 Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
2.2 PDE3 Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
2.3 PDE1 and PDE4 Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
Abstract Pulmonary hypertension in the neonate is associated with multiple
underlying problems such as respiratory distress syndrome, meconium aspiration
syndrome, congenital diaphragmatic hernia, bronchopulmonary dysplasia, sepsis,
or congenital heart disease. Because of the heterogeneous group of disorders, the
therapeutic approach and response often depends on the underlying disease. In
many of these conditions, there is evidence that cyclic nucleotide signaling and
specifically phosphodiesterases (PDEs) are disrupted. PDE inhibitors represent an
emerging class of pulmonary vasodilators in adults. Studies are now under way to
evaluate the utility, efficacy, and safety of such therapies in infants with pulmonary
hypertension.
K.N. Farrow (
*
)
Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of
Medicine, 310 E. Superior St., Morton 4-685D, Chicago, IL 60611, USA
e-mail: k-farrow@northwestern.edu
R.H. Steinhorn
Division of Neonatology, Children's Memorial Hospital and Northwestern University, 2300
Children's Plaza #45, Chicago, IL 60611, USA
e-mail: r-steinhorn@northwestern.edu
