New approaches for persistent pulmonary hypertension of newborn
Section snippets
Conditions associated with persistent pulmonary hypertension of newborn
PPHN can occur without associated parenchymal lung disease (idiopathic) or with a variety of lung diseases. PPHN occurs most commonly in association with meconium aspiration syndrome (50%), followed by idiopathic PPHN (20%), pneumonia/sepsis (20%), respiratory distress syndrome (5%), and other causes (asphyxia, maternal diabetes, polycythemia, etc) [2], [4]. Alveolar-capillary dysplasia, a developmental defect in the proper alignment of alveoli and pulmonary vessels to form the air-blood
Inhaled nitric oxide
Few recent advances in neonatology rival the impact that INO made on the management of PPHN. INO was initially tested in animal models and adults with pulmonary hypertension [46], [47]. INO administered in doses <100 parts per million (ppm) causes selective pulmonary vasodilation [46]. NO diffuses across alveolar space (Fig. 5) to pulmonary artery smooth muscle where it initiates vasodilation by increasing cGMP levels. As it continues to diffuse to the lumen of the pulmonary artery, it is
Alternate approaches to inhaled nitric oxide therapy in persistent pulmonary hypertension of newborn
INO therapy improved oxygenation in nearly 70% of neonates with PPHN in previous randomized trials. Infants who do not show an initial response to INO and those that deteriorate subsequently while on INO therapy may continue to have significant pulmonary hypertension. Investigation of alternate and complementary approaches to INO therapy is needed. The alternatives include (1) vasodilator prostaglandins such as prostacyclin or PGE1, (2) the NO precursor l-arginine, (3) phosphodiesterase
Summary
The management of PPHN entered a new era with the development of inhaled NO therapy for the relief of pulmonary hypertension. The wider application of INO therapy and improved ventilation strategies led to a decrease in the need for invasive life-sustaining therapies such as ECMO. The remarkable advances in the understanding and treatment of PPHN were made possible by the extensive investigations in the laboratory using animal models. Further decreases in morbidity and mortality are possible
Acknowledgements
This work was supported by grant RO1 HL57268 from NIH and a grant-in-aid from AHA.
References (109)
- et al.
Pulmonary vascular biology during neonatal transition
Clin Perinatol
(1999) - et al.
Heat shock protein 90 mediates the balance of nitric oxide and superoxide anion from endothelial nitric oxide synthase
J Biol Chem
(2001) - et al.
The structural basis of PPHN
Clin Perinatol
(1984) - et al.
Possible association between maternal indomethacin therapy and primary pulmonary hypertension of the newborn
Am J Obstet Gynecol
(1976) - et al.
Serum salicylate levels and right to left ductus shunts in newborn infants with persistent pulmonary hypertension
J Pediatr
(1980) - et al.
Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension
Lancet
(1991) - et al.
Inhaled nitric oxide in persistent pulmonary hypertension of the newborn
Lancet
(1992) - et al.
Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn
Lancet
(1992) - et al.
Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn
J Pediatr
(1997) - et al.
Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response
J Pediatr
(1994)