Elsevier

Clinics in Perinatology

Volume 31, Issue 3, September 2004, Pages 591-611
Clinics in Perinatology

New approaches for persistent pulmonary hypertension of newborn

https://doi.org/10.1016/j.clp.2004.04.001Get rights and content

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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.

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References (109)

  • J.P. Kinsella et al.

    Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial

    Lancet

    (1999)
  • A. Lotze et al.

    Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. Survanta in Term Infants Study Group

    J Pediatr

    (1998)
  • A.P. Bos et al.

    Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy

    J Pediatr Surg

    (1993)
  • L.K. Kelly et al.

    Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide

    J Pediatr

    (2002)
  • W.W. Fox et al.

    Pulmonary hypertension in the perinatal aspiration syndromes

    Pediatrics

    (1977)
  • M.C. Walsh-Sukys et al.

    Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes

    Pediatrics

    (2000)
  • J.D. Roberts et al.

    Inhaled nitric oxide and persistent pulmonary hypertension of the newborn

    N Engl J Med

    (1997)
  • Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure

    N Engl J Med

    (1997)
  • J. Alameh et al.

    Alveolar capillary dysplasia: a cause of persistent pulmonary hypertension of the newborn

    Eur J Pediatr

    (2002)
  • D. Bohn

    Congenital diaphragmatic hernia

    Am J Respir Crit Care Med

    (2002)
  • G.S. Dawes et al.

    Changes in the lungs of the newborn lamb

    J Physiol (Lond)

    (1953)
  • S. Cassin et al.

    The vascular resistance of the foetal and newly ventilated lung of the lamb

    J Physiol (Lond)

    (1964)
  • H. Velvis et al.

    Prostaglandin inhibition prevents the fall in pulmonary vascular resistance as a result of rhythmic distension of the lungs in fetal lambs

    Pediatr Res

    (1991)
  • S.H. Abman et al.

    Role of endothelium-derived relaxing factor during transition of pulmonary circulation at birth

    Am J Physiol

    (1990)
  • R.M. Palmer et al.

    Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

    Nature

    (1987)
  • F. Murad et al.

    Guanylate cyclase: activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin

    Adv Cyclic Nucleotide Res

    (1978)
  • P.W. Shaul et al.

    Pulmonary endothelial nitric oxide production is developmentally regulated in the fetus and newborn

    Am J Physiol

    (1993)
  • T.S. Brannon et al.

    Ontogeny of cyclooxygenase-1 and cyclooxygenase-2 gene expression in ovine lung

    Am J Physiol

    (1998)
  • P.W. Shaul et al.

    Oxygen modulates nitric oxide production selectively in fetal pulmonary endothelial cells

    Am J Respir Cell Mol Biol

    (1994)
  • P.W. Shaul et al.

    Oxygen modulates prostacyclin synthesis in ovine fetal pulmonary arteries by an effect on cyclooxygenase

    J Clin Invest

    (1992)
  • G.G. Konduri et al.

    Role of oxidative phosphorylation and ATP release in birth related pulmonary vasodilation in fetal lambs

    Am J Physiol Heart Circ Physiol

    (2002)
  • G.G. Konduri et al.

    Purine nucleotides contribute to pulmonary vasodilation caused by birth related stimuli in the ovine fetus

    Am J Physiol Heart Circ Physiol

    (1997)
  • G.G. Konduri et al.

    Decreased association of HSP90 impairs endothelial nitric oxide synthase in fetal lambs with persistent pulmonary hypertension

    Am J Physiol Heart Circ Physiol

    (2003)
  • J.D. Pearson et al.

    Stimulation of prostaglandin production through purinoceptors on cultured porcine endothelial cells

    Biochem J

    (1983)
  • K.D. Bloch et al.

    Pulmonary soluble guanylate cyclase, a nitric oxide receptor, is increased during the perinatal period

    Am J Physiol

    (1997)
  • K.A. Hanson et al.

    Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message

    Am J Respir Crit Care Med

    (1998)
  • T. Michel

    Targeting and translocation of endothelial nitric oxide synthase

    Braz J Med Biol Res

    (1999)
  • U. Landmesser et al.

    Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension

    J Clin Invest

    (2003)
  • Y. Song et al.

    Inhibition of superoxide generation from neuronal nitric oxide synthase by heat shock protein 90: implications in NOS regulation

    Biochemistry

    (2002)
  • A. Friebe et al.

    Stimulation of soluble guanylate cyclase by superoxide dismutase is mediated by NO

    Biochem J

    (1998)
  • Y. Liu et al.

    High glucose impairs voltage gated K+ channel current in rat small coronary arteries

    Circ Res

    (2001)
  • U. Landmesser et al.

    Oxidative stress and vascular damage in hypertension

    Coron Artery Dis

    (2001)
  • S.H. Abman et al.

    Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs

    J Clin Invest

    (1989)
  • F.C. Morin

    Ligating the ductus arteriosus before birth causes persistent pulmonary hypertension in newborn lamb

    Pediatr Res

    (1989)
  • M.A. Alano et al.

    Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn

    Pediatrics

    (2001)
  • L.M. Wild et al.

    Ligating the ductus arteriosus before birth remodels the pulmonary vasculature of the lamb

    Pediatr Res

    (1989)
  • M.E. Villanueva et al.

    Decreased gene expression of endothelial nitric oxide synthase in newborns with persistent pulmonary hypertension

    Pediatr Res

    (1998)
  • D.L. Pearson et al.

    Neonatal pulmonary hypertension: urea-cycle intermediates, nitric oxide production and carbamoylphosphate synthetase function

    N Engl J Med

    (2001)
  • P.W. Shaul et al.

    Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension

    Am J Physiol Lung Cell Mol Physiol

    (1997)
  • E. Villamor et al.

    Chronic intrauterine pulmonary hypertension impairs endothelial nitric oxide synthase in the ovine fetus

    Am J Physiol Lung Cell Mol Physiol

    (1997)
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